acyclovir and Herpes-Simplex

Herpes simplex virus-1 (HSV-1) and -2 (HSV-2) are large, spherically shaped, double-stranded DNA viruses that coevolved with

Topics: Acyclovir; Antiviral Agents; Biological Products; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans

This review examines the recent literature on the management of herpes simplex virus (HSV) infections in neonates. We summarized the three clinical categories of maternal HSV infection during pregnancy (primary first episode, nonprimary first episode, or recurrent episode) and the mechanisms of fetal damage. Considering when the transmission of the infection from the mother to the fetus/newborn occurs, three types of neonatal infection can be distinguished: intrauterine infection (5% of cases), postnatal infection (10% of cases), and perinatal infections (85% of cases). Neonatal presentation could range from a limited disease with skin, eye, and mouth disease to central nervous system disease or disseminated disease: the treatment with acyclovir should be tailored according to symptoms and signs of infection, and virological tests. These children need a multidisciplinary follow-up, to timely intercept any deviation from normal neurodevelopmental milestones. Prevention strategies remain a challenge, in the absence of an available vaccine against HSV.

Topics: Acyclovir; Child; Female; Herpes Simplex; Humans; Infant, Newborn; Mothers; Pregnancy; Skin

Apitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results.. Thus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes.. The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library.. The search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against Herpes simplex virus-induced wounds (95% CI: 3.58 to -0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to -0.42; p = 0.18).. Overall, these results confirm the use of honey and propolis as potent antiherpetic agents.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Honey; Humans; Propolis; Simplexvirus

Herpes simplex virus encephalitis (HSVE) is one of the most common infectious causes of sporadic encephalitis. Coronavirus disease (COVID-19) has been associated with immune dysregulation of the host that might increase the risk of infections like HSVE following SARS-CoV-2 infection. There is paucity of literature on post COVID-19 HSVE. This study was conducted with the aim of analyzing the clinical presentation, brain imaging, and outcome of patients presenting with HSVE within 6 weeks of COVID-19 and providing a comprehensive review on the possible mechanisms of post-COVID-19 HSVE.. This observational study included patients who had laboratory-confirmed HSVE (type 1 or type 2) and a history of COVID-19 within the previous 6 weeks. Patients were followed up for 3 months.. Eight patients were included and all of them had type 1 HSVE. The mean latency of onset of neurological symptoms from being diagnosed with COVID-19 is 23.87 days and a majority of the patients have received injectable steroids with a mean duration of 6.5 days. Behavioral abnormality was the commonest neurological presentation and typical brain imaging involved T2 FLAIR hyperintensities of the medial temporal lobes. All patients received intravenous acyclovir 10 mg/kg every eight hourly for atleast 14 days. One patient with concomitant rhinocerebral mucormycosis succumbed while the majority had a complete recovery.. Possible immune dysregulation in COVID-19 may increase the susceptibility of HSVE in patients with a history of recent SARS-CoV-2 infection. The clinical manifestations and laboratory findings of HSVE in such patients are similar to typical HSVE.

Topics: Acyclovir; COVID-19; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Observational Studies as Topic; SARS-CoV-2

Herpes simplex virus types 1 and 2 HSV1 and 2, namely varicella-zoster VZV and cytomegalovirus CMV, are among the most common pathogens worldwide. They remain in the host body for life. The course of infection with these viruses is often asymptomatic or mild and self-limiting, but in immunocompromised patients, such as solid organ or bone marrow transplant recipients, the course can be very severe or even life-threatening. Unfortunately, in the latter group, the highest percentage of infections with strains resistant to routinely used drugs is observed. On the other hand, frequent recurrences of genital herpes can be a problem even in people with normal immunity. Genital herpes also increases the risk of acquiring sexually transmitted diseases, including HIV infection and, if present in pregnant women, poses a risk to the fetus and newborn. Even more frequently than herpes simplex, congenital infections can be caused by cytomegalovirus. We present the most important anti-herpesviral agents, the mechanisms of resistance to these drugs, and the associated mutations in the viral genome. Special emphasis was placed on newly introduced drugs such as maribavir and brincidofovir. We also briefly discuss the most promising substances in preclinical testing as well as immunotherapy options and vaccines currently in use and under investigation.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; HIV Infections; Humans; Infant, Newborn; Pregnancy

Neonatal herpes simplex disease (HSV) is a rare but life-threatening infection associated with high rates of morbidity and mortality. Recent studies indicate that the incidence rate has continued to rise over the past decades, while the mortality remains unchanged. Early clinical suspicion of HSV and parenteral antiviral treatment of acute disease is essential for the prognosis. The subsequent use of suppressive therapy with oral acyclovir has further enhanced the long-term prognosis. This review presents evidence of risk factors, clinical presentation, prevention, and management of HSV in newborns.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Incidence; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Prognosis

This review summarizes the literature on acyclovir resistant herpes infections and the most recent data pertinent to diagnosis and treatment in the immunocompromised patient population.. Although fairly rare, acyclovir resistant herpes infections can be challenging to diagnose. Clinicians should be aware of this entity when facing refractory herpes infections. With updated diagnostics, the diagnosis is usually made through viral culture and sequencing. Therapeutic choices depend on the extent of disease. Topical therapy may be appropriate for mucocutaneous disease. Intravenous antiviral therapies such as foscarnet and cidofovir may be necessary for disseminated, ophthalmologic, central nervous system, or visceral disease. Experimental therapies such as pritelivir are in clinical trials.. Immunosuppressed patients are at risk for developing acyclovir-resistant herpes, which can be challenging to diagnose and treat, although emerging therapeutic options look promising.

Topics: Acyclovir; Antiviral Agents; Cytosine; Foscarnet; Herpes Simplex; Herpesviridae Infections; Humans; Organophosphonates

Herpes simplex viruses (HSV), the causative agents of recurrent orofacial and anogenital infections, can cause significant morbidity and mortality in both immunocompetent and immunocompromised individuals. In immunocompromised patients, HSV tends to be more persistent with chance of dissemination. The nucleoside analogue acyclovir has drastically improved the management of HSV infections although acyclovir resistant strains have been reported in the clinic. We performed a systematic search to summarize the prevalence data reported in both the immunocompetent and immunocompromised populations. Defining the global prevalence of acyclovir resistance in HSV infections is hampered by the high variability in methodology, patient selection, study design, and treatment history among the studies. Acyclovir resistant HSV is infrequent in the immunocompetent population (generally below 1%), irrespective of treatment history. Exceptions are infections at immune-privileged sites such as the cornea, where frequent recurrences and extensive acyclovir therapy favor the emergence of acyclovir resistance. Higher frequencies of acyclovir resistant HSV infections are reported among immunocompromised individuals, with the highest prevalence seen among hematopoietic stem cell transplant recipients. All antivirals approved for the treatment of HSV infections have the same target, i.e. the viral DNA polymerase, and cross-resistance to different antivirals has been described, complicating therapy of acyclovir resistant strains. In this review we will discuss acyclovir mode of action, mechanisms of resistance, prevalence of resistance, and alternative antiviral treatments for acyclovir resistant HSV infections.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Humans; Prevalence; Simplexvirus

The typical herpes simplex viral encephalitis (HSVE) course is an acute illness, less commonly it may present as a chronic course, mainly in children, and rarely may it be subacute. Subacute HSVE is rarely described in the literature being reported 4 times only.. We here report 2 cases of subacute HSV1 encephalitis diagnosed based on cerebrospinal fluid polymerase chain reaction and magnetic resonance imaging findings and review the literature trying to find any specific clinical, laboratory, radiologic diagnostic or prognostic criteria regarding this subacute form of HSVE.. There is subacute form of HSVE and should be suspected with any subacute febrile illness with nonspecific cognitive impairment even in the absence of focal neurological symptoms and in cases with rapidly progressive dementia. This form has similar radiologic finding and good response to acyclovir but carry even better prognosis than that the acute HSVE.

Topics: Acyclovir; Child; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Magnetic Resonance Imaging; Polymerase Chain Reaction

To report a rare case of herpes virus type 2-related conjunctivitis, resistant to aciclovir (ACV).. Case report and review of literature.. A 28-year-old human immunodeficiency virus-positive man presented with chronic, recurrent follicular conjunctivitis. Multiplex reverse transcription polymerase chain reaction assay testing was positive for herpes simplex virus (HSV); subsequent typing with HSV assay revealed the presence of HSV type 2. Oral ACV failed to control the disease, and the patient continued to worsen clinically until resistance testing was performed. This revealed an M183stop within thymidine kinase, thus confirming the suspected resistance. The patient improved after 14 days of high-dose continuous intravenous infusion of ACV.. This is a rare case of isolated conjunctivitis due to herpes virus type 2, in an human immunodeficiency virus-positive patient, which was found to be resistant to ACV. Drug-resistant HSV is likely to emerge as an important clinical entity in the future, increasing the need for new drugs with novel mechanisms of action.

Topics: Acyclovir; Adult; Antiviral Agents; Conjunctivitis; Drug Resistance, Viral; Eye Infections, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Microbial Sensitivity Tests; RNA, Viral

Acyclovir is an antiviral drug poorly absorbed in the gastrointestinal tract due to its hydrophilicity, with low oral bioavailability (~20%). Although acyclovir is prescribed in the management of herpes simplex encephalitis (HSE), the disease has a poor prognosis, particularly if the treatment is delayed, reaching mortality rates of 70% if left untreated. Thus, high acyclovir doses are administered by intravenous (IV) infusion, usually at a dosage of 10 mg kg

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infusions, Intravenous; Prodrugs

Pneumonia due to herpes simplex virus (HSV) is uncommon but can be seen in immunocompromised patients and has been associated with poor prognosis in this population.. The aim was to study the results, outcome and mortality of HSV pneumonia in immunocompromised patients and patients receiving mechanical ventilation. Furthermore, it has been unclear whether to initiate prophylactic treatment with acyclovir or not.. We have conducted a literature search using the keywords herpes simplex pneumonia, critically ill patients and intensive care unit for identification of relevant publications.. HSV pneumonia can cause severe infection or even death in immunocompromised patients and critically ill patients. A clear diagnosis of HSV pneumonia can be difficult to establish. Respiratory condition may improve after initiation of acyclovir but data is scarce.. HSV pneumonia should be considered in the immunocompromised patient and/or the intensive care patient who continues to deteriorate despite appropriate treatment. The value of prophylactic treatment with acyclovir is unproven but should be considered.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Intensive Care Units; Pneumonia, Viral

This article defines neonatal herpes simplex virus (HSV) disease and describes the progress over the past 40 years that has revolutionized the management of HSV disease in neonates to improve their outcomes. These advancements include the introduction of acyclovir in the 1980s, polymerase chain reaction (PCR) for the detection of HSV DNA in the 1990s, and recommendations on managing infants born to mothers with active genital lesions. Despite these advancements, however, there remain high morbidity and mortality in affected neonates, with need for continued improvement. Areas of high interest include vaccine development and rapid PCR detection at time of delivery.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus

In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barré syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir.

Topics: Acyclovir; Aged; Antiviral Agents; Guillain-Barre Syndrome; Herpes Simplex; Herpesvirus 2, Human; Humans; Liver Transplantation; Male; Treatment Outcome

The goal was to characterize the clinical-epidemiological profile of patients with mucocutaneous tumoural herpes simplex virus (MCT HSV) lesions across the world. Two researchers extracted and independently reviewed data from the literature search engine PubMed/MEDLINE through October 2018. From 110 reported patients, the following data were available: the patients' ages ranged from 7 to 76 years; the majority was male (62.73 %-69/110) and immunosuppression was found in 97.25 % (106/109, missing 1) cases, of whom 88 were HIV- related. Lesions size varied from 0.2-13 cm, settling in the anogenital region in 76.36 % (84/110) patients; 84.13 % (53/63, missing 47) complained of pain and multiple recurrences were found in 44.94 % (40/89, missing 21) cases. On clinical basis, the initial hypothesis was neoplasia in 36/53 patients. Histopathological diagnosis was achieved in 90 % (90/100, missing 10) cases and was sample size-dependent. Type 2 HSV was detected in 86.07 % (68/79, missing 31) lesions. MCT HSV lesions recurrence after treatment was reported in 33.96 % (18/53, missing 57) patients. Pathophysiology is poorly understood. Physicians should be aware of MCT HSV lesions in immunosuppressed patients to avoid inappropriate therapeutic strategies.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Female; Herpes Simplex; Humans; Male; Middle Aged; Neoplasms; Recurrence; Simplexvirus; Young Adult

Herpes simplex virus (HSV), a member of the Herpesviridae family, is a well-known cause of infections including genital herpes and herpes labialis in the adolescent and adult population. Transmission of HSV infection to an infant during the first 4-6 weeks of life can lead to devastating disease with the potential for poor outcomes. Early diagnosis is imperative when evaluating neonatal HSV infection in order to prevent further disease progression, neurological complications, and even death. In the past 4 decades, significant advancements have been made in the diagnosis, treatment, and prevention of neonatal HSV infection, but there remains room for improvement as efforts continue to reduce the burden of disease caused by this infection.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious

Neonatal herpes simplex virus infection (HSV) is rare in neonates, with an estimated global incidence of 10 per 100,000 live births. Neonatal HSV is challenging to diagnose due to often vague signs and symptoms. Untreated, the mortality of some HSV subtypes exceeds 80%. Overtesting and overtreatment can result in prolonged hospitalizations and expose neonates to medication toxicity. In contrast, prompt evaluation and use of empiric antiviral therapy before the results of definitive testing can improve outcomes for infants with HSV. A wide degree of practice variation exists with respect to testing and treatment for neonatal HSV, and more research is required to safely risk-stratify this population. This review presents the epidemiology, risk factors, presenting features, and emergency department management of neonatal HSV infection.

Topics: Acyclovir; Antiviral Agents; Emergency Service, Hospital; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Risk Factors; Vidarabine

Hyaluronic acid injections is relatively safe with little risk of complications. Although herpes reactivation after the injection of hyaluronic acid is rare, it produces quite a huge pressure and panic on patients. Quite a lot cosmetic practitioners have no awareness of preventing, diagnosing, and giving correct treatment in time due to lack of experience.. A 24-year-old woman presented with erythema, crusted papules, pain and swelling on the nose after receiving the injection of hyaluronic acid. A swab of the discharge fluid was obtained for bacterial and viral culture, showing positive for herpes simplex virus.. The patient was diagnosed as herpes reactivation after the injection of hyaluronic acid.. The patient underwent antiviral therapy with acyclovir 400 mg, 3 times daily for seven days.. After a week of antiviral treatment, the clinical signs improved.. Herpes reactivation after the injection of hyaluronic acid is quite rare but needed sufficient attention of cosmetic practitioners to make the proper diagnosis, prevention and treatment.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Dermal Fillers; Female; Herpes Simplex; Humans; Hyaluronic Acid; Nose; Simplexvirus; Treatment Outcome; Young Adult

Haemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition that can be triggered by infections, malignancies, or auto-immune diseases. Here, we present a patient with rapidly progressive HLH triggered by a herpes simplex virus type 2 (HSV-2) primary infection. The patient was successfully treated with intravenous high-dose acyclovir, immunoglobulins, and dexamethasone. This is the first report of HSV-2-associated HLH in an immunocompetent adult patient.

Topics: Acyclovir; Adult; Herpes Simplex; Herpesvirus 2, Human; Humans; Lymphohistiocytosis, Hemophagocytic

Herpes simplex virus (HSV) hepatitis is a rare condition with a high mortality rate. Immunocompromised individuals, including pregnant women, are the most susceptible. When primary infection occurs during pregnancy, risk for disseminated HSV is greatly increased. Disseminated HSV can manifest in the form of HSV hepatitis.. We aim to review the literature and summarize what is known about HSV hepatitis in pregnancy to aid in the diagnosis and treatment of this condition.. A literature search of PubMed and Web of Science was performed. A total of 237 citations were found. All citations were independently reviewed. Thirty-eight full-text articles were identified and included in this review. Additional data from 1 unpublished case from our institution was included.. Fifty-six cases were included with average gestational age at diagnosis of 30 weeks. Patients presented with a wide variety of gastrointestinal, respiratory, neurologic, and urogenital symptoms. The most common examination findings were fever and abdominal tenderness. Only 18.2% of patients had a vesicular rash. All patients had a transaminitis, and 85% had positive viral cultures. A multitude of treatments were used with the majority of favorable outcomes occurring after treatment with acyclovir.. Although HSV hepatitis is rare, it carries a mortality rate of up to 39% for mothers and neonates. Therefore, it is crucial that HSV hepatitis be included on the differential diagnosis when a patient presents with fever and transaminitis. When HSV hepatitis is suspected, empiric therapy with acyclovir can be initiated with no additional risk to the fetus.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Simplexvirus

Recognition and timely adequate treatment of erythema multiforme remain a major challenge. In this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. The diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histological findings. Clinically, erythema multiforme can be differentiated into isolated cutaneous and combined mucocutaneous forms. Atypical erythema multiforme manifestations include lichenoid or granulomatous lesions as well as lesional infiltrates of T cell lymphoma and histiocytes. Herpes simplex virus infection being the most common cause, other infectious agents like-especially in children-Mycoplasma pneumoniae, hepatitis C virus, Coxsackie virus, and Epstein Barr virus may also trigger erythema multiforme. The second most frequently identified cause of erythema multiforme is drugs. In different studies, e.g., allopurinol, phenobarbital, phenytoin, valproic acid, antibacterial sulfonamides, penicillins, erythromycin, nitrofurantoin, tetracyclines, chlormezanone, acetylsalicylic acid, statins, as well as different TNF-α inhibitors such as adalimumab, infliximab, and etanercept were reported as possible implicated drugs. Recently, cases of erythema multiforme associated with vaccination, immunotherapy for melanoma, and even with topical drugs like imiquimod have been described. In patients with recurrent herpes simplex virus-associated erythema multiforme, the topical prophylactic treatment with acyclovir does not seem to prevent further episodes of erythema multiforme. In case of resistance to one virostatic drug, the switch to an alternative drug, and in patients non-responsive to virostatic agents, the use of dapsone as well as new treatment options, e.g., JAK-inhibitors or apremilast, might be considered.

Topics: Acyclovir; Dapsone; Drug-Related Side Effects and Adverse Reactions; Erythema Multiforme; Herpes Simplex; Histiocytes; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Practice Guidelines as Topic; Simplexvirus; Skin; T-Lymphocytes; Thalidomide

Neonatal herpes simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease.

Topics: Acyclovir; Antiviral Agents; Cesarean Section; Delivery, Obstetric; Disseminated Intravascular Coagulation; Encephalitis, Herpes Simplex; Extraction, Obstetrical; Extraembryonic Membranes; Female; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Keratitis, Herpetic; Labor, Obstetric; Liver Failure; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Respiratory Insufficiency; Risk Factors; Skin Diseases, Viral; Time Factors

Tattooing is a procedure where ink is applied to an area of the skin, mostly intraepidermally (1). This procedure is carried out mainly for aesthetic purposes. Lately, it has been used as a corrective medical procedure following amputation of mammilla. The procedure is aggressive (2), and the fact that skin is punctured many times with the same needle which cannot be fully sterilized may cause infection of the treated area with bacterial, fungal, or viral agents that may lead to health consequences manifesting in the form of verrucae vulgaris, molluscum contagiosum, and herpes simplex. On the other hand, complications such as granulomas, allergic reactions, Koebner phenomenon, lupus erythematosus, psoriasis, lichen ruber planus, hepatitis C, and HIV infections should also be considered as potential consequences of tattooing (3-7). Even systemic reactions have been reported. Herein we describe a case of herpes infection activation after tattooing. Herein we present the case of a 46-year-old woman, employed in the medical sector, with a two-day history of herpes simplex in the labial area that manifested following application of a cosmetic tattoo meant to outline the lips (Figure 1). Two days after tattoo application, the vesicular lesions appeared along the area that was filled with ink, followed by sub-febrile temperature and fever and a subjective feeling of itching initially, followed by burning sensation and pain. The skin signs located on erythematous base were mainly grouped vesicles with sharply demarcated borders. Regional lymphatic nodes, mainly retro auricular, were enlarged. Within 48 hours, the patient was treated with acyclovir tablets in a dose of 800 mg three times a day and an antipyretic. Acyclovir ointment was administered during the first two days, as well as tetracycline ointment after the second day of the eruption. On the fifth day, we observed regression of the skin changes (Figure 2), and complete healing was achieved after one week. We assessed the medical history of the patient, which revealed the following: hypothyreosis due to lobectomy performed for the treatment of toxic adenoma. The patient was under substitutional therapy with 75 mg levothyroxine. The patient had herpes simplex before, and this was the second herpetic eruption. Herpes simplex is caused by a herpes simplex virus (HSV) type-1 infection that is transmitted through droplets of saliva or direct contact with the affected area, for example during kissing (8-10). Hi

Topics: Acyclovir; Administration, Cutaneous; Administration, Oral; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Herpes Simplex; Humans; Middle Aged; Risk Assessment; Tattooing; Tetracycline; Treatment Outcome

The discovery of acyclovir and penciclovir has led to the development of a successful systemic therapy for treating herpes simplex virus infection and varicella-zoster virus infection, and the orally available prodrugs, valacyclovir and famciclovir, have improved antiviral treatment compliance. Acyclovir and penciclovir are phosphorylated by viral thymidine kinase and are incorporated into the DNA chain by viral DNA polymerase, resulting in chain termination. Helicase-primase plays an initial step in DNA synthesis to separate the double strand into two single strands (replication fork) and is a new target of antiviral therapy. The helicase-primase inhibitors (HPIs) pritelivir and amenamevir have novel mechanisms of action, drug resistance properties, pharmacokinetic characteristics, and clinical efficacy for treating genital herpes. The clinical study of amenamevir in herpes zoster has been completed, and amenamevir has been submitted for approval for treating herpes zoster in Japan. The clinical use of HPIs will be the beginning of a new era of anti-herpes therapy.

Topics: Acyclovir; Animals; Antiviral Agents; Clinical Trials as Topic; Guanine; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Oxadiazoles; Simplexvirus

To define a clinically tailored therapeutic strategy for the treatment of viral anterior uveitis (VAU).. A PubMed search spanning the past 5 years was conducted using the MesH-terms "viral anterior uveitis" and "therapy.". The herpes simplex virus (HSV), the varicella zoster virus (VZV), and the cytomegalovirus (CMV) are the predominant pathogens in VAU. Other viruses, including rubella, chikungunya, and zika, have been linked with distinct forms of the disease. Depending on the causative agent and the host immunocompetence, the mainstay treatment for suspected VAU is a combination of topical or systemic antivirals and topical corticosteroids, supplemented with cycloplegics and intraocular-pressure-lowering medication.. Oral acyclovir, valacyclovir, and famciclovir are the mainstay of treatment for HSV- and VZV-induced infections. Brivudin serves as an alternative in insufficiently responsive cases. CMV-induced infections respond well to valganciclovir. A 3- to 12-month course of prophylactic treatment against recurrences is worth considering.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chikungunya Fever; Cytomegalovirus Infections; Eye Infections, Viral; Famciclovir; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Rubella; Uveitis, Anterior; Valacyclovir; Zika Virus Infection

Septic thrombophlebitis of the facial vein (STFN) commonly presents with facial erythema, tenderness, and swelling above the involved vessel. Due to its rarity, diagnosis and treatment remain a challenge. Lemierre syndrome (LS), which consists of a triad of internal jugular vein thrombophlebitis, septicemia, and distant septic emboli, is a more common entity of which physicians are more familiar. Whether tonsillitis-related STFN is actually LS in a different anatomical area and shares the same characteristics is still left to be answered. We present a case of STFN with a review of all cases reported in the literature.

Topics: Acyclovir; Adult; Anti-Bacterial Agents; Antiviral Agents; Face; Herpes Simplex; Humans; Jugular Veins; Lemierre Syndrome; Male; Sepsis; Tomography, X-Ray Computed

Topics: Acyclovir; Animals; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 3, Human; Humans; Varicella Zoster Virus Infection

Newborn infants are a population which is especially susceptible to viral infections that frequently affect the central nervous system. Herpes infections can be transmitted to the foetus and to the newborn infant, and give rise to severe clinical conditions with long-term sensory and cognitive deficits. Two thirds of newborn infants with encephalitis due to herpes simplex virus and half of the children with symptomatic congenital infection by cytomegalovirus develop sequelae, which results in high community health costs in the long term. Fortunately, the better knowledge about these infections gained in recent years together with the development of effective antiviral treatments have improved the patients' prognosis. Valganciclovir (32 mg/kg/day in two doses for six months) prevents the development of hypoacusis and improves the neurological prognosis in symptomatic congenital infection due to cytomegalovirus. Acyclovir (60 mg/kg/day in three doses for 2-3 weeks) prevents the development of severe forms in skin-eyes-mouth herpes disease, and lowers the rate of mortality and sequelae when the disease has disseminated and is located in the central nervous system.. Actualizacion en infecciones herpeticas congenitas y neonatales: infeccion por citomegalovirus y herpes simple.. Los neonatos son una poblacion especialmente susceptible a las infecciones viricas que frecuentemente afectan al sistema nervioso central. Las infecciones herpeticas pueden transmitirse al feto y al recien nacido, y ocasionar cuadros clinicos graves con deficits sensoriales y cognitivos a largo plazo. Dos terceras partes de los neonatos con encefalitis por virus herpes simple y la mitad de los niños con infeccion congenita sintomatica por citomegalovirus desarrollan secuelas, lo cual supone un alto coste sociosanitario a largo plazo. Afortunadamente, el mejor conocimiento de estas infecciones en los ultimos años y el desarrollo de tratamientos antivirales efectivos han mejorado el pronostico de los pacientes. El valganciclovir (32 mg/kg/dia en dos dosis durante seis meses) previene el desarrollo de hipoacusia y mejora el pronostico neurologico en la infeccion congenita sintomatica por citomegalovirus. El aciclovir (60 mg/kg/dia en tres dosis durante 2-3 semanas) previene el desarrollo de formas graves en la enfermedad herpetica cutanea-ocular-oral, y disminuye la mortalidad y las secuelas en la enfermedad diseminada y localizada en el sistema nervioso central.

Topics: Acyclovir; Antiviral Agents; Brain Damage, Chronic; Cytomegalovirus Infections; Early Diagnosis; Female; Fetal Diseases; Ganciclovir; Hearing Loss, Sensorineural; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Valganciclovir

Recurrent meningitis is a rare clinical scenario that can be self-limiting or life threatening depending on the underlying etiology. This review describes the causes, risk factors, treatment, and prognosis for recurrent meningitis. As a general overview of a broad topic, the aim of this review is to provide clinicians with a comprehensive differential diagnosis to aide in the evaluation and management of a patient with recurrent meningitis.. New developments related to understanding the pathophysiology of recurrent meningitis are as scarce as studies evaluating the treatment and prevention of this rare disorder. A trial evaluating oral valacyclovir suppression after HSV-2 meningitis did not demonstrate a benefit in preventing recurrences. The data on prophylactic antibiotics after basilar skull fractures do not support their use. Intrathecal trastuzumab has shown promise in treating leptomeningeal carcinomatosis from HER-2 positive breast cancer. Monoclonal antibodies used to treat cancer and autoimmune diseases are new potential causes of drug-induced aseptic meningitis. Despite their potential for causing recurrent meningitis, the clinical entities reviewed herein are not frequently discussed together given that they are a heterogeneous collection of unrelated, rare diseases. Epidemiologic data on recurrent meningitis are lacking. The syndrome of recurrent benign lymphocytic meningitis described by Mollaret in 1944 was later found to be closely related to HSV-2 reactivation, but HSV-2 is by no means the only etiology of recurrent aseptic meningitis. While the mainstay of treatment for recurrent meningitis is supportive care, it is paramount to ensure that reversible and treatable causes have been addressed for further prevention.

Topics: Acyclovir; Antibodies, Monoclonal; Antiviral Agents; Diagnosis, Differential; Herpes Simplex; Herpesvirus 2, Human; Humans; Meningitis; Meningitis, Aseptic; Prognosis; Recurrence; Secondary Prevention; Valacyclovir; Valine

Identify measures to diagnose, prevent and treat genital herpes infection during pregnancy and childbirth and neonatal infection.. Bibliographic search from Medline, Cochrane Library databases and research of international clinical practice guidelines.. Genital herpes lesion is most often due to HSV2 (LE2). The risk of HSV seroconversion during pregnancy is 1 to 5% (LE2). Genital herpes ulceration during pregnancy in a woman with history of genital herpes corresponds with a recurrence. In this situation, there is no need for virologic confirmation (grade B). In case of genital lesions in a pregnant woman that do not report any genital herpes before, it is recommended to perform a virological confirmation by PCR and HSV type specific IgG (Professional consensus). In case of first episode genital herpes during pregnancy, antiviral treatment with acyclovir (200mg 5 times daily) or valacyclovir (1000mg twice daily) for 5 to 10 days is recommended (grade C). In case of recurrent herpes during pregnancy, antiviral therapy with acyclovir (200mg 5 times daily) or valacyclovir (500mg twice daily) can be administered (grade C). The risk of neonatal herpes is estimated between 25% and 44% in case of initial episode (LE2) and 1% in case of recurrence (LE3) at the time of delivery. Antiviral prophylaxis should be offered for women with first episode genital herpes or recurrent genital herpes during pregnancy from 36 weeks of gestation and until delivery (grade B). In case of a history of genital herpes without episode of recurrence during pregnancy, it is not recommended routinely offer a prophylactic treatment (professional consensus). A cesarean section should be performed if there is a suspicion of first episode genital herpes at the onset of labor (grade B), in the event of premature rupture of the membranes at term (professional consensus), or in case of first episode genital herpes less than 6 weeks before delivery (professional consensus). In case of recurrent genital herpes at the onset of labor, cesarean delivery will be all the more considered if the membranes are intact and vaginal delivery will be all the more considered in case of prolonged rupture of membranes (professional consensus). Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most of the case of neonatal herpes, the mothers have no history of genital herpes (LE 3). In case of suspicion of neonatal herpes, different samples (blood and cerebrospinal fluid) for HSV PCR must be carried out to confirm the diagnosis (professional consensus). Any newborn suspected of neonatal herpes should be treated with intravenous acyclovir (60mg/kgs/day 3 times daily) (grade A) prior to the results of HSV PCR (professional consensus). The duration of the t

Topics: Acyclovir; Antiviral Agents; Cesarean Section; Female; Fetal Membranes, Premature Rupture; Gestational Age; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; MEDLINE; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Risk Factors; Serotyping

To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN).. Literature searches of the PubMed and Cochrane Library databases were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective.. Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear.. Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time.

Topics: Academies and Institutes; Acyclovir; Antiviral Agents; Aqueous Humor; Biomedical Technology; DNA, Viral; Eye Infections, Viral; Foscarnet; Herpes Simplex; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Ophthalmology; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Simplexvirus; United States; Valacyclovir; Valine; Vitrectomy; Vitreous Body

Neonatal herpes simplex virus (HSV) disease is a serious, life-threatening condition that should be considered in neonates with fever, vesicular rash, culture negative sepsis, and/or seizure activity. Because signs and symptoms of neonatal HSV may closely resemble those of bacterial sepsis, a thorough history and appropriate testing are imperative to accurately confirm the diagnosis. Failure to treat vesicular lesions from HSV in the neonate leads to an approximate 75% chance of progression to disseminated disease and/or meningoencephalitis. Therefore, prompt recognition of symptoms and institution of treatment pending results of the investigation are imperative to minimize the high rates of morbidity and mortality associated with this diagnosis. [Pediatr Ann. 2017;46(2):e42-e46.].

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Infant, Newborn; Magnetic Resonance Imaging; Pregnancy Complications, Infectious; Simplexvirus; Tomography, X-Ray Computed

This review on herpes simplex virus type I and type II (HSV‑I, HSV‑II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV‑I infection; HSV-related folliculitis; verrucous HSV‑I and HSV‑II lesions; the role of recurrent HSV‑I infection in burning mouth syndrome; HSV‑I and HSV‑II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV‑I or HSV‑II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV‑I and anti-HSV‑II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV‑I and HSV‑II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.

Topics: Acyclovir; Antiviral Agents; Burning Mouth Syndrome; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Randomized Controlled Trials as Topic; Recurrence; Stomatitis, Herpetic; Vaccination; Virulence; Zoster Sine Herpete

Herpes simplex virus (HSV) types 1 and 2 can cause infections with clinical manifestations ranging from benign and generally self-limiting blisters or sores as seen in labial and genital herpes through to severe and in rare cases even life-threatening infections. At present, approved treatments for herpes simplex virus are almost all nucleoside analogs. Novel antiviral approaches include therapeutic vaccines, with the most advanced having successfully completed Phase 2 clinical development. Moreover, several small molecules approaches are being developed for the treatment of genital or labial HSV infections. Of particular interest are two novel compounds (amenamevir and pritelivir) belonging to the new class of helicase-primase inhibitors with promising Phase 2 data.

Topics: Acyclovir; Antiviral Agents; Clinical Trials, Phase II as Topic; DNA Helicases; DNA Primase; Drug Resistance, Viral; Herpes Genitalis; Herpes Simplex; Herpes Simplex Virus Vaccines; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Oxadiazoles; Pyridines; Sulfonamides; Thiazoles; Viral Proteins

Herpetic lesions most frequently occur on oral and genital areas. However, herpes simplex virus (HSV) can be a rare cause of breast infection. In few published articles, the route of transmission is predominantly from infant to mother. We report two cases about simultaneous mammary and extramammary (oral and genital) herpetic infection in nonlactating women. In both cases, HSV breast lesions were acquired by sexual contacts with partners who were asymptomatic HSV carriers. Through a review of literature, we highlight clinical signs for an early diagnosis. We also emphasize the advantage of the valacyclovir for treating this uncommon pathology.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Simplex; Humans; Mastitis; Valacyclovir; Valine

Aciclovir (ACV) is the first-line drug for the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Long-term administration of ACV for the treatment of severe infections in immunocompromised patients can lead to the development of drug resistance. Furthermore, the emergence of isolates resistant to ACV is increasingly recognized in immunocompetent individuals with herpetic keratitis. This review describes the mechanisms involved in drug resistance for HSV and VZV, the laboratory diagnosis and management of patients with infections refractory to ACV therapy.. Genotypic testing is more frequently performed for the diagnosis of infections caused by drug-resistant HSV or VZV isolates. Molecular biology-based systems for the generation of recombinant viruses have been developed to link unknown mutations with their drug phenotypes. Fast and sensitive methods based on next-generation sequencing will improve the detection of heterogeneous viral populations of drug-resistant viruses and their temporal changes during antiviral therapy, which could allow better patient management. Novel promising compounds acting on targets that differ from the viral DNA polymerase are under clinical development.. Antiviral drug resistance monitoring for HSV and VZV is required for a rational use of antiviral therapy in high-risk populations.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Immune Tolerance; Simplexvirus; Varicella Zoster Virus Infection

The epidemiology of cutaneous herpes simplex infection (CHSI) has dramatically changed over the past several decades. Valaciclovir is one of a new generation of antiviral medications that has expanded treatment options for the most common cutaneous manifestations of herpes simplex virus. However, the efficacy and safety of formulations with different doses of valaciclovir remain unclear.. To carry out hospital risk management by ascertaining the incidence and risk of CHSI in patients during treatment with varying doses of valaciclovir.. The PubMed, MEDLINE and Web of Science electronic databases were systematically searched from database inception to date of searching. Efficacy of drug treatment was measured by average easement score (AES). Safety was characterized as the proportion of patients with drug adverse reactions (DARs) such as fever, dizziness, headache, anxiety, irritability and yellowing of the skin. Outcomes for continuous and dichotomous data were estimated by standard mean difference (SMD) and risk ratio (RR), respectively.. Five randomized controlled trials involving 1753 randomized participants for efficacy assessment and 1874 randomized participants for safety assessment were identified. Valaciclovir dose increasing from 1000 mg/day improved AES only moderately, but significantly promoted the incidence of DARs. Twice-daily treatment showed no increase in therapeutic effect but greatly increased DAR incidence. The valaciclovir dose that produced a reduction in AES was 1000 mg/day: SMD = -0.73 (95% CI -0.98 to 0.48; P < 0.01) and RR = 0.95 (95% CI 0.81-1.09; P < 0.002).. Increasing the daily dose of valaciclovir does not substantially improve therapeutic efficacy for CHSI but may raise DAR incidence. Drug doses of 1000 and 2000 mg/day show no significant difference in efficacy scores, but the latter exhibits a higher incidence of DARs. The dose-dependent, long-term efficacy and safety of valaciclovir remain to be explored.

Topics: Acyclovir; Antiviral Agents; Dose-Response Relationship, Drug; Herpes Simplex; Humans; Risk Management; Valacyclovir; Valine

The seminal discovery of acyclovir 40 years ago heralded the modern era of truly selective antiviral therapies and this drug remains the therapy of choice for herpes simplex virus infections. Yet by modern standards, its antiviral activity is modest and new drugs against novel molecular targets such as the helicase-primase have the potential to improve clinical outcome, particularly in high-risk patients. A brief synopsis of current therapies for these infections and clinical need is provided to help provide an initial perspective. The function of the helicase-primase complex is then summarized and the development of new inhibitors of the helicase-primase complex, such as pritelivir and amenamevir, is discussed. We review their mechanism of action, propensity for drug resistance, and pharmacokinetic characteristics and discuss their potential to advance current therapeutic options. Strategies that include combinations of these inhibitors with acyclovir are also considered, as they will likely maximize clinical efficacy.

Topics: Acyclovir; Animals; Antiviral Agents; DNA Helicases; DNA Primase; Drug Design; Drug Resistance, Viral; Herpes Simplex; Humans; Molecular Targeted Therapy; Oxadiazoles; Pyridines; Sulfonamides; Thiazoles; Viral Proteins

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are highly prevalent viruses capable of establishing lifelong infection. Genital herpes in women of childbearing age represents a major risk for mother-to-child transmission (MTCT) of HSV infection, with primary and first-episode genital HSV infections posing the highest risk. The advent of antiviral therapy with parenteral acyclovir has led to significant improvement in neonatal HSV disease mortality. Further studies are needed to improve the clinician's ability to identify infants at increased risk for HSV infection and prevent MTCT, and to develop novel antiviral agents with increased efficacy in infants with HSV infection.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Keratitis, Herpetic; Male; Pregnancy; Pregnancy Complications, Infectious

Neonatal fungal and viral infections are associated with mortality and neurologic impairment among survivors. Advances in pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial medications have led to improved dosing guidance for neonates. This article discusses the basic PK/PD properties and dosing of the most common antifungal and antiviral medications used in neonates.

Topics: Acyclovir; Amphotericin B; Antifungal Agents; Antiviral Agents; Candidiasis, Invasive; Cytomegalovirus Infections; Deoxycholic Acid; Drug Combinations; Fluconazole; Ganciclovir; Herpes Simplex; Humans; Infant; Infant, Newborn; Mycoses; Practice Guidelines as Topic; Pregnancy Complications, Infectious; Valganciclovir; Virus Diseases

Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy.. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy.. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies.. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains.. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures.. Eleven trials, including 2883 participants, met the inclusion criteria and are included in the final analysis. We added four studies to the previous review for this update. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found no significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.47 to 1.02, n = 1715). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used (RR 0.64, 95% CI 0.41 to 0.99, n = 478). The outcome for the participants receiving corticosteroids alone was significantly better than for those receiving antivirals alone (RR 2.09, 95% CI 1.36 to 3.20, n = 1169). The treatment effect of placebo was significantly lower than that of antivirals plus corticosteroids (RR 0.56, 95% CI 0.41 to 0.76, n = 658). Antivirals alone had a non-significant detrimental effect on the outcome compared with placebo (RR 1.10, 95% CI 0.87 to 1.40, n = 658). Motor synkinesis or crocodile tearsIn three trials comparing antivirals and corticosteroids with corticosteroids and placebo that assessed this outcome, we found a significant difference in long-term sequelae in favour or antivirals plus corticosteroids (RR 0.73, 95% CI 0.54 to 0.99, n = 869). Three trials comparing antivirals alone with corticosteroids alone investigating this outcome showed fewer sequelae with corticosteroids (RR 1.44, 95% CI 1.11 to 1.85, n = 873). We found no data on long-term sequelae for other comparisons. Adverse events Adverse event data were available in three studies giving comparison data on 1528 participants. None of the four comparisons (antivirals plus corticosteroids versus corticosteroids plus placebo or no treatment; antivirals versus corticosteroids; antivirals plus corticosteroids versus placebo; antivirals versus placebo) showed significant differences in adverse events between treatment and control arms. We could find no correlation with specific treatment within these results.. Moderate-quality evidence from randomised controlled trials showed no additional benefit from the combination of antivirals with corticosteroids compared to corticosteroids alone or with placebo, and no benefit from antivirals alone compared to placebo, for the treatment of Bell's palsy. Moderate-quality evidence showed a small but just significant benefit of combination therapy compared with corticosteroids alone in severe Bell's palsy. We found no significant increase in adverse events from the use of antivirals compared with either placebo or corticosteroids.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Bell Palsy; Drug Therapy, Combination; Herpes Simplex; Humans; Prednisolone; Randomized Controlled Trials as Topic; Valacyclovir; Valine

Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy.. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy.. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies.. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains.. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures.. Eleven trials, including 2883 participants, met the inclusion criteria and are included in the final analysis. We added four studies to the previous review for this update. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found no significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.47 to 1.02, n = 1715). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used (RR 0.64, 95% CI 0.41 to 0.99, n = 478). The outcome for the participants receiving corticosteroids alone was significantly better than for those receiving antivirals alone (RR 2.09, 95% CI 1.36 to 3.20, n = 1169). The treatment effect of placebo was significantly lower than that of antivirals plus corticosteroids (RR 0.56, 95% CI 0.41 to 0.76, n = 658). Antivirals alone had a non-significant detrimental effect on the outcome compared with placebo (RR 1.10, 95% CI 0.87 to 1.40, n = 658). Motor synkinesis or crocodile tearsIn three trials comparing antivirals and corticosteroids with corticosteroids and placebo that assessed this outcome, we found a significant difference in long-term sequelae in favour of antivirals plus corticosteroids (RR 0.73, 95% CI 0.54 to 0.99, n = 869). Three trials comparing antivirals alone with corticosteroids alone investigating this outcome showed fewer sequelae with corticosteroids (RR 1.44, 95% CI 1.11 to 1.85, n = 873). We found no data on long-term sequelae for other comparisons. Adverse events Adverse event data were available in three studies giving comparison data on 1528 participants. None of the four comparisons (antivirals plus corticosteroids versus corticosteroids plus placebo or no treatment; antivirals versus corticosteroids; antivirals plus corticosteroids versus placebo; antivirals versus placebo) showed significant differences in adverse events between treatment and control arms. We could find no correlation with specific treatment within these results.. Moderate-quality evidence from randomised controlled trials showed no additional benefit from the combination of antivirals with corticosteroids compared to corticosteroids alone for the treatment of Bell's palsy of various degrees of severity. Moderate-quality evidence showed a small but just significant benefit of combination therapy compared with corticosteroids alone in severe Bell's palsy. Corticosteroids alone were more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no benefit from antivirals alone over placebo.Moderate-quality evidence indicated that the combination of antivirals and corticosteroids reduced sequelae of Bell's palsy compared with corticosteroids alone.We found no significant increase in adverse events from the use of antivirals compared with either placebo or corticosteroids, based on moderate-quality evidence.

Topics: 2-Aminopurine; Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Bell Palsy; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Humans; Prednisolone; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Bell Palsy; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Humans; Prednisolone; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. This review was first published in 2001 and revised several times, most recently in 2009. This version replaces an update of the review in Issue 7 of the Cochrane Library subsequently withdrawn because of an ongoing investigation into the reliability of data from an included study.. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy.. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies.. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains.. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures.. Ten trials, including 2280 participants, met the inclusion criteria and are included in the final analysis. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found a significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.39 to 0.97, n = 1315). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used, compared to corticosteroids alone (RR 0.64, 95% CI 0.41 to 0.99, n = 478). The outcome for the participants receiving corticosteroids alone was significantly better than for those receiving antivirals alone (RR 2.82, 95% CI 1.09 to 7.32, n = 768). The treatment effect of placebo was significantly lower than that of antivirals plus corticosteroids (RR 0.56, 95% CI 0.41 to 0.76, n = 658). Antivirals alone produced no benefit compared with placebo (RR 1.10, 95% CI 0.87 to 1.40, n = 658). Motor synkinesis or crocodile tearsIn two trials comparing antivirals and corticosteroids with corticosteroids and placebo that assessed this outcome, we found a significant difference in long-term sequelae in favour of antivirals plus corticosteroids (RR 0.56, 95% CI 0.36 to 0.87, n = 469). Two trials comparing antivirals alone with corticosteroids alone investigating this outcome showed fewer sequelae with corticosteroids (RR 1.52, 95% CI 1.08 to 2.12, n = 472). We found no data on long-term sequelae for other comparisons. Adverse events Adverse event data were available in three studies giving comparison data on 1528 participants. None of the four comparisons (antivirals plus corticosteroids versus corticosteroids plus placebo or no treatment; antivirals versus corticosteroids; antivirals plus corticosteroids versus placebo; antivirals versus placebo) showed significant differences in adverse events between treatment and control arms. We could find no correlation with specific treatment within these results.. Low-quality evidence from randomised controlled trials showed a benefit from the combination of antivirals with corticosteroids compared to corticosteroids alone for the treatment of Bell's palsy of various degrees of severity. Low-quality evidence showed a benefit of combination therapy compared with corticosteroids alone in severe Bell's palsy. Corticosteroids alone were more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no benefit from antivirals alone over placebo.Moderate-quality evidence indicated that the combination of antivirals and corticosteroids reduced sequelae of Bell's palsy compared with corticosteroids alone.We found no significant increase in adverse events from the use of antivirals compared with either placebo or corticosteroids, based on low-quality evidence.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Bell Palsy; Drug Therapy, Combination; Herpes Simplex; Humans; Prednisolone; Randomized Controlled Trials as Topic; Valacyclovir; Valine

Necrosis retiniana aguda por virus herpes simple tipo 1 a los tres años de una encefalitis herpetica.

Topics: Acyclovir; Antiviral Agents; Aspirin; Cataract Extraction; Causality; Drug Therapy, Combination; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Methylprednisolone; Middle Aged; Recurrence; Retinal Detachment; Retinal Hemorrhage; Retinal Necrosis Syndrome, Acute; Time Factors; Valacyclovir; Valine; Vitrectomy

Herpes simplex virus (HSV) hepatitis is an uncommon cause of liver failure, but may have a dramatic outcome. We herein present a case report of a liver graft infection by HSV-1 associated with liver failure and encephalitis. A complete hospital chart review of the case and a literature search were undertaken. Literature review suggests that herpes simplex acute liver failure is rare and associated with a poor prognosis, even with early treatment. Novel diagnostic and preventive approaches need to be instituted.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Fatal Outcome; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 1, Human; Humans; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Transplants

Herpes simplex virus is a common virus that causes a variety of clinical presentations ranging from mild to life-threatening. Orolabial and genital herpes are common disorders that can often be managed in an outpatient setting; however, some patients do present to the emergency department with those conditions, and emergency clinicians should be aware of possible complications in the pediatric population. Neonatal herpes is a rare disorder, but prompt recognition and initiation of antiviral therapy is imperative, as the morbidity and mortality of the disease is high. Herpes encephalitis is an emergency that also requires a high index of suspicion to diagnose. Herpes simplex virus is also responsible for a variety of other clinical presentations, including herpes gladiatorum, herpetic whitlow, eczema herpeticum, and ocular herpes. This issue reviews the common clinical presentations of the herpes simplex virus, the life-threatening infections that require expedient identification and management, and recommended treatment regimens.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Infant, Newborn; Male; Pregnancy Complications, Infectious

Forty years after the discovery of acyclovir (ACV), it remains the mainstay of therapy for herpes simplex virus (HSV) infections. Since then, other antiviral agents have also been added to the armamentarium for these infections but ACV remains the therapy of choice. As the efficacy of ACV is reassessed, however, it is apparent that a therapy with increased efficacy, reduced potential for resistance, and improved pharmacokinetics would improve clinical outcome, particularly in high risk patients. Inhibitors of viral targets other than the DNA polymerase, such as the helicase primase complex, are of particular interest and will be valuable as new therapeutic approaches are conceived. This review focuses on currently approved HSV therapies as well as new systemic therapies in development.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Drug Therapy; Herpes Simplex; Humans; Simplexvirus

This review starts with a brief description of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), the clinical diseases they cause, and the continuing clinical need for antiviral chemotherapy. A historical overview describes the progress from the early, rather toxic antivirals to acyclovir (ACV) which led the way for its prodrug, valacyclovir, to penciclovir and its prodrug, famciclovir (FCV). These compounds have been the mainstay of HSV therapy for two decades and have established a remarkable safety record. This review focuses on these compounds, the preclinical studies which reveal potentially important differences, the clinical trials, and the clinical experience through two decades. Some possible areas for further investigation are suggested. The focus shifts to new approaches and novel compounds, in particular, the combination of ACV with hydrocortisone, known as ME609 or zovirax duo, an HSV helicase-primase inhibitor, pritelivir (AIC316), and CMX001, the cidofovir prodrug for treating resistant HSV infection in immunocompromised patients. Letermovir has established that the human cytomegalovirus terminase enzyme is a valid target and that similar compounds could be sought for HSV. We discuss the difficulties facing the progression of new compounds. In our concluding remarks, we summarize the present situation including a discussion on the reclassification of FCV from prescription-only to pharmacist-controlled for herpes labialis in New Zealand in 2010; should this be repeated more widely? We conclude that HSV research is emerging from a quiescent phase.

Topics: Acyclovir; Antiviral Agents; Drug Discovery; Drug Resistance, Viral; Guanine; Herpes Simplex; Humans; Simplexvirus

The febrile young infant is commonly encountered in the emergency department, and the incidence of serious bacterial infection in these patients is as high as 15%. Undiagnosed bacterial infections such as meningitis and bacteremia can lead to overwhelming sepsis and death or neurologic sequelae. Undetected urinary tract infection can lead to pyelonephritis and renal scarring. These outcomes necessitate the evaluation for a bacterial source of fever; therefore, performance of a full sepsis workup is recommended to rule out bacteremia, urinary tract infection, and bacterial meningitis in addition to other invasive bacterial diseases including pneumonia, bacterial enteritis, cellulitis, and osteomyelitis. Parents and emergency clinicians often question the necessity of this approach in the well-appearing febrile young infant, and it is important to understand and communicate the evidence that guides the approach to these patients. Recent studies examining the risk of serious bacterial infection in young infants with bronchiolitis and the role of viral testing in the febrile young infant will also be discussed in this review.

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Biomarkers; Clinical Laboratory Techniques; Critical Pathways; Diagnosis, Differential; Emergency Medicine; Emergency Service, Hospital; Fever; Herpes Simplex; Humans; Infant; Physical Examination; Radiography, Thoracic; Risk Management

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Pregnancy; Pregnancy Complications, Infectious

Acyclovir (ACV) is the first-line treatment for the management of herpes simplex virus 1 (HSV-1) and 2 (HSV-2) diseases. Long-term administration of the drug for the treatment of chronic infections in the immunocompromised host can lead to the development of ACV-resistance. This review provides an update of the mutations linked to drug-resistance and issues to be considered in the management of HSV infections refractory to antiviral therapy.. Recent data have shown that HSV drug-resistance should be taken into account not only in immunocompromised individuals but also in immunocompetent persons when HSV infections involve 'immune-privileged sites'. Thus, drug-resistance typing is recommended in cases of ACV unresponsive herpetic keratitis and herpes simplex encephalitis. Several issues regarding HSV drug-resistance were highlighted by recent studies. Phenotypic and genotypic antiviral resistance may vary not only from different compartments but also over time, highlighting the importance of characterizing longitudinal HSV isolates from all sites. Combination therapy should be considered when viruses with distinct phenotype/genotype are identified at one or at distinct body sites.. Surveillance of HSV drug-resistance is highly recommended in immunocompromised patients and in immunocompetent individuals with infections implicating 'immune-privileged sites' to rationally adapt antiviral treatment.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Humans; Immunocompetence; Immunocompromised Host

Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Cytomegalovirus Retinitis; Eye Infections, Viral; Famciclovir; Fluorescein Angiography; Ganciclovir; Herpes Simplex; Humans; Laser Coagulation; Retinal Necrosis Syndrome, Acute; Valacyclovir; Valganciclovir; Valine

Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections.

Topics: Acyclovir; Amino Acid Sequence; Guanine; Herpes Simplex; Humans; Molecular Sequence Data; Patents as Topic; Prodrugs; Simplexvirus; Valacyclovir; Valine

Herpes simplex virus (HSV) prophylaxis may be underutilized in cosmetic surgery at a time when cosmetic procedures are increasing. Our goal is to review the data regarding HSV prophylaxis in order to remind cosmetic surgeons when to consider adding this regimen to their patient perioperative care.

Topics: Acyclovir; Antiviral Agents; Dermabrasion; Drug Utilization; Herpes Labialis; Herpes Simplex; Humans; Postoperative Complications; Simplexvirus; Surgery, Plastic

Parenteral therapy of viral infections of the newborn and infant began with vidarabine (adenine arabinoside) for the treatment of neonatal herpes simplex virus (HSV) infections in the early 1980s. Acyclovir has become the treatment of choice for neonatal HSV infections and a variety of other herpesvirus infections. Ganciclovir is beneficial for the treatment of congenital cytomegalovirus (CMV) infections involving the central nervous system (CNS). This article reviews the use of acyclovir and ganciclovir in the treatment of neonatal HSV and congenital CMV infections. A brief summary precedes a detailed discussion of available established and alternative therapeutics.

Topics: Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Drug Interactions; Female; Ganciclovir; Herpes Simplex; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy

Topics: Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Diagnostic Imaging; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Lymphocyte Count; Male; Polymerase Chain Reaction; Spinal Puncture

Neonatal HSV is most commonly transmitted at the time of delivery with the risk being dramatically higher if the mother has first-episode genital HSV and does not have an elective Cesarean section. Maternal HSV type-specific serology can be used to differentiate first-episode from recurrent infection in this setting, allowing for use of empiric acyclovir for the highest risk infants. There is a need for new strategies as current methods of prevention of transmission of HSV to neonates have limited effectiveness, as they do not account for the fact that the majority of transmission occurs from asymptomatic women. After transmission has occurred, early recognition of neonatal HSV improves the prognosis. Diagnosis needs to be considered in all infants who develop vesicles, unexplained seizures, or possible sepsis in the first 5 weeks of life.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious

Herpes simplex viruses (HSV) type 1 and type 2 are responsible for recurrent orolabial and genital infections. The standard therapy for the management of HSV infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valacyclovir and famciclovir. These compounds are phosphorylated by the viral thymidine kinase (TK) and then by cellular kinases. The triphosphate forms selectively inhibit the viral DNA polymerase (DNA pol) activity. Drug-resistant HSV isolates are frequently recovered from immunocompromised patients but rarely found in immunocompetent subjects. The gold standard phenotypic method for evaluating the susceptibility of HSV isolates to antiviral drugs is the plaque reduction assay. Plaque autoradiography allows the associated phenotype to be distinguished (TK-wild-type, TK-negative, TK-low-producer, or TK-altered viruses or mixtures of wild-type and mutant viruses). Genotypic characterization of drug-resistant isolates can reveal mutations located in the viral TK and/or in the DNA pol genes. Recombinant HSV mutants can be generated to analyze the contribution of each specific mutation with regard to the drug resistance phenotype. Most ACV-resistant mutants exhibit some reduction in their capacity to establish latency and to reactivate, as well as in their degree of neurovirulence in animal models of HSV infection. For instance, TK-negative HSV mutants establish latency with a lower efficiency than wild-type strains and reactivate poorly. DNA pol HSV mutants exhibit different degrees of attenuation of neurovirulence. The management of ACV- or PCV-resistant HSV infections includes the use of the pyrophosphate analogue foscarnet and the nucleotide analogue cidofovir. There is a need to develop new antiherpetic compounds with different mechanisms of action.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Guanine; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Microbial Sensitivity Tests; Mutation; Nucleosides; Prevalence; Viral Plaque Assay

Herpes esophagitis (HE) is common in immunosuppressed patients, but has rarely been reported in immunocompetent individuals, in whom it appears to be a self-limited illness. We describe 3 new cases of HE in otherwise healthy patients seen in our hospital within the last 5 years. We performed a comprehensive review of the previously reported cases of HE in immunocompetent adults and adolescents in the English and Spanish literature. We analyzed the clinical features, treatment, and outcome of this entity. A total of 56 patients were included (39 men and 17 women), with a mean age of 35 years. The most common clinical manifestations were odynophagia (60.7%), fever (51.8%), and retrosternal chest pain (46.4%). A prodrome of upper respiratory symptoms and concurrent orolabial herpetic lesions were present in 26.8% and 25% of cases, respectively. Gastrointestinal bleeding was a rare complication (5.3%). Endoscopy revealed multiple ulcers in most cases (58.9%), typically involving the distal or mid-esophagus (83%). The diagnosis was confirmed by histopathologic examination in 40 cases (71.4%), by tissue viral culture in 21 (37.5%), and by detection of viral genome in esophageal samples in 4 cases (7.1%). Herpes simplex virus type 1 (HSV-1) was identified in 27 cases and herpes simplex virus type 2 (HSV-2) only in 1 case. Serology was consistent with a primary infection in 11 of the 25 evaluable cases (44%). Acyclovir therapy was used in 45.4% of patients. The outcome was favorable in all cases, although an esophageal perforation occurred in 1 patient. HE is a rare but well-defined entity in healthy adults and adolescents, and is probably underdiagnosed. A high degree of suspicion and a prompt endoscopic examination are required for the diagnosis. It is usually a self-limited infection, but early treatment with acyclovir may hasten the resolution of symptoms. Nevertheless, the benefit of antiviral therapy remains unknown.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Esophagitis; Female; Herpes Simplex; Humans; Immunocompromised Host; Male; Middle Aged

Peripheral injury of the facial nerve is a frequent disorder. It is a stressful situation for the patient and it is functionally hazardous for the cornea. Facial palsy is due to a lesion involving the facial pontine nucleus or the nerve trunk in its route from the pontocerebellar angle to the parotid. The idiopathic facial paralysis or Bell's palsy (BP) is the most common cause but acute facial palsy can also be due to tumors. A rigorous clinical history and examination must be performed to guide the additional biological, radiological and cochleovestibular investigations in order to reach the diagnosis. The pathophysiology of BP remains unclear, but seems to be due to the reactivation of Herpes simplex virus type 1 within the intrapetrous pathway of facial nerve. The treatment remains controversial but, for most of the authors, consists of early administration of corticosteroids with or without antiviral agents. Ninety percent of the patients recover normal facial function with this treatment. The severe BP resulting in hemifacial spasm must be quickly identified by electrophysiological testing. They need appropriate rehabilitation and for some authors facial nerve surgical decompression in emergency.

Topics: Acyclovir; Administration, Oral; Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Antiviral Agents; Audiometry; Bell Palsy; Disease Models, Animal; Electromyography; Glucocorticoids; Herpes Simplex; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Mice; Multicenter Studies as Topic; Prednisone; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors

Herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted diseases worldwide. The first time infection of the mother may lead to severe illness in pregnancy and may be associated with virus transmission from mother to foetus/newborn. Since the incidence of this sexually transmitted infection continues to rise and because the greatest incidence of herpes simplex virus infections occur in women of reproductive age, the risk of maternal transmission of the virus to the foetus or neonate has become a major health concern. On these purposes the Authors of this review looked for the medical literature and pertinent publications to define the status of art regarding the epidemiology, the diagnosis, the therapy and the prevention of HSV in pregnant women and neonate. Special emphasis is placed upon the importance of genital herpes simplex virus infection in pregnancy and on the its prevention to avoid neonatal HSV infections.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Humans; Incidence; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious

The most common disorder of the facial nerve is acute idiopathic facial paralysis or Bell's palsy and there may be significant morbidity or incomplete recovery associated with severe cases.. To assess the efficacy of aciclovir or similar agents for treating Bell's palsy.. We searched the Cochrane Neuromuscular Disease Group register (searched April 2003), MEDLINE (from January 1966 to April 2003), EMBASE (from January 1980 to April 2003) and LILACS (from January 1982 to April 2003). We also contacted authors of identified trials.. Randomised or quasi-randomised trials of aciclovir or valaciclovir therapy, alone or in combination with any other drug, in patients with Bell's palsy.. We identified six randomised trials.. Three studies met our inclusion criteria, including 246 patients. One study evaluated aciclovir with corticosteroid versus corticosteroid alone, another study evaluated aciclovir alone versus corticosteroid and a further study evaluated valaciclovir with corticosteroid versus corticosteroid alone or versus placebo alone. Incomplete recovery after one year: data were not available. An analysis was performed on data reported at the end of the study period in each trial. The results from one study four months after the start of treatment significantly favoured the treatment group, whilst the results of the study three months after the start of treatment significantly favoured the control group. The results from the second study at four months showed no statistically significant difference between the three groups.Adverse events: relevant data were not reported in any of the three trials.Complete facial paralysis six months after start of treatment: only one patient had complete paralysis upon entering one of the studies. This patient was assigned to the control group and the level of recovery attained was not reported.Motor synkinesis or crocodile tears one year after start of treatment: data were available up to a maximum of four months after onset of paralysis. One study reported a significant difference between the treatment groups in favour of the aciclovir plus corticosteroid group over corticosteroid alone, another demonstrated an inconclusive result with no difference between the aciclovir and corticosteroid. The third study did not comment upon these sequelae.. More data are needed from a large multicentre randomised controlled and blinded study with at least 12 months' follow up before a definitive recommendation can be made regarding the effect of aciclovir or valaciclovir on Bell's palsy. Two trials, one with 551 participants comparing prednisolone with acyclovir with both and with neither, another with 221 participants comparing prednisolone and valacyclovir with prednisolone and placebo have just been published and will be included in an update of this review.

Topics: Acyclovir; Antiviral Agents; Bell Palsy; Herpes Simplex; Humans; Randomized Controlled Trials as Topic; Valine

The development of novel strategies to eradicate herpes simplex virus (HSV) is a global public health priority. While acyclovir and related nucleoside analogues provide successful modalities for treatment and suppression, HSV remains highly prevalent worldwide and is a major cofactor fueling the HIV epidemic. HSV is the predominant cause of genital ulcerative disease, and neonatal and sporadic infectious encephalitis. Asymptomatic shedding, which occurs more frequently than previously appreciated, contributes to viral transmission. Acyclovir resistance may be problematic for immunocompromised patients and highlights the need for new safe and effective agents. Ideally, vaccines to prevent infection, drugs to inhibit the establishment of or reactivation from latency, or vaginal microbicides to prevent sexual and perinatal transmission are needed to control the epidemic. This review summarizes current therapeutic options and strategies in development.

Topics: Acyclovir; Anti-Infective Agents; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpes Simplex; HIV Infections; Humans; Infant, Newborn; Keratitis, Herpetic; Male; Pregnancy; Stomatitis, Herpetic; Syndrome; Viral Vaccines

Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae.. To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression.. Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and reference lists of published trials.. Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included.. Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI).. Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period.. There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.

Topics: Acyclovir; Antiviral Agents; Developmental Disabilities; Disease Progression; Herpes Simplex; Humans; Infant, Newborn; Randomized Controlled Trials as Topic; Vidarabine

Epidemiological studies have demonstrated that HIV-1 and herpes simplex virus-2 (HSV-2) are responsible for two epidemics and that, by overlapping in risk populations, they reinforce the spreading of both HIV-1 disease and genital herpes. Randomized controlled trials have investigated whether acyclovir (ACV), a synthetic drug designed to suppress herpes viruses, might provide an inexpensive and safe way to drastically reduce HIV-1 spreading around the world. The controversial results of these trials are reviewed below in light of the recent discovery of the direct suppression of HIV-1 by ACV.. Recent studies have shown that although ACV therapy does not prevent HIV-1 transmission, it decreases plasma, genital, rectal, and seminal HIV-1 RNA levels. The decrease of HIV-1 load has been believed to be the result of an indirect mechanism and explained by reduction of HSV-2-mediated inflammation. The discovery of the direct inhibitory activity of ACV on HIV-1 reverse transcriptase brings new insights into the interpretation of these results. Also, it is important to understand why HSV-2-suppressive therapy with ACV did not reduce HIV-1 acquisition/transmission.. The direct suppression of HIV-1 by ACV activated by coinfecting HSV-2 may in part explain the ACV-induced decrease of HIV load reported in several clinical trials. If this is the case, other herpes viruses capable of ACV activation may contribute to this effect. New basic studies and new targeted clinical trials are needed to understand whether ACV therapy can also be beneficial for HSV-2-negative patients. These studies will show whether ACV therapy should be included in HIV-1 treatment as well as whether ACV-based drugs specifically targeting HIV-1 can be developed.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; HIV Infections; HIV Reverse Transcriptase; HIV-1; Humans; Randomized Controlled Trials as Topic; Viral Load

Antiviral prophylaxis is commonly prescribed to haematological cancer patients. We conducted a systematic review and meta-analysis to quantify its overall benefit in specific clinical scenarios.. Randomised controlled trials assessing antiviral prophylaxis versus placebo, no treatment, pre-emptive treatment or another antiviral drug were included. Patients undergoing haematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for acute leukaemia or high-grade lymphoma were included. No restrictions on language, year or publication status were applied. Overall mortality, herpes simplex virus (HSV) and cytomegalovirus (CMV) diseases were assessed as primary outcomes. Pooled relative risks (RRs) and numbers needed to treat (NNT) with 95% confidence intervals (CI) are reported.. HSCT was the condition assessed in 22 trials and intensive chemotherapy in 5 trials. In the pre-engraftment setting of autologous or allogeneic HSCT, antiviral prophylaxis (mainly acyclovir for HSV seropositive recipients) significantly reduced HSV (NNT 2, 2-2, control event rate (CER) 61.9%) and CMV disease, with no effect on overall mortality. In the allogeneic post-engraftment setting (mainly CMV-seropositive recipients/donors), antiviral prophylaxis resulted in a significant reduction in overall mortality, RR 0.79 (0.65-0.95), NNT 12 (7-50, CER 39.4%) and all viral-related outcomes. In this setting, acyclovir significantly reduced overall mortality (RR 0.71, 0.53-0.96, 4 trials) and ganciclovir/maribavir significantly reduced CMV disease (RR 0.26, 0.14-0.48, 5 trials). During chemotherapy, acyclovir significantly decreased HSV disease (NNT 3, 2-4, CER 37.4%) and infection rates, with no effect on mortality.. Antiviral prophylaxis reduced mortality with a small NNT in the post-engraftment setting of allogeneic HSCT. In the pre-engraftment phase and during chemotherapy only viral-related morbidity was reduced.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Benzimidazoles; Cytomegalovirus Infections; Ganciclovir; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Oral Ulcer; Randomized Controlled Trials as Topic; Ribonucleosides; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious

Antiviral agents against herpes simplex virus are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but their effectiveness is uncertain. Significant morbidity can be associated with severe cases.. This review addresses the effect of antiviral therapy on Bell's palsy.. We updated the search of the Cochrane Neuromuscular Disease Group Trials Register (December 2008), MEDLINE (from January 1966 to December 8 2008), EMBASE (from January 1980 to December 8 2008) and LILACS (from January 1982 to December 2008).. Randomized trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy.. Twenty-three papers were selected for consideration.. Seven trials including 1987 participants met the inclusion criteria, adding five studies to the two in the previous review.Incomplete recovery at one year. There was no significant benefit in the rate of incomplete recovery from antivirals compared with placebo (n = 1886, RR 0.88, 95% CI 0.65 to 1.18). In meta-analyses with some unexplained heterogeneity, the outcome with antivirals was significantly worse than with corticosteroids (n = 768, RR 2.82, 95% CI 1.09 to 7.32) and the outcome with antivirals plus corticosteroids was significantly better than with placebo (n = 658, RR 0.56, 95% CI 0.41 to 0.76).Motor synkinesis or crocodile tears at one year. In single trials, there was no significant difference in long term sequelae comparing antivirals and corticosteroids with corticosteroids alone (n = 99, RR 0.39, 95% CI 0.14 to 1.07) or antivirals with corticosteroids (n = 101, RR 1.03, 95% CI 0.51 to 2.07).Adverse events.There was no significant difference in rates of adverse events between antivirals and placebo (n = 1544, RR 1.06, 95% CI 0.81 to 1.38), between antivirals and corticosteroids (n = 667, RR 0.96, 95% CI 0.65 to 1.41) or between the antiviral-corticosteroid combination and placebo (n = 658, RR 1.15, 95% CI 0.79 to 1.66).. High quality evidence showed no significant benefit from anti-herpes simplex antivirals compared with placebo in producing complete recovery from Bell's palsy. Moderate quality evidence showed that antivirals were significantly less likely than corticosteroids to produce complete recovery.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Bell Palsy; Drug Therapy, Combination; Herpes Simplex; Humans; Prednisolone; Randomized Controlled Trials as Topic; Valacyclovir; Valine

Acute liver failure is a life threatening disease mostly triggered by drug-induced or toxic liver damage or viral hepatitis. Herpes Simplex virus (HSV) hepatitis is rare and accounts for only 1% of all acute liver failures. The importance of HSV-induced acute liver failure is based on its extremely severe clinical course with lethality rates of almost 75%. HSV hepatitis is just one of several clinical manifestations of HSV sepsis leading more frequently to encephalitis, pneumonia and esophagitis. Local herpes infection or recurrence of dermal lesions (herpes labialis, herpes genitalis), however, is common and account for the high prevalence of HSV-1 or HSV-2 infection in adults. Another rare entity is visual dissemination, which mostly affects immunocompromised patients. Compromised cellular immunity is a major risk factor for HSV sepsis because of either primary infection or reactivation of occult chronic HSV infection. Delayed diagnosis without antiviral therapy significantly contributes to the unfavorable outcome. Typically, anicteric hepatitis is seen in patients with HSV hepatitis. Because of its low incidence, however, and the lack of dermal manifestations, HSV hepatitis is rarely considered in the context of acute liver failure. In addition, diagnostic tests might not always be available. Therefore, it is a generally accepted consensus to begin antiviral therapy pre-emptively with acyclovir in cases of acute liver failure of unknown origin, in which high urgency (HU) liver transplantation remains the only therapeutical option. Even in the case of early specific therapy, sepsis may prevail and the indication for HU transplantation must be evaluated carefully. The outcome after liver transplantation for HSV-induced liver failure with reported survival rates of more than 40% is good. Because of the risk of recurrence, lifelong prophylaxis with acyclovir is recommended.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Humans; Liver Failure, Acute; Polymerase Chain Reaction; Sepsis

Topics: Acetaminophen; Acyclovir; Administration, Oral; Adult; Aged; Analgesics, Non-Narcotic; Antiviral Agents; Chickenpox; Child, Preschool; Female; Herpes Simplex; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Immunocompetence; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Recurrence; Seroepidemiologic Studies; Valacyclovir; Valine

A child suffered from herpes simplex virus encephalitis at the age of 6 months; a late relapse occurred 8.5 years after the initial episode, the longest latency period reported. Radiologic and autopsy findings suggest local reactivation of latent herpes simplex virus as the cause of relapse. All cases of late relapse of herpes simplex virus encephalitis in the last 15 years are reviewed, with emphasis on clinical characteristics and possible mechanisms.

Topics: Acyclovir; Antiviral Agents; Child; Encephalitis, Herpes Simplex; Fatal Outcome; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Male; Recurrence; Virus Activation; Virus Latency

Primary herpes simplex virus (HSV) infection may lead to severe illness in pregnancy and may be associated with transplacental virus transmission and fetal infection. The consequences may be abortion, stillbirth and congenital malformations. In neonates, the clinical findings after intrauterine HSV infection are characterized by skin lesions, diseases of the eye and neurologic damage. Herpes genitalis of pregnant women at the time of labor may result in life-threatening neonatal herpes. Currently, neither active nor passive immunization is available to prevent HSV infections during pregnancy and in the newborn infant. Therefore, antiviral treatment using aciclovir and/or valaciclovir must be considered in all primary episodes of genital herpes as well as in neonates who show signs of either infection. Clinical herpes lesions of the genitalia and/or positive test for virus detection at the time of delivery are an indication for cesarean section. However, this surgical intervention may be reduced by suppressive treatment of recurrent genital herpes with aciclovir or valaciclovir.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 3, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus; Valacyclovir; Valine

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are members of the Herpesviridae family. HSV infections have been known since ancient times and are one of the most common communicable diseases in humans. Although infections are often subclinical, HSV can cause mild to severe diseases, especially in immunocompromised patients. Herpes simplex viruses establish latency in the nuclei of neuronal cells and may reactivate, with or without symptoms, throughout the host's lifetime. Over one third of the world's population suffer from recurrent HSV infections several times a year and are thus capable of transmitting HSV by close personal contact. There are few drugs licensed for the treatment of HSV infections. Most target the viral DNA polymerase, and indeed acyclovir remains the reference treatment some thirty years after its discovery! Extensive clinical use of this drug has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the crucial need for the development of new anti-herpes drugs that can inhibit infection by both wild-type viruses and drug-resistant strains. Over the last few years, significant efforts have been made to set up a range of strategies for the identification of potential new anti-viral drugs. One alternative is to develop drugs with different mechanisms of action. The present article reviews potential viral and cellular targets that are now known to be involved in HSV infection and for which specific inhibitors with anti-HSV activity, at least in cell culture, have been identified.

Topics: Acyclovir; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Delivery Systems; Drug Design; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompromised Host; Neurons; Virus Latency

Topics: Acyclovir; Animals; Antiviral Agents; DNA, Viral; Drug Resistance, Viral; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; RNA, Viral; Simplexvirus; Thymidine Kinase

Concomitant herpetic and candidal esophagitis is a very rare disease that had not been reported in uremic patients. A 57-year-old woman receiving continuous ambulatory peritoneal dialysis (CAPD) therapy for 3 years was admitted due to CAPD-related peritonitis. Endoscopic examination was performed due to severe epigastralgia and upper gastrointestinal bleeding, and combined herpetic and candidal esophagitis was diagnosed. Intravenous acyclovir and fluconazole were prescribed and symptoms improved. The patient subsequently died due to progressive sepsis and respiratory failure. This is the first report of a dual infectious esophagitis in a uremic patient. Since infectious esophagitis may cause severe complications, early diagnosis and aggressive treatment are important.

Topics: Acyclovir; Antifungal Agents; Antiviral Agents; Candidiasis; Esophagitis; Fatal Outcome; Female; Fluconazole; Herpes Simplex; Humans; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Sepsis; Uremia

Topics: Acyclovir; Amantadine; Anti-HIV Agents; Antiviral Agents; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; HIV Infections; Humans; Influenza, Human; Oseltamivir; Protease Inhibitors; Reverse Transcriptase Inhibitors

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpes Zoster; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Meningitis, Aseptic; Meningitis, Viral; Polymerase Chain Reaction

Topics: Acyclovir; Antiviral Agents; Cytokines; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Prognosis; Vidarabine

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Secondary Prevention; Severity of Illness Index; Valacyclovir; Valine

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Drug Therapy, Combination; Eye Infections, Viral; Herpes Simplex; Herpes Zoster; Humans; Valacyclovir; Valine; Vitrectomy

Neonatal herpes simplex virus (HSV) infection usually is acquired during the birth process, as the neonate comes in contact with the virus during passage through an infected birth canal. After an incubation period which can last as long as 2 to 4 weeks, neonatal HSV disease then manifests in 1 of 3 ways: (1) disseminated disease, with visceral organ involvement (including infection of the brain in two-thirds to three-quarters of patients); (2) central nervous system disease (with no other visceral organ involvement, but with skin lesions in two-thirds of patients); or (3) disease limited to the skin, eyes, and/or mouth (ie, SEM disease). Diagnostic advances in recent years have focused primarily on applying polymerase chain reaction technology to babies suspected of having neonatal HSV disease. Treatment of neonatal HSV disease with intravenous acyclovir has improved the likelihood of survival substantially, although neurologic morbidity remains a common sequelae, especially among survivors of central nervous system disease. Despite these advances, the duration of time from onset of symptoms and initiation of antiviral therapy has remained unchanged for the past 20 years. The surest way to improve outcomes rapidly at this point is to raise awareness of neonatal HSV disease, resulting in the establishment of earlier diagnoses and more rapid institution of antiviral therapy. In the longer term, development of a bedside nucleic acid detection kit for real-time detection of HSV DNA in the maternal genital tract at the time of delivery could identify which babies are at risk of developing neonatal HSV disease.

Topics: Acyclovir; Antibodies, Monoclonal; Antiviral Agents; Female; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Vidarabine

Disseminated herpes simplex virus (HSV) infection usually manifests in the immunocompromised. However, anecdotal examples of visceral HSV disease and viremia have complicated type I diabetes. A case of a 53-year-old type I diabetic patient with bowel obstruction one week subsequent to bronchitis is reported. At laparotomy, a perforated segment of ileum was associated with an adhesive peritoneal band. HSV cytopathic atypia and HSV immunohistochemical staining were confined to fibrocytes and mesothelial cells without involvement of the epithelium. Dissemination of symptomatic HSV pneumonia was verified by histology, immunohistochemistry, in situ hybridization, polymerase chain reaction and direct fluorescence antibody. Intravenous acyclovir resolved symptoms. This is a novel documentation of HSV complicating ileal adhesive band disease. Furthermore, this case indicates that the HSV cytopathic effect is not unique to the epithelium. Disseminated infection can manifest in myofibrocytes and mesothelium, distinguishing it from standard epithelial atypia of localized HSV infection.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Diagnosis, Differential; DNA, Viral; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Ileal Diseases; In Situ Hybridization; Intestinal Mucosa; Middle Aged; Polymerase Chain Reaction

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Antiviral Agents; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Herpes simplex virus (HSV) is seen throughout the world and can be treated with acyclovir. We present a case of fulminant hepatic failure (FHF) as a result of disseminated HSV infection in a pregnant patient during the second trimester.. The medical records of a patient suffering from HSV-related fulminant hepatic failure were collected. A review of the literature was collected and reported.. A previously healthy female presented with fulminant hepatic failure at a local emergency room complaining of a 5-day history of fever, nausea, vomiting, and right side abdominal pain that radiated to the back. She was diagnosed with fulminant hepatic failure and progressed into a coma. The patient underwent orthotopic liver transplantation (OLT) prior to the diagnosis of HSV and then treated successfully with acyclovir.. Treatment of HSV fulminant hepatitis is dependent up on early suspicion and prompt intervention. In addition, antiviral therapy may need to be lifelong.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Hepatocytes; Herpes Simplex; Herpesvirus 1, Human; Humans; Liver Failure, Acute; Postoperative Period

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Keratitis, Herpetic; Prognosis

Increasing evidence demonstrates a substantial link between the epidemics of sexually transmitted HIV-1 and herpes simplex virus (HSV)-2 infection. More than 30 epidemiologic studies have demonstrated that prevalent HSV-2 is associated with a 2- to 4-fold increased risk of HIV-1 acquisition. Per-sexual contact transmission rates among couples from Rakai, Uganda indicate that at all levels of plasma HIV-1 RNA in the source partner, HSV-2-seropositive HIV-1-susceptible persons have a 5-fold greater risk of acquiring HIV-1 compared with HSV-2-negative persons. In vitro and in vivo studies suggest that mucosal HIV-1 shedding is more frequent and in greater amounts during mucocutaneous HSV-2 replication, including subclinical mucosal reactivations. Most HIV-1-infected persons are coinfected with HSV-2, and most experience frequent subclinical and clinical reactivations of HSV-2. Subclinical HSV reactivation elevates serum HIV-1 RNA levels, and daily therapy with acyclovir appears to reduce plasma HIV-1 RNA. These data show that greater attention to the diagnosis and treatment of HSV-2 among HIV-1-infected persons is warranted, especially those who continue to be sexually active, those not on antiretroviral therapy, or those whose disease is not well suppressed by antiretrovirals.

Topics: Acyclovir; Antibodies, Viral; Clinical Trials as Topic; Comorbidity; Disease Transmission, Infectious; Female; Global Health; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male; Prevalence; Risk Factors; Viral Load; Virulence; Virus Replication

To report the clinical features and evaluate the visual outcome of eleven cases of herpes simplex virus-2 (HSV-2) related acute retinal necrosis syndrome (ARN).. Retrospective interventional case series.. Twelve eyes of eleven patients from two European centers, diagnosed with HSV-2 related acute retinal necrosis syndrome were retrospectively reviewed. Herpes simplex virus-2 DNA was detected by polymerase chain reaction in intraocular fluids (aqueous and/or vitreous). Findings at initial examination, clinical evolution with antiviral therapy, complications and final visual acuity were evaluated.. Herpes simplex virus-2 DNA was detected in all cases. No sample was positive for more than one virus. The mean age of disease in the first eye was 36 years (ranged from 10 to 57 years). Five patients were women and six were men. All patients were immunocompetent. Previous medical history included neonatal herpes (n = 1), previous ARN (n = 3), trauma (n = 1) and systemic corticosteroid administration before occurrence of ARN (n = 3). Preexisting pigmented chorioretinal scars were found in three cases. Patients were treated with high dose intravenous acyclovir or foscarnet +/- intravitreal ganciclovir +/- interferon. The mean follow-up was 14.5 months (from 5 to 22 months). At the end of the follow-up period, five eyes (41.7%) showed improvement of visual acuity of two or more lines. Final visual acuity was 20/60 or better in four eyes (33.3%), 20/400 or better in four eyes (33.3%) and less than 20/400 in four eyes.. History of neonatal herpes, triggering events such as neurosurgery, periocular trauma, high-dose corticosteroids, and chorioretinal scars suggest that HSV-2 retinitis reflects reactivation of HSV-2 infection.

Topics: Acyclovir; Adult; Antiviral Agents; Aqueous Humor; Child; DNA, Viral; Drug Therapy, Combination; Eye Infections, Viral; Female; Foscarnet; Ganciclovir; Herpes Simplex; Herpesvirus 2, Human; Humans; Interferons; Male; Middle Aged; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Virus Activation; Visual Acuity; Vitreous Body

In spite of the availability of antiviral therapy for the treatment of neonatal herpes simplex virus infections, the outcome remains poor, particularly for babies with disseminated multi-organ infection or central nervous system disease. This review considers recent advances that impact on disease management.. Two areas of investigation have impacted on our understanding of neonatal herpes simplex virus infection. First, the transmission of infection from mother to baby has been clarified by extensive epidemiological investigations of genital herpes in pregnant women at term. Risk factors for neonatal herpes simplex virus disease include first-episode maternal infection in the third trimester, invasive monitoring, delivery before 38 weeks, and maternal age of less than 21 years. Regarding the management of neonatal herpes simplex virus disease, the utilization of high-dose acyclovir (20 mg/kg every 8 h) for 21 days significantly reduces mortality for babies with either encephalitis or disseminated disease.. Recent findings from epidemiological studies have identified women at risk of delivering a child who develops neonatal herpes simplex virus infection, and suggest methods to decrease maternal-fetal transmission. If infection is identified in the pregnant woman, cesarean delivery decreases the frequency of neonatal disease. With neonatal disease, acyclovir should be administered promptly at higher dosages and for longer periods than previously reported.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Risk Factors

Presented here is a new case of benign recurrent aseptic meningitis, or Mollaret's meningitis, in which cerebrospinal fluid was positive for herpes simplex virus type 2 using the polymerase chain reaction test. A search of the existing medical literature revealed 58 previously reported cases of Mollaret's meningitis in which samples of cerebrospinal fluid were tested for herpes simplex virus. Discussed here are the history, clinical and laboratory findings, differential diagnoses and therapeutic options for this illness.

Topics: Acyclovir; Adult; DNA, Viral; Follow-Up Studies; Herpes Simplex; Herpesvirus 2, Human; Humans; Infusions, Intravenous; Meningitis, Aseptic; Polymerase Chain Reaction; Recurrence; Risk Assessment; Severity of Illness Index; Treatment Outcome

The most common disorder of the facial nerve is acute idiopathic facial paralysis or Bell's palsy and there may be significant morbidity or incomplete recovery associated with severe cases.. To assess the efficacy of aciclovir or similar agents for treating Bell's palsy.. We searched the Cochrane Neuromuscular Disease Group register (searched April 2003), MEDLINE (from January 1966 to April 2003), EMBASE (from January 1980 to April 2003) and LILACS (from January 1982 to April 2003). We also contacted authors of identified trials.. Randomised or quasi-randomised trials of aciclovir or valaciclovir therapy, alone or in combination with any other drug, in patients with Bell's palsy.. We identified six randomised trials.. Three studies met our inclusion criteria, including 246 patients. One study evaluated aciclovir with corticosteroid versus corticosteroid alone, another study evaluated aciclovir alone versus corticosteroid and a further study evaluated valaciclovir with corticosteroid versus corticosteroid alone or versus placebo alone. Incomplete recovery after one year: data were not available. An analysis was performed on data reported at the end of the study period in each trial. The results from one study four months after the start of treatment significantly favoured the treatment group, whilst the results of the study three months after the start of treatment significantly favoured the control group. The results from the second study at four months showed no statistically significant difference between the three groups. Adverse events: relevant data were not reported in any of the three trials. Complete facial paralysis six months after start of treatment: only one patient had complete paralysis upon entering one of the studies. This patient was assigned to the control group and the level of recovery attained was not reported. Motor synkinesis or crocodile tears one year after start of treatment: data were available up to a maximum of four months after onset of paralysis. One study reported a significant difference between the treatment groups in favour of the aciclovir plus corticosteroid group over corticosteroid alone, another demonstrated an inconclusive result with no difference between the aciclovir and corticosteroid. The third study did not comment upon these sequelae.. More data are needed from a large multicentre randomised controlled and blinded study with at least 12 months' follow up before a definitive recommendation can be made regarding the effect of aciclovir or valaciclovir on Bell's palsy.

Topics: Acyclovir; Antiviral Agents; Bell Palsy; Herpes Simplex; Humans; Randomized Controlled Trials as Topic; Valacyclovir; Valine

Herpes simplex encephalitis (HSE) is a life-threatening consequence of herpes simplex virus (HSV) infection of the central nervous system (CNS). Although HSE is rare, mortality rates reach 70% in the absence of therapy and only a minority of individuals return to normal function. Antiviral therapy is most effective when started early, necessitating prompt diagnosis. The International Herpes Management Forum (IHMF) has issued guidelines to aid the diagnosis and treatment of HSE. Polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF) is the diagnostic method of choice for HSE, but negative results need to be interpreted in the context of the patient's clinical presentation and the timing of the CSF sampling. CSF virus culture is of little value in all but patients under the age of 6 months. CSF (intrathecal) antibody measurements are not recommended for acute diagnostic purposes. However, demonstration of an intrathecal HSV antibody response may be helpful in retrospective diagnosis or in cases in which CSF is sampled only late after onset of infection and PCR is negative. Serum HSV antibody measurements are not of utility in the diagnosis of HSV encephalitis in adults. In children and young adults, HSV serology may help define whether HSE is part of a primary or a reactivated HSV infection, although the clinical features, therapy, and prognosis of these two forms of HSV encephalitis are similar. The IHMF recommends that all patients with HSE receive intravenous aciclovir 10 mg/kg every 8 h for 14-21 days. Owing to the life-threatening nature of the disease, if there is a delay in diagnostic test results therapy should not be withheld until they become available. After completion of therapy, PCR of the CSF can confirm the elimination of replicating virus, aiding further management of the patient. Clinical trials of other antiviral agents (i.e. adjunctive oral valaciclovir after intravenous aciclovir) for the treatment of HSE are underway. Herpes infection of the CNS, especially with HSV-2, can also cause both monophasic and recurrent aseptic meningitis, as well as myelitis or radiculitis. Limited evidence suggests that aciclovir may be effective in its treatment. Recurrent aseptic meningitis is predominantly caused by HSV-2 infection, and is characterized by self-limited episodes of fever, meningismus and severe headache. Many cases are indistinguishable from cases previously classified as "Mollaret's meningitis", a term that should now be reserve

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infusions, Intravenous; Meningitis, Viral; Practice Guidelines as Topic; Simplexvirus

The consequences of neonatal herpes simplex virus (HSV) infection can be severe. Disease can be localized to skin, eye and mouth (SEM disease), involve the central nervous system (CNS) or manifest as disseminated infection involving multiple organs. Most surviving infants in the latter two categories have neurological sequelae, and the mortality rate in the absence of therapy is very high (80%) for babies in the latter category. The International Herpes Management Forum (IHMF) has produced guidelines on the diagnosis, prevention and effective management of neonatal herpes. Neonatal herpes may occur in the absence of skin lesions, so if the infection is suspected, swabs of the oropharynx, conjunctiva, rectum, skin lesions, mucosal lesions and urine should be promptly taken and submitted for virus culture. Cerebrospinal fluid (CSF) should be submitted for polymerase chain reaction (PCR) detection of HSV DNA. Evidence for disseminated or CNS infection should be sought using liver function tests, complete blood cell count, CSF analysis and chest X-ray, if respiratory abnormalities are present. Neonates with suspected HSV infection should be treated with intravenous aciclovir (20 mg/kg) every 8 h for 21 days. If disease is localized to the SEM, treatment should be limited to 14 days. The neutrophil count for children receiving intravenous aciclovir should be monitored. If the absolute neutrophil count falls below 500/mm3, decreasing the aciclovir dose or administering granulocyte colony stimulating factor (GCSF) should be considered. At the end of therapy in CNS and disseminated disease, PCR assessment of CSF should be used and treatment continued if the child remains PCR positive at this site.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Granulocyte Colony-Stimulating Factor; Herpes Simplex; Humans; Infant, Newborn; Infusions, Intravenous; Meningitis, Viral; Polymerase Chain Reaction; Practice Guidelines as Topic; Simplexvirus

Sports participation may result in myriad cutaneous manifestations, from mundane findings to life-threatening illnesses. Skin infections are among the most common dermatologic ailments in athletes; herpes simplex is clearly among the most serious for the individual athlete, and ultimately the team. Herpes simplex infection most often involves athletes with extensive skin to skin contact. For a variety of reasons, wrestlers and rugby players seem particularly prone. The keys to thwarting epidemics and reducing an athlete's disqualification period include early diagnosis, rapid institution of therapy, and routine systematic preventative measures. This clinical review examines the classification, epidemiology, diagnosis, treatment, and prevention of herpes simplex virus infection as it relates to contact sports. Attention to evidence-based medicine is paid to treatment and prevention techniques. Practical implications for all concerned parties, including athletes, parents, coaches, trainers, and physicians, are discussed.

Topics: Acyclovir; Herpes Simplex; Humans; Sports; Valacyclovir; Valine; Wrestling

We report a case of indolent herpetic whitlow of the toe occurring in an elderly male patient with poorly controlled diabetes mellitus. In this case, the mechanism of transmission was not clear, although he was in a habit of taking a hot spring bath. This patient's symptoms were unusual for herpes simplex; he had no pain in the presence of diabetic neuropathy. The standard therapeutic dose of acyclovir was not effective in suppressing the lesions, and a higher dose was required to induce complete healing.

Topics: Acyclovir; Aged; Antiviral Agents; Cellulitis; Diabetic Foot; Diabetic Neuropathies; Foot Dermatoses; Herpes Simplex; Herpesvirus 1, Human; Humans; Hypesthesia; Male; Toes

Topics: Acyclovir; Aphasia; Brain; Encephalitis, Viral; Fever; Herpes Simplex; Humans; Infant; Male; Seizures; Simplexvirus; Tomography, X-Ray Computed; Treatment Outcome; Vomiting

Viral shedding of HSV occurs frequently in infected individuals. HSV is shed asymptomatically from multiple anatomical sites and shedding, like exposure, is a significant risk for transmission. However, the relationship between shedding frequency, viral titer and transmission is unknown. HSV-2 shedding is affected by the site and time since acquisition of infection. The advent of sensitive PCR techniques has shown that the magnitude and frequency of viral shedding is higher than shown previously with viral culture techniques. It has also clearly demonstrated that suppressive (daily) antiviral therapy reduces clinical and subclinical reactivation rates, and has been successfully used in the prevention of recurrent oral and genital HSV infections. A recent study has demonstrated that daily antiviral therapy with valaciclovir can significantly reduce transmission of HSV-2 between discordant heterosexual couples in monogamous relationships.

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Polymerase Chain Reaction; Simplexvirus; Valacyclovir; Valine; Virus Shedding

Antiviral treatment of herpes simplex virus (HSV) infections with nucleoside analogues has been well established for >2 decades, but isolation of drug-resistant HSV from immunocompetent patients has remained infrequent (0.1%-0.7% of isolates) during this period. Even when drug-resistant HSV is isolated from an immunocompetent patient, this virus, with rare exceptions, is cleared normally without adverse clinical outcome. Although drug-resistant HSV is more commonly isolated from immunocompromised patients (4%-7% of isolates) and is more likely to be clinically significant, the prevalence of drug-resistant HSV even among these patients, has been stable over the past 2 decades. Despite this stable prevalence, disease due to drug-resistant HSV remains an important problem for many immunocompromised patients, including those with HIV infection. This article reviews the prevalence, pathogenesis, and implications of drug-resistant HSV infections in HIV-infected patients.

Topics: Acyclovir; Animals; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; HIV Infections; Humans; Immunity, Cellular; Immunocompetence; Immunocompromised Host; Nucleosides; Recurrence; Simplexvirus

There are eight members of the herpesviridae family: herpes simplex virus-1 (HSV-1), HSV-2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpes virus-6, human herpes virus-7 and human herpes virus-8. The diseases caused by viruses of the herpesviridae family are treated with and managed by systemic and topical antiviral therapies and immunomodulating drugs. Because these viruses establish a latent state in hosts, antiherpetic agents, such as nucleoside analogues, only control symptoms of disease or prevent outbreaks, and cannot cure the infections. There is a need for treatments that require less frequent dosing, can be taken even when lesions are more advanced than the first signs or symptoms, and can treat resistant strains of the viruses without the toxicities of existing therapies. Immunomodulating agents, such as resiquimod, can act on the viruses indirectly by inducing host production of cytokines, and can thereby reduce recurrences of herpes. The new helicase primase inhibitors, which are the first non-nucleoside antiviral compounds, are being investigated for treatment of HSV disease, including infections resistant to existing therapy.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus; Drug Therapy; Herpes Simplex; Herpes Zoster; Herpesviridae; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans

Acyclovir, penciclovir, and their prodrugs have been widely used during the past two decades for the treatment of herpesvirus infections. In spite of the distribution of over 2.3 x 10(6) kg of these nucleoside analogues, the prevalence of acyclovir resistance in herpes simplex virus isolates from immunocompetent hosts has remained stable at approximately 0.3%. In immuncompromised patients, in whom the risk for developing resistance is much greater, the prevalence of resistant virus has also remained stable but at a higher level, typically 4 to 7%. These observations are examined in the light of characteristics of the virus, the drugs, and host factors.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Guanine; Herpes Simplex; Humans; Microbial Sensitivity Tests; Simplexvirus

Herpes simplex virus (HSV) infections are efficiently treated with antiviral drugs such as acyclovir (ACV). However, resistance has been reported, mainly among immunocompromised patients (prevalence around 5%) and particularly allogeneic bone marrow transplant patients (prevalence reaching 30%). Resistance to ACV is associated with mutations on one of the two viral enzymes involved in the ACV mechanism of action: thymidine kinase (TK) and DNA polymerase. In 95% of the cases, ACV resistance is associated with a mutation in the TK gene as this enzyme is not essential for viral replication, unlike viral DNA polymerase, which is rarely involved in resistance. Strains resistant to ACV are almost always cross-resistant to other TK-dependent drugs such as penciclovir and famciclovir. Resistant infections can be managed by foscarnet or cidofovir but both are more toxic than ACV. These drugs also inhibit viral DNA polymerase but they are active on most ACV-resistant HSV as they do not depend on TK; nevertheless virus resistant to ACV because of a mutation in the DNA polymerase may be cross-resistant to these molecules. Published data on genetic characterization of resistant clinical isolates point out hot spots in viral TK and DNA polymerase genes. TK mutations associated with resistance are either insertion or deletion (codons 92 and 146 of TK gene) or substitution (codon 176-177, 336 of TK gene). DNA polymerase mutations are mainly located in conserved sites of the enzyme. A high level of gene polymorphism has also been reported for these genes, especially for TK. These results are useful for the development of rapid genotypic assays for the detection of mutations associated with resistance.

Topics: Acyclovir; Antiviral Agents; Cidofovir; Cytosine; DNA-Directed DNA Polymerase; Drug Resistance, Multiple, Viral; Drug Resistance, Viral; Enzyme Inhibitors; Exodeoxyribonucleases; Foscarnet; Herpes Simplex; Humans; Immunocompromised Host; Mutation; Nucleic Acid Synthesis Inhibitors; Organophosphonates; Organophosphorus Compounds; Simplexvirus; Thymidine Kinase; Viral Proteins; Virus Replication

Topics: Acyclovir; Antiviral Agents; Female; Guidelines as Topic; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompetence; Treatment Outcome

Topics: Acyclovir; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infusions, Intravenous; Male; Pregnancy; Pregnancy Complications, Infectious; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Encephalitis, Viral; Herpes Simplex; Humans; Infusions, Intravenous; Japan; Prognosis

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Molecular Diagnostic Techniques; Prognosis; Secondary Prevention; Serologic Tests

In immunocompetent patients, HSV is controlled rapidly by the human host's immune system, and recurrent lesions are small and short lived. When treated with antiviral agents, these patients rarely develop resistance to these drugs. In contrast immunocompromised patients might not be able to control HSV infection. Thus, frequent and severe reactivations are often seen and might lead to fatal herpetic encephalitis or disseminated HSV infection. Treatment in these patients is limited because immunocompromised hosts often develop severe herpes disease refractory to antiviral drug therapy. It is therefore imperative that physicians develop regimens to deal with both receptive and refractory HSV disease. The following treatment protocol (modified from Balfour and colleagues) might serve as a guide until further investigation of new drugs is performed. In all patients standard oral ACV therapy should be initiated at a dose of 200 mg orally, five times a day for the first 3 to 5 days. Prior to treatment, cultures the lesions should be obtained to verify HSV etiology. If the response is poor, the dose of oral ACV should be increased to 800 mg five times a day. If no response seen after 5 to 7 days, it is unlikely that the lesion will respond to intravenous ACV (or chemically and structurally related drugs such as VCV or famciclovir), so an alternative regimen must be assigned. First, repeat cultures for vital, fungal, and bacterial pathogens must be performed. In addition, ACV susceptibility studies should be ordered, if available. If the mucocutaneous lesion is accessible for topical treatment, TFT (as ophthalmic solution) should be applied to the area three to four times a day until the lesion is completely healed. If the lesion is inaccessible or if the response to TFT is poor, therapy with intravenous foscarnet should be given for 10 days or until complete resolution of the lesions. The dosage of foscarnet should be 40 milligrams per kilogram three times per day or 60 milligrams per kilogram twice daily. If foscarnet fails to achieve clinical clearing, consideration should be given to use of intravenous cidofovir (or application of compounded 1% to 3% topical cidofovir ointment). Vidarabine is reserved for situations in which all of these therapies fail. If lesions reoccur in the same location following clearing, the patient should started on high-dose oral ACV (800 mg, five times daily) or intravenous foscarnet (40 mg/kg tid or 60 mg/kg bid) as soon as possib

Topics: Acyclovir; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Foscarnet; Herpes Simplex; Humans; Organophosphonates; Organophosphorus Compounds; Stomatitis, Herpetic; Trifluridine; Vidarabine

Genital herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted diseases in the United States. Perinatal transmission of the virus to the fetus or neonate is a major concern in affected pregnancies. Our objective was to systematically review published data to estimate the effect of prophylactic acyclovir provided to pregnant women near term on the rate of recurrent genital herpes at delivery; the number of cesarean deliveries performed for clinical HSV recurrences or prodromal symptoms; and the prevalence of HSV virologic detection at delivery.. Our search included MEDLINE (1966-March 2003), LILACS, EMBASE, conference proceedings, abstracts from scientific forums and bibliographies of published articles with the following medical headings: acyclovir, pregnancy, Herpes viridae, and Herpesviridae.. Prospectively designed criteria included randomized, clinical trials detailing the use of acyclovir in pregnancy for women with HSV published in either abstract or article form. Five trials with a total enrollment of 799 patients were included in the analysis.. The studies were reviewed independently by three of the authors. With RevMan software, a fixed-effects model was used to calculate a summary odds ratio (OR) comparing the effect of treatment with placebo. Acyclovir prophylaxis beginning at 36 weeks' gestation was effective in reducing clinical HSV recurrences at the time of delivery (OR 0.25; 95% confidence interval [95% CI] 0.15, 0.40), cesarean deliveries for clinical recurrence genital herpes (OR 0.30; 95% CI 0.13, 0.67), total HSV detection at delivery (OR 0.11; 95% CI 0.04, 0.31), and asymptomatic HSV shedding at delivery (OR 0.09; 95% CI 0.02, 0.39).. The results of this meta-analysis indicate that prophylactic acyclovir beginning at 36 weeks' gestation reduces the risk of clinical HSV recurrence at delivery, cesarean delivery for recurrent genital herpes, and the risk of HSV viral shedding at delivery.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Obstetric Labor Complications; Pregnancy; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Famciclovir; Female; Herpes Genitalis; Herpes Simplex; Humans; Treatment Outcome

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Herpes simplex virus (HSV) infections are among the infections most frequently encountered by humans. Two types of HSV infections have been identified-HSV-1, which usually causes orolabial disease, and HSV-2, which is associated more frequently with genital and newborn infections. Usually, HSV causes mild and self-limited disease of the mouth and lips or at genital sites. However, on occasion, the disease can be life-threatening. Such is the case with neonatal HSV infection and HSV infections of the central nervous system. Furthermore, in the immunocompromised host, severe infection has been encountered and is a source of morbidity. Even in the immunocompetent host, frequent recurrences, particularly those of the genital tract, can be debilitating. Because HSV does cause genital ulcerative disease, it is associated with an increased risk of acquiring a human immunodeficiency virus infection. During the past 2 decades, selective and specific inhibitors of HSV replication have been developed. These agents, acyclovir, valaciclovir, and famciclovir, all accelerate the events of healing and decrease the probability of excreting the virus when they are taken in a suppressive fashion. The long-term safety of acyclovir has been unequivocally established. Its prodrug, valaciclovir, and the prodrug of penciclovir, famciclovir, have not been used in practice as long and, therefore, less is known about these agents; however, neither is available as a pediatric formulation.

Topics: 2-Aminopurine; Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Antiviral Agents; Central Nervous System Viral Diseases; Child, Preschool; Drug Resistance, Viral; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Infant; Infant, Newborn; Injections, Intravenous; Simplexvirus; Valacyclovir; Valine; Virus Replication

Herpes is a pandemic infection in the human species. The purpose of this work was to conduct a critical analysis of the literature devoted to the pathophysiology and treatment of orofacial herpes an other localizations (genital herpes and neonatal herpes excluded).. We searched for articles in English and French devoted to orofacial herpes and other herpetic localizations indexed in Medline (1980-July 001), EmBase, and the Cochrane Library (1995-July 2001). Critical analysis was based on level of proof using the ANAES methodology.. More than 700 articles were identified. One hundred four were selected for this report. Primary HSV1 infection usually occurred before adulthood and involved acute gingivo-stomatitis in the majority of the cases. Several primary HIV1 infections were asymptomatic or aspecific and non-recognized. After the primary infection, the virus remains in the ganglion of the trigeminal nerve in a latent state and can be reactivated sporadically. Reactivation is associated with viral excretion and can be symptomatic (herpetic recrudescence) or not (recurrence). Recrudescence of orofacial herpes is typically labial. No currently available vaccine can prevent acquisition of HSV1. Treatment of acute gingivostomatitis has been standardized and is based on aciclovir. Inversely, the effectiveness of aciclovir and other nucleoside analogs with anti-herpes activity has not been clearly established for prevention or cure of recrudescence of orofacial herpes. Other localizations (hand, anus, diffuse skin localizations in contact sports, Kaposi-Juliusberg syndrome) are much more exceptional. Treatment has not been standardized.. Despite the abundance of the literature on orofacial herpes, consistent quality is lacking, particularly concerning therapeutic studies. The quality of these reports is generally inferior to those devoted to genital herpes. There has however been a general trend towards improved methodology over the last years. Very little has been reported on exceptional localizations of orofacial herpes.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Facial Dermatoses; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompetence; Stomatitis, Herpetic; Virus Activation

Neonatal herpes is a serious condition. The objectives of this critical review of the literature are to: 1) define the modes of mother-infant and indirect transmission of HSV infection; 2) determine current treatments and perspectives for the future.. We searched for articles published since 1980 in databases using a series of key words. The articles were classed into three categories by level of scientific proof: good (level 1), fair (level 2), poor (level 3, 4 or 5). General reviews were excluded.. We selected 153 articles and retained 96. Man to woman contamination was generally reported: 10p.100 of the couples were serodiscordant. Presence of anti-HSV1 antibodies was partially protective against HSV2 infection. Neonates can be contaminated in utero via transplacental hematogenic transmission, at delivery (the most frequent route), or during the postnatal period (indirect transmission). The risk of neonatal contamination is greatest for primary infection (PI) or non-primary infection occurring the last month of pregnancy (50p.100), but transmission is low for maternal recurrence during the week before delivery (5p.100). Cesarean section is mandatory in case of genital PI or non-primary maternal infection during the last month of pregnancy, especially in case of membrane rupture<6 hr, but does not protect the infant in two-thirds of the cases. The decision for cesarean is controversial in case of recurrence. Antiviral treatment of the mother using aciclovir (ACV) is well tolerated. ACV-cesarean combination provides maximal protection for the neonate. A neonate with proven or suspected HSV infection should be isolated from other neonates but not from the mother. Breastfeeding is contraindicated in case of breast lesions. Parenteral ACV 60 g/kg/d is preferred over vidarabine. It should be started immediately after the first virology samples. The risk of recurrence is estimated at 7p.100 for all neonates and warrants treatment using a high oral dose (90-100mg/kg/d) due to the low bioavailability, if the number of recurrences is>3 in 6 months. Antiviral treatment is formally indicated if: 1) neonate viral cultures are positive at day 1 and day 3, 2) clinical lesions suggest herpes, 3) neurological disorders or signs of sepsis with negative bacteriology are present and the mother has a history of herpes or contact with labial herpes; and can be discussed if: 4) PI is proven at delivery or during the last month of pregnancy (irrespective of the delivery route, even if the mother is treated or if the membranes are intact), 5) late cesarean (membrane rupture>4 h) with clinical herpes at delivery, 6) vaginal delivery and recurrent herpes within the last month with associated clinical risk factor(s).. Many points remain to be clarified concerning optimal management of the mother-infant couple in case of maternal herpes during pregnancy or at delivery. New perspectives concerning diagnosis and prevention of neonatal contamination include: identification of asymptomatic primary infections using rapid identification of genital viral antigen during delivery, identification of women with a risk of asymptomatic excretion using specific serology tests for the pregnant woman and her partner, antiviral treatment for men, topical genital treatments, vaccination of women at risk, monoclonal antibodies, new antiviral agents with mechanisms of action independent of viral thymidine kinase.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Interferons; Male; Pregnancy; Vidarabine

Neonatal herpes infection is secondary to pre/perinatal viral contamination from mother by HSV2 (70 p. 100) or HSV1 (30 p. 100). Incidence in French population is closed to 3/100,000 live births corresponding to 20 cases per year. Risk for maternal viral transmission to the neonate is 30 p. 100 with genital herpetic primo infection and 3 p. 100 in recurrence. However, in 70 p. 100 of cases, maternal history is not contributive. Three main clinical presentations are described However atypical symptoms - as isolated fever - can be a telltale sign. Mean clinical delay from birth to first clinical symptoms is 6 to 12 days and neonate is usually symptom - free at birth. Viral cultures from pharynx, stools, cutaneous lesions and specific PCR in blood and cerebrospinal fluid confirm the diagnosis. Curative treatment is acyclovir at high dosage - 60 mg/kg/d - during 14 days for localized forms and 21 days for neurological and disseminated diseases. Compared to conventional dosages, this treatment leads to a reduction in mortality which however remains high in disseminated forms, 31 p. 100 and 6 to 11 p. 100 in CNS infection. Morbidity is also high in survived patients, 17 p. 100 and 31 p. 100 respectively. Efficacy of prophylactic viral decontamination by anti-herpetic eye drops and cutaneous polyvidone iodine bath, which is largely used at birth in France, has never been evaluated.

Topics: Acyclovir; Anti-Infective Agents, Local; Antiviral Agents; Drug Therapy, Combination; Female; France; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infant, Newborn, Diseases; Povidone-Iodine; Pregnancy; Pregnancy Complications, Infectious

Topics: 2-Aminopurine; Acyclovir; Aminoquinolines; Antiviral Agents; Cidofovir; Cytosine; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Simplex Virus Vaccines; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Imiquimod; Interferon Inducers; Organophosphonates; Organophosphorus Compounds; Valacyclovir; Valine

In contrast to the frequent occurrence of localized herpes simplex virus (HSV) infections during pregnancy, disseminated disease has rarely been reported.. A 21-year-old woman in the 27th week of gestation developed a catastrophic illness characterized by fever, progressive pneumonia, respiratory failure, leukopenia, disseminated intravascular coagulation (DIC), anicteric hepatitis, septic shock and acute renal failure. Initial studies for an infectious etiology were negative. In spite of empiric broad-spectrum antimicrobial therapy, her condition continued to deteriorate. Sparse vesicular skin lesions suggestive of HSV infection subsequently appeared. Despite initiation of acyclovir therapy, the patient died. HSV type 2 was cultured from a skin vesicle, and at autopsy there was extensive necrosis of the liver and lung with immunohistochemical stains positive for HSV antigen.. In the third trimester of pregnancy, HSV can occasionally disseminate in immunocompetent women. A clinical syndrome of unexplained fever, pneumonia, anicteric hepatitis, leukopenia and DIC without mucocutaneous lesions should prompt investigation and possible treatment for disseminated HSV infection.

Topics: Acyclovir; Adult; Antigens, Viral; Antiviral Agents; Diagnosis, Differential; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunohistochemistry; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Viremia

Any new patient with suspected genital herpes should have diagnostic testing with virus identification. Type-specific serological tests that distinguish between antibodies for type 1 and type 2 herpes simplex virus (HSV) may be useful to determine previous exposure but cannot be used to diagnose recurrences of genital herpes. Initial episodes of genital herpes usually require antiviral therapy, while recurrences may be treated with continuous antiviral suppression (if frequent) or episodic therapy; patient counselling and education (including how to recognise lesions) are essential. Topical or systemic therapy is available for initial and recurrent non-genital herpes simplex. Primary varicella infection (chickenpox) and herpes zoster (shingles) are usually diagnosed clinically, but can be confirmed by detection of varicella-zoster virus antigens or nucleic acid from swabs of lesions or by antibody tests. Antiviral therapy should be considered in chickenpox if disease is complicated or the patient is immunocompromised. In herpes zoster, antiviral therapy should be given within 72 hours of onset to patients aged over 50 years or with severe pain or neurological abnormalities to reduce the likelihood and duration of postherpetic neuralgia. The availability of effective antiviral therapy makes early diagnosis vital

Topics: Acyclovir; Adult; Antiviral Agents; Australia; Female; Herpes Simplex; Herpes Zoster; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Male; Pregnancy; Pregnancy Complications, Infectious

The current arsenal of antiviral agents available to the practitioner is expanding rapidly, such that by the time this article goes to press, new drugs may have already been added. Although the majority of approved drugs have been developed for use in only a few viral infections (eg, HIV, herpesviruses, and papillomavirus), discoveries made in the development of these drugs may lead to antiviral agents effective against other viruses. In addition, new uses for the currently available drugs are under evaluation. This review of antiviral agents discusses the treatments available for viral infections such as herpes simplex virus, varicella zoster virus, cytomegalovirus, human papillomavirus, chronic viral hepatitis, and others.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Famciclovir; Foscarnet; Guanine; Hepatitis B; Hepatitis C; Herpes Genitalis; Herpes Simplex; Herpesvirus 3, Human; Herpesvirus 8, Human; Humans; Papillomavirus Infections; Sarcoma, Kaposi; Skin Diseases, Viral; Valacyclovir; Valine

An extensive clinical trial program combined with 5 years' postmarketing experience with valacyclovir provides evidence of favorable safety and efficacy in herpes simplex virus (HSV) management. Valacyclovir enhances acyclovir bioavailability compared with orally administered acyclovir. Long-term use of acyclovir for up to 10 years for HSV suppression is effective and well tolerated. Acyclovir is also approved for use in children, is available in some countries over the counter in cream formulation for herpes labialis, and has been monitored in over 1000 pregnancies. Safety monitoring data from clinical trials of valacyclovir, involving over 3000 immunocompetent and immunocompromised persons receiving long-term therapy for HSV suppression, were analyzed. Safety profiles of valacyclovir (

Topics: Acyclovir; Administration, Oral; Administration, Topical; Adult; Antiviral Agents; Child; Clinical Trials as Topic; Drug Resistance, Viral; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Infections; Humans; Immunocompetence; Immunocompromised Host; Pregnancy; Pregnancy Complications, Infectious; Prodrugs; Valacyclovir; Valine

A meta-analysis of 12 randomized trials (1574 patients) examined herpesvirus and related outcomes following organ transplantation over a range of acyclovir exposures (including valacyclovir). Overall, cytomegalovirus (CMV) infection (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.34-0.57; P<.001), CMV disease (OR, 0.41; 95% CI, 0.31-0.54; P<.001), death (OR, 0.60; 95% CI, 0.40-0.90; P=.01), opportunistic infection (OR, 0.70; 95% CI, 0.53-0.91; P=.009), acute graft rejection (OR, 0.67; 95% CI, 0.52-0.86; P<.001), herpes simplex virus disease (OR, 0.17; 95% CI, 0.12-0.24; P<.001), and varicella-zoster virus disease (OR, 0.06; 95% CI, 0.01-0.25; P<.001) were significantly reduced. Increased acyclovir exposure influenced more end points: Maximum efficacy resulted from valacyclovir (8 g/day). Increasing acyclovir exposure to that achieved with valacyclovir extends benefits of prophylaxis to include impact on graft rejection and opportunistic infections.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Graft Rejection; Herpes Simplex; Humans; Odds Ratio; Opportunistic Infections; Organ Transplantation; Postoperative Complications; Prodrugs; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Approximately 2000 neonates contract infection due to herpes simplex virus each year in the United States. Although herpes simplex virus type 2 is responsible for most neonatal infections, approximately 30% of infections are caused by herpes simplex virus type 1. Infections are categorized by extent of disease into skin/eye/mouth, central nervous system and disseminated disease categories. Each disease category is responsible for roughly one third of neonatal infections. Mortality is highest in disseminated disease. Morbidity is highest for survivors of central nervous system infection. Treatment with high dose parenteral acyclovir (60 mg/kg/day) for 14-21 days improves outcome. Since most neonatal infections are acquired from contact with infected maternal genital tract secretions, potential preventative strategies include: Caesarean delivery, serologic screening of pregnant women, prophylactic acyclovir and vaccination. The two strategies currently accepted by most obstetricians are Caesarean delivery for women with active lesions or prodromal symptoms and prophylactic acyclovir for women with gestational herpes.

Topics: Acyclovir; Antiviral Agents; Cesarean Section; Female; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Child, Preschool; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; France; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Pemphigoid Gestationis; Polymerase Chain Reaction; Pregnancy; Recurrence; Simplexvirus; Stomatitis, Herpetic; Time Factors

Herpes simplex viruses (HSV) are ubiquitous pathogens which can be transmitted vertically causing significant morbidity and mortality in neonates. Neonatal HSV infection is infrequent with an incidence ranging from 1 in 3,500 to 1 in 20,000, depending on the population. Neonatal HSV infection is much more frequent in infants born to mothers experiencing a primary HSV infection with an incidence approaching 50%, while infants born to mothers experiencing recurrent HSV infection have an incidence of less than 3%. Neonatal infections are clinically categorised according to the extent of the disease. They are: (i) skin, eye and mouth (SEM) infections; (ii) central nervous system infection (encephalitis)--neonatal encephalitis can include SEM infections; and (iii) disseminated infection involving several organs, including the liver, lung, skin and/or adrenals. The central nervous system may also be involved in disseminated infections. Caesarean section, where the amniotic membranes are intact or have been ruptured for less than 4 hours, is recommended for those women who have clinical evidence of active herpes lesions on the cervix or vulva at the time of labour. This procedure significantly decreases the risk of transmission to the infant. Diagnosis of neonatal infection requires a very high level of clinical awareness as only a minority of mothers will have a history of genital HSV infection even though they are infected. Careful physical examination and appropriate investigations of the infant should accurately identify the infection in the majority of cases. Treatment is recommended where diagnosis is confirmed or there is a high level of suspicion. The current recommendation for treatment is aciclovir 20 mg/kg 3 times daily by intravenous infusion. Careful monitoring of hydration and renal function as well as meticulous supportive care of a very sick infant is also required. The newer anti-herpes agents, valaciclovir and famciclovir, offer no advantage over aciclovir and are not recommended for neonatal HSV infection. Prognosis is dependent upon the extent of disease and the efficacy of treatment, with highest rates of morbidity and mortality in disseminated infections, followed by central nervous system infection and the least in SEM infection. However, SEM infection is associated with poor developmental outcome even in infants who do not have encephalitis. Studies to improve the outcome of SEM infection are in progress. Neonatal HSV infections, although

Topics: Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Vidarabine

The most common disorder of the facial nerve is acute idiopathic facial paralysis or Bell's palsy and there may be significant morbidity or incomplete recovery associated with severe cases. Although the cause remains unknown, recent evidence suggests a possible association with Herpes simplex virus (HSV) infection. To test this hypothesis clinically four clinical trials have used aciclovir, an antiviral agent, either alone or in combination with corticosteroids to treat Bell's palsy.. To assess the efficacy of aciclovir for treating Bell's palsy and to evaluate any adverse effects of the drug treatment.. Search of the Cochrane Neuromuscular Disease Group register, MEDLINE, EMBASE and LILACS databases for randomised trials. We also contacted authors of identified trials.. Randomised or quasi-randomised trials of aciclovir therapy, alone or in combination with any other drug, in patients with Bell's palsy.. We identified four randomised trials. One author extracted the data and the other checked them. We wrote to all the authors of the trials identified. No additional data were obtained.. Only two studies met our inclusion criteria and provided results from 200 patients. One study evaluated aciclovir with corticosteroid versus steroid alone and the other study evaluated aciclovir alone versus corticosteroid. PRIMARY OUTCOME Proportion of patients with incomplete recovery after one year: These data were not available. However an analysis was performed on data reported at the end of the study period, three (De Diego 1998) or four months (Adour 1996) after the start of treatment. The results from the Adour study significantly favoured the treatment group whilst the De Diego study significantly favoured the control group. Adverse events: This analysis was not performed as the data were not reported. Complete facial paralysis six months after start of treatment: Only one patient had complete paralysis upon entering only one of the studies (De Diego 1998). This patient was assigned to the control group and the level of recovery attained was not reported. Motor synkinesis/Crocodile tears one year after start of treatment: Data were available up to a maximum of four months after onset of paralysis. One study reported a significant difference between the treatment groups in favour of the aciclovir group and the other demonstrated an inconclusive result.. More data are needed from a large multicentre randomised controlled and blinded study with at least 12 months' follow up before a definitive recommendation can be made regarding the routine use of aciclovir in Bell's palsy.

Topics: Acyclovir; Antiviral Agents; Bell Palsy; Herpes Simplex; Humans; Randomized Controlled Trials as Topic

Flamel Technologies is developing Genvir (formerly known as Viropump), a twice-daily controlled-release formulation of aciclovir, for potential use in the treatment of herpes simplex virus and varicella zoster virus infections. Genvir utilizes Flamel's proprietary Micropump technology, a microparticle-based drug delivery system designed to extend the time of absorption of drugs in the small intestine. The drug shows a comparable therapeutic efficacy to valaciclovir and famciclovir (both GlaxoSmithKline) [313393]. Phase III trials have been completed [302829]. In August 2000, Flamel filed for regulatory approval for the treatment of herpes in France, as a prelude to a pan-European approval [378641] and is preparing an IND application to begin clinical trials for genital herpes in the US [245970].

Topics: Acyclovir; Animals; Antiviral Agents; Chickenpox; Enzyme Inhibitors; Herpes Simplex; Humans; Nucleic Acid Synthesis Inhibitors; Thymidine Kinase

Antiviral prophylaxis in pediatric oncology and pediatric bone marrow transplantation (BMT)/stem cell transplantation (SCT) focuses herpes viruses: herpes simplex virus (HSV), varicella zoster virus (VZV) and cytomegalovirus (CMV) since these viruses cause significant morbidity and mortality due to primary infection or to reactivation in long term latency. The majority of studies on antiviral prophylaxis, especially those on CMV-prophylaxis, have been conducted in adult patients. Recommendations for antiviral prophylaxis have been published recently by the German "Deutsche Gesellschaft für pädiatrische Infektiologie" and by the following American institutions and societies "Centers for Disease Control and Prevention", "Infectious Diseases Society of America", "American Society of Blood and Marrow Transplantation" who published the "Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients". Concerning HSV- and VZV-prophylaxis there are almost no differences between recommendations of the german society and the american institutions, however recommendations for preventing CMV-disease and CMV-recurrence do differ considerably. Controversial aspects of antiviral prophylaxis, e.g. VZV vaccination or CMV prevention, should be studied in oncology and infectious diseases working groups to define consensus in the near future.

Topics: Acyclovir; Adult; Age Factors; Antiviral Agents; Bone Marrow Transplantation; Chickenpox; Child; Cytomegalovirus Infections; Ganciclovir; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunization, Passive; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recurrence; Time Factors; Viral Vaccines; Virus Diseases

Herpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers characterised by erythema and painful, non-purulent vesicles. In children it typically occurs after auto-inoculation from herpes stomatitis, herpes labialis or genitalis. Occasionally, person-to-person transmission occurs from family members with herpes labialis. We report a 4-year-old girl with multiple herpetic whitlows secondary to herpetic stomatitis and present a review of the medical literature based on a systematic MEDLINE search of published paediatric patients (English, French and German language). Of 42 identified patients, 72% were younger than 2 years, most had endogenous or exogenous inoculation of herpes simplex virus type 1 and 65% were initially misdiagnosed as having "bacterial felon". Recurrences were reported in 23%.. herpetic whitlow should be suspected based on clinical signs. Specific diagnosis can be made by polymerase chain reaction or culture. The high rate of misdiagnosed cases indicates that this entity is not sufficiently known. Lesions are self-limited; surgical interventions can be harmful and should be avoided. Recurrences occur as frequently as in adults.

Topics: Acyclovir; Antiviral Agents; Child, Preschool; Diagnosis, Differential; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Polymerase Chain Reaction; Recurrence

The most common disorder of the facial nerve is acute idiopathic facial paralysis or Bell's palsy and there may be significant morbidity or incomplete recovery associated with severe cases. Although the cause remains unknown, recent evidence suggests a possible association with Herpes simplex virus (HSV) infection. To test this hypothesis clinically four clinical trials have used aciclovir, an antiviral agent, either alone or in combination with corticosteroids to treat Bell's palsy.. To assess the efficacy of aciclovir for treating Bell's palsy and to evaluate any adverse effects of the drug treatment.. Search of the Cochrane Neuromuscular Disease Group register, MEDLINE, EMBASE and LILACS databases for randomised trials. We also contacted authors of identified trials.. Randomised or quasi-randomised trials of aciclovir therapy, alone or in combination with any other drug, in patients with Bell's palsy.. We identified four randomised trials. One author extracted the data and the other checked them. We wrote to all the authors of the trials identified. No additional data were obtained.. Only two studies met our inclusion criteria and provided results from 200 patients. One study evaluated aciclovir with corticosteroid versus steroid alone and the other study evaluated aciclovir alone versus corticosteroid. PRIMARY OUTCOME Proportion of patients with incomplete recovery after one year: These data were not available. However an analysis was performed on data reported at the end of the study period, three or four months after the start of treatment. The results from the Adour study significantly favoured the treatment group whilst the De Diego study significantly favoured the control group. Adverse events: This analysis was not performed as the data were not reported. Complete facial paralysis six months after start of treatment: Only one patient had complete paralysis upon entering only one of the studies. This patient was assigned to the control group and the level of recovery attained was not reported. Motor synkinesis/Crocodile tears one year after start of treatment: Data were available up to a maximum of four months after onset of paralysis. One study reported a significant difference between the treatment groups in favour of the aciclovir group and the other demonstrated an inconclusive result.. More data are needed from a large multicentre randomised controlled and blinded study with at least 12 months' follow up before a definitive recommendation can be made regarding the routine use of aciclovir in Bell's palsy.

Topics: Acyclovir; Antiviral Agents; Bell Palsy; Herpes Simplex; Humans; Randomized Controlled Trials as Topic

Herpes simplex virus (HSV) infection in the burn patient is thought to occur relatively frequently. Most commonly, children with significant burns, particularly involving the head and neck, are affected. Burn related immunosuppression is thought to allow reactivation of latent HSV in most cases, although primary HSV infection has been recognized. Clinical manifestations vary from asymptomatic viral shedding, to prolonged fever with eruption of vesicles, to rare cases of systemic visceral dissemination. Healing partial thickness wounds and donor sites are most prone to infection. Laboratory confirmation of HSV infection relies on direct demonstration of the virus and/or observation of a rise in antibody titer. Treatment of an established HSV infection includes use of IV Acyclovir, meticulous wound care, and efforts to prevent nosocomial spread. The vast majority of cases resolve without sequelae unless complicated by systemic, multiorgan HSV infection.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Burns; Cross Infection; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Injections, Intravenous; Skin Transplantation; Wound Healing; Wound Infection

Herpes simplex virus infection is increasingly common in the United States. New antiviral medications have expanded treatment options for the two most common cutaneous manifestations, orolabial and genital herpes. Acyclovir therapy remains an effective and often less expensive option. Famciclovir and valacyclovir offer improved oral bioavailability and convenient oral dosing schedules but are more expensive than acyclovir. Patients who have six or more recurrences of genital herpes per year can be treated with one of the following regimens: acyclovir, 400 mg twice daily; valacyclovir, 1 g daily; or famciclovir, 250 mg twice daily. These regimens are effective in suppressing 70 to 80 percent of symptomatic recurrences. Episodic treatment of recurrent genital herpes is of questionable benefit, but it may be helpful in appropriately selected patients. There is little evidence indicating benefit from treatment of recurrent orolabial herpes, which tends to be mild and infrequent.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chronic Disease; Diagnosis, Differential; Drug Costs; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Patient Education as Topic; Teaching Materials; Valacyclovir; Valine

The objective of this article is to review and evaluate risks and benefits associated with the use of acyclovir in the treatment and prophylaxis of common manifestations of herpes simplex virus (HSV) infections in immunocompetent and immunocompromised patients. Information was found through a MEDLINE search using keywords: herpes simplex virus, genital herpes, herpes labialis, acyclovir and acyclovir. Selected articles were randomised, double-blind, placebo-controlled, clinical trials. 30 such trials involving 3364 persons were evaluated. All articles were reviewed by the authors and the data were extracted and summarised. In both immunocompetent and immunocompromised hosts, acyclovir therapy demonstrated a high degree of clinical efficacy. None of the studies reported statistically significant differences between acyclovir and placebo for mild or major adverse events. This evaluation found that acyclovir is both effective and well tolerated for treatment and prophylaxis of genital, oral and mucocutaneous HSV infections in immunocompetent and immunocompromised patients. In most clinical scenarios. the benefit of acyclovir exceeded any risks by a comfortable margin. The availability of acyclovir as a generic preparation further improves the benefit to cost ratio.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Humans; Immunocompromised Host; Risk

The aim of this study was to delineate the characteristics of herpes simplex virus esophagitis (HSVE) in the immunocompetent host.. The study entailed a case report and a review of relevant literature through a MEDLINE search back to 1966. All cases with documented HSVE in patients without immunosuppression were selected and their characteristics defined.. A total of 38 cases were identified. The age range was 1-76 yr and the male/female ratio 3.2/1. Antecedent exposure to HSV disease was described in eight cases (21.1%). A prodrome of systemic manifestations preceded the onset of esophageal symptoms in nine subjects (23.6%). Manifestations included acute odynophagia (76.3%), heartburn (50%), and fever (44.7%). Concurrent oropharyngeal lesions were uncommon (n = 8, 21.1%). Endoscopically, extensive involvement was common, showing friable mucosa (84.2%), numerous ulcers (86.8%), and whitish-exudates (39.5%). The distal esophagus was most commonly affected (63.8%). Microscopic examination showed characteristic viral cytopathology in 26 (68.4%) cases. Virus was recovered from esophageal-brushes or biopsies in 23 of 24 (95.8%) patients and immunocytochemistry was positive in seven of eight (87.5%) cases. Immune status was consistent with primary HSV infection in eight (21.1%) cases. The disease was self-limiting, although esophageal perforation and upper GI bleeding were reported in one case each.. HSVE in the immunocompetent host is a rare but distinct entity, and is significantly more common in male subjects. It represents either primary infection or reactivation, and is characterized by acute onset, systemic manifestations, and extensive erosive-ulcerative involvement of the mid-distal esophagus. Histopathological examination alone may miss the diagnosis; adding tissue-viral culture optimizes the diagnostic sensitivity. It is usually self-limiting; whether antiviral therapy is beneficial remains unknown.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Biopsy; CD4-CD8 Ratio; Diagnosis, Differential; Esophagitis; Esophagoscopy; Esophagus; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Retrospective Studies

Treatment options for peripheral facial palsy (PFP) are an often discussed problem in neurologic practice. Following a short description of the complex anatomy of the seventh cranial nerve we therefore review possible etiologies in the context of leading clinical signs, with idiopathic PFP or Bell's palsy (BP) being most frequent. A rather typical clinical course of BP allows to focus differential diagnostic workup predominantly on the rapid identification of treatable infections such as with Herpes zoster or Borrelia burgdorferi. Neuroimaging studies are needed only in case of trauma, with slowly developing PFP or in the presence of associated signs and symptoms. As BP is characterized by an overall high rate of spontaneous recovery, major emphasis has to be put on avoiding complications by protecting the eye. Meta-analysis of four randomized controlled studies suggests a marginal benefit of steroids concerning eventual achievement of complete recovery. Beneficial effects of a combination of acyclovir and prednisone have also been claimed. While such therapies may be considered in patients with a presumptive bad prognosis, more general recommendations on medical treatment of BP will have to await further trials.

Topics: Acyclovir; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antiviral Agents; Clinical Trials as Topic; Diabetic Neuropathies; Diagnosis, Differential; Diagnostic Imaging; Eye Injuries; Facial Nerve; Facial Nerve Injuries; Facial Paralysis; Herpes Simplex; Humans; Neoplasms; Pons; Postoperative Complications; Prednisone; Prognosis; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Encephalitis, Japanese; Encephalitis, Viral; Herpes Simplex; Humans; Prognosis; Vidarabine

Topics: Acyclovir; Adenoviridae Infections; Antiviral Agents; Cytomegalovirus Infections; Diagnosis, Differential; Herpes Simplex; Humans; Pleurisy; Prognosis

Topics: Acyclovir; Adolescent; Antiviral Agents; Encephalitis, Viral; Female; Herpes Simplex; Humans; Retinal Necrosis Syndrome, Acute

Recently, acyclovir use has been proposed for the treatment of Bell's palsy in view of the hypothetical viral origin of the disorder. Recent studies suggest that the maximum effect is achieved by combining acyclovir with prednisone. Nevertheless, acyclovir alone appears to be useful in the treatment of some patients (hypertensive subjects). Protocols are defined for the medical treatment of Bell's palsy.

Topics: Acute Disease; Acyclovir; Antiviral Agents; Facial Paralysis; Herpes Simplex; Humans

Topics: Acyclovir; Animals; Antiviral Agents; Herpes Simplex; Humans; Mice; Simplexvirus; Virus Latency

Fulminant hepatic dysfunction in the third trimester of pregnancy accompanied by fever may result from disseminated herpes simplex virus. Since 1969, 24 cases of herpes simplex hepatitis, including the current case, have been reported. Mucocutaneous lesions are present in only half of cases; therefore, suspicion for diagnosis of this disease is low. Twenty-five percent of cases were not diagnosed until autopsy. Maternal and perinatal mortality are high, approaching 39 percent for both mother and fetus. Early recognition with initiation of antiviral therapy appears to be most important in maximizing survival.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Pregnancy; Pregnancy Complications, Infectious

The majority of peripheral seventh cranial nerve palsy cases remain without an identified etiology and will eventually be diagnosed as idiopathic or Bell's palsy. Some features of this condition may be characteristic of a viral infection. Indeed, several herpes viruses have been implicated as potential causative pathogens. Besides varicella-zoster virus, shown to cause Bell's palsy under the Ramsay-Hunt syndrome, recent years have seen an increased interest and focus on the possible herpes simplex virus type 1 (HSV-1) etiology in idiopathic facial paralysis. We review the clinical, biological and virological basis for the potential herpetic cause of Bell's palsy and the rational for antiviral therapy in this condition.

Topics: Acyclovir; Antiviral Agents; Bell Palsy; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Famciclovir; Guanine; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Prodrugs; Simplexvirus; Virus Replication

Topics: Acyclovir; Aged; Antiviral Agents; Erythema Multiforme; Herpes Simplex; Humans; Male; Recurrence; Skin

The rates of herpes simplex virus (HSV) infection are rising, the highest prevalence being in the group infected with the human immunodeficiency virus (HIV). We review the relation between these 2 infections. The presence of genital ulcers increases the transmission of HIV, and the presence of HIV adversely affects the natural history of HSV infection. The detection and treatment of sexually transmitted diseases such as genital herpes actually decrease the rates of HIV infection in groups studied. The treatment of HSV in persons with HIV is challenging because the incidence of immunosuppression increases. Acyclovir resistance is more common in this group, but acyclovir use may prolong survival in some HIV-seropositive patients. Further studies are needed to determine whether persons with HIV disease should routinely be given HSV-specific therapy.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Female Urogenital Diseases; Herpes Genitalis; Herpes Simplex; HIV; HIV Infections; Humans; Immune Tolerance; Incidence; Male Urogenital Diseases; Prevalence; Simplexvirus; Survival Rate; Ulcer

With increasing use of acyclovir and ganciclovir, primarily due to the increased number of AIDS and transplant patients, further cases of neurologic toxicity will undoubtedly be encountered. Discontinuation or dosage reduction of acyclovir and ganciclovir is necessary to manage neurologic toxicity that is directly attributed to either agent. Renal dysfunction is a known risk factor for acyclovir neurotoxicity, and case reports indicate that renal dysfunction may also be a risk factor for ganciclovir neurotoxicity. Since ganciclovir is structurally related to acyclovir, clinicians should monitor for signs and symptoms of neurotoxicity as they would with acyclovir until the risk factors are more clearly defined. Dosage reduction for both agents and increased monitoring should occur when renal dysfunction is present, to minimize the risk of neurotoxicity and other serious adverse effects. Tables 1 and 2 summarize the recommended dosages of acyclovir and ganciclovir, respectively, in the presence of renal dysfunction. However, as a few case reports describe, neurotoxicity from these agents has also occurred in patients with normal renal function. Therefore, clinicians should always remain vigilant in monitoring for signs of neurotoxicity when acyclovir or ganciclovir is administered, and have a high index of suspicion for these agents if neurotoxicity is encountered during therapy.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Central Nervous System Diseases; Cytomegalovirus Infections; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Renal Insufficiency; Risk Factors

Ocular herpes simplex is usually diagnosed by its typical clinical presentation. It is generally accepted to be a unilateral disease, with lid eruptions typically occurring in primary ocular herpes simplex, while absent or mild in recurrent disease. Recurrent ocular herpes simplex is generally thought to be characterized by corneal involvement.. A 35-year-old woman had a 2-day history of a progressive bilateral, erythematous, vesicular rash of the upper and lower eyelids and associated preseptal cellulitis. She had a history of a recurrent, unilateral eyelid rash that was previously diagnosed as herpes zoster. The eyelid involvement was unusual because it was bilateral, severe, recurrent, vesicular, and isolated, with no additional ocular manifestations of herpes simplex. These atypical features are in contrast to the generally accepted manifestations of recurrent ocular herpes simplex. A cytologic evaluation and a viral culture confirmed infection by HSV Type 1.. Lid involvement occurs in recurrent ocular herpes simplex disease more often than generally accepted, while simultaneous bilateral disease is uncommon. As in this case, when atypical presentations occur, critical review of the differential diagnosis and use of laboratory tests are helpful.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Eye Infections, Viral; Eyelid Diseases; Eyelids; Female; Follow-Up Studies; Herpes Simplex; Herpesvirus 1, Human; Humans; Recurrence

Several antiviral agents are available to treat viral illnesses in healthy children. In some children, treatment with acyclovir is an alternative to vaccination for the treatment and prevention of chickenpox. Acyclovir also can be useful in the treatment or prevention of herpes simplex infections in neonates. Ribavirin, once recommended as routine therapy for high-risk infants with respiratory syncytial virus disease, is now reserved for use in selected children. Amantadine and rimantidine are effective against influenza type A and can be used to protect children from influenza, as well as to lessen the duration and severity of illness in those who are already ill.

Topics: Acyclovir; Amantadine; Antiviral Agents; Chickenpox; Child; Child, Preschool; Drug Administration Schedule; Herpes Simplex; Humans; Respiratory Syncytial Virus Infections; Ribavirin; Rimantadine; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Encephalitis, Viral; Female; Herpes Simplex; Humans; Infant; Male; Movement Disorders

To evaluate the utility of an assay based on a polymerase chain reaction (PCR) of cerebrospinal fluid in the management of patients with suspected herpes simplex encephalitis.. A decision model was constructed and used to compare a PCR-based approach with empiric therapy. Inputs required by the model included the sensitivity (96%) and specificity (99%) of PCR (derived from review of the literature), the prevalence of herpes simplex encephalitis (5%, based on the actual prevalence at Barnes Hospital among patients treated empirically with acyclovir), the outcomes for patients with and without herpes simplex encephalitis (derived from clinical studies of the Collaborative Antiviral Study Group and the actual experience at Barnes Hospital), and the average duration of empiric acyclovir therapy for patients with possible herpes simplex encephalitis (5.3 days based on actual experience at Barnes Hospital).. Using these input values, the decision model predicted better outcomes with empiric therapy. However, low rates of inappropriate discontinuation of empiric therapy in patients with herpes simplex encephalitis or improved diagnosis and outcome resulting from a negative PCR assay result in patients without herpes simplex encephalitis led to better outcomes with the PCR-based approach. The PCR-based approach was associated with 9.2 fewer doses of acyclovir per patient.. Based on the decision model using conservative assumptions, a PCR-based approach can yield better outcomes and reduced acyclovir use compared with empiric therapy.

Topics: Acyclovir; Antiviral Agents; Bayes Theorem; Decision Support Techniques; Diagnosis, Differential; Encephalitis, Viral; Herpes Simplex; Humans; Polymerase Chain Reaction; Prevalence; Sensitivity and Specificity; Simplexvirus; Treatment Outcome

A 35-yr-old, immunocompetent male was admitted complaining of severe odynophagia. He was diagnosed as having herpes simplex esophagitis and was started on intravenous acyclovir 5 mg/kg every 8 h on the day of admission. His response was dramatic. Within 24 h he was virtually asymptomatic. Acyclovir therapy in immunocompetent adults with esophagitis has been described in only a handful of cases in the literature, although the therapy is well established in immunocompromised patients. We review the English literature and discuss the efficacy of the therapy. Acyclovir therapy may be beneficial in immunocompetent patients with particularly severe odynophagia.

Topics: Acyclovir; Adult; Esophagitis; Herpes Simplex; Humans; Immunocompetence; Injections, Intravenous; Male

Hepatitis due to herpes simplex virus (HSV) is unusual in healthy individuals. To date, only 56 cases of HSV hepatitis in adult patients have been reported, including 21 pregnant patients. We describe a 25-year-old white woman in her 30th week of gestation who had progressive acute hepatitis. Histologic examination of the liver biopsy specimen showed diffuse microabscesses involving more than 50% of the hepatic parenchyma, with multiple hepatocytes containing Cowdry type A and ground-glass nuclear inclusions. The diagnosis of herpes hepatitis was confirmed by positive immunoreactivity to HSV antibodies in the tissue sections. Intravenous acyclovir therapy was immediately initiated, and the patient's condition improved dramatically. She then had a normal baby at term. Subsequently, the patient had a second pregnancy and an uncomplicated vaginal delivery without recurrence of the disease. Even though alterations of the humoral and cell-mediated immunity occur during pregnancy, herpes hepatitis is rare in pregnant women. Since the prompt administration of antiviral drugs is a lifesaving measure, we recommend including HSV hepatitis in the differential diagnosis of acute hepatitis in pregnancy.

Topics: Acute Disease; Acyclovir; Adult; Antibodies, Viral; Antibody Formation; Antiviral Agents; Biopsy; Diagnosis, Differential; Female; Hepatitis, Viral, Human; Herpes Simplex; Humans; Immunity, Cellular; Injections, Intravenous; Liver Abscess; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Simplexvirus

Herpes simplex virus and varicella-zoster virus are common infections and are seen frequently in clinical practice. Infection with these viruses results in cutaneous lesions that may be diagnosed clinically, but widely available laboratory testing is useful for confirmation. Asymptomatic herpes simplex virus shedding, or "subclinical reactivation," likely occurs in all persons infected with herpes simplex virus and results in the transmission of virus despite the absence of signs or symptoms that suggest active infection. Oral and intravenous acyclovir are effective in treating initial and recurrent herpes simplex and varicella-zoster virus infections. The daily administration of oral acyclovir as suppressive therapy is effective in patients with frequently recurring genital infection with herpes simplex virus by reducing the number of symptomatic recurrences and the frequency of asymptomatic virus shedding. Two new antiviral agents, famciclovir and valacyclovir hydrochloride, have been approved for the short-term treatment of recurrent genital herpes simplex virus and recurrent zoster in nonimmunocompromised hosts. Famciclovir and valacyclovir demonstrate superior pharmacokinetics compared with acyclovir and allow for less frequent daily dosing with higher achievable serum drug concentrations. The attenuated live varicella virus vaccine is now available in the United States and prevents primary varicella-zoster virus infection in susceptible children and adults.

Topics: 2-Aminopurine; Acyclovir; Adult; Antiviral Agents; Chickenpox; Child; Famciclovir; Female; Herpes Simplex; Herpes Zoster; Humans; Male; United States; Valacyclovir; Valine

Herpes infections continue to be prevalent, especially in immunocompromised patients. Some of these patients will develop resistant HSV infections. Therefore, it is important to explore new treatment options. Animal studies have shown cidofovir to be effective in the treatment and prevention of HSV infections. Human data are limited, with only one randomized, double-blind, placebo-controlled trial performed to date. The results from this study look promising; however, due to the small sample size, a larger clinical trial is warranted. The human data available as case reports are suboptimal in the quality of reporting time frames for resolution of lesions/symptoms and outcomes of therapy. Another problem with the case report data is that the TK status of the herpes simplex isolates was not reported. This would have helped substantiate the acyclovir resistance seen in these patients. It was evident in these case reports that acyclovir resistance can be overcome, as acyclovir-resistant strains became sensitive following cidofovir therapy. This may be because TK(+) viruses have been shown to establish latency more readily than do TK(-) viruses. This pattern suggests that alternating between acyclovir and cidofovir therapies may provide a strategy to manage the emergence of alternatively acyclovir-sensitive and -resistant infections. At present, only the intravenous formulation of cidofovir is commercially available. Advantages of the intravenous formulation include weekly dosing and efficacy. Disadvantages are the complexity of administration and the adverse effect profile. The most common adverse effects with this formulation include nephrotoxicity manifested as proteinuria (12%), and increased creatinine (5%) and neutropenia (15%). Administration of probenecid and NaCl 0.9% hydration are used to reduce the incidence and severity of nephrotoxicity in patients who are receiving cidofovir. Probenecid also has toxicities, including nausea, vomiting, headache, fever, and flushing. The topical formulation of cidofovir looks promising for mucocutaneous HSV infection because it is usually undetectable in the blood following topical administration. Therefore, systemic adverse effects should be minimized. A cidofovir gel product (Forvade, Gilead Sciences) is currently being reviewed by the Food and Drug Administration for the treatment of refractory HSV. Ultimately, more controlled clinical studies are necessary to determine whether routine cidofovir use can be justi

Topics: Acyclovir; Animals; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Microbial; Herpes Simplex; Humans; Organophosphonates; Organophosphorus Compounds; Simplexvirus

Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Arabinofuranosyluracil; Bromodeoxyuridine; Chickenpox; Drug Resistance, Microbial; Encephalitis, Viral; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Prodrugs; Simplexvirus; Valacyclovir; Valine

Topics: Acyclovir; Animals; Antiviral Agents; Ganciclovir; Herpes Simplex; Humans; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured

Topics: Acyclovir; Animals; Antiviral Agents; Chickenpox; Drug Resistance, Microbial; Herpes Simplex; Herpesvirus 3, Human; Humans; Simplexvirus

Herpes simplex virus (HSV) infections in the neonate can be acquired during pregnancy and during and following the birth process. The most common mode of transmission is from exposure to the virus in the birth canal at the time of delivery. HSV is among the less common infections in neonates. This often leads to delay in diagnosis and treatment, increasing the risk of a poor or fatal outcome. Clinically, HSV infection often presents in preterm or term infants with signs and symptoms similar to those of bacterial sepsis. Their immature immune systems puts preterm infants at higher risk for serious disease. A positive maternal history of HSV is not needed to support diagnosis; typically the mother is asymptomatic. Primary maternal infection usually leads to more serious disease in the neonate. It is important that caregivers recognize the subtle signs and symptoms of HSV infection so early diagnosis and prompt treatment can be instituted.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Neonatal Nursing; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Risk Factors

Herpes simplex encephalitis (HSE) is a life-threatening condition with high mortality as well as significant morbidity in survivors. In most cases herpes simplex virus type 1 (HSV-1) is responsible for the diseases, however, the type 2 virus (HSV-2) is involved in 4-6% of cases. Primary HSV infection is identified in only one-third of patients with HSE. The majority of cases are recorded in adults with recurrent HSV infection who are already seropositive for HSV at the onset of symptoms, but only 6-10% of these patients have a history of labial herpes. Acute focal, necrotizing encephalitis with inflammation and swelling of the brain tissue are consistent features of the pathology of HSE. HSV-induced cytolysis certainly damages neurones, oligodendrocytes and astrocytes, but the role of cellular and humoral immunopathology is important. A complex network of cytokines seems to be active in regulating the local immune response and inflammation during and after HSE. Brain biopsy, serological analysis of intrathecal HSV antibodies and detection of HSV-DNA in the cerebrospinal fluid (CSF) are all useful techniques to confirm the aetiology of HSE. Neurodiagnostic tests which support a presumptive diagnosis of HSE include: CSF analysis, electroencephalography, computer-assisted tomography and magnetic resonance imaging. Although aciclovir is the treatment of choice in HSE, mortality and morbidity still remain problematic. Long-term follow-up indicates that intrathecal cellular and humoral activation persist in HSE.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Clinical Trials as Topic; Diagnosis, Differential; DNA, Viral; Encephalitis, Viral; Herpes Simplex; Humans; Magnetic Resonance Imaging; Middle Aged; Polymerase Chain Reaction; Prognosis; Serologic Tests; Simplexvirus; Survival Rate

This paper focuses on the advances that have been made in our understanding of the pathogenesis, diagnosis, treatment, and prevention of herpes simplex virus (HSV) infections. Insights have been gained into the immune defense mechanisms that may be active in protecting the fetus from HSV infection. An animal model that closely mimics human neonatal HSV disease may permit exploration of novel interventional strategies. Brain biopsy for the diagnosis of HSV encephalitis has been supplanted by polymerase chain reaction detection of HSV DNA in the cerebrospinal fluid and, to a lesser extent, by detection of intrathecal HSV-specific antibodies. Prolonged immune activation within the nervous system following HSV encephalitis has been demonstrated and may implicate immune activation in the pathogenesis of HSV-induced neurologic damage. The continuing emergence of antiviral drug resistance further underscores the need for new strategies for treatment and prevention of HSV infections.

Topics: Acyclovir; Child; Encephalitis, Viral; Herpes Simplex; Humans; Polymerase Chain Reaction; Vaccines, Synthetic

Herpes simplex virus infections of the central nervous system remain a significant cause of morbidity and mortality, in spite of safe and efficacious antiviral therapy. Advances in the treatment of neonatal herpes and herpes simplex encephalitis with acyclovir have improved outcome. The application of polymerase chain reaction has allowed for the prompt and specific diagnosis of herpes simplex virus infections of the brain. This review summarizes our current knowledge on the pathogenesis, diagnosis, and treatment of herpes simplex virus infections of the brain. Opportunities for the future will be defined.

Topics: Acyclovir; Adult; Central Nervous System Diseases; Herpes Simplex; Humans; Infant; Infant, Newborn; Polymerase Chain Reaction

Herpes simplex virus (HSV) infections are very common in the general population and can be treated with the nucleoside analogue acyclovir. Acyclovir is initially phosphorylated intracellularly in HSV-infected cells by a viral-specific thymidine kinase to acyclovir-monophosphate. The monophosphate is subsequently di- and triphosphorylated by host cellular kinases to the active form of the drug, which inhibits HSV DNA polymerase and incorporates into the elongating viral DNA and causes chain termination. Acyclovir resistance has been increasingly described and is caused by mutations in either the thymidine kinase or the DNA polymerase genes. These mutations result in decreased or absent HSV thymidine kinase production, altered affinity of the thymidine kinase for acyclovir-triphosphate, or altered affinity of the HSV DNA polymerase for acyclovir-triphosphate. Thymidine kinase deficiency accounts for approximately 95% of acyclovir-resistant isolates. Clinical disease due to acyclovir-resistant HSV occurs primarily in immunocompromised patients and is usually characterized by a chronic, progressive ulcerative mucocutaneous disease with prolonged shedding of virus. Several large surveys have been done in an effort to determine the incidence of in vitro and clinical acyclovir resistance. Among immunocompetent hosts, even those who have received > or = 6 years of continuous acyclovir, the prevalence of acyclovir-resistant isolates has remained stable at approximately 3%. Only three cases of clinical resistance of HSV to acyclovir have been reported. However, the incidence in immunocompromised patients, particularly those with AIDS and those who have had bone marrow transplants, is increasing. Transmission of acyclovir-resistant isolates from person to person has not been documented, but due to the increased use of acyclovir and newer drugs, such as famciclovir, there is great concern that this transmission might occur in the future. Continued surveillance in both immunocompetent and immunocompromised hosts for the development of clinical acyclovir-resistant HSV disease is necessary.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Resistance, Microbial; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompromised Host; United States

Neurotoxicity associated with acyclovir use is infrequently encountered. However, the half-life of acyclovir is greatly prolonged in patients with end-stage renal disease, predisposing these patients to neurological side effects that are generally reversible but occasionally severe. In general, renal dialysis effectively decreases the serum level of acyclovir, which correlates with toxicity. We report an unusual case of delirium and coma in a patient undergoing hemodialysis who was receiving what appeared to be an appropriately adjusted dose of acyclovir.

Topics: Acyclovir; Aged; Coma; Delirium; Herpes Simplex; Humans; Kidney Failure, Chronic; Male; Penile Diseases; Renal Dialysis; Ulcer

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Drug Resistance, Microbial; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Valacyclovir; Valine

Topics: Acute Disease; Acyclovir; Adult; Child; Diagnosis, Differential; Encephalitis, Arbovirus; Encephalitis, Tick-Borne; Encephalitis, Viral; Encephalomyelitis; Glucocorticoids; Herpes Simplex; Humans; Immunoglobulins; Infant; Subacute Sclerosing Panencephalitis

In herpes simplex virus, the simplest path to resistance to the drug acyclovir is a mutation that knocks out the enzyme thymidine kinase. Such mutants are highly attenuated in mouse models of viral pathogenesis, but have been reported to be associated with severe disease in immunocompromised patients. This review discusses possible resolution of this paradox.

Topics: Acyclovir; Animals; Drug Resistance, Microbial; Herpes Simplex; Humans; Immunocompetence; Immunocompromised Host; Mice; Mice, SCID; Mutation; Simplexvirus; Thymidine Kinase

Hepatitis is a rare but serious complication of a herpes simplex viral infection. Pregnancy is a risk factor and has been associated with a high maternal and fetal mortality rate. Acyclovir appears to improve the outcome.

Topics: Acyclovir; Adolescent; Biopsy; Female; Gestational Age; Herpes Simplex; Humans; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Prognosis; Risk Factors

Acyclovir produces neurologic symptoms that resemble extension of viral infection into the central nervous system. We discuss our observations in the cases of two patients with acyclovir neurotoxicity and review the findings of all previous reports in the English language literature. Systemic disease, most commonly renal dysfunction, preceded all 30 reported cases of acyclovir neurotoxicity. The most common symptoms were mental status disorder and involuntary movements. Measurement of serum acyclovir levels substantiated the diagnosis in only a subset of patients. Although all patients recovered, hemodialysis hastened the rate of recovery.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Central Nervous System Diseases; Cytomegalovirus Infections; Female; Herpes Simplex; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Although infrequent, untreated neonatal herpes results in death in half the cases and neurologic sequelae in three quarters of the survivors. Neonatal infection is usually acquired from maternal genital herpes, which is asymptomatic or unrecognized in 60% to 80% of women. The greatest risk of neonatal infection occurs when the mother has primary genital herpes involving the cervix at delivery, and the infant is premature and delivered with instrumentation (eg, scalp electrodes). More than 80% of neonates with herpes will have typical herpetic lesions of the skin, eye, or mouth, and most of the remainder will have either encephalitis or a sepsis syndrome with pneumonitis and hepatitis and negative bacterial cultures. Because herpes can mimic other neonatal infections, laboratory diagnosis is important, using cultures of the virus from lesions, peripheral blood white cells, or CSF. Treatment with intravenous acyclovir does reduce mortality and neurologic sequelae, but outcome is still guarded in babies with disseminated disease or encephalitis. Prevention focuses on caesarean section in women with active lesions at the time of impending delivery and avoidance of postnatal exposure. Further studies are needed to determine whether maternal screening (eg, HSV-2 type specific antibodies and vaginal cultures in selected women at delivery) will be cost effective in preventing neonatal herpes.

Topics: Acyclovir; Antibodies, Viral; Cesarean Section; Female; Fetal Diseases; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious

Topics: Acyclovir; Herpes Simplex; Herpesvirus 1, Human; Humans; Incidence; Respiratory Distress Syndrome; Respiratory Tract Infections; Risk Factors; Virus Activation

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Herpes Simplex; Humans

Seventeen cases of disseminated herpes simplex virus (HSV) infection have occurred during pregnancy. Acyclovir therapy was associated with prolongation of the time from admission until spontaneous rupture of the membranes or delivery and an improved maternal outcome. This life-threatening condition has a typical presentation, which includes a nonspecific viral prodrome. During pregnancy, fever and anicteric hepatitis unresponsive to empiric antibiotics should prompt an evaluation for disseminated herpes simplex. Pharyngitis or skin lesions with a positive herpes simplex culture are common, specific signs associated with dissemination. The fever resolves within 48 hours in response to acyclovir therapy. One case of maternal disseminated HSV occurred at 22 weeks' gestation and resolved with acyclovir therapy; a healthy neonate was delivered vaginally at term.

Topics: Acyclovir; Adult; Female; Herpes Simplex; Humans; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome

Over the past 15 years, acyclovir has become established as standard therapy for the management of herpes simplex virus infections, but there are areas where improvements might be made. Acyclovir has a relatively low oral bioavailability. As a result, valaciclovir, the L-valine ester of acyclovir, is being developed. This new drug produces enhanced plasma levels of acyclovir following oral dosing, which will not only allow more convenient dosing for the treatment of herpes simplex virus and varicella zoster virus (VZV) infections, but also mean that valaciclovir has the potential for superior clinical efficacy over acyclovir. This may broaden the potential utility of the drug to include human cytomegalovirus prophylaxis. Other new drugs in the antiherpes area include penciclovir and its pro-drug famciclovir, which have antiviral characteristics similar to acyclovir but no clinical benefit over and above that seen with acyclovir has been demonstrated. The synthesis of new specific antiherpes compounds has led to the discovery of a novel nucleoside analogue, 882C87, which has significantly greater activity against VZV than acyclovir. The compound also has a longer plasma half-life than acyclovir which may permit less frequent dosing.

Topics: Acyclovir; Arabinofuranosyluracil; Cytomegalovirus Infections; Ganciclovir; Guanine; Herpes Simplex; Herpesvirus 3, Human; Humans; Valacyclovir; Valine

Topics: Acyclovir; Child; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infant

Neonatal herpes simplex virus infections cause significant morbidity and mortality among infected babies, despite the availability of antiviral therapy. These infections manifest in one of three forms: skin, eye, and mouth involvement; encephalitis; or disseminated infection. The latter two forms of disease account for more than 50% of babies with neonatal herpes and are associated with mortality and severe morbidity rates that exceed 75% in infected children. Thus future therapeutic efforts must be directed toward improved disease outcome. One such effort is the evaluation of immunoglobulin products (humanized monoclonal antibodies, human monoclonal antibodies and hyperimmune globulin) as part of a concomitant therapeutic regimen for babies with encephalitis and disseminated infection. The logic for such an approach becomes especially apparent for babies with disseminated disease because little transplacental maternal antibody is received at the time of birth. Thus concomitant administration of antiviral therapy with antibody may improve disease outcome.

Topics: Acyclovir; Antibodies, Monoclonal; Female; Herpes Simplex; Humans; Immunization, Passive; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Vidarabine

Persons with AIDS who have CD4+ counts < or = 100 and transplant patients, especially bone marrow allograft recipients, may experience clinically significant infections with acyclovir-resistant herpes simplex virus (HSV) or varicella-zoster virus (VZV). Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Algorithms for the management of these infections were developed at a recent roundtable symposium. The consensus of the panelists was that treatment with foscarnet should be initiated within 7-10 days in patients suspected to have acyclovir-resistant HSV or VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Algorithms; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Immunocompromised Host; Male; Recurrence; Simplexvirus; Trifluridine; Vidarabine

Topics: Acyclovir; Adolescent; Female; Herpes Genitalis; Herpes Simplex; Humans; Male; Papillomaviridae; Papillomavirus Infections; Tumor Virus Infections

Acyclovir, an antiviral nucleoside analogue, is a widely used agent highly specific for herpes simplex and varicella-zoster viruses. Unintended exposure to acyclovir early in pregnancy, which is not uncommon, may cause excessive maternal and physician anxiety. This drug has not been studied prospectively in large numbers of pregnant women and lacks the Food and Drug Administration's approval for gestational use unless benefits clearly outweigh potential fetal harm. However, data published since acyclovir became available do not indicate increased adverse effects related to its use in pregnancy, especially if prescribed in selected situations, such as disseminated primary herpes simplex infections or maternal varicella pneumonia. This article reports the impact of inadvertent acyclovir exposure on a woman during the first trimester of pregnancy and reviews the literature on acyclovir's pharmacology, safety profile, and potential uses during pregnancy.

Topics: Acyclovir; Adult; Female; Fetus; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Trimester, First; Teratogens

The authors report two cases of cutaneous recurrent herpes occurring after a neonatal herpes simplex virus type 2 (HSV2) infection and comment on the role of acute or suppressive therapy by aciclovir (ACV). The two infants were not treated by ACV after the neonatal period. None of the recurrent cutaneous herpes episodes was followed by viral widespread. One case reported by Bergström et al on a relapse of HSV2 encephalitis occurring after a cutaneous herpes in a child argues for the use of ACV in recurrent herpes. However, ACV might alter host defense response to HSV2 infection in neonates and children. Thus, it seems not yet recommended to use ACV either as acute or suppressive therapy in recurrent cutaneous herpes unless a progression of the viral disease is noted.

Topics: Acyclovir; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Recurrence

Topics: Acyclovir; Burns, Chemical; Diagnosis, Differential; Esophageal Stenosis; Esophagitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Lye

Neonatal herpes simplex virus infections are a common problem in the United States, occurring at an incidence of one in approximately 3,500 deliveries. In the absence of antiviral therapy significant morbidity and mortality is attendant with disease. Disease manifestations in the newborn include multiorgan involvement (disseminated disease), encephalitis, and/or infection limited to the skin, eye, or mouth. These three broad classifications provide distinctions in severity of disease for evaluation of outcome following antiviral therapy. The availability of antiviral therapy for life-threatening disease, particularly that which is disseminated or involves the brain, has been of particular benefit for children with neonatal herpes. Both acyclovir and vidarabine have proven effective in the management of neonatal herpes simplex virus infection. With current therapeutic modalities, mortality from disease localized to the skin, eye, and mouth is virtually non-existent, yet a few children (approximately 5%) are still at risk for a long-term neurologic sequelae. For babies with encephalitis, the mortality has been reduced to approximately 15% and nearly 50% of survivors develop normally 3 years after treatment. Outcome with disseminated infection is of less value as mortality remains high (50%), but the number of survivors who develop normally is approximately 85%. The introduction of new antivirals with enhanced lipophilicity and, potentially, greater activity in the central nervous system may further improve outcome from this devastating disease.

Topics: Acyclovir; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious

Inhibitors of the ribonucleotide reductase of herpes simplex viruses (HSV) potentiate the activity of acyclovir in vitro and in animal studies. In addition, the combination of the ribonucleotide reductase inhibitor 348U87 and acyclovir has synergistic therapeutic effects against infections in mice due to thymidine kinase-deficient, thymidine kinase-altered, and DNA polymerase mutants of HSV. We performed a pilot study of topical combination therapy with 348U87 (3%) and acyclovir (5%) cream for acyclovir-resistant, anogenital HSV infections in ten human immunodeficiency virus (HIV)-infected patients. Our results, with lack of complete reepitheliazation of lesions in all patients and poor virologic response, suggest that this therapy is unlikely to be useful for this indication.

Topics: Acyclovir; Animals; Antiviral Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Herpes Simplex; HIV Infections; Humans; Hydrazones; Pilot Projects; Pyridines

The development and use of acyclovir accelerated in the area of the natural history, epidemiology, and biology of herpes simplex viruses. The development of serologic assays that differentiate HSV-1 from HSV-2 demonstrated the worldwide distribution of genital herpes, the role genital ulcers play in facilitating HIV transmission, and the high frequency in which pregnant women acquire HSV infection. The high reactivation rate of HSV-2 infections, the often silent nature of genital herpes, and its widespread anatomic distribution in the genitourinary tract lead to frequent subclinical transmission. Identification and counselling of the asymptomatic carrier is necessary if we are to decrease the transmission of genital herpes.

Topics: Acyclovir; Herpes Simplex; Humans

Topics: Acyclovir; Bone Marrow Transplantation; Herpes Simplex; Humans

Recent dynamic advances of molecular biology have been discovering the specific virus functions and replication strategies that differ greatly from their host cells. These studies made it possible to design the antiviral agents which block virus replication specifically. In this paper, we review the recent approach for development of anti-HIV agents and the problems of anti-herpes compounds applied in clinical treatment.

Topics: Acyclovir; Animals; Antiviral Agents; Herpes Simplex; HIV; Humans; Transcription, Genetic; Virus Replication

The nucleoside analog acyclovir is remarkably effective and selective in herpes simplex virus (HSF) infections. Acyclovir inhibits the viral enzyme DNA polymerase. Emergence of acyclovir-resistant HSV mutants occurs in immunocompromised patients, especially those with AIDS. Detection of HSV strains with resistance to antiviral drugs requires rapid in vitro tests to determine the IC50, i.e., the concentration of drug which inhibits viral replication by 50%. Studies of patterns of HSV resistance to the various antiviral agents used in medicine and characterization of mutant HSV strains have shown resistance to be due to loss or modification of the viral enzyme thymidine kinase or to changes in the viral DNA polymerase. The main clinically-significant acyclovir-resistant mutants are thymidine kinase-deficient and retain sensitivity to vidarabine and foscarnet. Development of resistance to both acyclovir and foscarnet due to changes in viral DNA polymerase is considerably less common but emphasizes the urgent need for new antiviral strategies for use in immunocompromised patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; DNA-Directed DNA Polymerase; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; In Vitro Techniques; Simplexvirus; Thymidine Kinase; Vidarabine

Herpes simplex virus may cause serious infections in neonates. In case of foetal infection in the first trimenon, abortions, stillbirth, prematurity, intrauterine growth retardation (not obligatory) and various malformations may result. Neonatal HSV infection is mostly the consequence of intrapartum virus acquisition during passage through the birth canal. The infection is mostly localised on the skin, at the eyes or the mouth or disseminated with or without HSV meningoencephalitis. It is difficult to establish the diagnosis, because neonatal herpes disease in the early stage is not easy to distinguish from other diseases in the newborn such as RDS, NEC or ICH. Antiviral therapy with aciclovir is the treatment of choice and seems to improve the outcome of neonatal herpes. Prognosis depends on early therapy. Treatment should be initiated in relation to clinical findings, because available diagnostic techniques do not always permit an early detection of the disease.

Topics: Acyclovir; Diagnosis, Differential; Female; Herpes Simplex; Humans; Infant, Newborn; Pneumonia, Viral; Pregnancy; Viremia

Topics: Acyclovir; Chickenpox; Herpes Simplex; Herpes Zoster; Humans

Virus infections account for considerable morbidity in bone marrow transplant (BMT) recipients. In all ages, members of the herpes virus group are the predominant pathogens. Of these, cytomegalovirus is pre-eminent in being the most frequent cause of death due to infection associated with the transplant procedure. Considerable effort is being invested in the development of preventative and therapeutic strategies to control this virus. Other potentially life-threatening virus infections may be acquired on the transplant unit as a result of cross-infection and can be caused by enteroviruses, rotaviruses and adenoviruses. Prevention of these infections is best achieved by implementation of strict infection-control measures.

Topics: Acyclovir; Adult; Bone Marrow Transplantation; Child; Cytomegalovirus Infections; Ganciclovir; Graft vs Host Disease; Herpes Simplex; Humans; Neutropenia; Respiratory Syncytial Viruses; Respiratory Tract Infections; Respirovirus Infections; Tissue Donors; Virus Diseases

Herpes simplex virus (HSV) infection is common in patients receiving cytotoxic therapy for cancer. Almost all infections result from reactivation of latent virus during treatment-induced immunosuppression. Typical, self-limited orolabial or genital ulceration does not always require laboratory diagnosis or treatment, but HSV may present in an atypical fashion in cancer patients and cause more severe and prolonged mucocutaneous infection or visceral disease. The presence of antibodies to HSV identifies patients at risk for recurrent HSV infection. The treatment of choice is acyclovir, which may also be used to prevent infection in high-risk patients. Acyclovir resistance has been reported in patients with profound and prolonged immune deficiency, but remains rare in patients treated for cancer.

Topics: Acyclovir; Drug Resistance; Herpes Simplex; Humans; Immunocompromised Host; Neoplasms; Simplexvirus

A case of cutaneous herpes relapse with meningitis is reported in a 1.5 month-old infant treated during the first three weeks of life with acyclovir (ACV) for a neonatal herpes infection. Such a relapse has previously been described in older children as well as in adults. In this case report, there was immunological response to herpes virus infection, 2.5 months after the onset of the infection. The relapse is discussed taking into account the mechanism of action of ACV, the age of the patient and the immunological response profile. Because of the high risk of neurological involvement, we suggest that the relapse should be treated with ACV for a period of time longer than actually recommended.

Topics: Acyclovir; Administration, Oral; Herpes Simplex; Humans; Infant, Newborn; Injections, Intravenous; Male; Recurrence; Skin Diseases, Infectious

Herpes simplex encephalitis (HSE) is the most common nonepidemic cause of acute viral encephalitis. Since successful therapy depends on a high level of suspicion that HSE is present and on the early administration of antiviral treatment, knowledge of clinical and laboratory findings of HSE is of great importance. The clinical hallmark of HSE are signs of both focal and diffuse neurologic involvement. Our case report exemplifies the diagnostic problems that can occur in HSE-patients. The validity of the different ancillary examinations is discussed. Up to the present time brain biopsy has been the method of choice for a reliable early diagnosis of HSE. In the foreseeable future early diagnosis is likely to become available in a non-invasive way by the polymerase-chain reaction. Immediate antiviral therapy with acyclovir in HSE has proved to be useful in rigorously controlled trials. The clinical picture of the acyclovir-induced encephalopathy represents a disorder that can be probably avoided by means of a sufficient hydration.

Topics: Acyclovir; Adult; Antigens, Viral; Encephalitis; Female; Herpes Simplex; Humans; Immunologic Techniques; Simplexvirus; Tomography, X-Ray Computed

Neonatal herpes simplex virus (HSV) infections are of increasing incidence in North America, now occurring at a rate of approximately one in 3,500 to one in 5,000 deliveries per year. Disease manifests as one of three forms; namely, infection: localized to the skin, eye and mouth (SEM), encephalitis (CNS), or disseminated disease. With the advent of antiviral therapy, it has become possible to decrease mortality and improve morbidity for babies suffering from infection. Advances in antiviral therapy have allowed for prevention of disease progression beyond states of SEM involvement. Furthermore, life threatening infections of the CNS or of multiple organs, have mortality with either acyclovir or vidarabine therapy. Now approximately 15% (CNS) and 50% (disseminated disease) of babies die from neonatal HSV disease. The results of ongoing studies in the United States will summarize the pathogenesis and treatment of neonatal HSV infection.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Nervous System Diseases; Pregnancy; Simplexvirus; Vidarabine

Topics: Acyclovir; Antiviral Agents; Chickenpox; Drug Resistance, Microbial; Herpes Simplex; Herpes Zoster; Humans; Interferons

Topics: Acyclovir; Adult; Child; Female; Herpes Labialis; Herpes Simplex; Humans; Immunocompromised Host; Infant; Male; Mouth Mucosa; Recurrence

Topics: Acyclovir; Animals; Antibodies, Viral; Herpes Simplex; Humans; Immunity, Maternally-Acquired; Immunologic Deficiency Syndromes

Topics: Acyclovir; Adult; Erythema Multiforme; Herpes Simplex; Humans; Recurrence

Herpes simplex virus type 1 and 2 may cause painful mucocutaneous lesions in both immunosuppressed and immunocompetent patients. Indications for the use of acyclovir (ACV) are reviewed. In the second part the management of infections caused by varicella-zoster virus are discussed. Primary varicella (chickenpox) in immunosuppressed children should be treated with i.v. ACV without delay. In healthy patients varicella pneumonia needs to be treated with ACV. Healthy patients with herpes zoster are not usually candidates for antiviral therapy. The only exception is herpes zoster ophthalmicus. In patients with severe immunosuppression, such as transplant recipients, ACV therapy is recommended in order to reduce the rate of dissemination. First reports and our own observations on the development of ACV-resistant HSV and VZV isolates stress the importance of discriminating use of ACV and other antiviral compounds in immunosuppressed patients.

Topics: Acyclovir; Antiviral Agents; Chickenpox; Child; Herpes Simplex; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Immunocompetence; Immunocompromised Host

Resistance to acyclovir in vitro in herpes simplex virus (HSV) isolates has been associated with failure of acyclovir therapy in immunosuppressed patients, and the frequency of reports of clinical resistance in patients with human immunodeficiency virus (HIV) infection is increasing. The primary mechanism of clinical resistance is mutation, producing deficiency in the virus-specified thymidine kinase. A number of case reports and patient series have suggested the efficacy of foscarnet in the treatment of acyclovir-resistant HSV infection in HIV-infected patients. In a recent AIDS Clinical Trials Group study comparing the efficacy of vidarabine and foscarnet in this indication, foscarnet therapy was found to be associated with statistically significant reductions in time to complete healing of lesions, cessation of viral shedding, and 50% reduction in pain, and all patients randomized to receive foscarnet had complete re-epithelialization of lesions. The majority of initial recurrences of herpetic lesions in patients in this study were susceptible to acyclovir; however, all patients ultimately experienced a recurrence due to acyclovir-resistant HSV. A trial comparing acyclovir suppression, foscarnet maintenance therapy, and no chronic antiviral therapy after successful initial treatment of acyclovir-resistant HSV infection would be useful in defining the optimal management of recurrent disease.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Resistance; Herpes Simplex; Humans

Antiviral drugs have proven effective in treatment of herpesvirus infections and in prevention of reactivation of latent virus. The prototype drug is acyclovir. Herpes simplex virus (HSV) is susceptible to acyclovir. There is increasing evidence in immunocompromised patients of acyclovir-resistant HSV causing clinical disease. Mechanisms of HSV resistance to acyclovir are known. These findings have implications for the future development and clinical use of antiviral drugs.

Topics: Acyclovir; Drug Resistance, Microbial; Herpes Simplex; Humans; Immunologic Deficiency Syndromes; Simplexvirus

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Drug Resistance, Microbial; Foscarnet; Ganciclovir; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Phosphonoacetic Acid

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans; Polymerase Chain Reaction; Treatment Outcome; Vidarabine

Affecting millions of Americans each year, herpes simplex virus infections are among the most common human viral infections. Many clinical forms exist, depending on the site of infection and the patient's age and immune status. Clinical evaluation and laboratory studies help establish the diagnosis. Acyclovir is the drug most often used to treat herpes simplex virus infections, although newer agents, such as phosphonoformate trisodium, may be required for acyclovir-resistant infections.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Diagnosis, Differential; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; Humans; Idoxuridine; Infusions, Intravenous; Phosphonoacetic Acid; Recurrence; Skin Diseases, Infectious; Trifluridine; Vidarabine

Significant progress has been made in the recognition and treatment of herpes simplex disease in the newborn. This review discusses four current issues surrounding this severe and important infection. First, the reasons underlying the failure of antenatal screening programs to identify high-risk pregnancies for herpes simplex are analyzed. Second, typical and atypical clinical manifestations of neonatal herpetic infection are reviewed. Third, determinants of disease, particularly the immune status of the mother and child, and their therapeutic implications are discussed. Finally, controversies surrounding antiviral therapy are examined.

Topics: Acyclovir; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Prenatal Diagnosis; Vidarabine

Erythema multiforme minor is an acute, self-limited cutaneous or mucocutaneous disorder. Although it most commonly afflicts young adults, it is also frequently seen in children. An antecedent infection with herpes simplex virus is often the precipitating factor. Recent studies detailing the usual clinical course and histologic features of erythema multiforme minor, together with investigative studies examining potential pathomechanisms, have begun to provide a clearer picture of this disease process such that a more rational approach to therapy is now possible.

Topics: Acyclovir; Adolescent; Adult; Age Factors; Child; Child, Preschool; Diagnosis, Differential; Erythema Multiforme; Herpes Simplex; Humans; Infant

Two cases of herpes simplex virus hepatitis in pregnancy are presented. Each case was characterized by extremely high serum aminotransferase levels with minimal bilirubin elevation. In both cases, liver biopsy was instrumental in arriving at the diagnosis. In addition, computed tomography showed a radiographic appearance of the liver not characteristically seen in other hepatic disorders of pregnancy. A high index of suspicion in the second case led to early recognition and treatment. Despite the presence of fulminant liver failure and evidence of herpes encephalitis in the other case, institution of therapy with acyclovir was associated with complete recovery in both patients. The present cases are compared and contrasted with the literature. The incidence of two cases within a 6-month period suggests that herpes simplex virus hepatitis in pregnancy may occur more frequently than previously reported.

Topics: Acyclovir; Adult; Female; Hepatitis, Viral, Human; Herpes Simplex; Humans; Pregnancy; Pregnancy Complications, Infectious

Patients with Herpes simplex encephalitis often are considered to be poor rehabilitation candidates because of their multiple deficits and grave prognosis. This report presents case reports on three patients with biopsy-proven Herpes simplex encephalitis, all of whom were treated with acyclovir in acute care and then admitted to an inpatient rehabilitation program. All had multiple brain lesions with minimal motor findings but cognitive and communication deficits. One patient, two weeks after admission, slipped into a coma and was transferred to an acute care hospital where he subsequently expired. The other two made useful functional gains and were discharged home in two weeks and 10 weeks, suggesting that a trial of rehabilitation may be warranted after Herpes simplex encephalitis.

Topics: Activities of Daily Living; Acute Disease; Acyclovir; Adaptation, Physiological; Adult; Encephalitis; Female; Herpes Simplex; Humans; Male; Middle Aged; Prognosis

Specific antivirals like acyclovir have ameliorated the outcome of severe herpesvirus infections, especially in immunocompromised patients. Varicella can be prevented in high-risk patients after exposure by therapy with varicella-zoster immunoglobulin. Despite this favorable development, there are many unresolved problems in the management of herpesvirus infections, such as the use of acyclovir during pregnancy, the treatment of both motoric neuropathy and postherpetic neuralgia. Chemotherapy-resistant herpesvirus may cause severe syndromes in patients suffering from HIV infection or from iatrogenic immunosuppression. Isolation of resistant viruses provides the stimulus to establish tests of viral resistance and to use antiviral drugs more carefully.

Topics: Acyclovir; Antiviral Agents; Chickenpox; Drug Resistance; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Immunologic Deficiency Syndromes; Interferons; Vidarabine

Topics: Acyclovir; Chickenpox; Clinical Trials as Topic; Cytomegalovirus Infections; Drug Resistance, Microbial; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans

Topics: Acyclovir; Adult; Antiviral Agents; Child; Child, Preschool; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Naphthoquinones; Pregnancy; Ribavirin; Vidarabine; Xanthenes; Xanthones

Aciclovir (ACV) is the most effective drug for the virostatic management of herpes simplex virus (HSV) infections, and the rate of side-effects is low. ACV resistance is rare, occurring only in highly immunocompromised patients (so far about 30 cases have been reported). Dosages and modes of application of ACV in different HSV infections are indicated and discussed.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Eczema; Encephalitis; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Herpes Simplex; Humans; Vidarabine

Viral pneumonitides are among the known pulmonary complications of human immunodeficiency virus (HIV) infection. Cytomegalovirus (CMV) pneumonitis is the most frequently recognized viral infection involving the lung. Although CMV may occasionally be the sole pathogen found to be responsible for severe pneumonitis in patients with the acquired immunodeficiency syndrome (AIDS), in most cases, its role in causing pulmonary disease is less clear, primarily because of the propensity to infect with a variety of other copathogens. CMV pneumonitis has been difficult to diagnose during life, although techniques utilizing in situ DNA hybridization or monoclonal antibodies for detection of the virus may improve the diagnostic yield of less invasive procedures such as bronchoalveolar lavage. Pneumonitis due to herpes simplex virus, varicella-zoster, and respiratory syncytial virus have occasionally been reported in AIDS patients, and are of practical importance because of the availability of effective treatment. The role of influenza and adenoviruses in causing HIV-related pulmonary complications is unknown, but could be of importance during outbreaks of these infections. Finally, data from several studies now suggest that Epstein-Barr virus or HIV itself or both have a role in the pneumonitis. Further study in this area could provide information leading to more effective management of this common complication of childhood AIDS.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Herpes Simplex; Herpesviridae Infections; Humans; Infectious Mononucleosis; Influenza, Human; Pneumonia, Viral; Retroviridae Infections

Genital herpes simplex infection remains an infectious disease having widespread consequences for both adult and neonatal populations. Physicians must understand that the psychologic impact of genital HSV infections frequently is more disabling than the physical manifestations. Sensitivity, compassion, and support are necessary from members of the medical community, and psychologic counseling may help patients cope with HSV and all its implications. Similarly, physicians must downplay the hysteria that has been associated with herpesvirus infections, emerging as a result of intense media coverage in the 1970s and 1980s. Minimizing the number of cases of neonatal herpes through identification of infected women during parturition continues to be important. Recent guidelines suggest a rationale for the management of women at risk for genital HSV. Nevertheless, until newer immunologic and serologic techniques become clinically reliable and allow a correct and rapid diagnosis of herpes simplex infection, identification of the infected woman in labor must be made using detailed clinical history, physical examination, and viral culture.

Topics: Acyclovir; DNA Replication; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Recurrence; Simplexvirus; Virus Replication

Herpes simplex and varicella-zoster infections of the skin are commonly seen in primary care practice. For the patient to be managed most effectively, clinical diagnoses must be accurately made and supported by laboratory confirmation using the Tzanck smear and/or viral culture. Topical therapy and systemic acyclovir can be of help to most patients with these infections.

Topics: Acyclovir; Herpes Simplex; Herpes Zoster; Humans; Recurrence; Skin Diseases, Infectious

Acyclovir (ACV), an antiviral nucleoside analog, is active against Herpes simplex viruses (HSV1, HSV2) and varicella virus (VZV). These viruses seems to be prejudicial to the pregnant woman and to the fetus. Yet, ACV is not recommended for use in pregnancy. However in certain cases, this drug has been used. We review in this paper, the pharmacokinetics and transplacental passage of ACV, indications, and whether the benefits of the administration of ACV in pregnancy outweigh the theoretical risks. Peak and trough plasma concentrations of ACV in pregnant women seem to be lower as compared to those of non-pregnant adults but effective. This drug crosses the placenta. Levels of ACV in cord blood ranged from 0.5 to 3 mumol/l. In as much as in vitro inhibitory doses 50 (ID 50) for HSV1, HSV2 and VZV ranged from 0.1 to 3 mumol/l, it is quite likely that levels noted above may be effective for in utero inhibition of viral replication. No adverse effects were noted in newborn exposed in utero to ACV. But one must be careful about the direct effects of this drug on nucleic acid metabolism despite encouraging results on animal fetuses. Based on these findings and from our experience, ACV can be administered in pregnancy in two particular situations: in cases of maternal severe viral infections and in order to inhibit in utero VZV replication. Doses required for pregnant women range from 5 to 15 mg/kg/8 hours given intravenously, and 200 mg of oral Acyclovir 5 times daily.

Topics: Acyclovir; Female; Herpes Simplex; Herpes Zoster; Humans; Pregnancy; Pregnancy Complications, Infectious

A young, previously healthy woman developed bilateral exudative tonsillitis that was associated with severe systemic symptoms. This was followed by evidence of multisystem disease with acute abdominal pain, raised liver enzyme levels, respiratory difficulty, increasing drowsiness and multiple vesicular skin lesions. Herpes simplex virus type-1 was isolated from skin lesions and a throat swab and herpes simplex virus type-1 antigen was detected in a liver biopsy sample. She recovered rapidly without any sequelae after treatment with intravenously administered acyclovir.

Topics: Abdominal Pain; Acyclovir; Adult; Female; Hepatitis, Viral, Human; Herpes Simplex; Humans; Immune Tolerance

A 41 year old female developed reactive haemophagocytic histiocytosis secondary to herpes simplex infection, during remission induction for acute lymphoblastic leukaemia. She recovered fully with acyclovir and supportive treatment. Previous publications on the association between acute lymphoblastic leukaemia and haemophagocytic syndrome are reviewed, and the nature of the haemophagocytic disorder is discussed.

Topics: Acyclovir; Adult; Female; Herpes Simplex; Histiocytic Sarcoma; Humans; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction

Acute viral and other infectious causes of encephalitis usually produce fever, headache, stiff neck and alterations in consciousness, focal neurologic signs and seizures. A large number of viral and nonviral agents can cause encephalitis. Arthropod-borne viruses peak in summer, the tick-borne infections occur in early summer, enterovirus infections in later summer and mumps in the winter and spring.

Topics: Acyclovir; Encephalitis; Encephalitis, Tick-Borne; Enterovirus Infections; Herpes Simplex; Humans; Mumps; Seasons

We now have a basis for a more rational approach to rapid evaluation and development of antiviral drugs by screening for activity in vitro, testing for toxicity and efficacy in animals, and clinical testing in humans. Acyclovir is a prototype of this improved process. Interferon has a beneficial effect against CMV infection in renal transplant patients and has promising results in the treatment of papillomas and rhinovirus infections. It does not seem to be as effective against genital herpes or varicella zoster as acyclovir. Ribavirin is effective against respiratory syncytial virus infections and Lassa fever. Varicella-zoster virus is highly sensitive to bromovinyl deoxyuridine in vitro. Phosphonoformate is effective in herpes simplex in animals but of little clinical benefit topically in human recurrent A2 herpes. Zidovudine may decrease mortality rates and infectious complications in patients with acquired immunodeficiency syndrome. DHPG (9-(1,3-dihydroxy-2-propoxymethyl]guanine is useful in treatment of cytomegalovirus and infection in immunocompromised patients. The prodrug of acyclovir results in high blood levels of acyclovir and shows promise in the treatment of varicella-zoster infections. Many halogenated pyrimidine nucleoside analogs are being developed. Buciclovir is another acyclic guanosine analog effective against herpes simplex virus in vitro. 2'-nor-cyclic guanosine monophosphate has a broad antiviral spectrum of action. Interleukin-2 is being investigated. Combined therapies of two or more antiviral drugs or antiviral drugs and other treatments are being studied.

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Interferons; Phosphonoacetic Acid; Ribavirin; Thymidine; Zidovudine

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Brain Edema; Bromodeoxyuridine; Dexamethasone; Drug Therapy, Combination; Encephalitis; Ganciclovir; Herpes Simplex; Humans; Immunoglobulins; Interferons; Vidarabine

Animal and human models of ultraviolet radiation-induced herpes simplex virus disease provide opportunities to study the mechanism of virus latency and reactivation. These models can also be used to study the efficacy of antiviral agents. Prophylactic oral acyclovir altered the development of ultraviolet radiation-induced herpes labialis under both natural and experimental conditions.

Topics: Acyclovir; Animals; Disease Models, Animal; Herpes Simplex; Humans; Simplexvirus; Ultraviolet Rays; Virus Activation

Cytomegalovirus, herpes simplex, and herpes zoster are responsible for the majority of cases of viral retinitis. Herpes zoster also has been strongly incriminated as a causal agent in acute retinal necrosis. Effective chemotherapy exists for retinitis caused by herpes simplex and herpes zoster, along with acute retinal necrosis. Conventional antiviral therapy and immunomodulators are ineffective in the treatment of cytomegalovirus retinitis in patients with acquired immune deficiency disorder. Ganciclovir, a new antiviral agent, has significantly reduced visual morbidity in these patients. Recurrence of the infection is not uncommon while patients are on the drug or when the agent is discontinued, because ganciclovir is virostatic and does not stop viral replication in the retina. The inability to control this viral retinitis using presently available chemotherapy indicates a need to examine other therapeutic modalities.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Ganciclovir; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Retinitis

The treatment of herpes simplex virus (HSV) infections in the past has been largely unsuccessful. Introduction of the drug acyclovir has been a positive development. Acyclovir has been extensively studied in the treatment of a a variety of HSV infections in immunocompromised patients and in otherwise healthy patients. The results have shown it to effectively inhibit HSV replication but to have no effect in preventing or eliminating the latent state of the virus. It has been shown to be very effective in certain instances and not so effective in others.

Topics: Acyclovir; Facial Dermatoses; Herpes Simplex; Humans; Recurrence; Stomatitis, Herpetic

Non-genital herpes simplex virus in immunocompetent hosts causes a variety of primary infections--gingivostomatitis, keratoconjunctivitis, herpetic whitlow, and encephalomyelitis. Recurrent infections with orolabialis are very common, but are usually mild and self-limiting. Cutaneous complications of herpes simplex virus infections include eczema herpeticum and erytherma multiforme. Systemic treatment with acyclovir is indicated in encephalomyelitis, progressive eczema herpeticum, and frequent severe erythema multiforme. Chronic, suppressive acyclovir treatment may be helpful in severe recurrent infections or those complicated by erythema multiforme/dissemination. Many primary and recurrent infections can be treated with simple topical therapy to control secondary infection. There is no evidence that systemic treatment affects viral latency or recurrent infections following discontinuation of treatment.

Topics: Acyclovir; Erythema Multiforme; Herpes Simplex; Humans; Idoxuridine; Immunity; Kaposi Varicelliform Eruption; Recurrence; Vaccination

Herpes simplex virus (HSV) infections are a significant cause of morbidity among immunocompromised patients, and in some instances these infections may be a primary cause of death. The overwhelming majority of these infections are caused by reactivation of the virus. The natural history of reactivated HSV infections in immunocompromised patients has been well described, and these infections occur predictably in particular patient populations. Antiviral therapy has been shown to be effective in treating or preventing HSV infections. Randomized, controlled, double-blind studies have demonstrated that acyclovir is the most effective compound currently available for treatment or prevention of HSV infections.

Topics: Acyclovir; Clinical Trials as Topic; Drug Administration Schedule; Herpes Simplex; Humans; Immune Tolerance; Vidarabine

Herpes simplex virus (HSV) infections of the central nervous system are a significant cause of mortality and morbidity. The introduction of antiviral therapy has improved the outcome for patients with life-threatening disease. Neonatal HSV infection is usually acquired at the time of delivery by contact of the fetus with infected maternal genital secretions resulting in disease that can be localized to the skin, eye, and mouth, and can lead to encephalitis or become disseminated. A total of 291 babies with neonatal HSV infection have been evaluated over a period of 14 years with mortality and morbidity rates determined at one year. Vidarabine therapy decreased the incidence of mortality and improved morbidity rates; however, further improvement in mortality rates with acyclovir therapy has not been apparent. No significant clinical toxicity appeared in either treatment group. In order to improve outcome, earlier intervention and prophylactic strategies must be developed. For patients with herpes simplex encephalitis, acyclovir therapy is superior to vidarabine therapy for biopsy-proven disease. When outcome is compared for 136 vidarabine- and 46 acyclovir-treated, biopsy-proven patients, mortality rates are decreased to 20 percent with acyclovir, and approximately 40 percent of survivors are evaluated as normal at one year after therapy. Despite better outcome with antiviral therapy for the treatment of biopsy-proven herpes simplex encephalitis, further improvement is required.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Infant; Infant, Newborn; Vidarabine

Lymphangitis and lymphedema are rarely reported complications of herpetic hand or genital infection. The natural history of these complications is gradual resolution over 14 to 21 days. Recognition of this presentation of herpes infection avoids unnecessary surgery and antibacterial therapy. Antiviral therapy may have a role in shortening the duration of symptoms and aborting recurrent lymphangitic episodes.

Topics: Acyclovir; Administration, Oral; Adult; Female; Fingers; Hand Dermatoses; Herpes Simplex; Humans; Lymphangitis; Male; Middle Aged; Recurrence

Topics: Acyclovir; Age Factors; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Vidarabine

The efficiency of nucleoside analogs for the management of herpes-simplex-infections has been established. It has been pointed out by many studies, that aciclovir is well tolerated and shortens both symptoms and lesions of herpes-simplex-infections. A continuous oral aciclovir management up to six month suppresses recurrences of genital herpes under therapy significantly.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Humans

Herpes simplex infections in neonates include (1) infections beginning in skin or mucous membranes, (2) infections of the central nervous system, and (3) disseminated herpes of the newborn. Early recognition of infections beginning in skin or mucous membranes is essential because 75% will disseminate internally if untreated. Skin lesions provide important diagnostic clues in herpes of the nervous system and disseminated herpes, but they often appear late and in only about 60% of infected neonates. Acyclovir and vidarabine are effective therapies but they must be administered early to prevent serious damage or death. Herpetic skin lesions in neonates may be confused with pyodermas. Direct immunofluorescence and cultures are reliable diagnostic tests. Congenital herpes may cause widespread skin involvement and multiple eye and nervous system diseases. The mother is the source of neonatal herpes in about two thirds of cases. Asymptomatic genital shedding of virus late in pregnancy does not accurately predict whether maternal cultures will be positive at the time of delivery. The risk of the infant acquiring neonatal herpes from a mother with recurrent herpes at birth is about 5%, but the risk is much higher if the mother has true primary genital infection.

Topics: Acyclovir; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Vidarabine

Topics: Acyclovir; Aphasia; Drug Administration Schedule; Encephalitis; Herpes Simplex; Humans; Immune Tolerance; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Recurrence

Herpes simplex encephalitis is a rapidly progressive disease in neonates and adults. Mortality is high, and there are severe neurologic sequelae in survivors. The reasons for centripetal transfer of virus to the brain are not fully understood. Prompt diagnosis followed by antiviral therapy with acyclovir significantly improves the prognosis. Controversy surrounds the need for brain biopsy before antiviral therapy is started.

Topics: Acyclovir; Encephalitis; Herpes Simplex; Humans

Herpes simplex encephalitis (HSE) is an uncommon disease, yet 25 to 30 per cent of cases involve children. The initial clinical findings are nonspecific (fever, altered mental status), but most cases evolve to demonstrate focal neurologic signs and symptoms. The CSF is abnormal in over 90 per cent of cases. The EEG, CT, and MRI will further help in detecting focal encephalitis. The clinician caring for a child with focal encephalitis should institute broad-spectrum antimicrobial therapy plus acyclovir, pending definitive diagnosis by ancillary tests or brain biopsy, which is positive for HSE 33 to 55 per cent of the time and is diagnostic for other treatable conditions 10 to 20 per cent of the time. Acyclovir is the drug of choice for HSE and substantially reduces mortality and morbidity. The management of HSE in a child requires an experienced team of specialists and laboratory support in a tertiary intensive care setting.

Topics: Acyclovir; Child; Encephalitis; Herpes Simplex; Humans; Vidarabine

Herpes simplex virus infections cause considerable morbidity in immunocompromised and immunocompetent individuals. The development of immunomodulatory agents and nucleoside analog drugs has been responsible for important advances in the treatment of HSV infections. Acyclovir, an acyclic guanosine derivative, has played a major role in the treatment and suppression of HSV episodes in immunocompromised and immunocompetent patients.

Topics: Acyclovir; Herpes Simplex; Humans; Idoxuridine; Immunocompetence; Infant, Newborn; Interferons; Vidarabine

Buciclovir is an example of an antiherpes, acyclic guanosine analog activated by the viral thymidine kinase and inhibiting viral DNA synthesis in infected cells. An investigation of closely related buciclovir-analogs with similar antiherpes activities in cell cultures and similar, or identical, modes of action but with disparate effects in vivo, revealed the following critical determinants of antiherpes efficacy. (1) The accumulation of guanosine analog-triphosphates in infected cells, which is cell-type-specific and analog-dependent. (2) The potencies of the triphosphates as inhibitors of the viral DNA polymerase. (3) The plasma kinetics of the analogs, which are widely different despite the similar structures. (4) The penetration into nervous tissue relative to penetration into non-nervous tissues, of importance in connection with the neurotropic behavior of the virus. (5) The concentration of the antagonist thymidine in certain tissues. (6) The difference in pathogenesis between primary infections and recurrent infections, exemplified in the different efficacies of topically applied drugs in cutaneous and genital HSV-2 infections in guinea pigs.

Topics: Acyclovir; Animals; Antiviral Agents; Chemical Phenomena; Chemistry; Herpes Simplex; Simplexvirus; Structure-Activity Relationship

Topics: Acyclovir; Adenine; Antiviral Agents; Drug Resistance, Microbial; Herpes Simplex; Humans; Organophosphonates; Organophosphorus Compounds; Simplexvirus; Thymidine Kinase; Viral Proteins

Topics: Acyclovir; Administration, Oral; Chickenpox; Child; Child, Preschool; Drug Resistance, Microbial; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Infant; Injections, Intravenous; Simplexvirus

Topics: Acyclovir; Adult; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious

In the 5 years since its release for clinical use, acyclovir (9-[2-hydroxyethoxymethyl]guanine) has proved to be a safe and effective agent for therapy of herpes simplex and varicella-zoster infections. The drug's availability in topical, oral, and intravenous preparations has allowed its use in a range of clinical situations. Acyclovir must be phosphorylated by viral thymidine kinase in infected cells, where it then acts to inhibit viral DNA replication specifically. Epstein-Barr virus and human cytomegalovirus infections do not seem to respond to acyclovir therapy, although in-vitro effects on these viruses may be seen. Acyclovir is well absorbed and distributed, with cerebrospinal fluid levels 50% that of plasma. Clearance is almost entirely by the renal route, with a half-life of 20 hours in the anuric patient. Acyclovir has an excellent safety profile, its major adverse effect being transient serum creatinine elevations during high-dose intravenous use. Major uses include treatment of primary and recurrent genital herpes and herpes encephalitis and prophyllaxis and therapy of mucocutaneous herpes and varicella-zoster infections in immunocompromised patients. Resistance to acyclovir in herpes simplex virus is rarely encountered and does not seem to be due to long-term chronic suppressive therapy.

Topics: Acyclovir; Chickenpox; Drug Interactions; Drug Resistance, Microbial; Ganciclovir; Herpes Simplex; Herpes Zoster; Herpesviridae; Humans; Postoperative Complications; Transplantation

Acyclovir has been widely used against the various manifestations of eye disease due to herpes simplex since it first became generally available in the UK nearly five years ago. This paper discusses the rational indications for its use, through considerations of its pharmacology and pharmacokinetics, and through results of the many clinical trials that have been carried out to investigate its effects since its clinical efficacy was first demonstrated in 1979.

Topics: Acyclovir; Clinical Trials as Topic; Conjunctivitis, Viral; Corneal Ulcer; Herpes Simplex; Humans; Keratitis, Dendritic; Uveitis

ACV is an effective agent for the treatment and prophylaxis of HSV infections in both IC and immunologically normal individuals. The drug is well tolerated in both populations and is not significantly associated with clinical or laboratory toxicities. Because of the great potential benefit and low risk, organ transplant recipients and patients with hematologic malignancies undergoing induction chemotherapy should be screened routinely for HSV antibodies; seropositive individuals should receive prophylactic ACV during the period of most profound immunosuppression. Immunologically normal individuals with frequently recurring genital HSV or serious complications associated with outbreaks are candidates for long-term suppression with ACV.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Resistance, Microbial; Herpes Simplex; Humans; Immune Tolerance

Topics: Acyclovir; Autonomic Nervous System Diseases; Encephalitis; Esophagitis; Facial Dermatoses; Female; Fingers; Hepatitis, Viral, Human; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Infant, Newborn; Keratitis, Dendritic; Male; Peripheral Nervous System Diseases; Recurrence; Respiratory Tract Infections; Stomatitis, Herpetic; Vaccination; Viral Vaccines

Herpes simplex viruses cause common mucocutaneous infections, but many aspects of their epidemiology and transmission are incompletely defined. Although the incidence of oral herpes remains relatively unchanged, the incidence of genital herpes is increasing significantly. Definitive diagnosis of herpes remains dependent on virus isolation, but techniques involving direct examination of clinical specimens are increasingly sensitive and may simplify and speed diagnosis. With the advent of acyclovir, effective therapy and suppression of infection are feasible for immunodeficient and selected normal patients. Unanswered questions remain regarding the long-term safety of acyclovir and the potential for emergence of clinically significant drug resistance. No effective vaccines are yet available for herpes virus infections. Promising strategies for vaccine development include preparation of immunogenic proteins, engineering of specially attenuated live virus strains, and incorporation of selected herpes genes into live vaccinia virus vectors.

Topics: Acyclovir; Adult; Animals; Antiviral Agents; Child, Preschool; Drug Resistance, Microbial; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant; Interferons; Male; Recurrence; Simplexvirus; Stomatitis, Herpetic; Viral Vaccines; Virus Activation; Virus Cultivation

Topics: Acyclovir; Chickenpox; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Infant, Newborn; Interferons; Papillomaviridae; Skin Diseases, Infectious; Tumor Virus Infections

The group of the human-pathogenic herpesviruses comprises five subgroups: Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Primary infection with these ubiquitous herpesviruses usually occurs in childhood or during adolescence and frequently remains inapparent. However, it can also give rise to a variety of clinical pictures. Important clinical manifestations of herpesvirus infections are mucocutaneous lesions (HSV-1, HSV-2, VZV) self-limited, lymphoproliferative diseases (CMV, EBV) and congenital malformations (CMV). Primary infection with herpesviruses leads to a persistent infection of the host. This clinically silent condition of latency can be interrupted and may cause pathological symptoms to recur by reactivation of latent herpesviruses. A classical example of the clinical manifestation of herpesvirus reactivation is herpes zoster following an overcome varicella disease. The mechanism of herpesvirus reactivation has not yet been fully clarified. Reactivation of herpesviruses might be attributable to a weakening of the cellular immunodefence. For the control of viral infections mainly two cellular effector systems are responsible: unspecific, cytotoxic, natural killer (NK) cells and specific cytotoxic thymus-dependent (T) lymphocytes. The functional impairment of these cytotoxic active cells my cause herpesvirus reactivation in immunodeficient or immunosuppressed persons. Interference with the immunological control function may also contribute to the genesis of herpesvirus-associated tumours. Such an association between herpesviruses and human tumours is assumed to exist especially in the case of EBV. The frequently life-endangering severity of local or disseminated herpesvirus infections calls for suitable measures ensuring efficient prophylaxis and therapy. However, the possibilities of a specific immunoprophylaxis (vaccine, special immunoglobulins) against herpesvirus infections are still rather limited. The development of antiviral substances has greatly benefited from the introduction of new agents (Acyclovir) and the production of sufficient quantities of interferon (IFN) preparations during the last few years. Impressive results were obtained with the nucleoside-related substance Acyclovir in the prevention and therapy of primary or reactivated HSV-1 or HSV-2 infections. The use of Acyclovir as prophylactic agent produced the effect tha

Topics: Acyclovir; Antiviral Agents; Burkitt Lymphoma; Chickenpox; Cytomegalovirus; Cytomegalovirus Infections; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesviridae; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Immunity, Cellular; Immunization, Passive; Infectious Mononucleosis; Male; Nasopharyngeal Neoplasms; Simplexvirus; Smallpox Vaccine; T-Lymphocytes; Vidarabine

Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Infant, Newborn, Diseases; Keratitis, Dendritic; Trifluridine; Vidarabine

New therapies and diseases causing immunosuppression have provoked new and devastating ocular diseases. The possible reasons for the vulnerability of the retina to opportunistic infections are discussed. The clinical patterns of disease caused by common opportunistic agents are described, and current treatment available is reviewed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Candidiasis; Chorioretinitis; Cytomegalovirus Infections; Eye Diseases; Herpes Simplex; Herpes Zoster; Humans; Immunity, Cellular; Immunosuppression Therapy; Infant, Newborn; Retina; Retinal Diseases; Retinal Vessels

Topics: Acyclovir; Animals; Drug Resistance, Microbial; Guinea Pigs; Herpes Simplex; Herpesviridae; Humans; Mice; Mutation; Simplexvirus; Thymidine Kinase

Topics: Acute Disease; Acyclovir; Animals; Ganglia; Genes, Viral; Herpes Simplex; Humans; Lymph Nodes; Mice; Mutation; Nerve Endings; Neurons; Simplexvirus; Thymidine Kinase; Virion; Virus Replication

Topics: Acyclovir; Chickenpox; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Interferon Type I; Recurrence; Vidarabine

Acyclovir is now established as an effective and well tolerated therapeutic agent for the management of at least the more common infections of the herpes virus group. Evaluation of the drug nevertheless continues, primarily to verify its value in those infections caused by cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Furthermore with the development of analogues of acyclovir with better absorption profiles or enhanced anti-viral activity the future for this area of anti-viral therapy looks optimistic.

Topics: Acyclovir; Cytomegalovirus Infections; Encephalitis; Forecasting; Hepatitis B; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immune Tolerance; Infectious Mononucleosis; Keratitis, Dendritic; Recurrence

Topics: Acyclovir; Allopurinol; Animals; Drug Therapy; Folic Acid Antagonists; Herpes Simplex; Herpes Zoster; Humans; Leishmania; Mercaptopurine; Neoplasms; Nucleic Acid Synthesis Inhibitors; Recurrence; Species Specificity

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Child; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Idoxuridine; Infant, Newborn; Male; Pregnancy; Stomatitis, Herpetic; Vidarabine

Topics: Acyclovir; Animals; Chlorocebus aethiops; Drug Resistance, Microbial; Herpes Simplex; Humans; Infant, Newborn; Mice; Mutation; Rabbits; Simplexvirus; Vidarabine

Topics: Acyclovir; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Keratitis, Dendritic; Keratoconjunctivitis; Male; Vidarabine

Infections with herpes simplex virus (HSV) are extremely common. HSV infection may be asymptomatic or may cause any one of a wide variety of disease syndromes. In this review, the physical properties and mode of replication of HSV are briefly described, and an outline of the different clinical manifestations associated with HSV infection is presented. Principles of diagnosis, treatment, and prevention of these infections are also discussed.

Topics: Acyclovir; Adult; Animals; Child; Encephalitis; Female; Genes, Viral; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Male; Meningitis, Viral; Pregnancy; Recurrence; Simplexvirus; Stomatitis, Herpetic; Transcription, Genetic; Vidarabine; Virus Replication

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a newly licensed acyclic nucleoside analog that is active in vitro and in vivo against herpes simplex virus (HSV) and varicella zoster virus (VZV). This agent is available in the United States in topical and intravenous forms, and the oral preparation is currently being evaluated in clinical trials. The precise therapeutic role for acyclovir in patients with herpesvirus infections is still evolving. This article reviews the current status of this exciting new antiviral agent.

Topics: Acyclovir; Aged; Chickenpox; Cytomegalovirus Infections; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Infant, Newborn; Infectious Mononucleosis; Injections, Intravenous; Keratitis, Dendritic; Male; Pregnancy; Risk; Virus Diseases

Topics: Acyclovir; Administration, Oral; Administration, Topical; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immune Tolerance; Immunization; Injections, Intramuscular; Interferon Type I; Vidarabine

Herpes viruses are among the most common and troublesome opportunistic pathogens infecting patients with neoplastic diseases. The recent development of partially effective and relatively nontoxic antiviral agents offers promise for the prophylaxis or therapy of these infections in high-risk groups. Vidarabine and acyclovir have shown efficacy in several herpes virus infections and are now licensed in the United States. Alpha interferon may also be useful in the prophylaxis or early therapy of certain herpes virus infections. Newer antiviral agents and combination therapies are under study. Early and rapid diagnosis of such infections is critical to the development of effective therapy.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Cloning, Molecular; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infectious Mononucleosis; Interferons; Kidney Transplantation; Leukemia; Lymphopenia; Neoplasms; Pulmonary Fibrosis; Vidarabine

Progress in antiviral chemotherapy has taken place as a logical strategy for the design of antiviral agents has emerged. The second-generation nucleoside analogues, led by acyclovir, have proved their worth against herpesviruses and should now become a standard part of medical practice. Meanwhile, recombinant DNA technology has lowered the cost of interferons to the point at which the several human subtypes of these naturally occurring hormones can be subjected individually to controlled clinical trials against the viral diseases in the treatment of which they show promise. Yet, optimism about the future of antiviral chemotherapy must be tempered by the observation that most of the agents discussed in this review are described more accurately as promising rather than proven, and several of these have not yet been released in Australia at the time of writing.

Topics: Acyclovir; Amantadine; Animals; Antiviral Agents; Bromodeoxyuridine; Female; Hepatitis B; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; In Vitro Techniques; Interferons; Male; Neoplasms; Papillomaviridae; Respiratory Tract Infections; Ribavirin; Rimantadine; Tumor Virus Infections; Vidarabine

Recent developments have increased the options for treatment of viral infections. Vidarabine, an agent originally released for herpes simplex encephalitis, has more recently been shown to be of benefit in neonatal herpes simplex infection and in varicella-zoster infections in immunocompromised hosts. The introduction of acyclovir represents a major advance in antiviral therapy because of its low host toxicity and marked selectivity for herpes simplex and varicella-zoster viruses. Extensive controlled clinical trials demonstrate efficacy in the treatment of infections caused by these viruses in the immunocompromised host and in genital herpes simplex infections in normal hosts. The use of recombinant DNA technology has increased the purity, variety, and availability of interferons for clinical trial. Earlier experience with natural buffy coat-derived alpha interferon showed efficacy in the treatment of varicella-zoster infections in the immunocompromised host, as well as prophylaxis of herpes virus infections in high-risk populations. These results have to be confirmed using the newer interferon preparations. Under development are a variety of new drugs with broadened viral spectrum and improved pharmacokinetic properties. These include nucleoside analogues and novel interferons with modified amino acid sequences. One or more of these agents, used singly or in combination, may prove useful in the more difficult therapeutic problems, such as cytomegalovirus and hepatitis B infections.

Topics: Acyclovir; Antiviral Agents; Chickenpox; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infant, Newborn; Interferons; Male; Respiratory Tract Infections; Vidarabine

Topics: Acyclovir; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Blood Transfusion; Bone Marrow Transplantation; Cytomegalovirus Infections; Drug Therapy, Combination; Graft vs Host Disease; Granulocytes; Herpes Simplex; Humans; Immunosuppressive Agents; Infection Control; Infections; Interferons; Intestines; Patient Isolation; Penicillins; Pneumonia; Vaccination; Viral Vaccines; Whole-Body Irradiation

Herpes zoster is a commonly encountered infectious disease primarily affecting the elderly and immunosuppressed. The natural history and complications of the disease and the principles of management are often not appreciated by clinicians in a variety of disciplines who may see the patient during the acute phase. Recent literature has furthered our understanding of the virology of herpes zoster and the roles of corticosteroid and antiviral therapy. We review the clinical features, diagnostic principles, and management controversies of herpes zoster.

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Aged; Antiviral Agents; Child; Diagnosis, Differential; Facial Paralysis; Herpes Simplex; Herpes Zoster; Herpes Zoster Ophthalmicus; Herpesviridae; Herpesvirus 3, Human; Humans; Immunity, Cellular; Interferons; Keratitis; Middle Aged; Neuralgia; Uveitis; Vidarabine

The recent profusion of antiviral research has resulted in significant advances toward prevention and treatment of herpes group virus infections. The most promising new agent is acyclovir, which is available in topical, intravenous, and oral formulations. Results of clinical trials of acyclovir for prevention and treatment of herpes simplex, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus infections are discussed, and the potential problem of antiviral resistance considered. Vidarabine therapy is reviewed briefly, and future new drugs with activity against herpesviruses are mentioned.

Topics: Acyclovir; Chickenpox; Cytomegalovirus Infections; Drug Resistance, Microbial; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Keratitis, Dendritic; Male; Vidarabine

Topics: Acyclovir; Administration, Topical; Adolescent; Amantadine; Antiviral Agents; Chickenpox; Child; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; Influenza, Human; Keratitis, Dendritic; Male; Rimantadine; Vidarabine

A number of antiviral compounds are currently available, and several others are of great interest. Trifluridine, idoxuridine, and vidarabine are effective topically in herpes simplex virus keratoconjunctivitis infection. Vidarabine (and presumably acyclovir) is effective in herpes simplex virus encephalitis and in herpes zoster infections in the immunocompromised host. Acyclovir is effective topically, orally, and intravenously in primary herpes genitalis, and the oral and intravenous forms are effective in recurrent herpes genitalis as well. Amantadine and rimantadine are effective prophylactically and therapeutically in influenza A infections. Ribavirin and interferon, although not licensed, are of great interest. Ribavirin may be useful in respiratory syncytial virus infections, and interferon may be of benefit in common colds and related disorders.

Topics: Acyclovir; Amantadine; Antiviral Agents; Clinical Trials as Topic; Female; Herpes Genitalis; Herpes Simplex; Humans; Idoxuridine; Influenza, Human; Interferons; Keratitis, Dendritic; Male; Ribavirin; Rimantadine; Trifluridine; Vidarabine

The patient with meningoencephalitis should be evaluated carefully for the presence of focal signs referable to involvement of the frontotemporal regions of the brain. A significant percentage of cases of encephalitis with discrete focal features are caused by infection with herpes simplex virus. If focal signs are not present, the patient should be managed conservatively but examined regularly because focal neurologic dysfunction may present at any time in the course of disease. If there is clinical and electrographic evidence of involvement of the frontotemporal lobes, radiographic imaging is indicated as well as studies of the serum and cerebrospinal fluid for antibodies indicative of a recent infection with herpes simplex virus. Assuming that the radiographic scans identify the characteristic changes of a focal encephalitis and that the antibody responses are indicative of a recent herpes simplex virus infection, brain biopsy should be done in order to confirm the diagnosis. With positive evidence for HSE, treatment with ara-A should be initiated and continued for 10 days. If the biopsy proves negative for virus, ara-A should be discontinued and the patient managed conservatively (Fig. 3). Although the NIAID study of ara-A treatment of HSE is encouraging, the numbers are small and the evidence is, at best, only suggestive. It is reasonable to use this drug until a better one becomes available for the treatment of known HSE, and treatment should be instituted early before cellular injury is extensive. In centers familiar with this problem, biopsy confirmation of the diagnosis is a simple and informative procedure and can be defended. If patients cannot be moved to a center of this type, physicians familiar with the many facets of this problem should be consulted, and a decision regarding biopsy and treatment should be individualized in light of the circumstances. Biopsy should only be undertaken when the procedure can be done with minimal risk to the patient and the assurance that the maximum amount of information can be gained.

Topics: Acyclovir; Antibodies, Viral; Biopsy; Combined Modality Therapy; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Pseudotumor Cerebri; Seizures; Simplexvirus; Tomography, Emission-Computed; Tomography, X-Ray Computed; Vidarabine; Vidarabine Phosphate

Acyclovir, the new virucidal drug recently approved by the Food and Drug Administration for the treatment of herpes simplex virus (HSV), is the first available effective drug to treat such infections. Acyclovir boasts activity against four of the five major herpes-group viruses, including herpes simplex (types 1 and 2), varicella-zoster, and Epstein-Barr. The drug, phosphorylated preferentially in viral cells, exclusively attacks infected cells possessing virus-specific DNA polymerase, giving acyclovir low toxicity coupled with high efficacy. Problems of renal toxicity and viral resistance now dampen some of the initial expectations. Present-day research continues to reveal insights into the mechanism and action of acyclovir.

Topics: Acyclovir; Animals; Child; DNA Polymerase II; Drug Resistance, Microbial; Guinea Pigs; Herpes Simplex; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Kinetics; Mice; Rabbits; Recurrence; Simplexvirus

Acyclovir (acycloguanosine) is a new antiviral compound with activity against certain herpes viruses. Acyclovir is phosphorylated preferentially in virus-infected cells into its active form, acyclovir triphosphate, an inhibitor of viral-induced DNA polymerase. Acyclovir, which possesses an acyclic carbohydrate moiety, also causes premature DNA chain termination. Acyclovir has shown clinical activity against herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV), but its usefulness in cytomegalovirus, Epstein-Barr virus, and chronic hepatitis B infections requires further study. In randomized clinical trials of infections caused by HSV and VZV, intravenous acyclovir has been shown to shorten the duration of viral shedding and lesion pain and hasten the resolution of skin lesions, with minimal toxicity.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Drug Resistance, Microbial; Herpes Simplex; Herpes Zoster; Humans; Injections, Intravenous; Kinetics; Virus Diseases

Topics: Acyclovir; Adult; Antiviral Agents; Burkitt Lymphoma; Chickenpox; Child; Cytomegalovirus Infections; Disease Susceptibility; Enterovirus Infections; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Infectious Mononucleosis; Orthomyxoviridae Infections; Respirovirus Infections; Vidarabine; Virus Diseases

Guidelines for the prophylaxis or therapy of herpesvirus infections are shown in Table 1. Progress is so rapid in this area that frequent revisions of such guidelines will be necessary. Newer drugs or new formulations of older agents are constantly being developed. Combination therapies--e.g., interferon plus acyclovir--appear promising in laboratory models of herpesvirus infections and will undoubtedly receive clinical investigation in the years ahead. The problem of dealing with latent virus infections still eludes us, and major breakthroughs will be necessary before we can discuss cure of recurrent infections. Nevertheless, important strides have been made in the past few years, and further progress is predictable in the years ahead.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesviridae Infections; Humans; Immune Tolerance; Infant, Newborn; Interferon Type I; Keratitis, Dendritic; Male; Vidarabine

Topics: Acyclovir; Animals; Herpes Simplex; Humans; Simplexvirus

The sensitivity to acyclovir of more than 800 herpes simplex virus (HSV) isolates from over 300 patients were tested by the dye-uptake method. While a broad spectrum of sensitivity was found, approximately 90% of the isolates were inhibited by less than 1 mg/l of acyclovir. Therapy usually did not significantly alter the sensitivity of HSV isolates except in a few severely immunocompromised patients in whom resistant viruses produced asymptomatic or indolent infections. The sensitivity of viruses isolated during subsequent recurrences was similar to that of the originally infecting virus, regardless of therapy. The requirement of convenient and standardized methods of virus sensitivity testing is emphasized so that additional data can be accumulated to allow more precise correlations between in-vitro virus sensitivity and clinical response to acyclovir therapy.

Topics: Acyclovir; Clinical Trials as Topic; Double-Blind Method; Drug Resistance, Microbial; Herpes Simplex; Humans; Microbial Sensitivity Tests; Recurrence; Simplexvirus

Two consecutive studies are reported. In study 1, 59 patients with acute leukaemia undergoing remission induction therapy or bone marrow transplantation were given either acyclovir (5 mg/kg) or placebo by intravenous infusion twice daily during the period of neutropenia. All patients were seropositive (greater than or equal to 1:8) for herpes simplex virus. Acyclovir provided total protection against herpes simplex virus infection in bone marrow transplant patients with 0/10 versus 5/10 infections in the placebo group (P = 0.033). For the remission induction therapy group 2/19 on acyclovir developed HSV versus 10/20 receiving placebo (P = 0.018). Only one episode of cytomegalovirus (CMV) infection was seen and this was in a patient on acyclovir. Epstein-Barr virus secretion studies were inconclusive. No varicella zoster virus (VZV) infections were seen. In Study 2, 20 consecutive HSV seropositive (greater than or equal to 1:8) bone marrow transplant recipients received oral acyclovir. Five (25%) developed HSV infections, one of which was in a non-compliant patient, who subsequently developed a fatal infection whilst receiving therapeutic (5 mg/kg 8 hourly) intravenous acyclovir for this HSV infection. Intravenous acyclovir is effective in preventing HSV infections in the immunocompromised host but it seems unlikely that CMV will be amenable to acyclovir in its present formulation.

Topics: Acyclovir; Administration, Oral; Bone Marrow Transplantation; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Female; Herpes Simplex; Humans; Immunosuppression Therapy; Infusions, Parenteral; Leukemia; Male; Random Allocation

In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Anemia, Aplastic; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Drug Administration Schedule; Graft vs Host Disease; Herpes Simplex; Humans; Immunosuppression Therapy; Intestinal Absorption; Leukemia; Random Allocation; Recurrence

In vitro sensitivity data suggest that acyclovir should be effective against clinical manifestations of herpes simplex virus types 1 and 2, varicella-zoster virus and possibly Epstein-Barr virus. The clinical potential against herpes simplex virus types 1 and 2 is further supported by results in animal models. Human cytomegalovirus and the veterinary herpes viruses, with the possible exception of equine herpes virus type 1, may be insufficiently sensitive to be amenable to treatment.

Topics: Acyclovir; Animals; Cytomegalovirus; Encephalitis; Guinea Pigs; Hepatitis B virus; Herpes Simplex; Herpesvirus 1, Cercopithecine; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; In Vitro Techniques; Keratitis, Dendritic; Mice; Rabbits; Recurrence; Simplexvirus

Topics: Acyclovir; Chickenpox; Cytomegalovirus Infections; Drug Resistance, Microbial; Female; Hepatitis B; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infectious Mononucleosis; Male; Recurrence

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major imp

Topics: Acyclovir; Animals; Clinical Trials as Topic; Cytomegalovirus; Drug Resistance, Microbial; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Immunity; Keratitis, Dendritic; Kinetics; Male; Mutagens; Recurrence

Only a few agents with antiviral activity are available for routine clinical use. Amantadine hydrochloride is effective in the prophylaxis of influenza A. In addition, accumulated evidence shows that amantadine has some therapeutic effect when used early in the course of an influenza A infection. Idoxuridine and adenine arabinoside have found application as topical agents in the treatment of herpes simplex keratitis. Adenine arabinoside has also been approved for the treatment of disseminated infections due to herpes zoster and herpes simplex. Acyclovir sodium has been approved as a topical agent in the treatment of limited mucocutaneous herpes simplex viral infections in immunosuppressed patients and of initial episodes of genital herpes simplex infections in patients with normal immunity. Ribavirin, an experimental agent with a wide spectrum of activity in vitro, has not fulfilled expectations in clinical trials. Because of the eradication of smallpox, methisazone has become obsolete as a prophylactic agent in smallpox.

Topics: Acyclovir; Amantadine; Animals; Antiviral Agents; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; Influenza A virus; Keratitis, Dendritic; Methisazone; Ribavirin; Smallpox; Vidarabine; Virus Diseases

The chief characters of infection by the human herpes viruses are considered with particular reference to herpes simplex viruses, types 1 and 2. Infection with type 1 virus is acquired very early in life though infrequently as a true congenital transmission of virus. Primary infections result from direct contact usually with infected saliva or skin vesicles. Kerato-conjunctivitis, when primary, may be severe yet superficial in extent. Vulvo-vaginitis, often acquired in adults as a result of type 2 infection by sexual transmission, can give extensive but superficial ulceration and discharge. Recurrent infections located on the dermatome with the same nerve supply as that of the organ affected primarily occur throughout life and at relatively short intervals. Sensory nerve ganglia harbour the virus particles as latent infection and when reactivation occurs virus spreads along nerve fibres to the skin. The most serious infections occur as disseminated disease with liver involvement in the neonatal period, in infants suffering from malnutrition or those undergoing immunosuppression for malignancies. Eczematous children are then at particular risk from spreading haemorrhagic skin lesions (Kaposi's eruption). Herpes encephalitis, commoner in adults than children, is an insidious severe disease with mortality related to the depth of coma. Antiviral therapy though successful may lead to chronic neurological sequelae. The success of antiviral therapy in herpes partly turns on the ability to bring the drug into close contact with the infected tissues. Latent virus is relatively unaffected by acyclovir and thus far recurrences have continued to occur.

Topics: Acyclovir; Adult; Antibodies, Viral; Encephalitis; Herpes Labialis; Herpes Simplex; Humans; Infant, Newborn; Keratitis, Dendritic; Recurrence; Time Factors

Herpes simplex encephalitis and neonatal herpes simplex virus infections are important consequences of herpes simplex virus infections of humans. The association of both diseases with significant mortality and morbidity has prompted intensive therapeutic trials designed to improve outcome. The NIAID Collaborative Antiviral Study Group has been able to demonstrate that vidarabine therapy decreases the mortality and improves morbidity for both herpes simplex encephalitis and neonatal herpes simplex virus infections. Nevertheless, mortality for both diseases is about 40% and many survivors are left with significant neurological impairment. With the hope of improving outcome, we initiated comparative trials of vidarabine and acyclovir for these two diseases. This report summarizes the status of these trials, which are still underway, with particular reference to the complexities of studies such as these. Because adequate numbers of patients for definitive statistical analyses have not been entered into the trial, data were assessed according to outcome for the entire group, irrespective of drug administered. The mortality of herpes simplex encephalitis and neonatal herpes simplex virus infections has been reduced to 34 and 30%, respectively, a decrease of approximately 10% for each disease. Further analyses await completion of the trials.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Random Allocation; Time Factors; Vidarabine

Acyclovir can prevent the establishment of latent herpes simplex virus (HSV) in sensory ganglia by early treatment of the primary infection in experimental animals. A delayed treatment may reduce the number of neurons that eventually become latently infected. Acyclovir can prevent virus reactivation in explant cultures of latently infected ganglia, experimentally induced recurrences of latently infected animals, and immunosuppressed patients. This effect is dependent on the continuous presence of the drug in the explant culture medium or organism. The treatment of recurrent lesions with acyclovir reduces the severity of the episode and may also prevent reinfection of ganglia, if this should be common in the maintenance of latency. It might be possible to eradicate a latent HSV, if conditions were created in which drugs such as acyclovir, activated by the virus-induced thymidine kinase, could interact with the enzyme before the assembly of mature virions.

Topics: Acyclovir; Animals; Antiviral Agents; Culture Techniques; Foscarnet; Ganglia; Guanine; Herpes Simplex; Mice; Neurons; Phosphonoacetic Acid; Simplexvirus; Time Factors

As reflected in the preclinical and early clinical data, acyclovir seems destined to have a very useful role in the treatment and/or prophylaxis of herpes virus (HSV) infections in immunosuppressed humans. If the preclinical predictions can be extrapolated to varicella-zoster (V-Z) infections, acyclovir could well also play a meaningful role in therapy of V-Z infections in the immunosuppressed host; however, this conjecture awaits proof of controlled studies in humans. Clearly the usefulness of acyclovir for treatment of V-Z infections should be compared with that of adenine arabinoside (ara-A) to put into proper perspective the relative efficacies of the two drugs for future therapeutic regimens. The need for comparative studies is most important at this early stage of antiviral drug development, to avoid ethical problems that will cloud the knowledge needed to move forward in a positive way. In any event, the development of acyclovir, with its targeted approach, represents a real fundamental advance in antiviral drug development. Together with the development and deployment of ara-A, it should provide the needed impetus for a surge in the creation of new antiviral compounds for tomorrow.

Topics: Acyclovir; Administration, Topical; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Guanine; Hepatitis B; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Immune Tolerance; Infectious Mononucleosis; Infusions, Parenteral

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Genes, Viral; Guanine; Herpes Simplex; Humans; Mice; Recurrence; Simplexvirus; Thymidine Kinase; Virus Replication

A review of the literature on acyclovir (Zovirax), a new antiherpes drug, with particular activity against herpes simplex virus types I and II and also against varicella-zoster, Epstein-Barr, cytomegalo and herpes B viruses, is presented. The article deals with 'in vitro' and 'in vivo' efficacy in animals, animal toxicity, latency and resistance, the mechanism of action and early clinical experience.

Topics: Acyclovir; Animals; Clinical Trials as Topic; Drug Resistance, Microbial; Guanine; Guinea Pigs; Herpes Simplex; Herpesviridae; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Intestinal Absorption; Keratitis, Dendritic; Kidney; Kinetics; Mice; Phosphorylation; Rabbits; Simplexvirus; Time Factors

Topics: Acyclovir; Animals; Antiviral Agents; Child; Guanine; Hepatitis B; Herpes Simplex; Humans; Interferons; Kidney Transplantation; Leukocytes; Nucleic Acid Synthesis Inhibitors; Protein Biosynthesis; RNA, Double-Stranded; RNA, Viral; Simplexvirus; Thymidine Kinase; Transplantation, Homologous; Virus Diseases; Virus Replication

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Female; France; Herpes Simplex; Humans; Latent Infection; Male; Middle Aged; Oropharynx; Respiration, Artificial; Retrospective Studies; Virus Shedding

The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown.. To determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation.. A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between February 2, 2014, and February 22, 2018.. Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo.. The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis.. Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median [IQR] age, 61 [50-70] years; 76 [32%] women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50]) for controls (P = .17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, -0.004 to 0.22, P = .06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group, P = .40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events.. In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting.. ClinicalTrials.gov identifier: NCT02152358.

Topics: Acyclovir; Aged; Antiviral Agents; Double-Blind Method; Female; France; Herpes Simplex; Humans; Male; Middle Aged; Oropharynx; Pharyngeal Diseases; Respiration, Artificial; Respiratory Insufficiency; Treatment Outcome; Virus Activation

Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as 'cold sores', which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban).. This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution.. New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants.. Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results.SCOTT Registration: 15/SCOTT/14 PROTOCOL VERSION: 4.0 (12 June 2017).

Topics: Acyclovir; Administration, Topical; Adolescent; Adult; Aged; Antiviral Agents; Apitherapy; Herpes Labialis; Herpes Simplex; Honey; Humans; Kunzea; Middle Aged; New Zealand; Pain; Recurrence; Research Design; Simplexvirus; Skin; Treatment Outcome

Herpes simplex virus type 2 (HSV-2) genital lesion recurrence is modulated by psychological factors, but no such link with viral shedding (and thus asymptomatic transmission) has been observed in humans.. The moderating effects of average psychological distress, emotional stability, and emotion regulation on HSV-2 recurrence were tested.. Nineteen HSV-2 seropositive women were followed over 22 weeks. Daily measures of HSV-2 recurrence and psychological distress were collected. HSV-2 lesions and viral shedding were modeled as linear oscillator systems, with psychological distress moderating the periodicity of each process.. High levels of distress, more labile moods, and less ability to regulate emotional states were associated with fewer days elapsed between the onset of lesion episodes. Viral shedding showed the same pattern.. Results are consistent with research indicating that psychological distress suppresses immune system functioning, and provide new evidence that genital HSV-2 viral shedding is related to, and regulated by, psychological distress.

Topics: Acyclovir; Adult; Antiviral Agents; Double-Blind Method; Emotions; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Middle Aged; Recurrence; Stress, Psychological; Virus Shedding; Young Adult

Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year. Participants applied resiquimod 0.01% gel or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod-vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod and 500 mg valacyclovir orally twice daily for 5 days (RESI-VAL), resiquimod and oral placebo (RESI-PLA), and vehicle and oral placebo (VEH-PLA). The median time to first recurrence was similar for resiquimod and vehicle (trial 1, 60 and 56 days, P=0.7; trial 2, 54 and 48 days, P=0.47; trial 3, 51 [RESI-VAL], 55 [RESI-PLA], and 44 [VEH-PLA] days, P=not significant [NS]). The median time to healing of initial treated recurrence was longer for resiquimod (trial 1, 18 compared to 10 days, P<0.001; trial 2, 19 compared to 13 days, P=0.16; trial 3, 14 [RESI-VAL], 16 [RESI-PLA], and 8 [VEH-PLA] days, P<0.001). In trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no posttreatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects.

Topics: Acyclovir; Adolescent; Adult; Aged; Cytokines; Double-Blind Method; Female; Gels; Herpes Simplex; Humans; Imidazoles; Male; Middle Aged; Recurrence; Simplexvirus; Valacyclovir; Valine; Wound Healing; Young Adult

We performed a pilot study examining the safety and tolerability of valacyclovir in veterans with herpes simplex virus type 2 and hepatitis C virus (HCV) coinfection.. We performed a randomized double-blind, placebo-controlled, crossover clinical trial in U.S. veterans with genotype 1 HCV/herpes simplex virus type 2 coinfection. Patients were randomized 1:1 in blocks of 10 to receive either 1 g twice-daily valacyclovir or matching placebo for 8 weeks followed by a 2-week washout phase with daily placebo. The alternate therapy (valacyclovir or placebo) was given for an additional 8-week period. Safety assessments were performed every 2 weeks. Changes in HCV RNA and alanine aminotransferase (ALT) were estimated using linear mixed models (SAS Proc Mixed).. Thirty patients were enrolled. Valacyclovir was not associated with toxicity or adverse events. ALT levels declined 6% to 10%; mean HCV RNA levels were reduced 24% (1.3 million IU/mL [0.21 log10 IU/mL]) during the valacyclovir phase (P = 0.08) with no carryover effect observed (P = 0.21).. Valacyclovir 1 g twice daily showed no evidence of hepatotoxicity in U.S. veterans with hepatitis C. A modest reduction in serum levels of ALT and plasma levels of HCV RNA was observed.

Topics: Acyclovir; Aged; Alanine Transaminase; Antiviral Agents; Coinfection; Cross-Over Studies; Double-Blind Method; Female; Hepacivirus; Hepatitis C, Chronic; Herpes Simplex; Herpesvirus 2, Human; Humans; Linear Models; Male; Middle Aged; Pilot Projects; RNA, Viral; Treatment Outcome; Valacyclovir; Valine; Veterans; Viral Load

To test our hypothesis that valacyclovir, an antiherpes virus-specific medication, added to antipsychotics (APs) would improve cognitive performance and psychopathology among schizophrenia subjects exposed to neurotropic herpes simplex virus, type 1 (HSV1).. Using a double-blind placebo-controlled design, we randomized 24 HSV1-seropositive schizophrenia subjects to receive either valacyclovir (n = 12) or placebo (n = 12) for 18 weeks in addition to stable doses of APs. Valacyclovir dose was stabilized at 1.5 g twice daily orally. At each visit, subjects were evaluated for severity of psychopathology and side effects using standardized scales and a study-specific semistructured checklist. A computerized neurocognitive battery validated on both schizophrenia and healthy subjects was administered at baseline and follow-up. Intent-to-treat analysis, using linear regression models that included all randomized subjects, were used to examine differential changes in cognition and psychopathology scores over 18 weeks between valacyclovir and placebo, accounting for placebo response.. Valacyclovir group improved in verbal memory, working memory, and visual object learning compared with placebo group. The effect sizes (Cohen's d) were 0.79 for working memory, 1.14 for immediate verbal memory, and 0.97 for the visual object learning. Psychotic symptom severity did not improve.. Supplemental valacyclovir may alleviate impairments in cognitive domains that are often observed in schizophrenia but not psychotic symptoms in those exposed to HSV1. If replicated, this approach could provide a novel strategy to treat cognitive impairments in a subgroup of schizophrenia subjects who can be reliably identified using a blood test.

Topics: Acyclovir; Adolescent; Adult; Antipsychotic Agents; Antiviral Agents; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Learning; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Psychotic Disorders; Schizophrenia; Valacyclovir; Valine; Young Adult

Herpes simplex virus-2 (HSV-2) suppression with acyclovir or valacyclovir reduces HIV-1 viral RNA levels; one hypothesis is that HSV-2 suppression reduces immune activation. We measured T cell immune activation markers among women participating in a randomized placebo-controlled trial of valacyclovir to reduce HIV-1 RNA levels among pregnant women. Although valacyclovir was associated with lower HIV-1 RNA levels, the distribution of both CD4(+) and CD8(+) CD38(+)HLA-DR(+) T cells was not different among women taking valacyclovir when compared to women taking placebo. Further study is needed to understand the mechanism of HIV-1 RNA reduction following herpes suppression among those coinfected with HIV-1 and HSV-2.

Topics: Acyclovir; Adult; Antiviral Agents; Coinfection; Double-Blind Method; Female; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Kenya; Lymphocyte Activation; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus; T-Lymphocytes; Valacyclovir; Valine; Young Adult

Intravenous acyclovir-induced acute kidney injury (AKI) from drug crystallization in the renal tubules is described in case reports, review articles, and drug prescribing manuals. Similarly, AKI from oral acyclovir is described in case reports, but the risk in routine practice is unknown.. Retrospective population-based cohort study.. We studied a large cohort of older patients in Ontario, Canada, receiving new outpatient prescriptions from 1997 to 2011 for oral acyclovir or valacyclovir (which is metabolized to acyclovir). The comparison drug was famciclovir, an antiviral used for indications similar to acyclovir, but with no known renal toxicity.. Outpatient prescription for oral acyclovir, valacyclovir, or famciclovir.. The primary outcome was hospital admission with AKI in the 30 days after the initial prescription.. We assessed the primary outcome with health care diagnostic codes. In a subpopulation, we assessed AKI using available laboratory serum creatinine measurements.. 76,269 patients received acyclovir or valacyclovir and 84,646 received famciclovir. On average, patients were aged 76 [IQR, 71-81] years and prescription duration was 7 days. Acyclovir or valacyclovir use was not associated with a higher risk of hospital admission with AKI (209 [0.27%] events with acyclovir or valacyclovir vs 238 [0.28%] events with famciclovir [relative risk, 0.97; 95% CI, 0.81-1.17]). Results were consistent in adjusted analyses, in all subgroups, and in the subpopulation with laboratory measurements.. Diagnostic codes had high specificity but low sensitivity and underestimated the incidence of AKI. Only a limited number of patients (n = 2,729) had serum creatinine values available.. In this population-based study of older adults, oral acyclovir use was not associated with a higher risk of AKI compared to famciclovir.

Topics: Acute Kidney Injury; Acyclovir; Administration, Oral; Aged; Aged, 80 and over; Antiviral Agents; Creatinine; Female; Herpes Simplex; Herpes Zoster; Humans; Male; Ontario; Outpatients; Population Surveillance; Retrospective Studies; Risk Factors

Topical Acyclovir has moderate efficacy on recurrent HSV symptoms, requiring repeat applications for several days. Topical Dynamiclear, which requires only a single dose application, may provide a more effective and convenient treatment option for symptomatic management of HSV.. The study assessed the comparative efficacy and tolerability of a single use, topical formulation containing copper sulfate pentahydrate and Hypericum perforatum that is marketed as Dynamiclear™ to a topical 5% Acyclovir cream standard preparation and use.. A prospective, randomized, multi-centered, comparative, open-label clinical study was conducted. A total of 149 participants between 18 and 55 years of age with active HSV-1 and HSV-2 lesions were recruited for the 14-day clinical trial. Participants were randomized into two groups: A (n=61), those receiving the Dynamiclear formulation, and B (n=59), those receiving 5% Acyclovir. Efficacy parameters were assessed via physical examination at baseline (day 1), day 2, 3, 8, and 14. Laboratory safety tests were conducted at baseline and on day 14.. Use of the Dynamiclear formulation was found to have no significant adverse effects and was well tolerated by participants. All hematological and biochemical markers were within normal range for the Dynamiclear group. Statistically, odds for being affected by burning and stinging sensation were 1.9 times greater in the Acyclovir group in comparison to the Dynamiclear group. Similarly, the odds of being affected by symptoms of acute pain, erythema and vesiculation were 1.8, 2.4, and 4.4 times higher in the Acyclovir group in comparison to the Dynamiclear group.. The Dynamiclear formulation was well tolerated, and efficacy was demonstrated in a number of measured parameters, which are helpful in the symptomatic management of HSV-1 and HSV-2 lesions in adult patients. Remarkably, the effects seen from this product came from a single application.

Topics: Acyclovir; Administration, Topical; Adolescent; Adult; Copper Sulfate; Erythema; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Hypericum; Male; Middle Aged; Plant Extracts; Prospective Studies; Treatment Outcome; Young Adult

Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda.. We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300-400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log(10) viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov, number NCT00405821.. 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58-0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50,000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43-0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50,000 copies per mL (0·90, 0·54-1·5; p=0·688). No safety issues related to aciclovir treatment were identified.. Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50,000 copies per mL or more before initiation of antiretroviral treatment.. National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA).

Topics: Acyclovir; Adult; Antiviral Agents; CD4 Lymphocyte Count; Coinfection; Disease Progression; Double-Blind Method; Female; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Uganda; Viral Load; Young Adult

Information on pregnancy rates and factors associated with pregnancy and contraceptive use is important for clinical trials in women in sub-Saharan Africa where withdrawal of investigational products may be required in the event of pregnancy with a consequent effect on sample size and trial power.. A prospective cohort analysis of pregnancy and contraceptive use was conducted in Tanzanian women enrolled in a randomised placebo-controlled trial of herpes simplex virus-suppressive therapy with acyclovir to measure the effect on HIV incidence in HIV-negative women and on genital and plasma HIV viral load in HIV-positive women. The cohort was followed every 3 months for 12-30 months. Women at each visit were categorised into users or non-users of contraception. Pregnancy rates and factors associated with pregnancy incidence and contraceptive use were measured.. Overall 254 of 1305 enrolled women became pregnant at least once during follow-up (pregnancy rate: 12.0/100 person-years). Younger age, being unmarried, higher baseline parity and changes in contraceptive method during follow-up were independently associated with pregnancy. Having paid sex and being HIV positive were associated with lower risk of pregnancy. Uptake of contraception was associated with young age, being unmarried, occupation, parity and the number and type of sexual partners.. Data on use of contraceptive methods and risk factors for pregnancy can help to guide decisions on trial eligibility and the need for additional counselling. Mandatory reliable contraceptive use in study participants may be required to reduce pregnancy rates in studies where pregnancy is contraindicated.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cohort Studies; Contraceptive Agents; Drug Utilization; Female; Herpes Simplex; HIV Infections; Humans; Placebos; Pregnancy; Pregnancy Rate; Prospective Studies; Tanzania; Young Adult

Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications.. One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years.. The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups.. Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.

Topics: Acyclovir; Adult; Antiviral Agents; Double-Blind Method; Female; Follow-Up Studies; Herpes Simplex; Herpesvirus 2, Human; Humans; Male; Meningitis, Viral; Prospective Studies; Secondary Prevention; Sweden; Treatment Outcome; Valacyclovir; Valine

Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.. We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy.. A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09).. Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Child Development; Double-Blind Method; Female; Herpes Simplex; Humans; Infant, Newborn; Kaplan-Meier Estimate; Male; Pregnancy Complications, Infectious; Secondary Prevention

Up-to-date conceptions of etiology and epidemiology of anogenital herpetic infection are described. The main mechanisms of immunological shifts in subjects with anogenital Herpes infection are discussed. The efficacy and safety of cycloferon in the combined treatment of patients with recurring anogenital herptic infection were estimated. The clinical efficacy of the combined therapy (acyclovir in a dose of 200 mg 5 times a day for 5 days + cycloferon liniment applied topically on the eruptions twice a day for 5 days) was 85% or 25% higher vs. the control.

Topics: Acridines; Acyclovir; Administration, Topical; Antiviral Agents; Herpes Genitalis; Herpes Simplex; Humans; Recurrence; Sexually Transmitted Diseases; Time Factors

Poor participant adherence to treatment may contribute to lack of impact in some biomedical HIV prevention trials. This qualitative study explored adherence in a randomized controlled trial of herpes suppressive therapy to reduce HIV acquisition and infectivity among 1305 Tanzanian women. The trial found participants completed 72% of visits on treatment; 52-56% of women on treatment had > or = 90% adherence by pill count estimate; and between six and nine months 30/86 (35%) of urine samples from acyclovir recipients tested acyclovir negative, and 7/86 (8%) from placebo recipients tested acyclovir positive. Twenty in-depth interviews (IDIs) were conducted after 30 months with respondents randomly selected from "acyclovir negative" acyclovir recipients and "acyclovir positive" placebo recipients, or by preliminary pill count adherence categories ("under users," "good users," and "over users"). Almost all respondents reported appropriate adherence and positive trial attitudes, e.g., trusting staff, appreciating services, perceiving pills as beneficial. Fourteen understood placebo use, and six understood the trial purpose. Notably, 5/9 acyclovir recipients and 1/11 placebo recipients believed their pills had treated pre-existing sexually transmitted infections. Limited understanding did not negatively affect reported adherence. Reported adherence problems usually related to illness, travel, and/or family obligations (e.g., husband's disapproval). "Acyclovir positive" placebo recipients denied taking other participants' pills. The IDIs also did not resolve discrepant reports of pill loss or theft. Biomedical HIV interventions often have strong behavioral components that require close attention during intervention development, trial design, and process and impact evaluation. This study identified topics which warrant further consideration, including: information reinforcement and comprehension assessment throughout a trial for long-term participant understanding; involving partners in adherence promotion activities; strategizing with participants to maintain adherence during familial illnesses or other crises; and close monitoring, identification, and follow-up of (1) individuals with discrepant biological tests, and (2) other sources of the treatment in the trial area. Methodological research is also needed to improve adherence measures.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Female; Health Knowledge, Attitudes, Practice; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Medication Adherence; Qualitative Research; Tanzania; Young Adult

A multicenter, open-label study evaluated the single-dose pharmacokinetics and safety of a pediatric oral famciclovir (prodrug of penciclovir) formulation in infants aged 1 to 12 months with suspicion or evidence of herpes simplex virus infection. Individualized single doses of famciclovir based on the infant's body weight ranged from 25 to 175 mg. Eighteen infants were enrolled (1 to <3 months old [n = 8], 3 to <6 months old [n = 5], and 6 to 12 months old [n = 5]). Seventeen infants were included in the pharmacokinetic analysis; one infant experienced immediate emesis and was excluded. Mean C(max) and AUC(0-6) values of penciclovir in infants <6 months of age were approximately 3- to 4-fold lower than those in the 6- to 12-month age group. Specifically, mean AUC(0-6) was 2.2 microg h/ml in infants aged 1 to <3 months, 3.2 microg h/ml in infants aged 3 to <6 months, and 8.8 microg h/ml in infants aged 6 to 12 months. These data suggested that the dose administered to infants <6 months was less than optimal. Eight (44.4%) infants experienced at least one adverse event with gastrointestinal events reported most commonly. An updated pharmacokinetic analysis was conducted, which incorporated the data in infants from the present study and previously published data on children 1 to 12 years of age. An eight-step dosing regimen was derived that targeted exposure in infants and children 6 months to 12 years of age to match the penciclovir AUC seen in adults after a 500-mg dose of famciclovir.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Body Weight; Capsules; Child; Child, Preschool; Famciclovir; Female; Guanine; Herpes Simplex; Humans; Infant, Newborn; Male; Models, Biological

Two multicenter, open-label, single-arm, two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection. Pooled pharmacokinetic data were generated after single doses in 51 participants (approximately 12.5 mg/kg of body weight [BW] for children weighing < 40 kg and 500 mg for children weighing > or = 40 kg). The average systemic exposure to penciclovir was similar (6- to 12-year-olds) or slightly lower (1- to < 6-year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). The apparent clearance of penciclovir increased with BW in a nonlinear manner, proportional to BW(0.696). An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV-infected patients who received famciclovir twice a day and 24 of 53 (45.3%) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chickenpox; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Famciclovir; Female; Herpes Simplex; Herpesvirus 3, Human; Humans; Infant; Male; Simplexvirus; Treatment Outcome

To evaluate a multipronged approach to promote dual contraceptive use by women within heterosexual HIV-1-serodiscordant partnerships.. For 213 HIV-1-serodiscordant couples in Thika, Kenya, participating in an HIV-1 prevention clinical trial, contraceptive promotion was initiated through a multipronged intervention that included staff training, couples family planning sessions, and free provision of hormonal contraception on-site. Contraceptive use and pregnancy incidence were compared between two time periods (before versus after June 2007, when the intervention was initiated) and between Thika and other Kenyan trial sites (Eldoret, Kisumu, and Nairobi). Generalized estimating equations and Andersen-Gill proportional hazards modeling were used.. Nonbarrier contraceptive use increased after implementation of the intervention: from 31.5 to 64.7% of visits among HIV-1-seropositive women [odds ratio 4.0, 95% confidence interval (CI) 3.0-5.3] and from 28.6 to 46.7% of visits among HIV-1-seronegative women (odds ratio 2.2, 95% CI 1.4-3.5). In comparison, at the other Kenyan sites, where the intervention was not implemented, contraceptive use changed minimally, from 15.6 to 22.3% of visits for HIV-1-seropositive women and from 13.6 to 12.7% among HIV-1-seronegative women. Self-reported condom use remained high during follow-up. Pregnancy incidence at the Thika was significantly lower after compared with before June 2007 (hazard ratio 0.2, 95% CI 0.1-0.6) and was approximately half that at other Kenyan sites during the intervention period (hazard ratio 0.5, 95% CI 0.3-0.8).. A multipronged family planning intervention can lead to high nonbarrier contraceptive uptake and reduced pregnancy incidence among women in HIV-1-serodiscordant partnerships.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Contraceptive Agents; Contraceptive Devices; Family Characteristics; Female; Follow-Up Studies; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV Seronegativity; HIV Seropositivity; HIV-1; Humans; Kenya; Male; Middle Aged; Patient Acceptance of Health Care; Pregnancy; Sex Education; Young Adult

Previous trials of corticosteroid or antiviral treatments for Bell's palsy have been underpowered or have had insufficient follow-up. The aim of this study was to compare the short-term and long-term effects of prednisolone and valaciclovir in the recovery of the affected facial nerve in a large number of patients.. In this randomised, double-blind, placebo-controlled, multicentre trial, patients aged 18 to 75 years who sought care directly or were referred from emergency departments or general practitioners within 72 h of onset of acute, unilateral, peripheral facial palsy, between May, 2001, and September, 2006, were assessed. Patients were randomly assigned in permuted blocks of eight to receive placebo plus placebo; 60 mg prednisolone per day for 5 days then reduced by 10 mg per day (for a total treatment time of 10 days) plus placebo; 1000 mg valaciclovir three times per day for 7 days plus placebo; or prednisolone (10 days) plus valaciclovir (7 days). Follow-up was for 12 months. The primary outcome event was time to complete recovery of facial function, as assessed with a regional Sunnybrook scale score of 100 points. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00510263.. Of 839 patients who were randomly assigned, 829 were included in the modified intention-to-treat analysis: 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 patients who did not (hazard ratio 1.40, 95% CI 1.18 to 1.64; p<0.0001). There was no difference in time to recovery between the 413 patients treated with valaciclovir and the 416 patients who did not receive valaciclovir (1.01, 0.85 to 1.19; p=0.90). The number of patients with adverse events was similar in all treatment arms.. Prednisolone shortened the time to complete recovery in patients with Bell's palsy, whereas valaciclovir did not affect facial recovery.

Topics: Acyclovir; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Antiviral Agents; Bell Palsy; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Herpes Simplex; Humans; Male; Middle Aged; Placebos; Prednisolone; Recovery of Function; Time Factors; Treatment Outcome; Valacyclovir; Valine; Young Adult

A randomized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg twice daily, or placebo for 8 weeks, a 2-week washout period, then the alternative therapy for 8 weeks) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who were not on antiretroviral therapy. Plasma samples (obtained weekly) and endocervical swab specimens (obtained thrice weekly) were collected for HIV-1 RNA polymerase chain reaction. Plasma HIV-1 level was significantly lower during the valacyclovir arm, compared with the placebo arm (-0.26 log10 copies/mL, a 45% decrease [P < .001]), as was cervical HIV-1 level (-0.35 log10 copies/swab, a 55% decrease [P < .001]). Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression.

Topics: Acyclovir; Adult; Antiviral Agents; Cross-Over Studies; Female; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Middle Aged; Valacyclovir; Valine; Virus Replication

Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial.. Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell counts >200 cells/ microL were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm.. HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P<.001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07-0.25; P=.0008; 33% decrease) log(10) copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23-0.42; P<.0001; 53% decrease) log(10) copies/mL lower plasma HIV-1 level, compared with values for placebo.. Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Cross-Over Studies; DNA, Viral; Double-Blind Method; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; Polymerase Chain Reaction; Rectum; RNA, Viral; Treatment Outcome; Valacyclovir; Valine; Viral Load

Varicella-zoster virus (VZV) disease occurs in 30% of allogeneic hematopoietic cell transplant recipients who had a history of VZV infection. A safe and effective prevention strategy has not been established. In a double-blind controlled trial, 77 hematopoietic cell transplant recipients at risk for VZV reactivation were randomized to acyclovir 800 mg twice daily or placebo given from 1 to 2 months until 1 year after transplantation. VZV disease at 1 year was the primary end point; VZV disease after discontinuation of prophylaxis, VZV-specific T-cell immunity, herpes simplex virus (HSV) infection, cytomegalovirus (CMV) disease, survival, and safety were secondary end points. Acyclovir significantly reduced VZV infections at 1 year after transplantation (HR, 0.16; 95% CI, 0.035-0.74; P = .006). In the post-intervention observation period, this difference was not statistically significant (2 years: HR, 0.52; 95% CI, 0.21-1.3; 5 years: HR, 0.76; 95% CI, 0.36-1.6). There was no statistically significant difference in reconstitution of VZV-specific T-helper cell responses, HSV infections, CMV disease, chronic graft-versus-host disease, and overall survival between the groups. Acyclovir was well tolerated. Post-study VZV disease predominantly occurred in patients with continued need for systemic immunosuppression. In conclusion, acyclovir effectively and safely prevents VZV disease during the first year after hematopoietic cell transplantation. Periods of prophylaxis longer than 12 months may be beneficial for those hematopoietic cell transplant recipients on continued immune suppression.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Chronic Disease; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Female; Follow-Up Studies; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpes Zoster; Humans; Male; Middle Aged; Simplexvirus; T-Lymphocytes, Helper-Inducer; Transplantation, Homologous; Virus Activation

Human herpesviruses (HHVs) are ubiquitous pathogens that intermittently reactivate from latency. Transmission is believed to be facilitated by their frequent appearance in saliva. This study sought to understand the factors that influence the appearance of these viruses in saliva by examining the prevalence, pattern, and quantity of all eight HHVs in saliva of immunocompetent adults with a history of recurrent oral herpes simplex virus (HSV) infections following dental treatment and antiviral therapy. Valacyclovir or matched placebo was given (2 g twice on the day of treatment and 1 g twice the following day) to 125 patients in a randomized, double-blind controlled trial. Saliva, collected on the day of dental treatment and 3 and 7 days later, was analyzed using real-time quantitative PCR. At all visits, HHVs coinfected saliva. Over the course of the week, the DNAs of HHV-6 and HHV-7 were detected significantly more often (97% to 99% of patients) than Epstein-Barr virus (EBV; 64.8%), HSV-1 (13.0%), HHV-8 (3.2%), cytomegalovirus (2.4%), HSV-2 (0%), and varicella-zoster virus (0%), irrespective of drug treatment (P < 0.002). Mean genome copy numbers were highest for HSV-1 and HHV-6. Dental treatment did not influence asymptomatic viral shedding patterns. However, valacyclovir treatment resulted in significantly fewer patients shedding EBV at both postoperative visits compared with placebo (P < 0.008). These results suggest that HHVs are simultaneously present in the saliva of healthy adults at levels that could facilitate transmission, and valacyclovir therapy decreases the prevalence of EBV in saliva but has little effect on HHV-6 and HHV-7.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Child; Dental Care; DNA, Viral; Female; Herpes Simplex; Humans; Male; Middle Aged; Recurrence; Saliva; Simplexvirus; Valacyclovir; Valine; Virus Shedding

To determine if valacyclovir usage expedites the clearance of recurrent herpes gladiatorum (HG) in wrestlers.. Double-blind, placebo-controlled, prospective study using valacyclovir from September 2001 through March 2003.. Twenty-nine wrestlers were recruited from the Minneapolis-St. Paul, Minnesota area. They ranged in ages from 18 to 36, of whom 7 were coaches and 22 active wrestlers. All participants had greater than 2-year history of recurrent HG.. Upon an outbreak, all participants would swab the area on a daily basis for 14 days. Swabs were analyzed for herpes simplex virus 1/2 via PCR. End point was determined as the last sample with measurable PCR detected. Individuals were randomly selected, yet equally distributed, to be in 1 of 3 groups: placebo x 7 days, valacyclovir 500 mg BID x 7 days, or valacyclovir 1,000 mg QD x 7 days.. Twenty participants (3 coaches and 17 active wrestlers) experienced outbreaks. All participants were compliant and started medication within 24 hours of developing symptoms. Valacyclovir usage showed significant reduction in mean time until PCR clearance, 8.14 days with placebo versus 6.43 days with valacyclovir 500 mg BID.. A 7-day regimen of valacyclovir 500 mg BID will reduce the length of time until clinical clearance of an outbreak of recurrent HG. Its usage reduced duration of viral presence by 21%.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Disease Outbreaks; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Polymerase Chain Reaction; Recurrence; Treatment Outcome; Valacyclovir; Valine; Wrestling

Focal viral encephalitis in childhood is a rare but life-threatening disease. Animal experiments and case reports suggest a positive effect of an additional therapy with interferon-beta on the course of the disease. Therefore, we initiated a prospective, double-blind placebo-controlled study to investigate the benefit of a combination therapy of Aciclovir (ACV) and recombinant interferon-beta (rIFN-beta) in juvenile focal viral encephalitis. - Initial inclusion criterium was suspicion of focal viral encephalitis. Diagnosis was proven by demonstration of characteristic focal lesions in cerebral imaging or virological evidence of HSV in cerebrospinal fluid. Patients were treated with ACV plus rIFN-beta or ACV plus placebo. Neurological outcome was determined 21 days and 3 months after onset of the disease. - Initially 59 patients were enrolled in the study. Encephalitis was proven in 14 patients (7 ACV + rIFN-beta, 7 ACV + placebo). The study groups were balanced in terms of important prognostic criteria. 10 patients (5 ACV + rIFN-beta, 5 ACV + placebo) were cured or had slight defects, 4 patients (2 ACV + rIFN-beta, 2 ACV + placebo) showed moderate to severe defects. There was no significant difference in favour of the additive therapy with rIFN-beta.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Encephalitis, Viral; Female; Focal Infection; Herpes Simplex; Humans; Infant; Interferon-beta; Male; Nervous System; Recombinant Proteins; Recovery of Function; Treatment Outcome

Reactivation of herpes simplex virus is a common event in patients undergoing dose-intensive remission induction or consolidation chemotherapy of acute leukemia, for which either intravenous or oral acyclovir provides effective prophylaxis. This drug's short serum half-life and low oral bioavailability make frequent dosing necessary, however, and we therefore sought to determine if the pro-drug valacyclovir, which has improved bioavailability, could be successfully substituted for this indication. Eighty-one patients with leukemia were randomized to receive either 500 mg or 1,000 mg of valacyclovir orally every 8 h and followed clinically, as well as with serial surveillance cultures. Over a total of 1,979 days on study between the groups, and 380 throat cultures, no documented episodes of herpes simplex reactivation were noted. Valacyclovir was tolerated well with no evident drug-related toxicities. We conclude that valacyclovir at either of the two doses studied can be safely substituted for oral or intravenous acyclovir, and that it provides effective prophylaxis against reactivation of herpes simplex virus in this patient population.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antineoplastic Agents; Antiviral Agents; Female; Herpes Simplex; Humans; Leukemia; Male; Middle Aged; Simplexvirus; Time Factors; Valacyclovir; Valine

Oral acyclovir has been demonstrated to prevent reactivation of herpes simplex virus (HSV) infections when administered prophylactically to autologous bone marrow transplant (BMT) recipients or patients undergoing stem cell rescue therapy. Oral valacyclovir, which is converted in the body to acyclovir, has greater oral bioavailability than oral acyclovir and compared with oral acyclovir yields similar acyclovir plasma concentrations with less frequent (twice-daily) dosing. This study compared the efficacy of oral valacyclovir with that of oral acyclovir at preventing HSV mucositis in BMT recipients. A total of 60 HSV-1-positive patients scheduled for BMT or stem cell rescue therapy were treated prophylactically with valacyclovir 500 mg twice daily until resolution of neutropenia. Data from these patients were compared with those of a historical control group of 60 patients who had received acyclovir 600 mg every 6 h until resolution of neutropenia or acyclovir 125 mg/m(2) intravenously every 6 h. The results show that none of the patients developed oral or oropharyngeal HSV infection while receiving either treatment. Of the 60 patients receiving valacyclovir, 38 (63%) completed treatment without the need for intravenous acyclovir compared with 12 of 60 (20%) patients in the acyclovir group. Additionally, the total number of doses of drug administered to the valacyclovir group was significantly less than the number received by patients in the acyclovir group. No serious adverse events occurred in either group of patients. This study demonstrates that oral valacyclovir and acyclovir are comparably effective and safe in preventing reactivation of HSV infections in autologous BMT and stem cell recipients. The less frequent dosing schedule with valacyclovir compared with acyclovir offers a potential advantage for patients undergoing BMT who frequently suffer with severe mucositis and have difficulty taking oral medications.

Topics: Acyclovir; Administration, Oral; Adult; Biological Availability; Bone Marrow Transplantation; Female; Herpes Simplex; Humans; Male; Middle Aged; Neoplasms; Patient Selection; Stem Cell Transplantation; Transplantation, Autologous; Valacyclovir; Valine

Acyclovir (ACY) is effective in the treatment of herpes simplex (HSV-1) & (HSV-2) but has systemic toxic effects if given orally or intravenously. ACY has not been used to treat the disease topically due to poor drug penetration into skin. A novel 1% liposomal ACY topical gel in a 5% Hydroxypropylmethyl cellulose (HPMC) K4M gel base has been developed and clinically evaluated in HSV-1 and HSV-2 patients.. 26 patients suffering from recurrent mild facial (HSV-1) and genital (HSV-2) infections (HSV-1: 4F, 6M, age 21-34 years; HSV-2: 16M, age 24-40 years) were subjected to double blind clinical evaluation. Plain ACY gel (PAG) and Liposomal ACY gel (LAG) were clinically evaluated by application five times daily on herpetic lesions for up to eight weeks.. A significant increase in the average percent improvement of lesion healing was observed in HSV-1 and HSV-2 patients after 2-3 weeks treatment with LAG, as well as a significant decrease in side effects associate with ACY, such as itching and burning in both HSV-1 and HSV-2, and burning micturation in HSV-2.. The results demonstrate that a five-fold reduction in the ACY content in liposomal gel is sufficient for the complete healing of herpetic lesions in HSV-1 and HSV-2 infection. The increased duration of topical therapy may be acceptable for patients suffering from mild herpetic lesions because of the advantage of avoiding systemic and local side effects

Topics: Acyclovir; Administration, Topical; Adult; Antiviral Agents; Double-Blind Method; Female; Gels; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Liposomes; Male

A subclinical viral labyrinthitis has been postulated in the literature to elicit idiopathic sudden sensorineural hearing loss (ISSHL). An etiologic role for the herpes family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, we evaluated the therapeutic value of the antiherpetic drug acyclovir (Zovirax) on hearing recovery in 91 patients with ISSHL who received prednisolone in a prospective, randomized, double-blind, placebo-controlled, multicenter trial. The audiometric parameters included pure tone and speech audiometry. Subjective parameters studied included hearing recovery, a pressure sensation in the affected ear, vertigo, and tinnitus. A 1-year follow-up was obtained. Hearing recovery for the whole group averaged about 35 dB and was independent of the severity of the initial hearing loss or vestibular involvement. Speech audiometry improved from 49% to 75%. After 12 months, pressure sensation and vertigo decreased to 15.6% (acyclovir) and 10.3% (placebo) and 12.5% (acyclovir) and 10.7% (placebo), respectively. Tinnitus decreased slightly, to 46.9% (acyclovir) and 55.2% (placebo), in the same period (p > .05 for all parameters). We conclude that no beneficial effect from combining acyclovir with prednisolone can be established in patients with ISSHL.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; Audiometry, Pure-Tone; Audiometry, Speech; Double-Blind Method; Drug Therapy, Combination; Female; Hearing Loss, Sensorineural; Hearing Loss, Sudden; Herpes Simplex; Humans; Labyrinthitis; Male; Prednisolone; Prospective Studies

It is common practice to administer acyclovir as prophylaxis to patients with hematologic malignancies during neutropenia; however, effective therapy requires frequent dosing, which is difficult in this setting. Valacyclovir has greater oral bioavailability and requires less frequent dosing.. To evaluate the efficacy and safety of valacyclovir compared with acyclovir.. Patients who had been treated with chemotherapy or stem-cell transplantation were randomized to receive acyclovir 400 mg orally 3 times daily (n = 51), valacyclovir 500 mg orally twice daily (n = 48), or valacyclovir 250 mg orally twice daily (n = 52) during neutropenia.. Clinical success, defined as the absence of an active herpes simplex virus (HSV) lesion or asymptomatic viral shedding, was similar between the 3 groups (acyclovir 96%, valacyclovir 500 mg 95%, valacyclovir 250 mg 100%). The overall rates of adverse events were similar in the 3 groups.. Prophylactic treatment with valacyclovir is an effective and safe alternative to acyclovir for the prevention of HSV reactivation in patients with hematologic malignancies.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Agents; Antiviral Agents; Biological Availability; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematologic Neoplasms; Herpes Simplex; Humans; Male; Middle Aged; Neutropenia; Single-Blind Method; Stem Cell Transplantation; Valacyclovir; Valine

The objective of this multicenter, randomized, double-blind, noninferiority trial was to investigate valacyclovir as treatment for facial herpes simplex virus (HSV) outbreaks. In total, 308 otherwise healthy outpatients self-initiated therapy with valacyclovir, either 1000 mg twice daily for 1 day or 500 mg twice daily for 3 days, for treatment of one facial HSV episode. Aborted lesions were the primary end point. Secondary end points included episode and pain resolution and lesion healing. By regimen (1 or 3 days), aborted lesions occurred in 42.2% versus 46.7% of patients, treatment difference, -4.5% (95% confidence interval, -16.3% to 7.4%; P=.49). Subgroup findings showed that about half the episodes aborted when therapy started during the prodrome/macule stages or within 6 h of first symptoms. Episode and pain resolved rapidly, with results similar for both treatments. Adverse events were infrequent and similar for the two regimens.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Denmark; Double-Blind Method; Drug Administration Schedule; Facial Dermatoses; Female; Finland; Herpes Simplex; Humans; Lithuania; Male; Middle Aged; Norway; Prodrugs; Time Factors; Treatment Outcome; Valacyclovir; Valine

Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (+/-SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11+/-1.41 and 5.19+/-1.96 microg/mL, respectively. Corresponding single dose area-under-curve values were 12.14+/-6.60 and 14.49+/-4.69h microg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discussed.

Topics: Acyclovir; Administration, Oral; Analysis of Variance; Area Under Curve; Belgium; Biological Availability; Child; Child, Preschool; Female; France; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Male; Pilot Projects; Prodrugs; Switzerland; Valacyclovir; Valine

In early trials of antiretroviral therapy, acyclovir was associated with increased survival by an unknown mechanism. The hypothesis that subclinical herpes simplex virus (HSV) reactivation was associated, in vivo, with increased plasma human immunodeficiency virus (HIV) RNA and suppression with a reduced plasma HIV RNA load was investigated. HSV cultures were performed daily on HSV-2-positive/HIV-positive patients, and plasma HIV-1 RNA loads were measured at regular intervals. A subset of patients prior to, during, and after HSV suppression with high-dose acyclovir was measured to determine whether HSV suppression was associated with a decrease in HIV replication. Most (25/27 HSV-2-positive/HIV-positive persons) reactivated HSV. Total HSV shedding rate was strongly correlated with plasma HIV-1 RNA load (R=0.54; P=.004), and the plasma HIV-1 RNA level at a given CD4 cell count was 48% lower when treated with acyclovir. These data indicate that frequent mucosal HSV reactivation influences HIV replication in vivo and daily HSV suppression may be important in the management of HSV-positive/HIV-positive persons.

Topics: Acyclovir; Adult; Antiviral Agents; CD4 Lymphocyte Count; Female; Follow-Up Studies; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; HIV Antibodies; HIV Infections; HIV-1; Humans; Male; Middle Aged; RNA, Viral; Simplexvirus; Time Factors; Virus Activation; Virus Shedding

Patients who are seropositive for herpes simplex virus (HSV) and are undergoing autologous marrow or peripheral blood stem cell transplantation require prophylaxis for HSV infection. Most prophylaxis regimens have used intravenous acyclovir (ACY). Oral valacyclovir (VAL), the L-valyl ester of ACY, can be used to achieve plasma concentrations equivalent to levels achieved with intravenous ACY. In this study, adults undergoing autologous stem cell transplantation were randomized to receive ACY, 250 mg/m2 intravenously (IV) every 12 hours from day 0 to engraftment, or VAL, 1 g orally every 12 hours from day 0 to engraftment. The primary study objective was to compare cost of HSV prophylaxis between study groups. Thirty patients were randomized to receive either oral VAL (n = 14) or IV ACY (n = 16) prophylaxis. Mean pharmacy cost of HSV prophylaxis in the patient group randomized to IV ACY was $1080 versus $320 for the group randomized initially to VAL. This study demonstrates the feasibility and significant cost savings of using oral VAL for HSV prophylaxis.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Female; Herpes Simplex; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasms; Stem Cell Transplantation; Valacyclovir; Valine

HSV can cause oral lesions that exacerbate chemotherapy-related mucositis. Intravenous acyclovir is effective in preventing HSV reactivations, but expensive. Valacyclovir has good bioavailability and has not been studied for prophylaxis of HSV among PCT patients. We compared the efficacy and costs of valacyclovir in preventing HSV reactivation among HSV seropositive autologous progenitor cell transplantation (APCT) patients with historical controls in whom intravenous acyclovir or no HSV prophylaxis were used. Valacyclovir group: From October 1997 to April 1999 108 adult patients received valacyclovir 500 mg twice daily from day -3 of APCT until neutropenia recovery or day +30. Valacyclovir was switched to intravenous acyclovir in cases of oral intolerance (17 patients) or suspected HSV reactivation (five patients). Intravenous acyclovir group: From January 1996 to October 1997 43 patients received 5 mg/kg twice-daily intravenous acyclovir from day -3 until recovery from neutropenia. No prophylaxis group: 38 patients from January 1996 to October 1997 did not receive HSV prophylaxis. HSV reactivations were seen in 2.7%, 2% and 45% of patients in the valacyclovir, intravenous acyclovir, and no prophylaxis groups, respectively. Valacyclovir was well tolerated and was the least expensive strategy. Oral valacyclovir was as effective as intravenous acyclovir for the prophylaxis of HSV reactivation in APCT patients.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Costs and Cost Analysis; Female; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Male; Middle Aged; Simplexvirus; Transplantation, Autologous; Treatment Outcome; Valacyclovir; Valine; Virus Activation

The CO2 laser for cutaneous resurfacing has been associated with the reactivation of herpes simplex virus (HSV), causing delayed reepithelialization and scarring. Antiviral agents appear to be effective in reducing reactivation, however, the optimal therapeutic regimen has yet to be clearly defined.. To assess the reactivation rates of HSV after CO2 laser resurfacing in patients who received prophylactic valacyclovir for either 10 or 14 days.. One hundred twenty patients received valacyclovir 500 mg twice a day for either 10 or 14 days starting the day prior to facial laser resurfacing. Serology levels and consecutive Tzank preparations were obtained to determine past exposure to HSV and the presence of virus.. No patients in either group developed an HSV infection or had a recurrence.. These results support the use of valacyclovir in a 10- or 14-day regimen as a preventive agent against HSV outbreaks following facial laser resurfacing.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Dermatologic Surgical Procedures; Face; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Laser Therapy; Male; Middle Aged; Prodrugs; Prospective Studies; Recurrence; Valacyclovir; Valine; Virus Activation

Herpes simplex facialis/labialis (HSFL) is a common infectious skin disorder, caused mainly by herpes simplex virus (HSV) type 1, for which the topical application of a cream containing an antiviral agent for treatment of the disease has been widely utilized.. To explore the efficacy of the topical application of 1% penciclovir cream in the treatment of HSFL, and to compare its efficacy and safety with 3% aciclovir cream.. A total of 248 patients with a diagnosis of HSFL were randomly allocated to one of the two treatment groups (n = 124 each), using stratified randomization based on a table of random numbers. Before treatment (day 0) and at every visit (days 3, 5 and 7) during the study, the sign and symptom scores were recorded by the same doctor.. Excluding 23 patients (10 in the penciclovir and 13 in the aciclovir groups), 225 completed the study, and no severe adverse events were noted with any of the treatment regimens. Results show that an encouraging improvement in the clinical course was found simultaneously for patients with each episode type and each treatment assignment. There were no significant differences in terms of efficacy endpoint, clinical cure rate, and safety between the two treatment arms, but there was a trend towards a shorter time to resolution of all symptoms, cessation of new blisters, and loss of crust (p

Topics: Acyclovir; Administration, Cutaneous; Adolescent; Adult; Aged; Antiviral Agents; Double-Blind Method; Drug Administration Schedule; Facial Dermatoses; Female; Guanine; Herpes Labialis; Herpes Simplex; Humans; Male; Middle Aged; Ointments; Pruritus; Treatment Outcome

The objective of this study was to evaluate the comparability of systemic aciclovir exposure at steady state in immunocompromised patients following oral valaciclovir 1000 mg tds and intravenous (iv) aciclovir 5 mg/kg tds. A two-centre, randomized, open label, two-way crossover study was undertaken. Patients aged 18-65 years who had undergone high-dose chemotherapy for cancer and were neutropenic (neutrophil count <0.5 x 109/mL) with normal renal function were recruited. The pharmacokinetic parameters of aciclovir after oral valaciclovir 1000 mg or iv aciclovir 5 mg/kg given as 1 h infusion, each administered every 8 h for seven doses, were compared. Fifteen patients were enrolled and 13 completed both treatments. The mean (s.d.) values for aciclovir after oral valaciclovir and iv aciclovir were: AUC0-8 76.3 (29.7) and 64.2 (20.0) microM x h; peak plasma concentration (Cmax) 26.6 (10.5) and 34.0 (11.9) microM; time to maximal plasma concentration (tmax) 2.01 (0.65) and 0.95 (0.19); and plasma elimination half-life (t1/2) 2.83 (0.91) and 2.44 (0.62) h, respectively. The mean absolute bioavailability of aciclovir from oral valaciclovir was 60 +/- 21%. Equivalent systemic exposure to aciclovir after oral valaciclovir 1000 mg and iv aciclovir 5 mg/kg was observed with AUC0-8 (oral/iv ratio = 1.16; 90% CI 0.98-1.39), whilst significantly reduced peak aciclovir concentrations were obtained with oral valaciclovir (ratio = 0.75; 90% CI 0.60-0.94). Oral valaciclovir offers a convenient, and possibly safer, alternative to iv aciclovir, delivering comparable systemic exposures with reduced peak levels. This may contribute to shorter hospitalization, reduced costs for healthcare providers and improved quality of life for patients.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Female; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Middle Aged; Neoplasms; Opportunistic Infections; Valacyclovir; Valine

The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed.. Infants who were

Topics: Acyclovir; Drug Administration Schedule; Herpes Simplex; Humans; Infant, Newborn; Infusions, Intravenous; Injections, Intravenous

Reactivation of herpes simplex virus-1 (HSV-1) after facial resurfacing has led to severe outbreaks, delayed reepitheliazation, and scarring. Current recommendations regarding the dosing of antivirals used prophylactically are based mostly on anecdotal experience. No studies have addressed the question of when such antiviral prophylaxis should begin.. The purpose of this study was to compare the efficacy of valacyclovir used as an antiviral prophylaxis when started the morning before versus the morning of facial resurfacing procedures.. Eighty-four patients who presented for facial resurfacing were enrolled. Resurfacing was performed using laser (CO2, Er:YAG), chemical peeling, dermabrasion/dermasanding, or some combination of these techniques. Patients were randomly assigned to start valacyclovir 500 mg twice daily either the morning before or the morning of the procedure. Viral cultures were performed at baseline on all patients, at any sign of infection, and at the end of the 14-day treatment period. All patients were followed for 21 days postoperatively.. Valacyclovir was 100% effective in the prevention of HSV reactivation in both regimens with no adverse effects reported.. This study demonstrates the efficacy of valacyclovir as a preventive agent against HSV outbreaks following facial resurfacing whether started the day before or the day of surgery.

Topics: Acyclovir; Antiviral Agents; Chemexfoliation; Dermabrasion; Drug Administration Schedule; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Laser Therapy; Male; Middle Aged; Postoperative Complications; Premedication; Recurrence; Rhytidoplasty; Valacyclovir; Valine; Virus Activation

To compare the efficacy and safety of 7 days' treatment with famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals.. Randomized, double-blind, parallel-group study to demonstrate equivalence for the primary efficacy parameter.. Forty-eight hospital-based or specialist public-health clinics in 12 countries.. Two-hundred and ninety-three HIV-positive patients with recurrent HSV infection (orolabial or genital) starting treatment within 48 h of first appearance of herpetic lesions.. Proportion of patients developing new lesions during treatment (primary outcome measures); Time to complete healing of lesions, time to cessation of viral shedding, time to loss of lesion-associated symptoms, number of withdrawals due to treatment failure (secondary outcome measures).. Equivalence was defined prospectively and famciclovir was equivalent to acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and 13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), -4.8-11.5]. The groups were comparable in time to complete healing (median 7 days for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29; P = 0.95), cessation of viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27; p = 0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio, 0.99; 95% CI, 0.75-1.30; P = 0.93). Similar numbers in each group withdrew because of treatment failure. There were no differences between groups in the incidence of adverse events.. Famciclovir given twice a day is as effective and well tolerated as high-dose acyclovir for mucocutaneous HSV infections in HIV-infected individuals, and has the convenience of less frequent dosing.

Topics: 2-Aminopurine; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Double-Blind Method; Famciclovir; Female; Herpes Simplex; HIV Infections; HIV Seropositivity; Humans; Male; Middle Aged; Prodrugs; Time Factors

The efficacy and safety of penciclovir (PCV) for the treatment of herpes simplex virus (HSV) infections in immunocompromised (IC) patients were studied in a double-blind, acyclovir (ACV)-controlled, multicenter study. A total of 342 patients with mucocutaneous HSV infections received 5 mg of PCV per kg every 12 or 8 h (q12h or q8h) or 5 mg of ACV per kg q8h, beginning within 72 h of lesion onset and continuing for up to 7 days. The mean age of the patients was 49 years; 94% were white and 52% were female. The main reasons for their IC states were hematologic disorder (63%) and transplant plus hematologic disorder (16%). Clinical and virological assessments were performed daily during the 7-day treatment and then every other day until lesion healing. The primary efficacy parameter addressed new lesion formation. Secondary end points focused on viral shedding, healing, and pain. Approximately 20% of patients in each treatment group developed new lesions during therapy; thus, equivalence with ACV (defined prospectively) was demonstrated for both q12h and q8h PCV regimens. For all three treatment groups, the median time to the cessation of viral shedding was 4 days and the median time to complete healing was 8 days; there were no statistically significant differences in the rates of complete healing or the cessation of viral shedding when the results for PCV q12h and q8h were compared with those for ACV q8h. In addition, there was no statistically significant difference between PCV q12h or q8h, compared with ACV q8h, for the resolution of pain. PCV was well tolerated, with an adverse event profile comparable to that of ACV. In conclusion, PCV q12h is a well-tolerated and effective therapy for mucocutaneous HSV infection in IC patients and offers a reduced frequency of dosing compared with ACV q8h.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Double-Blind Method; Female; Guanine; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Middle Aged; Simplexvirus; Treatment Outcome

The efficacy and toxicity of foscarnet cream for the treatment of mucocutaneous herpes simplex virus lesions or lesions that were clinically unresponsive to systemic acyclovir treatment (median, 30.5 days) in AIDS patients were studied in a phase I/II, open-label, nonrandomized multicenter trial. In the study, 20 patients with advanced stages of AIDS were treated with foscarnet 1% cream five times a day for a mean duration of 34.5 days. Response of index lesions (n = 20) was judged to be completely healed (8 lesions), excellent (4 lesions), or good (1 lesion) in 65% of lesions. The median time to first negative herpes simplex virus culture of index lesion was 8 days. Among 15 patients with pain at baseline, 11 had complete resolution of pain and 2 had at least a 50% reduction. Clinical adverse events included skin ulceration (4 patients), application site reactions (3 patients), fever (3 patients), and headache (3 patients). Five (25%) patients developed new lesions due to herpes simplex virus at sites other than those being treated topically while enrolled in the study. Topical foscarnet 1% cream appears to be a safe and effective treatment for acyclovir-unresponsive mucocutaneous herpes simplex virus infection in AIDS patients.

Topics: Acyclovir; Administration, Topical; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Eruptions; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Humans; Male; Middle Aged; Safety; Skin Ulcer

To determine whether nucleoside analogues can suppress recurrent outbreaks of herpes simplex virus type 1 (HSV-1) in wrestlers, commonly called herpes gladiatorum.. Double-blind and open study using valacyclovir over two wrestling seasons from 1996 through 1998.. Wrestling community in the Minneapolis-St. Paul area of Minnesota.. Volunteer sample of 42 male wrestlers from 13 to 31 years of age. For inclusion, patients had to have recurrent herpes gladiatorum and be active in a wrestling program.. Participants were treated during the first half of the season in a double-blind study using valacyclovir 500 mg a day, and in the second half as an open study with all wrestlers using valacyclovir 1,000 mg.. Outbreak of herpes gladiatorum based on clinical appearance or culture.. Participants were divided into two groups based on time interval since primary outbreak of herpes gladiatorum: less than 2 years or more than 2 years. For patients in whom primary outbreak was less than 2 years ago, outbreaks occurred in 21% (3/14) of those receiving valacyclovir 500 mg per day and 8% (2/25) of those receiving valacyclovir 1,000 mg per day. For patients in whom primary outbreak was more than 2 years ago, outbreaks occurred in 0% (0/7) of those receiving valacyclovir 500 mg per day and 0% (0/12) of those receiving valacyclovir 1,000 mg per day.. For patients with a history of herpes gladiatorum of more than 2 years, valacyclovir 500 mg daily suppresses recurrent outbreaks. Further studies need to be performed to determine proper dosing regimen for suppression of outbreaks in patients with a disease duration of less than 2 years.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Disease Outbreaks; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Minnesota; Recurrence; Sampling Studies; Treatment Outcome; Valacyclovir; Valine; Wrestling

Cytomegalovirus (CMV) is still a major pathogen in liver transplantation (LTX). The clinical efficacy of prophylactic high-dose acyclovir therapy (800 mg qid) was assessed for the prevention of CMV infection and disease in liver recipients. Fifty-five patients were enrolled in a prospective, randomised, double-blind and placebo-controlled trial; 28 on acyclovir vs. 27 on placebo. The therapy was given for 12 weeks. The patients were followed for 24 weeks. CMV infection was diagnosed in 60% (16 on acyclovir, 17 on placebo) and CMV disease developed in 38% (7 on acyclovir, 14 on placebo) of the patients. The total mortality was 27% (6 on acyclovir, 10 on placebo). Acyclovir delayed 32% of the CMV infections and prevented 59% of the CMV disease cases which occurred in the placebo cohort. The time to CMV disease was significantly prolonged in patients on acyclovir as compared to patients on placebo (P=0.013). Adverse events included neurotoxicity which occurred in 5 cases in the acyclovir, but none in the placebo arm, and nephrotoxicity which was detected in 6 patients in the acyclovir and 5 in the placebo arm, respectively. We conclude that acyclovir prophylaxis significantly reduced the incidence of CMV disease, and delayed the onset of CMV infection in liver transplant patients.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antiviral Agents; Creatinine; Cytomegalovirus Infections; Double-Blind Method; Female; Graft Survival; Herpes Simplex; Humans; Injections, Intravenous; Liver Transplantation; Male; Middle Aged; Monitoring, Physiologic; Placebos; Postoperative Complications; Proportional Hazards Models; Time Factors

A subclinical viral labyrinthitis has been postulated in the literature to elicit Idiopathic Sudden Sensorineural Hearing Loss. An etiological role for the herpes virus family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, the therapeutic value of the antiherpetic drug aciclovir (Zovirax) on hearing recovery in 44 ISSHL patients receiving prednisolone is evaluated in a multicentre clinical trial. The study is designed prospectively, randomized, double-blind and placebo-controlled. Subjective parameters include hearing recovery, a pressure sensation on the affected ear, disequilibrium or vertigo and tinnitus. Audiometric parameters include pure tone and speech audiometry. A one-year follow up is obtained. Both the pressure sensation and disequilibrium or vertigo have a good prognosis, but tinnitus, occurring in most patients, has a poor prognosis. Hearing recovery prognosis depends on the severity of initial hearing loss, and not on vestibular involvement. No beneficial effect from combining aciclovir with prednisolone can be established in ISSHL.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Audiometry; Double-Blind Method; Drug Therapy, Combination; Female; Hearing Loss, Sensorineural; Herpes Simplex; Humans; Male; Middle Aged; Prednisolone; Prognosis; Prospective Studies

A randomized, double-blind study of valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P < .0001). There was a dose-response relationship (P < .0001) across the once-daily valaciclovir regimens. Twice-daily valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of valaciclovir once daily. One gram of valaciclovir once daily, 250 mg of valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with > or = 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Herpes Simplex; Humans; Male; Recurrence; Simplexvirus; Treatment Outcome; Valacyclovir; Valine

To evaluate the efficacy of oral acyclovir in preventing stromal keratitis or iritis in patients with epithelial keratitis caused by herpes simplex virus (HSV).. Patients with HSV epithelial keratitis of 1-week or less duration were treated with topical trifluridine and were randomly assigned to receive a 3-week course of oral acyclovir, 400 mg 5 times a day (hereafter referred to as the acyclovir group), or placebo (hereafter referred to as the placebo group). The development of HSV stromal keratitis or iritis was assessed during 12 months of follow-up.. Stromal keratitis or iritis developed in 17 (11%) of the 153 patients in the acyclovir group and in 14 (10%) of the 134 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for the development of stromal keratitis or iritis in the acyclovir group was 1.16 (95% confidence interval, 0.56-2.43). The development of stromal keratitis or iritis was more frequent in patients with a history of HSV stromal keratitis or iritis than in those without such a history (23% vs 9%; P = .01).. For patients with HSV epithelial keratitis treated with topical trifluridine, no apparent benefit of a 3-week course of oral acyclovir in preventing HSV stromal keratitis or iritis was seen during the subsequent year. The 1-year rate of development of stromal keratitis or iritis was lower than previously reported in the literature, except in patients with a history of HSV stromal keratitis or iritis.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antiviral Agents; Cornea; Corneal Stroma; Epithelium; Female; Follow-Up Studies; Herpes Simplex; Humans; Iritis; Keratitis; Male; Middle Aged; Prognosis; Recurrence

A randomized, double-blind, placebo-controlled trial was performed to estimate the preventive effect of the antiherpetic drug acyclovir on fever, incidence of bacteremia, use of antibiotics, and presentation of infections in patients with acute myeloid leukemia (AML).. Ninety herpes simplex virus (HSV)-seropositive patients aged 18 to 84 years were included. Forty-five patients received acyclovir (800 mg by mouth daily) and 45 placebo. The patients were examined daily for 28 days from the initiation of remission-induction chemotherapy.. Fever developed in all patients in both groups. Acyclovir prophylaxis postponed the development of an oral temperature > or = 38.0 degrees C by 3 days (95% confidence interval [CI], 1 to 4 days; P = .03) and the initiation of antibacterial treatment by 3 days (95% CI, 1 to 5 days; P = .008). The duration of fever, use of antibacterial treatment, incidence of bacteremia, and need for systemic antifungal therapy were not affected by acyclovir prophylaxis. At fever development, acyclovir prophylaxis affected the incidence and localization pattern of oral ulcers. Thus, in the acyclovir group, the number of nonfungal oral infections was reduced (relative risk, 0.45 [95% CI, 0.24 to 0.85]) and mainly located on the soft palate (relative risk, 2.49 [95% CI, 1.19 to 5.22]).. Acyclovir prophylaxis has an impact on fever development, but not on the duration of fever or the need for antibiotics. It does not reduce the incidence of bacteremia, but the presentation of acute oral infections is changed.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; Antiviral Agents; Bacteremia; Double-Blind Method; Female; Fever; Herpes Simplex; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission Induction; Simplexvirus

The safety and efficacy of cidofovir gel for treatment of acyclovir-unresponsive herpes simplex virus infections in AIDS patients was evaluated in a randomized, double-blind, multicenter trial. Cidofovir (0.3% or 1%) or placebo gel was applied once daily for 5 days. Ten of 20 cidofovir-treated and none of 10 placebo-treated patients had complete healing or >50% decreased area (P = .008); 30% of cidofovir-treated patients versus 0 placebo recipients had complete healing (P = .031). Viral shedding ceased in 13 (87%) of 15 cidofovir-treated and 0 of 9 placebo-treated patients (P = .00004). For cidofovir-treated patients, median time to complete or good response was 21 days, and median time to negative viral culture was 2 days (P = .025, P = .0001, respectively). Median lesion area decreases were 58% for cidofovir-treated versus 0 for placebo-treated patients (P = .005), and mean pain score changes were -1.84 versus -0.34 (P = .042). Application site reactions occurred in 25% of cidofovir-treated and 20% of placebo-treated patients; none was dose-limiting. Cidofovir therapy provided significant benefits in lesion healing, virologic effect, and pain reduction.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Animals; Antiviral Agents; Cells, Cultured; Chlorocebus aethiops; Cidofovir; Cytosine; Double-Blind Method; Drug Resistance, Microbial; Female; Foscarnet; Gels; Herpes Simplex; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mouth Mucosa; Organophosphonates; Organophosphorus Compounds; Simplexvirus; Vero Cells

A 5% ointment acycloguanosine was tried in the treatment of recurrent herpes simplex of the skin and genitalia in 48 patients. The treatment brought limitation of the process, relief of the symptoms, control of local manifestations and toxicity, accelerated epithelization, complete regression and disappearance of the eruption.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Simplex; Humans; Male; Middle Aged; Naphthoquinones

Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29 percent) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had > or = 50 percent reduction in lesion area. The overall estimated median time to 50 percent healing was 2.4 weeks. Ten (42 percent) patients discontinued treatment for reasons other than primary treatment failure and seven (29 percent) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area (p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33 percent) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients.

Topics: Acyclovir; Administration, Topical; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chronic Disease; Drug Resistance, Microbial; Female; Herpes Simplex; Humans; Male; Middle Aged; Pilot Projects; Safety; Trifluridine

To assess the benefit of adding oral acyclovir to a regimen of topical prednisolone phosphate and trifluridine for the treatment of iridocyclitis caused by herpes simplex virus (HSV).. Patients with HSV iridocyclitis were enrolled in a multicenter controlled clinical trial supported by the National Eye Institute, Bethesda, Md, and randomly assigned to receive a 10-week course of either oral acyclovir, 400 mg, 5 times daily, or oral placebo in conjunction with regimens of topical trifluridine and a topical corticosteroid. Follow-up examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 26 weeks after enrollment in the trial. Treatment failure was defined as a persistence or worsening of ocular inflammation, withdrawal of medication because of toxicity, or a request by the patient to withdraw from the trial for any reason. The trial was stopped because of slow recruitment after only 50 of the originally planned 104 patients were enrolled in more than 4 years.. A treatment failure occurred in 11 (50%) of the 22 patients in the acyclovir-treated group and in 19 (68%) of the 28 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for a treatment failure in the acyclovir-treated group during the 10-week treatment period was 0.43 (90% confidence interval, 0.18-1.02; P = .06, 1-tailed) and during the 16-week follow-up period (10-week treatment period plus 6-week observation period) was 0.60 (90% confidence interval, 0.29-1.25; P = .13, 1-tailed in a proportional hazards model). The treatment effect seemed slightly greater when only the patients with a persistence or worsening of ocular HSV disease were considered as treatment failures (ie, excludes terminations because of toxic effects of the drug and patients who requested to withdraw from the trial). By life-table analysis, similar results were obtained; the possible benefit of acyclovir became apparent after the first 3 weeks of follow-up.. While the number of patients recruited in this trial was too small to achieve statistically conclusive results, the trend in the results suggests a benefit of oral acyclovir in the treatment of HSV iridocyclitis in patients receiving topical corticosteroids and trifluridine prophylaxis.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Antiviral Agents; Corneal Stroma; Female; Follow-Up Studies; Herpes Simplex; Herpesvirus 1, Human; Humans; Iridocyclitis; Keratitis, Herpetic; Male; Middle Aged; Ophthalmic Solutions; Patient Compliance; Prednisolone; Treatment Failure; Treatment Outcome; Trifluridine

Topics: Acyclovir; Adolescent; Adult; CD4 Lymphocyte Count; Child; Combined Modality Therapy; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunity, Cellular; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Stomatitis, Herpetic; Vaccines, Inactivated; Viral Vaccines

A randomized case-controlled trial of oral low-dose acyclovir (600-800 mg per day) has been conducted for the prevention of virus infections in 66 recipients of renal allografts since 1990. In comparison with the untreated controls, acyclovir could prevent herpes virus simplex (HSV), reduce morbidity of pneumonia from 10 cases (30%) to 3 cases (9%) (P < 0.05) and lower CMV-IgM positive rate from 30% to 12%. Serum Cr and BUN in acyclovir group were lower than those in control group. These results strongly suggested that oral administration low-dose acyclovir could prevent virus infections after renal transplantation.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Female; Herpes Simplex; Humans; Kidney Transplantation; Male; Middle Aged; Pneumonia, Viral; Postoperative Complications

To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers.. Randomised, double blind, placebo controlled trial.. 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days.. Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis.. The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)).. Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.

Topics: Acute Disease; Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Female; Gingivitis, Necrotizing Ulcerative; Herpes Labialis; Herpes Simplex; Humans; Leukemia, Myeloid; Male; Middle Aged; Mouth Diseases; Opportunistic Infections; Stomatitis, Herpetic; Ulcer

Herpetic skin lesions have importance and growing frequency in the population. The authors report a double blind study involving 51 patients suffering from recurrent labial herpes to compare the effectiveness and adverse reactions of two topical antiviral preparations, the aciclovir (Zovirax) and epervudine (Hevizos). There was no significant difference between the two treatment groups in the healing tendency of herpetic lesions. The rate of relapses in a two months period was 44.4% in the group treated with aciclovir and 20.8% in the group treated with epervudine, the difference is not significant. Both preparation was well tolerated, only itching occurred as adverse reaction in the group treated with aciclovir. According to the results of the study the original Hungarian product (Hevizos), is at least as effective as the other topical preparation.

Topics: Acyclovir; Administration, Topical; Adult; Aged; Antiviral Agents; Deoxyuridine; Double-Blind Method; Female; Herpes Labialis; Herpes Simplex; Humans; Male; Middle Aged; Ointments; Simplexvirus

Twenty patients who suffered from more than four attacks of erythema multiforme (EM) per year were enrolled in a 6-month double-blind, placebo-controlled trial of acyclovir 400 mg twice daily. Fifteen patients had disease precipitated by recurrent herpes simplex. In the acyclovir-treated group the median number of EM attacks during the treatment period was zero, compared with three in the placebo-treated group (P < 0.0005, Wilcoxon rank sum test). Seven of the 11 patients treated with continuous acyclovir did not have any attacks of EM while taking the drug, and one showed almost complete disease suppression. Following treatment with acyclovir, two patients went into complete remission, whereas all individuals in the placebo group continued to have attacks. In the acyclovir-treated group nine of the 11 patients had herpes simplex-precipitated disease. One of the two patients with idiopathic disease showed complete disease suppression while on acyclovir, lending support to the view that idiopathic recurrent EM may be related to subclinical herpetic infection. In this study, we have shown that continuous acyclovir therapy can completely suppress attacks of recurrent EM and, in some cases, may induce disease remission.

Topics: Acyclovir; Adult; Aged; Double-Blind Method; Erythema Multiforme; Female; Herpes Simplex; Humans; Male; Middle Aged; Recurrence

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Our aim was to study the prophylactic effect of high-dose intravenous acyclovir given around the time of BMT followed by oral acyclovir on CMV infection and survival. 310 BMT recipients at risk of developing CMV infection were randomised to one of three regimens in a double-blind and double-dummy design: intravenous acylclovir (500 mg/m2, three times a day) for 1 month followed by oral acyclovir (800 mg four times a day for a further 6 months) (intravenous/oral group); intravenous acyclovir followed by oral placebo (intermediate group); or low-dose oral acyclovir (200 or 400 mg, four times a day) followed by placebo ("controls"). Analysis was by intention-to-treat. Intravenous acyclovir significantly reduced the probability of and delayed the onset of CMV infection. There was no further reduction in infection risk with the addition of long-term oral acyclovir. Time to CMV viraemia was delayed in the intravenous/oral acyclovir group compared with controls. Extending the prophylaxis with oral acyclovir significantly improved survival: 79 of 105 recipients were still alive at 7 months compared with 60 of 102 controls (p = 0.012). Although the intravenous/oral acyclovir group did significantly better than controls in terms of survival, the difference between the intravenous/oral acyclovir group and the intermediate group was of borderline statistical significance (p = 0.054). Adverse events that were possibly treatment related were similar in all three groups. The most commonly reported events were nausea, vomiting, elevated creatinine, and renal failure. High-dose intravenous followed by oral acyclovir improved survival and was of benefit in prophylaxis against the effects of CMV after BMT. Interpretation of CMV infection was made difficult because an intermediate treatment (intravenous acyclovir followed by oral placebo) was as effective as high-dose intravenous/oral acyclovir.

Topics: Acyclovir; Administration, Oral; Adult; Bone Marrow Transplantation; Cytomegalovirus Infections; Double-Blind Method; Female; Herpes Simplex; Humans; Injections, Intravenous; Longitudinal Studies; Male; Premedication; Survival Rate; Viremia

Topics: Acyclovir; Administration, Oral; Adult; Antibodies, Viral; Female; Herpes Simplex; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Recurrence; Simplexvirus

To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients.. A randomized controlled trial.. Liver transplant center at a university-affiliated Veterans Affairs Medical Center.. 47 consecutive patients having liver transplantation.. Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days.. Cytomegalovirus shedding and CMV disease were measured in the two groups.. Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir.. Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense.

Topics: Acyclovir; Adult; Aged; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Graft Survival; Herpes Simplex; Humans; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Simplexvirus; Time Factors; Virus Shedding

Topics: Acyclovir; Adolescent; Adult; Aged; Herpes Simplex; Humans; Inosine Pranobex; Middle Aged; Peptides; Thymus Extracts

We prospectively tested the hypothesis that prevention of herpes simplex virus infection with acyclovir might also reduce the incidence of bacterial infections in adult patients with acute leukaemia. During the first induction therapy a double-blind, randomized and placebo-controlled study was undertaken. Fifty-two patients were treated with 200 mg acyclovir orally four times daily throughout the induction period, whereas 55 patients received placebo. The groups were comparable with regard to age, cytotoxic chemotherapy and duration of neutropenia. Bacteraemias were significantly fewer in the acyclovir group (20 versus 41 episodes; P = 0.007). The number of isolated microorganisms causing bacterial or fungal infections was also lower during acyclovir prophylaxis (52 isolates, versus 93 isolates; P = 0.02). There was no significant difference between the groups with regard to the number of clinically documented infections or fevers of unknown origin. Herpes simplex virus isolations occurred only in the placebo group (P = 0.001). Thus, oral acyclovir prophylaxis was associated with reductions of all microbiologically documented infections suggesting that prevention of herpes simplex virus reactivation in acute leukaemia patients may reduce the occurrence of other infections.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Bacteremia; Bacterial Infections; Double-Blind Method; Fever; Herpes Simplex; Humans; Incidence; Ketoconazole; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies

UV B light is a potent stimulus for inducing reactivation of latent herpes simplex virus (HSV) infections. Patients were enrolled in a double-blind placebo-controlled crossover trial to determine whether acyclovir can prevent UV light-induced HSV-2 recurrences. Twenty-four patients with a history of recurrent infection of perigenital sites (e.g., buttock, thigh) were exposed one to four times with 4 minimum erythema doses of UV light. Patients were given acyclovir 200 mg orally five times daily or matched placebo beginning 1 day before each exposure and continuing for 5 days after exposure. There were 13 UV-induced recurrences among 36 placebo treatments and 3 after 38 acyclovir treatments (P = .004). The mean time to recurrence (+/- SE) was 4.8 +/- 0.3 days. HSV-2 lesions developed primarily at the site of UV exposure. The cutaneous distribution and timing of UV-induced recurrences was consistent with a neural localization (dorsal root ganglia) of latent viral infection. This UV light model permits direct examination of events leading to HSV-2 recurrences in humans and can be used to evaluate approaches to prevention.

Topics: Acyclovir; Adolescent; Adult; Double-Blind Method; Female; Herpes Simplex; Humans; Male; Middle Aged; Simplexvirus; Ultraviolet Rays; Virus Activation

Neonatal herpes simplex virus (HSV) infections are of increasing incidence in North America, now occurring at a rate of approximately one in 3,500 to one in 5,000 deliveries per year. Disease manifests as one of three forms; namely, infection: localized to the skin, eye and mouth (SEM), encephalitis (CNS), or disseminated disease. With the advent of antiviral therapy, it has become possible to decrease mortality and improve morbidity for babies suffering from infection. Advances in antiviral therapy have allowed for prevention of disease progression beyond states of SEM involvement. Furthermore, life threatening infections of the CNS or of multiple organs, have mortality with either acyclovir or vidarabine therapy. Now approximately 15% (CNS) and 50% (disseminated disease) of babies die from neonatal HSV disease. The results of ongoing studies in the United States will summarize the pathogenesis and treatment of neonatal HSV infection.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Nervous System Diseases; Pregnancy; Simplexvirus; Vidarabine

Herpes simplex virus (HSV) resistant to acyclovir can produce persistent mucocutaneous ulcerative disease in patients with the acquired immunodeficiency syndrome (AIDS). The incidence of clinically significant acyclovir-resistant HSV disease has dramatically increased since the advent of the AIDS epidemic. The primary mechanism of acyclovir resistance is induction of viral mutants defective or deficient in thymidine kinase, the viral-encoded enzyme, which catalyzes the rate-limiting step in the triphosphorylation of acyclovir to its active form (acyclovir triphosphate). Foscarnet, a potent inhibitor of HSV DNA polymerase, does not require phosphorylation for its antiviral activity. This compound has been found to be effective in the treatment of acyclovir-resistant HSV infection by several investigators. A recently completed dose-comparative trial of foscarnet in AIDS patients with acyclovir-resistant HSV has confirmed the safety and efficacy of two doses of foscarnet (40 mg/kg every 8 or 12 hours) in the treatment of this disease, as well as providing preliminary evidence supporting the utility of foscarnet maintenance therapy in delaying recurrence of HSV lesions. Analysis of data from this trial has been complicated by the tremendous variability in lesion size at initiation of therapy, making any statistically valid comparison of treatment regimens almost impossible. A further trial in AIDS patients with acyclovir-resistant HSV infection has been designed to define better the role of foscarnet maintenance and, in light of evidence that a significant proportion of initial recurrences are due to acyclovir-sensitive HSV, to examine the potential utility of acyclovir maintenance following foscarnet induction therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; Humans; Phosphonoacetic Acid

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

Topics: Acyclovir; Adult; AIDS-Related Complex; Double-Blind Method; Drug Therapy, Combination; Female; Herpes Simplex; Humans; Male; Neoplasms; Opportunistic Infections; Safety; Zidovudine

Acyclovir was evaluated as treatment of recurrent herpes simplex virus type 2 infection of the hand in a double-blind, placebo-controlled crossover study. In nine fully evaluable patients, oral acyclovir (2 g/day in three doses for 10 days) initiated during the earliest phase of a recurrence reduced the mean durations (+/- standard deviation) of clinical symptoms from 10.1 (+/- 3.6) to 3.7 (+/- 3.0) days (P = 0.008), signs from 11.1 (+/- 3.7) to 6.2 (+/- 3.3) days (P = 0.024), and viral positivity from 5.3 (+/- 3.8) to 0.6 (+/- 1.1) days (P = 0.011).

Topics: Acyclovir; Adolescent; Adult; Double-Blind Method; Female; Hand; Herpes Simplex; Humans; Male; Middle Aged; Recurrence; Simplexvirus

Using the decision analysis technique and multivariate regression methods, a statistical model was established to define the utility of brain biopsy for diagnostic evaluation of patients with suspected herpes simplex encephalitis (HSE). Two strategies were compared: strategy I, brain biopsy with acyclovir (ACV) treatment for 10 days in biopsy-positive patients, and strategy II, ACV therapy without brain biopsy. Strategy I resulted in a greater 6-month survival rate when the likelihood of patients having HSE was less than 70%. Based on the current estimated prevalence of HSE (for patients with suspected HSE) of 35%, strategy I showed a slight advantage of a 3.2% increase in 6-month survival rate. An individual patient's chance of a positive brain biopsy can be predicted using a mathematical equation based on several important clinical assessments. This equation in conjunction with the decision analysis is a useful guide for the clinical management of patients with regard to brain biopsy.

Topics: Acyclovir; Biopsy; Brain; Encephalitis; Herpes Simplex; Humans; Models, Statistical; Multivariate Analysis; Prevalence; Probability; Regression Analysis

Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection.. Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease).. After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects.. In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.

Topics: Acyclovir; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Injections, Intravenous; Male; Recurrence; Vidarabine

Topics: Acyclovir; Administration, Oral; Child; Disease Outbreaks; Drug Evaluation; Herpes Simplex; Humans; Simplexvirus

Topics: Acyclovir; Drug Administration Schedule; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Trimester, Third

This study tests the hypothesis that reactivation of a latent herpes simplex virus infection may be a cause of recurrent duodenal ulceration. Patients with recently healed duodenal ulcer were entered into a double blind, randomised study of maintenance treatment with the antiviral drug acyclovir (400 mg bid) versus placebo, to determine if suppression of herpes virus infection would influence the natural history of the ulcer disease. One hundred and fifteen patients entered the trial and 76 patients completed it according to the protocol. Endoscopy was performed when ulcer symptoms recurred and at the end of the 25 week trial period. In the acyclovir group the cumulated relapse rate was 63% compared with 56% in the placebo group (NS). This result suggests that reactivation of herpes simplex virus is not a cause of recurrent duodenal ulcer.

Topics: Acyclovir; Double-Blind Method; Duodenal Ulcer; Female; Herpes Simplex; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Recurrence

Eighty-two patients were randomly allocated to receive intravenous acyclovir 5 mg kg-1 t.d.s. for 23 days followed by oral acyclovir 800 mg 6-hourly for 6 months or matching placebos after allogeneic bone marrow transplantation. Herpes simplex and varicella zoster virus infections were significantly reduced during the period of administration of acyclovir. No reduction in cytomegalovirus infection was demonstrated. The drug was not toxic.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Drug Administration Schedule; Female; Herpes Simplex; Herpes Zoster; Humans; Infusions, Intravenous; Male

Cytomegalovirus is a major viral pathogen in patients who undergo renal transplantation, and cytomegalovirus disease is difficult to treat. We therefore conducted a randomized, placebo-controlled, double-blind trial of acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts from cadavers. Acyclovir was given orally in doses of 800 to 3200 mg per day, according to the patients' estimated level of renal function. Patients took the first dose of either acyclovir or placebo six hours before transplantation and continued to take the assigned medication for 12 weeks. Of 118 patients enrolled in the study, 104 completed at least 30 days on the study medication and were included in our analysis of the results. During the first year after transplantation, 4 of 53 patients (7.5 percent) in the acyclovir group had symptomatic cytomegalovirus disease, as compared with 15 of 51 (29 percent) in the placebo group (P = 0.002). There was a single case of cytomegalovirus pneumonia in the acyclovir group, as compared with nine in the placebo group. The greatest prophylactic benefit of acyclovir was observed among seronegative patients who had received a kidney from a seropositive donor; only one of six such patients in the acyclovir group had cytomegalovirus disease, as compared with all seven in the placebo group. Acyclovir decreased the incidence of documented cytomegalovirus infection (with or without symptomatic disease) to 36 percent from 61 percent among the patients who received the placebo (P = 0.011). Among the patients who received acyclovir, the rates of recovery of virus from the blood and urine were significantly reduced, but the rate of viral shedding from the pharynx was not significantly different from that in the placebo group. There were no differences between the groups in the frequency of adverse events or in the rate of survival of either grafts or patients. We conclude that the oral administration of acyclovir, beginning before the transplantation of a renal allograft from a cadaver, reduces the rate of cytomegalovirus infection and disease without affecting the survival rate of either grafts or patients.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Drug Administration Schedule; Female; Graft Survival; Herpes Simplex; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Random Allocation

This report evaluates the incidence of clinically significant HSV infection among 23 renal allograft recipients receiving OKT3 for treatment of steroid- or ALG-resistant acute rejection. No HSV infections occurred among the five HSV seronegative patients studied; three of 11 HSV seropositive patients (27%) treated with a ten-day course of low-dose acyclovir prophylaxis developed HSV infection. All three occurred after acyclovir was stopped. Five of six evaluable seropositive patients (83%) who did not receive acyclovir prophylaxis suffered HSV infection. We conclude that low-dose oral acyclovir may be effective in the prevention of HSV infection during OKT3 treatment of seropositive patients. Continuation of acyclovir prophylaxis for two to four weeks following the conclusion of OKT3 therapy may prevent occurrence of delayed infections.

Topics: Acyclovir; Adult; Antibodies, Monoclonal; Clinical Trials as Topic; Female; Graft Rejection; Herpes Simplex; Humans; Kidney Transplantation; Male; Transplantation, Homologous

Topics: Acyclovir; Adult; Aged; Antineoplastic Agents; Bone Marrow Transplantation; Clinical Trials as Topic; Double-Blind Method; Female; Herpes Simplex; Herpes Zoster; Humans; Immune Tolerance; Leukemia; Male; Middle Aged; Risk

Topics: Acyclovir; Antiviral Agents; Clinical Trials as Topic; Ganciclovir; Herpes Simplex; Humans; Premedication

Topics: Acyclovir; Amputation, Surgical; Fingers; Herpes Simplex; Humans; Infant; Randomized Controlled Trials as Topic

In a multicenter study, the efficacy of oral acyclovir 800 mg daily in preventing the development of recurrent herpes simplex virus lesions in 379 patients was assessed. Medication given in two or four divided doses daily for one year was highly effective and well tolerated. A high therapeutic index of acyclovir was maintained throughout the period of study.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Drug Administration Schedule; Drug Tolerance; Europe; Female; Herpes Simplex; Humans; Male; Recurrence; Time Factors

Herpes simplex virus (HSV) infections are a significant cause of morbidity among immunocompromised patients, and in some instances these infections may be a primary cause of death. The overwhelming majority of these infections are caused by reactivation of the virus. The natural history of reactivated HSV infections in immunocompromised patients has been well described, and these infections occur predictably in particular patient populations. Antiviral therapy has been shown to be effective in treating or preventing HSV infections. Randomized, controlled, double-blind studies have demonstrated that acyclovir is the most effective compound currently available for treatment or prevention of HSV infections.

Topics: Acyclovir; Clinical Trials as Topic; Drug Administration Schedule; Herpes Simplex; Humans; Immune Tolerance; Vidarabine

Herpes simplex virus (HSV) infections of the central nervous system are a significant cause of mortality and morbidity. The introduction of antiviral therapy has improved the outcome for patients with life-threatening disease. Neonatal HSV infection is usually acquired at the time of delivery by contact of the fetus with infected maternal genital secretions resulting in disease that can be localized to the skin, eye, and mouth, and can lead to encephalitis or become disseminated. A total of 291 babies with neonatal HSV infection have been evaluated over a period of 14 years with mortality and morbidity rates determined at one year. Vidarabine therapy decreased the incidence of mortality and improved morbidity rates; however, further improvement in mortality rates with acyclovir therapy has not been apparent. No significant clinical toxicity appeared in either treatment group. In order to improve outcome, earlier intervention and prophylactic strategies must be developed. For patients with herpes simplex encephalitis, acyclovir therapy is superior to vidarabine therapy for biopsy-proven disease. When outcome is compared for 136 vidarabine- and 46 acyclovir-treated, biopsy-proven patients, mortality rates are decreased to 20 percent with acyclovir, and approximately 40 percent of survivors are evaluated as normal at one year after therapy. Despite better outcome with antiviral therapy for the treatment of biopsy-proven herpes simplex encephalitis, further improvement is required.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Infant; Infant, Newborn; Vidarabine

The occurrence of HSV infection and the effect of prophylaxis with oral acyclovir were evaluated prospectively in 34 consecutive patients undergoing bone marrow transplantation (BMT). All allogeneic BMT procedures involved T-lymphocyte depletion for prevention of graft-vs.-host disease (GVHD). Five HSV-seronegative patients did not receive acyclovir, and they did not develop HSV infection. Oral acyclovir was administered to 15 HSV-seropositive BMT recipients; 14 untreated HSV-seropositive BMT recipients served as a control group. The adult dose of acyclovir was 400 mg three times a day on Days -6 to +14 and 200 mg three times a day on Days +15 to +90. Children received 500 mg/m2 per day divided into three equal doses on Days -6 to +14 and 250 mg/m2 per day again divided into three on Days +15 to +90. In the group on prophylaxis, only one developed HSV infection during the time prior to engraftment. In the reference group, 12 of 14 (85.7%) developed oral HSV infection within 0 to 16 days (median 11 days) after the transplantation. Time for engraftment (duration of neutropenia) was shorter in patients receiving acyclovir. After engraftment, HSV infection was not observed during administration or following discontinuation of acyclovir on Day 90, but occurred in three patients in whom acyclovir was discontinued on Days 25, 35 and 40 after BMT. In the untreated group, two patients had recurrence of HSV infection on Days 40 to 60, and one had two infectious episodes. GVHD occurred in only two recipients, neither of whom had HSV infection. We conclude that the incidence of HSV infection during the period until engraftment in recipients of T-lymphocyte-depleted BMT is high, similar to that reported by others in recipients of whole BMT. Relatively low-dose oral acyclovir administered for 90 days can effectively prevent HSV infections in previously HSV-seropositive BMT recipients and may also shorten the period until engraftment.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Anemia, Aplastic; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Female; Graft vs Host Disease; Herpes Simplex; Histocompatibility Testing; HLA Antigens; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphocyte Depletion; Male; Middle Aged; Stomatitis, Herpetic; T-Lymphocytes; Transplantation, Homologous

Twenty-nine patients with first-episode rectal herpes simplex virus infection were enrolled in a double-blind trial of oral acyclovir, 400 mg five times daily, vs placebo treatment. Eighty percent of those receiving acyclovir compared with 25% of placebo recipients no longer had herpes simplex virus isolated from their rectal lesions three days after onset of therapy. The median duration of rectal lesions and viral excretion from rectal lesions (median, five and zero days, respectively) was significantly shorter in patients treated with acyclovir than in placebo-treated patients (14 and 11 days, respectively). Durations of local signs and symptoms of proctitis, such as rectal pain, discharge, and friability, were shorter in acyclovir recipients than in placebo recipients, but these differences were not statistically significant. Daily administration of 2 g of oral acyclovir for ten days alleviates some of the clinical signs of herpes simplex virus rectal infection.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Double-Blind Method; Drug Evaluation; Herpes Simplex; Homosexuality; Humans; Male; Proctitis; Random Allocation

Fifty-nine neonates with herpes simplex virus (HSV) infection were evaluated with use of assays for neutralizing antibody (NAb), lymphocyte transformation (LT), alpha interferon production, and virus-specific antibody (immunoblots). Infants with disseminated disease or onset in the first week of life were more likely to lack NAb. Patients treated with vidarabine were more likely than those treated with acyclovir to develop a fourfold rise in NAb titer. Infants with encephalitis showed a broader spectrum of IgG and IgM antibody reactivity against HSV proteins by immunoblotting than did those who had earlier onset of mucocutaneous illness. Only 10 of 33 infants had HSV-specific LT, compared with eight of eight adults with primary HSV. Neonates with positive LT were more likely to show a fourfold rise in NAb titer. In vitro alpha interferon production was diminished in infants, compared with values in adults.

Topics: Acyclovir; Adult; Antibodies, Viral; Antibody Formation; Antigens, Viral; Herpes Simplex; Humans; Immunity, Cellular; Immunity, Maternally-Acquired; Infant, Newborn; Interferon Type I; Lymphocyte Activation; Neutralization Tests; Simplexvirus; Vidarabine

A total of 208 patients underwent brain biopsy for presumptive herpes simplex encephalitis and were randomized to receive either vidarabine, vira-A, at 15 mg/kg/day, or acyclovir, at 30 mg/kg/day for ten days. 69 patients (33%) had biopsy-proven disease; 37 received vira-A and 32 acyclovir. With the exception of age, patient populations were balanced for demographic characteristics. Overall survival for acyclovir recipients was 72% compared with 46% for vira-A-treated patients 18 months after therapy (p = 0.008). After adjustment for differences of age between treatment populations by multivariant regression analyses, acyclovir treatment remained superior to vidarabine therapy (p = 0.041). Mortality varied according to the level of consciousness at the onset of therapy. For lethargic, semicomatose and comatose patients, mortality was 42%, 46%, and 67%, respectively, for the vira-A-treated patients and 0%, 25% and 25%, respectively, for acyclovir-treated patients. Six months post-therapy morbidity assessments revealed five (14%) vira-A versus 12 (38%) acyclovir recipients who had returned to normal function, while eight (22%) and three (9%), respectively, had moderate debility. Outcome differences were significant (p = 0.02; Wilcoxon, 2-sample test) using an adapted scoring system. Age and Glasgow coma scale greater than 10 predicted the best outcome following acyclovir treatment. Disoriented patients who flex and respond by eye to pain had no mortality and 50% returned to normal. These data indicate that acyclovir is the treatment of choice for biopsy-proven herpes simplex encephalitis.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Middle Aged; Random Allocation; Regression Analysis; Vidarabine

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Seizures; Vidarabine

Topics: Acyclovir; Adult; Clinical Trials as Topic; Cyclosporins; Double-Blind Method; Drug Interactions; Female; Herpes Simplex; Herpes Zoster; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Random Allocation

Acyclovir has been widely used against the various manifestations of eye disease due to herpes simplex since it first became generally available in the UK nearly five years ago. This paper discusses the rational indications for its use, through considerations of its pharmacology and pharmacokinetics, and through results of the many clinical trials that have been carried out to investigate its effects since its clinical efficacy was first demonstrated in 1979.

Topics: Acyclovir; Clinical Trials as Topic; Conjunctivitis, Viral; Corneal Ulcer; Herpes Simplex; Humans; Keratitis, Dendritic; Uveitis

To define an effective and convenient means for providing extended prophylaxis of herpes simplex virus (HSV) infection to chronically immunocompromised patients, we studied a two-part regimen of intravenous, followed by oral, acyclovir after marrow transplantation. Seropositive patients were first given intravenous acyclovir until day 30 after transplant. Intravenous acyclovir (250 mgm/m2) given twice daily to 34 patients during this period was 90% virologically effective among those completing the prophylactic course. A randomized, double-blind comparison of twice-daily oral acyclovir (800 mg) and placebo was then conducted from day 31 to day 75 after transplant in 51 patients. Oral acyclovir significantly delayed the median time to first excretion of HSV when compared with placebo (greater than 100 vs. 70 days after transplant, P = 0.0006) and was completely effective in all patients for the duration of drug administration. Patients receiving extended prophylaxis appeared to have less-severe HSV infection when later recurrences did occur. Sequential intravenous and oral acyclovir given twice daily is an effective and convenient regimen for extended prophylaxis of HSV infection following marrow transplantation, and should be useful in other transplant patients or other chronically immunosuppressed patients as well.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials as Topic; Female; Herpes Simplex; Humans; Injections, Intravenous; Male; Middle Aged; Random Allocation

In this randomized double-blind and placebo controlled trial of 6 months' prophylaxis with acyclovir (ACV) in 42 bone marrow transplant (BMT) recipients, patients receiving ACV had fewer herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections during the prophylaxis compared to the placebo treated patients (P less than 0.05). During the first 6 months after the prophylaxis had been discontinued the frequency of clinical HSV reactivations was low both in the ACV (1/13) and in the placebo (1/13) treated patient groups. Altogether the ACV treated patients had significantly fewer HSV reactivations during the first year after BMT (P less than 0.05). The HSV-specific lymphocyte proliferation response was also lower in the ACV treated group at 3, 6 and 12 months after BMT (P less than 0.05). VZV infections recurred rather frequently, however, after discontinuation of ACV prophylaxis. Therefore no difference was found in the number of VZV infections during the first year after BMT. The VZV-specific lymphocyte proliferation response was significantly lower in the ACV treated group only at 6 months (P less than 0.05). ACV prophylaxis had no effect on the frequency of CMV infections; CMV-specific lymphocyte proliferative responses were not decreased.

Topics: Actuarial Analysis; Acyclovir; Antigens, Viral; Bone Marrow Transplantation; Cell Transformation, Viral; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Graft vs Host Disease; Herpes Simplex; Humans; Lymphocyte Activation; Random Allocation; Simplexvirus

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.

Topics: Acyclovir; Adolescent; Adult; Biopsy; Brain; Child; Child, Preschool; Encephalitis; Female; Herpes Simplex; Humans; Infant; Male; Middle Aged; Random Allocation; Simplexvirus; Vidarabine

After a discussion of the principles of antiviral chemotherapy, treatment and chemoprophylaxis of the following virus infections are reviewed in detail: the various manifestations of herpes simplex virus infections, varicella-zoster, cytomegalovirus infections, Epstein-Barr virus infections, laryngeal papillomas, and influenza A. Special reference is made to the treatment of immunocompromized patients. Acycloguanosine (acyclovir) has been found particularly useful in the treatment of herpes simplex virus and varicella zoster virus infections in immunocompromized patients and for herpesencephalitis. Varicella-zoster can also be treated effectively with bromovinyldeoxyuridine (BVDU). Toxicity of the currently used antiviral drugs is discussed as well as the problem of drug resistance.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Pemphigoid Gestationis; Pregnancy; Vidarabine; Virus Diseases

Neonatal herpes simplex virus (HSV) infections are recognized to be severe because of their association with significant morbidity and mortality. Through ongoing studies performed by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, the presentation, natural history, outcome and value of antiviral chemotherapy have been considered. Infants developing neonatal HSV infections can be classified according to the extent of disease, disseminated or localized. Localized infection can be subdivided into either central nervous system (CNS) disease, occurring in 35% of infected infants, or skin, eye and mouth (SEM) disease, in 41% of infants. Disseminated disease accounts for 24% of neonatal HSV infection. Therapeutic outcome depends upon disease classification. Administration of either 15 or 30 mg/kg/day of vidarabine resulted in significantly decreased mortality for infants with life-threatening disseminated and CNS disease as compared to placebo recipients. Approximately one-third of children developed normally following disseminated disease or CNS infection. When disease was localized to the SEM, no death occurred, and 88% of treated infants developed normally. While these data indicate that therapy is effective for management of infants with neonatal HSV infection, improvements are necessary. Hopefully, a study in progress will demonstrate improved outcome with acyclovir treatment.

Topics: Acyclovir; Central Nervous System Diseases; Clinical Trials as Topic; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Keratitis, Dendritic; Pregnancy; Pregnancy Complications, Infectious; Recurrence; Risk; Skin Diseases, Infectious; Stomatitis, Herpetic; Vidarabine

Antiviral compounds have been developed for use in chemoprophylaxis and chemotherapy of a variety of infections in humans, including those caused by influenza viruses, respiratory syncytial virus, and herpesviruses. The efficacy of several of these compounds has been demonstrated in rigorously controlled trials. Advances in molecular virology have led to the identification of biochemically defined, virus-specific functions that serve as appropriate targets for the future development of antiviral compounds. Clinical investigators and practicing physicians are now confronting questions previously raised with the use of antibacterial antibiotics. These questions concern appropriate routes of administration for antiviral compounds, optimal dosage regimens, risks of long-term prophylaxis, and the emergence of resistant organisms.

Topics: Acyclovir; Adult; Aged; Amantadine; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Cytomegalovirus; Encephalitis; Foscarnet; Guanosine Triphosphate; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Influenza A virus; Influenza, Human; Phosphonoacetic Acid; Respiratory Tract Infections; Ribavirin; Rimantadine; Vidarabine; Virus Diseases

In a randomized, double-blinded, placebo-controlled trial, we compared the therapeutic effect of oral acyclovir (400 mg five times daily for 10 days) with that of placebo in patients with marrow transplants and culture-proven recurrent mucocutaneous herpes simplex. Twelve patients received acyclovir and nine received placebo. Acyclovir treatment significantly shortened the median duration of viral shedding, new lesion formation, and time to first decrease in pain, resolution of pain, 50% healing, and total healing. These results compared favorably with those previously obtained with intravenous or topical acyclovir preparations. Oral acyclovir is highly effective for the treatment of recurrent mucocutaneous infections caused by herpes simplex virus in immunocompromised patients.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Double-Blind Method; Female; Herpes Simplex; Humans; Immunosuppression Therapy; Male; Middle Aged; Random Allocation; Recurrence; Simplexvirus

Topics: Acyclovir; Adult; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Infant, Newborn, Diseases; Keratitis, Dendritic; Trifluridine; Vidarabine

To determine the most convenient and least expensive regimen for prevention of recurrent herpes simplex virus (HSV) infection after marrow transplantation, we conducted a randomized, double-blind comparison of intravenous acyclovir 250 mg/m2 and placebo given once daily for four weeks. Six of 14 acyclovir and nine of 13 placebo recipients shed HSV during prophylaxis. All nine culture-positive placebo recipients developed associated lesions during prophylaxis compared to four of six acyclovir recipients. Median time to first culture-positive lesion was significantly delayed by acyclovir compared to placebo (33 days after transplant vs. 10; P = 0.05). Acyclovir-resistant HSV was recovered from one acyclovir recipient while receiving prophylactic acyclovir, and from two placebo recipients during subsequent administration of therapeutic acyclovir. Once-daily intravenous acyclovir can significantly delay time to appearance of culture-positive HSV lesions after marrow transplant, but virological and clinical breakthrough may occur and optimal prevention will require administration of intravenous acyclovir more than once daily.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Drug Administration Schedule; Female; Herpes Simplex; Humans; Male; Middle Aged; Simplexvirus; Time Factors

Forty patients with serum antibody against herpes simplex virus (HSV) were enrolled in a randomized, placebo-controlled, double-blind investigation of acyclovir given orally in a low dosage as prophylaxis against recurrent HSV infection after renal transplantation. During 30 postoperative days of medication, 14 of 21 placebo-treated and one of 19 acyclovir-treated patient(s) developed reactivation of HSV infection. Eleven of the former, but not the latter, had herpetic lesions. The protection against active infection with HSV during the period of prophylaxis with acyclovir is statistically highly significant. From 30 to 90 days after transplantation when no antiviral medicine was given, 60% (3/5) of the remaining placebo recipients and 44% (7/16) of the acyclovir patients developed active HSV infections. Herpetic lesions occurred in two of three and two of seven of infected people in the respective groups. No adverse effects of the drug were observed. The results show that HSV infections in immunosuppressed renal allograft recipients can be safely prevented, deferred, and ameliorated by an initial period of prophylaxis with a low dose of oral acyclovir.

Topics: Acyclovir; Adult; Antibodies, Viral; Clinical Trials as Topic; Double-Blind Method; Female; Graft Survival; Herpes Simplex; Humans; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prospective Studies; Random Allocation; Recurrence; Simplexvirus

Topics: Acyclovir; Chickenpox; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Interferon Type I; Recurrence; Vidarabine

The efficacy of oral acyclovir to prevent reactivation of herpes simplex virus (HSV) in seropositive renal allograft recipients was tested in a double-blind placebo controlled study. None of the 18 patients allocated to acyclovir showed any signs of HSV infection. In contrast, 11/17 on placebo (p less than 0.001), had signs of HSV or varicella zoster virus (VZV) infection--in 5 patients severe enough to interrupt the trial and initiate treatment with oral acyclovir. Soon after cessation of the trial, HSV was isolated from the throats of 6 patients on acyclovir, and 1 developed shingles 3 months later. Oral acyclovir prophylaxis thus effectively protected the patients from reactivation of HSV and VZV while they were receiving the drug, but could not prevent disease once off the drug. Treatment with acyclovir brought rapid relief of both local and general symptoms in all patients. No adverse reactions were seen. As a consequence of these experiences our goal in subsequent transplant patients has been either early therapeutic intervention with oral acyclovir whenever signs of HSV or VZV infection have been noted, or prophylactic remedy in patients at particular risk to develop troublesome herpetic lesions after renal transplantation.

Topics: Acyclovir; Administration, Oral; Clinical Trials as Topic; Herpes Simplex; Herpes Zoster; Humans; Kidney Transplantation; Postoperative Complications; Premedication; Random Allocation

One hundred and twenty-seven patients with suspected herpes simplex encephalitis were entered in a randomised, controlled comparative study of therapy with acyclovir 10 mg/kg, 8-hourly, versus vidarabine, 15 mg/kg daily, for 10 days. Consecutive patients were included and nearly all diagnosed cases of HSV-encephalitis in Sweden were enrolled in the study. The diagnosis of HSV-encephalitis was verified by demonstration of intrathecal herpes simplex virus (HSV) antibody production and by HSV cultivation, or antigen detection, in brain biopsy or necropsy material. Of 53 confirmed cases of HSV-encephalitis (corresponding to 2.3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for therapeutic efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 12 month of observation 15 of 27 (56%) acyclovir recipients had no, or mild, sequelae compared with 3 of 24 (13%) vidarabine recipients (p = 0.002). Nineteen of 24 (79%) vidarabine-treated patients died or suffered severe sequelae, compared with 9 of 27 (33%) acyclovir-treated patients (p = 0.005). The effect of treatment was influenced by the level of consciousness at the start of therapy. The outcome for 20 vidarabine-treated patients above 30 years of age with HSE was similar to that for the 53 patients reported by an American collaborative study.

Topics: Acyclovir; Adolescent; Adult; Aged; Antibodies, Viral; Child; Child, Preschool; Clinical Trials as Topic; Encephalitis; Herpes Simplex; Humans; Infant; Middle Aged; Prospective Studies; Random Allocation; Vidarabine

In a double-blind, placebo-controlled, cross-over trial in 11 patients suffering eight or more episodes of recurrent non-genital herpes simplex virus (HSV) infection per annum, only two patients experienced a recurrence during treatment with oral acyclovir (200 mg 4 times daily) for up to 12 weeks, compared with nine during placebo treatment (P = 0.016). Although lesion development was effectively suppressed in nine of the patients whilst taking acyclovir, the development of prodromal symptoms, and occasionally erythema, was reported by five. There was no difference between acyclovir and placebo in the time to the next recurrence following completion of treatment. No patient reported any side effects of either placebo or acyclovir therapy. It is believed that this is the first report of any form of oral therapy which is effective in suppressing recurrent non-genital HSV infection in immunocompetent patients.

Topics: Acyclovir; Administration, Oral; Adult; Clinical Trials as Topic; Double-Blind Method; Female; Herpes Simplex; Humans; Male; Middle Aged; Recurrence

Sixty-three immunocompromised patients with infections caused by herpes simplex virus were evaluated in a double-blind, placebo-controlled study of topical acyclovir therapy; 33 patients received acyclovir and 30 received the placebo. The two populations of patients were balanced in terms of age, race, sex, underlying disease, preceding chemotherapy, and site, size, and duration of lesions. Acyclovir recipients experienced an acceleration in the clearance of virus (P = .0006), the resolution of pain (P = .004), and the total healing of lesions (P = .038); median temporal differences between populations averaged six days for each of these three parameters. The surface area of herpetic lesions continued to enlarge in placebo recipients after entry into the trial; in contrast, lesion surface area decreased progressively during therapy in drug recipients. The speed of healing was influenced by lesion size. Patients with lesions of greater than or equal to 50 mm2 benefited most from therapy, particularly in terms of pain resolution and time to total healing (median differences between groups, eight days). Irrespective of underlying disease, sex, preceding chemotherapy, or age, acyclovir therapy was of clinical benefit. No adverse clinical or laboratory reactions were encountered.

Topics: Acyclovir; Administration, Topical; Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Double-Blind Method; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Immune Tolerance; Male; Middle Aged; Recurrence; Simplexvirus; Stomatitis, Herpetic

In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.

Topics: Acyclovir; Antibodies, Viral; Bone Marrow Transplantation; Clinical Trials as Topic; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Herpes Simplex; Humans; Intestinal Absorption; Simplexvirus; Transplantation, Homologous

Topics: Acyclovir; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Keratitis, Dendritic; Keratoconjunctivitis; Male; Vidarabine

To evaluate the effect of acyclovir (ACV) therapy on the cellular immune response, we sequentially followed 43 patients with culture-proven first episodes of genital herpes simplex virus (HSV) infection. Twenty-three patients who were treated with ACV and 20 who received placebo had blood obtained weekly during the first 6 weeks after onset of lesions and had their in vitro lymphocyte transformation (LT) response to inactivated HSV antigens measured. The mean stimulation index to HSV antigens at week 3 among patients treated with systemic ACV was 3.5 +/- 0.64 compared to 18.4 +/- 6.89 in their placebo-treated counterparts (P less than 0.05). The mean time to the development of the peak LT response to HSV antigens was 4.3 weeks in systemic-treated versus 3.4 in placebo-treated patients (P less than 0.05). The time to the development of the peak in vitro LT response to HSV antigens and the height of that response were, however, similar between topical ACV- and topical placebo-treated patients. The geometric mean HSV-2-neutralizing titer in convalescent sera was 5.4 in recipients of systemic ACV compared to 10.0 in patients treated with systemic placebo (P less than 0.05). The LT response to HSV antigen was also measured at the first recurrence in 11 patients. No differences were found in the time to first recurrence, lesion duration, number of lesions, or mean stimulation index response to inactivated HSV antigens between the six patients treated with systemic ACV during their primary episode and the five given placebo during their primary episode. Systemic ACV therapy appears to diminish the peak in vitro LT response to inactivated HSV antigens as well as to delay the time to development of that peak response. However, the cell-mediated immune response to subsequent episodes appears similar.

Topics: Acyclovir; Administration, Topical; Antibody Formation; Cell Transformation, Viral; Female; Herpes Simplex; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Recurrence; Simplexvirus; Time Factors

127 patients with suspected herpes simplex encephalitis (HSE) were entered in a prospective randomised study of acyclovir 10 mg/kg 8-hourly versus vidarabine 15 mg/kg daily for 10 days. The patients were consecutive and nearly all Swedish cases of HSE were included; they were treated in six university infectious diseases departments. The diagnosis of HSE was verified by brain biopsy and/or antibody responses in serum and cerebrospinal fluid. Of 53 confirmed cases of HSE (corresponding to 2 X 3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for analysis of efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 6 months of observation 15 (56%) of 27 acyclovir-treated patients had returned to normal life compared with 3 (13%) of 24 vidarabine-treated patients (p = 0.002); and the numbers who died or had severe sequelae were 9 (33%) and 19 (76%), respectively (p = 0.005). No important or new adverse events were recognised.

Topics: Acyclovir; Adolescent; Adult; Aged; Antibodies, Viral; Brain; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Encephalitis; Follow-Up Studies; Herpes Simplex; Humans; Infant; Infant, Newborn; Middle Aged; Prospective Studies; Random Allocation; Simplexvirus; Vidarabine

Oral acyclovir was found to be safe and effective for the prevention of herpes simplex virus reactivation after marrow transplantation in a double-blind, placebo-controlled trial. Acyclovir or placebo was administered to 49 patients for 5 weeks beginning 1 week before transplantation: 5 of 24 patients receiving acyclovir developed herpes simplex virus infection during prophylaxis, compared to 17 of 25 patients receiving placebo (p less than 0.01). The median time to first virus reactivation was significantly longer among patients receiving acyclovir (78 days versus 9 days after transplant, p = 0.006). The effect was even more pronounced when the analysis was adjusted for drug compliance: Among patients taking a minimum of 40% of their prescribed drug, acyclovir was 96% virologically effective and 100% clinically effective during the period of administration. Acyclovir use was also associated with significantly more rapid marrow engraftment in patients receiving methotrexate. No virus resistant to acyclovir was isolated. Oral acyclovir provides effective prophylaxis against reactivation of herpes simplex virus among severely immunosuppressed patients able to take orally administered drugs.

Topics: Acyclovir; Adolescent; Adult; Bone Marrow Transplantation; Child; Clinical Trials as Topic; Double-Blind Method; Female; Herpes Simplex; Humans; Immunosuppression Therapy; Lymphocyte Activation; Male; Middle Aged; Patient Compliance; Postoperative Complications; Prospective Studies; Random Allocation; Simplexvirus

Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001).

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Double-Blind Method; Doxorubicin; Drug Resistance, Microbial; Female; Herpes Simplex; Humans; Leukemia, Lymphoid; Lymphoma; Male; Middle Aged; Procarbazine; Random Allocation; Vincristine

Topics: Acyclovir; Administration, Topical; Adolescent; Amantadine; Antiviral Agents; Chickenpox; Child; Clinical Trials as Topic; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; Influenza, Human; Keratitis, Dendritic; Male; Rimantadine; Vidarabine

The effect of topical acyclovir treatment of first episode genital herpes on the time to first recurrence in a group of 42 patients receiving either acyclovir or placebo was investigated. Topical acyclovir treatment had no effect on time to first recurrence in patients with either first episode HSV-1 or HSV-2 infections. There was no significant difference in the time to first recurrence in patients with either true primary or initial genital infections. However, the time to first recurrence in patients with first episode HSV-2 was significantly shorter than in patients with first episode HSV-1. Acyclovir treatment appeared to have no effect on the development of neutralising antibody in patients with either virus type.

Topics: Acyclovir; Antibodies, Viral; Female; Herpes Genitalis; Herpes Simplex; Humans; Male; Recurrence; Time Factors

In a double-blind controlled study, oral acyclovir was compared with placebo in 39 consecutive patients undergoing bone-marrow transplantation. Acyclovir was given at a dose of 200 mg every 6 h from 8 days before to 35 days after bone-marrow transplantation. Pharmacokinetic studies showed good absorption of the drug, despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease. There was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group compared with the placebo group even in patients with high anti-HSV antibody titres before transplantation. The same protection was observed against cytomegalovirus (CMV) infection. The frequencies of HSV and CMV infections were the same in both groups after the cessation of treatment.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Herpes Simplex; Humans; Postoperative Complications

A number of antiviral compounds are currently available, and several others are of great interest. Trifluridine, idoxuridine, and vidarabine are effective topically in herpes simplex virus keratoconjunctivitis infection. Vidarabine (and presumably acyclovir) is effective in herpes simplex virus encephalitis and in herpes zoster infections in the immunocompromised host. Acyclovir is effective topically, orally, and intravenously in primary herpes genitalis, and the oral and intravenous forms are effective in recurrent herpes genitalis as well. Amantadine and rimantadine are effective prophylactically and therapeutically in influenza A infections. Ribavirin and interferon, although not licensed, are of great interest. Ribavirin may be useful in respiratory syncytial virus infections, and interferon may be of benefit in common colds and related disorders.

Topics: Acyclovir; Amantadine; Antiviral Agents; Clinical Trials as Topic; Female; Herpes Genitalis; Herpes Simplex; Humans; Idoxuridine; Influenza, Human; Interferons; Keratitis, Dendritic; Male; Ribavirin; Rimantadine; Trifluridine; Vidarabine

Acyclovir (acycloguanosine) is a new antiviral compound with activity against certain herpes viruses. Acyclovir is phosphorylated preferentially in virus-infected cells into its active form, acyclovir triphosphate, an inhibitor of viral-induced DNA polymerase. Acyclovir, which possesses an acyclic carbohydrate moiety, also causes premature DNA chain termination. Acyclovir has shown clinical activity against herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV), but its usefulness in cytomegalovirus, Epstein-Barr virus, and chronic hepatitis B infections requires further study. In randomized clinical trials of infections caused by HSV and VZV, intravenous acyclovir has been shown to shorten the duration of viral shedding and lesion pain and hasten the resolution of skin lesions, with minimal toxicity.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Drug Resistance, Microbial; Herpes Simplex; Herpes Zoster; Humans; Injections, Intravenous; Kinetics; Virus Diseases

Guidelines for the prophylaxis or therapy of herpesvirus infections are shown in Table 1. Progress is so rapid in this area that frequent revisions of such guidelines will be necessary. Newer drugs or new formulations of older agents are constantly being developed. Combination therapies--e.g., interferon plus acyclovir--appear promising in laboratory models of herpesvirus infections and will undoubtedly receive clinical investigation in the years ahead. The problem of dealing with latent virus infections still eludes us, and major breakthroughs will be necessary before we can discuss cure of recurrent infections. Nevertheless, important strides have been made in the past few years, and further progress is predictable in the years ahead.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Encephalitis; Female; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpesviridae Infections; Humans; Immune Tolerance; Infant, Newborn; Interferon Type I; Keratitis, Dendritic; Male; Vidarabine

The sensitivity to acyclovir of more than 800 herpes simplex virus (HSV) isolates from over 300 patients were tested by the dye-uptake method. While a broad spectrum of sensitivity was found, approximately 90% of the isolates were inhibited by less than 1 mg/l of acyclovir. Therapy usually did not significantly alter the sensitivity of HSV isolates except in a few severely immunocompromised patients in whom resistant viruses produced asymptomatic or indolent infections. The sensitivity of viruses isolated during subsequent recurrences was similar to that of the originally infecting virus, regardless of therapy. The requirement of convenient and standardized methods of virus sensitivity testing is emphasized so that additional data can be accumulated to allow more precise correlations between in-vitro virus sensitivity and clinical response to acyclovir therapy.

Topics: Acyclovir; Clinical Trials as Topic; Double-Blind Method; Drug Resistance, Microbial; Herpes Simplex; Humans; Microbial Sensitivity Tests; Recurrence; Simplexvirus

Two consecutive studies are reported. In study 1, 59 patients with acute leukaemia undergoing remission induction therapy or bone marrow transplantation were given either acyclovir (5 mg/kg) or placebo by intravenous infusion twice daily during the period of neutropenia. All patients were seropositive (greater than or equal to 1:8) for herpes simplex virus. Acyclovir provided total protection against herpes simplex virus infection in bone marrow transplant patients with 0/10 versus 5/10 infections in the placebo group (P = 0.033). For the remission induction therapy group 2/19 on acyclovir developed HSV versus 10/20 receiving placebo (P = 0.018). Only one episode of cytomegalovirus (CMV) infection was seen and this was in a patient on acyclovir. Epstein-Barr virus secretion studies were inconclusive. No varicella zoster virus (VZV) infections were seen. In Study 2, 20 consecutive HSV seropositive (greater than or equal to 1:8) bone marrow transplant recipients received oral acyclovir. Five (25%) developed HSV infections, one of which was in a non-compliant patient, who subsequently developed a fatal infection whilst receiving therapeutic (5 mg/kg 8 hourly) intravenous acyclovir for this HSV infection. Intravenous acyclovir is effective in preventing HSV infections in the immunocompromised host but it seems unlikely that CMV will be amenable to acyclovir in its present formulation.

Topics: Acyclovir; Administration, Oral; Bone Marrow Transplantation; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Female; Herpes Simplex; Humans; Immunosuppression Therapy; Infusions, Parenteral; Leukemia; Male; Random Allocation

In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Anemia, Aplastic; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Drug Administration Schedule; Graft vs Host Disease; Herpes Simplex; Humans; Immunosuppression Therapy; Intestinal Absorption; Leukemia; Random Allocation; Recurrence

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major imp

Topics: Acyclovir; Animals; Clinical Trials as Topic; Cytomegalovirus; Drug Resistance, Microbial; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Immunity; Keratitis, Dendritic; Kinetics; Male; Mutagens; Recurrence

The clinical effects of a new anti-viral 9-(2-hydroxymethoxymethyl) guanine (Aciclovir) against Herpes virus infections have been investigated. The patients had malignant tumours or auto-immune disease complicated by shingles and chicken pox due to Vaicella zoster virus (VZV) (43 cases), Herpes simplex virus (HSV) (10 cases) and 9 cases which were clinically diagnosed as Herpes, though the virus was not confirmed as the causative agent. As a general principle the dosage of Aciclovir was 5 mg/kg, t. i. d. for 5 days by slow intravenous infusion. The clinically effective rate against VZV was 93%, being excellent in 42% and against HSV it was 80%, being excellent in 40% and when the results of the cases of unknown origin were included it was excellent in 40% and the cumulative effective rate was 88%. Concerning the efficacy in reduction of pain, swelling, disappearance of vesicles and new scab formation, the effect was most noticeable after the third day of treatment. Treatment given early in the disease is likely to provide better results. Concerning side effects, one of 62 patients had proteinuria and the other had a drug rash and an abnormal liver function test. It is likely that the combination of treatment and the primary disease had some influence, but the cause/effect relationship to Aciclovir treatment is not clear.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Female; Herpes Simplex; Herpes Zoster; Humans; Leukemia; Male; Middle Aged; Neoplasms

A total of 59 patients, including 20 undergoing bone marrow transplantation (BMT) and 39 who were receiving cytotoxic chemotherapy (CT), were included in a placebo-controlled trial of intravenous acyclovir as a prophylactic against herpes simplex virus infections. Fifty per cent of the patients (both BMT and CT) receiving placebo developed herpes simplex virus infections; in those receiving acyclovir, none of the BMT group and 10 per cent of the CT group became infected with herpes simplex. Prevention of herpes infections in the immunosuppressed is clearly both desirable and, in the case of herpes simplex virus, attainable.

Topics: Acyclovir; Bone Marrow Transplantation; Herpes Simplex; Humans; Immune Tolerance

Herpes simplex encephalitis and neonatal herpes simplex virus infections are important consequences of herpes simplex virus infections of humans. The association of both diseases with significant mortality and morbidity has prompted intensive therapeutic trials designed to improve outcome. The NIAID Collaborative Antiviral Study Group has been able to demonstrate that vidarabine therapy decreases the mortality and improves morbidity for both herpes simplex encephalitis and neonatal herpes simplex virus infections. Nevertheless, mortality for both diseases is about 40% and many survivors are left with significant neurological impairment. With the hope of improving outcome, we initiated comparative trials of vidarabine and acyclovir for these two diseases. This report summarizes the status of these trials, which are still underway, with particular reference to the complexities of studies such as these. Because adequate numbers of patients for definitive statistical analyses have not been entered into the trial, data were assessed according to outcome for the entire group, irrespective of drug administered. The mortality of herpes simplex encephalitis and neonatal herpes simplex virus infections has been reduced to 34 and 30%, respectively, a decrease of approximately 10% for each disease. Further analyses await completion of the trials.

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Random Allocation; Time Factors; Vidarabine

Twenty-nine adult patients with acute leukemia receiving timed sequential chemotherapy participated in a randomized, double-blind, placebo-controlled trial of acyclovir prophylaxis against reactivated herpes simplex virus infection. Patients with pretreatment antibody titers of 1:16 or greater received acyclovir or placebo starting 4 days after their initial chemotherapy. Treatment was given either for 32 days or until the patients were discharged from the hospital or until a culture-positive herpes simplex virus infection was found. Culture-positive herpes simplex virus infection developed in 11 of 15 patients who received placebo. No infection appeared in 14 patients who received acyclovir (p less than 0.00005). No obvious acute drug toxicity was seen. Recurrent infection was seen in 6 of 14 patients after cessation of acyclovir when retreated with chemotherapy, suggesting no effect on viral latency in these 6 patients. Acyclovir provided highly effective prophylaxis against reactivated herpes simplex virus infections in adult patients with acute leukemia receiving timed sequential chemotherapy.

Topics: Acute Disease; Acyclovir; Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Female; Herpes Simplex; Humans; Leukemia; Male; Middle Aged; Random Allocation; Virus Activation

That acyclovir is effective therapeutically in herpes simplex virus (HSV) and herpes zoster (VZV) infections in immunocompromised patients has been established [13]. This paper reviews our subsequent studies in prophylaxis of herpes group infections in a high risk group of patients suffering from acute leukaemia. In study 1 we randomised HSV seropositive (greater than or equal to 1:8) patients to receive intravenous acyclovir or placebo. In this stratified study bone marrow transplant (BMT) recipients were completely protected from HSV infections by acyclovir compared with a 50% failure rate for those on placebo. There was significant protection also in the non-BMT group [8]. In study 2 oral acyclovir prophylaxis failed to provide complete protection in BMT recipients despite the achievement of apparently adequate blood levels. In study 1 the secretion of EBV in saliva before and during the trial gave inconclusive results. In each of the first two studies one patient on "active" acyclovir developed a cytomegalovirus (CMV) infection. Thus, at the dosage of drug used, prophylaxis of CMV was unsuccessful suggesting that claims of therapeutic efficacy are unlikely to be supported in controlled trials. Study 3 is current and concerns the pharmacokinetics of an acyclovir prodrug (BW 134U) taken by mouth. This drug is near 100% absorbed and achieves approximately twice the level of active acyclovir in vivo, following conversion by adenosine deaminase (ADA), in normal volunteers.

Topics: Acyclovir; Bone Marrow Transplantation; Clinical Trials as Topic; Herpes Simplex; Herpes Zoster; Humans; Immunity; Leukemia; Neutropenia

A multicenter trial of Acyclovir was carried out in 50 immunodepressed patients. The dose used was 15 mg/kg/day for 5 days in herpes simplex and 30 mg/kg/day for 10 days in herpes zoster and chicken pox by three one-hourly intravenous infusion per day. Acyclovir had a clear cut effect in 42 cases, a partial effect in 1 case, no effect in 1 case, and its action could not be assessed in 6 cases. The cutaneous and mucous membrane lesions were stabilised after an average of two days' treatment, and regression was observed from the third day. Of the 21 cases of zoster, 15 were cured without sequellae and 5 with post-zoster pain. The treatment failed in one patient. Of the 21 cases of cutaneous and/or mucous membrane herpes simplex, 20 satisfactory and 1 partial result were obtained. The outcomes of the 2 cases of chicken pox were favourable. There were three relapses after the end of therapy (2 herpes simplex, 1 zoster) but their outcomes were favourable after a second course of Acyclovir. In 20 cases it was possible to maintain the immuno-suppressive therapy. General tolerance was satisfactory.

Topics: Acyclovir; Adolescent; Adult; Aged; Chickenpox; Child; Clinical Trials as Topic; Female; Herpes Simplex; Herpes Zoster; Humans; Immune Tolerance; Male; Middle Aged; Prognosis

Topics: Acyclovir; Administration, Topical; Clinical Trials as Topic; Double-Blind Method; Erythema Multiforme; Herpes Simplex; Humans; Recurrence

Topics: Acyclovir; Clinical Trials as Topic; Control Groups; Encephalitis; Ethics, Medical; Guanine; Herpes Simplex; Humans; Patient Selection; Research Subjects; Therapeutic Human Experimentation

Sensitivity of herpes simplex virus isolates to acyclovir became reduced in two bone-marrow transplant patients treated for established mucocutaneous infections. These isolates were thymidine-kinase-deficient mutants and were isolated within a week of discontinuation of a 1 week course of acyclovir therapy. The herpetic lesions in both patients continued to heal despite continued shedding of these viruses. Further studies and experience with this new class of antiviral agents are needed to determine the extent to which emergence of less sensitive virus will present clinical difficulties and to formulate treatment regimens that will minimise the emergence of such mutants.

Topics: Acyclovir; Adolescent; Bone Marrow Transplantation; Clinical Trials as Topic; Double-Blind Method; Guanine; Herpes Simplex; Humans; Male; Middle Aged; Mutation; Random Allocation; Simplexvirus; Thymidine Kinase

Topics: Acyclovir; Clinical Trials as Topic; Encephalitis; Guanine; Herpes Simplex; Humans; Research Design; Vidarabine

Acyclovir, a new antiviral agent, was compared to a placebo in a randomized double-blind trial of treatment for culture-proven herpes simplex virus infection after marrow transplantation. Patients received either intravenous acyclovir at 750 mg/m2 body surface area per day or a placebo for 7 days. Thirteen of 17 patients given acyclovir had a beneficial response as compared with two of 17 given the placebo (p less than 0.01). The duration of positive cultures was shorter among acyclovir recipients (3 versus 17 days, p less than 0.00005). Also shorter were the median days to resolution of pain (10 versus 16 days, p = 0.03), to crusting of lesions (7 versus 14 days, p = 0.01), and to total healing (14 versus 28 days, p = 0.03). No acyclovir toxicity was observed. Recurrent infection was common. Acyclovir provided significant antiviral and clinical efficacy without toxicity in highly immunosuppressed patients but had no effect on virus latency.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Guanine; Herpes Simplex; Humans; Immunosuppressive Agents; Infusions, Parenteral; Male; Mucous Membrane; Placebos; Postoperative Complications; Random Allocation; Recurrence

Topics: Acyclovir; Antiviral Agents; Clinical Trials as Topic; Guanine; Herpes Simplex; Humans; Microbial Sensitivity Tests; Mucous Membrane; Thymidine Kinase

Acyclovir, a new antiherpetic agent, was administered for 18 days to 10 recipients of bone marrow transplants as a part of a double-blind, randomized, placebo-controlled trial assessing its prophylactic efficacy and safety. Renal glomerular function diminished over the time of the study in the 10 acyclovir-treated and 10 placebo-treated patients. The decline in glomerular filtration rate (GFR) did not differ significantly between the two groups and is unlikely to be associated with acyclovir. The pharmacokinetics of acyclovir is expected to be altered by a change in GFR since glomerular filtration is probably the major process involved with the excretion of acyclovir. Such an alteration was seen as an increase over time of both peak (one hour after the end of an infusion) and trough (immediately before a dose) plasma acyclovir concentrations. Although peak and trough acyclovir concentrations rose from 8.5 to 15.8 microM and from 1.7 to 4.1 microM, respectively, these rises are fully attributable to the decreases in GFR seen in both drug- and placebo-treated groups. The placebo-controlled and blinded nature of this trial allows an assessment of the effects of acyclovir on a battery of hematologic, renal, and hepatic tests. The only adverse effects observed that statistically differed in the acyclovir-treated group compared with controls were the rises in SGOT (53.2 +/- (SEM) 19.9 versus 3.1 +/- 12.2) and SGPT (59.7 +/- 15.3 versus 12.3 +/- 13.8).

Topics: Acyclovir; Antiviral Agents; Blood Cell Count; Bone Marrow Transplantation; Drug Evaluation; Glomerular Filtration Rate; Guanine; Herpes Simplex; Humans; Kidney; Liver

Forty-three immunocompromised patients with progressive cutaneous herpes simplex virus infections were studied in a double-blind, placebo-controlled evaluation of topically applied acyclovir. Patients were randomized and 22 received acyclovir and 21 placebo; medications were applied four times daily for 10 days. Both study populations were balanced for all demographic characteristics. Acyclovir therapy resulted in no median differences in time to total healing compared with placebo responses, p = 0.13. However, those patients who received the acyclovir ceased shedding virus more rapidly, p less than 0.001, and lost pain more readily, p = 0.04, than placebo counterparts. Neither group experienced adverse effects. Because of the protracted nature of mucocutaneous herpes simplex infections in these patients, the immunocompromised host provides a good model for evaluation of topical antiviral therapy.

Topics: Acyclovir; Administration, Topical; Adult; Antiviral Agents; Clinical Trials as Topic; Double-Blind Method; Female; Guanine; Herpes Simplex; Humans; Immune Tolerance; Male; Pain; Placebos; Time Factors

11 of 24 immunocompromised patients with mucocutaneous herpes simplex virus (HSV) infections were given intravenous acyclovir in a randomised double-blind placebo-controlled study. Patients receiving acyclovir experienced no major adverse effects. The median times to cessation of new lesion formation, lesion crusting, lesion healing, cessation of pain, and termination of viral shedding were shorter in the acyclovir-treated group than in the placebo group. The time-to-event probability curves for the acyclovir and placebo groups were significantly different for cessation of pain (p=0.032) and termination of viral shedding (p=0.004). The median times to termination of viral shedding were also statistically different (p=0.045). Acyclovir seems to be a non-toxic and effective treatment for mucocutaneous HSV infections in immunocompromised patients.

Topics: Acyclovir; Adolescent; Adult; Aged; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Guanine; Herpes Simplex; Humans; Immunosuppression Therapy; Injections, Intravenous; Male; Middle Aged; Random Allocation; Simplexvirus; Virus Replication

Viral cultures of mucocutaneous herpes simplex lesions became negative in 5 heart-transplant patients given a 7-day course of intravenous acyclovir. Relief of pain and healing of lesions paralleled the virological response. Similar clinical and virological responses were not seen in the 5 placebo-treated patients in this double-blind placebo-controlled trial. No adverse reactions attributable to acyclovir were noted. Shedding of herpes simplex viruses recurred in 3 patients after acyclovir therapy.

Topics: Acyclovir; Adult; Clinical Trials as Topic; Double-Blind Method; Guanine; Heart Transplantation; Herpes Simplex; Humans; Immunosuppression Therapy; Injections, Intravenous; Male; Middle Aged; Postoperative Care; Random Allocation; Transplantation, Homologous

We conducted a double-blind, placebo-controlled study of acyclovir prophylaxis against infection with herpes simplex virus (HSV) in 20 seropositive recipients of bone-marrow transplants. Acyclovir or placebo was administered for 18 days, starting three days before transplantation. Culture-positive HSV lesions developed during the study in seven of the 10 patients who received placebo. In contrast, no such lesions appeared in the 10 patients who received acyclovir (P congruent to 0.003). None of the patients had evidence of drug toxicity. Five of the patients treated with acyclovir had mild culture-positive HSV infections after cessation of the drug, and two additional patients shed virus without having lesions. Acyclovir appears to be a potent inhibitor of HSV replication. Although acyclovir does no appear to eradicate latent infection, it can provide effective prophylaxis against reactivated infections.

Topics: Acyclovir; Adolescent; Adult; Bone Marrow Transplantation; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Female; Guanine; Herpes Simplex; Humans; Male; Prospective Studies; Random Allocation; Transplantation, Homologous

A review of the literature on acyclovir (Zovirax), a new antiherpes drug, with particular activity against herpes simplex virus types I and II and also against varicella-zoster, Epstein-Barr, cytomegalo and herpes B viruses, is presented. The article deals with 'in vitro' and 'in vivo' efficacy in animals, animal toxicity, latency and resistance, the mechanism of action and early clinical experience.

Topics: Acyclovir; Animals; Clinical Trials as Topic; Drug Resistance, Microbial; Guanine; Guinea Pigs; Herpes Simplex; Herpesviridae; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Intestinal Absorption; Keratitis, Dendritic; Kidney; Kinetics; Mice; Phosphorylation; Rabbits; Simplexvirus; Time Factors

Topics: Acyclovir; Antiviral Agents; Bone Marrow Transplantation; Clinical Trials as Topic; Guanine; Herpes Simplex; Humans; Transplantation, Homologous

Topics: Acyclovir; Antiviral Agents; Guanine; Herpes Labialis; Herpes Simplex; Herpesviridae Infections; Humans

Topics: Acyclovir; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Retinal Necrosis Syndrome, Acute

Topics: Acyclovir; Antiviral Agents; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Humans; Valacyclovir

Herpes simplex virus 2 (HSV-2) rarely causes severe disease, even in solid organ transplant recipients. This paper describes a fatal case of HSV-2 infection, probably transmitted from a donor to a kidney transplant recipient. The donor was seropositive for HSV-2 but not for HSV-1, whereas the recipient was seronegative for both viruses before transplantation, suggesting that the graft was the source of infection. The recipient received valganciclovir prophylaxis due to cytomegalovirus seropositivity. Three months after transplantation, the recipient presented with rapidly disseminated cutaneous HSV-2 infection with meningoencephalitis. The HSV-2 strain was resistant to acyclovir, probably acquired under valganciclovir prophylaxis. Despite early initiation of acyclovir therapy, the patient died. This fatal case of HSV-2 infection, probably transmitted by the kidney graft with acyclovir-resistant HSV-2 from the onset, is uncommon.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; Humans; Kidney Transplantation; Valganciclovir

We present two allogeneic hematopoietic cell transplantation recipients (HCTr) treated with pritelivir for acyclovir-resistant/refractory (r/r) HSV infection based on the expanded access program of the pritelivir manufacturer. Outpatient treatment with pritelivir was administered, with partial response by week 1 of treatment and complete response by week 4 of treatment in both patients. No adverse events were noted. Pritelivir appears to be an effective and safe option for the management of acyclovir-r/r HSV infections in highly immunocompromised patients in an outpatient setting.

Topics: Acyclovir; Antiviral Agents; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Salvage Therapy; Transplant Recipients

HSV-2 is a common human pathogen worldwide that causes genital herpes. Due to the lack of an effective HSV-2 vaccine in the foreseeable future, there is an urgent need to develop effective, safe and affordable anti-HSV-2 agents. Our previous studies confirmed that a small-molecule compound, Q308, effectively inhibits the reactivation of latent HIV and might be developed as an anti-HIV-1 agent. Patients infected with HSV-2 are generally more susceptible to HIV-1 infection than normal humans. In this study, we found that Q308 treatment had strong inhibitory activity against both HSV-2 and acyclovir-resistant HSV-2 strains in vitro and reduced the viral titers in tissue. And this treatment effectively ameliorated the cytokine storm and pathohistological changes caused by HSV-2 infection in HSV-2-infected mice. Unlike nucleoside analogs such as acyclovir, Q308 inhibited post-viral entry events by attenuating the synthesis of viral proteins. Furthermore, Q308 treatment blocked HSV-2-induced PI3K/AKT phosphorylation due to its inhibition on viral infection and replication. Overall, Q308 treatment exhibits potent anti-HSV-2 activity by inhibiting viral replication both in vitro and in vivo. Q308 is a promising lead compound for the development of new anti-HSV-2/HIV-1 therapies, particularly against acyclovir-resistant HSV-2 strains.

Topics: Acyclovir; Animals; Anti-HIV Agents; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Mice; Phosphatidylinositol 3-Kinases; Virus Latency; Virus Replication

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunocompromised Host

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Salvage Therapy; Transplant Recipients

Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with acyclovir is sufficient to manage the disease progression. However, the emergence of ACV-resistant strains drives the need for new therapeutics and molecular targets. HSV-1 VP24 is a protease indispensable for the assembly of mature virions and, as such, constitutes an interesting target for the therapy. In this study, we present novel compounds, KI207M and EWDI/39/55BF, that block the activity of VP24 protease and consequently inhibit HSV-1 infection in vitro and in vivo. The inhibitors were shown to prevent the egress of viral capsids from the cell nucleus and suppress the cell-to-cell spread of the infection. They were also proven effective against ACV-resistant HSV-1 strains. Considering their low toxicity and high antiviral potency, the novel VP24 inhibitors could provide an alternative for treating ACV-resistant infections or a drug to be used in combined, highly effective therapy.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Peptide Hydrolases

Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg

Topics: Acyclovir; Animals; Herpes Simplex; Herpesvirus 1, Human; Humans; Lipid Peroxidation; Mice; Neuroblastoma

We reported on a case involving an older patient with HSV-1 encephalitis who simultaneously experienced the onset of peripheral nerve symptoms associated with the presence of anti-GM3 immunoglobulin G (IgG).. A 77-year-old male was admitted to hospital with high fever, weakness of both lower limbs, and an unstable gait. A CSF test revealed a strikingly increased protein level (1,002 mg/L, normative values: 150-450 mg/L) and MRI revealed hyper-signal lesions in the right temporal lobe, right hippocampus, right insula, and right cingulate gyrus. The CSF was positive for HSV PCR (HSV-1,17870). In addition, the serum samples were positive for CASPR2 antibodies (antibody titer: 1/10) and anti-GM3 immunoglobulin G (IgG) (+). The patient was diagnosed with HSV-1-induced peripheral nerve symptoms that were associated with encephalitis and the presence of anti-GM3 IgG and anti-CASPR2 antibodies. The patient had received included intravenous immunoglobulin, intravenous acyclovir, and corticosteroids therapy. At the one-year follow-up examination, he had regained the necessary skills associated with daily life.. Herpes simplex virus infection often induces encephalitis, and reaction to the virus may trigger an autoimmune response. Early diagnosis and treatment can avoid the progression of the disease to include autoimmune encephalitis.

Topics: Acyclovir; Aged; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulin G; Male; Peripheral Nervous System Diseases

Herpes simplex virus 1 can cause severe infections in individuals who are immunocompromised. In these patients, emergence of drug resistance mutations causes difficulties in infection management.. Seventeen herpes simplex virus 1 isolates were obtained from orofacial/anogenital lesions in a patient with leaky severe combined immunodeficiency over 7 years, before and after stem cell transplantation. Spatial/temporal evolution of drug resistance was characterized genotypically-with Sanger and next-generation sequencing of viral thymidine kinase (TK) and DNA polymerase (DP)-and phenotypically. CRISPR/Cas9 was used to introduce the novel DP Q727R mutation, and dual infection-competition assays were performed to assess viral fitness.. Isolates had identical genetic backgrounds, suggesting that orofacial/anogenital infections derived from the same virus lineage. Eleven isolates proved heterogeneous TK virus populations by next-generation sequencing, undetectable by Sanger sequencing. Thirteen isolates were acyclovir resistant due to TK mutations, and the Q727R isolate additionally exhibited foscarnet/adefovir resistance. Recombinant Q727R mutant virus showed multidrug resistance and increased fitness under antiviral pressure.. Long-term follow-up of a patient with severe combined immunodeficiency revealed virus evolution and frequent reactivation of wild-type and TK mutant strains, mostly as heterogeneous populations. The DP Q727R resistance phenotype was confirmed with CRISPR/Cas9, a useful tool to validate novel drug resistance mutations.

Topics: Acyclovir; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Multiple; Drug Resistance, Viral; Gene Editing; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunologic Deficiency Syndromes; Mutation; Severe Combined Immunodeficiency; Thymidine Kinase

To estimate the incidence of neonatal herpes simplex virus (HSV) infection and the number of neonates with suspected invasive bacterial infection (IBI) needed to treat (NNT) with acyclovir to ensure prompt treatment of invasive HSV infections.. A nationwide population-based cohort study.. All neonatal and paediatric emergency departments in Denmark from 1 January 2010 to 31 December 2019.. Neonates aged 0-28 days with HSV infection.. The main outcome measures were incidence and NNT. The NNT was calculated based on neonates with invasive HSV infection whose onset symptoms resembled IBI and the estimated number of Danish neonates who received antibiotics for suspected IBI.. Fifty-four neonates with HSV infection were identified, that is, an incidence of 9 per 100 000 live births. Twenty presented with symptoms resembling IBI, all within the first 14 days of life. Of 18 (78%) neonates, 14 had elevated C reactive protein, 14 of 19 (74%) had elevated alanine aminotransferase and 11 of 17 (65%) had thrombocytopaenia. The estimated NNTs with empiric acyclovir at postnatal ages 0-3, 4-7 and 8-14 days were 1139 (95% CI 523 to 3103), 168 (95% CI 101 to 726) and 117 (95% CI 48 to 198), respectively.. The incidence of neonatal HSV infection was higher than in previous decades; however, the estimated NNT with empiric acyclovir was high. Therefore, we propose not to treat all neonates suspected of IBI with empiric acyclovir, as current European guidelines suggest. However, HSV should be considered in neonates with signs of infection, especially after the third postnatal day and in neonates with high alanine aminotransferases and thrombocytopaenia.

Topics: Acyclovir; Antiviral Agents; Child; Cohort Studies; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Thrombocytopenia

Recurrent herpes simplex encephalitis (HSE) can easily induce autoimmune encephalitis (AE). However, there are few reports of anti-contactin-associated protein-2 (CASPR2)-related encephalitis, especially with positive anti-aquaporin 4 (AQP4) antibodies.. A 14-year-old boy was admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University for "headache, dizziness, and fever for four days" with positive anti-CASPR2 and anti-AQP4 antibodies in the cerebrospinal fluid.. Cranial MRI showed lesions in the right hippocampus, amygdala, and insular lobe, with local sulcus enhancement in the right insular, temporal, and frontal lobes. The fluid-attenuated inversion recovery was significantly enhanced. Human herpes virus type I was detected by cerebrospinal fluid metagenomic testing. The patient was diagnosed with AE secondary to HSE, with positive anti-CASPR2 and anti-AQP4 antibodies.. After 2 weeks of immunoglobulin and methylprednisolone immunomodulatory therapy, acyclovir antivirus, mannitol dehydration, reducing intracranial pressure, and other symptomatic support therapy.. The patient's symptoms significantly improved, with no complaints of discomfort, and he was discharged for observation. The patient was followed up a month after discharge and had no complaints of discomfort.. CASPR2 and anti-aquaporin-4 antibody-positive AE have not been reported to be positive. This case will raise awareness of CASPR2 and anti-aquaporin-4 antibody-positive AE secondary to HSE, strengthen diagnostic capacities, and provide advice to treat it.

Topics: Acyclovir; Adolescent; Autoimmune Diseases of the Nervous System; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Male

Herpes simplex encephalitis is a life-threatening disease of the central nervous system caused by herpes simplex viruses (HSVs). Following standard of care with antiviral acyclovir treatment, most patients still experience various neurological sequelae. Here we characterize HSV-1 infection of human brain organoids by combining single-cell RNA sequencing, electrophysiology and immunostaining. We observed strong perturbations of tissue integrity, neuronal function and cellular transcriptomes. Under acyclovir treatment viral replication was stopped, but did not prevent HSV-1-driven defects such as damage of neuronal processes and neuroepithelium. Unbiased analysis of pathways deregulated upon infection revealed tumour necrosis factor activation as a potential causal factor. Combination of anti-inflammatory drugs such as necrostatin-1 or bardoxolone methyl with antiviral treatment prevented the damages caused by infection, indicating that tuning the inflammatory response in acute infection may improve current therapeutic strategies.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Organoids

Topics: Acyclovir; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunocompromised Host

Data on herpes simplex virus (HSV) polymorphism as well as acyclovir (ACV) and foscarnet (FOS) resistance mutations are not exhaustive and may hinder accurate diagnosis by next-generation sequencing (NGS). Here, we report novel UL23 and UL30 substitutions for HSV1 and HSV2 identified in immunocompromised patients treated for hematological malignancies during the last 6 years of HSV resistance surveillance at the University Hospital of Lyon. For HSV1, 35 novel UL23 substitutions and 52 novel UL30 substitutions were identified. For HSV2, 2 novel UL23 substitutions and 12 novel UL30 substitutions were identified. These results allow to complete the database of HSV1 and HSV2 substitutions, related either to polymorphism or to ACV and FOS resistance.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Foscarnet; Herpes Simplex; Herpesvirus 1, Human; Humans; Viral Proteins

Herpes simplex virus type 1 (HSV-1) can establish latency in humans and easily relapse in immunocompromised patients, with significant mortality. Treatment with acyclovir (ACV) can result in the emergence of HSV resistance. A total of 440 frozen HSV-1 isolates collected from 318 patients from January 2014 to July 2019 were obtained from National Cheng Kung University Hospital in southern Taiwan. These 440 isolates were subjected to phenotypic studies for ACV-resistance by initial screening with the plaque reduction assay (PRA) and further validation by the DNA reduction assay (DRA). The ACV-resistant strains were further investigated by Sanger sequencing for the full-length UL23 and UL30 genes, which encode thymidine kinase and DNA polymerase, respectively. Hematological malignancies or hematopoietic stem-cell transplantation patients accounted for 56.9% (124/218) among the immunocompromised patients (218/318) in this study. Repeated sampling for HSV testing was 50% (109/218) in immunocompromised patients. Only 1.38% (3/218) of immunocompromised patients and 0.9% (3/318) of all patients developed ACV-resistant HSV-1 as measured by phenotypic screening assays. It is noteworthy that a novel Y248D mutation in the UL23 gene from an immunocompromised patient was found by both PRA and DRA. In 3D protein predicting analysis, uncharged Y248 was located at an alpha-helix and substituted by negative-charged D248, which may alter the function of viral thymidine kinase. Besides, three unreported mutations related to natural polymorphism were found in virus isolates from two immunocompetent patients, including 683-688 deletion, R227H, and A351D in the UL30 gene. These data show that the prevalence of ACV-resistant HSV-1 among immunocompromised patients in southern Taiwan is low. These results will be helpful for the clinical management and treatment of HSV infections.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Mutation; Neoplasm Recurrence, Local; Prevalence; Taiwan; Thymidine Kinase

The incidence of acute liver failure from herpes simplex virus is rare.. A 71-year-old Japanese man was diagnosed with acute liver failure and was transferred to our hospital. Steroid therapy, plasma exchange, and hemodiafiltration were started for liver failure, and antimicrobial therapy was initiated for pneumonia. Staphylococcus epidermidis was detected in blood culture. Skin rash appeared; a positive anti-herpes simplex virus result led to the diagnosis of acute liver failure from herpes simplex virus. Hence, acyclovir was started. After blood tests improved, treatments for acute liver failure were discontinued. Antimicrobial therapy was continued; however, he died. In this case, persistent bacteremia and drug-induced liver damage due to acyclovir may have contributed to his death.. Acute liver failure can lead to complications and death. Thus, careful observation is crucial, even if the patient has shown some improvements.

Topics: Acyclovir; Aged; Antiviral Agents; Hepatitis, Viral, Human; Herpes Simplex; Humans; Liver Failure, Acute; Male

Antiviral resistance in human herpes simplex viruses (HSV) remains a significant clinical challenge in immunocompromised populations. Although molecular tests have largely replaced viral culture for HSV diagnosis and molecular antiviral resistance testing is available for many viruses, HSV resistance testing continues to rely on phenotypic, viral culture-based methods, requiring weeks for results. Consequently, treatment of suspected HSV resistance remains largely empiric.. We used HSV whole genome sequencing and a database of previously characterized HSV acyclovir and foscarnet resistance mutations to evaluate the performance of genotypic antiviral resistance testing among 19 control strains compared to in-house plaque reduction assay (PRA) and 25 clinical isolates sent for reference lab PRA antiviral resistance testing.. Among control strains, 23/29 (79.3%) results were concordant, 5 (17.2%) were indeterminate, and 1 (3.4%) was discordant. Indeterminate results were caused by variants of uncertain significance (VUS), including mutations without published phenotypes and mutations with contradictory results. Among clinical isolates, 14/40 (35%) results were concordant, 17 (42.5%) were indeterminate, and 9 (22.5%) were discordant. All discordant results were in reportedly phenotypically-susceptible HSV-1 strains yet possessed resistance mutations. Three contained resistant subpopulations. 6/8 (75%) discordant phenotypes were concordant with resistant genotypes upon repeat PRA.. These data support the combination of genotypic and phenotypic testing to diagnose HSV resistance more accurately and likely more rapidly than phenotypic testing alone. Genotypic context of resistance mutations and the ability of viral strains to form plaques in culture may affect phenotypic resistance results, highlighting the limitations of PRA alone as a gold standard method.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Foscarnet; Genotype; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans

To describe the clinical characteristics of anti-NMDAR encephalitis secondary to acute necrotizing encephalopathy caused by herpes simplex virus encephalitis in infants, and aid in its early recognition, diagnosis and treatment.. A total of 4 infants were included; all presented with fever, seizures, and progressive disturbances of consciousness and were diagnosed with herpes simplex virus (HSV-1) encephalitis. Cerebrospinal fluid (CSF) protein levels progressively increased, and the head MRI showed necrotizing encephalopathy. There was no significant improvement or recurrence after treatment with acyclovir, dexamethasone, or immunoglobulins. CSF reexamination at 3 weeks to 3 months showed positive anti-NMDAR IgG antibodies and gradual improvement after high-dose methylprednisolone therapy.. Infants with ANE associated with HSV can develop secondary anti-NMDAR encephalitis, recognition of which is critical to ensure the appropriate institution of immunotherapy after active CNS infection has been ruled out.

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Brain Diseases; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infant

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Topics: Acyclovir; Adolescent; Antiviral Agents; Asian People; Cellulitis; Facial Dermatoses; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Republic of Korea; Sports; Wrestling

Development of novel antiherpes simplex virus (HSV) agents with active mechanisms different from nucleoside analogues is of high importance. Herein, we investigated the anti-HSV activities and mechanisms of wedelolactone (WDL) both in vitro and in vivo.. Cytopathic effect (CPE) inhibition assay, plaque assay, and western blot assay were used to evaluate the anti-HSV effects of WDL in vitro. The immunofluorescence assay, RT-PCR assay, plaque reduction assay, sandwich ELISA assay, syncytium formation assay, tanscriptome analysis and western blot assay were used to explore the anti-HSV mechanisms of WDL. The murine encephalitis and vaginal models of HSV infection were performed to evaluate the anti-HSV effects of WDL in vivo.. WDL possessed inhibitory effects against both HSV-1 and HSV-2 in different cells with low toxicity, superior to the effects of acyclovir. WDL can directly inactivate the HSV particle via destruction of viral envelope and block HSV replication process after virus adsorption, different from the mechanisms of acyclovir. WDL may influence the host genes and signaling pathways related to HSV infection and immune responses. WDL can mainly interfere with the TBK1/IRF3 and SOCS1/STAT3 pathways to reduce HSV infection and inflammatory responses. Importantly, WDL treatment markedly improved mice survival, attenuated inflammatory symptoms, and reduced the virus titres in both HSV-1 and HSV-2 infected mice.. Thus, the natural compound WDL has the potential to be developed into a novel anti-HSV agent targeting both viral envelope and cellular TBK1/IRF3 and SOCS1/STAT3 pathways.

Topics: Acyclovir; Animals; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Mice; Viral Envelope; Virus Replication

The objective of this study was to explore the ocular and systemic outcomes of herpes simplex virus type 1 (HSV-1) infection in guinea pigs, to monitor the spontaneous reactivation of the virus, and to assess the effectiveness of various treatments, drawing comparisons to conventional rabbit models.. Guinea pigs and rabbits were infected in the right corneas with differing doses and strains of HSV-1. Observations were made over a 71-day period, focusing on comparing ocular lesions, viral shedding patterns, and weight loss between the two animal models. Postinfection, the effectiveness of trifluridine ophthalmic drops, oral acyclovir, and valacyclovir was evaluated. The confirmation of viral infection was done through virus titer assay, fluorescein staining, and corneal imaging.. Guinea pigs and rabbits manifested symptoms akin to human herpes stromal keratitis (HSK) when exposed to varying titers of viral suspension. Regardless of the initial viral load, all guinea pig groups demonstrated comparable ocular pathology, witnessing conditions like blepharitis and conjunctivitis within 3 days, progressing to severe conditions, including total corneal opacification and necrotizing keratitis. Tear film collection revealed nonsignificant differences in viral plaques between all groups. Notably, guinea pigs in the low-infection group experienced the most weight loss, although without significant differences. The replication of the same experiment on rabbits yielded consistent results in disease pathology across different groups, with occurrences of blepharitis and conjunctivitis. Interestingly, after initial resolution, guinea pigs presented a more frequent and broadly observed increase in disease score and corneal opacity, a phenomenon rarely seen in rabbits within the same timeframe. The effectiveness of 1% trifluridine was observed in mitigating ocular HSV-1 disease in both species, whereas oral acyclovir and valacyclovir were found to be detrimental and ineffective in guinea pigs but not in rabbits.. This study demonstrates the potential suitability of guinea pigs as new models for ocular HSV-1 investigations, filling a critical preclinical void of models capable of showcasing spontaneous HSV reactivation in the eye. The observed similarities and differences in the reactions of guinea pigs and rabbits to HSV-1 infection and treatments provide crucial insights, laying the foundation for future studies on ocular HSV pathogenesis, latency, and improved treatment options.

Topics: Acyclovir; Animals; Antiviral Agents; Blepharitis; Conjunctivitis; Cornea; Guinea Pigs; Herpes Simplex; Herpesvirus 1, Human; Humans; Rabbits; Trifluridine; Valacyclovir; Weight Loss

We previously showed that the anti-fungal drug ciclopirox olamine effectively inhibits replication of herpes simplex virus (HSV)-1 and HSV-2. Given the rise of HSV strains that are resistant to nucleos(t)ide analog treatment, as well as the incomplete efficacy of nucleos(t)ide analogs, new inhibitory compounds must be explored for potential use in the treatment of HSV infection. In the present study, we analyzed 44 compounds derived from the core structure of ciclopirox olamine for inhibitory activity against HSV. Thirteen of these derivative compounds inhibited HSV-2 replication by > 1000- to ∼100,000-fold at 1 μM and displayed EC

Topics: Acyclovir; Antifungal Agents; Antiviral Agents; Ciclopirox; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Virus Replication

When the nucleoside analogue acyclovir was introduced in the early 1980s, it presented a game-changing treatment modality for herpes simplex virus infections. Since then, work has been ongoing to improve the weaknesses that have now been identified: a narrow time window for therapeutic success, resistance in immunocompromised patients, little influence on frequency of recurrences, relatively fast elimination, and poor bioavailability. The present Drug Annotation focuses on the helicase-primase inhibitor pritelivir currently in development for the treatment of acyclovir-resistant HSV infections and describes how a change of the molecular target (from viral DNA polymerase to the HSV helicase-primase complex) afforded improvement of the shortcomings of nucleoside analogs. Details are presented for the discovery process leading to the final drug candidate, the pivotal preclinical studies on mechanism of action and efficacy, and on how ongoing clinical research has been able to translate preclinical promises into clinical use.

Topics: Acyclovir; Antiviral Agents; DNA Primase; Drug Resistance, Viral; Herpes Simplex; Humans; Nucleosides; Pyridines

Neonatal herpes simplex virus (HSV) infections can be challenging to diagnose and often occur without maternal history of infection. Routine initial pharmacologic management when a neonate presents with signs of sepsis in the first weeks of life typically targets antibiotic therapies. This case illustrates the importance of the addition of antiviral coverage, especially when a neonate demonstrates temperature instability and neurologic changes.. This case report describes the unique presentation of a 9-day old neonate with clinical findings significant for sepsis. This neonate was diagnosed with methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia with concomitant disseminated HSV-2 infection after presenting with temperature instability, lethargy, and signs of multisystem organ impairment.. This neonate was diagnosed with disseminated HSV infection, which occurs in 25% of neonatal HSV disease.. Treatment was initiated with high-dose intravenous acyclovir at 20 mg/kg/dose every 8 hours along with broad-spectrum antibiotics. Management should include anticipating and monitoring for progressive multisystem organ failure in bacterial or viral infection.. This patient did not survive despite maximal intervention from the neonatal intensive care unit team. Disseminated HSV neonatal infections are associated with high mortality rates when they are present alone, and mortality is higher with concurrent bacteremia.. Providers should have a high index of suspicion for HSV infection in neonates presenting in the first 1 to 3 weeks of life with signs of sepsis. Prophylactic treatment with high-dose acyclovir as an adjunct to broad-spectrum antibiotics while awaiting laboratory confirmation can be lifesaving.

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Bacteremia; Female; Herpes Simplex; Humans; Infant, Newborn; Methicillin; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Simplexvirus; Staphylococcus aureus

Topics: Acyclovir; Antiviral Agents; Child; Herpes Simplex; Humans; Recurrence

The clinical presentations of herpes simplex virus (HSV) infections are varied and range from asymptomatic to a prodrome of tingling and burning followed by painful vesicles, erosions and ulcers. Resolution leads to latent infection of the sensory ganglia. HSV-1 is associated with most of the nongenital HSV-induced infections and HSV-2 is generally associated with anogenital lesions; however, lesions at either site may be caused by both viruses. In persons living with HIV (PLHIV), the lesions have been described as verrucous/hypertrophic, exophytic or vegetative and may suggest a neoplastic rather than an infective process and this can be a diagnostic dilemma in resource-limited countries with no access to confirmatory diagnostic testing for HSV. We report on two PLHIV who developed rapidly growing lesions on the face that clinically mimicked neoplasia but were found to be HSV-associated squamous proliferative lesions which responded to high dose acyclovir.

Topics: Acyclovir; Antiviral Agents; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Neoplasms

Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV.. Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016.. One hundred thirty infants with a diagnosis of neonatal HSV were identified. Between 1980 and 2016, high-dose acyclovir treatment for neonatal HSV infection increased from 0% to close to 95%, with subsequent decrease in overall HSV-related mortality from 20.9% to 5.6%. However, even among infants treated with high-dose acyclovir, mortality was 40.9% for infants with disseminated (DIS) disease, and only 55% of infants with central nervous system (CNS) disease were without obvious neurologic abnormalities at 24 months. Over the study period, the time between initial symptoms and diagnosis decreased. Skin recurrences were more common with HSV-2 than HSV-1 (80% vs 55%; P = .02) and in infants with lesions at initial diagnosis (76% vs 47%; P = .02).. Changes in the standard of care for management of neonatal HSV disease have led to improvements in timeliness of diagnosis and outcome but mortality in infants with DIS disease and neurologic morbidity in infants with CNS disease remain high. Future research should focus on prevention of perinatal infection and subsequent recurrences.

Topics: Acyclovir; Antiviral Agents; Child; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious

Data on the clinical presentation are scarce and prognostic factors of herpes simplex virus type 2 (HSV-2) meningitis remain unknown.. Prospective, nationwide, population-based database identifying all adults treated for HSV-2 meningitis at departments of infectious diseases in Denmark from 2015 to 2020. Unfavorable outcome was defined as Glasgow Outcome Scale (GOS) scores of 1-4 and Extended GOS scores of 1-6. Modified Poisson regression was used to compute relative risks with 95% confidence intervals for unfavorable outcome.. HSV-2 meningitis was diagnosed in 205 patients (76% female; median age [interquartile range (IQR)], 35 [27-49] years) yielding an incidence of 0.7/100 000 population/y. Common symptoms were headache (195 of 204 patients [95%]), photophobia or phonophobia (143 of 188 [76%]), and neck stiffness (106 of 196 [54%]). The median (IQR) time to lumbar puncture was 2.0 (1-4.8) hours, and the median cerebrospinal fluid (CSF) leukocyte count was 360 (166-670) × 10 × 6/L, with a mononuclear predominance of 97% (91%-99%). Lumbar puncture was preceded by brain imaging in 61 of 205 patients (30%). Acyclovir or valacyclovir was administered in 197 of 205 patients (96%) for a median (IQR) of 10 (7-14) days. Unfavorable outcome was observed in 64 of 205 patients (31%) at discharge and 19 of 181 (11%) after 6 months and was not associated with female sex (relative risk [95% confidence interval], 1.08 [.65-1.79]), age ≥35 years (1.28 [.83-1.97]), immunocompromise (1.07 [.57-2.03]), or CSF leukocyte count >1000 × 10 × 6/L (0.78 [.33-1.84]).. HSV-2 meningitis often presented as meningeal symptoms in younger women. Unfavorable outcome at discharge was common and was not associated with sex, age, immunocompromise, or CSF leukocyte count. Sequelae persisted beyond 6 months in one-tenth of patients.

Topics: Acyclovir; Adult; Cohort Studies; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Male; Meningitis; Prospective Studies; Valacyclovir

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus.

Topics: Acyclovir; Antiviral Agents; Disease Management; Germany; Hematologic Neoplasms; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Neoplasms; Vaccination; Varicella Zoster Virus Infection; Virus Activation

To describe the clinical and virological profiles of patients with herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACV. Multicenter retrospective case series.. HSV-1 resistance to ACV was confirmed using sequencing of genes encoding HSV-1 thymidine kinase (TK) and DNA polymerase (DNA pol). Data were collected on the number of HSK episodes before and after the diagnosis of resistance, ocular findings including the type of HSK, immune status of patients, antiviral treatments, and HSV-1 genotypic resistance profiles.. HSV-1 resistance to ACV must be suspected in HSK patients with recurrences despite AVP and/or in cases that respond poorly to a suppressive antiviral regimen. Immunocompromised patients and/or those with longstanding disease may be particularly at risk for developing resistance.

Topics: Acyclovir; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Recurrence; Retrospective Studies; Thymidine Kinase

Herpes simplex virus (HSV) usually produces cytopathic effect (CPE) within 24-72 h post-infection (P.I.). Clinical isolates from recurrent HSV infections in patients on Acyclovir therapy were collected between 2016 and 2019 and tested in cell cultures for cytopathic effects and further in-depth characterization. Fourteen such isolates did not show any CPE in A549 or Vero cell lines even at 120 h P.I. However, these cultures remained positive for HSV-DNA after several passages. Sequence analysis revealed that the non-CPE isolates were all HSV-1. Analysis of the thymidine kinase gene from the isolates revealed several previously reported and two novel ACV-resistant mutations. Immunofluorescence and Western blot data revealed a low-level expression of the immediate early protein, ICP4. Late proteins like ICP5 or capsid protein, VP16 were almost undetectable in these isolates. AFM imaging revealed that the non-CPE viruses had structural deformities compared to wild-type HSV-1. Our findings suggest that these strains are manifesting an unusual phenomenon of being non-CPE herpesviruses with low level of virus protein expressions over several passages. Probably these HSV-1 isolates are evolving towards a more "cryptic" form to establish chronic infection in the host thereby unraveling yet another strategy of herpesviruses to evade the host immune system.

Topics: A549 Cells; Acyclovir; Adolescent; Adult; Aged; Animals; Antiviral Agents; Chlorocebus aethiops; Drug Resistance, Viral; Female; Herpes Simplex; Humans; Male; Middle Aged; Reinfection; Vero Cells; Young Adult

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Eye Infections, Viral; Herpes Simplex; Herpesvirus 2, Human; Humans; Retinal Necrosis Syndrome, Acute

Topics: Acyclovir; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

Immunosuppressed patients can suffer from Human alphaherpesvirus (HSV) infection with fast evolution, severe atypical symptomatology, and often-fatal outcome. Thus, the development and validation of new methods in vitro and in vivo to promote an early diagnosis and effective treatment of these patients are crucial. Therefore, this work aimed to develop a cell-based reporter assay for the detection of HSV through the transfection of Vero cells with the ICP10 promoter from HSV-2 linked to the pZsGreen1-1 plasmid. The assay was evaluated on Vero cells infected with HSV-1 or HSV-2 and followed by treating them with anti-HSV agents (acyclovir, gallic acid, convallatoxin, and Uncaria sp. extract) or with no anti-HSV activity agents (Passiflora edulis extract and cardenolide derivatives). The GFP expression was increased by both HSV cellular infection, which was detected by flow cytometry and fluorescence microscopy. F2R Zsgreen1-1 cells infection with 200 and 600 PFU/mL of HSV-2 increased the fluorescence intensity, when compared to the controls, by approximately 30% and 60%, respectively. Infection with 100 and 600 PFU/mL of HSV-1 also increased the fluorescence intensity by approximately 20% and 35%, when compared to the controls, respectively. The F2R ZsGreen1-1 system revealed to be an efficient assay, which can be used for clinical diagnosis, antiviral resistance evaluation, HSV cycle studies, and new antiviral drug research.

Topics: Acyclovir; Animals; Chlorocebus aethiops; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Vero Cells

Topics: Acyclovir; Amino Acids; Antiviral Agents; Drug Resistance, Viral; Female; Genitalia; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; South Africa; Thymidine Kinase; Ulcer

A neonatal patient with Herpes simplex virus type-2 meningoencephalitis was treated by high-dose intravenous acyclovir therapy. Serum and cerebrospinal fluid (CSF) concentrations were measured retrospectively, showing that the CSF-to-serum concentration ratio was 0.67-0.71, which was higher than the previously reported values in other age groups.

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Meningoencephalitis; Retrospective Studies

Encephalitis, the most significant of the central nervous system (CNS) diseases caused by Herpes simplex virus 1 (HSV-1), may have long-term sequelae in survivors treated with acyclovir, the cause of which is unclear. HSV-1 exhibits a tropism toward neurogenic niches in CNS enriched with neural precursor cells (NPCs), which play a pivotal role in neurogenesis. NPCs are susceptible to HSV-1. There is a paucity of information regarding the influence of HSV-1 on neurogenesis in humans. We investigated HSV-1 infection of NPCs from two individuals. Our results show (i) HSV-1 impairs, to different extents, the proliferation, self-renewing, and, to an even greater extent, migration of NPCs from these two subjects; (ii) The protective effect of the gold-standard antiherpetic drug acyclovir (ACV) varies with viral dose and is incomplete. It is also subject to differences in terms of efficacy of the NPCs derived from these two individuals. These results suggest that the effects of HSV-1 may have on aspects of NPC neurogenesis may vary among individuals, even in the presence of acyclovir, and this may contribute to the heterogeneity of cognitive sequelae across encephalitis survivors. Further analysis of NPC cell lines from a larger number of individuals is warranted.

Topics: Acyclovir; Encephalitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Neural Stem Cells; Neurogenesis

Herpes simplex keratitis is an important infectious cause of blindness worldwide. The mainstay of antiviral therapy is treatment with long-established nucleoside analogues orally or topically. However, the emergence of resistant strains may become a major health concern in the future. Therefore, the development of backup antiherpetic medicines is urgently needed. Small molecule PDSTP is known to be active against herpes simplex type 1 strains in vitro, affecting early host-pathogen interactions. Here, we evaluated its preclinical efficacy in a rabbit model of herpes simplex epithelial keratitis. The mean course of keratitis and the corneal lesions in the 1.0% PDSTP gel group was statistically significantly less than in the negative control group and was comparable to that in the aciclovir group. These findings open up new opportunities for the development of antiherpetic drugs with an original mechanism of action.

Topics: Acyclovir; Animals; Antiviral Agents; Herpes Simplex; Keratitis, Herpetic; Rabbits

Herpes simplex virus (HSV) has been the leading cause of genital ulcer syndrome (GUS) in South Africa for more than a decade, and acyclovir therapy is incorporated into syndromic management guidelines. We conducted surveillance at 3 sentinel sites to define the common sexually transmitted etiologies of GUS and to determine whether current syndromic management is appropriate. Secondary objectives of surveillance were to determine the seroprevalence of coinfections (HIV, syphilis, HSV-2) in persons presenting with GUS.. Consecutive, consenting adult men and women presenting with visible genital ulceration were enrolled between January 1, 2019, and December 31, 2020. Genital ulcer swab and blood specimens were collected and transported to a central sexually transmitted infection reference laboratory in Johannesburg.. Among 190 participants with GUS, HSV-2 was the most frequently detected ulcer pathogen (49.0%; 95% confidence interval [CI], 41.9%-56.1%). The relative prevalence of the second most common ulcer-derived pathogen, Treponema pallidum, was 26.3% (95% CI, 20.5%-33.1%), with 90% of primary syphilis cases having a positive rapid plasma reagin (RPR) titer. Male sex was independently associated with primary syphilis compared with herpetic ulcers, after adjusting for the effect of casual sex partners and other exposures (adjusted odds ratio, 3.53; 95% CI, 1.35-9.21; P = 0.010). The overall HIV prevalence among participants was 41.3% (78 of 189; 95% CI, 34.2%-48.6%).. Herpes simplex virus 2 remains the predominant cause of GUS, justifying the continued use of acyclovir in syndromic guidelines. Adequate supplies of benzathine penicillin G for syphilis treatment are essential at primary health care level, in addition to the provision of syphilis and HIV risk reduction services.

Topics: Acyclovir; Adult; Female; Genitalia; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Male; Seroepidemiologic Studies; Sexually Transmitted Diseases; South Africa; Syphilis; Ulcer

Topics: Acyclovir; Dyskinesias; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infant; Lethargy

Understanding the molecular mechanisms of herpes simplex virus 1 (HSV-1) latent infection and reactivation in neurons requires the use of

Topics: Acyclovir; Antiviral Agents; DNA Replication; DNA, Viral; Herpes Simplex; Herpesvirus 1, Human; Histone Demethylases; Humans; Latent Infection; MAP Kinase Kinase Kinases; Virus Activation; Virus Latency; Virus Replication

The article gives the clinical case of herpes simplex encephalitis relapse with the resistant seizures in a child. What we describe is a clinical approach towards the differential diagnostic of the seizures in structural epilepsy, which are resistant to anticonvulsants, or late herpes simplex encephalitis relapse. Good clinical perspective may be the indication of the intratecal synthesis of the IgG-specific antibodies to the herpes simplex type 1 and 2. Conducting etiotropic treatment with the appointment of acyclovir and pathogenetic therapy with the use of Cytoflavin contributed to the rapid and stable remission of epileptic seizures and regression of neurological deficit.. В статье представлено клиническое описание рецидива герпетического энцефалита (ГЭ) у ребенка, осложненного резистентными судорогами. Представлена тактика дифференциальной диагностики судорожного синдрома как проявления структурной эпилепсии, резистентной к противоэпилептической терапии, и позднего рецидива ГЭ. Диагностически ценным может быть обнаружение интратекального синтеза специфических IgG к вирусу простого герпеса 1-го и 2-го типов, что в представленном случае позволило подтвердить реактивацию герпетической инфекции в центральной нервной системе и явилось основанием для повторного курса специфической терапии. Проведение этиотропного лечения с назначением ацикловира и патогенетической терапии с применением Цитофлавина способствовало быстрой и стойкой ремиссии эпилептических приступов и регрессу неврологического дефицита.

Topics: Acyclovir; Child; Encephalitis, Herpes Simplex; Epilepsy; Herpes Simplex; Humans; Immunoglobulin G; Recurrence; Seizures

Herpes simplex virus type 1 (HSV-1) is a common pathogen that infects 50-90% of the world's population and causes a variety of diseases, some of which can be life-threatening. Silver nanoparticles (AgNPs) have been shown to have broad-spectrum antiviral activity. In this study, we investigated the activity of AgNPs against HSV-1 and found that AgNPs effectively inhibited plaque formation and HSV-1 progeny production, reduced the genomic load, and interfered with HSV-1 mRNA expression and protein synthesis. Transmission electron microscopy showed that AgNPs interacted with HSV-1 and altered the shape of the viral particles. Furthermore, AgNPs affected the entry of HSV-1 into cells as well as their release and cell-to-cell spread. AgNPs were also found to downregulate the expression of pro-inflammatory cytokines upon HSV-1 infection. Combined treatment with AgNPs and acyclovir (ACV) confirmed that AgNPs significantly enhanced the inhibitory effect of ACV against HSV-1. Our findings may contribute to an understanding of the mechanism of the antiviral effect of AgNPs against HSV-1 and help to provide a theoretical basis for their clinical application.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Metal Nanoparticles; Silver

Topics: Acyclovir; Adult; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Magnetic Resonance Imaging; Migraine Disorders; Paralysis; Stroke; Young Adult

Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991.. Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs).. We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model.. Infants <120 days of age with neonatal HSV discharged from four academic children's hospitals.. We identified clinical and laboratory adverse events (AEs).. We identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2-37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.

Topics: Acyclovir; Antiviral Agents; Child; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Pregnancy Complications, Infectious; Simplexvirus

Herpes simplex virus type 1 (HSV-1) is a common virus of mankind and HSV-1 infections are a significant cause of blindness. The current antiviral treatment of herpes infection relies on acyclovir and related compounds. However, acyclovir resistance emerges especially in the long term prophylactic treatment that is required for prevention of recurrent herpes keratitis. Earlier we have established antiviral siRNA swarms, targeting sequences of essential genes of HSV, as effective means of silencing the replication of HSV in vitro or in vivo. In this study, we show the antiviral efficacy of 2´-fluoro modified antiviral siRNA swarms against HSV-1 in human corneal epithelial cells (HCE). We studied HCE for innate immunity responses to HSV-1, to immunostimulatory cytotoxic double stranded RNA, and to the antiviral siRNA swarms, with or without a viral challenge. The panel of studied innate responses included interferon beta, lambda 1, interferon stimulated gene 54, human myxovirus resistance protein A, human myxovirus resistance protein B, toll-like receptor 3 and interferon kappa. Our results demonstrated that HCE cells are a suitable model to study antiviral RNAi efficacy and safety in vitro. In HCE cells, the antiviral siRNA swarms targeting the HSV UL29 gene and harboring 2´-fluoro modifications, were well tolerated, induced only modest innate immunity responses, and were highly antiviral with more than 99% inhibition of viral release. The antiviral effect of the 2'-fluoro modified swarm was more apparent than that of the unmodified antiviral siRNA swarm. Our results encourage further research in vitro and in vivo on antiviral siRNA swarm therapy of corneal HSV infection, especially with modified siRNA swarms.

Topics: Acyclovir; Antiviral Agents; Epithelial Cells; Herpes Simplex; Herpesvirus 1, Human; Humans; RNA, Double-Stranded; RNA, Small Interfering; Virus Replication

Herpes simplex virus type-1 (HSV-1) infection causes several disorders, and acyclovir is used as a reference compound. However, resistant strains are commonly observed. Herein, we investigate the effects of

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Herpes Simplex; Herpesviridae Infections; Herpesvirus 1, Human; Pyrazoles; Pyridines; Vero Cells; Virus Replication

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

Topics: Acyclovir; Antiviral Agents; Cidofovir; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Foscarnet; Genitalia; Herpes Simplex; Herpesvirus 2, Human; Humans; Imiquimod; Mutation; Obesity; Thymidine Kinase; Valacyclovir

Prolonged antiviral therapy in immunocompromised individuals can result in the emergence of (multi)drug-resistant herpes simplex virus 1 (HSV-1) infections, forming a therapeutic challenge.. To evaluate spatial and temporal differences in drug resistance of HSV-1 samples from a HSCT recipient and to determine the effect of resistance mutations on viral replication fitness.. Five HSV-1 isolates were recovered from a HSCT recipient who suffered from persistent HSV-1 lesions, consecutively treated with aciclovir, foscarnet, cidofovir and a combination of ganciclovir and cidofovir. Spatial and temporal differences in HSV-1 drug resistance were evaluated genotypically [Sanger sequencing and next-generation sequencing (NGS) of the viral thymidine kinase (TK) and DNA polymerase (DP)] and phenotypically (plaque reduction assay). Viral replication fitness was determined by dual infection competition assays.. Rapid evolution to aciclovir and foscarnet resistance was observed due to acquisition of TK (A189V and R222H) and DP (L778M and L802F) mutations. Virus isolates showed heterogeneous populations, spatial virus compartmentalization and minor viral variants in three out of five isolates (detectable by NGS but not by Sanger sequencing). Mutations in the TK and DP genes did not alter replication fitness without drug pressure. TK and/or DP mutants influenced replication fitness under antiviral pressure and showed increased fitness under pressure of the drug they showed resistance to.. The use of NGS and dual infection competition assays revealed rapid evolution of HSV-1 drug resistance in a HSCT recipient with spatial and temporal compartmentalization of viral variants that had altered replication fitness under antiviral pressure.

Topics: Acyclovir; Antiviral Agents; Cidofovir; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Foscarnet; Herpes Simplex; Herpesvirus 1, Human; Humans; Mutation; Thymidine Kinase; Virus Replication

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Herpes Simplex; Humans; Retinal Necrosis Syndrome, Acute

Herpes simplex virus (HSV) naturally infects skin and mucosal surfaces, causing lifelong recurrent disease worldwide, with no cure or vaccine. Biomimetic human tissue and organ platforms provide attractive alternatives over animal models to recapitulate human diseases. Combining prevascularization and microfluidic approaches, we present a vascularized, three-dimensional skin-on-chip that mimics human skin architecture and is competent to immune-cell and drug perfusion. The endothelialized microvasculature embedded in a fibroblast-containing dermis responds to biological stimulation, while the cornified epidermis functions as a protective barrier. HSV infection of the skin-on-chip displays tissue-level key morphological and pathophysiological features typical of genital herpes infection in humans, including the production of proinflammatory cytokine IL-8, which triggers rapid neutrophil trans-endothelial extravasation and directional migration. Importantly, perfusion with the antiviral drug acyclovir inhibits HSV infection in a dose-dependent and time-sensitive manner. Thus, our vascularized skin-on-chip represents a promising platform for human HSV disease modeling and preclinical therapeutic evaluation.

Topics: Acyclovir; Animals; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Interleukin-8

Herpes simplex virus type 1 (HSV-1) is a persistent human pathogen, and the emergence of strains resistant to Acyclovir (ACV, reference drug) shows the urgency to develop new treatments. We report the antiherpetic mechanism of the action of lasiodiplodan (LAS-N, (1 → 6)-β-d-glucan) and its sulfonated derivative (LAS-S3) in vitro and in vivo. LAS-S3 showed anti-HSV-1 action with high selectivity indices for HSV-1 KOS (88.1) and AR (189.2), sensitive and resistant to ACV, respectively. LAS-S3 inhibited >80% of HSV-1 infection in different treatment protocols (virucidal, adsorption inhibition, and post-adsorption effects), even at low doses, and showed a preventive effect and DNA and protein synthesis inhibition. The antiherpetic effect was confirmed in vivo by the cosmetic LAS-S3-CRÈME decreasing cutaneous lesions of HSV-1, including the AR strain. LAS-S3 possessed a broad-spectrum mechanism of action acting in the early and post-adsorption stages of HSV-1 infection, and LAS-S3-CRÈME is a potential antiherpetic candidate for patients infected by HSV-1-resistant strains.

Topics: Acyclovir; Antiviral Agents; Glucans; Herpes Simplex; Herpesvirus 1, Human; Humans

Though primarily used to improve neurodevelopmental outcomes, suppressive oral acyclovir therapy following neonatal herpes simplex virus disease also decreases cutaneous recurrences. Skin recurrences can still occur, however, and understanding their frequency is helpful in managing patients with this rare disease.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Humans; Infant, Newborn; Recurrence; Simplexvirus

Herpes simplex virus (HSV) rarely causes organ-invasive infection. Diagnosis and treatment for such infections are often delayed, and mortality is high. We present the first reported case of disseminated HSV-1 infection in an adult causing liver failure, myocarditis, and encephalitis in a patient who recovered after receiving parenteral acyclovir treatment.. A 46-year-old female presented with fever, chills, and malaise after 2 weeks of oral corticosteroid treatment for uveitis. She was diagnosed with disseminated HSV-1 infection with multi-organ involvement causing hepatitis, encephalitis, and myocarditis. Diagnosis was made timely using serum polymerase chain reaction (PCR) for HSV DNA and the patient was given intravenous acyclovir treatment promptly, which led to her survival without significant morbidity.. Clinicians should have a low threshold for suspecting HSV infection and ordering HSV PCR to decrease morbidity and mortality when there is a high clinical suspicion of systemic HSV infection with multi-organ involvement. Serum PCR for HSV DNA is an excellent modality for an initial diagnostic approach. Further research is warranted to elucidate causality between a course of corticosteroid therapy and systemic HSV-1 infection without major immunosuppressive comorbidities or treatments.

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Antiviral Agents; Encephalitis; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Middle Aged; Myocarditis

Intrauterine infections during pregnancy by herpes simplex virus (HSV) can cause significant neurodevelopmental deficits in the unborn/newborn, but clinical studies of pathogenesis are challenging, and while animal models can model some aspects of disease, in vitro studies of human neural cells provide a critical platform for more mechanistic studies. We utilized a reductionist approach to model neurodevelopmental outcomes of HSV-1 infection of neural rosettes, which represent the in vitro equivalent of differentiating neural tubes. Specifically, we employed early-stage brain organoids (ES-organoids) composed of human induced pluripotent stem cells (hiPSCs)-derived neural rosettes to investigate aspects of the potential neuropathological effects induced by the HSV-1 infections on neurodevelopment. To allow for the long-term differentiation of ES-organoids, viral infections were performed in the presence of the antiviral drug acyclovir (ACV). Despite the antiviral treatment, HSV-1 infection caused organizational changes in neural rosettes, loss of structural integrity of infected ES-organoids, and neuronal alterations. The inability of ACV to prevent neurodegeneration was associated with the generation of ACV-resistant mutants during the interaction of HSV-1 with differentiating neural precursor cells (NPCs). This study models the effects of HSV-1 infection on the neuronal differentiation of NPCs and suggests that this environment may allow for accelerated development of ACV-resistance.

Topics: Acyclovir; Animals; Antiviral Agents; Brain; Herpes Simplex; Herpesvirus 1, Human; Humans; Induced Pluripotent Stem Cells; Infant, Newborn; Neural Stem Cells; Organoids

There are different etiologies of neonatal ophthalmia such as viral ones. Among them, the Herpes simplex virus, both type I and II, is particularly relevant due to its potential severity. It is a rare, in frequent entity, but with a high rate of morbidity and mortality without appropriate diagnosis and management.. To describe a case of neonatal ophthalmia caused by Herpes Virus type I, its clinical characteristics, and correct diagnosis.. 8-days old newborn, with no notable history, presenting edema and erythema of eyelids, accompanied by bilateral ocular discharge. Her pes Virus type I infection was diagnosed by PCR, without evidence of disseminated disease or central nervous system involvement. He received full treatment with intravenous Acyclovir with complete clinical improvement.. Herpes Simplex Virus should always be considered as a diffe rential diagnosis in all neonatal ophthalmia. Early and timely diagnosis and treatment are of vital importance.

Topics: Acyclovir; Endophthalmitis; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Simplexvirus

Topics: Acyclovir; Antiviral Agents; COVID-19; Disease Management; Herpes Simplex; Herpesvirus 1, Human; Humans; Intensive Care Units; Male; Massive Hepatic Necrosis; Middle Aged; SARS-CoV-2; Severity of Illness Index; Viremia

Acute liver failure (ALF) is a life-threatening condition that remains challenging for physicians despite several advances in supportive care. Etiologies vary worldwide, with herpes simplex virus (HSV) hepatitis representing less than 1% of cases. Despite its low incidence, ALF is a lethal cause of acute necrotizing hepatitis and has a high mortality. Early antiviral treatment is beneficial for survival and decreased liver transplantation necessity. However, plasmapheresis, despite its theoretical potential benefit, is scarcely reported.. A 25-year-old woman with no known disease presented with painful pharynx ulcers, increased transaminases and impaired liver function.. ALF due to a disseminated HSV-2 primary infection was diagnosed with a positive polymerase chain reaction for HSV-2 in the biopsied liver tissue and blood.. Empiric antiviral treatment was initiated. After clinical deterioration, plasmapheresis was also initiated.. After 6 cycles of plasmapheresis and supportive care, the patient's condition improved without undergoing liver transplantation.. ALF is a life-threatening condition, and HSV as an etiology must be suspected based on background, clinical manifestation, and laboratory information. The potential role of plasmapheresis in HSV hepatitis should be considered.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Liver Failure, Acute; Plasmapheresis; Tomography, X-Ray Computed

Herpes simplex virus type 1 (HSV-1) is an important human pathogenic virus. It is urgent to develop novel antiviral targets because of the limited treatment options and the emergence of drug resistant strains. In this study, we tested the antiviral activity of lupeol, a triterpenoid compound, against HSV-1 and acyclovir (ACV) resistant strains. Lupeol significantly inhibited HSV-1 (F strain) and ACV-resistant strains including HSV-1/106, HSV-1/153, and HSV-1/Blue. Lupeol activity of the HSV-1α0 and α4 promoters, therefore down regulating the expression of the α0, α4, and α27 genes. Collectively, lupeol showed strong antiviral activity against HSV-1 and ACV-resistant strains, and could be a promising therapeutic candidate for HSV-1 pathogenesis. Keywords: herpes simplex virus 1; lupeol; ACV-resistant strains; promoter.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Genes, Immediate-Early; Herpes Simplex; Herpesvirus 1, Human; Humans; Pentacyclic Triterpenes

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Skin

Although the seroprevalence of Herpes simplex virus type 1 (HSV-1) currently amounts to ∼ 67% worldwide, the annual incidence of a severe disease progression, particularly herpes encephalitis, is approximately 2-4 cases per 1,000,000 infections. Nucleoside analogues, such as acyclovir (ACV), valacyclovir (VACV) or famciclovir, are still the therapeutic treatment of choice for HSV infections. However, nucleoside drugs have limited efficacy against severe HSV disease and for treatment of nucleoside-resistant viral strains, alternative therapies such as helicase-primase inhibitors (HPIs) which are highly potent by inhibiting viral replication are under development. In preclinical studies we analyzed the antiviral efficacy of drug candidates of a novel compound class of HPIs for the treatment of HSV to identify the most active eutomer structure in an intranasal infection mouse lethal challenge model. HSV-1 infected BALB/c mice treated with vehicle control developed fatal disease according to humane endpoints after 5-7 days. In contrast, the animals dosed orally once daily with the HPI compounds at 10 or 4 mg/kg/day showed a significantly increased survival (70% and 100% for 10 mg/kg/day; 90% and 100% for 4 mg/kg/day, respectively) compared to the vehicle treatment (0-10%), when therapy was initiated 6 h post HSV-1 inoculation. We observed a significantly improved outcome in clinical parameters and survival over 21 days in the group receiving novel HPI candidates using even the lowest dose of 4 mg/kg/day. With VACV treatment of 75 mg/kg daily survival was also significantly increased (80%-90% for 75 mg/kg/day) but to lesser extent. Initial IM-250 therapy at 10 mg/kg/day could be delayed up to 72 h resulting in significantly increased survival compared to the vehicle control. Furthermore, we detected significantly fewer viral genome copies in the lungs and brains of HPI treated animals compared to vehicle (440-fold reduction for 4 mg/kg/day IM-250 in the brain) or VACV controls by quantitative PCR. In conclusion the preclinical studies of the novel HPI compounds showed superior efficacy in comparison to the current standard HSV treatment represented by VACV with respect to the survival according humane endpoints, the clinical score and virus load in lungs and brains. Thus, candidates of this new drug class are promising antivirals of HSV infections and further translation into clinical trials is warranted.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Disease Models, Animal; DNA Helicases; DNA Primase; Female; Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Inbred BALB C; Survival Rate; Valacyclovir; Vero Cells; Viral Load

A significant increase in the incidence of various forms of herpesvirus infection (HVI) determines the need to search for new approaches to the modification of one of the basic antiviral drugs aciclovir (ACV) and its dosage forms to improve their biopharmaceutical characteristics and increase the effectiveness of therapy. In this aspect, an innovative organic germanium complex with aciclovir (OGCA) is promising.The aim of the study was to assess the antiviral activity of OGCA against the herpes simplex virus (HSV) (human herpes virus, HHV) on the HVI models both in vitro and in vivo.. We studied the activity of OGCA in a therapeutic regimen against HSV-1 (HHV-1) (Kl strain), HSV-2 (HHV-2) (VN strain) using virological and statistical research methods in the in vitro model of HVI on Vero cell culture and the model of genital herpes (GH) caused by HHV-2 (VN strain) in male guinea pigs (Canis porcellus).. It was found OGCA inhibits the replication of HHV-1 and HHV-2 in Vero cells, and has anti-HHV activity in the GH model in male guinea pigs, leading to a decrease in the severity and duration of the disease, the intensity and duration of viral shedding. The most pronounced activity was detected when preparation was applied topically 5 times a day for 5 days at the early stages of infection (3% gel). The delayed use of OGCA (48 hours after infection) also had statistically significant efficacy compared to commercial reference drugs containing aciclovir or its pro-drugs: aciclovir (5% cream), AIL (acyclovir+interferon alfa-2b+lidocaine, 3% ointment), penciclovir (1% cream). OGCA significantly reduced the number of days of the pathogen shedding, as well as its infectivity, compared to animals in the control group and ones receiving placebo. The activity of OGCA, apparently, is due to its improved biopharmaceutical characteristics compared to aciclovir, as well as the presence of a number of biological activities of its constituent components.. The results of the study allow us to consider OGCA as the basis for the development of antiviral agents for the treatment of HVI.

Topics: Acyclovir; Alphaherpesvirinae; Animals; Antiviral Agents; Chlorocebus aethiops; Female; Germanium; Guinea Pigs; Herpes Genitalis; Herpes Simplex; Herpesviridae; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Simplexvirus; Vero Cells

Patients with dedicator of cytokinesis 8 (DOCK8) deficiency are susceptible to development of severe viral cutaneous infections, including herpes simplex virus (HSV). We report a 32-month-old girl with homozygous DOCK8 deficiency who developed a posterior auricular cutaneous lesion that was culture positive for HSV despite acyclovir prophylaxis. Resolution of this lesion was only observed after addition of foscarnet to the treatment regimen. Prophylactic acyclovir may be insufficient for suppression of cutaneous HSV in patients with DOCK8 deficiency, and a high index of suspicion for viral resistance is necessary for prompt initiation of appropriate antiviral treatment in these patients.

Topics: Acyclovir; Antiviral Agents; Child, Preschool; Drug Resistance, Viral; Female; Foscarnet; Guanine Nucleotide Exchange Factors; Herpes Simplex; Humans; Simplexvirus

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Diagnosis, Differential; Esophagitis; Female; Glossitis; Herpes Simplex; Herpesvirus 1, Human; Humans

The early engraftment phase of allogeneic haematopoietic stem cell transplantation can be associated with a number of oromucosal infective complications. While the routine use of prophylactic acyclovir has reduced the incidence of herpes simplex virus (HSV) reactivation, there is an increasing prevalence of acyclovir resistance within this cohort of patients. The authors present a case of acyclovir-resistant HSV reactivation in a 26-year-old woman 7 days post T-deplete sibling allograft on a background of combined cyclophosphamide and total body irradiation myeloablative conditioning, successfully treated with foscarnet and cidofovir therapy and discuss the differential diagnoses for early/late engraftment oral disease.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans

We present a case of a 10-year-old boy with a longstanding history of seborrheic dermatitis (SD) referred to the Allergy and Immunology Department for recurrent Kaposi varicelliform eruption (KVE) secondary to herpes simplex 1 (HSV-1) infection and possible primary immunodeficiency. The patient was the second child of non-consanguineous parents, with an older, healthy brother. Family history was negative for primary immunodeficiency and skin disorders. The patient's skin problems began in infancy when he was diagnosed and treated by a dermatologist for SD. From preschool age, he was under the care of a pediatric neurologist and a defectologist for a sensory processing disorder. For the last two years, the patient had been receiving chlorpromazine therapy for aggressive behavior. The first episode of KVE was diagnosed at the age of six, following potent topical corticosteroid therapy for SD and sun exposure, another known risk factor for HSV infection. After the third KVE episode, prophylaxis with oral acyclovir was initiated. The skin changes were treated with topical steroids and oral antibiotics during disease flares, with poor clinical response. On presentation, the patient was in good general health, adipose, and of unremarkable somatic status, except for numerous symmetrical yellowish-brown keratotic papules and plaques on the forehead, cheeks, and the lateral side of the neck (Figure 1). The nail plate had multiple red and white longitudinal streaks and V-shaped notches on the distal free end of the nail plate (Figure 2). The allergy tests revealed increased total immunoglobulin E (IgE) and sensitization to ragweed. Immunological workup showed normal immunoglobulins and good specific immunity (good vaccine response and normal humoral response to HSV-1) but a decreased number of T- cells (CD3+ 1020/µL (1320-3300), CD3+CD8+ 281/µL (390-1100) with normal T-cell response after antigen stimulation. The diagnosis of Darier disease (DD) was confirmed based on medical history, clinical findings and histological finding of focal suprabasal acantholysis and dyskeratosis (Figure 3). Low-dose oral retinoid therapy was initiated with modest clinical response after 6 months of therapy. In the light of recent publication (1), we initiated intravenous immunoglobulin (IVIG) substitution (400 mg/kg every month) with excellent clinical response. After 4 months, the patient's skin improved in terms of reduced inflammation, scab healing, and reduced itching. Acyclovir p

Topics: Acyclovir; Adolescent; Adult; Child; Child, Preschool; Darier Disease; Dermatitis, Allergic Contact; Dermatitis, Seborrheic; Herpes Simplex; Humans; Immunoglobulins, Intravenous; Kaposi Varicelliform Eruption; Male; Retinoids; Young Adult

The incidence of acyclovir-induced hypersensitivity is rare. To our knowledge, there are four published case reports of oral acyclovir desensitization in adults. Evidence-based guidelines prompt the use of acyclovir for herpes simplex virus (HSV) prophylaxis and treatment. Literature on the cross-reactivity of structurally similar antiviral agents is conflicting, presenting a clinical challenge when choosing an alternative agent. This is a case of successful acyclovir desensitization in an allogeneic stem cell transplant patient.. A 69-year-old female patient, diagnosed with myelodysplastic/myeloproliferative neoplasm, presented to the hospital for donor mismatch allogeneic bone marrow transplant. The patient reported acyclovir-induced angioedema while receiving treatment for non-complicated herpes zoster (shingles) infection.

Topics: Acyclovir; Aged; Angioedema; Antiviral Agents; Bone Marrow Transplantation; Desensitization, Immunologic; Drug Hypersensitivity; Female; Herpes Simplex; Humans

A young woman presented with worsening bilateral periareolar mastitis associated with skin necrosis and delayed vesical formation after oral nipple manipulation by her sexual partner. After multiple failed antibiotic regimens, she was diagnosed with herpes simplex virus 1 (HSV-1) infection. This case demonstrates an uncommon etiology of breast mastitis. We highlight the importance of a timely diagnosis and early administration of antiviral therapy.

Topics: Acyclovir; Adult; Antiviral Agents; Breast Neoplasms; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Mastitis

Herpes simplex virus type 1 or 2 (HSV 1/2)-related infections in neonates are rare but associated with high morbidity and mortality, especially if specific treatment is delayed. Due to immaturity of the immunological system, premature infants are particularly at risk. In addition, symptoms of neonatal HSV infections may imitate prematurity-related problems, such as sepsis. So, a thorough patient's history and appropriate diagnostic measures are important to confirm the diagnosis. We present 2 premature infants with systemic HSV infections and discuss diagnostic and therapeutic management. Both were treated with intravenous acyclovir followed by enteral aciclovir suppressive therapy.. Herpes simplex Virus Typ 1 oder 2 (HSV-1/2) Infektionen bei Neugeborenen sind selten, aber insbesondere bei systemischen Verlauf mit einer hohen Morbidität und Mortalität belastet. Frühgeborene gehören aufgrund ihrer immunologischen Unreife und der häufig unspezifischen, Sepsis-ähnlichen Klinik einer HSV-1/2 Infektion zu einer besonders gefährdeten Gruppe. Wir stellen das diagnostische und therapeutische Management bei 2 unreifen Frühgeborenen mit systemischer HSV Infektion vor. Beide erhielten entsprechend aktuellen Empfehlungen nach initialer parenteraler Intensivtherapie eine orale Aciclovir Suppressionstherapie.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Infant, Premature; Pregnancy; Pregnancy Complications, Infectious

Herpes simplex viruses type 1 (HSV-1) are extremely widespread throughout the world and, similar to other herpesviruses, establish lifelong persistent infection in the host. Reactivating sporadically, HSV-1 elicits recurrences in both immunocompetent and immunocompromised individuals and can cause serious diseases (blindness, encephalitis, generalized infections). The currently available antiherpetic drugs that aimed mainly at suppressing replication of viral DNA are not always effective enough, for example, due to the development of drug resistance. As we showed earlier the newly discovered compound LAS-131 exhibits the strong and highly selective inhibitory activity against HSV‑1, including strain resistant to acyclovir (selective index, SI = 63). The presence of LAS-131 at a concentration of 20 μg/ml leads to a decrease in the titer of HSV-1 (strain L2) by 4 lg in a one round of HSV-1 replication.. To establish the step(s) of the virus life cycle that is sensitive to the action of LAS-131, we have applied a widely used approach, that made it possible to determine how long the addition of a compound can be postponed before it loses its antiviral activity (time-of-addition assay), and to compare this indicator with the crucial time of application of inhibitors with a well-known mechanism of action (in cell culture).. It has been shown for the first time that LAS-131 retains a pronounced antiviral effect when introduced into the experimental system no later than 9 hours post-infection (p.i.). However, LAS-131 does not affect the release of HSV-1 from the cell.. Together with published data on the termination of the synthesis of viral DNA 9-12 h after the adsorption in a cell culture infected with HSV with a high multiplicity (≥1 PFU/cell), our results suggest that LAS-131 interferes the life cycle of HSV-1 during synthesis of viral DNA. Further studies of the mechanism of action are necessary to establish definitely the biological target for this compound,.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Purines; Virus Replication

The herpes simplex virus, also known as HSV, is an important human pathogen. Acyclovir (ACV) is the first-line antiviral for the treatment of HSV infections; nevertheless HSV resistance to ACV has been increasingly reported and, therefore, search for alternative drugs have been encouraged. Herein, the effect of Cucumis melo sulfated pectin (SPCm) was evaluated in the HSV-1 infection. Pectin cytotoxicity and its antiherpetic action were determined by assays of MTT and plaque reduction, respectively. The SPCm concentration that reduced the cell viability by 50% (CC50) was 1440 μg/mL, while the concentration that reduced PFU in 50% (IC50) was 6 μg/mL against ACV-sensitive (KOS) strain and 12 μg/mL for ACV-resistant (AR-29) strain. The pectin showed high selectivity index (SI) for both viral strains. Therefore, we suggest that SPCm has been effective for HSV-1, strenghten by viral protein and DNA syntheses inhibition. In conclusion, we have found that SPCm is a promising alternative compound to control HSV infection.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Cucumis melo; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Inhibitory Concentration 50; Pectins; Vero Cells; Virus Replication

Neonatal herpes simplex virus (HSV) infection is rare, with an estimated incidence of 3.58 per 100 000 live births in the UK and should be suspected in any newborn with fever and bacterial culture-negative sepsis. We describe a case of a previously well full-term male neonate who presented with persistent fever and elevated ferritin level that was carried out during the era of the COVID-19 pandemic as part of SARS-CoV-2 panel investigations. Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. He made a full recovery after acyclovir therapy. This case highlights the importance of maintaining a high clinical index of suspicion of HSV infection in any febrile neonate even with absence of maternal history and negative serology, particularly if associated with hyperferritinaemia. We also address the challenge of interpreting inflammatory biomarkers' results for SARS-CoV-2 infection in neonates.

Topics: Acyclovir; Antiviral Agents; COVID-19; Female; Ferritins; Fever; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Male; Pandemics; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2; Treatment Outcome

Emergence of drug resistance and adverse effects often affect the efficacy of nucleoside analogues in the therapy of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Host-targeting antivirals could therefore be considered as an alternative or complementary strategy in the management of HSV infections. To contribute to this advancement, here we report on the ability of a new generation inhibitor of a key cellular enzyme of de novo pyrimidine biosynthesis, the dihydroorotate dehydrogenase (DHODH), to inhibit HSV-1 and HSV-2 in vitro replication, with a potency comparable to that of the reference drug acyclovir. Analysis of the HSV replication cycle in MEDS433-treated cells revealed that it prevented the accumulation of viral genomes and reduced late gene expression, thus suggesting an impairment at a stage prior to viral DNA replication consistent with the ability of MEDS433 to inhibit DHODH activity. In fact, the anti-HSV activity of MEDS433 was abrogated by the addition of exogenous uridine or of the product of DHODH, the orotate, thus confirming DHODH as the MEDS433 specific target in HSV-infected cells. A combination of MEDS433 with dipyridamole (DPY), an inhibitor of the pyrimidine salvage pathway, was then observed to be effective in inhibiting HSV replication even in the presence of exogenous uridine, thus mimicking in vivo conditions. Finally, when combined with acyclovir and DPY in checkerboard experiments, MEDS433 exhibited highly synergistic antiviral activity. Taken together, these findings suggest that MEDS433 is a promising candidate as either single agent or in combination regimens with existing direct-acting anti-HSV drugs to develop new strategies for treatment of HSV infections.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Line, Tumor; Chlorocebus aethiops; Dihydroorotate Dehydrogenase; DNA Replication; DNA, Viral; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; Gene Expression Regulation, Viral; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Oxidoreductases Acting on CH-CH Group Donors; Pyrimidines; Vero Cells; Virus Replication

A 77-year-old woman presented with a 2-week history of malaise, prostration, anorexia, abdominal pain, vomiting and diarrhoea. She had been taking systemic corticosteroids for the past year. During hospitalisation, renal insufficiency, ionic changes and liver function abnormalities were detected and corrected. However, the patient developed total dysphagia. UGE revealed multiple shallow ulcers below the cricopharyngeal level and in the distal oesophagus, with normal-appearing intervening mucosa. Histological examination allowed the diagnosis of herpes simplex virus esophagitis. Treatment with intravenous acyclovir was instituted for 14 days. In the elderly, herpetic esophagitis may present with non-specific complains, such as prostration or anorexia. In the reported case, dysphagia was only detected as a late symptom, addressing the importance of maintaining a high degree of suspicion for the diagnosis of herpes simplex virus esophagitis.

Topics: Acyclovir; Aged; Esophageal Diseases; Esophagitis; Female; Herpes Simplex; Humans; Simplexvirus

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompetence; Immunoglobulins, Intravenous; Liver Failure; Male; Middle Aged; Valganciclovir

Recurrence of mucocutaneous herpes simplex virus (HSV) infections is common in immunosuppressed patients. Thymidine kinase mutations conferring resistance to the antiviral agent aciclovir have been observed in such patients. Recommended second-line therapeutic agents against HSV are associated with significant side effects contributing to disease burden. We present a case of aciclovir-resistant herpes simplex virus 2 (HSV-2) in an immunosuppressed (HIV negative) allogenic peripheral blood stem cell transplant (SCT) recipient which was refractory to second-line therapy. Compassionate acquisition of the novel oral helicase-primase inhibitor pritelivir provided both symptomatic and virological control for the duration of its use. We believe this to be the first clinical use of this therapeutic agent in the United Kingdom.

Topics: Acyclovir; Aged; Antiviral Agents; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Pyridines; Sulfonamides; Thiazoles

Although the prognosis of neonatal herpes simplex virus (HSV) infection has improved with intravenous acyclovir, the morbidity and mortality of disseminated disease remains high. Transaminitis and thrombocytopenia have been reported to be sensitive markers of neonatal HSV disease; however, early diagnosis remains a challenge due to a lack of specific clinical and laboratory indicators for this disease process. Ferritin, an acute phase reactant known for its use in diagnosing hemophagocytic lymphohistiocytosis, has recently been reported as extremely elevated in neonates with disseminated HSV due to its high inflammatory nature. We report three cases of neonates at a single institution with hyperferritinemia in the setting of disseminated HSV. Based on this case series, we discuss whether ferritin can be used as an early diagnostic marker in the setting of suspected neonatal HSV disease.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Hyperferritinemia; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious

Recurrent erythema multiforme is a chronic relapsing disease that represents a therapeutic challenge. Our objective was to retrospectively evaluate the clinical-epidemiological characteristics and therapeutic response of patients with recurrent erythema multiforme and suggest a therapeutic protocol. We included patients with recurrent erythema multiforme diagnosed between January 2000 and December 2019. Clinical symptoms and a positive serology for herpes simplex virus were the inclusion criteria to initiate acyclovir in monotherapy or a combined treatment with dapsone, thalidomide, or immunosuppressants in refractory cases. Thirty-five patients were included and 71.4% were female. The median disease onset age was 35.7 years and the mean follow-up was 7.58 years. The skin was the most affected site (91.4%). Herpes simplex virus immunoglobulin (Ig)G serology was positive in 91.1% of cases. Acyclovir treatment was used in 33 of 35 patients, and complete remission was achieved in 22 of 33 after the first therapeutic course; 16 of 22 relapsed and required a second acyclovir cycle. Combined treatment with dapsone was required in nine of 33 due to partial response to acyclovir; thalidomide was an adjuvant drug in four of 33 due to adverse effects to dapsone. After the first cycle of acyclovir with or without combined therapy, 19 of 33 patients relapsed and received 2-6 additional cycles. Our results suggest that recurrent erythema multiforme presents a good response to acyclovir in monotherapy or in combined therapy with dapsone or thalidomide in the majority of patients. We propose a long-term therapeutic protocol to enable disease remission.

Topics: Acyclovir; Adult; Chronic Disease; Erythema Multiforme; Female; Herpes Simplex; Humans; Recurrence; Retrospective Studies

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol-gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.

Topics: Acyclovir; Administration, Oral; Aluminum Hydroxide; Aluminum Oxide; Animals; Antiviral Agents; Biological Availability; Caco-2 Cells; Cell Survival; Drug Delivery Systems; Drug Liberation; Herpes Simplex; Humans; Models, Animal; Nanogels; Rats; Rats, Wistar; Simplexvirus

BACKGROUND Herpes simplex virus-2 (HSV-2) affects nearly 1 in 5 adults in the United States. Complications such as viral hepatitis and dissemination are rare in immunocompetent hosts. In this report, we describe a case of viral hepatitis secondary to disseminated HSV-2 in an immunocompetent patient with recurrent fevers and elevated aminotransferases. CASE REPORT A 57-year-old man with a history of type 2 diabetes and hypertension was admitted with a right index finger lesion concerning for an abscess. He underwent successful incision and drainage and was started on ampicillin-sulbactam. On Day 2 of hospitalization, he developed recurrent fevers and elevated aminotransferases and inflammatory markers. An extensive infectious, rheumatologic, and malignancy workup were pursued without immediate findings. Imaging demonstrated cirrhotic morphology of the liver and splenomegaly, but lab markers were intact for liver synthetic function. On Day 7 of hospitalization, fever frequency decreased, and HSV-2 titers resulted, with positive IgM and negative IgG. He subsequently developed erythematous, raised lesions in multiple dermatomes. Nucleic acid amplification testing of biopsied lesions was positive for HSV-2, confirming viral hepatitis secondary to disseminated HSV-2. He was started on intravenous acyclovir and discharged on valacyclovir following improvement in symptoms. CONCLUSIONS We report a case of viral hepatitis secondary to disseminated HSV-2 in an immunocompetent host. Up to 25% of cases occur in immunocompetent hosts and many patients do not develop characteristic skin lesions. Early diagnosis and treatment of viral hepatitis secondary to disseminated HSV remains vital to minimize morbidity and mortality.

Topics: Acyclovir; Adult; Antiviral Agents; Diabetes Mellitus, Type 2; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 2, Human; Humans; Male; Middle Aged

Neonatal herpes simplex virus encephalitis (HSVE) often results in long-lasting neuro-disability in affected children. In addition to primary HSVE and HSVE relapses, children with herpes simplex virus are at increased risk of developing anti-

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antiviral Agents; Brain; Child, Preschool; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Magnetic Resonance Imaging; Male; Pregnancy; Pregnancy Complications, Infectious

Clinicians evaluating for herpes simplex virus (HSV) in febrile infants must balance detection with overtesting, and there is no universally accepted approach to risk stratification. We aimed to describe variation in diagnostic evaluation and empirical acyclovir treatment of infants aged 0 to 60 days presenting with fever and determine the association between testing and length of stay (LOS).. In this retrospective 44-hospital observational study, we used the Pediatric Health Information System database to identify infants aged ≤60 days evaluated for fever in emergency departments from January 2016 through December 2017. We described hospital-level variation in laboratory testing, including HSV, imaging and other diagnostic evaluations, acyclovir use, and LOS. We assessed the relationship between HSV testing and LOS using generalized linear mixed effects models adjusted for age and illness severity.. In 24 535 encounters for fever, the median HSV testing frequency across hospitals was 35.6% (interquartile range [IQR]: 28.5%-53.5%) for infants aged 0 to 21 days and 12% (IQR: 8.6%-15.7%) for infants aged 22 to 60 days. Among HSV-tested patients, median acyclovir use across hospitals was 79.2% (IQR: 68.1%-89.7%) for those aged 0 to 21 days and 63.6% (IQR: 44.1%-73%) for those aged 22 to 60 days. The prevalence of additional testing varied substantially by hospital and age group. Risk-adjusted LOS for HSV-tested infants was significantly longer than risk-adjusted LOS for those not tested (2.6 vs 1.9 days,. Substantial variation exists in diagnostic evaluation and acyclovir use, and infants who received HSV testing had a longer LOS than infants who did not. This variability supports the need for further studies to help clinicians better risk-stratify febrile infants and to guide HSV testing and treatment decisions.

Topics: Acyclovir; Child; Diagnostic Tests, Routine; Herpes Simplex; Humans; Infant; Retrospective Studies; Simplexvirus

Acyclovir (ACV) and penciclovir and their prodrugs are recommended for therapy or prophylaxis of Herpes simplex virus 1 (HSV-1) infections. Their administration, however, can lead to the emergence of resistant strains with altered viral thymidine kinase (TK) function, especially in immunocompromised patients. Furthermore, amino acid (aa) changes of the viral deoxyribonucleic acid polymerase (POL) may contribute to resistance to the aforementioned nucleoside analogues. Given this, treatment with foscarnet (FOS) or cidofovir (CDV) may represent an important alternative. Both drugs directly affect POL activity. Several aa changes of POL, such as L49I, E70K, L359I, E421V, P829S, T1121M, and M1226I, have been observed in ACV-resistant clinical strains which also carried relevant aa changes in their TK. Their contribution to ACV, FOS, and CDV resistance is not fully understood. In this study, these seven aa changes with unknown significance for ACV, FOS and CDV resistance were introduced separately into the POL of a recombinant HSV-1 strain rHSV-1(17+)Lox, equipped with or without information for expression of green fluorescent protein (GFP). The GFP-expressing variants were tested for susceptibility to ACV, FOS and CDV. An rHSV-1(17+)Lox GFP strain with the S724N change conferring resistance to ACV and FOS was generated and included as a control. Only the S724N change was confirmed to induce ACV and FOS resistance, whereas the other changes did not contribute to resistance. The underlying nucleotide substitutions of the POL gene should be therefore considered as natural polymorphism. These data will improve sequence-based prediction of antiviral susceptibility.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Cidofovir; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Foscarnet; Guanine; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Thymidine Kinase; Vero Cells

Current therapy against herpes simplex viruses (HSV) relies on the use of a few nucleoside antivirals such as acyclovir, famciclovir and valacyclovir. However, the current drugs are ineffective against latent and drug-resistant HSV infections. A series of amidinourea compounds, designed as analogues of the antiviral drug moroxydine, has been synthesized and evaluated as potential non-nucleoside anti-HSV agents. Three compounds showed micromolar activity against HSV-1 and low cytotoxicity, turning to be promising candidates for future optimization. Preliminary mode of action studies revealed that the new compounds act in an early stage of the HSV replication cycle, just after the viral attachment and the entry phase of the infection.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Guanidine; Herpes Simplex; Herpesvirus 1, Human; Humans; Simplexvirus; Urea

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; History, 20th Century; Humans; Infant, Newborn; Pediatrics; Pregnancy Complications, Infectious

Topics: Acyclovir; Animals; Antiviral Agents; Complement Inactivating Agents; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Inbred BALB C; Peptides; Thymidine Kinase

The synthesis of a lead anti-viral cyclopropyl carboxy acyl hydrazone 4F17 (5) and three sequential arrays of structural analogues along with the initial assessment and optimization of the antiviral pharmacophore against the herpes simplex virus type 1 (HSV-1) are reported.

Topics: Antiviral Agents; Cell Line; Chemistry Techniques, Synthetic; Herpes Simplex; Herpesvirus 1, Human; Humans; Hydrazones; Structure-Activity Relationship

Genetic aberrations in the toll-like receptor (TLR)3 pathway are associated with increased susceptibility to herpes simplex virus (HSV) infections. Leucine-rich repeat and PYD-containing protein (NLRP)12 is a component of the inflammasome apparatus, which is critical to an immediate innate inflammatory response. Aberrations in NLRP12 have been shown to mediate auto-inflammation. In this study, we present a 44-year old patient with severe HSV esophagitis and Crohn's disease. An immune and genetic investigation confirmed two coinciding genetic mutations in TLR3 and NLRP12. Our findings support conducting laboratory workup that targets TLR3 pathway in the immunocompetent host developing recurrent HSV infections.

Topics: Acyclovir; Adult; Antibodies, Monoclonal, Humanized; Antiviral Agents; Crohn Disease; Esophagitis; Female; Gastrointestinal Agents; Herpes Simplex; Humans; Intracellular Signaling Peptides and Proteins; Mutation; Signal Transduction; Toll-Like Receptor 3; Valganciclovir; Whole Genome Sequencing

Topics: Acyclovir; Drug Resistance, Viral; Herpes Simplex; High-Throughput Nucleotide Sequencing; Humans; Pharmaceutical Preparations; Simplexvirus

The molecular mechanisms of pain associated with alphaherpesvirus latency are not clear. We hypothesize that the voltage-gated sodium channels (VGSC) on the dorsal root ganglion (DRG) neurons controlling electrical impulses may have abnormal activity during latent viral infection and reactivation. We used herpes simplex virus 1 (HSV-1) to infect the human DRG-derived neuronal cell line HD10.6 in order to study the establishment and maintenance of viral latency, viral reactivation, and changes in the functional expression of VGSCs. Differentiated cells exhibited robust tetrodotoxin (TTX)-sensitive sodium currents, and acute infection significantly reduced the functional expression of VGSCs within 24 h and completely abolished VGSC activity within 3 days. A quiescent state of infection mimicking latency can be achieved in the presence of acyclovir (ACV) for 7 days followed by 5 days of ACV washout, and then the viruses can remain dormant for another 3 weeks. It was noted that during the establishment of HSV-1 latency, the loss of VGSC activity caused by HSV-1 infection could not be blocked by ACV treatment. However, neurons with continued ACV treatment for another 4 days showed a gradual recovery of VGSC functional expression. Furthermore, the latently infected neurons exhibited higher VGSC activity than controls. The overall regulation of VGSCs by HSV-1 during quiescent infection was proved by increased transcription and possible translation of Nav1.7. Together, these observations demonstrated a very complex pattern of electrophysiological changes during HSV infection of DRG neurons, which may have implications for understanding of the mechanisms of virus-mediated pain linked to latency and reactivation.

Topics: Acyclovir; Cell Line; Ganglia; Ganglia, Spinal; Gene Expression Regulation, Viral; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 1, Suid; Humans; Neuralgia, Postherpetic; Neurons; Transcriptome; Virus Activation; Virus Latency; Virus Replication

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Drainage; Female; Herpes Simplex; Histocytochemistry; Humans; Lymphangioma; Vulvar Neoplasms

Topics: Acyclovir; Critical Illness; Herpes Simplex; Humans; Respiration, Artificial; Simplexvirus; Virus Activation

Seventeen-day-old twins were hospitalized for neonatal herpes simplex virus 1 (HSV-1) with central nervous system disease and internal capsule and thalamic lesions on magnetic resonance imaging (MRI). They were treated with the usual intravenous (IV) treatment and oral therapy for 6 months. The clinical course was good in both children with negative HSV polymerase chain reaction on completion of IV therapy. The neurological condition recurred in one child with new radiological lesions at 7 months of age, 2 weeks after discontinuation of oral treatment. Cerebral lesions highlighted on the MRI scan are specific to the neonatal period and impact long-term prognosis. The likely genetic predisposition in this case is interesting and requires further investigation. In addition, this case raises questions about the duration of oral acyclovir suppressive therapy.

Topics: Acyclovir; Antiviral Agents; Central Nervous System Viral Diseases; Diseases in Twins; Electroencephalography; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Recurrence

Herpes simplex virus (HSV) causes only 2-4% of all acute hepatitis but has high morbidity and mortality. Pregnancy is a risk factor for HSV hepatitis. We describe a case of gestational HSV hepatitis.. A 32-year old woman, gravida 2 para 1, presented at 38 2/7 weeks of gestation with back pain and fetal tachycardia. She became febrile after admission, had spontaneous rupture of membranes, and was delivered by cesarean for malpresentation. Postpartum, she became persistently febrile and developed transaminitis, symptomatic hypotension, and pancytopenia despite antibiotics. Imaging revealed acute liver injury, splenomegaly, pleural effusions, and cardiomyopathy. Serum polymerase chain reaction (PCR) screening identified HSV-1 infection. The patient recovered on acyclovir. There was no evidence of neonatal seroconversion.. Herpes simplex virus hepatitis causes significant morbidity, and pregnant women are susceptible to severe infections. Pregnant or peripartum women with acute febrile hepatitis require prompt evaluation for HSV with serum PCR screening.

Topics: Acyclovir; Adult; Antiviral Agents; Cesarean Section; Diagnosis, Differential; Female; Hepatitis, Viral, Human; Herpes Simplex; Humans; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Simplexvirus

In previous studies, cold atmospheric plasma (CAP) was explored as an antibacterial and antiviral agent for the treatment of chronic wounds. The aim of the present study was to investigate whether CAP may also be suitable as an antiviral therapy against herpes simplex virus type 1 (HSV-1). HSV-1 most frequently manifests as recurrent herpes labialis, but it can also cause encephalitis, conjunctivitis or herpes neonatorum as a perinatal infection. HSV-1 encoding the reporter gene GFP was propagated. The CAP dose for HSV-1 treatment was gradually increased, ranging from 0-150 s, and aciclovir was used as a positive control. After CAP treatment, the virus suspension was applied to a standard HSV research cell line (Vero cells) and the neuroblastoma cell line SH-SY5Y as a model for neuronal infection. The results showed that plasma treatment had a negligible antiviral effect on HSV-1 in both Vero- and SH-SY5Y cells at high dose. However, when we lowered the viral load 100-fold, we observed a significantly decreased number of internalized HSV-1 genomes 3 h post-infection for CAP-treated viruses. This difference was less pronounced with respect to GFP expression levels 24 h post-infection, which was in sharp contrast to the acyclovir-treated positive control, for which the viral load was reduced from 95 to 25%. In summary, we observed a low but measurable antiviral effect of CAP on HSV-1.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Line; Chlorocebus aethiops; Herpes Simplex; Herpesvirus 1, Human; Humans; Plasma Gases; Vero Cells

Topics: Acyclovir; Antiviral Agents; Biopsy; Diagnosis, Differential; Ectodermal Dysplasia; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus

To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants.. We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age <60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment.. We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P = .002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P = .004), receipt of mechanical ventilation (OR, 5.97; P = .001), and admission to an intensive care unit (OR, 6.02; P = .006) as risk factors for AKI during acyclovir treatment.. Among our cohort of infants exposed to acyclovir, the rate of AKI was low. Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adolescent; Child; Child, Preschool; Cohort Studies; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Retrospective Studies; Risk Factors

Alzheimer's Disease (AD) is the sixth leading cause of death in the United States. Recent studies have established a potential link between herpes simplex virus 1 (HSV-1) infection and the development of AD. HSV-1 DNA has been detected in AD amyloid plaques in human brains, and treatment with the antiviral acyclovir (ACV) was reported to block the accumulation of the AD-associated proteins beta-amyloid (Aβ) and hyper-phosphorylated tau (p-tau) in Vero and glioblastoma cells. Our goal was to determine whether the accumulation of AD-related proteins is attributable to acute and/or latent HSV-1 infection in mature hippocampal neurons, a region of the brain severely impacted by AD. Primary adult murine hippocampal neuronal cultures infected with HSV-1, with or without antivirals, were assessed for Aβ and p-tau expression over 7 days postinfection. P-tau expression was transiently elevated in HSV-1-infected neurons, as well as in the presence of antivirals alone. Infected neurons, as well as uninfected neurons treated with antivirals, had a greater accumulation of Aβ

Topics: Acyclovir; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Antiviral Agents; Brain; Chlorocebus aethiops; Female; Herpes Simplex; Herpesvirus 1, Human; Hippocampus; Mice; Neurons; Peptide Fragments; Phosphorylation; Plaque, Amyloid; Primary Cell Culture; tau Proteins; Vero Cells; Virus Replication

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Female; Herpes Simplex; Herpes Simplex Virus Vaccines; History, 20th Century; Humans; Idoxuridine; Infant, Newborn; Infectious Disease Transmission, Vertical; Pediatrics; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Risk; Virus Shedding

Acyclovir (ACV) is the most commonly used drug for herpes simplex virus (HSV) infection therapy. Prolonged antiviral therapy or prophylaxis in immunocompromised patients may promote the development of drug-resistant strains. Due to the high polymorphism in genes involved in drug resistance, phenotypic methods, although work-intensive, are still required to test drug susceptibility. Real-time cell analysis (RTCA) based methods could offer a rapid and less labor-intensive alternative for phenotypic testing of ACV resistance.. To investigate the utility of a new RTCA based assay (RTCAA) to test acyclovir susceptibility of HSV clinical isolates.. Four reference strains and 93 clinical isolates (60 HSV-1 and 33 HSV-2) were tested by RTCAA. In the presence of ACV concentrations from 2.2 to 140.8 μM, Vero cells were infected with different virus dilutions. IC. IC. RTCAA agrees well with the dye-uptake assay. Compared with other phenotypic methods, RTCAA requires less manipulation, reduces the workload and the turnaround time, and appears to be an objective and reliable method to test ACV susceptibility.

Topics: Acyclovir; Animals; Antiviral Agents; Biological Assay; Cell Survival; Chlorocebus aethiops; Colorimetry; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Inhibitory Concentration 50; Phenotype; Vero Cells

Herpes simplex virus (HSV) acquired during delivery places the neonate at risk for mortality or long-term neurodevelopmental disability. Exposure generally occurs from recurrent genital herpes infection, although primary infections result in the highest risk of neonatal disease. Neonates generally present in the second or third week of life with lesions. Encephalitis with seizures indicates the presence of central nervous system involvement, and other end organs may also be impacted. Clinical suspicion for neonatal HSV infection warrants immediate initiation of appropriate antiviral therapy. In the last 50 years, antiviral therapy has progressed from agents with prohibitive toxicity or cumbersome administration to herpes virus-specific agents that dramatically improve clinical outcomes with manageable toxicity. Multicenter clinical trials have demonstrated the superiority of high-dose intravenous acyclovir for acute therapy, followed by long-term oral suppressive therapy. This work has dramatically reduced morbidity and mortality from neonatal HSV, representing the benchmark for future clinical trials in neonatal pharmacotherapy.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Hand Dermatoses; Herpes Simplex; Humans; Male; Middle Aged; Recurrence; Simplexvirus

To describe the characteristics of infants evaluated for serious bacterial infection, focusing on empirical testing and treatment of herpes simplex virus (HSV) and describe the characteristics of HSV-positive patients.. We included infants aged 0 to 60 days undergoing evaluation for serious bacterial infection in the emergency department. This descriptive study was conducted between July 2010 and June 2014 at a tertiary-care children's hospital. Eligible patients were identified on the basis of age at presentation to the hospital and laboratory specimens. Infant characteristics, symptoms on presentation, and laboratory workup were compared between HSV-positive and HSV-negative patients by using the 2-sample. A total of 1633 infants were eligible for inclusion, and 934 (57.2%) were 0 to 28 days of age. HSV was diagnosed in 19 infants, 11 of whom had disseminated disease. Compared with those without HSV, HSV-positive infants were younger, less likely to be febrile and to present with nonspecific symptoms, and more likely to have a mother with HSV symptoms (. The absence of fever should not preclude a workup for HSV in neonates, and when a workup is initiated, emphasis should be placed on obtaining samples from serum, cerebrospinal fluid, and surface specimens. Physicians may benefit from a guideline for evaluation of HSV with specific guidance on high-risk features of presentation and recommended testing.

Topics: Acyclovir; Bacterial Infections; Child; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Retrospective Studies; Simplexvirus

The emergence of herpes simplex virus (HSV) resistance to aciclovir (ACV) has increasingly been reported among hematopoietic stem cell transplant (HSCT) recipients and often associated with extended ACV prophylaxis.. Between June 2011 and June 2019, medical records of 532 HSCT recipients with suspected HSV infection were retrospectively analyzed. HSV-1 and HSV-2 positive samples were identified in 47 and 16 patients respectively. Analysis of HSV resistance to antivirals was performed at the Public Health England reference laboratory in London using phenotypic and/or genotypic resistance assays.. The prevalence of ACV-resistant HSV accounted for 17% (8/48) of infected HSV-1 cases. All 8 patients received T-cell depleted allogeneic HSCT for hematological malignancies. Half of these patients were male with a median age was 57.5 years (range; 26-63). Chronic Graft versus Host disease (cGVHD) affected 7 patients before HSV-1 diagnosis. HSV-1 infection developed while receiving either intravenous ACV (n = 2) or oral ACV (n = 6 patients) prophylaxis at a median of 373 [range,18-2183] days post-HSCT. ACV resistance was clinically suspected at a median of 25 [range,16-109] days after initial HSV diagnosis and subsequently laboratory confirmed at a median of 25 (range,10-59) days. All patients presented with hemorrhagic oral mucositis refractory to treatment dose ACV. Foscarnet (FOS) treatment was initiated in all 8 patients (pending laboratory confirmation of ACV resistance) with some effect but associated with significant toxicity burden. Four patients presented again with recurrent HSV infection or no resolution. Three with recurrent HSV died from other causes while suffering from persistent oral HSV lesions.. A prolonged immunosuppressed state following T-deplete HSCTs alongside extended use of ACV, early onset systemic HSV infection, presence of cGVHD, and treatment toxicities pose a significant challenge to the management of ACV resistant HSV infections and alternative effective antiviral options remains an unmet need in this clinical setting.

Topics: Acyclovir; Adult; Antiviral Agents; Bone Marrow Transplantation; Drug Resistance, Viral; Female; Herpes Simplex; Humans; Immunocompromised Host; London; Male; Middle Aged; Retrospective Studies; Transplantation, Homologous

Topics: Acyclovir; Anti-Bacterial Agents; Herpes Simplex; Humans; Pneumonia, Ventilator-Associated; Simplexvirus

Herpes simplex virus type 2 (HSV-2) causes recurrent lesions in the anogenital area that may be transmitted through sexual encounters. Nucleoside analogs, such as acyclovir (ACV), are currently prescribed clinically to curb this infection. However, in some cases, reduced efficacy has been observed due to the emergence of resistance against these drugs. In our previous study, we reported the discovery of a novel anti-HSV-1 small molecule, BX795, which was originally used as an inhibitor of TANK-binding kinase 1 (TBK1). In this study, we report the antiviral efficacy of BX795 on HSV-2 infection in vaginal epithelial cells

Topics: Acyclovir; Animals; Antiviral Agents; Female; Genitalia; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Mice; Pyrimidines; Thiophenes

Herpes simplex virus type 1 (HSV-1) is frequently detected in the BAL fluid of patients on mechanical ventilation.. The aim of the study was to investigate whether antiviral therapy is associated with improved overall survival within 30 days.. This was a retrospective cohort study in four ICUs between January 2011 and December 2017. All adult patients on mechanical ventilation with a respiratory tract infection with positive polymerase chain reaction testing for HSV-1 in the BAL were included. Patients already receiving antiviral agents on the day BAL was performed were excluded. We performed uni- and multivariable Cox and logistic regression modeling.. Overall, 306 patients were included in the analysis. Among them, 177 patients (57.8%) received antiviral therapy (90.9% acyclovir, 6.2% ganciclovir, 2.9% both). The overall 30-day mortality rate was 42.4% (n = 75) in the antiviral treatment group and 50.4% (n = 65) in the control group. The adjusted hazard ratio (HR) for the primary outcome was 0.62 (95% CI, 0.44-0.87; P = .005), indicating better overall survival within 30 days for the antiviral-treated group than for the untreated group. This benefit was also present in the subgroup of patients without immunosuppression (n = 246; adjusted HR, 0.53; 95% CI, 0.36-0.78; P = .001). Overall, the median lengths of hospital stay (31 vs 24 days, P = .002) and ICU stay (24 vs 17 days, P < .001), and the duration of mechanical ventilation (18 vs 11 days, P < .001), were longer for patients with therapy. No evidence for the treatment-related deterioration of renal function was observed.. These data suggest that detection of HSV-1 in the BAL of patients on mechanical ventilation may be of clinical significance and that specific antiviral treatment may improve clinical outcomes. However, this needs to be proven in multicenter randomized controlled trials before implementation into the clinical routine.

Topics: Acyclovir; Antiviral Agents; Bronchoalveolar Lavage Fluid; Female; Ganciclovir; Germany; Herpes Simplex; Herpesvirus 1, Human; Humans; Intensive Care Units; Male; Middle Aged; Mortality; Respiration, Artificial; Respiratory Tract Infections; Retrospective Studies; Treatment Outcome; Virology

Herpes simplex virus 1 (HSV) is a ubiquitous human virus resident in a majority of the global population as a latent infection. Acyclovir (ACV), is the standard of care drug used to treat primary and recurrent infections, supplemented in some patients with intravenous immunoglobulin (IVIG) treatment to suppress infection and deleterious inflammatory responses. As many diverse medications have recently been shown to change composition of the gut microbiome, we used Illumina 16S rRNA gene sequencing to determine the effects of ACV and IVIG on the gut bacterial community. We found that HSV, ACV and IVIG can all independently disrupt the gut bacterial community in a sex biased manner when given to uninfected C57BL/6 mice. Treatment of HSV infected mice with ACV or IVIG alone or together revealed complex interactions between these drugs and infection that caused pronounced sex biased dysbiosis. ACV reduced Bacteroidetes levels in male but not female mice, while levels of the Anti-inflammatory Clostridia (AIC) were reduced in female but not male mice, which is significant as these taxa are associated with protection against the development of graft versus host disease (GVHD) in hematopoietic stem cell transplant (HSCT) patients. Gut barrier dysfunction is associated with GVHD in HSCT patients and ACV also decreased Akkermansia muciniphila, which is important for maintaining gut barrier functionality. Cumulatively, our data suggest that long-term prophylactic ACV treatment of HSCT patients may contribute to GVHD and also potentially impact immune reconstitution. These data have important implications for other clinical settings, including HSV eye disease and genital infections, where ACV is given long-term.

Topics: Acyclovir; Animals; Antiviral Agents; Bacteroidetes; Clostridium; Dysbiosis; Female; Gastrointestinal Microbiome; Herpes Simplex; Immunoglobulins, Intravenous; Male; Mice; Mice, Inbred C57BL; Sex Factors

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Dermatitis, Allergic Contact; Diagnosis, Differential; Facial Dermatoses; Glucocorticoids; Herpes Simplex; Herpes Zoster Oticus; Humans; Impetigo; Mouth Mucosa; Prednisone; Tongue

Herpetic esophagitis (EH) usually affects those who are immunocompromised and is uncommon in immunocompetent patients. In these cases, EH may occasionally present as an acute and self-limited illness. Such cases are rare and only a few have beenreported and limited published reviews exist making the benefits of antiviral therapy in immunocompetent patients unknown.. We report four cases of young patients who presented dysphagia, odynophagia and epigastric pain. Endoscopic findings revealed lesions in the distal esophagus and histopathological changes compatible with herpes virus infection confirmed by viral DNA in every case. After treatment, every patient showed significant improvement and tolerated oral intake after discharge.. In this publication, we present four immunocompetent patients with EH, without relevant alterations in laboratory workup and with negative HIV status. This disease is infrequent in patients with such characteristics and there are few cases published. In order to better understand this pathology, we present the symptoms, the endoscopic alterations and the clinical evolution with treatment. In our series, 50% of patients had serology compatible with acute HVS type 1 infection, 25% had a subacute infection pattern (IgM and IgG positive antibodies) and in another 25% of patients, serology was not done. No patient presented leukocyte alterations, while all patients presented with anatomopathological findings compatible with acute herpetic esophagitis and responded to acyclovir therapy.

Topics: Acyclovir; Adolescent; Antiviral Agents; Endoscopy, Digestive System; Esophagitis; Esophagus; Female; Herpes Simplex; Humans; Immunocompromised Host; Male; Simplexvirus; Young Adult

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Humans; Retinitis; Simplexvirus

Herpes simplex virus 2 (HSV-2) is a very rare cause of central nervous system (CNS) infections. We report a case of a young woman with a left middle cerebral artery (MCA) ischemic stroke. The patient had history of HIV-1 infection, with periods of therapeutic non-compliance. Initial computed tomography (CT) imaging studies showed stenosis of the M1 segment of the left MCA, and magnetic resonance imaging (MRI) confirmed infarction of the MCA territory. Serial transcranial Doppler ultrasound revealed progressive occlusion of the MCA and stenosis of the left anterior cerebral artery. Systemic investigation for other causes of stroke was normal. Lumbar puncture revealed a mildly inflammatory cerebrospinal fluid, and HSV-2 DNA was identified by PCR, with a positive viral load in favor of active replication. No other viral or microbiological infections were identified. MRI angiography confirmed a vasculitic process involving the left carotid artery, and a HSV-2 vasculitis diagnosis was assumed. The patient started acyclovir with improvement of clinical features and imaging abnormalities. In the HIV-infected patient, stroke is a multifactorial common cause of morbidity. The physician should take into account a broad differential diagnosis including rare causes and atypical presentations of common etiologies, including HSV-1 and HSV-2 CNS infection.

Topics: Acyclovir; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Female; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Immunocompromised Host; Infarction, Middle Cerebral Artery; Ischemic Stroke; Magnetic Resonance Angiography; Patient Compliance; Vasculitis; Viral Load; Young Adult

We report on patients who developed severe acyclovir-resistant (ACVr) herpes simplex virus 1 (HSV-1) stomatitis after allogeneic hematopoietic cell transplantation (HCT).. HCT patients suffering from HSV-1 stomatitis without response after 1 week of high-dose acyclovir (ACV) were tested for ACV resistance. Patients with proven ACV resistance were treated either topically with cidofovir solution and gel or with topical foscavir cream or with intravenous foscavir.. Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III n = 1, WHO grade IV n = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT. ACVr stomatitis was treated topically with first-line (n = 4) or second-line (n = 2) cidofovir. Topical foscavir cream was applied as first-line (n = 1) or second-line (n = 1) therapy. Intravenous foscavir was used in 3 patients (first-line therapy, n = 1; second-line therapy, n = 2). Complete remission was reached by topical cidofovir (n = 3), topical foscavir (n = 1), and intravenous foscavir (n = 1), respectively. Five of the 6 patients died due to progression of leukemia. Only 1 patient survived.. ACVr HSV-1 stomatitis is a severe complication in AML patients relapsing after HCT. It reflects the seriously impaired general condition of these patients. This analysis shows that topical treatment with cidofovir or foscavir might be a sufficient first-line therapy approach in ACVr HSV-1 stomatitis. It might serve as a less toxic alternative to intravenous foscavir.

Topics: Acyclovir; Administration, Topical; Adult; Aged; Antiviral Agents; Cidofovir; Drug Resistance, Viral; Female; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Stomatitis; Treatment Outcome

Herpes simplex virus (HSV) infections remain an important cause of morbidity among immunocompromised patients, such as transplant recipients and human immunodeficiency virus [HIV]-infected individuals. Only few antiviral drugs are available to treat HSV infections: (val)acyclovir, foscarnet, and cidofovir. Prophylactic and curative antiviral treatments administered during prolonged periods among patients with altered T-cell immunity may lead to the emergence of HSV resistance to antivirals, contributing to a challenging therapeutic management of viral infection. The persistence of herpetic lesions after 10 days of well-conducted antiviral therapy is suggestive of viral resistance. Resistance to antivirals can be detected using genotypic methods (identifications of antiviral resistance-associated mutations by sequencing genes encoding viral proteins involved in the mechanism of action of antivirals) or phenotypic methods (measure of antiviral drug concentration inhibiting 50% of viral replication in cell culture). The prevalence of HSV resistance to acyclovir is below 1% in immunocompetent individuals, except those with herpetic keratitis for whom prevalence can reach 7%, and varies from 3.5% to 11% in immunocompromised patients. Adverse effects and the absence of eradication of viral latent infection constitute other limits to the use of antiviral drugs. New antiviral compounds undergoing clinical trials and novel potential viral targets seem very promising to enlarge the panel of efficient compounds to treat HSV infections.

Topics: Acyclovir; Antiviral Agents; Foscarnet; Herpes Simplex; Humans; Simplexvirus

Herpes simplex viruses (HSV) are neurotropic and known to cause central nervous system (CNS) infections. We aimed to describe the clinical and imaging features of cerebrovascular complications in patients with HSV CNS infections.. We reviewed records of patients with HSV infections by querying acyclovir use in a clinical registry of parenteral anti-infective therapy at a tertiary medical center from January 2010 until September 2018. One patient who met the inclusion criteria is subsequently added. Diagnostic criteria for HSV CNS infection were intrathecal presence of viral DNA with clinical signs of CNS involvement.. Of 36 patients who met the criteria for HSV CNS infections, cerebrovascular complications occurred in 6 patients (17%). Two patients with HSV-1 encephalitis had cerebrovascular complications (1 ischemic stroke, 1 intraparenchymal hemorrhage). Four patients had HSV-2 infection without encephalitis had cerebrovascular complications (3 ischemic strokes, 1 cerebral vein thrombosis). All 3 patients with ischemic strokes without encephalitis had pattern of vasculitis on vessel imaging on MRI with segmental narrowing and vessel wall irregularities of large intracranial arteries with circumferential wall enhancement.. Cerebrovascular complications of HSV can occur with encephalitis or as isolated events with vasculitis.

Topics: Acyclovir; Central Nervous System; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

Topics: Acyclovir; Adult; Antiviral Agents; Female; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunoglobulin G; Laparoscopy; Valacyclovir

Acyclovir is the drug of choice for the treatment of herpes simplex virus (HSV) infections. Acyclovir-resistant HSV strains may emerge, especially during long-term drug use, and subsequently cause difficult-to-treat exacerbations. Previously, we set up a novel treatment approach, based on enzymatically synthesized pools of siRNAs, or siRNA swarms. These swarms can cover kilobases-long target sequences, reducing the likelihood of resistance to treatment. Swarms targeting the

Topics: Acyclovir; Animals; Chlorocebus aethiops; DNA-Binding Proteins; Dose-Response Relationship, Drug; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Inhibitory Concentration 50; RNA Interference; RNA, Small Interfering; Vero Cells; Viral Proteins

Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1 alerts for the urgency in developing new antivirals with other therapeutic targets. Thus, this study evaluated a series of 1,4-disubstituted-1,2,3-triazole derivatives against HSV-1 acute infection and provided deeper insights into the possible mechanisms of action.. Human fibroblast cells (HFL-1) were infected with HSV-1 17syn+ and treated with the triazole compounds at 50 μM for 24 h. The 50% effective drug concentration (EC. Compounds 3 ((E)-4-methyl-N'-(2-(4-(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylenebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde) were the most promising, with an EC. Our findings demonstrated that these compounds are promising antiviral candidates with different mechanisms of action from acyclovir and further studies are merited.

Topics: Acyclovir; Adult; Antiviral Agents; DNA Replication; DNA, Viral; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Triazoles; Virus Replication

Herpes simplex virus (HSV) is rarely the cause of pneumonia in immunocompetent patients. We describe a previously healthy child, with no evidence of an immunodeficiency, who presented to the emergency department with severe pneumonia, wheezing, and pleural effusions with a history of orolabial HSV infection. On admission, he was started on antibiotics and systemic corticosteroids but continued to deteriorate. Oral lesions, blood, and pleural fluid tested positive for HSV, and improvement was achieved only after the addition of acyclovir and discontinuation of steroids. We suggest that steroids should be used with caution in patients presenting with lower respiratory tract symptoms and herpetic oral lesions.

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Child; Herpes Simplex; Humans; Male; Pneumonia, Viral; Respiratory Sounds; Simplexvirus

To investigate the clinical characteristics and visual outcome of bilateral acute retinal necrosis.. The study included 30 patients (60 eyes) who were diagnosed with bilateral acute retinal necrosis. The medical records were reviewed.. Twenty-five patients developed the disease in the contralateral eye within 5 months and 5 patients at >2 years after the initial onset. At presentation, 14 of 21 eyes suffered from retinal necrosis of more than 180° in the initially affected eye, whereas 3 of 22 eyes suffered it in the later-affected eye. Retinal detachment occurred in 23 of the 27 initially affected eyes and in 5 of the 27 later-affected eyes. The mean logarithm of the minimum angle of resolution best-corrected visual acuity decreased from 2.0 ± 1.1 (Snellen equivalent counting fingers) to 2.2 ± 1.0 (Snellen equivalent counting fingers) in the initially affected eyes after a follow-up of 34.1 ± 48.2 months (P = 0.529), and improved from 0.5 ± 0.4 (Snellen equivalent 20/66) to 0.3 ± 0.4 (Snellen equivalent 20/40) in the later-affected eyes after a follow-up of 21.2 ± 23.3 months (P = 0.005).. Bilateral acute retinal necrosis usually occurs in the contralateral eye within a few months, but sometimes after several years. Inflammation and retinal necrosis are less severe in the later-affected eye, with less retinal detachment and a better visual outcome.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Eye Infections, Viral; Female; Ganciclovir; Herpes Simplex; Herpes Zoster Ophthalmicus; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Male; Middle Aged; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Visual Acuity; Vitrectomy; Young Adult

A series of tricyclic penciclovir (PCV) and hydroxybutylguanine (HBG) derivatives have been prepared with enhanced lipophilicity following an efficient synthetic route. All the novel tricyclic derivatives were evaluated for inhibitory activity against herpes simplex virus 1 and 2 (HSV-1, HSV-2) and thymidine kinase deficient (ACV resistant) HSV-1. The tricyclic HBG derivatives were devoid of inhibitory activity however several of the tricyclic PCV derivatives showed promising antiviral activity, in particular 9g (R = 4-MeO-C

Topics: Acyclovir; Antiviral Agents; Guanine; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Models, Molecular

Herpes simplex virus (HSV) infection in infants is a devastating disease with an often subtle presentation. We examined cerebrospinal fluid (CSF) HSV PCR (polymerase chain reaction) testing and empiric acyclovir therapy in young febrile infants. Chart review identified hospitalized infants aged ≤60 days with fever ≥38°C who had undergone lumbar puncture. Previously published criteria were used to define patients at high risk for HSV. Primary outcomes were CSF HSV PCR testing and empiric acyclovir therapy. Of 536 febrile infants, 23% had HSV testing; empiric acyclovir was started in 15%. HSV testing and therapy were associated with younger age, seizure, maternal vaginal lesions, postnatal HSV contact, vesicles, poor tone, CSF pleocytosis, and enteroviral testing. Sixty-two percent of high-risk infants did not undergo HSV testing, and 75% did not receive acyclovir. High-risk infants were untested and untreated at relatively high rates. Evidence-based criteria to guide HSV testing and treatment are needed.

Topics: Acyclovir; Antiviral Agents; Female; Fever; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Polymerase Chain Reaction; Spinal Puncture; Treatment Outcome

Acyclovir use is limited by a high frequency of administration of five times a day and low bioavailability. This leads to poor patient compliance.. To overcome the problem of frequent dosing, we used nanotechnology platform to evaluate the proof of concept of substituting multiple daily doses of acyclovir with a single dose.. Acyclovir was formulated as solid lipid nanoparticles (SLN). The nanoparticles were characterized for particle size, surface charge and morphology and in vitro drug release. The pharmacokinetic and pharmacodynamic of SLN acyclovir were compared with conventional acyclovir in a mouse model.. SLN showed drug loading of 90.22% with 67.44% encapsulation efficiency. Particle size was found to be of 131 ± 41.41 nm. In vitro drug release showed 100% release in SIF in 7 days. AUC0-∞ (119.43 ± 28.74 μg/ml h), AUMC0-∞ (14469 ± 4261.16 μg/ml h) and MRT (120.10 ± 9.21 h) were significantly higher for ACV SLN as compared to ACV AUC0-∞ (12.22 ± 2.47 μg/ml h), AUMC0-∞ (28.78 ± 30.16 μg/ml h) and MRT (2.07 ± 1.77 h), respectively (p<0.05). In mouse model, a single dose of ACV SLN was found to be equivalent to ACV administered as 400mg TID for 5 days in respect to lesion score and time of healing.. The proof of concept of sustained-release acyclovir enabling administration as a single dose was thus demonstrated.

Topics: Acyclovir; Animals; Antiviral Agents; Biological Availability; Cell Survival; Disease Models, Animal; Drug Liberation; Female; Haplorhini; Herpes Simplex; Humans; Lecithins; Male; Mice; Mice, Inbred BALB C; Phospholipids; Polysorbates

Herpes simplex (HS) is an opportunistic infection, primarily in immunocompromised patients, caused by herpes simplex virus. Oral and genital mucosa are the most commonly involved sites; it is rare for HSV to invade the esophagus and cause esophagitis, especially in immunocompetent patients. Here, we present a case where an immunocompetent patient presented with HS esophagitis, which had evolved into esophageal ulcers. He was successfully treated with acyclovir. Subsequently, we did a comprehensive literature search and tabulated all the possible complications and management plans of previously reported cases of HS in immunocompetent patients.

Topics: Acyclovir; Antiviral Agents; Esophagitis; Herpes Simplex; Humans; Male

The incidence of neonatal herpes simplex virus (nHSV) infections is monitored periodically in the Netherlands, yet management and outcome is unknown. Comprehensive national guidelines are lacking. We aim to describe management and outcome in the last decade to explore current diagnostic and therapeutic challenges. We aim to identify possible variability in management of patients with a suspected nHSV infection.. We conducted a retrospective case series of management and outcome of nHSV infections at 2 tertiary care center locations in the Netherlands.. An nHSV infection was diagnosed in 1% (12 of 1348) of patients in whom polymerase chain reaction for HSV was performed. Of the patients with nHSV infection, 3 of 12 died, and 4 of 9 (44%) survivors suffered neurologic sequelae. Neurologic symptoms at presentation were seen in only 2 of 8 patients with nHSV encephalitis. A cerebral spinal fluid analysis was performed in 3 of 6 patients presenting with skin lesions. Only 3 of 6 patients with neurologic symptoms received suppressive therapy. nHSV infection was diagnosed in 8 of 189 (4%) patients who were empirically treated.. Management of nHSV infection, particularly when presented with skin lesions, is inconsistent. Many infants without a HSV infection are exposed to antiviral medication. There is substantial interhospital variation in diagnostic and therapeutic management of a suspected infection. Comprehensive guidelines need to be developed to standardize management of suspected nHSV infection.

Topics: Acyclovir; Antiviral Agents; Disease Management; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Netherlands; Polymerase Chain Reaction; Practice Patterns, Physicians'

Topics: Acute Disease; Acyclovir; Administration, Intravenous; Female; Fever; Herpes Simplex; Herpesvirus 2, Human; Humans; Pharyngitis; Young Adult

Recurrent lymphocytic meningitis or Mollaret's meningitis is a rare condition caused by a number of infectious, autoimmune, toxic and neoplastic diseases. Herpes simplex type 2 is the most commonly isolated agent. It usually compromises middle aged women, with a self-limited clinical presentation that resolves within a week leaving no sequelae. Its diagnosis is mainly based on nucleic acid detection on cerebrospinal fluid. Antiviral prophylaxis has not shown conclusive to avoid recurrences.. La meningitis linfocítica recurrente o meningitis de Mollaret es una entidad asociada a un gran número de etiologías infecciosas, autoinmunes, toxicológicas y neoplásicas. En la actualidad el virus herpes simple tipo 2 (HSV-2) es el agente más frecuentemente aislado. Afecta frecuentemente a mujeres de mediana edad y tiende a autolimitarse sin secuelas dentro de la primera semana de inicio de síntomas. El diagnóstico se basa en la detección de ácidos nucleicos virales en el líquido cefalorraquídeo. Al momento no se ha demostrado beneficio en el uso de tratamiento antiviral en la prevención de recurrencias.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Meningitis, Viral; Middle Aged; Polymerase Chain Reaction; Recurrence

Fractional photothermolysis was initially introduced by Manstein in 2004 .Fractional CO2 laser technology introduced has allowed physicians to obtain good cosmetic results with a lower rate of complications than non-fractionated ablative laser treatment. However, adverse effects may still occur.Reported cases of HSV infection after fractional photothermolysis are rare. A 48-year-old woman with Fitzpatrick skin type III presented with a scar in her perioral area desiring esthetic improvement of her burn scar. She didn't have a history of recurrent herpes simplex virus (HSV) infection periorally. A fractionated resurfacing laser Quadralase (Candela) was used to treat her perioral burn scar. Two sessions were performed with a month interval. Five days after the second session of laser therapy even after she took antiviral prophylaxis based on valacyclovir 500mg twice daily 24 hours before the laser session and 3 days after, she presented with a rash on the perioral area preceded by pain. Correlation of the history and the clinical presentation was consistent with HSV reactivation. Treatment was initiated with acyclovir 10mg/kg/8h administered intravenously for 10 days with a clearing of her vesicular eruption. Fractional CO2 laser is a very safe procedure when used with accepted parameters. Early recognition, close monitoring and careful wound care will prevent long term sequelae when complications occur.

Topics: Acyclovir; Administration, Intravenous; Antibiotic Prophylaxis; Antiviral Agents; Burns; Cicatrix; Dose Fractionation, Radiation; Female; Follow-Up Studies; Herpes Simplex; Humans; Lasers, Gas; Low-Level Light Therapy; Middle Aged; Mouth; Simplexvirus; Treatment Outcome; Virus Activation

Resistant herpes simplex virus type 1 (HSV-1) infection is sometimes fatal for immunocompromised patients. Here, we report 10-year-old girl receiving hematopoietic stem cell transplantation developed refractory HSV-1 infection, which was persisted to intermittent acyclovir (ACV) or foscarnet (FOS) administrations but was improved by continuous ACV administration. The isolates from the lesion were identified with low susceptibilities to ACV and FOS by plaque reduction assay due to DNA pol gene mutation. Continuous ACV administration overcomes the efficacy of intermittent administration and could be the best option to treat severe HSV-1 infectious patients.

Topics: Acyclovir; Antiviral Agents; Child; Drug Resistance, Viral; Female; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Humans; Infusions, Intravenous; Leukemia, Monocytic, Acute; Lip; Mutation

Topics: Acyclovir; Aged; Antiviral Agents; Esomeprazole; Esophagitis; Esophagus; Female; Gastroscopy; Herpes Simplex; Humans; Severity of Illness Index; Treatment Outcome

Topics: Acyclovir; Aged; Antiviral Agents; Biopsy; Candidiasis; Diagnosis, Differential; Esophagitis; Esophagoscopy; Herpes Simplex; Humans; Inclusion Bodies, Viral; Male

Herpes simplex virus (HSV) infections can cause considerable morbidity. Currently, nucleoside analogues such as acyclovir are widely used for treatment. However, HSV infections resistant to these drugs are a clinical problem among immunocompromised patients. To provide more efficient therapy and to counteract resistance, a different class of antiviral compounds has been developed. Pritelivir, a helicase primase inhibitor, represents a promising candidate for improved therapy. Here, we established an HSV-1 infection model on microneedle-pretreated human skin ex vivo. We identified HSV-1-specific histological changes (e.g., cytopathic effects, multinucleated giant cells), down-regulation of nectin-1, nuclear translocation of NF-κB (p65), interferon regulatory factor 3 (IRF3), and signaling of the IFN-inducible protein MxA. Accordingly, this model was used to test the potency of pritelivir compared with the standard drug acyclovir. We discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Biopsy, Needle; Case-Control Studies; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunohistochemistry; In Vitro Techniques; Male; Middle Aged; Models, Biological; Pyridines; Reference Values; Statistics, Nonparametric; Sulfonamides; Thiazoles; Virus Replication; Young Adult

The unexpected transmission of donor-derived infection through organ transplantation is a rare event with current donor screening practices. In this case report we describe a probable donor-derived transmission of Herpes Simplex Virus (HSV)-2 via deceased donor kidney transplantation resulting in HSV hepatitis in the recipient. This manifested as acute liver failure which resolved with appropriate anti-viral therapy. Following recovery from the acute liver insult, the patient developed fibrotic liver morphology and portal hypertension, an unusual departure from the typical course.

Topics: Acyclovir; Adult; Allografts; Antiviral Agents; Biopsy; Female; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 2, Human; Humans; Hypertension, Portal; Kidney; Kidney Transplantation; Liver; Liver Cirrhosis; Liver Failure, Acute; Treatment Outcome

Infections due to drug-resistant herpes simplex viruses (HSV) represent an important clinical concern, especially in immunocompromised patients. The present study was aimed at detecting acyclovir (ACV) susceptibility in HSV clinical samples.. A total of 13 HSV-positive clinical samples (5 HSV-1 and 8 HSV-2) recovered from patients (1 immunocompromised and 12 of unknown immune status) were included in the study. The genotypic analysis involved an initial UL23 (thymidine kinase) gene sequencing, followed by a confirmatory phenotypic assay using plaque reduction technique.. Two novel amino acid changes, A37V and H283N, were detected in HSV-1 positive clinical samples, which were found to be susceptible to acyclovir (half maximal effective concentration = 1.5 µM) by plaque reduction assay.. These two novel amino acid changes could be therefore considered as natural polymorphisms, a phenomenon widely associated with the HSV-UL23 gene.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Viral; Female; Genes, Viral; Genotype; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Microbial Sensitivity Tests; Mutation; Phenotype; Retrospective Studies; Sequence Analysis, DNA; Young Adult

Albumin is a highly successful tool of drug delivery providing drastically extended body and blood residence time for the associated cargo, but it only traffics single drug copies at a time. In turn, macromolecular prodrugs (MP) are advantaged in carrying a high drug payload but offering only a modest extension of residence time to the conjugated drugs. In this work, we engineer MP to contain terminal groups that bind to albumin via non-covalent association and reveal that this facile measure affords a significant protraction for the associated polymers. This methodology is applied to MP of acyclovir, a successful drug against herpes simplex virus infection but with poor pharmacokinetics. Resulting albumin-affine MP were efficacious agents against herpes simplex virus type 2 (HSV-2) both in vitro and in vivo. In the latter case, sub-cutaneous administration of MP resulted in local (vaginal) antiviral effects and a systemic protection. Presented benefits of non-covalent association with albumin are readily transferrable to a wide variety of MP in development for drug delivery as anticancer, anti-inflammatory, and anti-viral measures.

Topics: Acyclovir; Albumins; Animals; Antiviral Agents; Female; HeLa Cells; Herpes Simplex; Herpesvirus 2, Human; Humans; Injections, Subcutaneous; Mice, Inbred BALB C; Phosphatidylglycerols; Polyethylene Glycols; Polymethacrylic Acids; Prodrugs; Vaginal Douching

Laryngopharyngeal herpes simplex virus infection is rare and presents typically in the supraglottis. Findings on presentation can range from small mucosal lesions to fungating obstructive masses mimicking neoplasm. Laryngopharyngeal herpes is a medically treated disease.. Identify potential treatment in cases that are refractory to antiviral medications.. Individual case with treatment adapted from other case report.. We report a case of bulky, obstructive supraglottic and glottic herpes virus laryngitis that presented with dysphonia, dysphagia, and airway complaints resistant to acyclovir analogues that was treated effectively with intralesional cidofovir injection.. Our promising initial response suggests a potential novel treatment for this unusual condition.

Topics: Acyclovir; Antiviral Agents; Cidofovir; Herpes Simplex; Humans; Injections, Intralesional; Laryngitis; Male; Middle Aged

Herpes simplex virus (HSV) has various presentations, depending on the patient's immune status, age, and the route of transmission. In adults, HSV type 1 is found predominantly in the oral area, and HSV type 2 (HSV-2) is commonly found in the genital area. HSV-2 infection without genital lesions is uncommon. Herein we report a unique case of pharyngotonsillitis as an initial manifestation of disseminated HSV-2 infection without genital involvement.. A 46-year-old male was admitted to our hospital with a 1-week history of fever and sore throat. His past medical history included hypereosinophilic syndrome diagnosed at age 45 years. Physical examination revealed throat congestion, bilaterally enlarged tonsils with exudates, tender cervical lymphadenopathy in the left posterior triangle, and mild epigastric tenderness. The laboratory data demonstrated bicytopenia, elevated liver enzyme levels, and hyperferritinemia. A bone marrow smear showed hypocellular marrow with histiocytes and hemophagocytosis. The diagnosis of HLH was confirmed, and the patient was treated with methylprednisolone pulse therapy on days 1-3. On day 5, despite initial improvement of the fever and sore throat, multiple, new, small bullae developed on the patient's face, trunk, and extremities. Additional testing showed that he was positive for HSV-specific immunoglobulin M and immunoglobulin G. Disseminated HSV infection was suspected, and intravenous acyclovir (10 mg/kg every 8 h) was begun. A subsequent direct antigen test of a bulla sample was positive for HSV-2. Moreover, tonsillar and esophageal biopsies revealed viral inclusion bodies. Immunohistochemical staining and a quantitative real-time polymerase chain reaction (PCR) assay confirmed the presence of HSV-2. Disseminated HSV-2 infection with multiple bullae, tonsillitis, esophagitis, and suspected hepatic involvement was diagnosed. After a 2-week course of intravenous acyclovir, his hematological status and liver function normalized, and his cutaneous skin lesions resolved. He was discharged on day 22 in good general health and continued taking oral valacyclovir for viral suppression due to his immunosuppressed status.. Disseminated HSV-2 infection should be considered as one of the differential diagnoses in patients with pharyngotonsillitis and impaired liver function of unknown etiology even if there are no genital lesions.

Topics: Acyclovir; Esophagitis; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunocompromised Host; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Pharyngitis; Tonsillitis; Urogenital System

The aim of the study was the evaluation of the several immunological indices in HIV/AIDS-infected patients with viral skin lesions. 38 HIV/AIDS patients 18-53 years of age (20 men and 18 women) with skin pathology have been enrolled in the study. The skin pathology included 20 cases with recurrent herpes simplex and 18 with chronic ulcerative herpes simplex virus infections. There were 25 patients with HIV infection stage 2, and 13 with stage 3. Immunological studies were carried out before the treatment and 2 months after it. Together with ART, the treatment in cases of chronic ulcerative herpes and recurrent herpes simplex included acyclovir, 400 mg 5 times a day, and Cidipol solution externally. Group 1 received ART according to the standard antiviral therapy protocol, Group 2 received ART, antiviral medicines and Cidipol solution externally. The study showed that after 2 months of the complex therapy with Cidipol, patients from the treatment group demonstrated a reliable increase in the count of CD3+, CD16+ and CD56+ cells and phagocytic activity of neutrophils. There was also a significant decrease (approaching to the normal values) of the levels of immune globulins and heterophil haemolysins. The present study of the immune responses in the cases of skin viral lesions in HIV/AIDS-infected patients contributes to the better understanding of the cellular and cytokine responses, thereby enabling us to increase the efficacy of the therapy and prevention of viral dermatoses in immunocompromised patients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Female; Herpes Simplex; HIV; HIV Infections; Humans; Male; Middle Aged; Skin Diseases, Viral; Young Adult

Childbearing women with primary or secondary Herpes Simplex Virus type 1 infection are at risk of transmitting neonatal herpes infection to their infants; a medical emergency that is associated with high mortality and morbidity. Neonatal herpes infection has been commonly associated with Herpes Simplex Virus type 2, or genital herpes, but can be caused by either subtype and the presentations are indistinguishable. This case describes the course of diagnosis, treatment, and recovery for a mother and infant during a severe maternal and neonatal herpes infection, and how lactation was maintained and breastfeeding re-established. Our children's hospital coordinated its efforts to assist and monitor this breastfeeding family, and they were able to resume breastfeeding soon after discharge. It is our opinion that it is imperative that mothers receive evidence-based lactation care to maintain their breastfeeding relationship during extended hospital stays.. An acutely ill infant was admitted to our urban children's hospital with severe neonatal herpes infection for a total of 3 weeks. His mother was severely affected on her breasts and she required a brief hospitalization. The mother's breasts were covered with draining herpetic lesions that required daily dressing changes. However, her lesions were slow to heal, and a wound care consultation was facilitated and her treatment plan was adjusted. We were surprised that she experienced minimal discomfort with pumping and dressing changes. The mother maintained a positive outlook, complied with the plan to express frequently to maintain milk production, and was able to breastfeed again when they both recovered.. This mother received immediate support and appropriate pumping equipment from our hospital personnel and was subsequently able to establish and maintain her milk supply. The difficulty in this case was the management of the mother's extensive herpetic wounds that were slow to heal. A certified wound care specialist was required. Both mother and child recovered from their infections and were able to restart breastfeeding; eventually reaching their goal of breastfeeding for 2 years.. Neonatal herpes infection is a potentially fatal disease and maternal child health professionals should have a high suspicion for any ill-appearing newborn with or without a rash. When a breastfeeding infant and mother become infected with Herpes Simplex Virus type 1, it is the responsibility of the healthcare institution to support lactation and the return to breastfeeding rather than recommend cessation of lactation, which is rarely necessary. A multi-disciplinary evidence-based approach to lactation care is essential to preserve lactation during infant hospitalization.

Topics: Acyclovir; Antiviral Agents; Breast Feeding; Diagnosis, Differential; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Male; Perinatal Care; Pregnancy; Pregnancy Complications, Infectious

Herpetic whitlow of the toe is a common infection in an uncommon location, leading it to be frequently misdiagnosed; however, as the virus responds well to conservative management or antivirals alone, proper identification is necessary to prevent unnecessary interventions. We present a case of herpetic whitlow of the toe with an unusually ominous appearance in a previously healthy and otherwise well-appearing child. This case illustrates the spectrum of herpetic whitlow's clinical presentations and enourages consideration of the disease even for atypical location and severity.

Topics: Acyclovir; Antiviral Agents; Cellulitis; Child, Preschool; Foot Dermatoses; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Toes

Topics: Acyclovir; Animals; Bacterial Proteins; Carrier Proteins; Cell Line; Chlorocebus aethiops; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Male; Mice; Mice, Inbred BALB C; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Vero Cells

Darier disease (DD), also known as keratosis follicularis or Darier-White disease, is a rare autosomal dominant genodermatosis that presents as hyperkeratotic, warty papules affecting the seborrheic and intertriginous areas. Patients with DD are at risk of secondary infections including the rare complication of Kaposi varicelliform eruption (KVE), a widespread viral infection most commonly caused by herpes simplex virus (HSV). Darier disease with secondary KVE can lead to widespread systemic infection and death. This case report discusses an individual with DD who subsequently developed KVE due to disseminated HSV type 2 infection.

Topics: Acyclovir; Antiviral Agents; Darier Disease; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Kaposi Varicelliform Eruption; Male; Middle Aged

Viruses commandeer host cell 26S proteasome activity to promote viral entry, gene expression, replication, assembly, and egress. Proteasomal degradation activity is critical for herpes simplex virus (HSV) infection. The proteasome inhibitor bortezomib (also known as Velcade and PS-341) is a clinically effective antineoplastic drug that is FDA approved for treatment of hematologic malignancies such as multiple myeloma and mantle cell lymphoma. Low nanomolar concentrations of bortezomib inhibited infection by HSV-1, HSV-2, and acyclovir-resistant strains. Inhibition coincided with minimal cytotoxicity. Bortezomib did not affect attachment of HSV to cells or inactivate the virus directly. Bortezomib acted early in HSV infection by perturbing two distinct proteasome-dependent steps that occur within the initial hours of infection: the transport of incoming viral nucleocapsids to the nucleus and the virus-induced disruption of host nuclear domain 10 (ND10) structures. The combination of bortezomib with acyclovir demonstrated synergistic inhibitory effects on HSV infection. Thus, bortezomib is a novel potential therapeutic for HSV with a defined mechanism of action.

Topics: Acyclovir; Animals; Antiviral Agents; Bortezomib; Cell Nucleus; Chlorocebus aethiops; Drug Synergism; Fibroblasts; Foreskin; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Nucleocapsid; Proteasome Inhibitors; Vero Cells; Virus Internalization

Infections caused by herpes simplex viruses (HSV) are frequent in the human population. Because of the widespread use of long-term treatment or prophylaxis by anti-herpetic antivirals in various specific medical contexts (immunosuppression, recurrent infections), the level of antiviral resistance is increasing. According to previous studies, there is a low resistance level in immunocompetent populations but a relatively high level in populations with immunodeficiency. However, there has been no study from the Czech Republic. This study presents results of a single-centre retrospective study from the Czech Republic.. Deep frozen DNA from patients with suspected clinical antiviral failure over a long time period (2009-2016) - a total of 15 isolates of HSV1 and seven of HSV2 - were examined for the presence of mutations associated with antiviral resistance. Sequence analysis was performed using an ABI PRISM 3500xL Genetic Analyzer (Applied Biosystems®).. There were no mutations associated with resistance to antivirals inside the UL23 gene in HSV1 isolates. However, resistant mutation D672N (nucleotide change G2014A) was found inside the UL30 gene in seven of the isolates. One mutation associated with resistance to acyclovir (M183stop) was found inside the UL23 gene in one HSV2 isolate. Resistant mutation E678G (nucleotide change A2033G) was identified inside the UL30 gene in six of the HSV2 isolates.. This study confirmed the presence of resistance mutations within the Czech population, but it will be necessary to examine a higher number of isolates for further conclusions.

Topics: Acyclovir; Antiviral Agents; Czech Republic; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Exodeoxyribonucleases; Herpes Simplex; Humans; Microbial Sensitivity Tests; Mutation; Retrospective Studies; Simplexvirus; Treatment Failure; Viral Proteins

Clinical diagnosis of Herpes simplex-infected pemphigus erosions is challenging. Pemphigus and Herpes simplex both produce superficial erosions on the skin and mucosa after rupture of vesicles or bullae. Delay in diagnosis of herpes-infected pemphigus patients often causes prolonged morbidity. So far, there has been a paucity of literature describing the characteristic features of Herpes simplex-infected pemphigus erosions. In the present case series, we have illustrated the morphologic features of three Herpes simplex-infected pemphigus erosions and also have suggested characteristic clinical features that were consistently present in all cases.

Topics: Acyclovir; Adult; Antiviral Agents; Disease Progression; Female; Herpes Simplex; Humans; Male; Middle Aged; Pemphigus

Topics: Acyclovir; Anti-Infective Agents, Local; Antiviral Agents; Female; Fusidic Acid; Herpes Simplex; Humans; Lip Diseases; Middle Aged; Skin Cream

Topics: Acyclovir; Diagnosis, Differential; Dyspnea; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Laryngitis; Laryngostenosis; Larynx; Male; Middle Aged; Multiple Myeloma; Tracheotomy; Treatment Outcome; Valacyclovir

Neonatal herpes simplex virus (HSV) infections are associated with high mortality and long-term morbidity. However, incidence is low and acyclovir, the treatment of choice, carries risk of toxicity. We aimed to increase the percentage of patients 0 to 60 days of age who are tested and treated for HSV in accordance with local guideline recommendations from 40% to 80%.. This quality improvement project took place at 1 freestanding children's hospital. Multiple plan-do-study-act cycles were focused on interventions aimed at key drivers including provider buy-in, guideline availability, and accurate identification of high-risk patients. A run chart was used to track the effect of interventions on the percentage managed per guideline recommendations over time by using established rules for determining special cause. Pre- and postimplementation acyclovir use was compared by using a χ. The median percentage of patients managed according to guideline recommendations increased from 40% to 80% within 8 months. Acyclovir use decreased from 26% to 7.9% (. Point-of-care availability of an evidence-based guideline and interventions targeted at provider engagement improved adherence to a new guideline for neonatal HSV management and decreased acyclovir use in non-high-risk infants. Further study is necessary to confirm the safety of these recommendations in other settings.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Male; Practice Guidelines as Topic; Pregnancy Complications, Infectious; Quality Improvement; Retrospective Studies

The synthesis of emimycin, 5-substituted emimycin analogues and the corresponding ribo- and 2'-deoxyribonucleoside derivatives is described. Emimycin, its 5-substituted congeners and the ribonucleoside derivatives are completely devoid of antiviral activity against RNA viruses. In contrast, some of the 2'-deoxyribosyl emimycin derivatives are potent inhibitors of the replication of herpes simplex virus-1 and varicella-zoster virus, lacking cytotoxicity.

Topics: Antiviral Agents; Cell Line; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Nucleosides; Pyrazines; Varicella Zoster Virus Infection; Virus Replication

The present study was aimed to develop and evaluate a microemulsion-based dermal drug delivery of an antiviral agent, acyclovir. A water-in-oil microemulsion was prepared using isopropyl myristate, Tween 20, Span 20, water and dimethylsulphoxide. It was characterized for drug content, stability, globule size, pH, viscosity and ex vivo permeation through mice skin. In vivo antiviral efficacy of optimized formulation was assessed in female Balb/c mice against herpes simplex virus-I (HSV-I)-induced infection. It was observed that optimized formulation when applied 24-h post-infection could completely inhibit the development of cutaneous herpetic lesions vis-à-vis marketed cream.

Topics: Acyclovir; Animals; Disease Models, Animal; Drug Carriers; Drug Compounding; Emulsions; Female; Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Inbred BALB C; Oils; Permeability; Skin; Solubility; Thermodynamics; Water

We compared the clinical course of neonates with persistence of herpes simplex virus (HSV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF) after 21 days of treatment with high-dose acyclovir to that of neonates with clearance of the CSF after 21 days of therapy. Neonates with persistence of HSV DNA had a more severe clinical course with worse neurodevelopmental outcomes.

Topics: Acyclovir; Antiviral Agents; Biomarkers; Central Nervous System Infections; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Retrospective Studies; Treatment Outcome

Topics: Acyclovir; Administration, Intravenous; Administration, Oral; Antiviral Agents; Fingers; Foscarnet; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Male; Middle Aged

Herpes simplex virus, type 1 (HSV-1) infects over 3.4 billion people, world-wide. Though it can cause encephalitis, in the vast majority it is asymptomatic, with lifelong latent infection in neurons. HSV-1 infected individuals have greater cognitive dysfunction than uninfected individuals, particularly persons with schizophrenia - even without encephalitis. We investigated whether HSV-1 related cognitive dysfunction is progressive or remediable.. In a prospective naturalistic follow up sample (PNFU), temporal changes in cognitive functions were analyzed in relation to baseline HSV-1 infection in persons with/without schizophrenia (N=226). Independently, in a randomized controlled trial (RCT), HSV-1 infected, clinically stabilized SZ outpatients received Valacyclovir (VAL, an HSV-1 specific antiviral, 1.5G twice daily for 16weeks) or placebo (PLA) added to standard antipsychotic treatment, using a stratified randomization design, following placebo run-in (N=67). In both samples, HSV-1 infection (seropositivity) was estimated using serum IgG antibodies. Clinical evaluations were blinded to HSV-1 or treatment status. Standardized Z scores for accuracy on eight cognitive domains were analyzed for temporal trajectories using generalized linear models (PNFU) and VAL/PLA differences compared with intent to treat analyses (RCT).. PNFU: At baseline, HSV-1 infected participants had significantly lower accuracy scores for Emotion Identification and Discrimination (EMOD), Spatial memory and Spatial ability, regardless of SZ diagnosis (p=0.025, 0.029, 0.046, respectively). They also had significantly steeper temporal worsening for EMOD (p=0.03). RCT: EMOD improved in VAL-treated patients (p=0.048, Cohen's d=0.43).. A proportion of age related decline in EMOD is attributable to HSV-1 infection.

Topics: Acyclovir; Adolescent; Adult; Antipsychotic Agents; Antiviral Agents; Cognition Disorders; Emotions; Female; Follow-Up Studies; Herpes Simplex; Humans; Male; Middle Aged; Neuropsychological Tests; Randomized Controlled Trials as Topic; Severity of Illness Index; Valacyclovir; Valine; Young Adult

Topics: Acyclovir; Animals; Antiviral Agents; Circadian Clocks; Disease Models, Animal; DNA-Binding Proteins; Dose-Response Relationship, Drug; Female; Herpes Simplex; Herpesvirus 2, Human; Host Microbial Interactions; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Nectins; Severity of Illness Index; Skin; Survival Rate; Treatment Outcome

Ion Torrent next-generation sequencing (NGS) technology was applied to study the mode of emergence of acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) in patients with hematopoietic stem cell transplantation (HSCT) by quantitatively detecting mutations in the viral thymidine kinase (vTK) gene in the HSV-1 isolates recovered from HSCT patients. All of the mutations detected with the Sanger sequencing method in the vTK genes of HSV-1 isolates were also detected with the NGS assay. Furthermore, different mutations, which conferred ACV resistance and were not detected with the Sanger sequencing method, were also detected in a quantitative manner by using the NGS assay. The approach described here is applicable to studying the emergence process of vTK gene mutation-associated ACVr HSV-1 more in detail than the Sanger method. The NGS assay makes it possible to make a diagnosis of vTK gene mutation-associated ACVr HSV-1 infections at the early stage, which the ratio of ACVr HSV-1 is much lower than that of ACV-sensitive (ACVs) HSV-1.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Genotyping Techniques; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; High-Throughput Nucleotide Sequencing; Humans; Microbial Sensitivity Tests; Mutation; Thymidine Kinase

Genital herpes is an important cofactor for acquisition of human immunodeficiency virus (HIV) infection, and effective prophylaxis is a helpful strategy to halt both HIV and herpes simplex virus (HSV) transmission. The antiretroviral agent tenofovir, formulated as a vaginal microbicide gel, was shown to reduce the risk of HIV and HSV type 2 (HSV-2) acquisition.. HSV type 1 (HSV-1) and HSV-2 mutants were selected for resistance to tenofovir and PMEO-DAPy (6-phosphonylmethoxyethoxy-2,4-diaminopyrimidine, an acyclic nucleoside phosphonate with dual anti-HSV and anti-HIV activity) by stepwise dose escalation. Several plaque-purified viruses were characterized phenotypically (drug resistance profiling) and genotypically (sequencing of the viral DNA polymerase gene).. Tenofovir resistant and PMEO-DAPy-resistant viruses harbored specific amino acid substitutions associated with resistance not only to tenofovir and PMEO-DAPy but also to acyclovir and foscarnet. These amino acid changes (A719V, S724N, and L802F [HSV-1] and M789T and A724V [HSV-2]) were also found in clinical isolates recovered from patients refractory to acyclovir and/or foscarnet therapy or in laboratory-derived strains. A total of 10 (HSV-1) and 18 (HSV-2) well-characterized DNA polymerase mutants had decreased susceptibility to tenofovir and PMEO-DAPy.. Tenofovir and PMEO-DAPy target the HSV DNA polymerase, and clinical isolates with DNA polymerase mutations emerging under acyclovir and/or foscarnet therapy showed cross-resistance to tenofovir and PMEO-DAPy.

Topics: Acyclovir; Amino Acid Substitution; Antiviral Agents; Cells, Cultured; DNA Mutational Analysis; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Exodeoxyribonucleases; Foscarnet; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Mutation, Missense; Organophosphonates; Pyrimidines; Reverse Transcriptase Inhibitors; Selection, Genetic; Sequence Analysis, DNA; Tenofovir; Viral Proteins

Herpes simplex virus (HSV) infection represents significant morbidity and mortality in the neonatal period. Although clear guidelines exist on the evaluation and management of the otherwise well-appearing febrile neonate pertaining to occult serious bacterial infections, there is no standardized approach regarding when to initiate testing and treatment for HSV infection. It is vital we establish a unified guideline based on available clinical research to aid in our decision to evaluate and initiate therapy for this disease.. A PubMed search was performed using the keywords "neonate AND fever AND HSV" and "neonate AND fever AND acyclovir." The time period for the search was May 1982 to May 2016. Identified articles underwent further selection based on relevance to the clinical question. Selected articles then underwent detailed review and structured analysis.. Our search identified 93 articles, of which 18 were found to be relevant to our clinical question. Recommendations were then made based on thorough review and analysis of the selected articles.. Neonatal HSV infection carries significant morbidity and mortality if left untreated. High-quality clinical evidence on when to evaluate and treat for possible HSV infection is lacking. Based on available research, HSV infection in the febrile neonate should be strongly considered if age is < 21 days, or if presenting with concerning clinical features. If testing is performed, empiric treatment with high-dose acyclovir should be initiated. Additional research is needed to further clarify which cases mandate evaluation and treatment for HSV, and to better define treatment protocols.

Topics: Acyclovir; Antiviral Agents; Decision Making; Female; Fever; Guidelines as Topic; Herpes Simplex; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Simplexvirus

Chronic HSV infection is a cause of chronic perineal ulcerations. We report a case of a chronic and refractory HSV infection revealing chronic lymphoid leukaemia.. An 85-year-old woman with an 8-month history of chronic perineal ulcerations was referred to our dermatology department. She had no previous medical history of herpes infection. Skin biopsies ruled out carcinoma but were consistent with HSV infection. A local swab was positive for HSV2. Treatment with valaciclovir and intravenous acyclovir (ACV) at the recommended doses was ineffective. Laboratory tests revealed type-B chronic lymphoid leukaemia. Molecular biology studies confirmed the presence of ACV-resistant HSV via decreased thymidine kinase activity (stop codon: M183stop). Foscarnet was administered for a period of 3 weeks with almost complete healing of the ulcerations. Treatment was stopped prematurely due to acute renal insufficiency and the remaining lesions were treated using imiquimod cream. Valaciclovir was prescribed to prevent further episodes. The condition recurred a mere 11 months later.. The prevalence of ACV-resistant HSV is 0.32 % in immunocompetent patients and 3.5 % in immunocompromised patients. Insufficient dosing regimens or prolonged treatment with TK inhibitors result in the local selection of pre-existing mutant HSV viruses. Foscarnet, a DNA polymerase inhibitor, is the treatment of choice in HSV-resistant infections. ACV-resistant HSV is less virulent and replicates less, with reactivations being mainly due to wild-type HSV latent in the neural ganglia. Valaciclovir can be used as a preventive treatment. To our knowledge, this is the first case of ACV-resistant HSV infection revealing chronic lymphoid leukaemia.. Chronic perineal ulcerations can be the first manifestation of immunodeficiency seen for example with haematological diseases. In the event of clinical resistance of an HSV infection to recommended thymidine kinase inhibitor regimens, the use of foscarnet should be considered.

Topics: Acyclovir; Adjuvants, Immunologic; Administration, Cutaneous; Aged, 80 and over; Aminoquinolines; Antiviral Agents; Female; Foscarnet; Herpes Simplex; Humans; Imiquimod; Immunocompromised Host; Leukemia, Lymphocytic, Chronic, B-Cell; Perineum

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Viral; Herpes Simplex; Humans; Male; Penis

Topics: Acyclovir; Aged; Antiviral Agents; Coinfection; Cytomegalovirus Infections; Deglutition Disorders; Esophagitis; Esophagoscopy; Female; Ganciclovir; Herpes Simplex; Humans; Hypoalbuminemia; Immunocompetence; Pain; Parenteral Nutrition; Ulcer

Therapy or prophylaxis of herpes simplex virus type 2 (HSV-2) infections with the nucleoside analog aciclovir (ACV) can lead to the emergence of drug-resistant HSV-2 strains, particularly in immunocompromised patients. In this context, multiple amino acid (aa) changes can accumulate in the ACV-converting viral thymidine kinase (TK) which hampers sequence-based diagnostics significantly. In this study, the so far unknown or still doubted relevance of several individual aa changes for drug resistance in HSV-2 was clarified. For this purpose, ten recombinant fluorescent HSV-2 strains differing in the respective aa within their TK were constructed using the bacterial artificial chromosome (BAC) pHSV2(MS)Lox. Similar TK expression levels and similar replication behavior patterns were demonstrated for the mutants as compared to the unmodified BAC-derived HSV-2 strain. Subsequently, the resulting strains were tested for their susceptibility to ACV as well as penciclovir (PCV) in parallel to a modified cytopathic effect (CPE) inhibition assay and by determining the relative fluorescence intensity (quantified using units, RFU) as a measure for the viral replication capacity. While aa changes Y53N and R221H conferred ACV resistance with cross-resistance to PCV, the aa changes G25A, G39E, T131M, Y133F, G150D, A157T, R248W, and L342W maintained a susceptible phenotype against both antivirals. The CPE inhibition assay and the measurement of relative fluorescence intensity yielded comparable results for the phenotypic testing of recombinant viruses. The latter test showed some technical advantages. In conclusion, the significance of single aa changes in HSV-2 TK on ACV/PCV resistance was clarified by the construction and phenotypic testing of recombinant viral strains. This was facilitated by the fluorescence based method.

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Guanine; Herpes Simplex; Herpesvirus 2, Human; Humans; Mutation; Thymidine Kinase; Viral Proteins

To compare the visual outcomes of patients with acute retinal necrosis (ARN) treated initially with intravenous acyclovir vs oral valacyclovir therapy.. Retrospective, comparative, interventional case series.. Sixty-two patients (68 eyes) with ARN, treated at Moorfields Eye Hospital (United Kingdom) between 1992 and 2016, were identified through the hospital's electronic database. Exclusion criteria included insufficient patient records or follow-up (<150 days). Fifty-six patients had unilateral ARN, while 6 had bilateral ARN. Patients who received intravenous acyclovir on diagnosis (n = 33) were compared with patients treated with oral valacyclovir (n = 29) across outcomes including best-corrected visual acuity, retinal detachment, severe vision loss, and other complications. The impact of adjunctive intravitreal antiviral and prophylactic barrier laser treatment was also assessed.. Change in best-corrected visual acuity was not significantly different for eyes treated initially with intravenous therapy vs oral therapy over 5 years of follow-up data (P = .16). There was no difference in the rates of severe vision loss between the 2 groups (46% and 59%, respectively, P = .18), or of those eyes retaining good vision (28% vs 31%, respectively, P = .80). Retinal detachment occurred in 63% of cases and did not differ across treatment groups (62% vs 66%, respectively, P = .67). Barrier laser and intravitreal therapy had no effect on retinal detachment rate in either group.. Oral valacyclovir is clinically equivalent to intravenous therapy in the management of ARN. Oral valacyclovir as an outpatient therapy-with or without intravitreal foscarnet-can therefore be considered as an acceptable alternative to inpatient therapy required for intravenous treatment.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Eye Infections, Viral; Female; Herpes Simplex; Herpesvirus 3, Human; Humans; Infusions, Intravenous; Male; Middle Aged; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Retrospective Studies; RNA, Viral; Simplexvirus; Valacyclovir; Varicella Zoster Virus Infection; Visual Acuity

Acyclovir is commonly used to prevent and treat herpes simplex virus (HSV) reactivation after hematopoietic cell transplant (HCT), and only few reports have been published on acyclovir-resistant HSV in HCT recipients. We reviewed the medical records of patients with a microbiologic diagnosis of acyclovir-resistant HSV by plaque reduction test who received an HCT from 2002 through 2014. A total of 4 028 HCTs were performed during the study period, and 18 of the recipients met the diagnostic criteria for acyclovir-resistant HSV. All cases had undergone allogeneic HCTs. Most patients were in the pre-engraftment period or on systemic corticosteroid therapy for graft-versus-host disease (GVHD). The median time between diagnosis and susceptibility testing was 15 days, and antiviral therapy was changed at a median of 27 days. Patients required prolonged therapy (~80 days), and many had serious complications including renal failure and hospitalization. In conclusion, acyclovir-resistant HSV infection is more likely during the period of profound deficit in T-cell-mediated immunity and is associated with significant morbidities. Higher doses of acyclovir prophylaxis might be needed for patients with history of HSV during pre-engraftment or GVHD treatment. In patients who do not respond or progress after 1 week of acyclovir therapy, testing for drug-resistant HSV, and early switch to an alternative antiviral should be considered.

Topics: Acyclovir; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Antiviral Agents; Drug Resistance, Viral; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Male; Middle Aged; Retrospective Studies; Stem Cell Transplantation; Transplantation, Homologous; Treatment Outcome; Young Adult

Although muco-adhesive acyclovir 50mg tablets are only approved for the management of recurrent oro-labial HSV-1 infections, their ability to achieve extremely high concentrations in saliva and oral tissues suggests the potential for other uses. In this case, the agent was successfully utilized as a single tablet monotherapy leading to rapid clinical resolution of severe post-operative oro-labial infection.

J Drugs Dermatol. 2018;17(4):479-480.

Topics: Acyclovir; Adhesives; Administration, Topical; Adult; Antiviral Agents; Female; Herpes Labialis; Herpes Simplex; Humans; Severity of Illness Index; Treatment Outcome

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Cefuroxime; Child, Preschool; Dermatitis, Atopic; Diagnosis, Differential; Drug Therapy, Combination; Female; Hand; Herpes Simplex; Herpesvirus 1, Human; Humans; Wrist

Herpes simplex virus type I (HSV-I) is a latent neuroinfection which can cause focal brain lesion. The role of HSV-infection in nerve regeneration has not been studied so far. The aim of the work was to study sciatic nerve regeneration in the presence of HSV-infection and the influence of an antiviral drug. BALB/c line mice were divided into five groups. Group 1 animals were infected with HSV-I. After resolution of neuroinfection manifestations the sciatic nerve of these animals was crushed. Group 2 mice were administered acyclovir following the same procedures. Groups 3-5 mice served as controls. Thirty days after the operation distal nerve stumps and m.gastrocnemius were studied morphologically and biochemically. Ultrastructural organization of the sciatic nerve in control animals remained intact. Morphometric parameters of the nerves from the experimental groups have not reach control values. However, in the group 1 diameter of nerve fibers was significantly smaller than in the group 2. Both nerve regeneration and m.gastrocnemius reinnervation were confirmed. The muscle hypotrophy was found in groups 1, 2, and 3 (the muscle fibers diameter decreased). Metabolic changes in the muscles of the infected animals (groups 1 and 2) were more pronounced than in control groups 3 and 4. The levels of TBA-active products, conjugated dienes, carbonyl and SH-groups were reduced in m.gastrocnemius of the experimental groups, however no significant difference associated with acyclovir administration was found. HSV-infection is not limited to the local neurodegenerative changes in the CNS but affects regeneration of the injured sciatic nerve. Anat Rec, 301:1734-1744, 2018. © 2018 Wiley Periodicals, Inc.

Topics: Acyclovir; Animals; Antiviral Agents; Drug Evaluation, Preclinical; Herpes Simplex; Mice, Inbred BALB C; Nerve Regeneration; Random Allocation; Sciatic Nerve

Neonatal facial palsy is very uncommon and is generally diagnosed at birth. We present the first published case of neonatal facial palsy with identification of herpes simplex virus 1 in cerebrospinal fluid. A 35-day-old male was presented at the Emergency Department with mouth deviation to the left and impossibility of full closure of the right eye. There were no symptoms of infection or relevant medical history. Physical examination was compatible with peripheral facial palsy. Studies performed at admission were normal (blood count, biochemical analysis and coagulation blood tests and cerebrospinal fluid analysis). The patient was admitted on oral prednisolone and intravenous aciclovir. Cranial magnetic resonance was normal. Polymerase chain reaction test for herpes simplex virus 1 in cerebrospinal fluid was reported positive after 48 hours of admission. Patient followed good evolution and received prednisolone for 7 days and acyclovir for 21 days. At discharge, neurological examination was normal.. En los neonatos, la parálisis facial es muy infrecuente y, por lo general, diagnosticada al nacer. Se presenta el primer caso de parálisis facial neonatal con identificación del virus del herpes simple 1 en el líquido cefalorraquídeo. Un varón de 35 días de vida acudió a Urgencias por la desviación de la comisura bucal hacia la izquierda y la ausencia de cierre del ojo derecho, sin sintomatología infecciosa ni antecedentes relevantes. La exploración física fue compatible con parálisis facial periférica. Las exploraciones complementarias de urgencia (hemograma, bioquímica, coagulación y citoquímica de líquido cefalorraquídeo) fueron normales. Fue ingresado con prednisolona oral y aciclovir intravenoso. La resonancia magnética craneal fue normal. A las 48 horas, se recibió el resultado positivo de la reacción en cadena de la polimerasa para el virus del herpes simple 1 en el líquido cefalorraquídeo. Con evolución favorable, completó 7 días de prednisolona oral y fue dado de alta tras 21 días de aciclovir intravenoso, con exploración neurológica previa normal.

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Facial Paralysis; Glucocorticoids; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Male; Prednisolone; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Cord Blood Stem Cell Transplantation; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans

Although not common, herpes simplex virus (HSV) pneumonia can occur in immunocompromised patients. However, HSV pneumonia in immunocompetent hosts is very rare. The authors encountered a very rare case of severe HSV pneumonia in an immunocompetent host. The patient was an 85-year-old Japanese woman who presented with severe intractable pneumonia refractory to empirical antimicrobial therapy. Furthermore, the causative microorganisms remained unknown. Therefore, cytological examination of bronchoalveolar lavage fluid and protected brush biopsy of the lower respiratory tract were performed, which indicated herpes virus-infected cells with nuclear inclusions; PCR assay was positive for HSV DNA. Accordingly, the patient was diagnosed with HSV pneumonia. Her respiratory condition improved immediately after initiation of acyclovir monotherapy. In selected cases of intractable pneumonia refractory to standard antimicrobial therapy, the possibility of HSV pneumonia should be pursued.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Bronchoalveolar Lavage Fluid; Diagnostic Errors; DNA, Viral; Female; Herpes Simplex; Humans; Immunocompetence; Lung; Pneumonia, Viral; Simplexvirus; Tomography, X-Ray Computed

We present an atypical presentation of herpes simplex virus infection in a patient with Harlequin ichthyosis, which we attribute to abnormal cornification.

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Cephalexin; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Ichthyosis, Lamellar; Infant; Valacyclovir; Valine

Topics: Abdominal Pain; Acyclovir; Adolescent; Antiviral Agents; Diagnosis, Differential; Endoscopy, Gastrointestinal; Esophagitis; Esophagus; Herpes Simplex; Humans; Male; Simplexvirus

Topics: Acyclovir; Aged; Antiviral Agents; Bronchi; Bronchial Neoplasms; Diagnosis, Differential; Herpes Simplex; Humans; Male; Simplexvirus; Tomography, X-Ray Computed

Following our findings on the anti-human immunodeficiency virus (HIV) activity of acyclovir (ACV) phosphate prodrugs, we herein report the ProTide approach applied to a series of acyclic nucleosides aimed at the identification of novel and selective antiviral, in particular anti-HIV agents. Acyclic nucleoside analogues used in this study were identified through a virtual screening using HIV-reverse transcriptase (RT), adenylate/guanylate kinase, and human DNA polymerase γ. A total of 39 new phosphate prodrugs were synthesized and evaluated against HIV-1 (in vitro and ex vivo human tonsillar tissue system) and human herpes viruses. Several ProTide compounds showed substantial potency against HIV-1 at low micromolar range while the parent nucleosides were not effective. Also, pronounced inhibition of herpesvirus replication was observed. A carboxypeptidase-mediated hydrolysis study was performed for a selection of compounds to assess the formation of putative metabolites and support the biological activity observed.

Topics: Acyclovir; Anti-HIV Agents; Cell Line; Drug Design; Herpes Simplex; HIV Infections; HIV Reverse Transcriptase; HIV-1; Humans; Molecular Docking Simulation; Nucleosides; Simplexvirus; Virus Replication

Acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) infections are concern in immunocompromised patients. Most clinical ACVr HSV-1 isolates have mutations in the viral thymidine kinase (vTK) genes. The vTK-associated ACVr HSV-1 shows reduced virulence, but the association between the level of resistance and the virulence of the vTK-associated ACVr HSV-1 is still unclear.. The virulence in mice of 5 vTK-associated ACVr HSV-1 clones with a variety of ACV sensitivities, when inoculated through intracerebral and corneal routes, was evaluated in comparison with ACV-sensitive (ACVs) parent HSV-1 TAS.. Although all the 5 ACVr HSV-1 clones and ACVs HSV-1 TAS showed a similar single-step growth capacity in vitro, the virulence of ACVr HSV-1 clones significantly decreased. A 50% lethal dose (LD. A statistically significant correlation between the virulence and susceptibility to ACV among ACVr HSV-1 clones was demonstrated.

Topics: Acyclovir; Animals; Antiviral Agents; Disease Models, Animal; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Mice, Inbred BALB C; Mutant Proteins; Thymidine Kinase; Virulence

Topics: Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Exanthema; Hand Dermatoses; Herpes Simplex; Humans; Male; Skin Diseases, Vesiculobullous; Spider Bites; Thumb; Valacyclovir; Valine

Three-dimensional (3D) in vitro tissue models provide an approach for the systematic, repetitive, and quantitative study of drugs. In this study, we constructed an in vitro 3D acrylated hyaluronic acid (AHA) hydrogel model encapsulating fibroblasts, performed long-period 3D culture, and tested cellular topological changes and proliferation variation in the presence of herpes simplex virus-1 (HSV-1) as an infecting virus and acyclovir (ACV) as the treatment drug. The AHA hydrogels were formed by using Michael addition chemistry of bis-cysteine containing MMP-degradable cross-linker onto AHA prefunctionalized with cell adhesion peptides (RGD). Cellular structures of 3T3 fibroblasts in hydrogel presented different morphological evolution processes and proliferation rates between different groups, including HSV-1 treated alone, ACV treated alone, HSV-1 and ACV cotreated, and control samples. In AHA hydrogel, ACV blocked HSV-1 infection/replication on fibroblasts. Yet, the proliferation of ACV-treated fibroblasts was slower than that of the control group. A significantly longer period was required for cells in 3D AHA gel to regain a healthy status when compared with cells in two-dimensional (2D) culture. This hydrogel-based 3D culture model potentially lays a foundation for analyzing the response of self-organized 3D tissues to viruses and drugs in a way that is closer to nature.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Adhesion; Cell Line; Cell Proliferation; Fibroblasts; Herpes Simplex; Herpesvirus 1, Human; Hyaluronic Acid; Hydrogels; Mice; NIH 3T3 Cells; Virus Diseases

Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects. Therefore, we compared the effects of a panel of conventional and novel anti-herpetic compounds in monkey epithelial (Vero) cells, human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and hiPSC-derived neurons (N = 73 drugs). While the profiles of activity for the majority of the drugs were similar in all three tissues, Vero cells were less likely than NPCs to identify drugs with substantial inhibitory activity in hiPSC-derived neurons. We discuss the relative merits of each cell type for antiviral drug screens against neuronal infections with HSV-1.

Topics: Acyclovir; Animals; Antiviral Agents; Central Nervous System; Chlorocebus aethiops; Drug Evaluation, Preclinical; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Induced Pluripotent Stem Cells; Neurons; Pluripotent Stem Cells; Vero Cells

BACKGROUND Liver failure in the neonatal population is a life-threatening complication and has a wide array of etiologies, including infectious, immune-mediated, metabolic, or drug-induced. Although neonatal herpes simplex virus (HSV) hepatitis only accounts for 1% of all acute liver failures, it has an extremely aggressive clinical course that carries a mortality rate of 85%. CASE REPORT We report a rare case of disseminated neonatal HSV-2 with late presentation associated with fulminant liver failure. The patient recovered without obvious neurologic deficits or need for liver transplant. CONCLUSIONS This case study emphasizes and promotes awareness of early recognition and appropriate clinical management of neonatal HSV infection, and its positive outcome.

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Liver Failure, Acute; Male; Time-to-Treatment

A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v-

Topics: Acyclovir; Antiviral Agents; Cell Culture Techniques; Cell Line; Doxycycline; Ganglia, Spinal; Gene Expression Regulation, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Membrane Glycoproteins; Nerve Growth Factor; Peripherins; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-ret; Receptor, trkA; Receptor, trkB; Receptor, trkC; Sensory Receptor Cells; Virus Activation; Virus Latency; Virus Release; Virus Replication

Antiviral-resistant herpes simplex virus type 1 (HSV-1) has been recognized as an emerging clinical problem among patients undergoing hematopoietic stem cell transplantation (HSCT).. A prospective observational study was conducted at a hematological center over a 2-year period. Oropharyngeal swab samples were serially collected each week from 1 week before and up to 100 days after HSCT and were tested for virus isolation. The HSV-1 isolates were tested for sensitivity to acyclovir (ACV). The prognosis of patients with ACV-resistant (ACVr) HSV-1 and the genetic background of the ACVr HSV-1 isolates were assessed.. Herpes simplex virus type 1 was isolated in 39 of 268 (15%) HSCT patients within 100 days after transplantation. Acyclovir-resistant HSV-1 emerged in 11 of these 39 patients (28%). The 100-day death rates of HSCT patients without HSV-1 shedding, those with only ACV-sensitive HSV-1 shedding, and those with ACVr HSV-1 shedding were 31%, 39%, and 64%, respectively. Patients with HSV-1, including ACVr HSV-1, shedding showed a significantly higher mortality rate. Relapsed malignancies were a significant risk factor for the emergence of ACVr HSV-1. Acyclovir resistance was attributable to viral thymidine kinase and DNA polymerase mutations in 6 and 5 patients, respectively.. Herpes simplex virus type 1, including ACVr HSV-1, shedding was associated with poorer outcome in HSCT patients, even if HSV disease did not always occur. Patients with relapsed malignancies were at especially high risk for the emergence of ACVr HSV-1.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Female; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Humans; Japan; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Postoperative Complications; Prognosis; Proportional Hazards Models; Prospective Studies; Recurrence; Survival Rate; Thymidine Kinase; Young Adult

Neonatal herpes simplex virus infection is rare but important to recognize because of the major risk of sequelae or death. The diagnosis is mainly based on specific clinical and biological analyses. Aciclovir is the treatment of choice, duration of administration depending on the severity of the disease. A six-month treatment with suppressive-dose oral aciclovir is recommended to improve the child's prognosis. From a clinical case, we reviewed the literature to improve the management.. L’infection néonatale à Herpès est peu fréquente mais importante à reconnaître vu le risque important de séquelles ou de mortalité. Le diagnostic repose principalement sur des analyses cliniques et biologiques spécifiques. L’aciclovir est le traitement de choix, la durée d’administration varie en fonction de l’importance de l’atteinte. Un traitement de 6 mois par voie orale est conseillé pour améliorer le pronostic de l’enfant. A partir d’un cas clinique, nous avons revu la littérature pour connaître les dernières recommandations afin d’améliorer la prise en charge.

Topics: Acyclovir; Amoxicillin-Potassium Clavulanate Combination; Antiviral Agents; beta-Lactamase Inhibitors; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy Complications, Infectious

Congenital erosive and vesicular dermatosis (CEVD) is a rare entity of unknown etiology. We report a case of congenital herpes simplex virus (HSV) type 1 infection that healed with reticulated and supple scarring, similar to that seen in CEVD. Twenty percent of previously reported cases of CEVD had recurrent HSV infection throughout the first year of life. We postulate that at least some previous cases of CEVD may have been due to undiagnosed congenital HSV infection.

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Skin Diseases, Vesiculobullous

Topics: Acyclovir; Adult; Antiviral Agents; Esophagitis; Female; Herpes Simplex; Humans

Topics: Acyclovir; Administration, Topical; Adrenal Cortex Hormones; Adult; Female; Herpes Simplex; Humans; Simplexvirus; Skin Diseases; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Encephalitis; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

Topics: Acyclovir; Ampicillin; Anti-Bacterial Agents; Antiviral Agents; Cefpodoxime; Ceftizoxime; Doxycycline; Herpes Simplex; Humans; Immunocompetence; Liver Cirrhosis; Male; Middle Aged; Tonsillitis; Valacyclovir; Valine; Vibrio Infections; Vibrio vulnificus

Topics: Acyclovir; Antiviral Agents; Encephalitis; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Simplexvirus

Topics: Acyclovir; Adult; Anti-Bacterial Agents; Antiviral Agents; Face; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Nitric Oxide Synthase Type II; Rosacea; Symptom Flare Up; Toll-Like Receptor 2; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2

The present investigation focuses on the development and evaluation of acyclovir-loaded flexible membrane vesicles (ACY-FMVs) and evaluates their targeting potential to localize the drug into skin layers. The drug-loaded FMVs were prepared by thin-film hydration method and characterized for various attributes including micromeritics, entrapment efficiency, vesicle shape, size, and degree of deformability. The values of particle size and zeta potential of the developed carrier system were found to be 453.7 nm and - 11.62 mV, respectively. The system was further incorporated into a hydrogel and evaluated for skin permeability and retention characteristics in comparison to marketed formulation. The developed formulation demonstrated enhanced retention of drug deep inside the skin layers which can probably decrease the frequency of application of the drug, thereby reducing its adverse effects. Skin irritancy studies performed on Laca mice skin proved the safety and non-irritant nature of ACY-FMVs. The pharmacodynamic studies on murine model for HSV-1 infection demonstrated immense potential and safety of topically applied ACY-FMVs. However, more intensive studies need to be pursued to explore and exploit the potential of lipid-based systems in anti-viral therapeutics. These preclinical findings provide a hope for corroborating the efficacy in clinical situations.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Chemistry, Pharmaceutical; Chlorocebus aethiops; Disease Models, Animal; Drug Carriers; Herpes Simplex; Liposomes; Mice; Particle Size; Skin Absorption; Vero Cells

A 4-month-old female infant presented with a vesicular lesion on her left hand present since 1 day. A few days prior to presentation, she had a similar lesion on the lower lip. Two days after presentation, she returned with new lesions on her thorax and upper eyelid. PCR of the vesicle was positive for herpes simplex virus type 1. The transmission to her chest and face probably resulted from autoinoculation, caused by rubbing of the hand on other parts of the body. Transmission of herpes simplex through skin-to-skin contact is a common route of infection in people engaging in contact sports. Antiviral therapy was started because of the extensiveness and expansion of lesions and risk of developing herpetic keratitis. The patient completely recovered. This case shows that in an otherwise healthy infant, multiple herpetic skin lesions were not due to disseminated infection, but through autoinoculation.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Diagnosis, Differential; Disease Transmission, Infectious; Face; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic; Lip; Thorax; Treatment Outcome

Herpes simplex virus (HSV)-1/2 can still be reactivated after allogeneic haematopoietic stem cell transplantation (allo-HSCT) even when the prophylactic acyclovir is used. However, the risk factors for HSV-1/2 viremia and the clinical outcomes following unmanipulated haploidentical HSCT remain unknown.. Nineteen patients with HSV-1/2 viremia and fifty-seven patients without HSV-1/2 viremia which were selected using the case-pair method after undergoing haploidentical HSCT were enrolled. We analysed the risk factors for HSV-1/2 viremia and compared the clinical outcomes between the two groups.. The risk factors for HSV-1/2 viremia included HLA disparity ≥2 loci (p=0.049) and cytomegalovirus (CMV) reactivation (p=0.028). The incidences of platelet engraftment, oral mucositis and severe haemorrhagic cystitis (HC) in patients with and without HSV-1/2 viremia were 77% and 94% (p=0.003), 78% and 13% (p=0.000), and 25% and 6% (p=0.04), respectively. Moreover, the median time to platelet engraftment in patients with and without HSV-1/2 viremia was +25days (range, +11-+80) and +17days (range, +8-+67) (p=0.004), respectively. According to the multivariate analyses, HSV-1/2 viremia was associated with delayed platelet engraftment (p=0.038), a higher incidence of oral mucositis (p=0.000) and severe HC (p=0.038). However, HSV-1/2 viremia was not associated with non-relapse mortality (34.0% vs. 31.5%, p=0.26), leukaemia-free survival (60.9% vs. 57.9%, p=0.46) and overall survival (61.2% vs. 60.7%, p=0.37).. Based on our study results, we recommend that HSV-1/2 PCR should be performed upon clinical suspicion of HSV-1/2 infection.

Topics: Acyclovir; Adolescent; Adult; Child; Child, Preschool; Cystitis; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Retrospective Studies; Risk Factors; Transplantation, Haploidentical; Viremia; Young Adult

Hemophagocytic lymphohistiocytosis (HLH) associated with herpes simplex virus (HSV)-1 infection (HSV-1-HLH) is uncommon and is potentially fatal without appropriate treatment. We herein report the case of an adult patient with HSV-1-HLH who was successfully treated with acyclovir. A 69-year-old man developed fever, pancytopenia and liver enzyme elevation after the resolution of pneumonia. These findings and the presence of hemophagocytosis in the patient's bone marrow were consistent with a diagnosis of HLH. The patient was diagnosed with HSV-1-HLH based on the results of a polymerase chain reaction (PCR) for HSV-1. The early administration of acyclovir improved his clinical symptoms and laboratory results within two weeks. In the present case, the rapid and precise diagnosis facilitated the successful treatment of HSV-1-HLH.

Topics: Acyclovir; Aged; Herpes Simplex; Herpesvirus 1, Human; Humans; Lymphohistiocytosis, Hemophagocytic; Male

Recurrent herpes simplex keratitis (HSK) is a leading infectious cause of blindness in industrialized countries. Antiviral prophylaxis (AVP) may fail to prevent recurrence of HSK due to viral resistance, inadequate dosing, or poor patient compliance. In this prospective multicenter study, we enrolled immunocompetent patients with recurrent HSK despite AVP. Ocular samples were tested by PCR for herpes simplex virus 1 (HSV-1). HSV-1 drug resistance was assessed with a genotypic assay based on UL23 and UL30 gene sequencing. After curative full dose valacyclovir (VACV) treatment was started, peak and trough acyclovir (ACV) plasma concentrations were measured, and patient compliance to AVP was assessed with a questionnaire. The study sample was comprised of 43 patients. Six (14%) patients were positive for HSV-1 using PCR, of whom 5 (83%) harbored genotypically ACV-resistant (ACV

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic; Male; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Recurrence; Tears; Valacyclovir; Valine; Young Adult

A middle-aged man with decompensated cirrhosis and a dimorphic multisite skin rash is diagnosed with rare atypical herpes simplex infection, manifesting Sweet's syndrome (SS) in the absence of other described associations. SS, an acute febrile neutrophilic dermatosis, has three common forms-classical or idiopathic, malignancy associated and drug induced. Systemic autoimmune, connective tissue diseases and infections are also strong associations. The latter is commonly described in Gram-positive bacteria, salmonellosis and

Topics: Acyclovir; Antiviral Agents; Fatal Outcome; Herpes Simplex; Humans; Liver Cirrhosis; Male; Middle Aged; Multiple Organ Failure; Sepsis; Skin Diseases, Vesiculobullous; Sweet Syndrome

Topics: Acyclovir; Adult; Encephalitis; Herpes Simplex; Herpesvirus 3, Human; Humans; Male; Meningitis, Viral; Meningoencephalitis; Simplexvirus; Valacyclovir; Valine; Varicella Zoster Virus Infection

Herpes simplex virus (HSV) is rare in neonates but carries significant morbidity and mortality in that group. Emergency department (ED) clinicians have little guidance to decide when to test for HSV and give acyclovir. We created an institutional guideline to provide guidance in patients younger than 6 weeks. Our objective was to evaluate whether guideline implementation affected the ED's decision to test for HSV, and ED use of HSV polymerase chain reactions (PCRs) and acyclovir.. We reviewed charts for patients 1 year before implementation and 1 year after implementation of our guideline. Inclusion criteria were younger than 60 days, admitted through the ED, symptom onset younger than 6 weeks, and any one of the following criteria: (1) ED blood culture obtained, (2) ED or inpatient HSV PCR obtained, and (3) ED or inpatient acyclovir treatment. Premature patients and transfer patients were excluded. We compared whether the decision to initiate HSV testing, ED use of HSV PCRs, serum alanine aminotransferase, and acyclovir use changed post-guideline implementation.. We reviewed 173 charts pre-implementation and 129 post-implementation. We found a significant decrease in ED testing for HSV among patients who did not meet guideline criteria (P < 0.01). We saw an improvement in the use of alanine aminotransferase among patients who met criteria for testing (P = 0.02), but no change in the use of HSV PCRs or acyclovir use among tested patients.. Guideline implementation reduced HSV evaluations in low-risk patients, but did not improve test utilization or acyclovir administration among those tested. Additional work is needed to improve guideline utilization.

Topics: Acyclovir; Alanine Transaminase; Antiviral Agents; Decision Making; Emergency Service, Hospital; Female; Guidelines as Topic; Herpes Simplex; Humans; Infant, Newborn; Length of Stay; Male; Non-Randomized Controlled Trials as Topic; Polymerase Chain Reaction; Practice Patterns, Physicians'; Simplexvirus

Bell's palsy is caused by the reactivation of herpes simplex virus type 1 (HSV-1). Using Balb/c mice inoculated with the KOS strain of HSV-1, we previously developed an animal disease model that simulated mild Bell's palsy. The current study developed an animal disease model of more severe facial palsy than that seen in the mouse model.. Three-week-old female Wister rats weighing 60-80g were inoculated on the auricle with HSV-1 and acyclovir was administered intraperitoneally to deactivate the infected HSV-1. Instead of HSV-1, phosphate-buffered saline was used for inoculation as a negative control. Quantitative polymerase chain reaction (PCR), behavior testing (blink reflex), electroneuronography, histopathology of the peripheral nerve, and immunohistochemistry of the facial nerve nucleus were evaluated.. Facial palsy occurred 3-5 days after virus inoculation, and the severity of the facial palsy progressed for up to 7 days. Quantitative PCR showed an increase in HSV-1 DNA copies in the facial nerve from 24 to 72h, suggesting that HSV-1 infection occurred in the nerve. Electroneuronography values were 33.0±15.3% and 110.0±18.0% in HSV-1-inoculated and control rats, respectively. The histopathology of the peripheral nerve showed demyelination and loss of the facial nerve, and the facial nerve nucleus showed degeneration.. Facial palsy developed in Wister rats following inoculation of the KOS strain of HSV-1 onto the auricles. The behavioral, histopathological, and electroneuronography data suggested that the severity of facial palsy was greater in our rats than in animals in the previous mouse disease model.

Topics: Acyclovir; Animals; Antiviral Agents; Bell Palsy; Blinking; Disease Models, Animal; DNA, Viral; Ear; Facial Nerve; Facial Paralysis; Female; Herpes Simplex; Herpesvirus 1, Human; Immunohistochemistry; Mice, Inbred BALB C; Polymerase Chain Reaction; Rats; Rats, Wistar

Interstitial nephritis due to viruses is well-described after solid organ transplantation. Viruses implicated include cytomegalovirus; BK polyomavirus; Epstein-Barr virus; and, less commonly, adenovirus. We describe a rare case of hemorrhagic allograft nephritis due to herpes simplex virus type 1 at 10 days after living donor kidney transplantation. The patient had a favorable outcome with intravenous acyclovir and reduction of immunosuppression.

Topics: Acyclovir; Allografts; Antiviral Agents; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Hemorrhage; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Nephritis; Prognosis; Risk Factors

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Topics: Acyclovir; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Drug Substitution; Encephalitis, Herpes Simplex; Female; Foscarnet; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukocytosis; Magnetic Resonance Imaging; Middle Aged; Temporal Lobe

The use of empiric acyclovir for suspected neonatal herpes simplex virus (HSV) infection has been debated for years. To identify the gap in the decision to initiate empiric acyclovir, we performed a retrospective chart review and administered a survey to pediatricians to assess current practices regarding evaluation for possible HSV infection. Seventy infants received empiric acyclovir over a 1-year period; of these, 3 infants (4.3%) had positive HSV testing. Fourteen infants were identified as "high-risk" for HSV infection; of these, 13 infants had incomplete testing. Survey results revealed uncertainty in the decision to initiate acyclovir and in the composition of complete diagnostic testing. This study confirmed the clinical uncertainty in the decision to initiate empiric acyclovir. Using this chart review and survey as a baseline, future efforts will focus on a quality improvement project to reduce empiric acyclovir use in low-risk infants and to ensure complete diagnostic evaluation in high-risk infants.

Topics: Acyclovir; Herpes Simplex; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Prospective Studies; Retrospective Studies

Acyclovir is used to treat herpes simplex virus disease in infants. Treatment with high-dose acyclovir, 60 mg/kg/d, is recommended; however, the safety of this dosage has not been assessed in the past 15 years, and this dosage is not currently approved for infants by the US Food and Drug Administration.. We included infants with neonatal herpes simplex virus disease treated with ≥14 days of intravenous acyclovir starting in the first 120 days of life admitted to 1 of 42 neonatal intensive care units managed by the Pediatrix Medical Group between 2002 and 2012. We determined the frequency and proportion of infants with clinical and laboratory adverse events (AEs) as well as the number and proportion of infant days with laboratory AEs occurring during acyclovir exposure.. We identified 89 infants during the study period with 1658 days of acyclovir exposure. Almost all received high-dose acyclovir therapy (79/89, 89%). The most common clinical AEs were hypotension and seizure, both occurring in 9% of infants. Thrombocytopenia was the most common laboratory AE occurring in 25% of infants and on 9% of infant-days. Elevated creatinine occurred in 2% of infants and 0.2% of infant-days and no infants developed renal failure requiring dialysis. Overall, 45% of infants had ≥1 AE.. In this cohort of infants treated during the high-dose acyclovir era, AEs were common but usually not severe. Many of the AEs reported in this cohort may be related to the underlying infection rather than due to acyclovir exposure.

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Pregnancy Complications, Infectious; Retrospective Studies; Simplexvirus; Thrombocytopenia

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Keratitis, Dendritic; Keratitis, Herpetic; Simplexvirus

We previously reported that oral low-dose acyclovir (200 mg/day) for the prevention of herpes simplex virus (HSV) infections after allogenic hematopoietic stem cell transplantation (HSCT) is effective without the emergence of acyclovir-resistant HSV infections. However, HSV infections are of significant concern because the number of allogeneic HSCT with T-cell depletion, which is a risk factor of the emergence of drug-resistant HSV infections, has been increasing. We experienced a 25-year-old female who received allogenic HSCT from an unrelated donor with 1-antigen mismatch using anti-thymocyte globulin. Despite acyclovir prophylaxis (200 mg/day), she developed the right palatal ulcer that was positive for HSV-1 specific antigen by fluorescent antibody on day 20 and developed new hypoglossal and tongue ulcers on day 33. Replacement of acyclovir with foscarnet improved her ulcers. We isolated 2 acyclovir-resistant and foscarnet-sensitive strains from the right palatal and hypoglossal ulcers, which had the same frame shift mutation in the thymidine kinase genes. The rate of proliferation of the isolate from the hypoglossal ulcer was faster than that from the right palatal ulcer in the plaque reduction assay. HSV strains that acquired acyclovir-resistant mutations at the right palatal ulcer with larger plaque might spread to the hypoglossal ulcer as the secondary site of infection because of better growth property. Second-line antiviral agents should be considered when we suspect treatment failure of HSV infection, especially in HSCT with T-cell depletion. Further studies are required whether low-dose acyclovir prophylaxis leads to the emergence of virological resistance.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Viral; Female; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; T-Lymphocytes; Tongue; Transplantation, Homologous

Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV (dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sample-to-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h;

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Central Nervous System; Cerebrospinal Fluid; Child; Child, Preschool; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Infant, Newborn; Male; Meningitis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Young Adult

We report a 48 -year-old woman witherythrokeratoderma variabilis, which is a rarehereditary disorder of keratinization, who developednew, painful, blisters within her skin lesions. Thediagnosis of herpes simplex virus infection was madebased on the clinical history and histopathologicfeatures. She was successfully treated withprophylactic valacyclovir, and her herpetic outbreakshave halted. This case serves as a reminder thateven among the most rare skin disorders, commonsecondary complications may be easily overlooked.

Topics: Abdomen; Acyclovir; Antiviral Agents; Arm; Erythrokeratodermia Variabilis; Facial Dermatoses; Female; Herpes Simplex; Humans; Leg; Middle Aged; Simplexvirus; Thoracic Wall; Valacyclovir; Valine

Topics: Acyclovir; Aged; Antiviral Agents; Deglutition Disorders; Esophagitis; Esophagoscopy; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Ulcer; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; DNA, Viral; Eye Infections, Viral; Female; Gestational Age; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infusions, Intravenous; Male; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Retinopathy of Prematurity

Rituximab is a widely used biologic agent, which has shown favourable results in the treatment of vasculitis. But immunosuppressive treatment also bears the risk of severe complications.. A patient with rheumatoid arthritis, progressive scleromalacia, and acute retinal necrosis on therapy with rituximab is reported.. For the first time, a correlation between rituximab and acute retinal necrosis in a patient with progressive rheumatoid scleromalacia is shown.. Although rituximab is a promising biologic agent for the treatment of autoimmune diseases, it bears the risk of reactivation of viral infections, including the onset of acute retinal necrosis.

Topics: Acyclovir; Antiviral Agents; Aqueous Humor; Arthritis, Rheumatoid; Drug Therapy, Combination; Eye Infections, Viral; Female; Glucocorticoids; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Middle Aged; Prednisone; Retinal Necrosis Syndrome, Acute; Rituximab; Scleritis; Virus Activation

Herpes viruses cause threatening infections in humans and stand second as causative agents for most human viral diseases, after influenza and cold viruses.. A novel multiparticulate delivery system for acyclovir (ACV), based on ion-exchange resin, was developed to achieve a gastro-mucoadhesive effect in order to effectively combat the herpes simplex virus.. A combination of ACV and cholestyramine resin was optimized and further entrapped within sodium alginate and Carbopol microbeads. The developed systems were evaluated for drug entrapment efficiency (DEE), percentage of mucoadhesion, and in vitro release characteristics in simulated gastric fluid (SGF, pH 1.2).. With the aid of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR), the interaction of the resinate and polycations with alginate has been revealed, which consequently supports the formation of the membrane by the polyelectrolyte complex. The in vitro drug release studies demonstrate that formulations without the drug-resin complex (DRC) released the drug more rapidly than formulations containing DRC, which released the drug in a controlled manner, due the formation of a complex between drug and resin.. Preliminary results from this study suggest that these DRC-entrapped microbeads may be used to incorporate other antiviral drugs and could be effective against infections caused by herpes viruses. Such formulations developed could be subjected to in vivo studies in future, in order to prove complete clearance of herpes infections.

Topics: Acyclovir; Cholestyramine Resin; Drug Delivery Systems; Herpes Simplex; Humans; Models, Chemical

Antrodia camphorata, a traditional Chinese medicine, is widely used in the treatment of liver diseases and cancers. Anti-inflammatory properties have also been described. HSV infection represents one of the most serious public health concerns globally because of its devastating impact. Searching for new antiviral agents, especially those with different mechanisms of action, is a crucial goal and there is an unmet need for alternative and complementary therapy against HSV infection. In this study, anti-herpes screening was performed with extracts from A. camphorata mycelia.. MTT assay, fractional inhibitory concentration index and median-effect principle were used to evaluate antiviral activity and to calculate drug combination effect.. Crude ethanol extracts and isolated constituents showed inhibition of HSV replication at a very low concentration. Fraction A and antrodin A showed viral inhibitory effect with reduction of viral cell-to-cell spread. In addition, neither fraction A nor antrodin A showed interaction in combination with acyclovir.. A. camphorata mycelia and antrodin A might have potential use as anti-HSV agents and are promising candidates for future antiviral drug design.

Topics: Acyclovir; Animals; Antiviral Agents; Antrodia; Chlorocebus aethiops; Drugs, Chinese Herbal; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Maleic Anhydrides; Medicine, Chinese Traditional; Microbial Sensitivity Tests; Mycelium; Vero Cells; Viral Plaque Assay; Virus Replication

Topics: Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage; Herpes Simplex; Humans; Pediatricians; Rectum; Young Adult

Topics: Acyclovir; Aged; Antiviral Agents; Female; Herpes Simplex; Humans; Immunocompromised Host; Pleurisy; Scleroderma, Systemic

Topics: Acyclovir; Adrenal Cortex Hormones; Aged, 80 and over; Antiviral Agents; Herpes Simplex; Humans; Male; Respiratory Sounds; Simplexvirus; Ulcer; Vagus Nerve Diseases; Virus Activation; Vocal Cord Paralysis

Topics: Acyclovir; Anti-HIV Agents; Cicatrix; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Skin Diseases, Vesiculobullous

To determine efficacy of using oral antiviral medication to reduce herpes gladiatorum (HG) at summer high-school wrestling camps.. Usage of antiviral medication hypothetically reduces the likelihood of HG outbreaks. This is an observational study examining the effectiveness of oral antiviral medications in reducing outbreaks of HG because of Herpes Simplex type-1 virus (HSV).. A 28-day high-school summer wrestling camp at the University of Minnesota from 2003 to 2012.. Each summer approximately 300 high-school wrestlers, age 13 to 18 years of age, participated in this camp.. All athletes were recommended to take valacyclovir 1 g once a day for the duration of the camp. Athletes who did not use any antiviral medication comprised the comparison group for this study. Individuals were screened daily and those with outbreaks of HG were withheld from practice for 120 hours in accordance with National Collegiate Athletic Association/National Federation of State High School Associations guidelines.. To measure viral outbreaks of HG due to HSV-1, determine level of compliance, and determine efficacy of antiviral medication in reducing the occurrence of HG at this 28-day wrestling camp.. Of the 2793 athletes who completed camp, 1995 (71%) used antiviral medication, and 36 outbreaks occurred. Eighty-four athletes had a known history of HG/recurrent herpes labialis. Overall, prophylactic antiviral medication resulted in an 84.7% decrease in the probability of an outbreak. Prophylactic valacyclovir (1 g daily) lowered the incidence of individual outbreaks by 89.5%.. Prophylactic use of valacyclovir 1 g once a day is efficacious in lowering the incidence of HSV outbreaks among adolescents at a 28-day wrestling camp.

Topics: Acyclovir; Adolescent; Antiviral Agents; Disease Outbreaks; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Medication Adherence; Pre-Exposure Prophylaxis; Valacyclovir; Valine; Wrestling

Topics: Acyclovir; Antiviral Agents; Bites, Human; Disease Transmission, Infectious; Family; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Pregnancy Complications, Infectious

A physician has to perform a benefit-risk assessment each time acyclovir is prescribed "off label" for children. A group of Polish infectious disease experts was created to develop evidence-based guidelines on the use of acyclovir in the treatment and prevention of varicella zoster and herpes simplex infections. In primary varicella zoster virus infections, oral acyclovir treatment is recommended in children over 12 years of age and should be considered in younger children who fall into one of the groups at risk of severe varicella. Intravenous acyclovir therapy in varicella is recommended in patients with immune deficiencies, newborns and in complicated cases. When there is a justified need for prevention of varicella, oral acyclovir prophylaxis may be considered if immunoglobulin cannot be administered, and if it is too late for vaccination. Oral acyclovir treatment of herpes zoster may be beneficial to otherwise healthy patients with a rash in places other than the trunk and in patients over 50 years of age. In immunocompetent patients with herpes simplex infections, indications for treatment with oral acyclovir include primary (genital herpes, skin herpes in children with atopic dermatitis, ocular herpes simplex, severe gingivostomatitis, paronychia and pharyngitis) and recurrent infections. Intravenous acyclovir should be administered for herpes infections in neonates, immunocompromised patients and patients who develop complications including neurological.

Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Consensus; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Infant; Poland; Simplexvirus

Topics: Acyclovir; Antiviral Agents; Corpus Callosum; Diagnosis, Differential; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Magnetic Resonance Imaging; Meningitis, Viral; Middle Aged; Treatment Outcome

Topics: Acyclovir; Administration, Intravenous; Antacids; Antiviral Agents; Coronary Artery Bypass; Critical Illness; Endoscopy, Digestive System; Esophagitis; Esophagogastric Junction; Esophagus; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunohistochemistry; Middle Aged; Peptic Ulcer Hemorrhage; Postoperative Complications; Proton Pump Inhibitors; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Disease Management; Herpes Simplex; Humans; Infant, Newborn; Male; Practice Patterns, Physicians'; Pregnancy Complications, Infectious; Quality Improvement; Simplexvirus; Standard of Care

In this study, we demonstrated the in vitro and in vivo antiherpetic activities of a stable furan derivative, (1R,2R)-1-(5'-methylful-3'-yl)propane-1,2,3-triol (MFPT), which had originally been isolated from Streptomyces sp. strain FV60. In the present study, we synthesized MFPT from (5-methylfuran-3-yl)methanol in 6 steps for use in the experiments. MFPT showed potent in vitro antiviral activities against two acyclovir (ACV)-sensitive (KOS and HF) strains and an ACV-resistant (A4-3) strain of herpes simplex virus type 1 (HSV-1) and an ACV-sensitive HSV type 2 (HSV-2) UW 268 strain, their selectivity indices ranging from 310 to 530. By intravaginal application of MFPT to mice, the virus yields decreased dose-dependently against the three strains of HSV-1 and HSV-2. When MFPT was applied at a dose of 1.0 mg/day, the lesion scores, as clinical signs manifested by viral infection, were extensively suppressed in HSV-1-infected mice, whereas the lesion scores in HSV-2-infected mice were not markedly decreased. Interestingly, MFPT exerted an inhibitory effect against ACV-resistant HSV-1 in mice to a similar degree as in ACV-sensitive HSV-1-infected mice. Therefore, the compound might have potential for developing a topical antiviral agent that could be also applied to the infections caused by ACV-resistant viruses.

Topics: Acyclovir; Administration, Intravaginal; Animals; Antiviral Agents; Chlorocebus aethiops; Drug Resistance; Female; Furans; Glycerol; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Mice, Inbred BALB C; Propane; Streptomyces; Vero Cells

Topics: Acyclovir; Antiviral Agents; Esophageal Diseases; Fetal Blood; Herpes Simplex; Humans; Male; Middle Aged; Ulcer

Pyogenic tonsillitis may often be observed in the general Western population. In severe cases, it may require antibiotic treatment or even hospitalization and often a prompt clinical response will be noted. Here we present an unusual case of progressive multiple organ failure including fulminant liver failure following acute tonsillitis initially mistaken for "classic" pyogenic (that is bacterial) tonsillitis.. A 68-year-old previously healthy white man was referred with suspicion of pyogenic angina. After tonsillectomy, he developed acute liver failure and consecutive multiple organ failure including acute hemodynamic, pulmonary and dialysis-dependent renal failure. Immunohistopathological analysis of his tonsils and liver as well as serum polymerase chain reaction analyses revealed herpes simplex virus-2 to be the causative pathogen. Treatment included high-dose acyclovir and multiorgan supportive intensive care therapy. His final outcome was favorable.. Fulminant herpes simplex virus-2-induced multiple organ failure is rarely observed in the Western hemisphere and should be considered a potential diagnosis in patients with tonsillitis and multiple organ failure including acute liver failure. From a clinical perspective, it seems important to note that fulminant herpes simplex virus-2 infection may masquerade as "routine" bacterial severe sepsis/septic shock. This persevering condition should be diagnosed early and treated goal-oriented in order to gain control of this life-threatening condition.

Topics: Acute Disease; Acyclovir; Aged; Antiviral Agents; Critical Care; Herpes Simplex; Herpesvirus 2, Human; Humans; Liver; Liver Failure, Acute; Male; Multiple Organ Failure; Tonsillitis; Treatment Outcome

Topics: Acyclovir; Aged; Anus Diseases; Diagnosis, Differential; Diagnostic Errors; Female; Herpes Simplex; Histocytochemistry; Humans; Immunohistochemistry; Microscopy; Pyoderma Gangrenosum; Simplexvirus; Treatment Outcome

Herpes simplex viruses (HSV) are leading causes of human infections which result in severe manifestations, especially in neonates, immunocompromised and/or transplanted individuals. Current HSV type-1 (HSV-1) resistance to standard antiviral agents is a therapeutic challenge, especially for treating immunocompromised patients.. Herein we describe the promising antiviral profile of three 2-aminomethyl-3-hydroxy-1,4-naphthoquinones against HSV-1 using Vero cells.. The in silico theoretical analysis indicated that the lowest unoccupied molecular orbital (LUMO) and the conformational features of these molecules are important structural features for modulating their biological activity. Our in vitro results showed that these compounds have significant anti-HSV-1 activity comparable to acyclovir, the antiviral currently used clinically. Importantly two of them showed a lower cytotoxicity profile against Vero cells than acyclovir. The inhibitory mechanism analysis using a time-of-addition assay revealed that all compounds inhibit the late phase of lytic replication. Finally, the highest selectivity index of the first tested compound was almost twice as high as that of acyclovir.. Since resistance is still a problem for treating HSV infections, these compounds present a promising profile toward the development of new strategies for anti-HSV-1 therapy.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Survival; Chlorocebus aethiops; Computer Simulation; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Naphthoquinones; Vero Cells; Viral Plaque Assay

The etiologies of Bell's palsy and brachial neuritis remain uncertain, and the conditions rarely co-occur or reoccur. Here we present a woman in her twenties who had several relapsing-remitting episodes with left-sided facial palsy and brachial neuropathy. The episodes always started with painful left-sided oral blisters. Repeat PCRs HSV-1 DNA from oral vesicular lesions were positive. Extensive screening did not reveal any other underlying cause. Findings on MRI T2-weighted brachial plexus STIR images, using a 3.0-Tesla scanner during an episode, were compatible with brachial plexus neuritis. Except a mannose-binding lectin deficiency, a congenital complement deficiency that is frequently found in the general Caucasian population, no other immunodeficiency was demonstrated in our patient. In vitro resistance to acyclovir was tested negative, but despite prophylactic treatment with the drug in high doses, relapses recurred. To our knowledge, this is the first ever reported documentation of relapsing-remitting facial and brachial plexus neuritis caused by HSV-1.

Topics: Acyclovir; Antiviral Agents; Brachial Plexus; Brachial Plexus Neuropathies; Chemoprevention; DNA, Viral; Facial Paralysis; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Magnetic Resonance Imaging; Mannose-Binding Lectin; Mouth Mucosa; Recurrence; Young Adult

Topics: Acyclovir; Antihypertensive Agents; Antiviral Agents; Aqueous Humor; Eye Infections, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Intraocular Pressure; Lens Implantation, Intraocular; Male; Middle Aged; Ocular Hypertension; Phacoemulsification; Polymerase Chain Reaction; Uveitis; Virus Activation

Herpes simplex virus type 1 (HSV-1) initiates productive infection in mucocutaneous tissues to cause cold sores and establishes latent infection in the trigeminal ganglia. Under certain circumstances, HSV-1 may cause encephalitis. Here, we compared host innate defenses against HSV-1 in the two clinically relevant tissues, skin and brain, using a unique ex vivo system of organ culture. Upon HSV-1 infection and spread, apoptosis induction was observed in the skin, but not in brain tissues. While the two tissues elicited interferon (IFN-β) response upon HSV1 infection, IFN induction was more robust in the skin compared to the brain. Moreover, antiviral response to exogenous IFNβ treatment was much stronger in the skin compared to brain tissues. This observation was not related to the availability of the IFN receptor on cells' surface. Taken together, our study demonstrates differential innate antiviral responses to HSV-1 infection that may be exploited in future development of selective and tissue-specific anti-viral treatments.

Topics: Acyclovir; Animals; Antiviral Agents; Brain; Gene Expression; Genes, Reporter; Green Fluorescent Proteins; Herpes Simplex; Herpesvirus 1, Human; Host-Pathogen Interactions; Humans; Immunity, Innate; Interferon-beta; Lac Operon; Mice; Myxovirus Resistance Proteins; Organ Culture Techniques; Organ Specificity; Receptor, Interferon alpha-beta; Skin; Virus Replication

Over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. Fifteen were urinary tract infections, recurrent in 4 patients. There were 8 cytomegalovirus infections, three of them fatal when intravenous (IV) ganciclovir was not available. Seven patients had a reactivation of tuberculosis (TB) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-TB therapy. Three patients transplanted before routine prophylaxis with the use of acyclovir developed an extensive herpes zoster infection in the 1st 6 months after transplantation, which was resolved with the use of oral acyclovir, and 1 had a disseminated herpes simplex infection resolved with the use of IV acyclovir. Three patients transplanted before routine prophylaxis with trimethoprim sulfa developed Pneumocystis carinii pneumonia in the 1st 6 months after transplantation, which was fatal in one of them. In 2 patients, we found a Nocardia infection, confined to the lung, which was cured in one of the cases and systemic and fatal in the other. Two patients transplanted before routine prophylaxis with the use of nystatin developed esophageal candidiasis in the 1st 6 months after transplantation. One patient developed infective endocarditis in a stenotic bicuspid aortic valve and died 10 years later after another incident of infective endocarditis at the prosthetic aortic valve. Two patients developed an extensive condyloma at the penis, perianal region, and perineum owing to human papillomavirus, requiring extensive surgical resection and podophyllin applications. Another patient developed fatal post-transplantation lymphoproliferative disease due to Epstein-Barr virus infection 15 years after transplantation. One patient developed a severe and fatal mucocutaneous leishmaniasis with no response to conventional antimonial therapy. It is interesting to note that despite Chagas disease being endemic in Bolivia, we had no patients with reactivation or transmission through the graft even though many of the patients and donors were serologically positive for Chagas disease.

Topics: Acyclovir; Adolescent; Adult; Aged; Bolivia; Child; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Female; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Tuberculosis; Young Adult

The patient was first diagnosed with candida vaginitis, but a second opinion and a closer look at the clinical picture gave way to a different diagnosis.

Topics: Acyclovir; Adult; Antifungal Agents; Antiviral Agents; Candidiasis, Vulvovaginal; Female; Herpes Simplex; Humans; Panama; Pelvic Pain; Pregnancy; Pregnancy Complications, Infectious; Treatment Outcome

Neonatal herpes is a serious condition. Newborns can be contaminated in utero via transplacental hematogenic transmission, upon delivery (the most frequent route), or during the postnatal period (indirect transmission). Optimal management requires prompt and accurate recognition, particularly in newborns, in order to prevent complications. Acyclovir is the treatment of choice, but its implementation is often delayed while awaiting test results, such as PCR and serology. Cytology for diagnostic purposes is rarely used in dermatology, despite the quick and reliable results. We report a case of neonatal herpes caused by type 2 herpes simplex virus diagnosed by cytology.

Topics: Acyclovir; Antiviral Agents; Cytological Techniques; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Skin

Topics: Acyclovir; Adult; Antiviral Agents; Early Diagnosis; Encephalitis, Herpes Simplex; Father-Child Relations; Fathers; Female; Gestures; Herpes Labialis; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Male

Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH-gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans.

Topics: Acyclovir; Administration, Rectal; Animals; Anti-Infective Agents; Antiviral Agents; Chlorocebus aethiops; Dendrimers; Epithelial Cells; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Hydrogen-Ion Concentration; Male; Mice, Inbred BALB C; Models, Molecular; Polyelectrolytes; Polymers; Rectum; Silanes; Tenofovir; Vagina; Vero Cells; Viral Proteins

Recurrent erythema multiforme (EM) is rare and is most typically related to infections with herpes simplex virus. Prophylactic administration of valaciclovir is the first-line treatment, but there is no agreement about second-line treatment in cases of ineffectiveness. We present a 31-year-old man who was not infected with hepatitis C virus (HCV), and had a history of severe and recurrent EM, unresponsive to valaciclovir, colchicine and hydroxychloroquine. The patient noticed that an intermittent flu-like illness seemed to have abrogated an EM flare. Because of this observation, the next EM flares were treated with short courses of interferon, which gave rapid and complete efficacy. Efficacy of interferon in EM has only been reported in two previous patients, in whom the drug was administered to treat HCV infection. Efficiency was attributed to treatment of the underlying HCV infection, which was thought to be the origin of EM in both cases. This is the first case, to our knowledge, reporting a dramatic response to interferon-alfa in a patient who was not infected with HCV.

Topics: Acyclovir; Adult; Antiviral Agents; Erythema Multiforme; Herpes Simplex; Humans; Immunologic Factors; Interferon-alpha; Male; Mouth Mucosa; Rare Diseases; Treatment Outcome; Valacyclovir; Valine

To report a rare case of concurrent acute retinal necrosis in a patient with iridocorneal endothelial syndrome (ICE).. Case report.. A 42-year-old woman showed acute diminution of vision in the right eye. Her fundus examination revealed features of acute retinal necrosis. She had also experienced gradual diminution of vision in her left eye for 5 years. The examination of her left eye revealed corneal edema with mild corectopia and increased intraocular pressure with abnormal endothelium on specular microscopy pointing to a diagnosis of ICE.. This is a rare case where concurrent acute retinal necrosis and ICE syndrome are present in the same patient, possibly pointing to a common viral etiology causing both entities.

Topics: Acyclovir; Adult; Antiviral Agents; Aqueous Humor; Eye Infections, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Iridocorneal Endothelial Syndrome; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Vitreous Body

Topics: Acyclovir; Adult; Antiviral Agents; Breast Feeding; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Mastitis; Nipples; Valacyclovir; Valine

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Child; Erythema Multiforme; Eye Infections, Viral; Eyelid Diseases; Herpes Simplex; Herpesvirus 1, Human; Humans; Male

Infections with adenovirus (AdV) and herpesviruses can result in considerable morbidity and mortality in pediatric hematopoietic stem cell transplant (SCT) recipients. Herpes simplex virus (HSV) reactivations are usually prevented by acyclovir (ACV) prophylaxis, whereas cidofovir (CDV) has been used off indication to manage AdV infections. We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decreased with brincidofovir, resulting in viral clearance. A subsequent Epstein-Barr virus disease with relevant meningoencephalitis responded to rituximab.

Topics: Acyclovir; Adenoviridae; Adenovirus Infections, Human; Antibiotic Prophylaxis; Antiviral Agents; Child, Preschool; Cidofovir; Cytosine; DNA, Viral; Drug Resistance, Viral; Epstein-Barr Virus Infections; Female; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpes Zoster; Herpesvirus 1, Human; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Immunocompromised Host; Meningoencephalitis; Mucositis; Myelodysplastic Syndromes; Organophosphonates; Rituximab; Viral Load

Liver failure is a frequent and serious complication that causes morbidity and mortality in haematopoietic stem cell transplantation (HCT) recipients. Liver dysfunction in these patients can be related to infectious causes, most common viral hepatitis. We report a case of disseminated acyclovir-resistant herpes simplex virus (HSV) infection following HCT that led to acute liver failure and death. Although rare, HSV hepatitis leads to high morbidity and mortality and should be considered in the differential diagnosis of HCT recipients with marked elevation of hepatic transaminase. Acyclovir is a first-line therapy for HSV infection; however, acyclovir-resistant viral strains should be considered and alternative HSV therapies given in HCT recipients whose HSV infection does not improve on acyclovir therapy.

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Drug Resistance, Viral; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 2, Human; Humans; Liver Failure, Acute; Male; Middle Aged; Tomography, X-Ray Computed; Valacyclovir; Valine

A 55-year-old woman was diagnosed with aseptic meningitis at the age of 43 and 44. She developed sudden fever and headache, and she showed nuchal rigidity. Cerebrospinal fluid examination revealed pleocytosis (cell count 208/mm

Topics: Acyclovir; Antiviral Agents; Biomarkers; DNA, Viral; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Meningitis, Aseptic; Middle Aged; Polymerase Chain Reaction; Recurrence; Time Factors

On the basis of the potent antiviral activity of acyclovir and ganciclovir, selenoacyclovir (2a) and selenoganciclovir (2b) were designed based on bioisoteric rationale and synthesized via the diselenide 7 as the key intermediate. Compound 2a exhibited potent anti-HSV-1 and -2 activities while 2b exerted moderate anti-HCMV activity, indicating that these nucleosides can serve as a novel template for the development of new antiviral agents.

Topics: Acyclovir; Antiviral Agents; Cell Line; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Organoselenium Compounds

The finding of herpetic tonsillitis is rare. Tonsillectomies are usually done for children with recurrent chronic tonsillitis, while viral throat infections are generally self-limiting. We present two cases: A 5 year-old girl, with atypical hemolytic anemia managed with Eculizumab, who presented with a pharyngeal infection and tonsillar enlargement that did not respond to intravenous antibiotics or antifungal therapies; and a 30 year-old man who presented with upper airway obstruction and fever; bilateral tonsillectomies were performed. Histopathological examination showed a necrotizing tonsillitis with numerous ground-glass intranuclear inclusions, characteristic of herpes viral infection, further confirmed by Herpes simplex virus in situ hybridization. Both patients were managed by intravenous Acyclovir, with dramatic improvement.

Topics: Acyclovir; Adult; Antiviral Agents; Child, Preschool; Female; Herpes Simplex; Humans; Male; Tonsillitis

Atypical presentations of genital herpes simplex virus have been described in HIV. We report two cases with hypertrophic presentations which were effectively treated with imiquimod, one of which is the first reported case occurring in a patient with HIV-2.

Topics: Acyclovir; Adult; Aminoquinolines; Antiviral Agents; Herpes Genitalis; Herpes Simplex; HIV Infections; HIV-1; HIV-2; Humans; Imiquimod; Male; Polymerase Chain Reaction; Simplexvirus; Treatment Outcome; Ulcer

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Bronchoscopy; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Pneumonia; Pulmonary Disease, Chronic Obstructive; Tomography, X-Ray Computed; Tracheostomy

We report a case of a 62-year-old female with seizures and encephalitis. Molecular testing of the patient's cerebrospinal fluid was positive for both herpes simplex virus 1 and 2 (HSV-1 and HSV-2). To our knowledge, this is the first report of simultaneous detection of HSV-1 and HSV-2 in cerebrospinal fluid.

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Encephalitis; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Middle Aged; Seizures

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Endophthalmitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Plasma Cells; Retina; Retinal Detachment; Vitreous Body

We aimed to compare the changes in renal function indicators as a function of hydration volume in patients treated with acyclovir for suspected herpes simplex virus (HSV) infection.. We obtained data from 216 acyclovir-treated patients hospitalized between 2007 and 2012 for suspected HSV infection. Intravenous hydration volume and renal function indicators (serum creatinine [sCr], blood urea nitrogen [BUN], glutamate oxaloacetate transferase, glutamate pyruvate transferase, and uric acid levels; estimated glomerular filtration rate [eGFR]; and urine pH) were compared among the patients. The indicators were assessed before acyclovir infusion and after 3 days of acyclovir infusion.. Before acyclovir infusion, all the indicators were within normal ranges in all groups (hydration volume lower than 2 L/day, higher than 2 L/day, and without hydration). After acyclovir infusion for 3 days, the groups without hydration and with a volume lower than 2 L/day showed increased sCr (2.22 ± 0.51 and 1.70 ± 0.35 mg/dl, respectively), BUN levels (28.33 ± 0.57 and 22.14 ± 7.95 mg/dl, respectively), and glutamate oxaloacetate transferase (48.00 ± 2.65 IU/L, without hydration) and eGFRs lower than the normal range (53.03 ± 3.05 and 59.66 ± 10.25 ml/min, respectively; p < .001 for all parameters). The renal function indicators were within normal limits in the group with a hydration volume higher than 2 L/day.. Renal function indicators in acyclovir-treated patients varied according to hydration volume. Health care providers should consider whether the hydration volume in each patient receiving intravenous acyclovir is sufficient for preventing nephropathy.

Topics: Acyclovir; Adult; Antiviral Agents; Central Nervous System Diseases; Female; Fluid Therapy; Herpes Simplex; Humans; Infusions, Intravenous; Kidney Function Tests; Male; Middle Aged; Retrospective Studies

Disseminated herpes simplex virus (HSV) infection in neonates represents a devastating entity that yields high mortality. Acyclovir is the primary antiviral agent used to treat life-threatening HSV infections in neonates; however, even though the agent has reduced morbidity overall from these infections, mortality with disseminated disease remains high. Currently, to our knowledge, no data exist regarding therapeutic drug monitoring of acyclovir in the setting of extracorporeal life support (ECLS) or continuous renal replacement therapy (CRRT) coupled with ECLS. We describe the case of a 14-day-old female with disseminated HSV-1 infection that progressed to fulminant hepatic and renal failure, necessitating the use of ECLS for hemodynamic support and CRRT as a treatment modality for hepatic and renal failure. The standard dosage of acyclovir 20 mg/kg/dose intravenously every 8 hours had been initiated, but after conversion to ECLS and CRRT, the patient's dosage was increased to 30 mg/kg/dose every 8 hours. After a repeat viral load remained unchanged from the initial viral load at 1 × 10(8)  copies/ml, the patient was transitioned from intermittent dosing to a continuous infusion of acyclovir added to the dialysate solution for CRRT at a concentration of 5.5 mg/L. To provide an optimal outcome, dosing was designed to maintain acyclovir plasma concentrations of at least 3 mg/L in order to maintain an acyclovir concentration of at least 1 mg/L in the cerebrospinal fluid. The patient's acyclovir serum concentrations measured at 24 and 72 hours after starting continuous-infusion acyclovir via the dialysate were 8.8 and 5.3 mg/L, respectively, allowing for a continuous serum concentration above 3 mg/L. Unfortunately, before a repeat viral load could be obtained to assess the efficacy of the continuous infusion acyclovir, the patient experienced an intracerebral hemorrhage as a complication related to ECLS after which technological support was withdrawn. This is the first report to describe the pharmacokinetics of continuous-infusion acyclovir in a neonate receiving ECLS with concurrent CRRT. These data suggest that adding acyclovir to the dialysate fluid during CRRT is effective in achieving therapeutic drug concentrations despite the complications of adding ECLS and CRRT circuits to a small patient.

Topics: Acyclovir; Antiviral Agents; Drug Monitoring; Extracorporeal Circulation; Female; Herpes Simplex; Humans; Infant, Newborn; Liver Failure, Acute; Pregnancy Complications, Infectious; Renal Insufficiency; Renal Replacement Therapy

The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK) is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c) that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). Topical treatment was performed by periodical inoculations (5 times per day) of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c) was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

Topics: Acyclovir; Animals; Antibodies, Monoclonal; Antiviral Agents; Chlorocebus aethiops; Corneal Stroma; Female; Glycoproteins; Herpes Simplex; Immunoglobulins; Keratitis, Herpetic; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Simplexvirus; Vero Cells

Several derivatives of γ-aminopropyl silatrane containing acyclovir in their molecular structure were synthesized and evaluated for their immunomodulatory and antiviral activities. The structures of all these derivatives were confirmed by mass spectra, IR, and (1) H NMR. Based on WST-1 assay in vitro, these compounds could stimulate proliferation of splenic lymphocytes at certain concentrations. Furthermore, compound 3d could also potentiate the expression of IFN-γ, IL-2, CD4(+) , CD8(+) , and CD4(+) /CD8(+) in vivo. Our results show that these derivatives possess antiviral activity against herpes simplex viruses with a similar potency to acyclovir without a cellular immune response.

Topics: Acyclovir; Animals; Antiviral Agents; Bridged Bicyclo Compounds, Heterocyclic; Cells, Cultured; Chlorocebus aethiops; Drug Design; Herpes Simplex; Humans; Immunologic Factors; Interferon-gamma; Interleukin-2; Mice, Inbred BALB C; Organosilicon Compounds; Simplexvirus; Vero Cells

Whereas herpes simplex virus type 1 (HSV-1) is a recognized cause of acute oropharyngeal infection in young adults, HSV-2 infections are mostly associated with genital symptoms. We report a case of acute and prolonged febrile ulcerative pharyngotonsillitis with inflammatory syndrome which persisted despite antibiotic therapy for 8 days and required hospitalization in an 18-year old immune competent and sexually active female patient. HSV-2 was evidenced in tonsillar samples and blood by real time PCR, and HSV type-specific serology showed HSV-2 primary infection. Despite delayed diagnosis, acyclovir treatment led to rapid clinical improvement. This case highlights HSV-2 as an unusual cause of pharyngotonsillitis that should be reminded in sexually active patients.

Topics: Acyclovir; Adolescent; Antiviral Agents; Blood; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Palatine Tonsil; Pharyngitis; Real-Time Polymerase Chain Reaction; Sexually Transmitted Diseases, Viral; Tonsillitis; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Disease Management; Early Diagnosis; Herpes Simplex; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Pregnancy Complications, Infectious; Simplexvirus; Time-to-Treatment

We report a case of herpes esophagitis in a 35-year-old man with pemphigus vulgaris (PV) who was undergoing treatment with corticosteroids and mycophenolate mofetil (MMF). Pemphigus vulgaris is an autoimmune intraepithelial bullous disease resulting from pathogenic IgG antibodies toward desmoglein antigens that often requires long-term immunosuppressive therapy for control of disease symptoms. Herpes esophagitis is an ulcerative eruption caused by viral reactivation in the setting of immunosuppression. Acute odynophagia in patients undergoing systemic treatment of active PV has a broad differential and warrants prompt endoscopic evaluation.

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Antiviral Agents; Esophagitis; Esophagoscopy; Herpes Simplex; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Pemphigus

Polymerase chain reaction testing of blood for herpes simplex virus (HSV) is recommended for newborns delivered to mothers with active genital HSV lesions at delivery. We report an infant who had a positive blood HSV polymerase chain reaction test before the onset of clinical signs of HSV disease.

Topics: Acyclovir; DNA, Viral; Female; Hematologic Tests; Herpes Simplex; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus

Acute retinal necrosis (ARN) should be in the differential diagnosis of a neonate who presents with vitritis. This report includes three cases of neonatal ARN at the Bascom Palmer Eye Institute from 2004 to 2009. Medical treatment with acyclovir helped reduce sequelae of herpes simplex virus (HSV) 2 infection. Patients with ARN are at risk for retinal detachment and blindness. Although mothers are screened during pregnancy, they are at risk of reactivation or primary contraction of HSV. A neonate presenting with vitritis should raise suspicion of ARN.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Aqueous Humor; DNA, Viral; Eye Infections, Viral; Female; Gestational Age; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant; Male; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute

Limited data are available on prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) disease following autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively reviewed the clinical charts of 105 consecutive patients who underwent their first auto-HCT at our institution between September 2007 and June 2014. Before August 2009, 30 patients received oral acyclovir at 1000 mg/day until engraftment, whereas after September 2009, 69 patients received oral acyclovir at 200 mg/day. After engraftment, acyclovir was continued at 200 mg/day at the discretion of the attending physicians in both groups. The cumulative incidence of HSV disease at 1 year after auto-HCT was 7.7 and 4.5 % in patients who received oral acyclovir at 1000 and 200 mg/day, respectively (P = 0.75). Patients were next divided into three groups according to the timing at which acyclovir prophylaxis was stopped after auto-HCT; at engraftment, between engraftment and 1 year after auto-HCT, and later than 1 year. The cumulative incidence of VZV disease was 25.8, 7.7, and 0.0 % at 1 year, respectively. This study suggests that low-dose acyclovir prophylaxis may be effective for preventing HSV and VZV disease after auto-HCT. Our findings support the recommendation of acyclovir prophylaxis within the first year after auto-HCT.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Female; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpes Zoster; Humans; Incidence; Male; Middle Aged; Patient Outcome Assessment; Premedication; Retrospective Studies; Risk Factors; Transplantation Conditioning; Transplantation, Autologous; Young Adult

To evaluate the efficacy of photodynamic antimicrobial chemotherapy (PACT) with the new porphyrin derivative TONS 504 and a light-emitting diode (LED) against acyclovir (ACV)-sensitive and -resistant herpes simplex virus type 1 (HSV-1).. Human FL cells infected with the viral strains were subjected to PACT with TONS 504 at various concentrations (0.01 to 10 mg/l) and irradiation at various light energies (10 to 30 J/cm(2)) and were then incubated for 24 h before analysis.. Immunocytofluorescence analysis with antibodies to HSV-1 revealed that PACT eliminated HSV-1 and ACV-resistant HSV-1 in a manner dependent on the TONS 504 concentration and light energy. Complete eradication of both viruses was apparent at a TONS 504 concentration of 10 mg/l and light energy of 10 to 30 J/cm(2) as well as at a TONS 504 concentration of 1 mg/l and light energy of 20 or 30 J/cm(2). No antiviral effect was apparent with TONS 504 in the absence of irradiation or with irradiation in the absence of TONS 504. Staining of cell nuclei with 4', 6-diamidino-2-phenylindole revealed no apparent cytotoxicity of the PACT system, a finding that was confirmed by the system's failure to induce the release of lactate dehydrogenase from the host cells.. We conclude that our PACT system based on TONS 504 and an LED is effective for eliminating HSV-1 and ACV-resistant HSV-1 without a harmful effect on host cells.

Topics: Acyclovir; Antiviral Agents; Cell Line; Cell Survival; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; L-Lactate Dehydrogenase; Photochemotherapy; Photosensitizing Agents; Porphyrins

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Aqueous Humor; DNA, Viral; Drug Therapy, Combination; Eye Infections, Viral; Female; Fluorescein Angiography; Ganciclovir; Herpes Simplex; Herpesvirus 1, Human; Humans; Infusions, Intravenous; Intravitreal Injections; Macular Edema; Middle Aged; Polymerase Chain Reaction; Prednisolone; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Tomography, Optical Coherence

A total of 302 clinical herpes simplex virus 1 (HSV-1) strains, collected over 4 decades from 1973 to 2014, were characterized retrospectively for drug resistance. All HSV-1 isolates were analyzed genotypically for nonsynonymous mutations in the thymidine kinase (TK) and DNA polymerase (Pol) genes. The resistance phenotype against acyclovir (ACV) and/or foscarnet (FOS) was examined in the case of novel, unclear, or resistance-related mutations. Twenty-six novel natural polymorphisms could be detected in the TK gene and 69 in the DNA Pol gene. Furthermore, three novel resistance-associated mutations (two in the TK gene and one in the DNA Pol gene) were analyzed, and eight known but hitherto unclear amino acid substitutions (two encoded in TK and six in the DNA Pol gene) could be clarified. Between 1973 and 2014, the distribution of amino acid changes related to the natural gene polymorphisms of TK and DNA Pol remained largely stable. Resistance to ACV was confirmed phenotypically for 16 isolates, and resistance to ACV plus FOS was confirmed for 1 isolate. Acyclovir-resistant strains were observed from the year 1995 onwards, predominantly in immunosuppressed patients, especially those with stem cell transplantation, and the number of ACV-resistant strains increased during the last 2 decades. The data confirm the strong genetic variability among HIV-1 isolates, which is more pronounced in the DNA Pol gene than in the TK gene, and will facilitate considerably the rapid genotypic diagnosis of HSV-1 resistance.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Child, Preschool; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Female; Foscarnet; Genotype; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Infant, Newborn; Male; Middle Aged; Mutation; Polymorphism, Genetic; Retrospective Studies; Sequence Analysis, DNA; Thymidine Kinase; Viral Proteins; Young Adult

Piroxicam is a potent, nonsteroidal, anti-inflammatory agent (NSAID) which also exhibits antipyretic activity. The antiviral effect of piroxicam against herpes simplex virus type 1 (HSV-1) was examined in vitro on RC-37 monkey kidney cells using a plaque reduction assay. Piroxicam was dissolved in ethanol or dimethylsulfoxide (DMSO) and the 50% inhibitory concentration (IC50) was determined at 4 μg/ml and 75 μg/ml, respectively. The IC50 for the standard antiherpetic drug acyclovir was determined at 1.6 μM. At non-cytotoxic concentrations of these piroxicam solutions, plaque formation was significantly reduced by 62.4% for ethanolic piroxicam and 72.8% for piroxicam in DMSO. The mode of antiviral action of these drugs was assessed by time-on-addition assays. No antiviral effect was observed when cells were incubated with piroxicam prior to infection with HSV-1 or when HSV-1 infected cells were treated with dissolved piroxicam. Herpesvirus infection was, however, significantly inhibited when HSV-1 was incubated with piroxicam prior to the infection of cells. These results indicate that piroxicam affected the virus before adsorption, but not after penetration into the host cell, suggesting that piroxicam exerts a direct antiviral effect on HSV-1. Free herpesvirus was sensitive to piroxicam in a concentration-dependent manner and the inhibition of HSV-1 appears to occur before entering the cell but not after penetration of the virus into the cell. Considering the lipophilic nature of piroxicam, which enables it to penetrate the skin, it might be suitable for topical treatment of herpetic infections.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Line; Cell Survival; Chlorocebus aethiops; Herpes Simplex; Herpesvirus 1, Human; Piroxicam; Viral Plaque Assay

New sources for discovering novel antiviral agents are desperately needed. The current antiviral products are both expensive and not very effective.. The antiviral activity of methanol extract of mung bean sprouts (MBS), compared to Ribavarin and Acyclovir, on respiratory syncytial virus (RSV) and Herpes Simplex virus -1 (HSV-1) was investigated using cytotoxicity, virus yield reduction, virucidal activity, and prophylactic activity assays on Vero and MRC-5 cell lines. Moreover, the level of antiviral cytokines, IFNβ, TNFα, IL-1, and IL-6 was assessed in MBS-treated, virally infected, virally infected MBS-treated, and control groups of MRC-5 cells using ELISA.. MBS extract showed reduction factors (RF) 2.2 × 10 and 0.5 × 10(2) for RSV and HSV-1, respectively. The 2 h incubation virucidal and prophylactic selectivity indices (SI) of MBS on RSV were 14.18 and 12.82 versus Ribavarin SI of 23.39 and 21.95, respectively, and on HSV-1, SI were 18.23 and 10.9 versus Acyclovir, 22.56 and 15.04, respectively. All SI values were >10 indicating that MBS has a good direct antiviral and prophylactic activities on both RSV and HSV-1. Moreover, interestingly, MBS extract induced vigorously IFNβ, TNFα, IL-1, and IL-6 cytokines in MRC-5 infected-treated group far more than other groups (P < 0.05) and induced TNFα and IL-6 in treated group more than infected group (P < 0.05).. MBS extract has potent antiviral and to a lesser extent, prophylactic activities against both RSV and HSV-1, and in case of HSV-1, these activities were comparable to Acyclovir. Part of the underlying mechanism(s) of these activities is attributed to MBS potential to remarkably induce antiviral cytokines in human cells. Hence, we infer that MBS methanol extract could be used as such or as purified active component in protecting and treating RSV and HSV-1 infections. More studies are needed to pinpoint the exact active components responsible for the MBS antiviral activities.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Cytokines; Fabaceae; Herpes Simplex; Herpesvirus 1, Human; Humans; In Vitro Techniques; Phytotherapy; Plant Extracts; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Simplexvirus; Vero Cells

Optimal acyclovir dosing under continuous renal replacement therapy (CRRT) in neonates is unknown. We monitored serum acyclovir levels and herpes simplex virus 1 (HSV-1) DNA levels in a neonate with disseminated HSV-1 infection and renal failure undergoing CRRT. A full-term, 5-day-old female presented with a 2-day history of lethargy and fever. She developed fulminant hepatitis and was diagnosed with HSV-1 infection by real-time polymerase chain reaction. Acyclovir was initiated at 60 mg/kg/day, which was lowered to 20 mg/kg/day because of development of renal failure. She was placed on continuous hemodialysis. Acyclovir dosing was adjusted according to serum acyclovir levels, and HSV-1 viral load was sequentially monitored. Semiquantification of serum HSV-1 levels was performed by real-time polymerase chain reaction. Acyclovir levels were measured by using liquid chromatography-tandem mass spectrometry. Acyclovir was administered at 20 mg/kg intravenously over 1 hour; peak concentration was 18.9 μg/mL. The half-life of acyclovir was estimated to be 2 to 3 h. Viral load remained high during dosing every 24 hours, with a decline of 0.17 log copies/24 hours. Acyclovir dosing was changed to 20 mg/kg/dose every 8 hours, with an average viral load decline of 0.44 log copies/24 hours. Despite the guideline recommendation of 24-hour redosing, acyclovir was dialyzed at a rate that resulted in suboptimal treatment. Individual therapeutic drug monitoring for acyclovir and dosing adjustment may be required to optimize therapy for patients undergoing CRRT.

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; DNA, Viral; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hemodiafiltration; Herpes Simplex; Humans; Infant, Newborn; Pregnancy Complications, Infectious; Real-Time Polymerase Chain Reaction; Simplexvirus

This study aimed to formulate an optimized acyclovir (ACV) nanoemulsion hydrogel in order to provide a solution for the slow, variable, and incomplete oral drug absorption in patient suffering from herpes simplex viral infection. Solubility of ACV in different oils, surfactants, and cosurfactants was explored utilizing a cubic model mixture design to obtain a nanoemulsion with minimum globule size. Preparation of an optimized ACV nanoemulsion hydrogel using a three-factor, three-level Box-Behnken statistical design was conducted. The molecular weight of chitosan (X1), percentage of chitosan (X2), and percentage of Eugenol as a skin permeation enhancer (X3) were selected to study their effects on hydrogel spreadability (Y1) and percent ACV permeated through rat skin after 2.5 hours (Y2). A pharmacokinetic study of the optimized ACV nanoemulsion hydrogel was conducted in rats. Mixtures of clove oil and castor oil (3:1 ratio), Tween 80 and Span 80 (3:1 ratio), and propylene glycol and Myo-6V (3:1 ratio) were selected as the oil, surfactant, and cosurfactant phases, respectively. Statistical analysis indicated that the molecular weight of chitosan has a significant antagonistic effect on spreadability, but has no significant effect on the percent ACV permeated. The percentage of chitosan also has a significant antagonistic effect on the spreadability and percent ACV permeated. On the other hand, the percentage of Eugenol has a significant synergistic effect on percent ACV permeated, with no effect on spreadability. The ex vivo study demonstrated that the optimized ACV nanoemulsion hydrogel showed a twofold and 1.5-fold higher permeation percentage than the control gel and marketed cream, respectively. The relative bioavailability of the optimized ACV nanoemulsion hydrogel improved to 535.2% and 244.6% with respect to the raw ACV hydrogel and marketed cream, respectively, confirming improvement of the relative bioavailability of ACV in the formulated nanoemulsion hydrogel.

Topics: Acyclovir; Animals; Biological Availability; Chitosan; Eugenol; Herpes Simplex; Hydrogels; Male; Models, Theoretical; Molecular Weight; Nanoparticles; Nanotechnology; Particle Size; Rats; Rats, Wistar; Skin; Skin Absorption

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Follow-Up Studies; Herpes Simplex; HIV Infections; Humans; Simplexvirus

This report describes the clinical presentation and management of a rare case of herpes simplex virus infection in the larynx of a patient treated with methotrexate.. We report a case of a clinically suspicious laryngeal lesion in an 82-year-old woman who started methotrexate treatment for rheumatoid arthritis. Shortly afterwards she developed dysphonia, which worsened over four months. On microlaryngoscopy, there was bilateral erythema and ulceration of the vocal folds. No other mucocutaneous lesions or systemic features were present. Biopsies revealed herpes simplex virus infection of the vocal folds; there was complete resolution with oral aciclovir. A brief literature review for this rare entity is presented and the diagnostic challenges arising from under-recognition of atypical presentations are discussed.. To our knowledge, this is the first report of a rare complication of herpes simplex virus infection in the context of methotrexate-induced immunosuppression. It may present therapeutic challenges for conditions which rely on immunosuppressive treatments.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Arthritis, Rheumatoid; Female; Herpes Simplex; Humans; Immunosuppressive Agents; Laryngeal Diseases; Methotrexate

An elderly patient presented with a 4-month history of eroded hypertrophic condylomatous plaques with areas of vesiculation on the groin and lower extremities bilaterally, associated with swelling. Biopsy and immunofluorescence studies confirmed the diagnosis of pemphigus vegetans (PVeg). Further clinical evaluation revealed deep venous thrombosis of the lower extremities and septic shock from secondarily infected pemphigus lesions. Fluid obtained from vesicles was positive for herpes simplex virus (HSV) via PCR-based testing. The patient was therapeutically anticoagulated, treated with high-dose corticosteroid therapy, broad-spectrum intravenous antibiotics and acyclovir. This case represents a constellation of diagnoses not previously described. Although pemphigus vulgaris has been linked to thromboembolic events and has been associated with HSV, these associations have not been previously reported in PVeg. The coexistence of these diseases should encourage vigilance in the clinical work up of a patient with PVeg.

Topics: Acyclovir; Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Anticoagulants; Antiviral Agents; Groin; Herpes Simplex; Humans; Lower Extremity; Male; Pemphigus; Polymerase Chain Reaction; Shock, Septic; Simplexvirus; Venous Thrombosis

Herpes simplex encephalitis is rarely caused by herpes simplex virus type 2 (HSV-2) after the neonatal period. The pathogenesis of HSV-2 encephalitis is not known and its treatment has not been discussed. We report a case of mild meningoencephalitis secondary to HSV-2 primary infection after sexual risk behaviour in a healthy young man. The diagnosis was established upon clinical, biological and electroencephalographic criteria. Aciclovir treatment led to rapid clinical improvement. This case highlights HSV-2 as a rare cause of meningoencephalitis, and questions the management of this rare manifestation of HSV-2 infection.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Brain; Encephalitis, Herpes Simplex; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunocompetence; Male; Meningoencephalitis; Polymerase Chain Reaction; Radiography

We here report the case of a 52-year old man who presented hepatitis with hemophagocytic syndrome triggered by herpes simplex 1 (HSV-1) primary infection. A high-level viremia was observed, and HSV-1 DNA remained detectable in blood for a long time after patient's recovery.

Topics: Acyclovir; DNA, Viral; Etoposide; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulins, Intravenous; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Treatment Outcome; Viral Load

The conventional therapy for the management of Herpes Simplex Virus Type 1 (HSV-1) infections mainly comprises acyclovir (ACV) and other nucleoside analogues. A common outcome of this treatment is the emergence of resistant viral strains, principally when immunosuppressed patients are involved. Thus, the development of new antiherpetic compounds remains as a central challenge. In this work we describe the synthesis and the in vitro antiherpetic activity of a new family of steroidal compounds derived from the endogenous hormone pregnenolone. Some of these derivatives showed a remarkable inhibitory effect on HSV-1 spread both on wild type and ACV-resistant strains. The results also show that these compounds seem to interfere with the late steps of the viral cycle.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Drug Discovery; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Microbial Sensitivity Tests; Pregnenolone; Vero Cells

A boy at 12 days of age developed neonatal herpes simplex virus (HSV) type 2 infection with central nervous system (CNS) disease. After a 21-day course of high-dose intravenous acyclovir, the patient recovered with negative results for HSV DNA in serum and cerebrospinal fluid. Two weeks after a 6-month course of oral valacyclovir suppressive therapy with negative virological assessment, the disease recurred. Another 21-day course of intravenous acyclovir and subsequent 1-year course of oral suppressive therapy were completed. He showed mild developmental delay in language-social skills at 18 months of age. Although recurrences of neonatal HSV infection with CNS disease after suppressive therapy are uncommon, both clinical and virological assessments at the end of the suppressive therapy may be required. Administration of extended long-term suppressive ACV therapy should be considered to reduce the rate of recurrence.

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Recurrence

Topics: Acyclovir; Adolescent; Alpinia; Antiviral Agents; Erythema Multiforme; Herpes Simplex; Humans; Lip; Male; Medicine, Ayurvedic; Plant Preparations; Ulcer

The clinical observation of the patient at the age of 56 years, with lesions of the esophagus by the herpes simplex virus has been presented. The patient complained of odynophagia and dysphagia. Treatment with proton pump inhibitors in outpatient stage was not effective. On endoscopic examination revealed multiple ulcers in all parts of the esophagus. Herpes simplex virus has been detected in biopsy specimens of esophageal mucosa by the PCR method. Treatment with acyclovir led to rapid and complete clinical recovery. Analysis of the literature allowed making the conclusion about the importance and actuality this demonstration.

Topics: Acyclovir; Antiviral Agents; Esophagitis; Esophagoscopy; Female; Herpes Simplex; Humans; Middle Aged; Simplexvirus; Treatment Outcome

We present a case of a preterm infant of 28 weeks' gestation with unique cutaneous lesions characteristic of a congenital herpes simplex virus (HSV) type 1 infection. The infant was prematurely delivered due to intractable labour. The mother had no history or clinical signs of genital infection before or during pregnancy. The infant's skin lesions were described as rough white-yellow plaques; a skin biopsy demonstrated calcified plaques and absent epidermis. HSV type 1 was later determined using PCR on the infant's skin biopsy and cerebral spinal fluid as well as the mother's vaginal swab and the placenta. Calcifications have already been described by Allee et al, alongside a diagnosis of HSV type 2. As is well known, the morbidity and mortality of congenital herpes infections are very high.

Topics: Acyclovir; Antiviral Agents; Erythema; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Extremely Premature; Infant, Newborn; Leg Bones; Male; Radiography; Skin

Topics: Acyclovir; Aged; Follow-Up Studies; Herpes Simplex; Humans; Immunosuppression Therapy; Kidney Transplantation; Male; Nose; Risk Assessment; Transplant Recipients; Transplantation Immunology; Treatment Outcome

Erythema multiforme (EM) is an acute self-limiting condition considered to be hypersensitivity reaction associated commonly with infections or medications. It is characterized by skin lesions, with oral or other mucous membrane involvement. Occasionally EM may involve the mouth alone. We report a ten year-old healthy male child who developed skin lesions of both palms and soles associated with oral ulcerative lesions. The patient first noticed the lesions on the palms and soles followed by involvement of the oral cavity in form of multiple haemorrhagic crusting ulcerations involving lips and buccal mucosa. The diagnosis was established clinically based on the signs and symptoms as erythema multiforme minor associated with herpes simplex infection. Systemic corticosteroids as a treatment modality should always be considered for the treatment of erythema multiforme minor.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Child; Erythema Multiforme; Herpes Simplex; Humans; Hydrocortisone; Male

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Case-Control Studies; Drug Resistance, Viral; Female; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunocompromised Host; Male; Middle Aged; Risk Factors; Simplexvirus; Treatment Outcome

Topics: Acyclovir; Adult; Alanine Transaminase; Aspartate Aminotransferases; Female; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 2, Human; Humans; Kaposi Varicelliform Eruption; Valacyclovir; Valine

In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients' data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings-and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols-we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and-in those centers facilitating a research data warehouse-advocate an analogue data review as an appropriate multicenter approach.

Topics: Acyclovir; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibiotic Prophylaxis; Antiviral Agents; Encephalitis, Varicella Zoster; Female; Germany; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Polyradiculopathy; Risk Factors; Simplexvirus; Thalidomide

A woman with severe and longstanding systemic lupus erythematosus presented with a 1-week history of fever up to 38°C and pain in her right flank. Computed tomography scan of the chest revealed interstitial infiltrates and multiple nodules. Bronchoalveolar lavage did not show any inflammatory cells. Gram stain and cultures for aerobic and anaerobic bacteria, fungi, and Nocardia; acid-fast staining; polymerase chain reaction for tuberculosis, cytomegalovirus, herpesvirus 6, and parvovirus B19; and IF staining for pneumocystic and Legionella antigen were all negative. Transbronchial biopsy was nondiagnostic. Open lung biopsy with polymerase chain reaction and immunohistochemistry analyses revealed herpes simplex virus 1 infection. Acyclovir therapy was initiated and was followed by significant improvement. Herpes simplex virus 1 infection (although unusual) should be considered in patients with systemic lupus erythematosus with an atypical clinical presentation.

Topics: Acyclovir; Antiviral Agents; Biopsy; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Lung; Lupus Erythematosus, Systemic; Middle Aged; Pneumonia; Treatment Outcome

Topics: Acyclovir; Administration, Oral; Cytomegalovirus Infections; Drug Monitoring; Ganciclovir; Herpes Simplex; Humans; Infant, Newborn; Infusions, Intravenous; Long-Term Care; Prognosis; Risk Assessment

Topics: Acyclovir; Antiviral Agents; Bronchoscopy; Herpes Simplex; Humans; Male; Middle Aged; Pneumonia, Viral

Intravenous acyclovir is the treatment of choice for herpes simplex virus encephalitis. In 2006, the American Academy of Pediatrics updated its dosing recommendations for children aged 3 months to 12 years to receive high-dose acyclovir (60 mg/kg/day). The association between acyclovir dose and toxicity is unclear.. The purpose of our study was to review our institution's experience with standard- and high-dose acyclovir for the empiric treatment of encephalitis.. This retrospective cohort study included patients aged 1 month to 18 years who received acyclovir as empiric treatment for encephalitis between 2005 and 2009 at a tertiary care children's hospital. We excluded patients with baseline renal impairment and those without serum creatinine measurements prior to and during treatment.. The main outcome measure of this study was to compare the occurrence of renal injury or failure between children who received the standard- versus high-dose regimen.. Sixty-one patients were included (n = 32 standard-dose; n = 29 high-dose). There was no statistical difference in change in serum creatinine from baseline between children who received standard- versus high-dose acyclovir (0 vs. 5.1 %; p = 0.79). One child in the standard-dose group and three children in the high-dose group developed renal injury or failure during treatment (3.1 vs. 10.3 %; p = 0.34). Children with renal injury or failure were older, had a longer length of stay, and longer duration of therapy than children without.. The incidence of renal injury or failure was similar between children who received standard-dose and high-dose acyclovir.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; Encephalitis, Viral; Female; Herpes Simplex; Hospitals, Pediatric; Humans; Infant; Male; Renal Insufficiency; Retrospective Studies; Risk Factors; Tertiary Care Centers

Topics: Acyclovir; Aged; Biopsy, Needle; Black or African American; Follow-Up Studies; Herpes Simplex; Humans; Immunocompromised Host; Immunohistochemistry; Magnetic Resonance Imaging; Male; Myelodysplastic Syndromes; Nitriles; Pyrazoles; Pyrimidines; Recurrence; Risk Assessment; Severity of Illness Index; Simplexvirus; Treatment Outcome; Virus Activation

Acyclovir-resistant herpes simplex virus (HSV) infection is common in immunocompromised patients, but the course of such infection is little known. We describe the long-term follow-up of HIV-infected patients diagnosed once with acyclovir-resistant HSV infections. We retrospectively studied all HIV-infected patients between 2000 and 2010 diagnosed with virologically confirmed acyclovir-resistant HSV infection. Patients' socio-demographic and immunovirological characteristics were described. Response to foscarnet or cidofovir and recurrences were reported. Among 5295 HIV-infected patients, 13 (0.2%) were once diagnosed with an acyclovir-resistant HSV infection. Twelve patients were men, nine patients were of African origin. All patients reported previous acyclovir exposure and median CD4 count was 183 cells/mm(3) Ten patients presented exclusively with cutaneous lesions. Initially, 11 patients were treated with foscarnet and two with cidofovir. The median follow-up was 67 months (6-145). All patients recurred, 10 presenting at least one acyclovir-resistant HSV recurrence. The median number of acyclovir-resistant HSV recurrences per patient was 2 (0 - 5). Regarding the first and second recurrences, 7/13 (54%) and 5/11 (45%) HSV clinical isolates exhibited resistance to acyclovir, respectively. Acyclovir-resistant HSV infection prevalence was low in our cohort. The rate of acyclovir-resistant HSV episodes averaged 50% during the two first recurrences.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Female; Follow-Up Studies; Foscarnet; Herpes Simplex; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Organophosphonates; Retrospective Studies; Skin Diseases, Viral; Skin Ulcer; Socioeconomic Factors; Thymidine Kinase; Treatment Outcome

Herpes viruses are involved in a variety of human disorders. Herpes Simplex Virus type 1 (HSV-1) is the most common among the herpes viruses and is primarily involved in human cutaneous disorders. Although the symptoms of infection by this virus are usually minimal, in some cases HSV-1 might cause serious infections in the eyes and the brain leading to blindness and even death. A drug, acyclovir, is available to counter this virus. The drug is most effective when used during the early stages of the infection, which makes early detection and identification of these viral infections highly important for successful treatment. In the present study we evaluated the potential of Raman spectroscopy as a sensitive, rapid, and reliable method for the detection and identification of HSV-1 viral infections in cell cultures. Using Raman spectroscopy followed by advanced statistical methods enabled us, with sensitivity approaching 100%, to differentiate between a control group of Vero cells and another group of Vero cells that had been infected with HSV-1. Cell sites that were "rich in membrane" gave the best results in the differentiation between the two categories. The major changes were observed in the 1195-1726 cm(-1) range of the Raman spectrum. The features in this range are attributed mainly to proteins, lipids, and nucleic acids.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Herpes Simplex; Herpesvirus 1, Human; Humans; Spectrum Analysis, Raman; Vero Cells; Virus Replication

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Erythema Multiforme; Gram-Negative Bacterial Infections; Hand; Herpes Simplex; Humans; Male; Mycoplasma pneumoniae; Oral Ulcer; Simplexvirus; Valacyclovir; Valine; Young Adult

The role of mutations in the thymidine kinase (TK, UL23) and DNA polymerase (pol, UL30) genes of herpes simplex virus (HSV) for development of different resistance phenotypes has to be exactly determined before genotypic resistance testing can be implemented in patient's care. Furthermore, the occurrence of cross-resistance is of utmost clinical importance. In this study, clinical HSV-1 isolates obtained between 2004 and 2011 from 26 patients after stem cell transplantation were examined in parallel by phenotypic and genotypic resistance testing. Thirteen isolates, which were phenotypically cross-resistant to acyclovir (ACV), penciclovir (PCV) and brivudin (BVDU), exhibited consistently frameshift or non-synonymous mutations in the TK gene known to confer resistance. One of these mutations (insertion of C at the nucleotide positions 1061-1065) has not been described before. Seven strains, phenotypically resistant to ACV and PCV and, except one each, sensitive to BVDU and resistant to foscarnet (FOS), carried uniformly resistance-related substitutions in the DNA pol gene. Finally, 3 isolates, resistant to ACV, PCV and 2 out of these also resistant to BVDU, had known but also unclear substitutions in the TK and DNA pol genes, and 3 isolates were completely sensitive. In conclusion, clinical ACV-resistant HSV-1 isolates, carrying resistance-associated mutations in the TK gene, can be regarded as cross-resistant to other nucleoside analogs such as BVDU. In contrast, clinical FOS-resistant HSV-1 strains which are cross-resistant to ACV may be sensitive to BVDU. This has to be considered for drug changes in antiviral treatment in case of ACV resistance.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Child; DNA-Directed DNA Polymerase; DNA, Viral; Drug Resistance, Viral; Exodeoxyribonucleases; Female; Frameshift Mutation; Guanine; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mutagenesis, Insertional; Mutation, Missense; Point Mutation; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Thymidine Kinase; Viral Proteins; Young Adult

Topics: Acyclovir; Adult; Antiviral Agents; Blister; Diagnosis, Differential; Female; Hand Dermatoses; Herpes Simplex; Humans; Prodrugs; Real-Time Polymerase Chain Reaction; Recurrence; Valacyclovir; Valine

The relevance of the detection of herpes simplex virus type 1 (HSV-1) in the respiratory tract of patients in the intensive care unit (ICU) is unclear. Therefore, it is uncertain whether treatment with an antiviral agent could be beneficial for these patients.. We retrospectively reviewed the records of ICU patients with a positive HSV-1 culture in the respiratory tract or bronchoalveolar lavage (BAL) fluid. We evaluated whether acyclovir treatment (n=106) could have a beneficial effect on mortality as compared with the standard treatment (n=106).. Acyclovir treatment was positively linked to in-hospital and ICU-mortality reduction. This favourable influence remained present after correcting for possible confounders and using propensity-adjusted and propensity-matched cohorts: with an odds ratio in the treated group of 3.19 (95% CI 1.79-5.69, p=0.001) for ICU survival and of 3.55 (95% CI 2.16-5.85, p<0.001) for in-hospital survival. The subgroup with HSV-1 detected in the BAL-fluid is the sole contributor to this difference. In the BAL-fluid detected group, 48% (n=10) of non-treated patients died in the ICU, versus 21% (n=6) in the acyclovir-treated group (p=0.033), occurring despite an even longer duration of ventilation or ICU stay.. These data highlight the hypothesis that it might be worthwhile to consider treatment of HSV-1 in ICU patients depending on the type of respiratory sample in which the virus is detected. These results warrant a prospective trial to prove causality.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Bronchoalveolar Lavage Fluid; Critical Care; Critical Illness; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Intensive Care Units; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Acyclovir; Animals; Antiviral Agents; Drug Resistance, Viral; Female; Herpes Simplex; Humans; Keratitis, Herpetic; Male

Herpes simplex virus type 2 (HSV-2) meningitis dogmatically is benign and self-limited in the immune competent patient. However, we describe how left untreated HSV-2 meningitis can be complicated by vasculitis and both ischemic and hemorrhagic stroke. We report a 57-year-old woman with lymphocytic meningitis complicated by ischemic stroke and intracerebral hemorrhage in the setting of vasculopathy and HSV-2 DNA detected in CSF successfully treated with acyclovir and corticosteroids. Subsequent angiographic magnetic resonance imaging revealed improvement in the vasculopathy after treatment. This case demonstrates that HSV-2 meningitis may take a less benign course and further provides the first evidence of angiographic improvement in addition to clinical improvement after definitive treatment.

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Meningitis, Viral; Middle Aged; Stroke; Vasculitis

A previously well 11-month-old infant presented with lethargy, a blanching rash, vomiting and diarrhoea. She was diagnosed with suspected gastroenteritis and discharged. The patient deteriorated and re-presented 24 h later with lumbar puncture (LP) confirming Neisseria meningitidis. Following an initial good response to ceftriaxone, the patient then developed a blistering facial rash on day 3 for which topical aciclovir was started with no improvement. She subsequently developed fever and redeveloped a rising C reactive protein (CRP). A CT of the head on day 6 was normal, however a repeat LP on day 7 showed persistently raised cerebrospinal fluid (CSF), white cell count (WCC), high proteins and low CSF glucose. A CSF viral PCR confirmed concurrent herpes simplex virus (HSV) type 1 for which parenteral aciclovir was started. The patient responded well to bacterial and viral anti-infective treatments and was subsequently discharged on day 16 with no neurological sequelae.

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Ceftriaxone; Diagnosis, Differential; Drug Therapy, Combination; Female; Herpes Simplex; Humans; Immunocompetence; Infant; Meningitis, Meningococcal; Meningitis, Viral; Neisseria meningitidis; Sepsis; Simplexvirus

Neonatal herpes simplex virus (HSV) infection is uncommon, but mortality after disseminated disease and morbidity after encephalitis are high. For the last decade, increased dose and duration of acyclovir has been advised to prevent disease progression and recurrence. We sought to determine prospectively the epidemiologic, clinical, and secular trends of this condition in Australia.. This was prospective national active surveillance for neonatal HSV disease through the Australian Paediatric Surveillance Unit from 1997 to 2011. Case notification triggered a questionnaire requesting de-identified data from the pediatric clinician.. We identified 131 confirmed cases of neonatal HSV disease in 15 years from 261 notifications (95% response). The reported incidence (3.27 cases per 100 000 live births overall; 95% confidence interval [CI], 2.73-3.86) was stable. Overall mortality was 18.8% (95% CI, 12.1-25.5); the mortality rate was significantly lower in the latter part of the study period, 2005-2011, compared with 1997-2004 (P = .04). There were significantly more young mothers (<20 years of age) compared with Australian birth record data (18.5% vs 4.8%; P < .001). HSV-1 infection was more common than HSV-2 (62.7% vs 37.3%; P < .001), and the rate of HSV-1 infections increased significantly over the surveillance period (P < .05). From 2002, most infants received high-dose acyclovir. The time from symptom onset to initiation of therapy in survivors did not change over time.. Mortality from neonatal HSV infection has fallen but remains high. HSV-1 is the major serotype causing neonatal disease in Australia. Young mothers represent an important target group for prevention.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Australia; Drug Utilization; Epidemiological Monitoring; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Infant, Newborn; Male; Pregnancy Complications, Infectious; Prospective Studies; Surveys and Questionnaires; Survival Analysis; Young Adult

Topics: Acyclovir; Anti-Bacterial Agents; Antifungal Agents; Antimalarials; Antiviral Agents; Candidiasis; Child, Preschool; Clindamycin; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Intertrigo; Ketoconazole; Male; Staphylococcal Infections; Sulfamethoxazole; Trimethoprim

Topics: Acute Disease; Acyclovir; Antiviral Agents; Biopsy; Cesarean Section; Female; Hepatitis, Viral, Human; Herpes Simplex; Humans; Liver; Pregnancy; Pregnancy Complications; Simplexvirus; Treatment Outcome; Young Adult

We reviewed the characteristics of infants <3 months of age with central nervous system herpes simplex virus infection at our institution. Twenty-six cases were identified. The age range was 4-73 days. Most infants presented with fever, seizure activity and skin lesions. The blood herpes simplex virus polymerase chain reaction was positive in 91% of patients tested. Suppressive oral acyclovir therapy was likely helpful in preventing disease recurrence.

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Fever; Herpes Simplex; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Meningoencephalitis; Retrospective Studies; Seizures; Skin Diseases, Viral

A wide range of antiviral drugs is currently available; however, drug-resistant viruses have begun to emerge and represent a potential public health risk. Here, we explored the use of compounds that inhibit or interfere with the action of essential host factors to prevent virus replication. In particular, we focused on the cyclin-dependent kinase 9 (CDK9) inhibitor, FIT-039, which suppressed replication of a broad spectrum of DNA viruses through inhibition of mRNA transcription. Specifically, FIT-039 inhibited replication of herpes simplex virus 1 (HSV-1), HSV-2, human adenovirus, and human cytomegalovirus in cultured cells, and topical application of FIT-039 ointment suppressed skin legion formation in a murine HSV-1 infection model. FIT-039 did not affect cell cycle progression or cellular proliferation in host cells. Compared with the general CDK inhibitor flavopiridol, transcriptome analyses of FIT-039-treated cells revealed that FIT-039 specifically inhibited CDK9. Given at concentrations above the inhibitory concentration, FIT-039 did not have a cytotoxic effect on mammalian cells. Importantly, administration of FIT-039 ameliorated the severity of skin lesion formation in mice infected with an acyclovir-resistant HSV-1, without noticeable adverse effects. Together, these data indicate that FIT-039 has potential as an antiviral agent for clinical therapeutics.

Topics: Acyclovir; Adenoviruses, Human; Animals; Antiviral Agents; Cyclin-Dependent Kinase 9; Cytomegalovirus; Disease Models, Animal; DNA Viruses; Drug Resistance, Viral; Flavonoids; HEK293 Cells; HeLa Cells; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Host-Pathogen Interactions; Humans; Mice; Mice, Inbred ICR; Piperidines; Protein Kinase Inhibitors; Pyridines; Rats; Rats, Wistar; Transcription, Genetic; Transcriptome; Virus Replication

Topics: Acyclovir; Antiviral Agents; C-Reactive Protein; Diaper Rash; Disease Transmission, Infectious; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Leukocyte Count; Male

The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant herpes simplex virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5% and 10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002 and 2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002 and 2006 (7/182 patients) to 15.7% between 2007 and 2011 (28/178) (p=0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002 and 2006 to 46.5% (26/56) between 2007 and 2011 (p=0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Child; Child, Preschool; Drug Resistance, Viral; Female; France; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Male; Middle Aged; Mutation; Retrospective Studies; Viral Proteins; Young Adult

A 20-year-old man presented with a recurrent episode of herpetic keratouveitis in his right eye. The patient was treated with oral acyclovir and topical steroids. One week later the patient reported a sudden diminution of vision. Slitlamp biomicroscopy revealed the presence of a central anterior capsular defect and anterior subcapsular cataract. Dosage of steroids was temporarily increased and progression of cataract monitored. Subsequently, the anterior chamber reaction decreased and steroids were tapered.

Topics: Acyclovir; Adrenal Cortex Hormones; Anterior Capsule of the Lens; Antiviral Agents; Cataract; Herpes Simplex; Humans; Keratitis, Herpetic; Male; Recurrence; Uveitis, Anterior; Vision Disorders; Young Adult

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Esophagitis; Female; Frail Elderly; Herpes Simplex; Humans; Valacyclovir; Valine

The aim of this study was to assess current attitudes and approaches to the febrile neonate in terms of diagnostic investigations and empiric treatment of suspected herpes simplex virus (HSV) infection.. Between March 2010 and November 2010, a survey describing a hypothetical case of a febrile neonate presenting to the ED without clear signs of an HSV infection was sent to tertiary care pediatric emergency physicians across Canada. Participants were asked multiple choice and open-ended questions to obtain information about their choice of investigations, empiric treatment, and impression of the likelihood of HSV in the case. Survey data were analyzed using univariate statistics.. Blood culture (98.6%), complete blood count (99.3%), lumbar puncture (81.2%), and nasopharyngeal swabs for respiratory viruses (61.6%) were most commonly performed by the 139 respondents, whereas 33% reported they would send cerebrospinal fluid for HSV polymerase chain reaction. Most (76%) would administer empiric antibiotics, whereas 5.8% included acyclovir to their treatment regimen. Greater than 50% included positive maternal history as an important factor in determining a febrile neonate's risk of HSV infection. Thirty-four percent reported that the wellness of the child, the presence of skin changes (37%), and the presence of any worrisome neurologic sign or symptom (37%) would influence their decision for investigations and empiric administration of acyclovir.. Canadian pediatric emergency physicians are aware of risk factors for neonatal HSV infection and tailor their history and diagnostic investigations toward the diagnosis of HSV infection, but very few empirically administer acyclovir. Examination of future Canadian HSV guidelines for this patient population is warranted.

Topics: Acyclovir; Antiviral Agents; Canada; Diagnosis, Differential; Emergency Medicine; Female; Fever; Herpes Simplex; Humans; Infant, Newborn; Male; Practice Patterns, Physicians'; Pregnancy Complications, Infectious; Prospective Studies; Risk Factors; Surveys and Questionnaires

A 9-month-old baby girl presented multiple times with an erythematous, papular and pustular big toe in an otherwise healthy infant. A diagnosis of cellulitis was made and she was started on oral antibiotics, and bacterial swabs were taken. After 2 weeks of worsening appearance she was admitted for intravenous antibiotics. Inflammatory markers remained normal and viral swabs were taken. No improvement was seen after 2 days and she was referred for orthopaedic and dermatological opinions. The orthopaedic team recommended debridement whereas the dermatologist suspected a primary herpetic whitlow and recommended intravenous acyclovir in addition to intravenous antibiotics. A viral swab for Herpes simplex virus type 1 (HSV1) was positive by PCR on day 3. The toe continued to improve clinically and the patient received 21 days of acyclovir in total. 27 days after discharge the infection relapsed. She was treated with a further 14 days of oral acyclovir and recovered completely.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Diagnosis, Differential; DNA, Viral; Female; Foot Dermatoses; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Polymerase Chain Reaction; Recurrence; Toes

To identify the current practice patterns of physicians providing prenatal care in Alberta with respect to prevention of neonatal herpes simplex virus (HSV) infection.. A 22-item questionnaire was mailed to all obstetricians and family physicians providing obstetrical care in Alberta. The questionnaire included demographic and practice details, and details of management of patients with a history or symptoms of HSV lesions, including practice in prescribing antiviral therapy, recommending elective Caesarean section, and ordering serology. Two reminders were mailed as necessary.. Responses were received from 89 obstetricians (57%) and 94 family physicians (54%). Antiviral therapy was prescribed for the prevention of neonatal HSV infection in the third trimester by 97% of obstetricians versus 84% of family physicians (P = 0.007), with acyclovir being the most commonly prescribed agent. Caesarean section was offered "most of the time" to women with primary HSV infection in the third trimester by 65% of physicians, to women with prodromal symptoms during the intrapartum period by 57% (no significant differences between groups), and to women with HSV lesions by 92% of obstetricians and 82% of family physicians (P = 0.032). Women with a negative HSV history but whose partner had known HSV were offered serological testing "most of the time" by 30% of physicians (no significant difference between groups).. Despite the encouraging survey results, obstetrical providers should be encouraged to offer Caesarean section to women with a primary HSV infection in the third trimester and to offer serological testing in discordant couples. These simple strategies can help to prevent neonatal HSV infection and its long-term consequences.

Topics: Acyclovir; Adult; Aged; Alberta; Antiviral Agents; Cesarean Section; Family Practice; Female; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Middle Aged; Obstetrics; Practice Patterns, Physicians'; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Prenatal Care; Sexual Partners; Surveys and Questionnaires

Neonatal herpes simplex virus infections are uncommon, but because of the morbidity and mortality associated with the infection they are often considered in the differential diagnosis of ill neonates. The use of polymerase chain reaction for diagnosis of central nervous system infections and the development of safe and effective antiviral therapy has revolutionized the diagnosis and management of these infants. Initiation of long-term antiviral suppressive therapy in these infants has led to significant improvement in morbidity. This article summarizes the epidemiology of neonatal herpes simplex virus infections and discusses clinical presentation, diagnosis, management, and follow up of infants with neonatal herpes disease.

Topics: Acyclovir; Adult; Antiviral Agents; Central Nervous System Viral Diseases; Developmental Disabilities; Diagnosis, Differential; Evidence-Based Medicine; Female; Herpes Genitalis; Herpes Simplex; Herpes Simplex Virus Vaccines; Humans; Infant, Newborn; Morbidity; Mothers; Polymerase Chain Reaction; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Recurrence; Risk Factors; Severity of Illness Index; Simplexvirus

Herpes simplex virus 2 is a leading cause of viral meningitis and the most commonly recognized infectious cause of benign, recurrent meningitis. We report a retrospective, observational cohort study of patients with herpes simplex virus type 2 (HSV-2) meningitis, confirmed by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). The terms "herpes simplex," "meningitis," or "encephalitis" were searched in the medical records system of the Mayo Clinic in Rochester, Minnesota (1995-2008). Patients were included if they had a clinical diagnosis of meningitis and HSV-2 detected by PCR in the CSF. There were 28 patients with 33 episodes identified (83 % female; mean age at presentation of meningitis 36 years, range 17-53; mean time to HSV2 detection from symptom onset 3 days, range 0-6; history of genital herpes 23 %). No patient took oral antiviral treatment at the time of presentation. Episodes were most likely to include headache (100 %), photophobia (47 %), self-reported fever (45 %), meningismus (44 %), and nausea and/or vomiting (29 %). CSF at the time of meningitis was notable for elevated protein (mean 156 g/dL, range 60-258) and white cell count (mean 504 cells/μL, range 86-1,860) with normal glucose (mean 54 mg/dL, range 32-80). Mollaret cells were never detected. Neuroimaging was most often normal (83 %) when performed, although some cases showed nonspecific (14 %) or meningeal changes (3 %). There was no consistent relationship to genital herpes. The duration of treatment with intravenous acyclovir ranged from 3 to 14 days for the first meningitic episode (daily dose range from 500 to 1,000 mg and total dose range from 500 mg q8h for 3 days to 800 mg q8h for 14 days). For subsequent episodes, the duration of treatment of intravenous acyclovir ranged from less than 1 to 14 days (total dose range from 1,390 mg for 1 day to 900 mg q8h for 10 days). The dose of valacyclovir ranged from 500 mg once daily to 500 mg four times daily. The median duration of valacyclovir treatment following the first episode was 10 days (range 3 to 14 days, n = 13). The median duration of valacyclovir treatment following a subsequent meningitic episode was 9 days (range 7 days to indefinite period, n = 9). No patient was reported to have seizures, neurological disability, or death in extended follow-up (mean follow-up 3.4 years). Recurrence of meningitic symptoms was not universal.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Drug Administration Schedule; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Male; Meningitis, Viral; Middle Aged; Retrospective Studies; Secondary Prevention; Treatment Outcome; Valacyclovir; Valine

Cold sores are a common condition that can cause significant morbidity and mortality. Antivirals are the typical treatment for cold sores, but the ways in which these medications are used to treat cold sores are not well studied.. To determine the main treatments prescribed for cold sores and trends in their management over time.. A retrospective analysis of the National Ambulatory Medical Care Survey database was used to analyze outpatient visits for cold sores from 1993 to 2009. Patients were included in the data analysis if they had one of the following three diagnoses reported for their reason-for-visit codes: cold sores (CS), herpes simplex (HS) or herpes simplex with cold sores (HS/CS).. There was a decreasing trend in the number of annual patient visits for cold sores. The majority of patients were mainly young to middle adulthood, white women. The top two most commonly prescribed medications were acyclovir followed by valacyclovir. Valacyclovir use increased in all three populations, while acyclovir use decreased.. The trends observed may indicate that physicians are evolving their treatment strategies to implement newer antiviral medications. This may prove more efficacious for the treatment of cold sores.

Topics: Acyclovir; Adolescent; Adult; Ambulatory Care; Antiviral Agents; Female; Health Care Surveys; Herpes Labialis; Herpes Simplex; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies; Valacyclovir; Valine

Despite the availability of antiviral chemotherapy, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections remain a severe global health problem. Of particular concern is the growing incidence of drug resistance in immunocompromised patients, which stresses the urgency to develop new effective treatment alternatives. We have developed a humanized monoclonal antibody (mAb hu2c) that completely abrogates viral cell-to-cell spread, a key mechanism by which HSV-1/2 escapes humoral immune surveillance. Moreover, mAb hu2c neutralized HSV fully independent of complement and/or immune effector cell recruitment in a highly efficient manner. Prophylactic and therapeutic administration of mAb hu2c completely prevented infection-related mortality of severely immunodeficient mice being challenged with a lethal dose of HSV-1. The high neutralization capacity of mAb hu2c was fully maintained toward clinical HSV isolates being multiresistant to standard antiviral drugs, and infection was fully resolved in 7/8 nonobese diabetic/SCID mice being infected with a multidrug resistant HSV-1 patient isolate. Immunohistochemical studies revealed no significant cross-reactivity of the antibody toward human tissues. These features warrant further clinical development of mAb hu2c as an immunotherapeutic compound for the management of severe and particularly drug-resistant HSV infections.

Topics: Acyclovir; Animals; Antibodies, Monoclonal; Antibodies, Viral; Chlorocebus aethiops; Drug Resistance, Viral; Herpes Simplex; Immunohistochemistry; Mice; Mice, SCID; Microscopy, Fluorescence; Neutralization Tests; Simplexvirus; Vero Cells

Acyclovir (ACV) is the antiviral drug of choice to treat patients with herpes simplex virus type 1 (HSV-1) uveitis. The prevalence of intra-ocular ACV-resistant (ACV(R)) HSV-1 in herpetic uveitis is unknown and may have clinical consequences. In addition to its predictive value on ACV susceptibility, the polymorphic HSV-1 thymidine kinase (TK) gene facilitates differentiation between HSV-1 strains.. The objective of this study was to determine the genetic composition and ACV susceptibility of the causative virus in intra-ocular fluid samples (IOF) of HSV-1 uveitis patients.. The intra-ocular HSV-1 pool from 11 HSV-1 uveitis patients was determined by sequencing IOF-derived viral TK genes. The ACV susceptibility profile of the cloned intra-ocular TK variants was defined by mass spectrometry. In addition, the ganciclovir (GCV) susceptibility of the ACV(R) HSV-1 TK variants was defined.. Intra-ocular fluid samples of HSV-1 uveitis patients contain HSV-1 quasispecies, principally consisting of one major and multiple genetically related minor patient-specific TK variants. Four of 10 patients analyzed had an intra-ocular ACV(R) HSV-1 of which 3 were cross-resistant to GCV. The ACV(R) profile of intra-ocular HSV-1 did not correlate with symptomatic ACV treatment.. Affected eyes of HSV-1 uveitis patients are commonly infected with a patient-specific HSV-1 quasispecies, including one major and multiple genetically related minor variants. A relatively high prevalence of intra-ocular ACV(R) HSV-1, mainly ACV/GCV cross-resistant viruses, was detected in HSV-1 uveitis patients.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Aqueous Humor; DNA, Viral; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Sequence Data; Sequence Analysis, DNA; Thymidine Kinase; Uveitis

Topics: Acyclovir; Antiviral Agents; Female; Fever; Herpes Simplex; Humans; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus; Viremia

The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent.

Topics: Acyclovir; Antiviral Agents; Cell Line; Fibroblasts; Ganciclovir; Guanine; Herpes Simplex; Herpesvirus 1, Human; Humans; Positron-Emission Tomography; Pyrimidine Nucleosides; Radiography; Thymidine Kinase

Topics: Acyclovir; Adult; Antiviral Agents; Back Pain; Exanthema; Face; Female; Hepatitis; Herpes Simplex; Herpesvirus 2, Human; Humans; Lumbosacral Region; Magnetic Resonance Imaging; Neck; Serositis

Previous studies examining the teratogenic effects of antiherpetic medications have found no associations for birth defects overall but have not examined the risk of specific birth defects.. The National Birth Defects Prevention Study ascertains population-based cases with birth defects and live-born controls without birth defects in 10 states across the United States for the purpose of identifying potential teratogenic risk factors. Mothers of cases and controls are interviewed within 2 years of their estimated date of delivery about demographic, medical and behavioural factors before and during pregnancy. This analysis examined the possible association between use of antiherpetic medications (acyclovir, valacyclovir or famciclovir) during early pregnancy and gastroschisis, a birth defect of the abdominal wall.. The mothers of 1.1% (n = 10) of 941 gastroschisis cases and 0.3% (n = 27) of 8339 controls reported antiherpetic medication use during the month before conception through the third month of pregnancy. The adjusted odds ratios for such use in relation to gastroschisis were 4.7 [95% confidence interval 1.7, 13.3] and 4.7 [95% CI 1.2, 19.0] among women with and without self-reported genital herpes, respectively, when compared with women without antiherpetic use or herpes. Among women reporting no antiherpetic medication use, the odds ratio for self-reported genital herpes in relation to gastroschisis was 3.0 [95% CI 1.6, 5.7].. Our study raises the possibility of an increased risk of gastroschisis because of either antiherpetic medication use during early pregnancy or the underlying genital herpes infection for which it was indicated.

Topics: 2-Aminopurine; Acyclovir; Adolescent; Adult; Antiviral Agents; Case-Control Studies; Famciclovir; Female; Gastroschisis; Herpes Simplex; Humans; Infant, Newborn; Maternal Exposure; Middle Aged; Pregnancy; Regression Analysis; United States; Valacyclovir; Valine; Young Adult

A young woman presented with a febrile illness in the third trimester of pregnancy. Laboratory investigation revealed severe acute hepatitis with thrombocytopenia and coagulopathy. Liver injury progressed despite emergent caesarian section and delivery of a healthy infant. Therefore, therapeutic plasma exchange (TPE) was performed on three consecutive days post-partum for a presumed diagnosis of acute liver failure (ALF) associated with pregnancy due to hemolysis, elevated liver enzymes, and low platelets (HELLP) or acute fatty liver of pregnancy (AFLP). Treatment with TPE was followed by biochemical and clinical improvement but during her recovery herpes simplex virus type 2 (HSV-2) infection was diagnosed serologically and confirmed histologically. Changes in the immune system during pregnancy make pregnant patients more susceptible to acute HSV hepatitis, HSV-related ALF, and death. The disease is characterized by massive hepatic inflammation with hepatocyte necrosis, mediated by both direct viral cytotoxicity and the innate humoral immune response. TPE may have a therapeutic role in acute inflammatory disorders such as HSV hepatitis by reducing viral load and attenuating systemic inflammation and liver cell injury. Further investigation is needed to clarify this potential effect. The roles of vigilance, clinical suspicion, and currently accepted therapies are emphasized.

Topics: Acute Disease; Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Cesarean Section; Combined Modality Therapy; Dexamethasone; Emergencies; Female; Fetal Organ Maturity; Hepatitis, Viral, Human; Herpes Simplex; Humans; Hydrocortisone; Infant, Newborn; Liver Failure; Male; Plasma Exchange; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Puerperal Disorders; Systemic Inflammatory Response Syndrome; Young Adult

Herpes simplex virus type 1 (HSV1) infection of cultured cells causes the formation of β-amyloid (Aβ) and abnormal tau (P-tau). These molecules comprise the main components of the abnormal protein deposits, amyloid plaques and neurofibrillary tangles, respectively, in Alzheimer's disease (AD) brains, and they have been implicated in disease development. The formation of P-tau, but not of Aβ, depends on viral DNA replication, but nonetheless, three antiviral agents that inhibit HSV1 DNA replication, including acyclovir (ACV), were found to reduce greatly the level of Aβ as well as P-tau, the former probably through prevention of viral spread. Previous studies showed that HSV1 DNA is present and is active in the brain of many elderly people, including AD patients, and that in combination with the type 4 allele of the apolipoprotein E gene, it is likely to play a role in the disease, perhaps via Aβ and P-tau production. With the aim of finding the most suitable antiviral for inhibiting Aβ and P-tau formation as well as HSV1 DNA replication, for future use in a clinical trial for treating AD, we compared the efficacy of ACV with that of another antiviral, BAY 57-1293, which acts by a different mechanism from ACV. We found that BAY 57-1293 is more efficient than ACV not only in inhibiting HSV1 replication, confirming previous studies, but also in decreasing Aβ and P-tau formation. Also, the cell clusters that are formed during infection are reduced in size much more efficiently by BAY 57-1293 than by ACV. These data suggest that BAY 57-1293 would be a more effective agent than ACV for treating AD.

Topics: Acyclovir; Alzheimer Disease; Amyloid beta-Peptides; Antiviral Agents; DNA Helicases; DNA Primase; Down-Regulation; Enzyme Inhibitors; Herpes Simplex; Herpesvirus 1, Human; Humans; Pyridines; Sulfonamides; tau Proteins; Thiazoles; Viral Proteins; Virus Replication

Currently, acyclovir (ACV) at 1000 mg/day is widely used as prophylaxis in the early phase of hematopoietic stem cell transplant (HSCT) in Japan. However, low-dose ACV (200 mg/day) has been shown to prevent varicella zoster virus reactivation in the middle and late phases of HSCT.. Therefore, in this study, we decreased the dose of ACV to 200 mg/day in the early phase after HSCT. We analyzed 93 consecutive herpes simplex virus (HSV)-seropositive patients who underwent allogeneic HSCT for the first time in our center between June 2007 and December 2011.. Before August 2009, 38 patients received oral ACV at 1000 mg/day (ACV1000) until day 35 after HSCT, whereas 55 patients received oral ACV at 200 mg/day (ACV200) after September 2009. We compared the cumulative incidence of HSV infection in the 2 groups. Oral ACV was changed to intravenous administration because of intolerance in 66% and 45% of the patients in the ACV1000 and ACV200 groups, respectively (P = 0.060). The probability of severe stomatitis (Bearman grade II-III) was 76% and 60% in the ACV1000 and ACV200 groups, respectively (P = 0.12). The number of patients who developed HSV disease before day 100 after HSCT was 0 in the ACV1000 group and 2 in the ACV200 group, with a cumulative incidence of 3.6% (P = 0.43). HSV disease in the latter 2 patients was limited to the lips and tongue and was successfully treated with ACV or valacyclovir at a treatment dose.. ACV at 200 mg/day appeared to be effective for preventing HSV disease in the early phase after HSCT.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Female; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Incidence; Japan; Male; Middle Aged; Retrospective Studies; Simplexvirus; Transplantation, Homologous; Virus Activation; Young Adult

Topics: Acyclovir; Animals; Antiviral Agents; Drug Resistance, Viral; Female; Herpes Simplex; Humans; Keratitis, Herpetic; Male

Long-term acyclovir (ACV) prophylaxis, recommended to prevent recurrent herpes simplex virus type 1 (HSV-1) ocular disorders, may pose a risk for ACV-refractory disease due to ACV resistance. We determined the effect of ACV prophylaxis on the prevalence of corneal ACV-resistant (ACV(R)) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK).. Frequencies of ACV(R) viruses were determined in 169 corneal HSV-1 isolates from 78 rHK patients with a history of stromal disease. The isolates' ACV susceptibility profiles were correlated with clinical parameters to identify risk factors predisposing to ACV(R) rHK.. Corneal HSV-1 isolates with >28% ACV(R) viruses were defined as ACV(R) isolates. Forty-four isolates (26%) were ACV-resistant. Multivariate analyses identified long-term ACV prophylaxis (≥12 months) (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.32-8.87) and recurrence duration of ≥45 days (OR 2.23; 95% CI, 1.02-4.87), indicative of ACV-refractory disease, as independent risk factors for ACV(R) isolates. Moreover, a corneal ACV(R) isolate was a risk factor for ACV-refractory disease (OR 2.28; 95% CI, 1.06-4.89).. The data suggest that long-term ACV prophylaxis predisposes to ACV-refractory disease due to the emergence of corneal ACV(R) HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients.

Topics: Acyclovir; Aged; Animals; Antiviral Agents; Chemoprevention; Chlorocebus aethiops; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Keratitis, Herpetic; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence; Risk Factors; Vero Cells

Neonatal Herpes Simplex Virus (HSV) infection is a serious illness with significant mortality and morbidity for disseminated disease. Clinical diagnosis of neonatal HSV infection is often difficult without evidence of HSV exposure, for example, absence of a rash or the presence of non-specified manifestations in an infant. Early recognition and treatment with high-dose Acyclovir may dramatically improve the short and long-term outcomes. We describe an infant with disseminated disease due to HSV-1 infection, who first presented clinical and radiologic features of pneumonia. The diagnosis was performed post-mortem by Real-Time Polymerase Chain Reaction (PCR) analysis of blood, cerebrospinal fluid and pleural liquid of the infant. Tissue PCR revealed a disseminated HSV-1 infection, with a high viral load detected in liver, lungs, brain, heart, striated muscle, kidneys, and thymus tissues. This case report highlights the need for neonatologists to raise awareness about the different clinical manifestations of disseminated neonatal HSV infection. HSV infections should be prominent in the differential diagnosis of an infant under four weeks of age with fever, pneumonia, unexplained seizures or sepsis-like disease, particularly if unresponsive to antibiotics. Early initiation of appropriate antiviral therapy for high-risk infants undergoing testing for HSV infection can be essential to prevent significant morbidity and mortality.

Topics: Acyclovir; Brain; Diagnosis, Differential; DNA, Viral; Early Diagnosis; Fatal Outcome; Heart; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Kidney; Liver; Liver Diseases; Lung; Lymphoid Tissue; Male; Muscle, Striated; Organ Specificity; Pneumonia, Viral; Pregnancy Complications, Infectious; Radiography; Real-Time Polymerase Chain Reaction; Viral Load

Topics: Acyclovir; Aged; Antibodies, Viral; Antiviral Agents; Coloring Agents; Conjunctival Diseases; Eye Infections, Viral; Female; Herpes Simplex; Humans; Immunoglobulin G; Lissamine Green Dyes; Simplexvirus; Ulcer; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Herpes Simplex; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Skin Diseases, Vesiculobullous

Eleven strains of acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) were generated from HSV-1 clinical isolates by exposure to ACV. Genotype of the thymidine kinase (TK) and DNA polymerase (pol) genes from these mutants were further analyzed. Genotypic analysis revealed four non-synonymous mutations in TK gene associated with gene polymorphism and two to three non-synonymous mutations in DNA pol gene. Seven and six strains contained at least one resistance-associated mutation at TK and DNA pol gene, respectively. Resistance-associated mutations within the TK gene consisted of 64% of non-synonymous frameshift mutations within the homopolymer region of G's and C's, and 36% of non-synonymous nucleotide substitutions of the conserved gene region (C336Y, R51W and R222H), nucleotide that produced stop codon (L288Stop) and two amino acid substitutions outside the conserved region (E39G & L208F). There were 10 non-synonymous amino acid substitutions located outside the conserved region with the unclear significance to confer resistance observed. Resistance-associated mutations in DNA pol gene include insertion of G at the homopolymer region of G's (794-797) and amino acid substitutions inside (V621S) or outside (H1228D) the conserved region. In silico analysis of the mutated TK (C336Y, R51W and L208F), and DNA pol (V621S and H1228D) suggested structural changes that might alter the stability of these proteins. However, there were several mutations with unclear significance to confer ACV-resistance identified, especially mutations outside the conserved region.

Topics: Acyclovir; Antiviral Agents; DNA Mutational Analysis; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Microbial Sensitivity Tests; Mutation; Selection, Genetic; Serial Passage; Viral Proteins; Virus Cultivation

Herpes simplex virus (HSV) resistance to antivirals constitutes a therapeutic challenge, especially among immunocompromised patients. This observational survey on HSV resistance to antivirals was conducted retrospectively over a 4-year period (2008-2012). A total of 211 HSV-positive clinical samples (94 HSV-1 and 117 HSV-2) recovered from 139 patients (11 immunocompetent patients, 85 immunocompromised patients, and 43 patients with unknown immune status) with suspected HSV drug-resistance were analyzed for acyclovir and foscarnet susceptibility. Antiviral resistance testing consisted in a two-step procedure including a first-step genotypic assay, based on UL23 (thymidine kinase, TK) and UL30 (Pol) gene sequencing, and a second-step phenotypic assay (i.e., plaque reduction assay) performed when unpreviously described mutations were detected. As a whole, susceptibility and resistance to antivirals were evidenced for 58 (30.7%) and 86 (45.5%) HSV, respectively, whereas antiviral profile remained undetermined for 45 (23.8%) HSV. The prevalence of drug resistance was significantly higher among HSV-2 isolates than among HSV-1 isolates (53.8% vs. 34.9%; p=0.012). The majority (i.e., 79.7%) of cases of ACV resistance conferred by TK mutations resulted from UL23 gene frameshift reading. Apart from the changes surely related to natural polymorphism or drug-resistance, 91 unpreviously reported mutations were identified in TK and Pol, including 51 potential natural polymorphisms, 22 mutations likely conferring resistance to antivirals, and 18 mutations of unclear significance.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Child, Preschool; Drug Resistance, Viral; Epidemiological Monitoring; Female; Foscarnet; Genotype; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence; Retrospective Studies; Viral Proteins; Young Adult

Herpes simplex virus (HSV) is a recognized cause of gastrointestinal infection in immunodeficient patients. Although a few cases of HSV gastritis and colitis in immunocompromised patients have been reported, there are no reports of HSV duodenitis in patients with Crohn's disease (CD). A 74-year-old female was admitted with general weakness and refractory epigastric pain. She had been diagnosed with CD three years ago. Esophagogastroduodenoscopy (EGD) revealed diffuse edematous and whitish mucosa with multiple erosions in the duodenum. Considering the possibility of viral co-infection, cytomegalovirus (CMV) immunohistochemical staining, PCR, and cultures of duodenal biopsies were performed, all of which were negative with the exception of the isolation of HSV in culture. After administration of intravenous acyclovir for 1 week, follow-up EGD showed almost complete resolution of the lesions and the patient's symptoms improved. In CD patients with refractory gastro-intestinal symptoms, HSV, as well as CMV, should be considered as a possible cause of infection, so that the diagnosis of viral infection is not delayed and the appropriate antiviral treatment can be initiated.

Topics: Acyclovir; Aged; Antiviral Agents; Crohn Disease; DNA, Viral; Duodenitis; Endoscopy, Digestive System; Female; Herpes Simplex; Humans; Intestinal Mucosa; Polymerase Chain Reaction; Simplexvirus

Outcome misclassification is widespread in epidemiology, but methods to account for it are rarely used. We describe the use of multiple imputation to reduce bias when validation data are available for a subgroup of study participants. This approach is illustrated using data from 308 participants in the multicenter Herpetic Eye Disease Study between 1992 and 1998 (48% female; 85% white; median age, 49 years). The odds ratio comparing the acyclovir group with the placebo group on the gold-standard outcome (physician-diagnosed herpes simplex virus recurrence) was 0.62 (95% confidence interval (CI): 0.35, 1.09). We masked ourselves to physician diagnosis except for a 30% validation subgroup used to compare methods. Multiple imputation (odds ratio (OR) = 0.60; 95% CI: 0.24, 1.51) was compared with naive analysis using self-reported outcomes (OR = 0.90; 95% CI: 0.47, 1.73), analysis restricted to the validation subgroup (OR = 0.57; 95% CI: 0.20, 1.59), and direct maximum likelihood (OR = 0.62; 95% CI: 0.26, 1.53). In simulations, multiple imputation and direct maximum likelihood had greater statistical power than did analysis restricted to the validation subgroup, yet all 3 provided unbiased estimates of the odds ratio. The multiple-imputation approach was extended to estimate risk ratios using log-binomial regression. Multiple imputation has advantages regarding flexibility and ease of implementation for epidemiologists familiar with missing data methods.

Topics: Acyclovir; Antiviral Agents; Bias; Computer Simulation; Data Interpretation, Statistical; Eye Diseases; Female; Herpes Simplex; Humans; Logistic Models; Male; Middle Aged; Monte Carlo Method; Multicenter Studies as Topic; Odds Ratio; Outcome Assessment, Health Care; Regression Analysis; Reproducibility of Results; Research Design; Secondary Prevention

Cidofovir is a deoxycytidine monophosphate analog with broad spectrum activity against various deoxyribonucleic acid viruses. Cidofovir is marketed as an injectable for intravenous use; however, there is a topical cidofovir formulation utilized for viral dermatologic infections. Here, we present a case of a successful clearance of a perianal acyclovir resistant and foscarnet refractory herpes simplex virus (HSV1) ulcer in a 34 year-old woman who had undergone allogeneic hematopoietic stem cell transplantation. After 1 week of therapy with cidofovir gel, the patient's ulcer was clinically improved, and the lesion was negative for herpes simplex virus transcripts by real-time polymerase chain reaction testing. The wound remained herpes simplex virus negative by real-time polymerase chain reaction on repeat testing 1 week later. Based on this and other reports in HIV/AIDS patients, we believe that cidofovir gel has utility in the management of cutaneous, acyclovir-resistant HSV infections.

Topics: Acyclovir; Administration, Topical; Adult; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Female; Foscarnet; Gels; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Humans; Organophosphonates; Real-Time Polymerase Chain Reaction; Transplantation, Homologous; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Female; Herpes Simplex; Humans; Male

Herpes simplex virus type 1 (HSV-1) is known to cause diseases of various severities. There is increasing interest to find drug combinations to treat HSV-1 by reducing drug resistance and cytotoxicity. Drug combinations offer potentially higher efficacy and lower individual drug dosage. In this paper, we report a new application of fractional factorial designs to investigate a biological system with HSV-1 and six antiviral drugs, namely, interferon alpha, interferon beta, interferon gamma, ribavirin, acyclovir, and tumor necrosis factor alpha. We show how the sequential use of two-level and three-level fractional factorial designs can screen for important drugs and drug interactions, as well as determine potential optimal drug dosages through the use of contour plots. Our initial experiment using a two-level fractional factorial design suggests that there is model inadequacy and that drug dosages should be reduced. A follow-up experiment using a blocked three-level fractional factorial design indicates that tumor necrosis factor alpha has little effect and that HSV-1 infection can be suppressed effectively by using the right combination of the other five antiviral drugs. These observations have practical implications in the understanding of antiviral drug mechanism that can result in better design of antiviral drug therapy.

Topics: Acyclovir; Antiviral Agents; Drug Combinations; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Interferon-alpha; Interferon-beta; Interferon-gamma; Models, Statistical; Ribavirin; Tumor Necrosis Factor-alpha

Topics: Acyclovir; Aged; Antibodies, Monoclonal, Murine-Derived; Antiviral Agents; Biopsy; Cytomegalovirus Infections; Drug Therapy, Combination; Glucocorticoids; Herpes Simplex; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Pemphigus; Prednisolone; Rituximab; Skin; Treatment Outcome; Valacyclovir; Valine

A neonate with herpes simplex virus 1 encephalitis was treated with intravenous acyclovir. During the course of therapy, the infection became intractable to the treatment and a mutation in the viral thymidine kinase gene (nucleotide G375T, amino acid Q125H) developed. This mutation was demonstrated in vitro to confer acyclovir resistance.

Topics: Acyclovir; Amino Acid Substitution; Antiviral Agents; DNA, Viral; Drug Resistance, Viral; Encephalitis, Herpes Simplex; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation, Missense; Pregnancy Complications, Infectious; Sequence Analysis, DNA; Thymidine Kinase

Rapid alternative methods are required to evaluate easily acyclovir (ACV) sensitivity of clinical herpes simplex virus (HSV) isolates. The objective of this study was to screen 54 ACV-sensitive and 41 ACV-resistant clinical HSV-1 isolates, well characterized by phenotypic and genotypic methods, for the phosphorylation activity of the viral thymidine kinase (TK) using a commercially available and modified non-radioactive DiviTum® test on the basis of an indirect enzyme linked immunosorbent assay. The ACV-sensitive HSV-1 isolates had high TK activity values between 31.5±6.4 DiviTum® Units per liter (DU/L) and 487.4±60.1 DU/L. The mean activity of all ACV-sensitive isolates was calculated as 212.3±15.7 DU/L. By contrast, the mean activity of all ACV-resistant HSV-1 isolates was significantly lower at 5.5±1.3 DU/L. Out of the 41 ACV-resistant HSV-1 isolates, 38 had no or very low phosphorylation activities of the viral TK between 0 DU/L and 9.3±3.2 DU/L. The remaining three ACV-resistant viral isolates had TK activities between 44.6±5.1 DU/L and 80.9±13.3D U/L. In conclusion, the modified DiviTum® test can be used to screen HSV-1 isolates for their sensitivity to ACV. Acyclovir-sensitive HSV-1 isolates show TK activities >30 DU/L and ACV-resistant isolates have activity values <10 DU/L. However, single ACV-resistant HSV-1 isolates can have TK activity values >30 DU/L. These strains are most likely ACV-resistant TK-altered mutants, but no evidence was provided for an alteration of the TK.

Topics: Acyclovir; Drug Resistance, Viral; Enzyme-Linked Immunosorbent Assay; Herpes Simplex; Herpesvirus 1, Human; Humans; Microbial Sensitivity Tests; Thymidine Kinase; Viral Proteins

The tropism of herpes simplex virus (HSV-1) for human sensory neurons infected in vivo was examined using dorsal root ganglion (DRG) xenografts maintained in mice with severe combined immunodeficiency (SCID). In contrast to the HSV-1 lytic infectious cycle in vitro, replication of the HSV-1 F strain was restricted in human DRG neurons despite the absence of adaptive immune responses in SCID mice, allowing the establishment of neuronal latency. At 12 days after DRG inoculation, 26.2% of human neurons expressed HSV-1 protein and 13.1% expressed latency-associated transcripts (LAT). Some infected neurons showed cytopathic changes, but HSV-1, unlike varicella-zoster virus (VZV), only rarely infected satellite cells and did not induce fusion of neuronal and satellite cell plasma membranes. Cell-free enveloped HSV-1 virions were observed, indicating productive infection. A recombinant HSV-1-expressing luciferase exhibited less virulence than HSV-1 F in the SCID mouse host, enabling analysis of infection in human DRG xenografts for a 61-day interval. At 12 days after inoculation, 4.2% of neurons expressed HSV-1 proteins; frequencies increased to 32.1% at 33 days but declined to 20.8% by 61 days. Frequencies of LAT-positive neurons were 1.2% at 12 days and increased to 40.2% at 33 days. LAT expression remained at 37% at 61 days, in contrast to the decline in neurons expressing viral proteins. These observations show that the progression of HSV-1 infection is highly restricted in human DRG, and HSV-1 genome silencing occurs in human neurons infected in vivo as a consequence of virus-host cell interactions and does not require adaptive immune control.

Topics: Acyclovir; Animals; Ganglia, Spinal; Gene Expression; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Luciferases; Mice; Mice, SCID; Satellite Cells, Perineuronal; Severe Combined Immunodeficiency; Transplantation, Heterologous; Valacyclovir; Valine; Viral Proteins; Viral Tropism; Virus Latency; Virus Replication

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Diagnosis, Differential; Female; Fever; Hepatitis, Viral, Human; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Neutropenia; Recurrence; Risk; Transaminases

Knowledge on pediatric herpes simplex virus encephalitis is limited. Here we summarize 6 neonates and 32 children diagnosed by polymerase chain reaction (n = 37) or serological studies (n = 1), respectively. Diagnosis was difficult, as only 15 patients presented neurologic symptoms. Moreover, cerebrospinal fluid glucose, protein, and leukocytes were normal in 6 patients. Subsequently, all but 2 showed neurologic symptoms. Diffusion-weighted neuroimaging was the most sensitive early imaging method. Despite acyclovir treatment, 8 patients experienced early relapses, showing movement abnormalities, impaired vigilance, and seizures. Diffuse white matter changes, found in 3 of 5 relapse patients on neuroimaging, and a negative cerebrospinal fluid herpes simplex virus polymerase chain reaction suggested inflammatory processes. All relapse patients were again treated with acyclovir, and 3 responded to additional corticosteroid treatment. Whereas outcome after relapses was poor, overall outcome was good. No child died; 14 were asymptomatic at discharge, and neuroimaging remained normal in 7 of 30 patients studied.

Topics: Acyclovir; Adolescent; Antiviral Agents; Brain; Child; Child, Preschool; Diffusion Magnetic Resonance Imaging; Encephalitis, Viral; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Nerve Fibers, Myelinated; Prospective Studies; Recurrence; Retreatment; Retrospective Studies; Simplexvirus; Treatment Outcome

The incidence and the clinical characteristics of neonatal herpes simplex virus (NHSV) infection in Israel are unknown.. We reviewed the medical records of NHSV cases who were born between January 2001 and December 2007 in 5 medical centers located in central Israel. Cases were identified using International Classification of Diseases, 9th revision codes. In addition, parents of survivors were interviewed by telephone.. In the 8-year study period, 22 cases of NHSV were identified (an incidence rate of 8.4 per 100,000 live births). Most patients (77.2%, 17 cases) manifested as skin, eye and/or mouth infection, 13.6% (3 cases) as localized central nervous system disease and 9.1% (2 cases) as disseminated disease. Most (76.4%) herpes viruses typed in our series were HSV-1. None of the mothers had documented intrapartum visible genital HSV lesions or a previous history of genital herpes. Ritual circumcision was the source of HSV-1 transmission in 7 infants (31.8% of cases).. The incidence of NHSV infection in Israel was found to be similar to the lower part of the scale reported in the United States, however higher than the incidence reported in Canada or in Europe. Similar to more recent reports, our series demonstrates the shift toward the predominance of HSV-1 in NHSV infection. In addition, none of the mothers in our series had a previous history of genital herpes. This study emphasizes the need for awareness of HSV infection in Israeli neonates.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Gestational Age; Herpes Simplex; Humans; Incidence; Infant, Newborn; Israel; Male; Pregnancy Complications, Infectious; Retrospective Studies; Treatment Outcome

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Black or African American; Blood Coagulation Disorders; Diagnosis, Differential; DNA, Viral; Hepatitis; Herpes Simplex; Herpesvirus 2, Human; Humans; Male; Polymerase Chain Reaction; Skin Diseases, Viral; Young Adult

Herpes simplex virus (HSV)-induced sepsis affects immunocompromised patients. We report here the case of an immunocompetent adult with sepsis, hepatitis, renal failure and esophagitis. The possibility of HSV should be considered in cases of sepsis without any evident cause, even in immunocompetent patients. The characteristic endoscopic and histological findings of the associated esophagitis may assist the etiology of sepsis.

Topics: Acyclovir; Antiviral Agents; Endoscopy, Digestive System; Esophagitis; Hepatitis, Viral, Human; Herpes Simplex; Humans; Immunocompetence; Male; Middle Aged; Sepsis; Ulcer

We present an unreported coexistence: eczema herpeticum (EH) with histopathological findings of herpetic folliculitis (HF) after allogeneic bone marrow transplantation (BMT). A patient with atopic dermatitis (AD) underwent allogeneic BMT for idiopathic acquired aplastic anemia. She had been receiving cyclosporine (150 mg/12 h) and acyclovir (400 mg/12 h) for 6 months. A facial rash was observed, composed of monotonous erythematous, umbilicated papulo-vesicles and papulo-crusts <4 mm in size. The histopathological study showed herpetic cytopathic changes within the epidermis that extended into the hair follicle epithelium. Interestingly, microscopic HF has not previously been associated with post-transplant patients or EH. However, it is reasonable to hypothesize that the coexistence of these herpes simplex virus-related events may be underreported in the literature. Although further studies are necessary, we suggest that the prophylactic antiviral dose after BMT be enhanced in patients with underlying dermatologic diseases, especially in those with AD.

Topics: Acyclovir; Adult; Anemia, Aplastic; Antiviral Agents; Bone Marrow Transplantation; Cyclosporine; Dermatitis, Atopic; Female; Folliculitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Kaposi Varicelliform Eruption; Risk Factors

Five new sesquiterpene derivatives, including dihydroagarofuran pyridine macrolides 1-4 and dihydroagarofuran ester 18, and 13 known dihydroagarofuran derivatives were isolated from the aqueous EtOH extract of the dried roots of Tripterygium wilfordii. An in vitro antiherpetic activity assay indicated that compounds 11 and 17 displayed weak and moderate inhibition against herpes simplex virus type II, respectively.

Topics: Acyclovir; Alkaloids; Antiviral Agents; Drugs, Chinese Herbal; Herpes Simplex; Herpesvirus 2, Human; Macrolides; Molecular Structure; Plant Roots; Sesquiterpenes; Tripterygium

New chiral purinyl and 8-azapurinyl carbanucleoside derivatives based on indanol were synthesized from commercial available (1S,2S)-trans-1-amino-2-indanol and (1R,2R)-trans-1-amino-2-indanol using a linear methodology. The antiviral activity and cytotoxicity of these compounds were evaluated against herpes simplex virus type 1 (HSV-1) in Vero cells, bovine viral diarrhea virus (BVDV) in Mardin-Darby bovine kidney (MDBK) cells and hepatitis B virus (HBV) in HepG2 2.2.15 cell line. Three compounds, showed an inhibition of the HBsAg levels similar to reference drug lamivudine. One chloropurinyl nucleoside, derived from the cis-1-amino-2-indanol, was cytotoxic on MDBK cells and it could be a lead for developing anticancer agents.

Topics: Animals; Antiviral Agents; Bovine Virus Diarrhea-Mucosal Disease; Cattle; Cell Line; Chlorocebus aethiops; Diarrhea Viruses, Bovine Viral; Dogs; Hep G2 Cells; Hepatitis B; Hepatitis B virus; Herpes Simplex; Herpesvirus 1, Human; Humans; Indans; Nucleosides; Stereoisomerism; Vero Cells

The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; HEK293 Cells; Herpes Simplex; Herpesvirus 1, Human; HIV Infections; HIV-1; Humans; Vero Cells; Virus Replication

The number needed to treat (NNT) is a simple measure of a treatment's impact, increasingly reported in randomized trials and observational studies. Its calculation in studies involving varying follow-up times or recurrent outcomes has been criticized. We discuss the NNT in these contexts, illustrating using several published studies. The computation of the NNT is founded on the cumulative incidence of the outcome. Instead, several published studies use simple proportions that do not account for varying follow-up times, or use incidence rates per person-time. We show that these approaches can lead to erroneous values of the NNT and misleading interpretations. For example, after converting the incidence rate to a cumulative incidence, we show that a trial reporting a NNT of 4 "to prevent one exacerbation in 1 year" should have reported a NNT of 9. A survey of all papers reporting NNT, published in four major medical journals in 2009, found that 6 out of all 10 papers involving varying follow-up times did not correctly estimate the NNT. As the "number needed to treat" becomes increasingly used in complex studies and in the comparative effectiveness of therapies, its accurate estimation and interpretation become crucial to avoid erroneous clinical and public health decisions.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Breast Neoplasms; Data Interpretation, Statistical; Diphosphonates; Evidence-Based Medicine; Female; Follow-Up Studies; Herpes Simplex; Humans; Imidazoles; Kaplan-Meier Estimate; Life Tables; Periodicals as Topic; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Risk Factors; Sample Size; Survival Rate; Time Factors; Valacyclovir; Valine; Zoledronic Acid

Topics: Acyclovir; Adrenal Cortex Hormones; Adult; Antiviral Agents; Cyclosporine; Dermatitis, Atopic; Eczema; Herpes Simplex; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; PUVA Therapy; Simplexvirus; Virus Activation

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Male; Recurrence; Skin Diseases, Viral; Valacyclovir; Valine

Because neonatal herpes simplex virus (NHSV) infection is difficult to diagnose, there has been a move towards using more empiric acyclovir (ACV).. The purpose of this study was to review the use of ACV to optimize future management of NHSV.. Charts were reviewed for infants started on intravenous ACV up to day 43 of life--January 2001 through February 2007--at five hospitals in Edmonton and Calgary.. ACV was started for possible (N = 115) or proven (N = 3) herpes simplex virus (HSV) infection. Six of the infants with possible HSV infection later had proven HSV infection. Seizures (34%), hemodynamic instability (29%) and skin lesions (24%) were the most common indications for ACV. Among the 118 infants, 106 (90%) had cerebrospinal fluid obtained and 82 (69%) had at least one surface swab for HSV but 4 (3%) had no specimens submitted for HSV detection. ACV was continued for 3.9 ± 3.5 days in the infants with no proven HSV disease. Possible nephrotoxicity from ACV was recorded in 3 of these 109 infants and in none of the infants with proven HSV disease.. Clinicians in Alberta primarily consider the diagnosis of NHSV infection when confronted with a neonate with seizures, hemodynamic instability or suspicious skin lesions, but need to consider the diagnosis more often if all cases are to be treated at first presentation. They often perform incomplete investigations to rule out NHSV infection. Adverse events from ACV appear to be uncommon when the drug is used for suspected NHSV disease.

Topics: Acyclovir; Antiviral Agents; Canada; Empirical Research; Female; Gestational Age; Herpes Simplex; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Simplexvirus

The clinical and histopathological features of cutaneous herpes simplex virus (HSV) infection have been well described. Genital herpetic infections are largely induced by HSV type 2, but 30% of cases can be caused by HSV type 1. Immunocompromised patients are known to exhibit atypical patterns of clinical presentation with variable lesion morphology and anatomic location. A subset of patients may show morphology such as nodules or verrucous lesions. Analogously, some biopsy specimens may show unusual microscopical features, such as a lack of keratinocyte cytopathology, lymphocyte infiltration or vasculopathic changes that are expected irrespective of the patient's immune status. We present the case of a patient carrying a previous diagnosis of pemphigus vulgaris, status posttreatment with methotrexate and prednisone, who developed a perineal ulcer exhibiting significant numbers of plasma cells, many of which were cytologically atypical. This morphology was suggestive of a hematopoietic malignancy. Immunoperoxidase staining for HSV decorated a focal collection of keratinocytes that lacked appreciable viral changes expected of HSV infection.

Topics: Acyclovir; Adult; Antiviral Agents; Dermatologic Agents; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Methotrexate; Pemphigus; Perineum; Plasma Cells; Prednisolone; Skin; Skin Diseases; Ulcer; Valacyclovir; Valine

Crude ethanol extracts from Ficus benjamina leaves strongly inhibit Herpes Simplex Virus 1 and 2 (HSV-1/2) as well as Varicella Zoster Virus (VZV) cell infection in vitro. Bioassay-guided fractionation of the crude extract demonstrated that the most efficient inhibition of HSV-1 and HSV-2 was obtained with the flavonoid fraction. The present study was aimed to further isolate, purify and identify substances with potent antiviral activity from the flavonoid fraction of F. benjamina extracts. Flavonoids were collected from the leaf ethanol extracts through repeated purification procedure and HPLC analysis. The antiviral activity of each substance was then evaluated in cell culture. Three known flavone glycosides, (1) quercetin 3-O-rutinoside, (2) kaempferol 3-O-rutinoside and (3) kaempferol 3-O-robinobioside, showing highest antiviral efficiency were selected and their structure was determined by spectroscopic analyses including NMR and mass spectrometry (MS). These three flavones were highly effective against HSV-1 reaching a selectivity index (SI) of 266, 100 and 666 for compound 1, 2 and 3, respectively, while the SI of their aglycons, quercetin and kaempferol amounted only in 7.1 and 3.2, respectively. Kaempferol 3-O-robinobioside showed similar SI to that of acyclovir (ACV), the standard anti-HSV drug. Although highly effective against HSV-1 and HSV-2, these flavone glycosides did not show any significant activity against VZV.

Topics: Acyclovir; Antiviral Agents; Biological Assay; Cell Survival; Cytopathogenic Effect, Viral; Ficus; Flavones; Glycosides; Herpes Simplex; Herpes Zoster; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Molecular Structure; Plant Extracts; Plant Leaves

Aciclovir (ACV)-resistant Herpes simplex virus type-2 (HSV-2) infections are observed commonly in patients also infected with HIV-1. The use of foscarnet (FOS) in these patients may also lead to resistance. This situation can become a difficult therapeutic challenge. Four cases of patients infected with HIV and with mucocutaneous HSV-2 resistant to ACV and FOS are reported. These patients were treated successfully with topical 5% imiquimod. Imiquimod treatment also appeared to delay the time to recurrence of HSV lesions.

Topics: Acyclovir; Administration, Topical; Adult; Aminoquinolines; Antiviral Agents; Drug Resistance, Viral; Foscarnet; Herpes Simplex; HIV Infections; HIV-1; Humans; Imiquimod; Lamivudine; Male; Middle Aged; Nelfinavir; Simplexvirus; Zidovudine

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Child Development; Female; Herpes Simplex; Humans; Male; Pregnancy Complications, Infectious

Disseminated neonatal herpes simplex virus (HSV) infection causes a typical systemic inflammatory response syndrome and has a high mortality rate. However, the validity of anti-inflammatory intervention against this condition remains unknown.. We sought to demonstrate the sequential changes in the pathophysiology of disseminated neonatal HSV infections.. The HSV serum copy number as well as high-mobility group box 1 (HMGB1) and cytochrome c concentrations, which predict the severity and mortality rate of sepsis, were sequentially evaluated in a patient with disseminated neonatal HSV infection caused by HSV-2.. As the patient presented with evidence of hyper-inflammation and severe illness, we empirically undertook anti-inflammatory intervention that included the administration of prednisolone, high-dose immunoglobulin, and blood exchange therapy in addition to high-dose acyclovir (ACV) therapy. The patient survived without significant neurological sequela. We found that (1) the serum concentrations of both HMGB1 and cytochrome c were extremely high, (2) temporal increases in these biomarkers were observed after admission, and (3) interestingly, the increase in HMGB1 level preceded that of cytochrome c. These results suggested that the pathophysiology of this condition changed sequentially in a dramatic manner, and the timing of our anti-inflammatory intervention was prior to the transition of pathological status from hyper-inflammation to massive apoptosis.. Anti-inflammatory intervention may only be effective if it is undertaken during the early phase of disseminated neonatal HSV infections.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Cytochromes c; DNA, Viral; Herpes Simplex; HMGB1 Protein; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Viral Load; Viremia

Herpes simplex virus type 2 (HSV-2) can cause radiculo-myelitis as a neurological manifestation. We report a case of ongoing HSV-2 DNA positivity in the cerebrospinal fluid (CSF) of at least eight weeks under antiviral therapy with acyclovir in a highly immunocompromised hemato-oncologic patient with HSV-2-associated radiculitis. Upon admission, the patient presented with pain, leg paresis, and urinary incontinence, as well as pleocytosis in the CSF. Quantitative real-time PCR of the CSF at day 3 after admission revealed HSV-2 with a concentration of 2.0×10(5) copies/ml and treatment with acyclovir intravenously and prednisolone by mouth was started. Clinical symptoms resolved almost completely after approximately 3 weeks of antiviral therapy. However, CSF samples of day 12, 19, 26, 33, 39, 48 and 54 after admission showed a slow decline of HSV-2 DNA concentrations. HSV-2 DNA was still detectable (1.6×10(4) copies/ml) at day 54 after admission. Genotypic resistance testing showed, as far as available, no mutations indicative for acyclovir resistance. Since an increasing specific antibody index for HSV was observed, we speculate that the prolonged detectability of HSV-2 DNA in the CSF might not necessarily indicate ongoing viral replication but neutralized virus. Other hypotheses and the consequences on treatment are discussed. To our knowledge this is the first report about the long-term viral load kinetics of HSV-2 in the CSF of a patient with radiculitis under antiviral therapy, highlighting the need for further studies on HSV DNA kinetics in the CSF and their significance for an appropriate antiviral treatment.

Topics: Acyclovir; Aged; Antiviral Agents; DNA Copy Number Variations; DNA, Viral; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Lymphoma, B-Cell; Prednisolone; Radiculopathy; Real-Time Polymerase Chain Reaction; Time Factors; Viral Load

Herpes simplex virus (HSV) hepatitis is an uncommon cause of acute liver failure (ALF), primarily affecting immunocompromised patients. So far, 148 cases have been published, of which 9 underwent liver transplantation (LT). The reported post-transplant survival is poor, with over 60% dying in the first year. Dosing and duration of antiviral therapy after LT are not established. Concerns include both the risk of hepatic recurrence after LT and emergence of viral resistance during prolonged therapy. HSV DNA plasma levels might be helpful to monitor therapeutic response and guide duration of therapy. We present a case of ALF complicating a primary HSV-1 infection in an immunocompetent host, who required emergency LT. We further discuss the value of measuring serial HSV DNA plasma loads to monitor antiviral therapy.

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Hepatitis; Herpes Simplex; Herpesviridae Infections; Herpesvirus 1, Human; Humans; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Simplexvirus; Viral Load

We describe a patient with pemphigus foliaceus who developed two distinct disseminated cutaneous viral infections. Our patient is an 83-year-old female with a recent diagnosis of pemphigus foliaceus, who presented with painful ulcerations while on corticosteroids. Histopathology examination revealed disseminated herpes simplex virus (HSV). Despite adequate treatment with anti-herpetic treatment, some ulcerations failed to heal. A second biopsy revealed the presence of cytomegalovirus (CMV). This was treated successfully with appropriate antiviral therapy. In patients with autoimmune bullous disease, the development of new skin pain or new constitutional symptoms, change in primary morphology, rapid disease progression, or failure to respond to appropriate therapies should prompt the clinician to consider a concurrent cutaneous viral infection. There should be a low threshold to perform ancillary tests, to re-biopsy, and in severe cases, to consider empiric treatment with antiviral treatment therapy and modification of immunosuppressive regimens.

Topics: Acyclovir; Aged, 80 and over; Anti-Inflammatory Agents; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Herpes Simplex; Humans; Pemphigus; Prednisolone; Valganciclovir

The goal was to describe herpes simplex virus (HSV) disease in neonates whose mothers received suppressive acyclovir therapy for HSV infection.. A multicenter case series of 8 infants who developed neonatal HSV disease following maternal antiviral suppressive therapy during pregnancy.. Eight infants were identified from New Jersey (5), Maine (1), New York (1), and Texas (1) between 2005 and 2009. All 6 mothers of infants infected with HSV who were screened prenatally for group B Streptococcus were positive; 1 mother was not tested and the other had bacterial vaginosis and genital human papillomavirus infection. Six mothers had a first clinical episode of genital HSV infection during this pregnancy; mothers with a prior history of genital HSV had no clinically recognized outbreak during the pregnancy. Perinatal transmission of HSV occurred in 7 infants (despite suppressive therapy until the day of delivery in 5 instances). Seven of 8 patients were born at term; 6 infants were male. In 7 of 8 cases, HSV was diagnosed by 8 days of age. Five infants had skin, eye, and mucous membrane disease, 2 had central nervous system disease (without and with disseminated disease), and one had intrauterine/disseminated disease.. Although maternal antiviral suppressive therapy is an increasingly wide practice, physicians caring for neonates should be aware that suppressive therapy does not prevent neonatal HSV disease, which can have an atypical clinical presentation and drug resistance.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Simplex; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; Treatment Failure; Young Adult

Topics: Acyclovir; Antiviral Agents; Disease Progression; Female; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male

Specific mutations within the hypervariable herpes simplex virus (HSV) gene thymidine kinase (TK) gene lead to acyclovir (ACV) resistance. To uncover the existence of latent ACV-resistant (ACV(R)) HSV-1, we determined the genetic and functional variability of the HSV-1 TK gene pool in paired trigeminal ganglia (TG) of 5 immunocompetent individuals. The latent virus pool consisted of a donor-specific HSV-1 quasispecies, including one major ACV-sensitive (ACV(S)) and multiple phylogenetic-related minor ACV(S) and ACV(R) TK variants. Contrary to minor variants, major TK variants were shared between paired TG. The data demonstrate the coexistence of phylogenetic-related ACV(S) and ACV(R) latent HSV-1 in human TG.

Topics: Acyclovir; Aged; Aged, 80 and over; Animals; Antiviral Agents; Autopsy; Base Sequence; Chlorocebus aethiops; COS Cells; DNA, Viral; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompetence; Male; Molecular Sequence Data; Mutation; Phylogeny; Prevalence; Sequence Analysis, DNA; Thymidine Kinase; Trigeminal Ganglion; Virus Latency

Topics: Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; DNA, Viral; Female; Fluorescein Angiography; Herpes Simplex; Herpes Zoster Ophthalmicus; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Male; Middle Aged; Polymerase Chain Reaction; Retinal Artery Occlusion; Retinal Necrosis Syndrome, Acute; Retinal Vein Occlusion; Valacyclovir; Valine; Visual Acuity

Serologic studies indicate that herpes simplex virus (HSV)-1 and HSV-2 infections are highly prevalent among people infected with HIV. As an ulcerative genital disease, HSV may be important to HIV transmission and HIV-comorbidity. Routine clinical care of HSV in this population has not been described.. Data were abstracted from medical records of HIV-infected individuals by the Adult/Adolescent Spectrum of HIV Disease Project. Clinician-documented HSV diagnosis and HSV treatment, defined as any prescription for acyclovir, valacyclovir, or famciclovir, were the outcomes of interest. We present descriptive statistics and trends in HSV diagnosis and treatment.. Between 1989 and 2004, 61,299 people were followed in this study. HSV was diagnosed in 20% of the population, and 32% of the population received HSV antiviral prescriptions. Prescriptions for episodic treatment were given to 28% of patients, and 11% received prescriptions for suppressive therapy. The average annual rate of HSV diagnosis declined by 31% during the course of the study.. Clinically recognized HSV infections were frequent despite declining rates of diagnosis. Providers should have a high index of suspicion for HSV and consider routine screening and suppressive therapy for patients at risk of clinical disease.

Topics: 2-Aminopurine; Acyclovir; Adult; Antiviral Agents; Comorbidity; Famciclovir; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Seropositivity; Humans; Male; Middle Aged; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Female; Fingers; Gingivitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Lymphangitis; Stomatitis, Herpetic

Topics: Acyclovir; Adult; Antigens, Viral; Antiviral Agents; Biomarkers; Diagnosis, Differential; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunohistochemistry; Male; Penile Diseases; Polymerase Chain Reaction; Treatment Outcome; Valacyclovir; Valine

To report a case of bilateral vocal cord abductor paralysis in the context of primary herpes simplex infection.. A 63-year-old man was urgently admitted to hospital with laryngeal dyspnoea associated with dysphagia but without dysphonia. Physical examination demonstrated the vocal cords in a paramedian position with paralysis of abduction. The patient reported primary herpes simplex infection two weeks prior to this episode. HSV serology indicated recent infection and lumbar puncture demonstrated the presence of herpes simplex virus type 1 in the cerebrospinal fluid. Complete resolution of respiratory symptoms was observed after 21 days of treatment with intravenous aciclovir.. Gerhardt syndrome comprises inspiratory dyspnoea without dysphonia. It used to be mainly due to syphilis, but is now mostly observed in the setting of neurodegenerative disease. The authors report a case of Gerhardt syndrome occurring after an episode of primary herpes simplex infection with the presence of herpes simplex virus in the CSF. Treatment by intravenous antiviral drugs allowed rapid resolution of the symptoms. The pathophysiology of Gerhardt syndrome remains unexplained, but the possible role of herpes simplex infection should be considered in cases of laryngeal palsy.

Topics: Acyclovir; Antiviral Agents; Follow-Up Studies; Herpes Simplex; Herpesvirus 1, Human; Humans; Injections, Intravenous; Male; Middle Aged; Time Factors; Treatment Outcome; Vocal Cord Paralysis

A 24-year-old black female (HIV-positive) was referred to our clinic with a 4-week history of an ulcerative lesion of the right upper and lower eyelids. She was on treatment for pulmonary tuberculosis and had been admitted to a secondary level hospital. She had no other ocular symptoms or signs. A tissue biopsy of the lesion revealed multinucleate squamous cells with ground glass viral nuclear inclusion bodies, indicative of herpes simplex virus (HSV) infection. The ulcer healed with oral and topical acyclovir therapy, confirming a herpetic origin. There is only one other reported case of this type of ulcerative eyelid lesion caused by HSV; the patient in this case was also immunocompromised.

Topics: Acyclovir; Adult; Antiviral Agents; Eyelid Diseases; Female; Herpes Simplex; HIV Infections; Humans; Opportunistic Infections; Ulcer; Young Adult

We report the case of a 44-year-old, heterosexual, man, who presented for lesions of the face that appeared 3 days earlier; the eruption was associated with a burning sensation. He had sexual intercourse 12 days prior to presentation with a new partner. On clinical examination, there were confluent vesicules and a few pustules localized on the cheeks, forehead, nose, mouth, and ears. A swab for immunofluorescence (IF) came back as positive for HSV-2. The patient was treated with oral acyclovir. The lesions were healed when he was seen for follow-up 1 week later. The virus responsible for herpes is a double-stranded DNA virus named Herpes simplex virus (HSV). The virus generally enters damaged epithelium or mucosal surfaces, secondary to abrasions or trauma. Most primary orolabial infections occur during childhood as herpetic gingivostomatitis. However, there are forms that could be more atypical. The spread of the virus was probably promoted by shaving the beard. In immunocompromised patients or those with skin barrier disorders, HSV infection tends to disseminate and is accompanied by visceral involvement. Hence, the need to detect a state of immunodepression (including AIDS) in any patient with diffuse herpes infection. Three oral antiviral agents are commonly used: acyclovir, famciclovir, and valaciclovir.

Topics: Acyclovir; Adult; Antiviral Agents; Face; Herpes Simplex; Herpesvirus 2, Human; Humans; Male

To describe the clinical characteristics, treatment, and outcomes of herpes simplex virus (HSV) infections of the cornea and adnexae to raise awareness and to improve management of this important eye disease in children.. Retrospective case series.. Fifty-three patients (57 eyes) 16 years of age or younger with HSV keratitis (HSK), HSV blepharoconjunctivitis (HBC), or both in an academic cornea practice.. The following data were collected: age at disease onset, putative trigger factors, coexisting systemic diseases, duration of symptoms and diagnoses given before presentation, visual acuity, slit-lamp examination findings, corneal sensation, dose and duration of medications used, drug side effects, and disease recurrence.. Presence of residual corneal scarring, visual acuity at the last visit, changes in corneal sensation, recurrence rate, and manifestations of HSK were assessed in patients receiving long-term prophylactic systemic acyclovir.. The median age at onset was 5 years. Mean follow-up was 3.6 years. Eighteen eyes had HBC only; 4 patients in this group had bilateral disease. Of 39 eyes with keratitis, 74% had stromal disease. Thirty percent of HSK cases were misdiagnosed before presentation. Seventy-nine percent of patients with keratitis had corneal scarring and 26% had vision of 20/40 or worse at the last visit. Eighty percent of patients had recurrent disease. Six of 16 patients (37%) receiving long-term oral acyclovir had recurrent HSV, at least one case of which followed a growth spurt that caused the baseline dosage of acyclovir to become subtherapeutic.. In a large series, pediatric HSK had a high rate of misdiagnosis, stromal involvement, recurrence, and vision loss. Oral acyclovir is effective, but the dosage must be adjusted as the child grows.

Topics: 2-Aminopurine; Acyclovir; Administration, Topical; Adolescent; Age of Onset; Anterior Eye Segment; Antiviral Agents; Blepharitis; Child; Child, Preschool; Conjunctivitis, Viral; Eye Infections, Viral; Famciclovir; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant; Keratitis, Herpetic; Male; Ointments; Retrospective Studies; Trifluridine; Valacyclovir; Valine; Vidarabine

Herpes simplex virus (HSV) is an unusual cause of postpartum endometritis. We describe a rare case of primary disseminated maternal HSV in the postpartum period associated with endometritis.. A previously healthy patient developed fundal tenderness and postpartum fevers after an uncomplicated vaginal delivery. Despite traditional broad-spectrum antimicrobial therapy, she had persistent fevers and systemic symptoms. Concurrently, her neonate developed fevers and a nonvesicular rash, with viral cultures ultimately returning positive for HSV. The patient developed active pharyngeal and genital herpetic lesions and was diagnosed with HSV endometritis and disseminated HSV. Symptoms and fevers in both the mother and neonate responded to antiviral therapy.. Herpes simplex virus endometritis should be included in the differential diagnosis for postpartum fevers and fundal tenderness that are unresponsive to broad-spectrum antimicrobial treatment.

Topics: Acyclovir; Adult; Antiviral Agents; Endometritis; Exanthema; Female; Fever; Herpes Simplex; Herpesvirus 2, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Tomography, X-Ray Computed

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are responsible for lifelong latent infections in humans, with periods of viral reactivation associated with recurring ulcerations in the orofacial and genital tracts. In immunosuppressed patients and neonates, HSV infections are associated with severe morbidity and, in some cases, even mortality. Today, acyclovir is the standard therapy for the management of HSV infections. However, the need for novel antiviral agents is apparent, since HSV isolates resistant to acyclovir therapy are frequently isolated in immunosuppressed patients. In this study, we assessed the anti-HSV activity of the antiadenoviral compounds 2-[2-(2-benzoylamino)-benzoylamino]benzoic acid (benzavir-1) and 2-[4,5-difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid (benzavir-2) on HSV-1 and HSV-2. Both compounds were active against both viruses. Importantly, benzavir-2 had potency similar to that of acyclovir against both HSV types, and it was active against clinical acyclovir-resistant HSV isolates.

Topics: Acyclovir; Adult; Aged, 80 and over; Animals; Antiviral Agents; Benzamides; Cell Line; Chlorocebus aethiops; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Middle Aged; Viral Load; Viral Plaque Assay

Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE.. Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined.. Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differential diagnosis, despite suggestive clinical features. Where therapy was delayed in HSE patients, the decision to begin acyclovir was prompted by transfer of the patient to a different service (55%), recommendations by consultants (18%), imaging results (18%), and CSF pleocytosis (9%).. Delays in initiating acyclovir for HSE are common, and are most often due to a failure to consider HSE in a timely fashion on presentation. In order to improve patient outcomes, physicians should be more vigilant for HSE, and begin acyclovir therapy expeditiously on the basis of clinical suspicion rather than waiting for confirmatory tests.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Diagnosis, Differential; DNA, Viral; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Time Factors; Young Adult

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Diagnosis, Differential; Drug Therapy, Combination; Exanthema; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infectious Disease Transmission, Vertical; Mouth Mucosa; Skin Diseases, Vesiculobullous

The physicochemical properties of the optimized microemulsion and the permeating ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1) infection in mice was examined. The optimized microemulsion was composed of 10% w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol, and 20% w/w of water. The mean particle diameter was 9.67 ± 0.58 nm, and the solubility of oxyresveratrol in the microemulsion was 196.34 ± 0.80 mg/ml. After accelerated and long-term stability testing, the microemulsion base and oxyresveratrol-loaded microemulsion were stable. The cumulative amount of oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was 93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20% w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7 days after infection, was significantly effective in delaying the development of skin lesions and protecting from death (p < 0.05) compared with the untreated control. Oxyresveratrol microemulsion at 25% and 30% w/w was significantly more effective than that of 30% w/w of oxyresveratrol in Vaseline (p < 0.05) and was as effective as 5% w/w of acyclovir cream, topically applied five times daily (p > 0.05). These results demonstrated that topical oxyresveratrol microemulsion at 20-30% w/w was suitable for cutaneous HSV-1 mouse infection.

Topics: Acyclovir; Administration, Topical; Animals; Antiviral Agents; Chlorocebus aethiops; Drug Stability; Emulsions; Female; Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Inbred BALB C; Particle Size; Permeability; Petrolatum; Plant Extracts; Skin; Skin Cream; Skin Diseases, Viral; Snakes; Solubility; Stilbenes; Vero Cells

Herpes simplex encephalitis is a diagnostic challenge and causes high morbidity and mortality in children. Early suspicion of the disease and a rapid, safe and useful diagnostic test are relevant because up to 70% of the cases may die. We report the case of a newborn girl aged 25 days, who presented with a clinical picture that was compatible with herpes simplex encephalitis where the confirmation of the etiological diagnosis was delayed. Only by repeated real-time polymerase chain reaction it was possible to confirm the presence of herpes simplex virus type 1 in the cerebrospinal fluid.

Topics: Acyclovir; Antiviral Agents; Delayed Diagnosis; Encephalitis, Herpes Simplex; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Real-Time Polymerase Chain Reaction

Topics: Acyclovir; Afatinib; Aged; Antineoplastic Agents; Antiviral Agents; Carcinoma, Non-Small-Cell Lung; Cystitis; ErbB Receptors; Esophagitis; Hematuria; Herpes Simplex; Humans; Intestinal Perforation; Lung Neoplasms; Male; Molecular Targeted Therapy; Neoplasm Proteins; Peritonitis; Protein Kinase Inhibitors; Quinazolines; Valacyclovir; Valine; Viremia; Virus Activation

Acute liver diseases of pregnancy are common and usually transient and reversible. Given the number of different possible diagnoses, performing a large biological screening and a proper iconographic documentation is key. It makes sure no etiology fatal to the mother and her fetus is missed.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Female; Herpes Simplex; Humans; Liver Diseases; Liver Failure; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third

Series of novel acyclic nucleoside phosphonates (ANPs) with various nucleobases and 2-(2-phosphonoethoxy)ethyl (PEE) chain bearing various substituents in β-position to the phosphonate moiety were prepared. The influence of structural alternations on antiviral activity was studied. Several derivatives exhibit antiviral activity against HIV and vaccinia virus (middle micromolar range), HSV-1 and HSV-2 (lower micromolar range) and VZV and CMV (nanomolar range), although the parent unbranched PEE-ANPs are inactive. Adenine as a nucleobase and the methyl group attached to the PEE chain proved to be a prerequisite to afford pronounced antiviral activity.

Topics: Animals; Antiviral Agents; Cell Line; Cell Survival; Herpes Simplex; HIV; HIV Infections; Humans; Mice; Nucleosides; Organophosphonates; Simplexvirus; Structure-Activity Relationship; Vaccinia; Vaccinia virus; Virus Diseases; Viruses

Infection because of herpes simplex virus (HSV) that is resistant to acyclovir (ACV) poses treatment challenges in hematopoietic cell transplant (HCT) patients. We present a series of patients with ACV-resistant HSV following HCT who were successfully treated with continuous infusion high-dose ACV after failing standard treatment regimens for ACV-resistant HSV.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Multiple, Viral; Drug Resistance, Viral; Female; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Middle Aged; Simplexvirus; Treatment Outcome

To report a case of herpes simplex virus-induced herpetic necrotizing retinitis after placement of a flucinolone acetonide (Retisert) intravitreal implant.. Interventional case report.. Retrospective chart review.. A 22-year-old male with idiopathic unilateral panuveitis since 2002 that was intolerant of systemic immunosuppressive therapy received a flucinolone acetonide implant 6 years later. Intraocular inflammation was completely quiescent until 1 year following the implant, when he developed retinitis. To the authors' knowledge, this is the first reported case of polymerase chain reaction-proven herpetic necrotizing retinitis following implantation of a Retisert device.. Although rare, herpetic necrotizing retinitis can occur in the setting of local ocular immunosuppression with the Retisert intravitreal implant. This potential infection should be considered in the face of recurrent uveitis following Retisert implantation.

Topics: Acyclovir; Antiviral Agents; Azathioprine; Cataract; Drug Implants; Eye Infections, Viral; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Panuveitis; Pregnadienetriols; Retinal Necrosis Syndrome, Acute; Treatment Outcome; Valacyclovir; Valine; Visual Acuity; Young Adult

Fulminant hepatic failure (FHF) is a rare but well-recognized complication of primary herpes simplex virus (HSV) infection in immunocompromised patients. Here, we report two cases of acute hepatitis and FHF secondary to primary HSV type 1 infection following renal transplantation in the absence of any mucocutaneous manifestation. High levels of HSV type-1 DNA were detected in the blood. Both patients were seronegative for HSV 1 and HSV 2 immunoglobulin G (IgG) before transplantation, whereas the donor of patient 1 was HSV 1 IgG-positive but had no viremia and the donor of patient 2 was HSV-seronegative. Patient 1 recovered with acyclovir and immunoglobulin whereas patient 2 did not respond and succumbed to death. HSV-seronegative patients are potentially at risk of developing severe primary HSV disease following transplantation, particularly in the absence of routine anti-viral prophylaxis. HSV infection should always be excluded in transplant patients with hepatic dysfunction.

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Fatal Outcome; Female; Hepatitis, Viral, Human; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Liver Failure, Acute; Male; Middle Aged; RNA, Viral; Tomography, X-Ray Computed; Treatment Outcome

We report the case of an 81-year-old male patient who developed a reactivation of herpes simplex virus localized to the right forehead, where photodynamic therapy (PDT) for actinic keratosis was performed. Considering the wide use of PDT, herpes virus infection or reactivation as well as other infections seem to be a very rare but potentially serious complication that has to be distinguished from common inflammatory reactions after PDT. Further applications of PDT under antiviral prophylaxis were well tolerated by our patient, with no further herpetic reactivation and successful treatment of actinic keratoses.

Topics: Acyclovir; Aged, 80 and over; Antibiotic Prophylaxis; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Photochemotherapy; Recurrence; Valacyclovir; Valine

Topics: Acrodermatitis; Acyclovir; Child, Preschool; Gingivitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Stomatitis

Topics: Acyclovir; Antiviral Agents; Cowpox; Cowpox virus; Darier Disease; Herpes Simplex; Humans; Male; Middle Aged; Treatment Outcome

To describe the clinical presentation of HSV-infected young infants and to seek distinctive features that could permit a targeted approach to empiric use of acyclovir.. Case study of neonatal HSV during a 22-year period of an institutional strategy of consistent use of acyclovir empirically in all infants with onset of an illness at ≤ 21 days of age for which antibiotics were given empirically. Multiple sources were used to optimize HSV case data, and to estimate the rate of HSV infection in empirically treated infants.. A total of 32 infants with perinatally acquired HSV infection were identified. All received acyclovir empirically at admission. At presentation, 50% of infants had only nonspecific complaints, which was fever in 75%. After testing, 75% of infants with HSV had central nervous system (CNS) infection, including 40% who presented with mucocutaneous lesions, 83% with seizures, and 94% with nonspecific complaints. Cerebrospinal fluid (CSF) polymerase chain reaction confirmed CNS infection in 16 of 22 (73%) patients tested. Cultures of mucocutaneous lesion yielded HSV in 8 of 10 cases, but culture of CSF was negative in all 26 cases tested, and screening cultures of unaffected mucosal sites were the only HSV-confirmatory test in a single patient. Laboratory and CSF findings were not distinctive in patients with HSV. Age of ≤ 21 days at onset of symptoms captured 90% of all infants with HSV and 94% of those with nonspecific complaints. An estimated 1.3% of empirically treated patients had HSV infection.. Early manifestations of perinatally acquired HSV are frequently nonspecific, yet CNS infection is common. Empiric acyclovir strategy narrowly restricted to infants with onset of illness at ≤ 21 days of age, who would receive antibiotics empirically, captured 90% of HSV cases and anticipated a rate of HSV CNS infection similar to that of bacterial meningitis.

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Male; Meningoencephalitis; Mouth Mucosa; Polymerase Chain Reaction; Simplexvirus; Stomatitis, Herpetic; Virus Cultivation

Topics: Acyclovir; Antibodies, Monoclonal; Antiviral Agents; Colitis, Ulcerative; Colonic Pouches; Erythema Multiforme; Female; Gastrointestinal Agents; Herpes Simplex; Humans; Ileostomy; Immunosuppressive Agents; Infliximab; Proctocolectomy, Restorative; Simplexvirus; Treatment Outcome; Valacyclovir; Valine; Virus Activation; Young Adult

Topics: Acyclovir; Chlamydia trachomatis; Chlamydiaceae Infections; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Liver Failure, Acute; Pregnancy; Pregnancy Complications, Infectious; Sepsis

Neonatal herpes simplex virus (HSV) is a rare disease associated with high mortality and morbidity rates. HSV infection can be subdivided into 3 clinical manifestations: isolated skin, eye and mouth (SEM) disease, central nervous system (CNS) disease and disseminated disease. Consensus guidelines for diagnostic and therapeutic management are not available.. To evaluate the diagnostic work-up and therapeutic management in neonates with suspected or proven HSV infection.. Retrospective study of diagnostic and therapeutic management in all neonates with suspected HSV infection admitted to our neonatal nursery between January 2005 and July 2010.. A total 53 neonates with suspected HSV infection were included in the study and classified as SEM disease (n=2), CNS disease (n=41) or disseminated disease (n=10). None of the included infants tested positive for HSV infection. Correct and complete diagnostic work-up was performed in only 11% (6/53) of the cases. All neonates were treated with intravenous acyclovir.. None of the neonates with suspected HSV tested positive. Diagnostic management in neonates with suspected HSV infection was often improper and incomplete. Consensus guidelines to identify low-risk infants in whom HSV testing and acyclovir treatment is not warranted, are urgently needed.

Topics: Acyclovir; Antiviral Agents; Echoencephalography; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Polymerase Chain Reaction; Pregnancy Complications, Infectious; Retrospective Studies; Simplexvirus

Fulminant hepatitis is an uncommon complication of herpes simplex virus infection. Patients at risk, in particular pregnant women and immunosuppressed patients presenting with fulminant liver failure, receiving delayed acyclovir intervention may lose significant liver parenchyma prompting the need for liver transplantation. The diagnosis is often not straight forward due to the lack of specific signs or symptoms, while many patients are diagnosed at autopsy. Although herpes simplex virus associated fulminant hepatic failure carries a high mortality risk, early intervention with acyclovir may prove to be life saving. In fact, acyclovir given in the early stages of fulminant hepatic failure may prevent mortality and avoid the need for liver transplantation. We report here two pregnant women with fulminant herpes simplex virus hepatitis in whom a difference of a few hours in the initiation of empirical treatment made a vast difference to their hospital stay. The above results demonstrate a significant impact to fulminant hepatic failure and should prompt clinicians to consider empiric acyclovir therapy for at risk patients.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Hepatitis, Viral, Human; Herpes Simplex; Humans; Pregnancy; Pregnancy Complications, Infectious

A dual reporter cell assay (DRCA) that allows real-time detection of herpes simplex virus (HSV) infection was developed. This was achieved by stable transfection of cells with an expression cassette that contains the dual reporter genes, secreted alkaline phosphatase (SEAP) and enhanced green fluorescent protein (EGFP), under the control of an HSV early gene promoter. Baby hamster kidney (BHK) and Chinese hamster ovary (CHO) cell lines were used as parental cell lines because the former is permissive for both HSV serotypes, HSV-1 and HSV-2, whereas the latter is susceptible to infection only by HSV-2. The DRCA permitted differential detection of HSV-1 and HSV-2 by observation of EGFP-positive cells, as substantiated by screening a total of 35 samples. The BHK-based cell line is sensitive to a viral titer as low as a single plaque-forming unit with a robust assay window as measured by a chemiluminescent assay. Evaluations of the DRCA with representative acyclovir-sensitive and acyclovir-resistant HSV strains demonstrated that their drug susceptibilities were accurately determined by a 48-h format. In summary, this novel DRCA is a useful means for serotyping of HSV in real time as well as a rapid screening method for determining anti-HSV susceptibilities.

Topics: Acyclovir; Alkaline Phosphatase; Animals; Cell Line; CHO Cells; Cricetinae; Cricetulus; Drug Evaluation, Preclinical; Drug Resistance, Viral; Genes, Reporter; Green Fluorescent Proteins; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Promoter Regions, Genetic; Serotyping

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Viral; Foscarnet; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Herpesvirus 1, Human; Hodgkin Disease; Humans; Male; Middle Aged; Mouth; Treatment Outcome

Anti-herpes simplex virus (HSV) activities of oxyresveratrol in vitro and topical administration in cutaneous HSV-1 infection in mice were examined. The inhibitory concentrations for 50% plaque formation (IC(50)) of oxyresveratrol against HSV-1 clinical isolates and HSV-2 clinical isolates were 20.9-29.5 and 22.2-27.5 μg/ml, respectively. In topical administration in cutaneous HSV-1 infection in mice, 2.5%, 5%, 10% and 20% oxyresveratrol in cream vehicle applied three times daily for 7 days after infection were evaluated and 10% and 20% oxyresveratrol cream were significantly effective in delaying the development of skin lesions and protection from death (P < 0.01). The concentration of 10% oxyresveratrol in cream was significantly more effective than that of 30% oxyresveratrol in vaseline applied three times daily (P < 0.01). Oxyresveratrol cream at 20% was as effective as 5% ACV cream applied three times daily (P < 0.01). Both 10% and 20% oxyresveratrol cream were as effective as that of 5% ACV cream applied two times daily (P > 0.05). Therapeutic efficacy of oxyresveratrol in cream vehicle was dose-dependent and the maximum efficacy observed on day 6 after infection was shown at 10% oxyresveratrol in cream applied three times daily. The frequency of application of 10% oxyresveratrol cream at three, four and five times daily was as effective as that of 5% ACV cream applied five times daily (P > 0.05). These results demonstrated that topical administration of oxyresveratrol in novel cream vehicle reduced the concentration of oxyresveratrol to 10% and was suitable for cutaneous HSV infection.

Topics: Acyclovir; Administration, Cutaneous; Animals; Antiviral Agents; Artocarpus; Chlorocebus aethiops; Dose-Response Relationship, Drug; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Inhibitory Concentration 50; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Plant Extracts; Skin Diseases, Infectious; Stilbenes; Vero Cells; Viral Plaque Assay

Topics: Acyclovir; Adult; Angioedema; Cosmetic Techniques; Disease Progression; Female; Follow-Up Studies; Herpes Simplex; Humans; Hyaluronic Acid; Injections, Subcutaneous; Lip; Methylprednisolone; Severity of Illness Index

Benign recurrent aseptic meningitis is a rare disorder described by Mollaret in 1944. When initially described, this form of aseptic meningitis had no identifiable infecting agent. New sophisticated diagnostic tools have now identified herpes simplex type 2 virus as the most commonly isolated agent. Antiviral treatment has been used successfully for prophylaxis and treatment.

Topics: Acyclovir; Antiviral Agents; Chemoprevention; Herpes Simplex; Herpesvirus 2, Human; Humans; Meningitis, Aseptic; Secondary Prevention

The clinical and histopathological diagnosis of pityriasis rubra pilaris (PRP) can be difficult because clinical findings are often subtle in early stages, and microscopic findings can overlap with those of other skin diseases. Focal acantholytic dyskeratosis (FAD) can rarely be seen in PRP and can mimic Darier's disease, Grover's disease or other disorders characterized by these histopathologic features. Kaposi's varicelliform eruption is a widespread infection due to herpes simplex virus (HSV) types 1 and 2, coxsackievirus A16 or vaccinia virus, occurring in a preexisting dermatosis; only one case has been reported in PRP. We report a patient with PRP whose biopsies showed both herpes simplex infection and FAD. A complete understanding of the mechanism behind this eruption evolved gradually, aided in great measure by the histopathologic findings.

Topics: Acantholysis; Acyclovir; Aged; Antiviral Agents; Darier Disease; Diagnosis, Differential; Herpes Simplex; Humans; Ichthyosis; Kaposi Varicelliform Eruption; Male; Methotrexate; Pityriasis Rubra Pilaris; Valacyclovir; Valine

A 62-year-old woman with an autoimmune disease presented with panuveitis and was treated with immune suppression. She subsequently developed herpetic acute retinal necrosis and later died of herpes simplex encephalitis. Acute retinal necrosis usually occurs months to years after herpes simplex encephalitis. In our case, the ocular findings were present for 5 weeks before the encephalitis presented. To our knowledge, this is the first Australian case of acute retinal necrosis preceding herpes simplex encephalitis.

Topics: Acyclovir; Antiviral Agents; Encephalitis, Herpes Simplex; Female; Glucocorticoids; Herpes Simplex; Herpesvirus 1, Human; Humans; Middle Aged; Panuveitis; Prednisolone; Retinal Necrosis Syndrome, Acute

The occurrence of herpes simplex virus (HSV) with acyclovir (ACV) resistance is a cause for concern due to the frequent use of ACV for treatment, suppressive therapy, and prophylaxis of HSV infection. Although HSV infection is prevalent among children, very little is known about the drug susceptibility of HSV circulating in this patient population.. To determine the status of ACV resistant HSV-1 among children.. A reporter cell-based HSV infection assay (mVILA) was developed to conveniently evaluate the ACV susceptibility of HSV-1 clinical strains and used to analyze 68 HSV-1 primary isolates from oral lesions in children.. Compared with PRA, mVILA is easier to perform. Using mVILA, HSV-1 isolates C106, C153, and C174 were found completely resistant to ACV, with a greater than 100-fold increase in IC50s. Sequence analysis of thymidine kinase (TK) and DNA polymerase (DNA POL) genes identified 11 new mutations. Structural modeling of the TK and DNA POL proteins suggested structural changes that might alter their interactions with ACV and ACV triphosphate, respectively. The insertion of a single G in a seven-guanine homopolymeric repeat sequence generated a truncated TK protein in C106.. This study provides preliminary data on the ACV susceptibility status of HSV-1 in children. The prevalence rate of ACV-resistant HSV-1 in children was higher than predicted. Moreover, multiple mechanisms leading to the resistance were identified. These results suggest that new anti-herpetics with different working mechanisms should be valuable.

Topics: Acyclovir; Animals; Antiviral Agents; Child, Preschool; Chlorocebus aethiops; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Models, Molecular; Mutation; Protein Conformation; Thymidine Kinase; Vero Cells; Viral Proteins

Although acyclovir (ACV) has proven to be of value in the therapy of certain herpes simplex virus (HSV) infections, there is a need for more effective therapies, particularly for serious infections in neonates and immunocompromised individuals, where resistance to this drug can be problematic. CMX001 is an orally bioavailable lipid conjugate of cidofovir that is substantially less nephrotoxic than the parent drug and has excellent antiviral activity against all the human herpesviruses. This compound retains full antiviral activity against ACV-resistant laboratory and clinical isolates. The combined efficacy of CMX001 and ACV was evaluated in a new real-time PCR combination assay, which demonstrated that the combination synergistically inhibited the replication of HSV in cell culture. This was also confirmed in murine models of HSV infection, where the combined therapy with these two drugs synergistically reduced mortality. These results suggest that CMX001 may be effective in the treatment of ACV-resistant HSV infections and as an adjunct therapy in individuals with suboptimal responses to ACV.

Topics: Acyclovir; Animals; Antiviral Agents; Cells, Cultured; Cytosine; Drug Resistance, Viral; Drug Synergism; Drug Therapy, Combination; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Mice; Mice, Inbred BALB C; Organophosphonates

Topics: Acyclovir; Child; Female; Fingers; Herpes Labialis; Herpes Simplex; Humans; Lip

The outcome of neonatal herpes simplex (HSV) infection, even after therapy with high dose acyclovir (ACV), is not optimum. We therefore evaluated N-Methanocarbathymidine ((N)-MCT) using the guinea pig model of neonatal herpes. Treatment with ACV (60 mg/kg/day) was compared to doses of 1, 5, and 25 mg/kg/day of (N)-MCT initiated 1, 2, or 3 days postinoculation (dpi). Both ACV and (N)-MCT significantly improved survival, but only (N)-MCT significantly reduced the number of animals with symptoms when begun at 1 dpi. When therapy was begun at 2 dpi, only (N)-MCT (1, 5, or 25 mg/kg/day) significantly increased survival. In fact, (N)-MCT improved survival up to 3 dpi, the last time point evaluated. (N)-MCT was highly effective and superior to high dose ACV therapy for the treatment of neonatal herpes in the guinea pig model.

Topics: Acyclovir; Animals; Animals, Newborn; Antiviral Agents; Disease Models, Animal; Guinea Pigs; Herpes Simplex; Humans; Infant, Newborn; Pregnancy Complications, Infectious; Survival Analysis; Thymidine; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Central Nervous System Diseases; Child Development; Female; Herpes Simplex; Humans; Male; Pregnancy Complications, Infectious

Topics: Acyclovir; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Male; RNA, Viral; Valacyclovir; Valine

To determine the association of delayed acyclovir therapy with death among neonates with herpes simplex virus (HSV) infection.. A multicenter, retrospective, cohort study was conducted between January 1, 2003, and December 31, 2009, with 1086 neonates (age: ≤28 days) with HSV infection from 41 tertiary care children's hospitals. Early acyclovir therapy was defined as initiation of intravenous acyclovir treatment within 1 day after hospital admission, and delayed acyclovir therapy was defined as initiation of treatment >1 and ≤7 days after hospital admission. Multivariate logistic regression models determined the association between delayed acyclovir therapy and death, with the use of propensity scores for each neonate's likelihood of receiving delayed acyclovir treatment to control for differences in illness severity between groups.. The median age was 10 days. Delayed acyclovir therapy was administered to 262 neonates (24.1%). In most cases (86.2%) of delayed receipt, acyclovir administration occurred on the second or third day of hospitalization. The overall mortality rate was 7.3% (95% confidence interval: 5.8%-9.0%); 9.5% of those who received delayed acyclovir treatment and 6.6% of those who received early acyclovir treatment died. In a multivariate analysis, delayed acyclovir therapy was associated with significantly greater odds of death (adjusted odds ratio: 2.63 [95% confidence interval: 1.36-5.08]) compared with early acyclovir therapy.. In this multicenter observational study of neonates with HSV infection, delayed initiation of acyclovir therapy was associated with in-hospital death. Our data support the use of empiric acyclovir therapy for neonates undergoing testing for HSV infection.

Topics: Acyclovir; Antiviral Agents; Cohort Studies; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Retrospective Studies; Time Factors

Studies to verify correlations between phenotypes and genotypes of herpes simplex virus (HSV) are an important tool to establish a database of resistance-associated mutations.. In this study, 32 acyclovir (ACV)-resistant clinical HSV-1 and 4 ACV-resistant clinical HSV-2 isolates were examined in parallel by both phenotypic and genotypic resistance testing. Additionally, five non-viable HSV-1 strains and two non-viable HSV-2 strains with clinical resistance were included in genotypic resistance analysis.. All ACV-resistant HSV isolates showed cross-resistance to brivudin and penciclovir, and were sensitive to foscarnet and cidofovir. Acyclovir resistance was assigned to frameshift and single non-synonymous mutations of the thymidine kinase (TK) gene in 32 out of 37 HSV-1 strains and in 4 out of 6 HSV-2 strains. In three HSV-1 isolates, there were resistance-associated amino acid substitutions of the DNA polymerase (pol). Six substitutions in the TK and two in the DNA pol gene could not be attributed without doubt to either ACV resistance or natural gene polymorphism. Altogether, 10 resistance-related mutations in the TK and 1 in the DNA pol gene have not been reported previously.. The novel non-synonymous mutations found in this study enrich the knowledge about the genetic alterations of TK and DNA pol genes in ACV-resistant clinical HSV strains. Together with data from the literature, the findings justify the generation of a HSV database that contains resistance mutations associated with ACV resistance phenotype.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Bromodeoxyuridine; Child; Child, Preschool; Cidofovir; Cytosine; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Female; Foscarnet; Genotype; Guanine; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Infant; Male; Middle Aged; Mutation; Organophosphonates; Sequence Analysis, DNA; Thymidine Kinase; Viral Proteins

In vitro activity of interferon-alpha-2b in combination with various antioxidants against the influenza virus and Herpes simplex was studied. The standard strains and a clinical strain of Herpes simplex isolated from a patient with resistance to acyclovir were used. The in vitro studie showed that antioxidants, such as alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes simplex variants. They protected up to 100% of the cell monolayer from the virus cytopathic effect. The taurin solutions had no antiviral activity irrespective of the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic effect: the antiviral activity of interferon increased several times. The antiinfluenza activity of interferon-a-2b in the presence of various concentrations of taurin did not change.

Topics: Acyclovir; alpha-Tocopherol; Animals; Antioxidants; Antiviral Agents; Ascorbic Acid; Cell Line; Chlorocebus aethiops; Drug Synergism; Herpes Simplex; Humans; Influenza A Virus, H5N1 Subtype; Influenza, Human; Interferon alpha-2; Interferon-alpha; Kidney; Lung; Recombinant Proteins; Simplexvirus; Swine; Taurine; Unithiol; Vero Cells

Topics: Acyclovir; Antiviral Agents; Diabetes Mellitus, Type 1; Female; Hand Dermatoses; Herpes Simplex; Humans; Immunohistochemistry; Middle Aged; Pseudolymphoma; Valacyclovir; Valine

A 52-year-old woman with a 6-year history of systemic lupus erythematosus (SLE) developed acute abdominal pain, nausea, vomiting, and diarrhea accompanied by hypocomplementemia. Herpes simplex virus (HSV) esophagitis and lupus enteritis were diagnosed on the basis of the results of endoscopic and histological examinations and abdominal computed tomography (CT) findings. Treatment with acyclovir followed by high-dose intravenous steroids improved her symptoms. To our knowledge, this is the first case of simultaneous HSV esophagitis and lupus enteritis.

Topics: Acyclovir; Antiviral Agents; Drug Therapy, Combination; Enteritis; Esophagitis; Female; Glucocorticoids; Herpes Simplex; Humans; Lupus Erythematosus, Systemic; Methylprednisolone; Middle Aged; Pulse Therapy, Drug; Simplexvirus; Treatment Outcome

Hypertrophic pseudo tumoral herpetic lesion is an uncommon presentation in immunocompromized hosts that can be refractory to established therapies. We describe bipolar anal and tonsilar herpetic tumoral lesions related to acyclovir-resistant HSV-2 in a human immunodeficiency virus-infected patient. Treatment with valacyclovir, cidofovir, and thalidomide failed and surgical excision was required.

Topics: Acyclovir; Animals; Antiretroviral Therapy, Highly Active; Antiviral Agents; Anus Diseases; Chlorocebus aethiops; Drug Resistance, Viral; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Hypertrophy; Male; Middle Aged; Palatine Tonsil; Pharyngeal Diseases; Vero Cells

Acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) causes severe diseases in immunocompromised patients, so identification of new therapies is needed. Interferons (IFNs) are used to treat several other viral infections in the clinic, and IFN-beta and IFN-gamma are known to cooperatively reduce wild-type HSV-1 replication in the corneas of immunocompetent mice. Because IFN-gamma has been shown to exert an antiviral effect mostly through T cells, whether combined IFN treatment can still inhibit ACV-resistant HSV-1 replication, especially in immunocompromised hosts, is unknown. The present study evaluated the efficacy of combined IFN treatment on ACV-resistant HSV-1 mutants. In vitro results showed that IFN-beta acted synergistically with IFN-gamma to inhibit HSV-1 replication in both human and mouse cell lines. Some ACV-resistant mutants were actually hypersensitive to combined IFN treatment. In vivo results showed that topical treatment with a low dose of IFN-beta plus IFN-gamma (200 U each) on mouse corneas efficiently reduced the viral loads by up to 4, 4 and 3 logs, respectively, in the eyes, trigeminal ganglia and brainstems of wild-type and also immunocompromised nude mice infected or co-infected with ACV-resistant HSV-1 in a manner independent of T cells. A highly efficient reduction in HSV acute replication by combined IFN treatment led to a dramatic decrease in subsequent virus reactivation from neural tissues, trigeminal ganglia, brainstems and spinal cords of latently infected mice. Thus, a combination of IFN-beta and IFN-gamma could be a potential treatment for ACV-resistant HSV-1 in immunocompromised patients.

Topics: Acyclovir; Animals; Antiviral Agents; Brain Stem; Cell Line; Cornea; Drug Resistance, Viral; Drug Therapy, Combination; Herpes Simplex; Herpesvirus 1, Human; Humans; Interferon-beta; Interferon-gamma; Mice; Mice, Inbred ICR; Mice, Nude; T-Lymphocytes; Treatment Outcome; Trigeminal Ganglion; Viral Load; Virus Replication

Although the standard of care in febrile neutropenic patients includes the initiation of empirical antibacterial and antifungal therapy, many patients do not respond and need further diagnostic work up and treatment. Here, we report on an immunosuppressed neutropenic patient with a prolonged episode of fever unresponsive to empirical antibacterial therapy. Herpes polymerase chain reaction revealed systemic reactivation of herpes simplex virus type 1 (HSV-1) infection and treatment with acyclovir was associated with the prompt resolution of signs and symptoms of infection. Screening for HSV in persistently febrile neutropenic patients may discover HSV reactivation that can be treated successfully by acyclovir administration.

Topics: Acyclovir; Child; Fever; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Neutropenia; Viremia; Virus Activation

To study the effects of intravitreal foscarnet and the clinical differences between varicella zoster virus (VZV) and herpes simplex virus (HSV) induced acute retinal necrosis (ARN).. Retrospective comparative case series.. Eighty-one eyes of 74 patients.. A retrospective case note analysis was performed in 2 tertiary referral centers.. Presenting and final visual acuity, and progression to retinal detachment.. Thirty-three eyes had HSV-ARN and 48 had VZV-ARN. The average age for HSV-ARN was 34 years and 51 for VZV-ARN (P<0.001). Visual acuity on presentation was similar (P = 0.48), but a larger proportion had better vision (> or =20/60) in the HSV-ARN group (52%) than the VZV-ARN group (35%). A greater proportion of eyes with poor vision (< or =20/200) was found at the 12-month follow-up in the VZV-ARN group (60%) compared with the HSV-ARN group (35%). A greater degree of visual loss in the VZV-ARN group (0.4 logarithm of the minimum angle of resolution [logMAR]) compared with the HSV-ARN group (0.04 logMAR) was detected (P = 0.016). Retinal detachment was 2.5-fold more common in VZV-ARN (62%) compared with HSV-ARN (24%). When comparing eyes treated with (n = 56) and without (n = 25) intravitreal foscarnet, there was a 40% lower rate in retinal detachment (53.6% vs 75.0%) for VZV-ARN (P = 0.23). The numbers with HSV-ARN were too small for analysis.. The results support the difference of outcome in HSV-ARN and VZV-ARN. Therefore, viral identification serves as a key to predicting outcome in these patients. Intravitreal foscarnet seems to be a useful adjunct for the treatment of ARN in that it reduced rate of retinal detachment.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Child; Eye Infections, Viral; Female; Foscarnet; Herpes Simplex; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Infusions, Intravenous; Male; Middle Aged; Polymerase Chain Reaction; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Simplexvirus; Visual Acuity; Vitreous Body; Young Adult

Herpes simplex virus bronchopneumonitis is a clinical entity described in critically ill patients and classically associated to immunosuppression. Recent reports have shown a higher frequency of virus detection from samples obtained by bronchoalveolar lavage of immunocompetent critically ill patients undergoing mechanical ventilation. This fact suggests its role as an independent pathogenic substrate. We report the case of a female patient who was admitted after an elective surgery of rectal tumor with suspected bronchoaspiration during anesthetic induction. The patient presented persistent fever despite broad spectrum antibiotic treatment. All cultures were negative for bacterial growth. The chest X-ray did not show opacifities. Prolonged mechanical ventilation with repeated failures to wean made it mandatory to perform percutaneous tracheostomy. A fibrobronchoscopy with bronchoalveolar lavage, performed previously, showed positive result for herpes simplex virus (PCR and specific nuclear inclusions in cells). Thus, treatment was initiated with acyclovir, with clinical improvement and weaning from mechanical ventilation.

Topics: Acute Disease; Acyclovir; Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antiviral Agents; Bronchoalveolar Lavage Fluid; Bronchopneumonia; Combined Modality Therapy; Diagnosis, Differential; Female; Fluorouracil; Herpes Simplex; Humans; Immunocompromised Host; Pneumonia, Aspiration; Pneumonia, Viral; Postoperative Complications; Radiotherapy, Adjuvant; Rectal Neoplasms; Respiration, Artificial; Respiratory Insufficiency

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Facial Dermatoses; Herpes Simplex; Humans; Injections, Intralesional; Male; Organophosphonates

To assess the effect of high doses of valacyclovir (VCV) on HSV-1 DNA shedding into tears of latently infected rabbits.. Three oral doses of VCV were tested. Corneas were inoculated with HSV-1, and latent infection was allowed to establish. Starting on postinoculation (PI) day 28, tear swabs were collected once daily for 6 consecutive days before treatment. The rabbits were placed in five balanced groups: group 1 had no treatment, group 2 received placebo, group 3 received 7 mg/kg VCV, group 4 received 70 mg/kg, and group 5 received 140 mg/kg. The treatment was administered by oral gavage twice daily, starting on PI day 36 and continuing for 14 days. The ocular swabs were collected beginning on PI day 40 and continuing for 10 days.. The mean copy number of HSV-1 DNA before treatment was 370+/-70, 569+/-273, 368+/-86, 408+/-108, and 396+/-91, and the mean HSV-1 DNA copy number after treatment was 232+/-183, 564+/-186, 518+/-122, 67+/-63, and 13+/-7 in groups 1 to 5, respectively.. There was no observable toxicity in any group. The 70- and 140-mg/kg doses of VCV significantly reduced the HSV-1 DNA copy number, compared with that of the other three groups. A daily dose of 500 mg (approximately 7 mg/kg) VCV in healthy human volunteers did not suppress HSV-1 DNA shedding in tears and saliva. Thus, higher doses of VCV may be necessary to reduce asymptomatic shedding in healthy human subjects.

Topics: Acyclovir; Animals; Antiviral Agents; DNA, Viral; Dose-Response Relationship, Drug; Gene Dosage; Herpes Simplex; Herpesvirus 1, Human; Rabbits; Tears; Valacyclovir; Valine; Virus Latency

Topics: Acyclovir; Adult; Antiviral Agents; Anus Diseases; Female; Herpes Simplex; Humans; Skin Ulcer

Topics: Acyclovir; Aspirin; Basement Membrane; Dapsone; Glycoproteins; Herpes Simplex; Humans; Immunization, Passive; Immunoglobulin A; Infant; Male; Mucocutaneous Lymph Node Syndrome; Prednisolone; Skin Diseases, Vesiculobullous

Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii. Recently, complicated cases have been more frequently reported, even in previously healthy patients. We describe a case of severe MSF complicated by acute renal failure and associated with herpetic oesophagitis. Acyclovir therapy resulted in remission of oesophageal symptoms within 48 h.

Topics: Acute Kidney Injury; Acyclovir; Antibodies, Viral; Antiviral Agents; Boutonneuse Fever; Esophagitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Middle Aged; Rickettsia conorii; Treatment Outcome

Topics: Acyclovir; Female; Herpes Simplex; Humans; Leukemia, Myeloid, Acute; Middle Aged; Mupirocin; Nose; Nose Diseases; Simplexvirus

Hemophagocytic syndrome represents a severe hyperinflammatory condition by activated macrophages. Leading viral triggering agents are Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus.. We present a patient with Wegener's granulomatosis on azathioprine and prednisone medication, who developed a life-threatening hemophagocytic syndrome. Positive plasma polymerase chain reaction (PCR) with negative serology revealed a primary, disseminated infection with herpes simplex virus-1 as the triggering pathogen. After treatment with acyclovir, high-dose steroids, immunoglobulins, and etoposide, the patient recovered.. Early diagnosis of potentially underlying infections of hemophagocytic syndrome influences the therapeutic approach. It is important to consider a variety of infectious agents, particularly in immunosuppressed individuals. The reported case emphasizes the importance of screening for herpes simplex virus 1.

Topics: Acyclovir; Etoposide; Herpes Simplex; Herpesvirus 1, Human; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Middle Aged; Steroids

Herpes simplex virus (HSV) is considered to be one of the most frequent viral infectious agents in humans. Transmission of HSV from mother to foetus during pregnancy is uncommon with about 85% of transmission occurring perinatally, when neonates acquire HSV during vaginal birth from infected genital tract secretions. For women, who present with an episode of recurrent genital herpes several weeks before the expected delivery date, suppressive therapy with acyclovir or valacyclovir is recommended during the last 4 weeks of pregnancy. The study group consists of 21 women with recurrent genital tract herpes, who delivered between the years 2007-2009 at the Department of Obstetrics and Gynaecology, University Hospital Na Bulovce. Women in the last month of pregnancy were administered prophylactic viralstatic treatment with acyclovir 3 x 400 mg per day orally until delivery. In this study, no patient showed signs of acute lesions and viral DNA was not detectable on PCR in vaginal secretions. One woman delivered by acute caesarean section following signs of foetal hypoxia during the first stage of labour, two women were delivered by forceps. No newborns showed signs of HSV neonatal infection. Antiviral prophylaxis in the last month of pregnancy in women with recurrent genital herpes infection is considered to be safe and effective in the prevention of vulvar lesions and in decreasing the incidence of caesarean sections in this group of women.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Herpes Genitalis; Herpes Simplex; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious

Topics: Acyclovir; Antiviral Agents; Combined Modality Therapy; Drug Therapy, Combination; Epstein-Barr Virus Infections; Eye Infections, Viral; Glucocorticoids; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Prednisolone; Retinal Necrosis Syndrome, Acute; Treatment Outcome; Visual Acuity; Vitrectomy; Vitreous Body

The purpose of the present study was to investigate the skin irritation and pharmacodynamics of penciclovir-loaded microemulsion (PCV-ME). The formulation of PCV-ME was comprised of oleic acid (OA) (5%, w/w), Cremorphor EL (20%, w/w), ethanol (30%, w/w) and water (45%, w/w). PCV-ME presented as spherically shaped under transmission electron microscopy with an average diameter of 36.5 nm, and the solubility of PCV in microemulsion (ME) was 7.41 mg/g, almost 6 times that in water. Skin irritation test was performed in male guinea pigs, which demonstrated that no irritation effect was caused after single or multiple applications of PCV-ME. Likewise, male guinea pigs were employed as animal models which were infected with herpes simplex virus type 1 (HSV-1) in pharmacodynamics study. Real-time PCR was utilized to investigate the inhibition effect on HSV-1 exerted by commercial PCV-cream and PCV-ME. The results indicated that compared with commercial PCV-cream, PCV-ME could significantly inhibit the replication of HSV-1 in skin. In conclusion, PCV-ME could be a promising formulation which possessed the virtues of low irritation and high effectiveness.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Line, Tumor; Emulsions; Guanine; Guinea Pigs; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Skin; Skin Irritancy Tests

Herpes simplex and herpes zoster infections are common and often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir. Safety of these antivirals when used in the first trimester of pregnancy is insufficiently documented.. To investigate associations between exposure to acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and risk of major birth defects.. Population-based historical cohort study of 837,795 live-born infants in Denmark from January 1, 1996, to September 30, 2008. Participants had no diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections. Nationwide registries were used to ascertain individual-level information on dispensed antiviral drugs, birth defect diagnoses (categorized according to a standardized classification scheme), and potential confounders.. Prevalence odds ratios (PORs) of any major birth defect diagnosed within the first year of life by exposure to antiviral drugs.. Among 1804 pregnancies exposed to acyclovir, valacyclovir, or famciclovir in the first trimester, 40 infants (2.2%) were diagnosed with a major birth defect compared with 19,920 (2.4%) among the unexposed (adjusted POR, 0.89; 95% confidence interval [CI], 0.65-1.22). For individual antivirals, a major birth defect was diagnosed in 32 of 1561 infants (2.0%) with first-trimester exposure to acyclovir (adjusted POR, 0.82; 95% CI, 0.57-1.17) and in 7 of 229 infants (3.1%) with first-trimester exposure to valacyclovir (adjusted POR, 1.21; 95% CI, 0.56-2.62). Famciclovir exposure was uncommon (n = 26), with 1 infant (3.8%) diagnosed with a birth defect. Exploratory analyses revealed no associations between antiviral drug exposure and 13 different subgroups of birth defects, but the number of exposed cases in each subgroup was small.. In this large nationwide cohort, exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects.

Topics: 2-Aminopurine; Abnormalities, Drug-Induced; Acyclovir; Adolescent; Adult; Antiviral Agents; Cohort Studies; Denmark; Famciclovir; Female; Herpes Simplex; Herpes Zoster; Humans; Middle Aged; Pregnancy; Pregnancy Trimester, First; Retrospective Studies; Risk; Valacyclovir; Valine; Young Adult

Topics: Abnormalities, Drug-Induced; Acyclovir; Antiviral Agents; Cohort Studies; Data Collection; Denmark; Female; Herpes Simplex; Humans; Pregnancy; Pregnancy Trimester, First; Registries; Sample Size; United States

To report recurrent conjunctivitis and scleritis secondary to coexistent conjunctival pemiphigus vulgaris and cryptic herpes simplex infection.. Case report.. Retrospective review.. A 54-year-old woman presented with recurrent left eye irritation and redness. Four years earlier, she was diagnosed (biopsy) with cutaneous pemphigus vulgaris requiring immunomodulatory therapies. She was receiving oral acyclovir for recurrent genital herpes and intravenous immunoglobulin for pemphigus. Examination revealed unilateral necrotizing scleritis and conjunctivitis. Immunohistochemical staining of biopsies demonstrated conjunctival pemphigus and herpes in conjunctiva and sclera. Valacyclovir therapy brought resolution.. Cryptic ocular herpes may confound matters in someone with an autoimmune disease thought to be the sole source of ocular inflammation. Immunohistochemical analysis can resolve the mystery.

Topics: Acyclovir; Antiviral Agents; Conjunctival Diseases; Conjunctivitis; Female; Herpes Simplex; Humans; Immunoglobulins, Intravenous; Medical Records; Middle Aged; Necrosis; Pemphigus; Recurrence; Retrospective Studies; Scleritis; Valacyclovir; Valine

Topics: Acyclovir; Adult; Analgesia, Epidural; Analgesia, Obstetrical; Antiviral Agents; Dura Mater; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Medical Errors; Meningitis, Viral; Pregnancy

Inflammatory dilated cardiomyopathy (DCMi) represents an acquired form of dilated cardiomyopathy. Viral infection is the most common cause of DCMi. In contrast with other cardiotropic viruses, herpes simplex virus (HSV) is a very rare finding in endomyocardial biopsies of patients with dilated cardiomyopathy. We report a case of HSV-induced cardiomyopathy successfully treated with acyclovir.

Topics: Acyclovir; Antiviral Agents; Cardiomyopathy, Dilated; Herpes Simplex; Humans; Male; Middle Aged; Myocarditis; Treatment Outcome

Topics: Acyclovir; Adult; Antibodies, Monoclonal; Antiviral Agents; Crohn Disease; Diagnostic Errors; Female; Folliculitis; Herpes Simplex; Humans; Immunocompromised Host; Immunologic Factors; Infliximab; Perineum; Simplexvirus; Tumor Necrosis Factor-alpha; Valacyclovir; Valine; Virus Activation

Thoracic disc herniations are commonly found in asymptomatic individuals, sometimes with genetic predisposition. Congenital fusions of cervical vertebrae occur in Klippel-Feil syndrome, which may be asymptomatic or cause compressive myelitis due to cervical instability or associated herniated discs. We report the case of a 72-year-old man with monophasic acute transverse myelitis probably caused by herpes simplex virus, coexistent with fused cervical vertebrae (C4-C5) and thoracic herniated discs. Establishment of the aetiology in cases of transverse acute myelitis can constitute a challenge in patients with cervical spine anomaly and disc herniations.

Topics: Acyclovir; Aged; Antibodies, Viral; Antiviral Agents; Cervical Vertebrae; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunoglobulin G; Immunoglobulin M; Intervertebral Disc Displacement; Klippel-Feil Syndrome; Magnetic Resonance Imaging; Male; Myelitis, Transverse; Remission Induction; Thoracic Vertebrae

Herpes simplex virus hepatitis is a rare but potentially fatal condition that usually affects the immunocompromised, including pregnant women. This case report details the course of fulminant hepatic failure in a woman at 31 weeks gestation resulting in emergent delivery of the fetus and liver transplant in the mother.

Topics: Acyclovir; Adult; Antiviral Agents; Cardiotocography; Cesarean Section; Female; Hepatitis, Viral, Human; Herpes Simplex; Herpesviridae Infections; Herpesvirus 2, Human; Humans; Infant, Newborn; Liver Failure, Acute; Liver Transplantation; Male; Pregnancy; Pregnancy Complications, Infectious

We describe a rare case of a 79-year-old woman who developed herpes simplex virus pneumonia after mitral valve replacement. The patient showed persistent hypoxemia with bilateral glass-like shadows on chest radiography. Cytopathology examination of intratracheal secretions revealed herpes simplex virus infection. The patient, who improved gradually after acyclovir administration, was taken off the ventilator completely. Physicians should consider viral pulmonary infection to be a potential cause of unexplained hypoxemia that does not respond to conventional antibiotic treatment in critically ill, immunocompromised patients.

Topics: Acyclovir; Aged; Antiviral Agents; Female; Heart Valve Prosthesis Implantation; Herpes Simplex; Humans; Hypoxia; Mitral Valve; Mitral Valve Insufficiency; Pneumonia, Viral; Respiration, Artificial; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ventilator Weaning

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Clostridioides difficile; Enterocolitis, Pseudomembranous; Female; Herpes Simplex; Humans; Immunocompromised Host; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Trimester, Third; Risk Factors; United States

Acute retinal necrosis (ARN), which is characterized by rapidly progressing peripheral retinal necrosis, is caused mainly by herpes simplex virus type 1, herpes simplex virus type 2 (HSV-2), or varicella-zoster virus. A previously healthy 3-year-old Japanese boy developed ARN in his left eye after being bruised by a milk container. HSV-2 DNA was detected in the aqueous humor of the affected eye. Serological testing suggested that the route of infection was from mother to child, although there was no past history of apparent HSV-2 infection. Childhood ARN has not been previously reported in Japan, possibly because of the low seroprevalence of HSV-2 in Japanese women. Pediatricians must be aware of this rare disease, which can affect individuals without a previous history of HSV even in a country with a low seroprevalence of HSV-2.

Topics: Acyclovir; Anti-Inflammatory Agents; Antiviral Agents; Child, Preschool; Disease Progression; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Herpes Simplex; Herpesvirus 2, Human; Humans; Immunoglobulin G; Infusions, Intravenous; Intraocular Pressure; Japan; Male; Prednisone; Retinal Necrosis Syndrome, Acute

We report the case of a 34-year-old man who had uncomplicated cataract surgery in his left eye. Medical history was significant for atopic dermatitis, requiring oral immunosuppressive medications. Two days after the surgery, the patient presented with pain, photophobia, decreased vision, and a small corneal abrasion. On postoperative day 5, the patient returned with left upper lid vesicular lesions and 2 corneal dendrites. Corrected vision was 20/100 OS, with intraocular pressure of 18 mm Hg and 1+ pigmented cells in the anterior chamber. Cultures of the lid lesions revealed herpes simplex virus (HSV) type 1. The patient was placed on oral acyclovir 800 mg 5 times a day. By day 8, the dendrites had resolved, and by day 15, the lid lesions healed over. HSV keratitis is an uncommon complication after cataract surgery. Ophthalmologists should be aware of the possibility of developing HSV keratitis even after the most routine cataract extraction.

Topics: Acyclovir; Administration, Oral; Adult; Anti-Inflammatory Agents; Antifungal Agents; Antiviral Agents; Cataract Extraction; Drug Administration Schedule; Drug Therapy, Combination; Eyelid Diseases; Herpes Simplex; Humans; Keratitis, Herpetic; Male; Postoperative Complications; Prednisolone; Treatment Outcome; Wound Healing

Here we report the case of an immunocompetent 8-year-old child who developed acute retinal necrosis concomitant with a primary herpes simplex virus type I infection. Ocular inflammation changed along with the development of a specific antibody titer in the serum. This evidence suggests that the immune response of the host can significantly modulate the clinical aspect of the ocular infection.

Topics: Acyclovir; Anterior Chamber; Anti-Inflammatory Agents; Antiviral Agents; Child; Fundus Oculi; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompetence; Male; Prednisone; Retina; Retinal Necrosis Syndrome, Acute

Topics: Acyclovir; Administration, Topical; Allergens; Dermatitis, Allergic Contact; Drug Hypersensitivity; Female; Follow-Up Studies; Herpes Simplex; Humans; Patch Tests; Risk Assessment; Young Adult

Topics: Acyclovir; Adult; Antiviral Agents; Facial Dermatoses; Female; Herpes Simplex; Herpesvirus 2, Human; Humans

In the previous study, we discovered a polyether antibiotic CP-44161, which was reported earlier as an anticoccidal agent, as an anti-varicella zoster virus compound. In this study, we demonstrated that CP-44161 had a very strong and broad anti-herpes virus activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro. To determine the antiviral activity of CP-44161 in vivo, we examined its effect on the cutaneous HSV-2 infection model in Balb/c mice. CP-44161 showed inhibitory effect on lesion development as well as acyclovir (ACV) when the treatment was started from day 3. Meanwhile, in case the start of treatment was delayed until day 4, when ACV was no longer effective, the effectiveness of CP-44161 still remained. In this model, CP-44161 also showed inhibitory effect on the proliferation of HSV-2 DNA in dorsal root ganglia. This is the first article to report that polyether antibiotics can be effective on viral infection in vivo.

Topics: Acyclovir; Animals; Antiviral Agents; Bridged-Ring Compounds; Carbohydrate Conformation; Carbohydrate Sequence; Cell Survival; Chlorocebus aethiops; DNA, Viral; Ethers; Female; Furans; Ganglia, Spinal; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Pyrans; Vero Cells

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antiviral Agents; Epiglottitis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Methylprednisolone; Pharyngitis; Recurrence; Stroboscopy

Topics: Acyclovir; Antiviral Agents; Disease Susceptibility; Herpes Genitalis; Herpes Simplex; Humans; Male; Placebos; Valacyclovir; Valine

Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis) or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the in vitro skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores), using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm2 of acyclovir 5% cream or penciclovir 1% cream.. After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physico-chemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips.. Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells.. Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of penciclovir through the epidermis into the deeper basal cells.

Topics: Abdomen; Acyclovir; Antiviral Agents; Dermis; Diffusion; Drug Evaluation, Preclinical; Epidermis; Gene Expression Regulation; Guanine; Herpes Simplex; Humans; Hydrophobic and Hydrophilic Interactions; In Vitro Techniques; Keratin-5; Ointments; Permeability; Skin Absorption

The main predictor of outcomes in herpes simplex virus (HSV) encephalitis (HSE) is the delay between hospital admission and initiation of acyclovir. In this study, factors associated with late initiation of acyclovir were identified. The study included adults from northern France whose cerebrospinal fluid (CSF) was positive for HSV by PCR. Late initiation of acyclovir was defined as a delay of >1 day from hospital admission. In total, 184 patients were retrospectively enrolled from January 1991 to December 2002. The median age was 60 years (range: 17-91), and 102 (55.4%) were male. Acyclovir was initiated >1 day after hospital admission in 68 patients (37.0%). According to multivariate analysis, independent risk factors for late initiation of acyclovir were severe underlying disease (Knaus score >or=C) (OR 4.1; 95% CI 1.5-11.7); alcohol abuse (OR 3.4; 95% CI 1.3-8.9); and a delay of >1 day from admission to first brain imaging (OR 8.4; 95% CI 3.9-18.0). In addition, univariate analysis suggested an association between a finding of <10 leukocytes/mm(3) in CSF at admission (OR 2.5; 95% CI 0.7-5.8). These characteristics were found in 26 (14.1%), 23 (12.5%), 66 (35.9%) and 27 (14.7%) patients, respectively. One risk factor was identified in 109 (59.2%) patients, two in 29 (15.8%), and three in six (3.3%). Patients with HSE often present with severe underlying disease, chronic alcohol abuse, or atypical CSF findings, and such factors should not be allowed to delay diagnosis and administration of acyclovir.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Cerebrospinal Fluid; Encephalitis, Viral; Female; France; Herpes Simplex; Humans; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Simplexvirus; Time Factors; Treatment Outcome; Young Adult

To assess the etiology, prognosis, and appropriate treatment of hemophagocytic lymphohistiocytosis (HLH) in neonates.. We collected information on neonates in whom HLH was diagnosed between 1997 and 2007 from participating members of the Japanese Society of Pediatric Hematology.. HLH was diagnosed in 20 patients within 4 weeks after birth. Of the diagnostic criteria for HLH-2004, the incidence of fever was quite low in preterm infants, and hypertriglyceridemia and neutropenia were uncommon. Familial HLH (n = 6) or severe combined immunodeficiency-associated HLH (n = 1) was diagnosed in 7 patients, and 2 of them have survived. Herpes simplex virus-associated HLH was diagnosed in 6 patients, and 2 of them have survived. The overall survival rate for the 20 patients was 40%.. HLH is rare in neonates and has a poor prognosis. Early diagnosis and immediate treatment are required when considering the possibility of herpes simplex virus-associated or familial HLH.

Topics: Acyclovir; Adrenal Cortex Hormones; Antineoplastic Agents, Phytogenic; Antiviral Agents; beta 2-Microglobulin; Consciousness Disorders; Cyclosporine; Erythema; Etoposide; Exanthema; Female; Fetal Distress; Fever; gamma-Globulins; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunologic Factors; Immunosuppressive Agents; Infant, Newborn; Infant, Premature; Japan; L-Lactate Dehydrogenase; Leukocytosis; Lymphohistiocytosis, Hemophagocytic; Male; Ocular Motility Disorders; Plasma Exchange; Prognosis; Respiratory Distress Syndrome, Newborn; Seizures; Severe Combined Immunodeficiency

The present investigation aims at developing microemulsion-based formulations for topical delivery of acyclovir. Various microemulsions were developed using isopropyl myristate/Captex 355/Labrafac as an oil phase, Tween 20 as surfactant, Span 20 as cosurfactant, and water/dimethylsulfoxide (1:3) as an aqueous phase. Transcutol, eucalyptus oil, and peppermint oil were used as permeation enhancers. In vitro permeation studies through laca mice skin were performed using Franz diffusion cells. The optimum formulation containing 2.5% Transcutol as the penetration enhancer showed 1.7-fold enhancement in flux and permeation coefficient as compared to marketed cream and ointment formulation. In vivo antiviral studies were performed in female Balb/c mice against induced herpes simplex virus I infection. A single application of microemulsion formulation containing 2.5% Transcutol given 24 h post-injection resulted in complete suppression of development of herpetic skin lesions.

Topics: Acyclovir; Administration, Cutaneous; Adult; Animals; Antiviral Agents; Chemistry, Pharmaceutical; Emulsions; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Mice; Mice, Inbred BALB C; Permeability; Skin; Skin Diseases, Viral; Solubility

To determine the viral diagnosis and the outcome of eyes with acute retinal necrosis (ARN) treated with intravenous acyclovir and oral prednisolone alone or combined with early vitrectomy and intravitreal acyclovir lavage.. Nonrandomized, retrospective, interventional, comparative, consecutive series.. A cohort of 27 human immunodeficiency virus-negative patients with ARN comprising 24 unilateral and 3 bilateral cases.. Vitreous biopsy for viral diagnosis. Twenty eyes were treated with intravenous acyclovir in combination with oral prednisolone (group A). Ten eyes were treated additionally with early vitrectomy, intravitreal acyclovir lavage, laser demarcation of necrotic retinal areas when feasible-with or without scleral buckling, and gas or silicone oil tamponade (group B). Vitrectomy was performed in all cases of secondary rhegmatogenous retinal detachment (RD).. Results of vitreous biopsy, rate of RD, rate of phthisis bulbi, and course of best-corrected visual acuity (BCVA).. Varicella zoster virus (VZV) was detected in 26 eyes, followed by herpes simplex virus (5 eyes), and Epstein-Barr virus (2 eyes, in conjunction with VZV). An RD developed in more eyes in group A (18 of 20 eyes) than in group B (4 of 10 eyes; P = 0.007). In 2 of 20 eyes in group A and in 0 of 10 eyes in group B, phthisis bulbi developed without a significant difference between groups A and B. Mean BCVA (logarithm of the minimum angle of resolution) at first visit was 1.09 (standard deviation [SD], 0.83), and mean final BCVA was 1.46 (SD, 0.88) without significant difference between groups A and B.. Varicella zoster virus is the leading cause of ARN. Visual prognosis is guarded. Early vitrectomy with intravitreal acyclovir lavage was associated with a lower incidence of secondary RD; however, it did not improve mean final visual acuity.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Combined Modality Therapy; Drug Therapy, Combination; Epstein-Barr Virus Infections; Eye Infections, Viral; Female; Glucocorticoids; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Male; Middle Aged; Prednisolone; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Treatment Outcome; Visual Acuity; Vitrectomy; Vitreous Body; Young Adult

Neonatal herpes simplex virus (HSV) infection, while uncommon, is associated with substantial morbidity and mortality. However, there is little nationally representative data describing resource utilization.. This retrospective cohort study was conducted using the Pediatric Health Information System, an administrative database that contains discharge diagnosis and resource utilization data from 35 free-standing children's hospitals. Patients

Topics: Acyclovir; Antiviral Agents; Cohort Studies; Female; Health Resources; Heart Defects, Congenital; Herpes Simplex; Hospital Charges; Humans; Infant; Infant, Newborn; Information Systems; Length of Stay; Male; Pennsylvania; Retrospective Studies; Simplexvirus

To determine clinical features, viral aetiology and treatment outcomes of eyes with acute retinal necrosis (ARN).. Retrospective, interventional, non-comparative case series.. Twenty-two patients (23 eyes) were identified between 1996 and 2007. Varicella zoster virus was the causative agent in 12 patients (nine confirmed by polymerase chain reaction), herpes simplex virus type 1 in six (five polymerase chain reaction-confirmed) and unknown in three patients. Five patients had documented herpes zoster infection in the month prior to the onset of ARN. Twelve patients (55%) had identifiable (clinical or subclinical) immune dysfunction. At 6 months, 3 out of 15 eyes (20%) maintained vision 6/12 or better and 7 (47%) were 6/60 or worse. Median final VA was 6/60. Nine eyes developed retinal detachment and two-thirds of these had received prior barrier laser. Poor prognostic factors for severe visual loss by univariate analysis were male gender (P = 0.019), and the development of retinal detachment (P = 0.05). Delay between onset of symptoms and diagnosis was associated with moderate visual loss (P = 0.018). Barrier laser did not reduce the risk of retinal detachment.. Acute retinal necrosis still has poor visual prognosis. Early diagnosis and initiation of treatment may improve outcome.

Topics: Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Aqueous Humor; Child; DNA, Viral; Female; Glucocorticoids; Herpes Simplex; Herpes Zoster Ophthalmicus; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Male; Middle Aged; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Treatment Outcome; Vitreous Body; Young Adult

Two cases of recurrent lumbosacral herpes simplex without concomitant genital lesions are reported. Both patients presented with vesicular lesions on the middle of the lower back and on the left thigh, respectively, and had positive serum antibody to herpes simplex virus type 2 and negative antibody to HIV. The lesions healed completely within 1 week by oral administration of acyclovir.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Herpes Simplex; Herpesvirus 2, Human; Humans; Low Back Pain; Lumbosacral Region; Male; Recurrence; Unsafe Sex

To characterize in detail persistent and recalcitrant infectious scleritis resulting from herpes simplex virus (HSV).. Retrospective and interventional clinical and immunopathologic case series.. Nine patients with chronic scleral redness, edema, and pain refractory to conventional therapy underwent a scleroconjunctival biopsy for routine histopathologic evaluation and definitive immunodiagnosis for the presence of HSV. Immunofluorescent probing for HSV was performed on the patient specimens. Negative controls for HSV included elimination of anti-HSV and anti-varicella zoster virus antibody in the probing process and the use of normal human conjunctiva and sclera as substrates. Response to therapy with acyclovir was monitored and recorded.. The average age of the affected patients was 50.2 years, and the average duration of symptoms before tissue diagnosis of herpetic scleritis was 3.2 years (median, 4 years). Three histopathologic patterns were discovered: granulomatous inflammation (2 cases), plasma cell-rich pyogenic granuloma-like pattern (1 case), and reactive fibroinflammatory pattern (6 cases). Herpes antigen was demonstrated uniformly by immunofluorescence in a perivascular distribution and less commonly in the interstitium. Varicella zoster virus was not detected, and all controls for nonspecific antibody reagent binding to tissue showed negative results. Acyclovir caused a dramatic improvement in the chronic or recurrent ocular inflammation in all instances, with an average duration of improvement of inflammation of 15.3 months.. Unrecognized HSV infection can cause longstanding scleritis. Histopathologic features of HSV scleritis are varied and nonspecific; immunofluorescent demonstration of HSV protein can make a definitive diagnosis. Prolonged administration of acyclovir is required for effective therapy.

Topics: Acyclovir; Adult; Aged; Antigens, Viral; Antiviral Agents; Chronic Disease; Eye Infections, Viral; Female; Fluorescent Antibody Technique, Indirect; Herpes Simplex; Humans; Male; Middle Aged; Retrospective Studies; Scleritis; Simplexvirus; Time Factors

Herpes simplex esophagitis (HSE) occurs mostly in immunocompromised patients and rarely in immunocompetent patients. We encountered an elderly patient, a biologically immunocompromised patient with HSE who had characteristic endoscopic features and responded to acyclovir therapy. An 82-year-old woman presented with high-grade fever and epigastric discomfort for several days. A diagnosis of bacterial pneumonia was made based on imaging studies and cultures. Despite antibiotic treatment, epigastric discomfort persisted. Endoscopy revealed multiple exudative and circumscribed shallow ulcers with slightly raised edges in the mid-distal esophagus. Esophageal biopsy specimens showed multinucleated giant cells with Cowdry type A intranuclear inclusion bodies in epithelial cells, which were positive for herpes simplex virus-type 1 DNA by polymerase chain reaction. Because a diagnosis of HSE was made, she was treated with acyclovir, resulting in esophageal mucosal healing. In elderly patients with esophageal symptoms, HSE should be considered.

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Esophagitis; Female; Herpes Simplex; Humans; Immunocompromised Host

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Valacyclovir; Valine

Topics: Acyclovir; Adolescent; Anti-Bacterial Agents; Antiviral Agents; Facial Paralysis; Female; Herpes Simplex; Humans; Meningitis, Meningococcal

Topics: Acyclovir; Antiviral Agents; Delayed Diagnosis; Diagnosis, Differential; Diagnostic Errors; Esophageal Diseases; Herpes Simplex; Humans; Male; Middle Aged; Peptic Ulcer; Wound Healing

A 42-year-old woman was referred with fever and abdominal pain with peritoneal irritation. A diagnostic laparoscopy showed hepatic lesions. Histopathological investigation of the liver biopsy showed hepatitis caused by herpes simplex virus (HSV). The patient was treated with acyclovir and recovered well. HSV is a rare cause of viral hepatitis and has a high mortality rate.

Topics: Abdominal Pain; Acyclovir; Adult; Antiviral Agents; Female; Hepatitis, Viral, Human; Herpes Simplex; Humans; Immunocompetence; Treatment Outcome

A 33-year-old woman presented with a 5-year history of a relapsing erythematous, indurated plaque on the left cheek. Herpes simplex virus (HSV) immunostain revealed the presence of HSV in the follicular and perifollicular keratinocytes. After oral treatment with valaciclovir for a period of 3 months the lesion disappeared without leaving a scar. At the last check-up, no recurrence had occurred. Herpes folliculitis has various clinical presentations. In rare cases it mimics a pseudolymphoma, as was the case for this patient. A viral aetiology, such as HSV or varicella-zoster virus, should be considered in patients with folliculitis, especially when the condition does not respond to antibacterial and antifungal therapy.

Topics: Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Facial Dermatoses; Female; Folliculitis; Herpes Simplex; Humans; Simplexvirus; Valacyclovir; Valine

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Female; Herpes Simplex; Humans; Lupus Erythematosus, Systemic; Skin; Treatment Outcome; Valacyclovir; Valine; Vasculitis

Testing for herpes simplex virus type 2 (HSV-2) antibody is not common in clinical practice. Client characteristics associated with HSV-2 rapid antibody test uptake and test positivity were analyzed in clients attending an urban sexually transmitted disease clinic.. This optional test was available for $30. The HerpeSelect Express assay was performed on serum. Demographic and behavioral characteristics were compared between clients who requested testing and those who did not and between those who were HSV-2 antibody positive and negative.. In 4 months, 3498 individuals attended the clinic and 443 (12.7%) opted for HSV-2 testing. Clients who were black, younger, or female were less likely to request testing. Recent sexual behavior and self-reported sexual orientation were not associated with uptake of testing. Of the 442 clients with results available, 109 were positive for HSV-2 antibody (24.7%). Women were significantly (P <0.001) more likely to test positive; 42 of 111 (38.4%) versus only 67 of 331 (20.2%) men. A positive HSV-2 antibody test was also associated with increasing age and black race. There was an association with the number of partners in the last 30 days, but no association with the number of partners in the last year. Of the 109 clients who had a positive HSV-2 antibody test, 71 (64.5%) accepted a prescription for suppressive acyclovir therapy.. Uptake of testing was modest in this population, especially among the highest risk individuals, possibly due to the cost of the test. Improved education regarding HSV-2 and subsidized testing may be needed in the populations that have the highest prevalence in order to encourage testing.

Topics: Acyclovir; Adult; Ambulatory Care Facilities; Antibodies, Viral; Antiviral Agents; Diagnosis, Differential; Female; Health Plan Implementation; Health Services Accessibility; Herpes Simplex; Herpesvirus 2, Human; Humans; Indiana; Male; Patient Compliance; Reagent Kits, Diagnostic; Urban Health

We report a 31-year-old man with an obstructive bronchial lesion due to herpes simplex type 2 infection, who responded promptly to endoscopic resection and oral treatment with acyclovir. Exophytic lesions of the respiratory tract are rare, potentially life-threatening, but readily treated complication of herpes simplex virus infection in HIV-infected individuals.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Bronchial Neoplasms; Diagnosis, Differential; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Lung Diseases, Obstructive; Male; Radiography; Tomography Scanners, X-Ray Computed

Topics: Acyclovir; Antiviral Agents; Cerebrospinal Fluid; Drug Monitoring; Encephalitis, Viral; Herpes Simplex; Humans; Infant; Plasma; Recurrence; Simplexvirus; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Erythema Multiforme; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Male; Military Personnel; Triamcinolone Acetonide; Turkey; United Kingdom; Young Adult

Viral infections are common complications following renal transplantation. However, there have been few reported cases of viral cystitis secondary to herpes simplex virus or adenovirus infection. Herein, we have reported four cases of hemorrhagic cystitis secondary to infections with herpes simplex virus and adenovirus following renal transplantation. The etiology was adenovirus in three cases and herpes simplex virus in the remaining case. In all four cases, the primary cause of the renal dysfunction was diabetic nephropathy. All four patients presented with a clinical profile characterized by dysuria, pollakiuria, macroscopic hematuria, and graft dysfunction. Three of the four patients developed these symptoms within the first 3 months after renal transplantation. In all four cases, there was an increase, albeit slight, in creatinine levels, which returned to normal or near-normal values upon resolution of the symptoms. Acute cellular rejection was observed in only one case. Although rare, hemorrhagic cystitis secondary to infection, which typically occurs early in the posttransplant period, causes pronounced symptoms. The infection appears to be self-limiting, resolving completely within 4 weeks.

Topics: Acyclovir; Adenovirus Infections, Human; Aged; Aged, 80 and over; Antiviral Agents; Cystitis; Diabetic Nephropathies; Herpes Simplex; Humans; Kidney Transplantation; Male; Middle Aged; Treatment Outcome; Valacyclovir; Valine

To describe a case of HSV2 acute retinal necrosis (ARN) diagnosed and monitored with quantitative polymerase chain reaction (PCR) in ocular fluids.. Case report.. Quantitative PCR was performed in the aqueous humor (AH) and vitreous using primers specific for herpes virus.. A positive PCR was found for HSV2 in the AH (>100,000,000 viral copies - 8.00 log/ml). After therapy, another anterior chamber tap showed a reduction of the viral load at 4.28 log/ml (19205 copies), confirming the efficacy of the treatment. After six months, PCR on the vitreous still showed the presence of HSV2 viral particles in the eye (3.14 log DNA copies/ml, 1379 copies) although the lesion was healed.. This case demonstrates that PCR is useful to detect viral DNA in AH and vitreous and to monitor viral activity and therapeutic response. Viral DNA persists in ocular fluids for months in the presence of a healed infection.

Topics: Acyclovir; Administration, Oral; Adult; Antiviral Agents; Aqueous Humor; Female; Ganciclovir; Herpes Simplex; Herpesvirus 2, Human; Humans; Infusions, Intravenous; Retinal Necrosis Syndrome, Acute; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Valganciclovir; Viral Load

Topics: Acyclovir; Antiviral Agents; Biopsy; Hepatitis, Viral, Human; Herpes Simplex; Humans; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiography; Treatment Outcome

To determine the clinical effectiveness and cost-effectiveness of testing for and empirically treating herpes simplex virus (HSV) infection in neonates with fever aged from birth to 28 days.. Cost-effectiveness analysis.. Decision model.. Neonates with fever with no other symptoms and neonates with fever with cerebrospinal fluid (CSF) pleocytosis.. Four clinical strategies: (1) HSV testing and empirical treatment while awaiting test results; (2) HSV testing and treatment if test results were positive for HSV or the patient had symptoms of HSV; (3) treatment alone without testing; or (4) no HSV testing or treatment unless the patient exhibited symptoms. The 2 HSV testing methods used were CSF HSV polymerase chain reaction (PCR) and comprehensive evaluation with blood HSV PCR, CSF HSV PCR, and multiple viral cultures.. Twelve-month survival and quality-adjusted life expectancy with a cost-effectiveness threshold of $100,000 per quality-adjusted life year (QALY) gained.. Clinical strategy 1, when applied in febrile neonates with CSF pleocytosis, saved 17 lives per 10,000 neonates and was cost-effective using CSF HSV PCR testing ($55,652/QALY gained). The cost-effectiveness of applying clinical strategy 1 in all febrile neonates depended on the cost of the CSF HSV PCR, prevalence of disease, and parental preferences for neurodevelopmental outcomes. Clinical strategies using comprehensive HSV testing were not cost-effective in febrile neonates ($368,411/QALY gained) or febrile neonates with CSF pleocytosis ($110,190/QALY gained).. Testing with CSF HSV PCR and empirically treating with acyclovir sodium saves lives and is cost-effective in febrile neonates with CSF pleocytosis. It is not a cost-effective use of health care resources in all febrile neonates.

Topics: Acyclovir; Antiviral Agents; Cost-Benefit Analysis; Decision Support Techniques; Disease Progression; Female; Fever; Herpes Simplex; Humans; Infant, Newborn; Leukocytosis; Male; Probability; Quality-Adjusted Life Years; Treatment Outcome

By a plaque reduction assay, methanolic extracts from Lobelia chinensis (LC) significantly blocked herpes simplex virus type 1 (HSV-1) replication in HeLa cells without apparent cytotoxicity. The 50% inhibitory concentration (IC(50)) of LC on HSV-1 replication is 139.2 microg/ml. To elucidate LC anti-HSV-1 activity in vivo, BALB/c mice were injected subcutaneously with HSV-1 (2.5 x 10(6)PFU/50 microl), treated orally thrice a day with acyclovir (60 mg/kg/dose) or LC (20 and 50 mg/kg/dose) for 7 days, and inspected daily for signs of disease. Data from the scoring system indicated that animals infected with HSV-1, developed progressive zoster lesions starting 2 days postinfection (p.i.) and appeared the most serious syndromes at 4-5 days p.i. In marked contrast to the results with control mice, treatment with acyclovir or 50 mg/kg/dose LC resulted in a sustained protective effect. The HSV-1 titers and DNA levels in ground skin samples were significantly reduced by LC. No toxic effect of LC on liver and kidney functions was apparent. These results indicated that LC was a potent inhibitor of the in vitro and in vivo replication of HSV-1.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Survival; Drug Administration Schedule; HeLa Cells; Herpes Simplex; Herpesvirus 1, Human; Humans; Kidney; Liver; Lobelia; Mice; Mice, Inbred BALB C; Plant Extracts; Skin; Virus Replication

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Drug Administration Schedule; Herpes Simplex; Humans; Infant, Newborn; Meningitis, Bacterial

Topics: Acyclovir; Antiviral Agents; Diagnosis, Differential; Herpes Simplex; Humans; Infant, Newborn; Sepsis

Acyclovir-induced nephrotoxicity is well known, but published literature lacks information on the safety of substitution with other antiviral agents. We describe four patients with acyclovir-induced renal toxicity that were subsequently managed with hydration and famciclovir. All four patients subsequently had improvements in their symptoms with full recovery of their baseline renal function.

Topics: 2-Aminopurine; Acyclovir; Aged; Aged, 80 and over; Antiviral Agents; Famciclovir; Female; Herpes Simplex; Herpes Zoster; Humans; Kidney Diseases; Male; Middle Aged

Herpes simplex virus (HSV) infections in immunocompromised individuals may require prolonged antiviral therapy resulting in the emergence of viral strains resistant to the currently employed antiviral drugs. Distamycin A (DA), a basic antibiotic belonging to the lexitropsin DNA minor groove binding drugs, exhibits antiviral properties. In this study we evaluated the in vitro cytotoxicity and antiviral activity of DA against HSV type 1 and HSV type 2 clinical isolates from transplanted patients and compared them with those of acyclovir (ACV) in search of alternative antiviral drugs.. Viral detection and typing was performed by multiplex PCR and immunofluorescence assay; the in vitro cytotoxicity of DA and the antiviral activity of ACV and DA was evaluated respectively by neutral red uptake assay and plaque reduction assay for HSV2 isolates and fluorescence reduction assay for HSV1 isolates.. Tissue culture 50% cytotoxic concentration of DA was 58 muM. Tissue culture 50% inhibitory concentration values ranged from 0.16 to 7.4 muM for the ACV-sensitive and from 5.4 to 32 muM for the ACV-resistant viral strains.. In spite of the lower activity against ACV-resistant strains, DA may be used as an antiherpetic drug.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Distamycins; Fluorescence; Herpes Simplex; Herpesvirus 1, Human; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Molecular Sequence Data; Neutral Red; Simplexvirus; Transplantation; Vero Cells; Viral Plaque Assay

Topics: Acyclovir; Antiviral Agents; Carcinoma, Non-Small-Cell Lung; Endoscopy, Gastrointestinal; Esophagitis; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Lung Neoplasms; Male; Middle Aged

Topics: Acyclovir; Adult; Antiviral Agents; Drug Therapy, Combination; Female; Glucocorticoids; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Japan; Male; Middle Aged; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Scleral Buckling; Visual Acuity; Vitrectomy

The antiherpes drug acyclovir was found to inhibit HIV following its phosphorylation by human herpesviruses, providing a hypothesis to explain the observed beneficial effects of acyclovir therapy on HIV viral load and HIV disease progression. This report underscores the importance of studying HIV in the context of microbial copathogens.

Topics: Acyclovir; Anti-HIV Agents; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Phosphorylation; Prodrugs

For most viruses, there is a need for antimicrobials that target unique viral molecular properties. Acyclovir (ACV) is one such drug. It is activated into a human herpesvirus (HHV) DNA polymerase inhibitor exclusively by HHV kinases and, thus, does not suppress other viruses. Here, we show that ACV suppresses HIV-1 in HHV-coinfected human tissues, but not in HHV-free tissue or cell cultures. However, addition of HHV-6-infected cells renders these cultures sensitive to anti-HIV ACV activity. We hypothesized that such HIV suppression requires ACV phosphorylation by HHV kinases. Indeed, an ACV monophosphorylated prodrug bypasses the HHV requirement for HIV suppression. Furthermore, phosphorylated ACV directly inhibits HIV-1 reverse transcriptase (RT), terminating DNA chain elongation, and can trap RT at the termination site. These data suggest that ACV anti-HIV-1 activity may contribute to the response of HIV/HHV-coinfected patients to ACV treatment and could guide strategies for the development of new HIV-1 RT inhibitors.

Topics: Acyclovir; Anti-HIV Agents; Biotransformation; Cells, Cultured; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; In Vitro Techniques; Lymphoid Tissue; Phosphorylation; Prodrugs; Reverse Transcriptase Inhibitors; Virus Replication

Infections with human herpesviruses types 1 and 2 (HHV-1 and HHV-2) are common worldwide and cause a wide range of signs and symptoms. Antiviral drugs, in particular aciclovir are used in therapy of herpetic infections. The aim of the study was determination of susceptibilities of HHV-1 isolates (n+46) for antiviral drugs (acyclovir and cidofovir) in vitro. Swabs taken from different lesions were used for infection of Vero cells and cythopathic effect was observed. Viruses from cell cultures with positive CPE were later identified with in-house PCR and efficacy of acyclovir and cidofovir in HHV-1 infected Vero cell monolayer cultures was tested by the yield reduction assay. Obtained data indicate, that aciclovir ID50 average value for HHV-1 clinical isolates was 0.74 microg/ml--the value about 10% greater then described in literature. Similarly in vitro analysis of sensitivity of viruses for cidofovir, shows that concentrating is over ten-fold higher in comparison for aciclovir.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Cidofovir; Cytosine; Herpes Simplex; Herpesvirus 1, Human; Humans; Microbial Sensitivity Tests; Organophosphonates; Vero Cells

Topics: Acyclovir; Anal Canal; Child Abuse, Sexual; Child, Preschool; Follow-Up Studies; Herpes Genitalis; Herpes Simplex; Humans; Male; Risk Assessment; Severity of Illness Index

Bell"s palsy is a neuropathy of the peripheral seventh cranial nerve, resulting from traumatic, compressive, infective, inflammatory or metabolic abnormalities or it can be idiopathic. HIV, Epstein-Barr virus and hepatitis B virus have been suspected as initiating organisms, but herpes simplex virus is the most frequently implicated. This report describes 2 cases of Bell"s palsy in children that were managed with antiviral agents. Both patients experienced complete recovery within 28 days; after 1 year follow-up, no recurrence was observed and both patients have normal facial movement. Differential diagnosis is essential to guide the treatment plan in Bell"s palsy. Special attention should be given to children with respect to prescription of medications that can cause important side effects.

Topics: Acyclovir; Antiviral Agents; Bell Palsy; Child; Diagnosis, Differential; Dry Eye Syndromes; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Ophthalmic Solutions; Virus Activation

Topics: Acyclovir; Antiviral Agents; Herpes Simplex; Herpesvirus 2, Human; Humans; Male; Meningitis, Aseptic; Meningitis, Viral; Middle Aged