title: In vitro susceptibility of Leishmania donovani to miltefosine in Indian visceral leishmaniasis.
abstract: 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 μM) was significantly higher than that of the post-treatment group (N = 26, mean IC50 ± SEM = 6.15 ± 0.52 μM; P = 0.0006) but was similar in the cured patients (N = 22, mean IC50 ± SEM = 5.58 ± 0.56 μM) and those who failed treatment (N = 28, mean IC50 ± SEM = 4.53 ± 0.47 μM). 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.
authors: Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP, India; Unit of Epidemiology and Control of Tropical Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium; National Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India; Unit of Molecular Parasitology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, Antwerp University, Antwerp, Belgium.
authors: Vijay Kumar
authors: VK
authors: Prajapati
authors: Smriti
authors: S
authors: Sharma
authors: Madhukar
authors: M
authors: Rai
authors: Bart
authors: B
authors: Ostyn
authors: Poonam
authors: P
authors: Salotra
authors: Manu
authors: M
authors: Vanaerschot
authors: Jean-Claude
authors: JC
authors: Dujardin
authors: Shyam
authors: S
authors: Sundar
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D006801:Humans; D007194:India / Q000453:epidemiology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000453:epidemiology* / Q000469:parasitology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine
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