Trial of oral miltefosine for visceral leishmaniasis

Background There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs w orldwide. Miltefosine, an alkyl phospholipid developed as an oral antineopl astic agent, is active against visceral infection in animal models. We test ed safety, tolerance, and efficacy of miltefosine in kala-azar. Methods Oral doses of miltefosine were given to six groups of five Indian m en for 28 days: 50 mg every second day (group 1), 100 mg every second day ( group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6), Assessment for apparent cure-taken as an afebril e state with decreased spleen size and a splenic-aspirate parasite-density score of 0-was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse. Findings 21 of 30 patients were apparently cured on day 14. Transient episo des of vomiting and diarrhoea, were common during weeks 1-2 and were seen i n 22 patients. Four other patients in groups 5 and 6 had miltefosine withdr awn after 7-10 days because of vomiting. One patient in group 6 developed r enal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten pati ents in groups 1 and 2 had relapsed; however, 18 of 19 patients treated dai ly (groups 3-6) appeared to be cured. Among the 21 definitive cures were th e four patients treated for 10 days or less and 12 for whom previous therap y with pentavalent antimony had failed. Interpretation Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection.