New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine.

Abstract

BACKGROUND:

In Bihar, India, home to nearly one-half of the world's burden of visceral leishmaniasis, drug resistance has ended the usefulness of pentavalent antimony, which is the traditional first-line treatment. Although monotherapy with other agents is available, the use of 2 drugs with different modes of action might increase efficacy, shorten treatment duration, enhance compliance, and/or reduce the risk of parasite resistance. To test the feasibility of a new approach to combination therapy in visceral leishmaniasis (also known a kala-azar), we treated Indian patients with a single infusion of liposomal amphotericin B (L-AmB), followed 1 day later by short-course oral miltefosine.

METHODS:

We used a randomized, noncomparative, group-sequential, triangular design and assigned 181 subjects to treatment with 5 mg/kg of L-AmB alone (group A; 45 subjects), 5 mg/kg of L-AmB followed by miltefosine for 10 days (group B; 46 subjects) or 14 days (group C; 45 subjects), or 3.75 mg/kg of L-AmB followed by miltefosine for 14 days (group D; 45 subjects). When it became apparent that all regimens were effective, 45 additional, nonrandomized patients were assigned to receive 5 mg/kg of L-AmB followed by miltefosine for 7 days (group E).

RESULTS:

Each regimen was satisfactorily tolerated, and all 226 subjects showed initial apparent cure responses. Nine months after treatment, final cure rates were similar: group A, 91% (95% confidence interval [CI], 78%-97%]; group B, 98% (95% CI, 87%-100%); group C, 96% (95% CI, 84%-99%]; group D, 96% (95% CI, 84%-99%); and group E, 98% (95% CI, 87%-100%).

CONCLUSIONS:

These results suggest that treatment with single-dose L-AmB followed by 7-14 days of miltefosine is active against Indian kala-azar. This short-course, sequential regimen warrants additional testing in India and in those regions of endemicity where visceral leishmaniasis may be more difficult to treat.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT00370825 .

• Authors: Shyam Sundar, M Rai, J Chakravarty, D Agarwal, N Agrawal, Michel Vaillant, Piero Olliaro, Henry W Murray
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 47 Issue 8 Pg. 1000-6 (Oct 15 2008) ISSN: 1537-6591 [Electronic] United States
• PMID: 18781879 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• liposomal amphotericin B
• Phosphorylcholine
• miltefosine
• Amphotericin B

Topics

• Adult
• Amphotericin B (administration & dosage, adverse effects, therapeutic use)
• Drug Therapy, Combination
• Female
• Humans
• India
• Leishmaniasis, Visceral (drug therapy)
• Male
• Phosphorylcholine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Treatment Outcome