Eradication of a Primary Filariasis Vector Population at an Endemic Field Site

描述（由申请人提供）：淋巴丝虫病（象皮病）影响80个国家的1.2亿多人，全世界有12亿人处于危险之中。90%以上的感染是由班氏乌切里氏菌引起的，人类是其唯一的宿主。没有非人类宿主表明，通过社区范围的治疗（大规模药物管理，MDA）消除微丝虫病宿主可以阻断传播，这是目前全球消除淋巴丝虫病规划的重点。虽然MDA战略可能有效，但历史表明，如果没有病媒控制，就无法在波利尼西亚消除淋巴丝虫病。法属波利尼西亚的Maupiti提供了一个例子，尽管五十年来持续不断地进行MDA，但丝虫病仍然存在。主要蚊媒波利尼西亚伊蚊（Aedes polynesiensis）的生物学特性被认为是预防措施失败的原因。由于蚊子是bancroffti氏白丝虫的专性媒介，这提示了消除丝虫病的另一种方法：消灭蚊子媒介将打破疾病传播周期。不幸的是Ae。波利尼西亚人目前无法控制，更不用说根除了。在此，我们提出了一种新的策略，即释放雄性伊蚊。感染沃尔巴克氏菌的波利尼西亚蚊导致丝虫病传播流行现场的雌蚊绝育。反复释放雄蚊可以消灭目标伊蚊。polynesiensis人口。我们强调，雄蚊不吸血，因此不是疾病媒介。此外，拟议的策略采用自然发生的细菌感染，不包括转基因生物。初步研究部分描述了l/Vo/bac/7/a感染的Ae。已经产生了波利尼西亚菌株，并显示可以使毛皮提岛的雌蚊绝育。研究计划描述了消灭策略的实验室和现场笼试验，随后是伊蚊的现场试验。从丝虫病的地方性焦点消灭波利尼西亚种群。额外的实验描述了在实地试验之前、期间和之后的目标实地地点（Maupiti的一个无人居住的小岛）的特征。在田间试验之前，实验将比较释放菌株和田间种群的适应性、种群动态和遗传结构、交配竞争和媒介能力。最近开发的通过显微注射在蚊子中产生新的沃尔巴克氏体感染类型的技术将用于产生用于病媒根除战略的额外蚊子菌株。我们讨论了从田间试验过渡到媒介根除运动的模型的发展。我们强调，与波利尼西亚正在进行的病媒控制相比，病媒根除战略在经济上更为可行。此外，波利尼西亚的地理位置将通过减少通过移民传播的病媒重新感染问题来简化根除方法。相关性：历史表明，如果继续仅仅依靠大规模给药战略，目前在太平洋地区消灭淋巴丝虫病的全球努力可能会失败。拟议的研究将展示一种在流行现场消灭丝虫病主要蚊媒的策略。将病媒消灭战略与大规模预防措施相结合，将有助于在单独大规模预防措施失败的地区消除丝虫病。

DESCRIPTION (provided by applicant): Lymphatic filariasis (Elephantiasis) affects over 120 million people in 80 countries, with 1.2 billion people at risk worldwide. Over 90% of infections are caused by Wuchereria bancrofti, for which humans are the exclusive host. The absence of a nonhuman reservoir suggests that transmission can be interrupted by elimination of the microfilariae reservoir via community-wide treatment (Mass Drug Administration, MDA), which is the current focus of the Global Programme for the Elimination of Lymphatic Filariasis. While MDA strategies can be effective, history suggests that elimination of lymphatic filariasis in Polynesia is unachievable without vector control. An example is provided by Maupiti in French Polynesia, where filariasis persists despite five decades of constant MDA. The biology of the primary mosquito vector, Aedes polynesiensis, has been blamed for MDA failure. Since mosquitoes are obligate vectors of W. bancrofti, this suggests an additional approach for filariasis elimination: eradication of the mosquito vectors will break the disease transmission cycle. Unfortunately Ae. polynesiensis currently cannot be controlled, much less eradicated. Here, we propose a novel strategy in which releases of male Ae. polynesiensis mosquitoes infected with Wolbachia bacteria result in the sterilization of female mosquitoes at a field site endemic for filariasis transmission. Repeated male releases will permit the eradication of the targeted Ae. polynesiensis population. We emphasize that male mosquitoes do not blood feed and therefore are not disease vectors. Furthermore, the proposed strategy employs a naturally occurring bacteria infection and does NOT include genetically modified organisms. The preliminary studies section describes how a l/Vo/bac/7/a-infected Ae. polynesiensis strain has been generated and shown to sterilize female mosquitoes from Maupiti. The research plan describes laboratory and field cage tests of the eradication strategy, followed by field trials in which the Ae. polynesiensis population is eradicated from an endemic focus of filariasis. Additional experiments describe the characterization of the targeted field site (an uninhabited islet in Maupiti) prior to, during, and following the field trial. Prior to the field trial, experiments will compare the release strain and field population in their fitness, population dynamics and genetic structure, mating competitiveness, and vector competency. Recently developed techniques for generating new Wolbachia infection types in mosquitoes via microinjection will be used to generate additional mosquito strains for use in vector eradication strategies. We discuss the development of a model for the transitioning from field trials to a vector eradication campaign. We emphasize that a vector eradication strategy is more feasible economically relative to ongoing vector control in Polynesia. Furthermore, the geography of Polynesia will simplify an eradication approach by reducing problems of vector reinfestation via immigration. Relevance: History demonstrates that the current global effort to eliminate lymphatic filariasis can fail in the Pacific if it continues to rely solely upon a mass drug administration (MDA) strategy. The proposed research will demonstrate a strategy for eradicating the primary mosquito vector of filariasis at an endemic field site. Integration of the vector eradication strategy and the MDA approach will facilitate filariasis elimination in areas where MDA alone has failed.