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）： 柬埔寨疟原虫在葡萄球菌中的氯喹的出现威胁着该地区的整个疟疾控制策略。与柬埔寨的巴斯德研究所合作，我们 将收集来自感染疟原虫的280名个体的血液样本，并使用下一代测序研究整个疟原虫基因组中遗传多样性的模式。首先，我们将进行人群基因组分析，以表征寄生虫种群的结构，并更好地了解耐药性等位基因在全国各地的耐药性耐药性如何传播。我们还将使用这些数据来识别可能导致耐药性的阳性选择下的基因座。其次，我们将通过体内和离体方法组合确定100例疟疾疟疾患者中存在的疟原虫菌株的药物敏感性。然后，我们将进行一项全基因组关联研究，以鉴定统计的遗传多态性与耐药性耐药性相关。我们的发现将提高我们对这种被忽视的人类疟疾寄生虫的耐药性的理解，并有可能显着改善疟疾疟疾的控制。

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.

• 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