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New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine.
Clin Infect Dis. 2008 Oct 15; 47(8):1000-6.CI

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 .

Links

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Authors+Show Affiliations

Sundar S
Kala-Azar Medical Research Center, Department of Medicine, Banaras Hindu University, Institute of Medical Sciences, Varanasi, India. drshyamsundar@hotmail.com
Rai M
No affiliation info available
Chakravarty J
No affiliation info available
Agarwal D
No affiliation info available
Agrawal N
No affiliation info available
Vaillant M
No affiliation info available
Olliaro P
No affiliation info available
Murray HW
No affiliation info available

MeSH

AdultAmphotericin BDrug Therapy, CombinationFemaleHumansIndiaLeishmaniasis, VisceralMalePhosphorylcholineTreatment Outcome

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18781879

Clinical Trial Links

Clinical trial which this article describes

Citation

Sundar, Shyam, et al. "New Treatment Approach in Indian Visceral Leishmaniasis: Single-dose Liposomal Amphotericin B Followed By Short-course Oral Miltefosine." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 47, no. 8, 2008, pp. 1000-6.
Sundar S, Rai M, Chakravarty J, et al. New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine. Clin Infect Dis. 2008;47(8):1000-6.
Sundar, S., Rai, M., Chakravarty, J., Agarwal, D., Agrawal, N., Vaillant, M., Olliaro, P., & Murray, H. W. (2008). New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 47(8), 1000-6. https://doi.org/10.1086/591972
Sundar S, et al. New Treatment Approach in Indian Visceral Leishmaniasis: Single-dose Liposomal Amphotericin B Followed By Short-course Oral Miltefosine. Clin Infect Dis. 2008 Oct 15;47(8):1000-6. PubMed PMID: 18781879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New treatment approach in Indian visceral leishmaniasis: single-dose liposomal amphotericin B followed by short-course oral miltefosine. AU - Sundar,Shyam, AU - Rai,M, AU - Chakravarty,J, AU - Agarwal,D, AU - Agrawal,N, AU - Vaillant,Michel, AU - Olliaro,Piero, AU - Murray,Henry W, PY - 2008/9/11/pubmed PY - 2008/10/24/medline PY - 2008/9/11/entrez SP - 1000 EP - 6 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin Infect Dis VL - 47 IS - 8 N2 - 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 . SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/18781879/New_treatment_approach_in_Indian_visceral_leishmaniasis:_single_dose_liposomal_amphotericin_B_followed_by_short_course_oral_miltefosine_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1086/591972 DB - PRIME DP - Unbound Medicine ER -