Oral miltefosine for Indian visceral leishmaniasis

N Engl J Med. 2002 Nov 28;347(22):1739-46. doi: 10.1056/NEJMoa021556.

Abstract

Background: There are 500,000 cases per year of visceral leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian visceral leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B.

Methods: The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections).

Results: The groups were well matched in terms of age, weight, proportion with previous failure of treatment for leishmaniasis, parasitologic grade of splenic aspirate, and splenomegaly. At the end of treatment, splenic aspirates were obtained from 293 patients in the miltefosine group and 98 patients in the amphotericin B group. No parasites were identified, for an initial cure rate of 100 percent. By six months after the completion of treatment, 282 of the 299 patients in the miltefosine group (94 percent [95 percent confidence interval, 91 to 97]) and 96 of the 99 patients in the amphotericin B group (97 percent) had not had a relapse; these patients were classified as cured. Vomiting and diarrhea, generally lasting one to two days, occurred in 38 percent and 20 percent of the patients in the miltefosine group, respectively.

Conclusions: Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis. Miltefosine may be particularly advantageous because it can be administered orally. It may also be helpful in regions where parasites are resistant to current agents.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Amphotericin B / adverse effects
  • Amphotericin B / therapeutic use
  • Animals
  • Antiprotozoal Agents / adverse effects
  • Antiprotozoal Agents / therapeutic use*
  • Female
  • Humans
  • India
  • Infusions, Intravenous
  • Leishmania donovani / isolation & purification
  • Leishmaniasis, Visceral / drug therapy*
  • Male
  • Phosphorylcholine / adverse effects
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / therapeutic use*
  • Recurrence
  • Spleen / parasitology

Substances

  • Antiprotozoal Agents
  • Phosphorylcholine
  • miltefosine
  • Amphotericin B