Impact of seasonality and vector control on population structure of P.falciparum

季节性和媒介控制对恶性疟原虫种群结构的影响

• 批准号: 8642699
• 负责人: Karen Patricia Day
• 金额: $ 45万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-28 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8642699
• 关键词: Address; Age; Blood; Communities; Complex; Couples; Data; Development; Epidemiologic Studies; Epidemiologist; Epidemiology; Erythrocyte Membrane; Exposure to; Genes; Genetic; Genetic Recombination; Genome; Ghana; Haploidy; Human; Immune; Individual; Intervention; Lead; Malaria; Membrane Proteins; Microsatellite Repeats; Modeling; Molecular; Multigene Family; Outcome; Parasites; Plasmodium falciparum; Population; Population Genetics; Recording of previous events; Residual state; Sampling; Seasons; Staging; Structure; Surface Antigens; System; Time; base; innovation; lens; member; public health relevance; theories; transmission process; vector; vector control

DESCRIPTION (provided by applicant): Transmission dynamics of the malaria parasite Plasmodium falciparum have been proposed to be largely driven by immune selection to the major surface antigen of the blood stages known as erythrocyte membrane protein 1 (PfEMP1) encoded by up to 60 members of the var multigene family per haploid genome. Emerging population genetic data have revealed that the malaria transmission system is remarkably complex necessitating a much deeper molecular sampling of parasite populations and the development of computational approaches that extend previous 'strain theory' through the lens of var genetics. This project aims to define the population structure of P. falciparum in the context of var gene diversity and explore epidemiological dynamics in this framework. A team project has been created that brings together mathematical modelers, epidemiologists, entomologists, bioinformaticians, population geneticists and malaria epidemiologists from Ghana and US. Our approach combines both modeling and empirical studies to explore malaria transmission dynamics of P. falciparum at the level of local parasite populations in northern Ghana in the context of var genetics. Specific objectives are: (1) An individual-based, stochastic modeling framework that couples within and between-host transmission and describes the individual-host immunological history of exposure to different var gene repertoires to explore strain dynamics of P. falciparum in relation to age, seasonality and vector intervention. (2): For the first time in malaria epidemiology research, the longitudinal seasonal sampling of entire asymptomatic P. falciparum populations in human communities using deep 454 sequencing of var genes. (3): The quantitative description of var gene diversity and of var repertoires in wet and dry seasons, as well as across a major vector control intervention using indoor residual spraying (IRS), in comparison to microsatellite diversity. Through these objectives',-we-will address the fundamental question of strain structure despite extensive recombination and driven by immune selection, competitive interactions between parasites for hosts in the transmission dynamics. In turn, we will also ask how this structure and associated parasite diversity influence transmission dynamics.

描述（由申请人提供）：疟原虫疟原虫恶性疟原虫的传播动力学已被提议在很大程度上由免疫选择驱动到血液阶段的主要表面抗原，称为红细胞膜蛋白1（PFEMP1），该蛋白1（PFEMP1）被编码多达60个成员，由多数杂种家族的60个成员。新兴的种群遗传数据表明，疟疾传播系统非常复杂，需要对寄生虫种群进行更深得多的分子采样，并开发通过VAR遗传学镜头扩展先前的“应变理论”的计算方法。该项目旨在在VAR基因多样性的背景下定义恶性疟原虫的种群结构，并在此框架中探索流行病学动态。创建了一个团队项目，该项目将数学建模者，流行病学家，昆虫学家，生物信息学家，人群遗传学家和来自加纳和美国的疟疾流行病学家汇集在一起​​。我们的方法结合了建模和经验研究，以探索恶性疟原虫在加纳北部局部寄生虫种群水平上的疟疾传播动力学。特定目标是：（1）一个基于个体的随机建模框架，该框架在宿主传播内和宿主之间融合，并描述了暴露于不同VAR基因曲目的个人宿主免疫学历史，以探索恶性疟原虫的应变动态，以与年龄，季节性和媒介干预有关。 （2）：在疟疾流行病学研究中，第一次使用VAR基因的深454个测序对人类社区中整个无症状恶性疟原虫种群进行了纵向季节性采样。 （3）：与微磷灰石多样性相比，使用室内残留喷涂（IRS）的湿季度以及在主要的矢量控制干预措施中的VAR基因多样性和VAR曲目的定量描述。通过这些目标”， - 我们将解决尽管重组的重组，并由免疫选择，寄生虫之间的竞争相互作用驱动，但寄生虫在传输动力学中的竞争性相互作用。反过来，我们还将询问这种结构和相关的寄生虫多样性如何影响传递动态。