Genomic Analyses of Plasmodium vivax Responses to Antimalarial Drugs in Cambodia

柬埔寨间日疟原虫对抗疟药物反应的基因组分析

• 批准号: 9254424
• 负责人: David Serre
• 金额: $ 35.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-13 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9254424
• 关键词: Address; Aftercare; Antimalarials; Area; Binding Proteins; Bioinformatics; Biological Assay; Blood; Blood specimen; Cambodia; Cambodian; Chloroquine; Chloroquine resistance; Collaborations; Country; DNA; Data; Development; Drug resistance; Event; Evolution; Gene Proteins; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genome; Genomics; Geography; Haplotypes; Human; Individual; Infection; Institutes; Laboratories; Link; Liver; Malaria; Measures; Membrane Proteins; Microscopic; Modernization; Monitor; Nucleotides; Parasitemia; Parasites; Patient Recruitments; Patients; Pattern; Pharmaceutical Preparations; Plasmodium falciparum; Plasmodium vivax; Population; Predisposition; Recrudescences; Recruitment Activity; Recurrence; Relapse; Reporting; Resistance; Scanning; Site; Southeastern Asia; Stratification; Structure; Technology; Testing; Treatment Failure; Vivax Malaria; base; circumsporozoite; experience; forest; genome wide association study; genome-wide; improved; in vitro Assay; in vivo; neglect; next generation sequencing; public health relevance; resistance allele; response; southeast Asian; whole genome

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.

描述（由申请人提供）： 柬埔寨间日疟原虫对氯喹的抗药性威胁到该区域的整个疟疾控制战略。通过与柬埔寨巴斯德研究所的合作， 将从280名感染间日疟原虫的个体中收集血液样本，并使用下一代测序技术研究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快速在全国范围内传播。我们还将使用这些数据来确定正选择下的基因座，这可能是耐药性的原因。第二，我们将使用体内和体外方法的组合来确定存在于100名间日疟患者中的间日疟菌株的药物敏感性。然后，我们将进行全基因组关联研究，以确定与间日疟原虫耐药性统计学相关的遗传多态性。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，并有可能显着推进间日疟控制。

项目成果

Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand.

• DOI: 10.1093/infdis/jiw323
• 发表时间: 2016-10-15
• 期刊: The Journal of infectious diseases
• 作者: Auburn S;Serre D;Pearson RD;Amato R;Sriprawat K;To S;Handayuni I;Suwanarusk R;Russell B;Drury E;Stalker J;Miotto O;Kwiatkowski DP;Nosten F;Price RN
• 通讯作者: Price RN

Therapeutic and Transmission-Blocking Efficacy of Dihydroartemisinin/Piperaquine and Chloroquine against Plasmodium vivax Malaria, Cambodia.

• DOI: 10.3201/eid2408.170768
• 发表时间: 2018-08
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Popovici J;Vantaux A;Primault L;Samreth R;Piv EP;Bin S;Kim S;Lek D;Serre D;Menard D
• 通讯作者: Menard D

Genomic Analyses Reveal the Common Occurrence and Complexity of Plasmodium vivax Relapses in Cambodia.

基因组分析揭示了柬埔寨疟原虫复发的常见发生和复杂性。

• DOI: 10.1128/mbio.01888-17
• 发表时间: 2018-01-23
• 期刊: mBio
• 影响因子: 6.4
• 作者: Popovici J;Friedrich LR;Kim S;Bin S;Run V;Lek D;Cannon MV;Menard D;Serre D
• 通讯作者: Serre D