Phase II: Feasibility assessment of a novel tool for mosquito vector control: Auto-Dissemination Augmented by Males (ADAM)

项目摘要/摘要 控制蚊子仍然是防治许多由蚊子传播的疾病的主要工具，例如 登革热、基孔肯雅热、寨卡病毒和西尼罗河病毒，因为没有批准的疫苗、疗法或预防措施 目前可供使用。现有媒介生物控制方法的主要缺陷包括抵抗现有的 杀虫剂以及无法找到和治疗隐秘的繁殖地，这为幼稚提供了避难所 它可以减少蚊子的数量，并使蚊子数量在常规控制措施后迅速恢复。这个 通过使用蚊子作为“自动传播”的自我传递方法来解决这一缺陷 将一种有效的蚊子生长调节剂运送到神秘的滋生地点的车辆。第一阶段的结果包括 包括试验性实验室和实地工作，作为对抗埃及伊蚊和伊蚊的原则证明 白纹伊蚊。 寨卡病毒的流行病学导致迫切需要采取预防性的媒介控制方法。 具体地说，大多数寨卡病毒在人类中的感染并没有被迅速检测到。延迟检测可能 破坏以被动方式为基础的公共卫生保护计划，即启动战略 只有在检测到疫情后才会进行密集的媒介控制，因为在检测到 人类人口的比例已经可以被感染了。拟议中正在开发的方法 工作作为一种先发制人的方法是理想的，因为(1)它需要少量的化学物质，即更少 环境影响和(2)人工饲养的蚊子携带者可以在任何时间，例如在 土著病媒人口已达到危险水平。 “雄性增强的自动传播”(ADAM)是基于大规模生产的雄性蚊子， 它们不会叮咬或传播病原体。亚当方法可以利用野生型蚊子沃尔巴克氏菌- 受感染的蚊子或转基因蚊子。与现有的蚊子大规模饲养相结合 这些计划可以加快ADAM技术的普及。成年雄性亚当接受昆虫生长治疗 然后释放，将致死剂量的IGR输送到产卵地点。第一阶段工作 包括：1)实验室开发，2)监管工作，例如，批准研究授权 加州农药法规，3)在肯塔基州进行的田间试验。白纹伊蚊，以及4)在 与综合灭蚊区(CMAD)合作，测试ADAM方法，以防止 天哪。埃及伊蚊。实验室结果表明，Ae.白纹伊蚊Ae.埃及伊蚊和淡色库蚊雄蚊可以：1) 耐受IGR，对雄性携带者的成本微乎其微；2)直接将杀幼虫剂输送到繁殖地；3) 用IGR剂量交叉感染雌虫，随后对幼虫致死。田间试验均为Ae. Aegypti和Ae.白纹伊蚊显示ADAM法对幼虫造成显著的死亡率和显著的 与未经治疗的地点相比，成年人口的减少。第一阶段的工作还包括 成虫雄蚊批量生产方法的改进。 在拟议的第二阶段工作中，我们将开展复制和扩大针对Ae的现场试验的工作。 Aegypti和Ae.白化病，从原则证明试验到足以由 蚊子消除区。通过与来自不同州的多个减排区进行田间试验， 我们建议的第二阶段工作将满足美国环保局对商业注册的要求，即 在多个生态背景下展示安全性。除了环保局，这些数据还将提交给 作为咨询机构的世界卫生组织(世卫组织)病媒控制咨询小组 关于新形式的病媒控制。世界卫生组织的批准预计将增加ADAM的国际接纳量 技术额外的第二阶段工作将延长与CX的第一阶段工作。西方的重要媒介--蚊子 尼罗河病毒。具体地说，一项或多项田间试验将提供药效数据，用于对抗这一额外的、 重要的蚊子种类，这是消减地区病媒控制工作的另一个重点。

Project summary/abstract Mosquito control remains the primary tool for combating many mosquito-vectored diseases, such as Dengue, Chikungunya, Zika, and West Nile, because no approved vaccine, therapeutant or prophylaxis is currently available for use. Key deficiencies of existing vector control methods include resistance to existing insecticides and the inability to find and treat cryptic breeding sites, which provide refuge to immature mosquitoes and allow for the rapid recovery of mosquito populations following conventional control efforts. The self-delivering method known as `auto-dissemination' addresses this deficiency by using mosquitoes as the vehicle to deliver a potent mosquito growth regulator to cryptic breeding sites. The Phase 1 results have included pilot laboratory and field work, as a proof-of-principle against both Aedes aegypti and Aedes albopictus. The epidemiology of Zika has led to an urgent need for preemptive vector control approaches. Specifically, a majority of Zika virus infections in humans are not detected quickly. Delayed detection can undermine a public health protection plan that is based on reactive approaches, i.e., a strategy of initiating intensive vector control only after the detection of an epidemic, because by the time of detection, a large proportion of the human population can be infected already. The approach being developed in the proposed work is ideal as a preemptive approach, because (1) it requires small amounts of chemical, i.e., less environmental impact and (2) the artificially-reared mosquito carriers can be delivered at any time, e.g., before an indigenous vector population reaches dangerous levels. The “Auto-Dissemination Augmented by Males” (ADAM) is based on mass-producing male mosquitoes, which do not bite or transmit pathogens. The ADAM method can utilize wild type mosquitoes, Wolbachia- infected mosquitoes or Genetically Modified mosquitoes. Integration with existing mosquito mass rearing programs can speed the uptake of the ADAM technology. Adult ADAM males are treated with an Insect Growth Regulator (IGR) and then released to deliver lethal doses of the IGR to oviposition sites. Phase I work included: 1) laboratory development, 2) regulatory work, e.g., approval of a Research Authorization from the California Department of Pesticide Regulation, 3) field trials in KY against Ae. albopictus, and 4) field trials in collaboration with the Consolidated Mosquito Abatement District (CMAD) to test the ADAM approach against Ae. aegypti. The laboratory results show that Ae. albopictus, Ae. aegypti, and Culex pipiens males can: 1) tolerate the IGR with negligible cost to the male carriers, 2) directly deliver larvicide to breeding sites, and 3) cross-contaminate females with IGR doses that are subsequently lethal to larvae. Field trials with both Ae. aegypti and Ae. albopictus show the ADAM method to cause significant larval mortality and significant reductions in the adult population, when compared to the non-treated sites. Phase 1 work also included an improvement of methods for the mass manufacturing of adult male mosquitoes. In the proposed Phase II work, we will conduct work to replicate and expand field trials against Ae. aegypti and Ae. albopictus, from proof-of-principle trials to a scale that is adequate for operational use by mosquito abatement districts. By performing field trials with multiple abatement districts from different states, our proposed Phase II work will satisfy an EPA requirement for commercial registration, i.e., that efficacy and safety be demonstrated in multiple ecological contexts. In addition to the EPA, the data will be submitted to the World Health Organization (WHO) Vector Control Advisory Group (VCAG), which serves as an advisory body on new forms of vector control. WHO approval is anticipated to increase international uptake of the ADAM technology. Additional Phase II work will extend Phase I work with Cx. pipiens, an important vector of West Nile Virus. Specifically, one or more field trials will provide efficacy data for use against this additional, important mosquito species, which is another focus of abatement districts' vector control efforts.