acyclovir and Developmental-Disabilities

We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye.

Topics: Acyclovir; Adult; Antibodies, Viral; Antiviral Agents; Child; Developmental Disabilities; DNA, Viral; Drug Combinations; Encephalitis, Herpes Simplex; Eye Infections, Viral; Glucocorticoids; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Simplexvirus; Virus Activation; Vitreous Body

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

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

Infants with neonatal herpes, classified as central nervous system or disseminated disease, have a high incidence of moderate and severe neurologic deficits despite standard acute therapy.. Following completion of parenteral therapy, infants with central nervous system and/or disseminated disease received 2 years of continuous oral acyclovir therapy. Target minimum peak serum acyclovir concentrations were >2 microg/ml for the first three patients, and >3 microg/ml for the subsequent 13 patients. Safety assessments were made every 3 months. We evaluated neurodevelopmental outcomes with Bayley Scales of Infant Development.. A total of 16 consecutive herpes simplex virus-infected infants born during 1990 to 2003 received the treatment plan; 13/16 infants had central nervous system disease; 3 had disseminated disease without central nervous system involvement. A total of 69% (11/16) had Bayley scores in the normal range for mental development and 79% (11/14) had motor scores in the normal range. At the final assessment, five children had developmental delays. One child had severe mental delay with normal motor development. Four children had mild mental delays, with severe motor delays in three. All children were independently mobile, without seizure disorder, had normal vision, and had speech development. During the 2-year course of treatment, five children had brief recurrences of dermal lesions, and none had evidence of neurologic deterioration. There were no serious or sustained adverse drug reactions.. This pilot study reports improved outcomes in a small cohort of infants with a prolonged course of oral acyclovir. A minority of these children exhibited mild or significant developmental delays. Further investigation of this approach to treatment is warranted.

Topics: Acyclovir; Administration, Oral; Brain; Brain Diseases; Child Development; Child, Preschool; Developmental Disabilities; Herpes Simplex; Humans; Infant; Infant, Newborn; Pilot Projects; Treatment Outcome