Epidemiological dynamics of antimonial resistance in Leishmania donovani:: Genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal
Epidemiological dynamics of antimonial resistance in Leishmania donovani:: Genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal
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DOI：
10.1016/j.meegid.2006.08.005
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发表时间：
2007-03-01
影响因子：
3.2
通讯作者：
Dujardin, Jean-Claude
中科院分区：
文献类型：
--
作者：
Laurent, Thierry;Rijal, Suman;Dujardin, Jean-Claude
五价锑(SBV)是世界范围内治疗利什曼病的一线药物，但耐药性的报道越来越多，特别是在印度次大陆，在那里它对人类内脏利什曼病(VL)的控制构成了主要威胁。为了了解人源性VL对锑的耐药性的流行病学动态，我们分析了从尼泊尔东部人源性VL患者中分离的24个杜氏利什曼原虫的种群结构：13个SBV自然耐药，11个SBV敏感。通过kDNA小环的PCR-RFLP分析和微卫星分析对这些寄生虫进行了基因分型，发现抗性菌株之间存在多克隆结构。此外，对同一患者在治疗前和失败后获得的配对样本的分析显示出原始耐药和获得性耐药。耐药发生的独立事件假说被提出，并面临其他解释。我们的结果显示了耐药性流行病学的动态，并突出了监测网络的重要性。(C)2006爱思唯尔B.V.保留所有权利。
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. (c) 2006 Elsevier B.V. All rights reserved.