Genomic Analyses of Plasmodium vivax Responses to Antimalarial Drugs in Cambodia

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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.