Impact of Environmental Modifications on Pathogenesis and Immunity of Plasmodium falciparum and P. vivax Malaria

项目3 项目总结 环境改造对致病机理和环境保护的影响 恶性疟原虫和间日疟原虫的免疫力 旨在提高和维持农业生产力的水电站和灌溉计划 目前正在埃塞俄比亚和肯尼亚进行。然而，人们对这些问题的了解非常有限。 水和土地利用的改变将影响到不同的疟疾生态系统，并正在产生影响 媒介干预措施减少了但没有消除疟疾传播。研究 在这个项目中将讨论与理解强度如何快速变化相关的主题 间日疟原虫和间日疟原虫传播的地理空间特征 从环境变化影响自然获得性免疫(NAI)到疟疾 致病机制和寄生虫从人到蚊子的传播。从翻译版 从长远来看，目标是1)开发、评估和验证NAI的体外相关性 可适应标准化格式，如人口监测和诊断工具，可以 用于预测疟疾发病率的回升或减少，以及2)提前 对自然获得性恶性疟原虫抗体介导的传播减少的认识 活动。从基本的角度来看，我们的目标是1)定义 疟疾免疫中的抗体和补体，以及2)填补主要的知识空白 与非洲间日疟原虫发病机制的NAI有关。这些目标将通过一个 涉及西部两个疟疾流行地点的现场和实验室设施的合作 肯尼亚和埃塞俄比亚的三个疟疾流行地点，在美国有疟疾研究团队。 和澳大利亚，与研究科学家和 埃塞俄比亚和肯尼亚的疟疾公共卫生专家。这是与流行病学相结合的 该项目将产生生物样本、临床数据和抗体血清转换 数据，以及传播项目，这将确定媒介物种组成， 蚊虫叮咬行为和接触按蚊的空间模式与 传播的变化降低了免疫力。管理和数据管理以及 生物统计核心将对这一项目的后勤、管理和科学价值至关重要 项目。

PROJECT 3 PROJECT SUMMARY Impact of Environmental Modifications on Pathogenesis and Immunity of Plasmodium falciparum and P. vivax Malaria Hydropower dam and irrigation initiatives to improve and sustain agricultural productivity are underway in Ethiopia and Kenya. However, there is very limited knowledge of how these water and land use modifications will affect diverse malaria ecosystems and impact ongoing vector interventions that have decreased but not eliminated malaria transmission. Research in this project will address topics pertinent to understanding how rapid changes in intensity and geospatial features of Plasmodium falciparum vivax and P. vivax transmission resulting from environmental modifications impact naturally acquired immunity (NAI) to malaria disease pathogenesis and parasite transmission from humans to mosquitoes. From a translational perspective, the goals are to 1) develop, evaluate and validate in vitro correlates of NAI adaptable to standardized formats as population surveillance and diagnostic tools that could be used to predict resurgences or reductions of malaria morbidity, and 2) advance understanding of naturally acquired P. falciparum antibody-mediated transmission reducing activity. From a basic perspective, our goals are to 1) define the mechanistic roles of antibodies and complement in malaria immunity, and 2) fill in major gaps of knowledge related to NAI to P. vivax pathogenesis in Africa. These goals will be achieved through a collaboration involving field and laboratory facilities in two malaria endemic sites in western Kenya and three malaria endemic sites in Ethiopia with malaria research teams in the U.S. and Australia that have long standing working relationships with research scientists and malaria public health experts in Ethiopia and Kenya. This is integrated with the Epidemiology project, which will generate biological samples, clinical data, and antibody seroconversion data, and the Transmission project, which will determine whether vector species composition, biting behavior and spatial patterns of exposure to anopheline mosquitoes correlate with changes in transmission reducing immunity. The Administrative and Data Management and Biostatistics Cores will be critical to the logistics, management, and scientific value of this project.