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

描述（由申请人提供）：已经提出疟疾寄生虫恶性疟原虫的传播动力学主要是由对血液阶段主要表面抗原的免疫选择驱动的，即红细胞膜蛋白1 (PfEMP1)，每个单倍体基因组由多达60个var多基因家族成员编码。新出现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入的分子采样，并开发计算方法，通过变异遗传学的视角扩展以前的“菌株理论”。本项目旨在确定var基因多样性背景下的恶性疟原虫种群结构，并在此框架下探讨流行病学动态。来自加纳和美国的数学建模师、流行病学家、昆虫学家、生物信息学家、种群遗传学家和疟疾流行病学家已经创建了一个团队项目。我们的方法结合了建模和实证研究，在var遗传学背景下，在加纳北部当地寄生虫种群水平上探索恶性疟原虫的疟疾传播动力学。具体目标是：(1)建立基于个体的随机建模框架，将宿主内部和宿主之间的传播偶联起来，并描述暴露于不同变异基因库的个体宿主免疫史，以探索恶性疟原虫菌株动态与年龄、季节性和媒介干预的关系。(2)：在疟疾流行病学研究中首次采用var基因深度454测序对人类社区无症状恶性疟原虫全种群进行纵向季节性采样。(3)：对干湿季节var基因多样性和var基因库的定量描述，以及采用室内残留喷洒（IRS）的主要病媒控制干预措施，与微卫星多样性进行比较。通过这些目标，我们将解决菌株结构的基本问题，尽管在广泛重组和免疫选择的驱动下，寄生虫之间对宿主的竞争相互作用在传播动力学中。反过来，我们也将询问这种结构和相关的寄生虫多样性如何影响传播动力学。

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.