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

基本信息

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
项目类别：
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

项目摘要

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）：淋巴丝虫病（LF）主要由班氏丝虫引起，疟疾主要由恶性疟原虫和间日疟原虫引起，是两种最重要的蚊媒疾病。它们导致世界热带和亚热带地区数亿人死亡和发病，并使超过 20 亿人面临风险。这些疾病对人口造成的经济和健康影响无疑是最近制定控制和/或消除这些疾病的全球战略的推动力。这些控制计划需要定义和量化流行病学上有效的终点，以实现计划目标，但要做到这一点，有必要对媒介和人类宿主之间的传播动态有一个批判性的了解。了解寄生虫与其蚊子媒介之间的关系，即媒介能力，对于这项工作至关重要。蚊子对 LF 或疟原虫寄生虫的媒介能力受到蚊子媒介先天免疫反应的影响，但媒介免疫反应对这些寄生虫在流行地区传播的影响很少得到评估。去年，我们在巴布亚新几内亚 (PNG) 进行了初步研究，结果表明，斑按蚊（班氏按蚊的主要媒介）对这种寄生虫产生了强烈的黑化免疫反应。根据这些发现，我们提出总体假设，即按蚊载体的黑化免疫反应显着影响巴布亚新几内亚W. bancrofti的传播。因为 LF 和疟疾在巴布亚新几内亚同时流行，而且因为 An.点状疟原虫复合体可传播 LF 寄生虫和所有地方性疟原虫物种，我们还提出这样的假设：当蚊子暴露于两种寄生虫时，班氏疟原虫激活的免疫反应会对恶性疟原虫的发育产生负面影响。为了检验这些假设，我们在此建议与巴布亚新几内亚医学研究所 (PNGIMR) 合作，该项目将 (1) 确定黑化免疫反应对巴布亚新几内亚按蚊中班克罗夫氏菌发育的影响，以及 (2) 评估影响蚊子抗丝虫反应对恶性疟原虫发育的影响。这项研究将主要在 PNGIMR 与 Peter Siba 合作在巴布亚新几内亚进行，作为 NIH 拨款号 RO1AI19769（1983 年 4 月 1 日至 2012 年 2 月 29 日）的延伸。公共卫生相关性：疟疾和淋巴丝虫病是蚊媒疾病，对人类健康造成毁灭性损害，尤其是热带地区的弱势群体。该提案中描述的研究将使科学界更好地了解蚊子与寄生虫之间的相互关系，这种关系可能会影响这些媒介的疾病传播效率。对影响传输动态的因素的进一步了解将为控制和/或消除程序的设计和监控提供有价值的信息。