Epidemiological dynamics of antimonial resistance in Leishmania donovani: Genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal.


Laurent, T; Rijal, S; Yardley, V; Croft, S; De Doncker, S; Decuypere, S; Khanal, B; Singh, R; Schönian, G; Kuhls, K; Chappuis, F; Dujardin, JC; (2006) Epidemiological dynamics of antimonial resistance in Leishmania donovani: Genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal. Infection, genetics and evolution , 7 (2). pp. 206-12. ISSN 1567-1348 DOI: 10.1016/j.meegid.2006.08.005

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Abstract

Pentavalent antimonials (SbV) are the first line drug against leishmaniasis worldwide, but drug resistance is increasingly reported, particularly in the Indian sub-continent, where it represents a major threat for the control of anthroponotic visceral leishmaniasis (VL). In order to understand the epidemiological dynamics of antimonial resistance in anthroponotic VL, we analysed here the population structure of 24 Leishmania donovani stocks isolated from anthroponotic VL-patients from Eastern Nepal: 13 SbV-naturally resistant and 11 SbV-sensitive, as demonstrated by in vitro drug susceptibility assays. The parasites were genotyped by PCR-RFLP analysis of kDNA minicircles and by microsatellite analysis and the encountered polymorphism revealed a polyclonal structure among resistant isolates. Furthermore, analysis of paired samples obtained from the same patients before treatment and after failure revealed primary as well as acquired resistance. The hypothesis of independent events of drug resistance emergence is proposed and confronted to alternative explanations. Our results show the dynamics of drug resistance epidemiology and highlight the importance of surveillance networks.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Antimicrobial Resistance Centre (AMR)
Leishmaniasis Group
PubMed ID: 17010679
Web of Science ID: 244351400009
URI: http://researchonline.lshtm.ac.uk/id/eprint/10646

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