Journal
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Volume 89, Issue 4, Pages 750-754Publisher
AMER SOC TROP MED & HYGIENE
DOI: 10.4269/ajtmh.13-0096
Keywords
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Funding
- Kaladrug-R [EC-FP7-222895]
- Directorate-General for Development Cooperation of the Belgian Government
- Sitaram Memorial Trust, Muzaffarpur
- Indian Council of Medical Research, New Delhi
- Paladin Labs
- Institute for One World Health
- GlaxoSmithK line
- Bharat Serum and Vaccine Ltd
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Promastigote miltefosine (MIL) susceptibility was performed on Leishmania donovani isolates from Indian patients with visceral leishmaniasis treated with MIL. Isolates that were obtained before the onset of MIL treatment, after completion of treatment (29th day), or at the time of treatment failure, were screened using in vitro promastigote assay. The MIL susceptibility of the pre-treatment isolates (N = 24, mean IC50 +/- SEM = 3.74 +/- 0.38 mu M) was significantly higher than that of the post-treatment group (N = 26, mean IC50 +/- SEM = 6.15 +/- 0.52 mu M; P = 0.0006) but was similar in the cured patients (N = 22, mean IC50 +/- SEM = 5.58 +/- 0.56 mu M) and those who failed treatment (N = 28, mean IC50 +/- SEM = 4.53 +/- 0.47 mu M). The pre/post-treatment results thus showed a 2-fold difference, whereas isolated from cured versus failed patients showed a similar susceptibility, suggesting that this higher tolerance is not responsible for MIL-treatment failure. Our work highlights the need for careful monitoring of MIL susceptibility for implementation in national VL elimination programs.
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