Genomic Analyses of Plasmodium vivax Responses to Antimalarial Drugs in Cambodia

描述(由申请人提供)： 柬埔寨间日疟原虫出现氯喹抗药性，威胁到该地区的整个疟疾控制战略。在与柬埔寨巴斯德研究所的合作下，我们 将从280名感染间日疟原虫的人身上采集血液样本，并使用下一代测序来调查整个间日疟原虫基因组的遗传多样性模式。首先，我们将进行种群基因组分析，以表征寄生虫种群的结构，并更好地了解耐药等位基因如何以及如何以多快的速度在全国传播。我们还将使用这些数据来确定正选择下可能导致耐药性的基因座。其次，我们将采用体内和体外相结合的方法，确定100名间日疟患者体内存在的间日疟原虫菌株的药物敏感性。然后，我们将进行全基因组关联研究，以确定统计上与间日疟原虫耐药性相关的基因多态。我们的发现将提高我们对这种被忽视的人类疟疾寄生虫耐药性的理解，并有可能显著推进间日疟的控制。

DESCRIPTION (provided by applicant): Emergence of chloroquine resistance in Cambodian Plasmodium vivax threatens the entire malaria control strategy in the region. In collaboration with the Pasteur Institute in Cambodia, we will collect blood samples from 280 individuals infected with P. vivax and use next generation sequencing to investigate the patterns of genetic diversity across the entire P. vivax genome. First, we will conduct population genomic analyses to characterize the structure of the parasite population and better understand how and how fast drug resistance alleles can spread across the country. We will also use these data to identify loci under positive selection which could be responsible for drug resistance. Second, we will determine drug susceptibility of the P. vivax strains present in 100 vivax malaria patients using a combination of in vivo and ex vivo approaches. We will then conduct a genome-wide association study to identify genetic polymorphisms statistically associated with drug resistance in P. vivax. Our findings will improve our understanding of drug resistance in this neglected human malaria parasite and have the potential to significantly advance vivax malaria control.