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

描述(申请人提供)：淋巴丝虫病(大象病)影响着80个国家的1.2亿人，全世界有12亿人处于危险之中。超过90%的感染是由班克罗夫氏舞蹈菌引起的，人类是唯一的宿主。没有非人类宿主表明，可以通过社区范围的治疗(大众药物管理局，MDA)消除微丝虫病宿主来阻断传播，这是全球消除淋巴丝虫病方案目前的重点。虽然MDA策略可能是有效的，但历史表明，如果没有媒介控制，在波利尼西亚消除淋巴丝虫病是不可能实现的。法属波利尼西亚的毛皮提提供了一个例子，尽管持续了50年的丙二醛，丝虫病仍然存在。主要蚊子媒介多尼斯伊蚊的生物学被指责为MDA失败的罪魁祸首。由于蚊子是W.Bancrofti的专有媒介，这就提出了消除丝虫病的另一种方法：消灭蚊媒将打破疾病传播周期。不幸的是，艾。波尼西亚病目前无法控制，更不用说根除了。在这里，我们提出了一种新的策略，其中释放男性Ae。在丝虫病传播的地方性地点，感染沃尔巴克氏菌的波氏蚊子会导致雌性蚊子绝育。重复释放雄性将允许根除目标Ae。波里尼西山种群。我们强调，雄性蚊子不吸血，因此不是疾病媒介。此外，拟议的战略使用了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a L/Vo/bac/7/a感染Ae的情况。已经产生了Polynesiens菌株，并证明它可以使毛皮提的雌性蚊子绝育。研究计划描述了根除战略的实验室和野外笼养试验，随后是Ae。多尼斯虫种群从丝虫病的地方性疫源地被根除。其他实验描述了在现场试验之前、期间和之后对目标现场(毛皮提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在适应度、种群动态和遗传结构、交配竞争力和媒介能力方面的差异。最近开发的通过显微注射在蚊子中产生新的沃尔巴克氏菌感染类型的技术将被用来产生更多的蚊子品系，用于消灭媒介的战略。我们讨论了从现场试验过渡到消灭病媒运动的模型的开发。我们强调，与波利尼西亚正在进行的病媒控制相比，消灭病媒的战略在经济上更可行。此外，波利尼西亚的地理位置将简化根除方法，减少通过移民造成的媒介再感染问题。相关性：历史表明，当前全球消除淋巴丝虫病的努力如果继续仅仅依靠大规模药物管理(MDA)战略，就可能在太平洋地区失败。拟议的研究将展示一种在流行现场根除丝虫病主要蚊媒的战略。将病媒根除战略与丙型肝炎防治方法相结合，将有助于在仅有丙型肝炎防治方案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.