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

项目3 项目摘要 环境改变对发病机制和 恶性疟原虫和间日疟原虫的免疫研究 提高和维持农业生产力的水电大坝和灌溉举措， 在埃塞俄比亚和肯尼亚。然而，对这些问题的了解非常有限。 水和土地使用的改变将影响各种疟疾生态系统， 病媒干预措施减少了但没有消除疟疾传播。研究 在这个项目中，将讨论与理解强度的快速变化有关的主题， 间日疟原虫和恶性疟原虫传播的地理空间特征 从环境改变影响自然获得性免疫（NAI）到疟疾疾病 病原体和寄生虫从人传播到蚊子。从一个翻译 的观点，目标是1）开发，评估和验证体外相关NAI 适用于作为人口监测和诊断工具的标准化格式， 用于预测疟疾发病率的复发或减少，以及2）促进 自然获得性恶性疟原虫抗体介导的传播减少的认识 活动从一个基本的角度来看，我们的目标是1）定义的机械作用， 疟疾免疫中的抗体和补体，以及2）填补知识的主要空白 NAI与非洲间日疟原虫发病机制有关。这些目标将通过一个 * 在西区两个疟疾流行地点进行实地和实验室设施合作 肯尼亚和埃塞俄比亚的三个疟疾流行点，以及美国的疟疾研究小组。 和澳大利亚，与研究科学家有着长期的工作关系， 埃塞俄比亚和肯尼亚的疟疾公共卫生专家。这与流行病学相结合， 该项目将产生生物样本、临床数据和抗体血清转化 传播项目，该项目将确定病媒物种的组成， 叮咬行为和暴露于按蚊的空间模式与 传播的变化降低免疫力。行政和数据管理以及 生物统计学核心将是至关重要的后勤，管理和科学价值， 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.