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

消灭流行现场的原发性丝虫病媒介种群

• 批准号: 7143176
• 负责人: Stephen Leonard Dobson
• 金额: $ 33.04万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7143176
• 关键词: clinical research; infection; male

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.

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，全球有 12 亿人面临风险。超过 90% 的感染是由班氏乌策菌引起的，人类是其唯一宿主。不存在非人类宿主表明，可以通过社区范围内的治疗（大众药物管理局，MDA）消除微丝蚴宿主来中断传播，这是消除淋巴丝虫病全球计划当前的重点。虽然 MDA 策略可能有效，但历史表明，如果不控制病媒，就无法消除波利尼西亚的淋巴丝虫病。法属波利尼西亚的毛皮提岛提供了一个例子，尽管五年来MDA持续存在，但丝虫病仍然持续存在。主要蚊子媒介波利尼西亚伊蚊的生物学特性被认为是 MDA 失败的原因。由于蚊子是班氏丝虫病的专性媒介，这表明消除丝虫病的另一种方法：根除蚊子媒介将打破疾病传播周期。不幸的是艾。波利尼西亚虫目前无法得到控制，更不用说根除了。在这里，我们提出了一种新颖的策略，其中释放雄性 Ae。感染沃尔巴克氏体细菌的波利尼西亚蚊子导致丝虫病传播流行地区的雌性蚊子绝育。雄性的重复释放将能够根除目标白斑蚊。波利尼西亚人人口。我们强调，雄性蚊子不吸血，因此不是疾病媒介。此外，所提出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 感染的伊蚊是如何发生的。波利尼西亚菌株已经产生，并被证明可以使莫乌皮蒂岛的雌性蚊子绝育。该研究计划描述了根除策略的实验室和现场笼子测试，以及随后的现场试验，其中伊蚊。波利尼西亚人种群已从丝虫病流行焦点中被消灭。其他实验描述了现场试验之前、期间和之后目标现场地点（莫皮提岛无人居住的小岛）的特征。在田间试验之前，实验将比较释放品系和田间种群的适应性、种群动态和遗传结构、交配竞争力和载体能力。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额外的蚊子菌株，用于媒介消灭策略。我们讨论了从田间试验过渡到病媒根除运动的模型的开发。我们强调，相对于波利尼西亚正在进行的病媒控制，消灭病媒战略在经济上更加可行。此外，波利尼西亚的地理位置将通过减少移民导致病媒再次感染的问题来简化根除方法。相关性：历史表明，如果继续仅仅依赖大规模药物管理（MDA）策略，目前全球消除淋巴丝虫病的努力可能会在太平洋地区失败。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。病媒根除战略和 MDA 方法的结合将有助于在单靠 MDA 失败的地区消除丝虫病。