Epidemiological dynamics of antimonial resistance in Leishmania donovani: genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal.
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.
Laurent
Thierry
T
Department of Parasitology, Unit of Molecular Parasitology, Institute of Tropical Medicine, Antwerp B-2000, Belgium.
Rijal
Suman
S
Yardley
Vanessa
V
Croft
Simon
S
De Doncker
Simonne
S
Decuypere
Saskia
S
Khanal
Basudha
B
Singh
Rupa
R
Schönian
Gabriele
G
Kuhls
Katrin
K
Chappuis
François
F
Dujardin
Jean-Claude
JC
D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000469:parasitology; D018105:DNA, Kinetoplast / Q000235:genetics; D004351:Drug Resistance; D005838:Genotype; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology*; D009390:Nepal; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length
D000981:Antiprotozoal Agents; D018105:DNA, Kinetoplast; D000666:Amphotericin B