Mosquito-parasite interactions and filariasis transmission in Papua New Guinea

巴布亚新几内亚的蚊虫相互作用和丝虫病传播

• 批准号: 8080937
• 负责人: BRUCE MARTIN CHRISTENSEN
• 金额: $ 5.52万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8080937
• 关键词: Address; Affect; Affinity Chromatography; Anopheles Genus; Area; Biochemical; Bioinformatics; Blood; Collaborations; Communities; Competence; Complex; Computing Methodologies; Culicidae; Data; Development; Disease; Exposure to; Filaria bancrofti; Filarial Elephantiases; Filariasis; Fluorescence; Gene Expression Profile; Gene Proteins; Gene Targeting; Genes; Genetic Transcription; Glucans; Goals; Grant; Health; Hemolymph; Human; Immune response; Immunity; Individual; Infection; Institutes; Isotopically-Coded Affinity Tagging; Knock-out; Life; Link; Malaria; Medical Research; Modification; Monitor; Morbidity - disease rate; Mosquito Control; Mosquito-borne infectious disease; Papua New Guinea; Parasites; Pathway interactions; Pattern; Phenotype; Plasmodium; Plasmodium falciparum; Population; Post-Translational Protein Processing; Proteins; Proteome; Proteomics; RNA Interference; Research; Risk; Role; Sampling; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Techniques; Testing; United States National Institutes of Health; base; comparative; curdlan; density; design; disease transmission; driving force; gel electrophoresis; health economics; liquid chromatography mass spectrometry; meetings; mortality; parent grant; pro-phenoloxidase; programs; public health relevance; research study; response; transcriptomics; transmission process; two-dimensional; vector; vector mosquito

DESCRIPTION (provided by applicant): Lymphatic filariasis (LF), caused primarily by Wuchereria bancrofti, and malaria, caused primarily by Plasmodium falciparum and P. vivax, are two of the most important mosquito-borne diseases. They cause mortality and morbidity in hundreds of millions of people living in the tropical and subtropical regions of the world and place over two billion more at risk. The economic and health impacts these diseases place on populations have undoubtedly been driving forces in the recent development of global strategies for their control and/or elimination. These control programs need to define and quantify epidemiologically valid endpoints for meeting program objectives, but to do this it is necessary to obtain a critical understanding of transmission dynamics operating between vectors and human hosts. Understanding the relationship a parasite has with its mosquito vector, i.e., vector competence, is critical to this effort. Vector competence of mosquitoes to LF or Plasmodium parasites is affected by the innate immune response of mosquito vectors, but the impact of vector immune responses on transmission of these parasites in endemic areas has seldom been evaluated. During the last year, we conducted preliminary studies in Papua New Guinea (PNG) that demonstrate that Anopheles punctulatus, a principal vector of W. bancrofti, mounts a strong melanization immune response against this parasite. As a result of these findings, we propose the overall hypothesis that melanization immune responses by anopheline vectors significantly impact transmission of W. bancrofti in PNG. Because LF and malaria are co-endemic in PNG, and because the An. punctulatus complex of species transmits both LF parasites and all endemic species of Plasmodium, we also propose the hypothesis that immune response activation by W. bancrofti negatively impacts the development of P. falciparum when mosquitoes are exposed to both parasites. To test these hypotheses we herein propose collaboration with the PNG Institute of Medical Research (PNGIMR) that will (1) determine the impact of melanization immune responses on the development of W. bancrofti in anopheline mosquitoes in PNG, and (2) evaluate the impact of mosquito anti-filarial worm responses on the development of P. falciparum. This research will be done primarily in PNG at the PNGIMR in collaboration with Peter Siba, as an extension of NIH Grant No. RO1AI19769, 04/01/1983 to 02/29/2012. PUBLIC HEALTH RELEVANCE: Malaria and lymphatic filariasis are mosquito-borne diseases that exact a devastating toll on human health, especially amongst less privileged populations in the tropics. The research described in this proposal will give the scientific community a better understanding of mosquito-parasite interrelationships that can influence the efficiency of disease transmission by these vectors. This increased understanding of factors influencing transmission dynamics will provide valuable information for the design and monitoring of control and/or elimination programs.

描述（由申请人提供）：主要由bancrofti wuchereria bancrofti引起的淋巴丝虫病（LF），主要由恶性疟原虫和Vivax引起的疟疾是最重要的两种蚊子 - 纳马 - - 纳马 - 纳马 - - 纳马 - - 元素 - 裔 - 裔疾病。它们在世界上热带和亚热带地区的数亿人中引起死亡率和发病率，并在危险中增加了超过20亿。经济和健康影响这些疾病对人群的影响无疑是在最近制定全球控制和/或消除的全球战略的驱动力。这些控制程序需要定义和量化流行病学上有效的终点以实现计划目标，但是要做到这一点，有必要对向量和人类宿主之间运行的传输动态进行批判性理解。了解寄生虫与其蚊子媒介（即矢量能力）之间的关系对于这一努力至关重要。蚊子对LF或疟原虫的载体能力受蚊子载体的先天免疫反应的影响，但是很少评估载体免疫反应对这些寄生虫在地方性地区传播的影响。在过去的一年中，我们在巴布亚新几内亚（PNG）进行了初步研究，该研究表明W. Bancrofti的主要向量是Anopheles Punctulatus，对这种寄生虫具有强烈的黑素化免疫反应。这些发现的结果，我们提出了一个总体假设，即瞬间载体的黑素化免疫反应显着影响了bancrofti在PNG中的传播。因为LF和疟疾在PNG中是共同的，并且是因为An。物种的点状复合物传递LF寄生虫和所有地方性疟原虫，我们还提出了这样的假设，即W. bancrofti的免疫反应激活时，当蚊子暴露于两种寄生虫时，对恶性疟原虫的发育产生了负面影响。为了测试这些假设，我们在此提议与PNG医学研究所（PNGIMR）合作，该研究将（1）确定黑色素化免疫反应对PNG中蚊子中W. Bancrofti的发展的影响，以及（2）评估Mosquito Anti-Filarial Worm Repperse the P. falcip的影响。这项研究将主要在PNGIMR的PNG中与Peter Siba合作，作为NIH赠款号RO1AI19769，04/01/1983至02/29/2012的扩展。 公共卫生相关性：疟疾和淋巴丝虫病是蚊子传播的疾病，对人类健康造成了毁灭性的损失，尤其是在热带地区特权较低的人群中。该提案中描述的研究将使科学界更好地了解蚊子 - 寄生虫相互关系，这些相互关系可以影响这些向量的传播效率。对影响传输动态因素的增强理解将为设计和监视控制和/或消除计划提供有价值的信息。