Elsevier

The Lancet

Volume 352, Issue 9143, 5 December 1998, Pages 1821-1823
The Lancet

Early Report
Trial of oral miltefosine for visceral leishmaniasis

https://doi.org/10.1016/S0140-6736(98)04367-0Get rights and content
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Summary

Background

There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kalaazar.

Methods

Oral doses of miltefosine were given to six groups of five Indian men 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 afebrile 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 episodes of vomiting and diarrhoea, were common during weeks 1–2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7–10 days because of vomiting. One patient in group 6 developed renal 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 patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3–6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy 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 antimonyresistant infection.

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