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）：疟疾寄生虫恶性疟原虫的传播动力学被认为主要是由对血液阶段主要表面抗原的免疫选择驱动的，该主要表面抗原被称为红细胞膜蛋白1（PfEMP 1），由每个单倍体基因组多达60个var多基因家族成员编码。新兴的人口遗传学数据显示，疟疾传播系统是非常复杂的，需要更深入的寄生虫种群的分子采样和计算方法的发展，通过变异遗传学的透镜扩展以前的“应变理论”。本项目旨在从var基因多样性的角度确定恶性疟原虫的种群结构，并在此框架下探讨恶性疟原虫的流行病学动态。已经创建了一个团队项目，汇集了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、人口遗传学家和疟疾流行病学家。我们的方法结合了建模和实证研究，探讨疟疾传播动力学的恶性疟原虫在当地寄生虫种群的水平在北方加纳的背景下，变异遗传学。具体目标是：（1）基于个体的随机建模框架，结合宿主内和宿主间传播，描述暴露于不同var基因库的个体-宿主免疫史，以探索与年龄、季节性和媒介干预相关的恶性疟原虫菌株动态。(2)在疟疾流行病学研究中，首次使用var基因的深度454测序对人类社区中整个无症状恶性疟原虫种群进行纵向季节性采样。(3)：与微卫星多样性相比，定量描述了在雨季和旱季以及在使用室内滞留喷洒的主要病媒控制干预措施中的var基因多样性和var库。通过这些目标，我们将解决的基本问题，尽管广泛的重组和驱动的免疫选择，寄生虫之间的竞争相互作用的主机在传输动力学的菌株结构。反过来，我们也会问这种结构和相关的寄生虫多样性如何影响传播动态。