amphotericin-b and Immunologic-Deficiency-Syndromes

Defective cell-mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM.. Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200 mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4-6 weeks to prevent immune reconstitution inflammatory syndrome, common in CM. CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.

Topics: Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Cryptococcus; Drug Therapy, Combination; Fluconazole; Flucytosine; HIV Infections; Humans; Immunologic Deficiency Syndromes; Intracranial Hypertension; Meningitis, Cryptococcal; Risk Factors

Three cases of central nervous system (CNS) aspergillosis in immunocompromised patients are reported. All three had neurological symptoms with normal cerebrospinal fluid (CSF). The CT scan showed poorly defined low density lesions which were not enhanced by contrast medium. They also had pulmonary signs and fever despite antibiotic treatment. Aspergillus fumigatus was isolated from bronchoalveolar lavage fluid. Antifungal therapy was started promptly, associating amphotericin B, itraconazole and flucytosine. Unfortunately, they died within 2 days to 2 weeks after admission in the intensive care unit. Postmortem examinations revealed disseminated aspergillosis with colonization of brain, lung, heart and kidney. The CT scan signs were quite different from those seen with the more usual bacterial ring lesions. In immunocompromised patients, the agents responsible for producing these findings are Aspergillus, Nocardia, Cryptococcus, Toxoplasma and Mycobacterium tuberculosis. Signs involving organs other than the CNS, and an examination of the CSF, should provide elements for establishing a differential diagnosis. Early antifungal treatment is the only chance of survival. Recrudescent fever and pulmonary signs occurring in neutropenic patients after antibacterial antibiotic treatment has been started are sufficient criteria for empirically starting amphotericin B administration unless clinical judgement dictates otherwise.

Topics: Adult; Amphotericin B; Aspergillosis; Brain Diseases; Bronchoalveolar Lavage Fluid; Female; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Prognosis; Tomography, X-Ray Computed

Topics: Amphotericin B; Cryptococcosis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Opportunistic Infections

The authors report a case of mycotic osteitis of the upper maxillary bone due to Candida Albicans occurring in a 56 year old female patient under treatment for chronic myeloid leukemia. The etiologically difficult diagnosis could only be confirmed after deep surgical biopsy with mycological study of a fragment. A review of the literature confirmed the rarity of upper maxillary involvement by Candida Albicans. Particularly when there is isolated involvement and no evidence of a distant primary focus. The differential diagnosis essentially includes centro-facial malignant granuloma.

Topics: Amphotericin B; Candidiasis; Diagnosis, Differential; Facial Bones; Female; Flucytosine; Granuloma, Lethal Midline; Humans; Immunologic Deficiency Syndromes; Middle Aged; Osteitis

Topics: Amphotericin B; Antifungal Agents; Cross Infection; Fungi; Humans; Immunologic Deficiency Syndromes; Mycoses; Risk Factors; Virulence

We reviewed the published reports of skeletal cryptococcosis and added three cases to the fifty-six in the literature. Eight of the patients in the reported cases probably did not have primary skeletal cryptococcosis. The potential toxicity of antifungal drugs in current use and the apparent effectiveness of surgical treatment for patients who only have a single focus of infection in bone, without involvement of other tissues, should be noted. The association of cryptococcosis with other diseases and the difficulty in differentiating purely skeletal involvement from more extensive disease are emphasized.

Topics: Adolescent; Adult; Aged; Amphotericin B; Bone Diseases; Cryptococcosis; Diagnosis, Differential; Female; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Sarcoidosis

Topics: Amphotericin B; Candidiasis, Cutaneous; Chronic Disease; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunization, Passive; Immunologic Deficiency Syndromes; Sarcoidosis; T-Lymphocytes; Transfer Factor; Wiskott-Aldrich Syndrome

Topics: Amphotericin B; Anti-Bacterial Agents; Antibody Formation; Bacitracin; Cephalosporins; Child; Humans; Immunity, Cellular; Immunoglobulins; Immunologic Deficiency Syndromes; Nystatin; Penicillins; Polymyxins; Structure-Activity Relationship

Topics: Amphotericin B; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Burns; Candida albicans; Candidiasis; Catheterization; Central Nervous System Diseases; Diabetes Complications; Diagnosis, Differential; Fluorescent Antibody Technique; Fluorouracil; Hemagglutination Inhibition Tests; Humans; Hydrogen-Ion Concentration; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lung Diseases, Fungal; Nystatin; Pneumonia, Pneumocystis; Pyelonephritis; Respiratory Hypersensitivity; Sepsis; Serologic Tests

Topics: Amphotericin B; Candida; Candidiasis; Candidiasis, Cutaneous; Candidiasis, Oral; Candidiasis, Vulvovaginal; Cheilitis; Female; Folliculitis; Gastrointestinal Diseases; Humans; Immunologic Deficiency Syndromes; Intertrigo; Leukoplakia, Oral; Male; Nystatin; Paronychia

Topics: Aged; Amphotericin B; Antifungal Agents; Benzene Derivatives; Candidiasis, Cutaneous; Chronic Disease; Cytosine; Fluorides; Histocompatibility Antigens; Humans; Imidazoles; Immunoglobulin A; Immunologic Deficiency Syndromes; Injections, Intravenous; Iron; Leukocytes; Male

The most common infection in patients positive for anti-interferon-gamma autoantibodies (anti-IFN-γ AAbs) is disseminated nontuberculous mycobacterial (dNTM) infection. Here, we report a rare case of triple infection caused by Cryptococcus, varicella-zoster virus (VZV), and nontuberculous mycobacterium in a patient with anti-IFN-γ AAbs.. A 53-year-old Thai man presented with a progressively enlarging right cervical mass with low-grade fever and significant weight loss for 4 months. He also developed a lesion at his left index finger. A biopsy of that lesion showed granulomatous inflammation with yeast-like organisms morphologically consistent with cryptococcosis. Serum cryptococcal antigen was positive. Histopathology of a right cervical lymph node revealed chronic granulomatous lymphadenitis, and the lymph node culture grew Mycobacterium abscessus. One month later, he complained of vision loss in his left eye and subsequently developed a group of painful vesicles at the right popliteal area of S1 dermatome. Lumbar puncture was performed and his cerebrospinal fluid was positive for VZV DNA. His blood test for anti-HIV antibody was negative. Anti-IFN-γ AAbs was positive, but test for anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF AAbs) was negative. He was treated with amphotericin B plus fluconazole for cryptococcosis; a combination of amikacin, imipenem, azithromycin, and levofloxacin for dNTM infection; and, intravenous acyclovir for disseminated VZV infection. After treatment, our patient's fever and cervical lymphadenopathy were subsided, and his vision and visual acuity were both improved.. This is the first case of triple infection with cryptococcosis, VZV, and dNTM in a patient who tested positive for anti-IFN-γ AAbs and negative for anti-GM-CSF AAbs. This case will increase awareness and heighten suspicion of these infections in patients with the described presentations and clinical characteristics, and this will accelerate diagnosis and treatment.

Topics: Acyclovir; Amphotericin B; Autoantibodies; Coinfection; Cryptococcosis; Fluconazole; Herpesvirus 3, Human; Humans; Immunologic Deficiency Syndromes; Interferon-gamma; Lymphadenopathy; Male; Middle Aged; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Varicella Zoster Virus Infection

Visceral leishmaniasis (VL) is becoming endemic in São Paulo state, in the southeastern region of Brazil. Unusual manifestations with non-specific signs and symptoms may make diagnosis difficult and delay treatment, increasing the risk of severity and death, particularly in new endemic areas. There are few studies on patients with these characteristics in Brazil. We describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state.. From 2009 to 2014, five clinical cases involving children treated in the Regional Hospital of Presidente Prudente (RH) were selected. Two patients had multiple relapses requiring liposomal amphotericin B; one patient had VL-cytomegalovirus-dengue co-infection and liver injury; one patient was diagnosed with X-linked agammaglobulinemia, a primary immunodeficiency; and one patient was diagnosed with VL-human immunodeficiency virus/acquired immunodeficiency syndrome (VL-HIV/AIDS) co-infection. Primary or secondary immunodeficiencies were found in four children, and associated viral infections were found in three children. Three patients were referred from other hospitals to RH. With regard to the geographic spread of VL, more cases were found in the northern area, in the epicenter of the infection where the first cases were registered, flowing south; a spatial-temporal occurrence was found.. Primary and secondary immunodeficiencies and viral co-infectious should be considered among unusual manifestations of VL, especially in those with multiple relapses. Spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.

Topics: Acquired Immunodeficiency Syndrome; Agammaglobulinemia; Amphotericin B; Animals; Antiprotozoal Agents; Brazil; Child; Child, Preschool; Coinfection; Cytomegalovirus Infections; Dogs; Female; Genetic Diseases, X-Linked; Humans; Immunologic Deficiency Syndromes; Infant; Leishmaniasis, Visceral; Male

We present a case of a 2 year old apparently healthy child who presented with fever and mass on the mitral valve. Excision histopathology of the mass revealed mucormycosis. After 4 months, she had CNS embolisation with recurrence of cardiac lesion when investigations revealed associated T-cell immunodeficiency.

Topics: Amphotericin B; Antifungal Agents; Female; Fluconazole; Humans; Immunologic Deficiency Syndromes; Infant; Mitral Valve; Mitral Valve Insufficiency; Mucormycosis; T-Lymphocytes; Ultrasonography

The use of conventional amphotericin B is limited by toxicity, side-effects, drug interactions and the need for large infusion volumes, especially for infants. Use of liposomal amphotericin B (AmBisome) in 15 paediatric BMT patients with primary immunodeficiency (PID) was therefore studied. Adverse clinical reactions to AmBisome and biochemical profiles were monitored daily for 2 weeks before, during and after each treatment episode. Fungal cultures were obtained weekly and when patients were pyrexial. There were 18 treatment episodes. Mean daily dose was 5 mg/kg (2-6 mg/kg). Mean duration of treatment was 25 days (5-90 days). Clinical reactions to AmBisome were observed in one infant who had a pyrexia of 38 degrees C. One of the 15 infants had a significant increase in creatinine level while on concomitant nephrotoxic therapy. Four developed mild hypokalaemia on AmBisome which resolved with increased potassium supplementation. AmBisome was well tolerated and without significant renal or hepatic toxicity in severely ill immunodeficient infants receiving multiple nephrotoxic and hepatotoxic drugs such as cyclosporin, vancomycin and foscarnet.

Topics: Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Child, Preschool; Creatinine; Drug Interactions; Drug Tolerance; Female; Humans; Hypokalemia; Immunologic Deficiency Syndromes; Infant; Kidney; Liposomes; Liver; Male; Potassium, Dietary; Retrospective Studies; Safety; Severe Combined Immunodeficiency

We describe the case reports of two patients with immunodeficiency secondary to paracoccidioidomycosis (PCM) and opportunistic Cryptococcus neoformans infections. Secondary immunodeficiency likely occurred as a consequence of the intestinal loss of proteins and lymphocytes associated with malabsorption syndrome due to obstructed lymphatic drainage. Both patients had had severe abdominal involvement during the acute PCM disease. Immunological evaluation showed cellular and humoral immunity impairment. Cryptococcosis manifested as relatively well circumscribed lesions: osteolytic lesions of the skull in one patient, and pulmonary nodules in the other. The latter was treated surgically and with amphotericin B, whereas the other was treated with the combination amphotericin-B and flucytosine. Both patients had a good response to treatment with complete regression of the lesions. They have now 2 and 4 years of follow-up with maintenance therapy and no indication of reactivation of the infection. PCM also did not reactivate. The clinical and immunological characteristics of these patients are discussed and compared to the opportunistic C. neoformans infections of AIDS and transplant patients.

Topics: Adult; Amphotericin B; Antifungal Agents; Cryptococcosis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Opportunistic Infections; Paracoccidioidomycosis

Case report on a lethal meningo-encephalitis due to Cryptococcus neoformans in a 14-year-old girl without serious immunodeficiency inclusive HIV-infection. The detection of high quantities of cells of Cryptococcus neoformans (about 10,000/ml) and high levels of Cryptococcus antigen (up to 1:2048) in the cerebrospinal fluid are remarkable. The patient was treated with a triple combination of amphotericin B, flucytosine and fluconazole. After 18 days the cerebrospinal fluid was sterile. Nevertheless considerable lesions of the brain arised. The patient died from the Cryptococcus infection on day 74 of the antimycotic therapy. Cryptococcosis should be included into the differential diagnosis of the chronic lymphocytic pleocytosis of the cerebrospinal fluid connected with symptoms of intracranial pressure and ocular symptoms.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Antigens, Fungal; Cryptococcosis; Cryptococcus neoformans; Diagnosis, Differential; Drug Therapy, Combination; Encephalitis; Fatal Outcome; Female; Fluconazole; Flucytosine; HIV Seronegativity; Humans; Immunologic Deficiency Syndromes

We describe an unusual example of cellular immunodeficiency associated with interleukin-2 deficiency in an otherwise healthy 15-year-old boy who had isolated cryptococcal osteomyelitis of the scapula at 10 years of age. His previous medical history was remarkable only for prolonged, severe varicella infection at 6 years of age. He had persistent moderate lymphopenia, anergy, and absent lymphocyte blastogenic responses to mitogens, antigens, or monoclonal T cell antibodies. Subnormal blastogenic responses were seen after exposure to high concentrations of phorbol esters. Immunoglobulin levels and specific antibodies were normal. The patient has been in good health since treatment of his osteomyelitis. However, his lymphocyte blastogenic responses to mitogens have remained absent during 4 years of observation; investigation of the cause revealed a specific interleukin-2 deficiency resulting from defective generation of interleukin-2 messenger ribonucleic acid. Secretion of interleukin-1 by monocytes was normal, suggesting that the abnormal blastogenic response and interleukin-2 production were due to a problem intrinsic to T lymphocytes. The generation of messenger ribonucleic acid for interleukin-4 was not affected. Interferon-gamma was produced at subnormal levels. The addition of recombinant interleukin-2 restored lymphocyte blastogenic responses and increased the expression of interleukin-2 receptors. The clinical findings and immunologic abnormalities present in this patient differ from other primary and secondary immunodeficiencies associated with interleukin-2 deficiency. Thus our observations in this patient extend the spectrum of immunodeficiencies associated with abnormalities in the production of this important cytokine.

Topics: Adolescent; Amphotericin B; Cryptococcosis; Drug Therapy, Combination; Flucytosine; HLA Antigens; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunologic Deficiency Syndromes; Interleukin-2; Lymphocyte Activation; Lymphocyte Subsets; Male; Osteomyelitis; Scapula

Amphotericin B (AMB) is a mainstay in the treatment of serious systemic fungal infections, such as those occurring prevalently in immuno-compromised patients treated with immunosuppressive agents or affected by Acquired Immunodeficiency Syndrome (AIDS). However AMB is an extremely toxic agent whose therapeutical utilization is often accompanied by acute side effects and chronic impairment of renal function. It is here reported that the preactivation of polymorphonucleated cells (PMN) in vivo, by a new immunomodulatory agent (PCF 39:N alpha-5[1,6,dihydro-(6-oxo-9 purinyl) pentoxycarbonyl]-L-Arginine) allows marked reduction of the AMB doses with full retention of therapeutic efficacy. This was observed in an experimental fungal infection induced in mice by intravenous inoculation of Candida albicans.

Topics: Adjuvants, Immunologic; Amphotericin B; Animals; Arginine; Candidiasis; Cyclophosphamide; Drug Synergism; Drug Therapy, Combination; Female; Hypoxanthines; Immunocompromised Host; Immunologic Deficiency Syndromes; Mice; Mice, Inbred BALB C; Neutrophils; Phagocytosis

Topics: Amphotericin B; Aspergillosis; Humans; Immunologic Deficiency Syndromes; Lung Diseases, Fungal; Pneumonia

Hepatic candidiasis has been increasingly recognized as a variant of disseminated candidiasis in immunocompromised patients. Five leukemic patients with antemortem diagnosis of hepatic candidiasis are described, and 32 additional cases reported in the literature are reviewed. Cultures of the liver and/or spleen and blood cultures usually give negative results; histopathologic demonstration of Candida organisms in tissue specimens is necessary for a definitive diagnosis. Response to conventional therapy with amphotericin B is poor, and 34.4 percent of the patients died with evidence of active fungal disease. Liposome-encapsulated amphotericin B, which has been successfully used in a limited number of patients with invasive fungal disease, may be an effective and relatively nontoxic drug.

Topics: Adult; Amphotericin B; Biopsy; Candida; Candidiasis; Drug Therapy, Combination; Female; Flucytosine; Humans; Immunologic Deficiency Syndromes; Ketoconazole; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Liver; Liver Diseases; Male

Candida seldom has been reported to be a cause of epiglottitis. The clinical manifestations and management of three patients with Candida epiglottitis complicating their neoplastic disease are described. All patients were granulocytopenic. Candida epiglottitis occurred either as a localized infection, as a source of Candida bronchopneumonia, or as a manifestation of disseminated infection. Candida epiglottitis may be under-diagnosed and should be considered, especially in immunocompromised patients with symptoms of refractory pharyngitis. Treatment of Candida epiglottitis with intravenous amphotericin B is warranted in patients with sustained granulocytopenia. Prompt endotracheal intubation is indicated if the airway patency cannot be maintained.

Topics: Adult; Agranulocytosis; Amphotericin B; Candidiasis; Child, Preschool; Epiglottitis; Female; Humans; Immunologic Deficiency Syndromes; Intubation, Intratracheal; Laryngitis; Laryngoscopy; Male; Middle Aged

Bare lymphocyte syndrome (BLS) is a rare, severe combined immunodeficiency characterized by lack of expression of HLA A, B and C antigens and the absence of B2 microglobulins. Patients with BLS exhibit functional deficiency of both T and B cells resulting in bacterial as well as viral and fungal infection. Ophthalmic findings in this group of disorders have not been reported. We present a case of candida retinitis in a terminally ill 5-year-old girl with BLS.

Topics: Amphotericin B; Candidiasis; Child, Preschool; Female; Humans; Immunologic Deficiency Syndromes; Retinitis

Topics: Amphotericin B; Candidiasis; Flucytosine; Humans; Immunologic Deficiency Syndromes; Infant; Male; Meningitis

Rhinocerebral mucormycosis is, with few exceptions, only reported in patients with severe metabolic or immunologic imbalances. Factors which may predispose to the development of mucormycosis are reviewed. These factors include ketoacidosis and immunologic deficiency states due either to the primary disease or to the treatment for other diseases. An appreciation for these predisposing factors is very important in order that aggressive diagnosis and therapy be undertaken without delay.

Topics: Acidosis; Adrenal Cortex Hormones; Aged; Amphotericin B; Anemia; Brain Diseases; Diabetes Complications; Humans; Immunologic Deficiency Syndromes; Keto Acids; Leukemia; Male; Mucormycosis; Neutropenia; Nose Diseases; Turbinates; Uremia

Topics: Adult; Amphotericin B; Fever of Unknown Origin; Histoplasmosis; Humans; Immunologic Deficiency Syndromes; Male

The authors present a review of the epidemiology, pathology, diagnosis and treatment of candidiasis in the child. Their studies on the favoring factors in cutaneous forms as well as their experiences in pulmonary forms are emphasized.

Topics: Amphotericin B; Candidiasis; Candidiasis, Cutaneous; Candidiasis, Oral; Candidiasis, Vulvovaginal; Child; Clotrimazole; Complement C5; Female; Flucytosine; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Miconazole; Nystatin

During the period 1969 to 1974, 41 patients having cultures positive for aspergillus were seen on the thoracic surgical services of the University of Maryland and Mt. Wilson State Hospitals. Intracavitary mycetoma was present in 36 patients. In 32 the underlying disease was chronic cavitary tuberculosis, 5 had decreased immunity due to other diseases, and in 3 no underlying disease was noted. One final patient developed a mycetoma following repair of tetralogy of Fallot. Hemoptysis, the predominant symptom, occurred in 23 patients, all of whom were from the group with intracavitary mycetoma. Hemoptysis was life-threatening in 8 patients, severe but not life-threatening in 12, and minimal in 3. Fifteen patients underwent pulmonary resection with 2 deaths. Both patients who died had undergone emergency resection for life-threatening hemoptysis; the fungus ball had developed following a previous resection for tuberculosis, and both had poor pulmonary reserve. Of 10 patients with hemoptysis who were not treated surgically, chiefly because they were poor operative risks, 4 died. This study suggests that pulmonary aspergillosis, particularly of the intracavitary type, is a potentially life-threatening disease. Because of the suddenness with which massive hemoptysis may occur, pulmonary resection is recommended for all patients with intracavitary mycetoma who do not constitute prohibitive operative risks.

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Female; Hemoptysis; Humans; Immunologic Deficiency Syndromes; Lung Diseases, Fungal; Male; Middle Aged; Mycetoma; Pneumonectomy; Postoperative Complications; Radiography; Tuberculosis, Pulmonary

Topics: Amphotericin B; Antifungal Agents; Child; Clotrimazole; Drug Resistance; Flucytosine; Griseofulvin; Humans; Immunologic Deficiency Syndromes; Miconazole; Mycoses; Nystatin

Since secondary deep mycoses are frequently seen in internal medicine nowadays, increasing interest has been focused on antimycotic therapy. This report deals with the limited available range of antimycotic substances which can be administered systemically. Since severe adverse effects are often observed with Amphotericin-B, the most effective antifungal agent, the advent of three new systemic antifungal drugs (Clotrimazole, Miconazole, 5-Fluorocytosine) has proven to be a real advance in our therapeutic approach to deep mycoses. To avoid unwanted side-effects, combined therapy with low doses of Amphotericin-B and another antimycotic agent promises to become increasingly important.

Topics: Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Burns; Cardiac Surgical Procedures; Catheterization; Clotrimazole; Flucytosine; Humans; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Miconazole; Mycoses

Two patients with chronic mucocutaneous candidiasis and a defect in cellular immunity received a single injection of dialysable transfer factor from Candida-positive donors in an effort to reconstitute immunologic function. The transfer of cellular hypersensitivity was successful in one of the two patients and was monitored by skin tests and MIF production; however, the effect was temporary and did not change the clinical course of the patient's infection. The other patient did not respond eitherimmunologically or clinically to transfer factor at this time, although she did respond subsequently to repeated doses of transfer factor and amphotericin B therapy (Pabst and Swanson: Brit. med. J. 2:442, 1972). In another instance transfer factor from tuberculin-positive donors was used successfully to eradicate an infection in a patient with progressive primary tuberculosis and an acquired defect in cellular immunity. The patient had not responded clinically or bacteriologically after 7 1/2 months of antituberculous therapy, although the organism was shown to be sensitive in vitro to the drugs she was receiving. She received 6 doses of dialysable transfer factor over a 3-month period and during this time she responded clinically, bacteriologically and roentgenographically.

Topics: Adult; Amphotericin B; Antigens, Fungal; Candida albicans; Candidiasis, Cutaneous; Cell Migration Inhibition; Cells, Cultured; Child; Chronic Disease; Female; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Immunologic Deficiency Syndromes; Immunotherapy; Lymphocyte Activation; Lymphocytes; Macrophage Migration-Inhibitory Factors; Male; Phagocytosis; Skin Tests; Streptodornase and Streptokinase; Transfer Factor; Tuberculin Test; Tuberculosis, Pulmonary

Use of transfer factor in the treatment of chronic mucocutaneous candidiasis is discussed. The clinical experience in treating 2 patients with different clinical expressions of the syndrome and their different responses to treatment with repeated injections of transfer factor given in conjunction with amphotericin-B are reported. Results indicate that this form of therapy is a safe and effective way of restoring cell-mediated immunity to Candida and successfully treating some patients with chronic mucocutaneous candidiasis.

Topics: Amphotericin B; Candida albicans; Candidiasis, Cutaneous; Candidiasis, Oral; Child; Female; Humans; Hypoparathyroidism; Immunity, Cellular; Immunologic Deficiency Syndromes; Lymphocyte Activation; Paronychia; Skin Tests; Thymidine; Transfer Factor; Tritium; Vitiligo

Transfer factor is a dialyzable extract of sensitized leukocytes, which transfers reactivity from skin test-positive donors to skin test-negative recipients. Transfer factor supplied by our laboratory has been used therapeutically to induce cellular immunity in 78 patients around the world. Many patients received multiple doses of transfer factor ranging from 1 unit given every 6 months for 3 years to 1 unit every week for 6 months to as much as 8 units per week for a brief period. A total of 299 units of transfer factor have been given. Diseases in which transfer factor appeared to cause improvement include the Wiskott-Aldrich syndrome, severe combined immunodeficiency disease, mucocutaneous candidiasis, chronic active hepatitis, coccidioidmycosis, dysgammaglobulinemia, Behcet disease, aphthous stomatitis, linear morphea, familial keratoacanthoma and malignancy.

Topics: Amphotericin B; Behcet Syndrome; Binding Sites, Antibody; Candidiasis, Cutaneous; Coccidioidomycosis; Dysgammaglobulinemia; Hepatitis; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Immunotherapy; Keratoacanthoma; Macrophage Migration-Inhibitory Factors; Monocytes; Neoplasms; Scleroderma, Localized; Stomatitis, Aphthous; Transfer Factor; Wiskott-Aldrich Syndrome

Topics: Amphotericin B; Antibodies, Viral; Antibody Formation; Candidiasis, Cutaneous; Child; Clotrimazole; Fetus; Herpes Zoster; Histocompatibility; Humans; Hypersensitivity, Delayed; Immune Adherence Reaction; Immunity, Cellular; Immunologic Deficiency Syndromes; Lymphocyte Activation; Male; Mumps virus; Nitrobenzenes; Skin Tests; Thymidine; Thymus Gland; Tritium

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis, Cutaneous; Candidiasis, Oral; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Female; Flucytosine; Fluorouracil; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Immunotherapy; Lymphocyte Activation; Microbial Sensitivity Tests; Nystatin; Skin Diseases; Staphylococcal Infections

Topics: Adolescent; Amphotericin B; Antibody Formation; Candidiasis, Cutaneous; Child; Child, Preschool; Chronic Disease; Female; Follow-Up Studies; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Infant; Infections; Lymphokines; Male; Mucous Membrane; Nails; Skin Diseases; Transfer Factor

Topics: Amphotericin B; Biopsy; Candida albicans; Candidiasis, Oral; Cheilitis; Diabetes Complications; Endocrine System Diseases; Fluorescent Antibody Technique; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Leukoplakia, Oral; Metabolic Diseases; Nutrition Disorders; Nystatin; Sjogren's Syndrome; Stomatitis, Denture

Topics: Amphotericin B; Antibody Formation; Antigens, Fungal; Autoimmune Diseases; Candidiasis, Cutaneous; Child; Diphtheria Toxoid; Female; Humans; Hypersensitivity, Delayed; Immunoglobulin A; Immunologic Deficiency Syndromes; Lymphocyte Activation; Lymphopenia; Macrophage Migration-Inhibitory Factors; Muscle, Smooth; Nitrobenzenes; Pertussis Vaccine; Skin Tests; Tetanus Antitoxin; Tetanus Toxoid; Thymidine; Typhoid-Paratyphoid Vaccines

Topics: Amphotericin B; Anemia, Hypochromic; Candidiasis, Cutaneous; Candidiasis, Oral; Chronic Disease; Genes, Recessive; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes

Dialyzable transfer factor, obtained from frozen-thawed peripheral blood leukocytes from a single donor, was given to five anergic patients with chronic mucocutaneous candidiasis. Studies of immunological responses including delayed cutaneous hypersensitivity, in vitro antigen-induced thymidine incorporation, and production of macrophage migration inhibition factor (MIF) were conducted both before and after injection of transfer factor. Before transfer factor, none of the patients had delayed skin responses to any of the natural antigens studied. Their lymphocytes did not produce MIF after exposure to antigens in vitro and only one patient showed increased thymidine incorporation when his lymphocytes were cultured with candida and streptokinase-streptodornase (SK-SD). After injection of transfer factor, four patients developed delayed skin responses to antigens to which the donor was sensitive; no recipient reacted to an antigen to which the donor was nonreactive. Lymphocytes from recipients produced MIF when cultured with antigens that evoked positive delayed skin tests. Only one patient developed antigen-induced lymphocyte transformation and this response occurred only intermittently. Attempts to sensitize three of the patients with the contact allergen, chlorodinitrobenzene, both before and after transfer factor, were unsuccessful. The fifth patient, a 9-yr old boy with an immunologic profile similar to the Nezelof syndrome, did not become skin test-reactive or develop positive responses to the in vitro tests. These findings suggest that transfer factor acts on the immunocompetent cells that respond to antigens with lymphokine production, but has little, if any, effect on cells that respond to antigens by blastogenesis. The failure to sensitize the subjects with chlorodinitrobenzene illustrates the specificity of the immunologic effects of transfer factor, and implies that it does not function through nonspecific, adjuvant-like mechanisms. Failure of transfer factor to produce positive skin tests or MIF production in a patient with Nezelof's syndrome may be evidence that lymphokine-producing cells are thymus derived.

Topics: Adult; Allergens; Amphotericin B; Antigens; Candidiasis, Cutaneous; Cell Migration Inhibition; Female; Humans; Hypersensitivity; Hypersensitivity, Delayed; Immunity, Cellular; Immunity, Maternally-Acquired; Immunologic Deficiency Syndromes; Leukocytes; Lymphocyte Activation; Lymphocytes; Macrophages; Male; Skin; Skin Tests; Thymidine

Topics: Amphotericin B; Candidiasis, Cutaneous; Female; Granuloma; Humans; Immunologic Deficiency Syndromes; Infant, Newborn

Topics: Adrenal Glands; Agammaglobulinemia; Amphotericin B; Brain; Carcinoma; Carcinoma, Hepatocellular; Cryptococcosis; Cryptococcus; Diabetes Complications; Granuloma; Humans; Immunologic Deficiency Syndromes; Kidney Neoplasms; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged