Genetic epidemiology of malaria in the Democratic Republic of the Congo

刚果民主共和国疟疾的遗传流行病学

• 批准号: 8509376
• 负责人: Steven Richard Meshnick
• 金额: $ 48.84万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509376
• 关键词: Adult; Africa South of the Sahara; Antimalarials; Area; Blood; Country; Culicidae; DNA Sequence; Data; Democratic Republic of the Congo; Demographic and Health Surveys; Drug resistance; Epidemiology; Evaluation; Evolution; Failure; Foundations; Funding; Future; Genes; Genetic; Genetic Variation; Genotype; Geography; Goals; Grant; Health; Individual; Intervention; Knowledge; Lead; Maintenance; Malaria; Maps; Measures; Methods; Microsatellite Repeats; Molecular; Mutation; Parasites; Plasmodium falciparum; Population; Population Genetics; Positioning Attribute; Prevalence; Public Health; Risk; Role; Sampling; Spottings; Surveys; System; Time; USAID; Work; genetic analysis; genetic epidemiology; human migration; insight; intervention effect; molecular marker; multilevel analysis; population genetic structure; prevent; programs; resistance mutation; scale up; success; tool; uptake; Adult; Africa South of the Sahara; Antimalarials; Area; Blood; Country; Culicidae; DNA Sequence; Data; Democratic Republic of the Congo; Demographic and Health Surveys; Drug resistance; Epidemiology; Evaluation; Evolution; Failure; Foundations; Funding; Future; Genes; Genetic; Genetic Variation; Genotype; Geography; Goals; Grant; Health; Individual; Intervention; Knowledge; Lead; Maintenance; Malaria; Maps; Measures; Methods; Microsatellite Repeats; Molecular; Mutation; Parasites; Plasmodium falciparum; Population; Population Genetics; Positioning Attribute; Prevalence; Public Health; Risk; Role; Sampling; Spottings; Surveys; System; Time; USAID; Work; genetic analysis; genetic epidemiology; human migration; insight; intervention effect; molecular marker; multilevel analysis; population genetic structure; prevent; programs; resistance mutation; scale up; success; tool; uptake

DESCRIPTION (provided by applicant): Malaria is very highly endemic in the Democratic Republic of the Congo (DRC). We propose to use >16,000 dried blood spots from the 2007 and 2012 Demographic and Health Surveys (DHS) in the DRC to conduct the first longitudinal, nation-wide study of malaria genetic epidemiology. We have already measured and mapped malaria in the DRC from the 2007 DHS by high-throughput real-time PCR. Our first aim is to determine the effects of malaria control efforts on the prevalence of P. falciparum and other malaria species. We have a unique opportunity to do this now; malaria control programs were minimal in 2007 but are being dramatically scaled up this year (by the Global Fund, USAID and other agencies). Multilevel modeling will be used to identify individual- and cluster-level variables associated with increases or decreases in malaria prevalence. Our second aim is to measure molecular markers of drug resistance (dhps, pfcrt and pfmdr1) in P. falciparum samples from 2007 and 2012, and identify individual- and cluster-level factors associated with changes in the prevalence of drug resistance. Our third aim is to measure neutral microsatellite markers in P.falciparum from 2007 and 2012. Landscape genetic analyses will measure genetic distances in the P. falciparum populations between clusters and over time. This will allow the identification of dispersal corridors and barriers. It will also permit estimation of the rate of gene flow. The latter could be used to predict the rate at which malaria might reinvade an area from which it was eliminated. Taken together, our findings could offer a scientific foundation for malaria control programs.

描述（由申请人提供）：疟疾在刚果民主共和国（DRC）中非常流行。我们建议在刚果民主共和国中使用2007年和2012年人口统计学和健康调查（DHS）的16,000个干血点，以进行首次对疟疾遗传流行病学的全国性纵向研究。 我们已经通过高通量实时PCR测量了DRC中DRC中的疟疾和映射。 我们的第一个目的是确定疟疾控制努力对恶性疟原虫和其他疟疾物种患病率的影响。 我们现在有一个独特的机会来做到这一点。疟疾控制计划在2007年很少，但今年（由全球基金，美国国际开发署和其他机构）大大扩展。 多级建模将用于识别与疟疾患病率增加或降低相关的个体和集群级变量。 我们的第二个目的是测量2007年和2012年恶性疟原虫样品中耐药性（DHP，PFCRT和PFMDR1）的分子标记物，并鉴定与耐药性患病率变化相关的个体和集群水平因子。 我们的第三个目的是测量2007年和2012年的脂肪疟原虫中的中性微卫星标志物。景观遗传分析将测量群集和随着时间的时间之间的恶性疟原虫种群中的遗传距离。 这将允许识别分散走廊和障碍。 它还将允许估计基因流量的速率。 后者可以用来预测疟疾可能从中消除的区域的速度。 综上所述，我们的发现可以为疟疾控制计划提供科学基础。