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

• Published in: Clinical infectious diseases Vol. 47; no. 8; pp. 1000 - 1006
• Main Authors: Sundar, Shyam, Rai, M., Chakravarty, J., Agarwal, D., Agrawal, N., Vaillant, Michel, Olliaro, Piero, Murray, Henry W.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.10.2008; University of Chicago Press; Oxford University Press
• Subjects: Adult; Amphotericin B - administration & dosage; Amphotericin B - adverse effects; Amphotericin B - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antiparasitic agents; Articles and Commentaries; Biological and medical sciences; Dosage; Drug resistance; Drug therapy; Drug Therapy, Combination; Experimentation; Female; Human protozoal diseases; Humans; India; Infectious diseases; Intravenous injections; Leishmaniasis, Visceral - drug therapy; Leshmaniasis; Male; Medical cures; Medical research; Medical sciences; Parasites; Parasitic diseases; Pharmacology. Drug treatments; Phosphorylcholine - administration & dosage; Phosphorylcholine - adverse effects; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - therapeutic use; Protozoal diseases; Skin diseases; Sodium; Treatment Outcome; Tropical medicine; Visceral leishmaniasis; Asia; India; Bihar India; Antineoplastic agent; Protozoal disease; Single dose; Oral administration; Phospholipid; Kala azar; Leishmaniasis; Parasitosis; Infection; Antiprotozoal agent; Miltefosine; Antibiotic; Antifungal agent; Treatment; Amphotericin B; Polyenic compound; Lysophospholipid; Parasiticide; Indian
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1086/591972

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.