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

第二阶段：蚊媒控制新工具的可行性评估：雄性自动传播（ADAM）

• 批准号: 9255783
• 负责人: Patrick Kelly
• 金额: $ 59.72万
• 依托单位: MOSQUITOMATE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9255783
• 关键词: Abate; Address; Adult; Aedes; Affect; Animals; Attention; Authorization documentation; Behavior; Blood; Breeding; California; Chemicals; Chikungunya virus; Collaborations; Culex (Genus); Culex pipiens; Culicidae; Dangerousness; Data; Dengue; Dengue Virus; Detection; Disease; Disease Vectors; Dose; Environmental Impact; Epidemic; Epidemiology; Face; Female; Florida; Flowers; Goals; Growth; Health protection; Human; Indigenous; Insecta; Insecticide Resistance; Insecticides; International; Juvenile Hormones; Laboratories; Larva; Lead; Measurement; Measures; Methods; Minor; Monitor; Mosquito Control; Mosquito-borne infectious disease; Native-Born; Outcome; Oviposition; Partner in relationship; Pesticides; Phase; Plant Leaves; Population; Practice Management; Production; Prophylactic treatment; Public Health; Recommendation; Recovery; Regulation; Research; Resistance; Risk; Safety; Site; Speed; Sterility; Techniques; Technology; Testing; Time; Trees; Vaccines; Virus Diseases; Visit; Water; West Nile virus; Wolbachia; Work; World Health Organization; Zika Virus; base; chikungunya; combat; commercialization; cost; drinking water; experimental study; feeding; killings; laboratory development; male; meetings; milliliter; mortality; novel; pathogen; programs; success; tool; uptake; vector; vector control; vector mosquito; wasting

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.

项目概要/摘要 灭蚊仍然是对抗蚊媒疾病的主要工具，例如 登革热、基孔肯雅热、寨卡病毒和西尼罗河病毒，因为尚无批准的疫苗、治疗或预防措施 目前可供使用的现有病媒控制方法的主要缺陷包括对现有病媒的抵抗力。 杀虫剂以及无法找到和处理为未成熟动物提供庇护的加密繁殖地 蚊子，并允许在常规控制努力后蚊子种群迅速恢复。 被称为“自动传播”的自我传播方法通过使用蚊子作为媒介来解决这一缺陷。 向神秘繁殖地提供有效的蚊子生长调节剂的车辆，第一阶段的结果已经公布。 包括试点实验室和现场工作，作为针对埃及伊蚊和伊蚊的原理验证 白纹伊蚊。 寨卡病毒的流行病学导致迫切需要采取先发制人的病媒控制方法。 具体来说，人类中的大多数寨卡病毒感染都无法快速检测到，延迟检测是可以的。 破坏基于反应性方法的公共卫生保护计划，即启动策略 仅在发现流行病后才进行强化病媒控制，因为到发现时，大量病媒 拟议中正在开发的方法已经有一定比例的人口可能被感染。 作为一种先发制人的方法，工作是理想的，因为 (1) 它需要少量的化学品，即更少 (2)人工饲养的蚊媒可以随时交付，例如在 本土病媒种群达到危险水平。 “雄性自动传播增强型”（ADAM）基于大规模生产雄性蚊子， ADAM 方法可以利用野生型蚊子 Wolbachia-。 受感染的蚊子或转基因蚊子与现有的蚊子群饲养相结合。 项目可以加速 ADAM 技术的吸收，成年 ADAM 雄性接受昆虫生长治疗。 调节剂（IGR），然后释放以将致死剂量的 IGR 输送到产卵部位，进行第一阶段的工作。 包括：1) 实验室开发，2) 监管工作，例如，批准研究授权 加州农药管理部，3) 在肯塔基州针对白纹伊蚊进行的田间试验，以及 4) 在肯塔基州进行的田间试验。 与综合灭蚊区 (CMAD) 合作测试 ADAM 方法 实验室结果显示，白纹伊蚊、埃及伊蚊和淡色库蚊可以： 1) 耐受 IGR，且雄性携带者的成本可以忽略不计，2) 直接将杀幼剂递送至繁殖地，以及 3) 使用 IGR 剂量交叉污染雌性，随后对两种伊蚊幼虫进行了致命性的田间试验。 埃及伊蚊和白纹伊蚊表明 ADAM 方法会导致显着的幼虫死亡率和显着的死亡率。 与未处理地点相比，第一阶段工作还包括成年人口的减少。 改进大规模生产成年雄性蚊子的方法。 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。 埃及伊蚊和白纹伊蚊，从原理验证试验到足以供操作使用的规模 通过对不同州的多个灭蚊区进行实地试验， 我们提议的第二阶段工作将满足 EPA 对商业注册的要求，即功效和 除了 EPA 之外，数据还将提交给多个生态环境中的安全性。 世界卫生组织 (WHO) 病媒控制咨询小组 (VCAG)，作为咨询机构 世界卫生组织批准新的病媒控制形式预计将增加 ADAM 的国际接受度。 额外的第二阶段工作将扩展 Cx 的第一阶段工作，Cx 是 West 的一个重要媒介。 具体来说，一项或多项现场试验将提供针对这一额外的功效数据。 重要的蚊种，这是消减地区病媒控制工作的另一个重点。