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. ? ? ?
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