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

环境改造对恶性疟原虫和间日疟原虫疟疾发病机制和免疫的影响

基本信息

批准号：
10608071
负责人：
James Walter Kazura
金额：
$ 107.89万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-15 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10608071
关键词：
Affect Africa Africa South of the Sahara Agriculture Anopheles Genus Antibodies Antibody-mediated protection Australia Behavior Binding Biological Biological Assay Biomass Biostatistics Core Bite Blocking Antibodies Blood Blood typing procedure Clinical Data Collaborations Community Surveys Complement Country Culicidae Data Demography Detection Development Diagnostic tests Disease Ecosystem Enrollment Environment Environmental Impact Epidemiology Erythrocytes Ethiopia Ethiopian Ethnic Origin Exposure to Germ Cells Goals Hand High Prevalence Human Humoral Immunities Immune Immunity Immunoglobulin G Impairment In Vitro Individual Infection Intervention Invaded Irrigation Kenya Knowledge Logistics Maintenance Malaria Malaria prevention Mediating Membrane Membrane Proteins Memory B-Lymphocyte Modification Monitor Morbidity - disease rate Office of Administrative Management Parasites Pathogenesis Pattern Peripheral Blood Mononuclear Cell Persons Phagocytosis Plasma Plasmodium falciparum Plasmodium vivax Population Population Surveillance Predictive Value Predisposition Prevalence Productivity Prospective, cohort study Protein Binding Domain Proteins Public Health Recovery Research Research Project Grants Resource-limited setting Role Sampling Scientist Serology test Site Specimen Standardization Surface Time Vivax Malaria Water acquired immunity antibody test blood group data management diagnostic tool feeding improved insight laboratory facility land use malaria infection malaria transmission malaria transmission-blocking vaccine novel seroconversion synergism transmission blocking transmission process vector

项目摘要

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.

项目3 项目概要环境改变对发病机制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大坝和灌溉举措埃塞俄比亚和肯尼亚正在进行中。然而，人们对于这些是如何实现的了解非常有限。水和土地利用的改变将影响不同的疟疾生态系统并持续影响媒介干预措施已减少但并未消除疟疾传播。研究在这个项目中将讨论与了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改变影响自然获得性免疫（NAI）到疟疾疾病发病机制和从人类到蚊子的寄生虫传播。来自翻译从角度来看，目标是 1) 开发、评估和验证 NAI 的体外相关性适应标准化格式作为人口监测和诊断工具，用于预测疟疾发病率的复苏或减少，以及 2) 推进了解自然获得的恶性疟原虫抗体介导的传播减少活动。从基本角度来看，我们的目标是 1）定义疟疾免疫中的抗体和补体，2) 填补主要知识空白非洲 NAI 与间日疟原虫发病机制有关。这些目标将通过涉及西部两个疟疾流行地区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区，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项目，将生成生物样本、临床数据和抗体血清转化数据和传输项目，这将确定媒介物种的组成，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。行政和数据管理以及生物统计核心对于该研究的后勤、管理和科学价值至关重要项目。