Efficacy and tolerabiliy of loposomal amphotericin B (Ambisome) in the treatment of visceral leishmaniasis in Brazil

Thirty-two patients were enrolled in an open-label, dose/schedule ranging clinical trial to evaluate the efficacy and tolerability of loposomal amphotericin B (Ambisome) in the treatment of visceral leishmaniasis. All the patients received a dose of 2mg/kg daily for the first 4 days, followed by a single repeat dose of 2mg/kg at day 10 in 4 patients (total dose 10mg/kg); repeat doses on days 5, 6, and 10 in 13 patients (total dose 14/kg); or daily doses were continued on days 5 through 10 in 15 patients (total dose 20mg/kg). Patients had a mean age of 9 years, ranging between 3 and 26 years. Their mean weight was 25.9kg, ranging between 9.5kg and 75kg. All patients had splenomegaly,31/32 hepatomegaly, and 20 patients tested had leishmania documented on splenic aspirate. Six of the 32 patients were treated after relapse following antimony therapy. The duration of illness prior to therapy was a mean of 2 months, ranging between 2 weeks and 23 months. During and after treatment, there were significant reductions in liver and spleen size, and significant increases in body weight, hemoglobin levels and white blood cell counts. All patients showed initial cure at the 1 mouth follow-up. Seven patients relapsed between 2 and 6 months after the start of treatment. There was no dose relationship to the occurrence of relapse. The relapse rate in children 5 years of age or less was 7/15 (47 percent). Associated causes of relapse were refractory disease (i.e., previous relapses) in 2, severe malnutrition in 1, and concurrent disease (meningococcal meningitis) in 1. In the other 2 cases, no associated event was observed except young age (ages 3 and 5 years). One relapsed patient was treated successfully with 14 days of lipid amphotericin B, and the others were cured by use of antimony for 20 to 30 days. There were no dose related adverse events. The most common event was fever which occurred in 13/32 patients (41 percent); 3/4 patients in the 10mg dose group, 7/13 in the 14mg dose group, and 3/15 in the 20mg dose group. Three patients had cardiac arrhythmia, one also with myocarditis diagnosed 2 weeks after therapy was discontinued. One patient developed hepatitis after dose 3 and the drug was discontinued. We concluded that liposomal amphotericin B is effective in a daily dose of 2mk/kg given for 5-10 doses as an initial cure, but that relapse occurs in young children, particularly those with documented treatment resistant disease or concurrent malnutrition...

Leprosy and AIDS: report of a fatal case and literature review

We report a severe fatal lepromatous leprosy case in an adult homosexual male 2 years after AIDS class IV was diagnosed. Multidrug therapy including thalidomide for erythema nodosum leprosum (ENL) was ineffective. The patient died with multiple large skin ulcerations due to multibacillary leprosy. Leprosy in AIDS patients may present as a severe uncontrolled disease, with extensive ENL unresponsive to therapy.

Imunidade humoral e celular em indivíduos curados de leishmaniose visceral / Humoral and cellular immunity in subjects cured of visceral leishmaniasis

Foi realizada avaliaçäo imunológica em 48 indivíduos com história pregressa de leishmaniose visceral (L.V.) e em seis pacientes durante a fase aguda da doença e após o tratamento. Títulos significativos de anticorpos determinados pela técnica de imunofluorescência e/ou ELISA foram observados em 32 (67%) dos 48 casos. A avaliaçäo da resposta imune humoral e celular nos seis pacientes durante a fase ativa da doença demonstrou títulos elevados de anticorpos (média 9536 + ou - 7169) e resposta linfoproliferativa ausente (323 + ou - 24). Após o tratamento (3 e 6 meses) os títulos de anticorpos só caíram em três dos seis pacientes, ao passo que linfócitos passaram a responder "in vitro" a antígenos de leishmânia (11909 + ou - 5637). Estes dados demonstram que os indivíduos que adquirem leishmaniose visceral näo säo geneticamente incapacitados de responder a antígeno de leishmânia e que a persistência de títulos elevados de anticorpos anos após o tratamento, sugere que o parasita permaneça no hospedeiro após a cura clínica da doença