Controlling Arbovirus Transmission: PopulationSuppression and Virus-Induced Mosquito Death

摘要： 伊蚊继续传播登革热、寨卡和黄热病等病毒，世界上大部分地区的 人口处于危险之中。在巴西尤其如此，那里的登革热疫情持续不断， 这一流行病受到的打击最严重，城市黄热病不断有重新出现的危险。以建立新 在病媒控制战略方面，巴西率先测试和批准了一项新战略， 基于Oxitec，LLC知识产权的显性致死性昆虫（RIDL）。RIDL依赖于 大量释放雄性Ae.埃及蚊;与野生雌蚊交配产生的后代作为晚期幼虫死亡 或者是脓包虽然田间试验已经证明了成功的种群抑制，但广泛传播的障碍 该技术的使用包括监测困难、释放的男性的竞争力、使用抗生素的成本 在工厂规模上抑制致死表型，并在释放后迅速恢复蚊子种群 停止。模型表明，释放病原体抗性蚊子后，人口抑制 运动可以导致抗性表型的建立，即所谓的“减少和替换”方法 可以更持久地阻断病毒传播开发一个减少和替换系统，用于控制 登革热/寨卡病毒传播，Ae.将建立埃及（目标1）。 不像目前的方法，其中释放的雄性的工厂规模饲养必须在存在的情况下发生， 四环素，这种方法需要抗生素的使用，只有在鸡蛋生产的殖民地， 降低成本。早期胚胎致死性反过来将简化监测方法。该项目还将开发 一种感染后死亡的Ae病毒埃及，将提供广泛的抵抗所有蚊子传播的 黄病毒（Aim 2）。这种创新的方法利用了在导航方面已经取得的进展， 转基因Ae.埃及通过巴西的监管程序，预计将开发的产品 在这项工作结束时直接进入基于现场的测试的风险评估过程。

Abstract: Aedes mosquitoes continue to transmit viruses such as dengue, Zika and yellow fever, with much of the world’s population at risk. This is particularly true in Brazil, where dengue epidemics are continuous, where the Zika epidemic hit hardest, and where urban yellow fever continually threatens to re-emerge. In order to establish new vector control strategies, Brazil has pioneered the testing and approval of a new strategy called Release of Insects with Dominant Lethality (RIDL), based on the intellectual property of Oxitec, LLC. RIDL relies on the mass release of male Ae. aegypti mosquitoes; mating with wild females results in progeny that die as late larvae or pupae. While field trials have demonstrated successful population suppression, obstacles to the widespread use of the technology include difficulty in monitoring, competitiveness of released males, cost of antibiotic used to suppress the lethal phenotype at factory scale, and rapid recovery of the mosquito population once releases cease. Modeling suggests that the release of pathogen-resistant mosquitoes following a population suppression campaign can result in the establishment of the resistance phenotype, a so called “reduce and replace” approach that could more permanently block transmission. To develop a reduce and replace system for the control of dengue/Zika transmission, a transgenic conditional sterility system in Ae. aegypti will be established (Aim 1). Unlike current approaches where factory-scale rearing of released males must occur in the presence of tetracycline, such an approach necessitates antibiotic use only in the egg production colony, substantially reducing costs. Early embryonic lethality will in turn simplify monitoring approaches. This project will also develop a death-upon-infection strain of Ae. aegypti that will provide broad resistance across all mosquito-borne flaviviruses (Aim 2). This innovative approach takes advantage of progress already made in navigating transgenic Ae. aegypti through the regulatory process in Brazil, and the products to be developed are anticipated to directly enter the risk assessment process for field-based testing at the conclusion of this work.