Mosquito-parasite interactions and filariasis transmission in Papua New Guinea

描述（由申请人提供）：淋巴丝虫病（LF）主要由班氏乌切里氏菌引起，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。它们导致生活在世界热带和亚热带地区的数亿人死亡和发病，并使20多亿人处于危险之中。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。这些控制规划需要定义和量化流行病学上有效的终点，以实现规划目标，但要做到这一点，有必要对媒介与人类宿主之间的传播动力学有一个关键的了解。了解寄生虫与其蚊子媒介的关系，即媒介能力，对这项工作至关重要。蚊媒对LF或疟原虫的传播能力受蚊媒固有免疫反应的影响，但在流行地区，媒介免疫反应对这些寄生虫传播的影响很少被评估。去年，我们在巴布亚新几内亚（PNG）进行了初步研究，证明斑按蚊（W. bancrofti的主要媒介）对这种寄生虫产生了强烈的黑化免疫反应。基于这些发现，我们提出了一个总体假设，即按蚊载体的黑化免疫反应显著影响了班氏瓦氏菌在巴布亚新几内亚的传播。因为小儿麻痹症和疟疾在巴布亚新几内亚同时流行。我们还提出了一种假设，即当蚊子暴露于这两种寄生虫时，W. bancrofti激活的免疫反应会对恶性疟原虫的发展产生负面影响。为了验证这些假设，我们在此提议与巴布亚新几内亚医学研究所（PNGIMR）合作，将(1)确定黑化免疫反应对巴布亚新几内亚按蚊中W. bancrofti发育的影响，(2)评估蚊子抗丝虫反应对恶性疟原虫发展的影响。这项研究将主要在巴布亚新几内亚的PNGIMR进行，与Peter Siba合作，作为NIH拨款号的延伸。RO1AI19769, 1983年1月4日至2012年2月29日。

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.