Journal Article

New Treatment Approach in Indian Visceral Leishmaniasis: Single-Dose Liposomal Amphotericin B Followed by Short-Course Oral Miltefosine

Shyam Sundar, M. Rai, J. Chakravarty, D. Agarwal, N. Agrawal, Michel Vaillant, Piero Olliaro and Henry W. Murray

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 47, issue 8, pages 1000-1006
Published in print October 2008 | ISSN: 1058-4838
Published online October 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/591972
New Treatment Approach in Indian Visceral Leishmaniasis: Single-Dose Liposomal Amphotericin B Followed by Short-Course Oral Miltefosine

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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.

Journal Article.  3717 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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