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 蚊虫控制仍然是对抗许多蚊媒疾病的主要工具， 登革热，基孔肯雅，寨卡和西尼罗河，因为没有批准的疫苗，治疗剂或预防措施， 目前可供使用。现有病媒控制方法的主要缺陷包括对现有病媒的耐药性 杀虫剂和无法找到和处理神秘的繁殖地点，这为未成熟的 在常规的控制措施之后，可以迅速恢复蚊子的数量。的 一种称为“自动传播”的自我传播方法解决了这一缺陷， 这是一种将强效蚊子生长调节剂运送到隐蔽繁殖地点的载体。第一阶段的结果是 包括试验性实验室和实地工作，作为对埃及伊蚊和伊蚊的原理证明， 白纹伊蚊 寨卡病毒的流行病学导致迫切需要先发制人的媒介控制方法。 具体而言，人类中的大多数寨卡病毒感染不会很快被发现。延迟检测可以 破坏基于反应性方法的公共卫生保护计划，即，一种战略， 只有在发现流行病之后才进行密集的病媒控制，因为到发现时， 一部分人已经被感染了。在拟议的 工作作为先发制人的方法是理想的，因为（1）它需要少量的化学品，即，少 环境影响，以及（2）人工饲养的蚊子载体可以在任何时间递送，例如，之前 本地病媒种群达到危险水平。 “雄性自动传播增强”（ADAM）是基于大量生产雄性蚊子， 它们不会叮咬或传播病原体。ADAM方法可以利用野生型蚊子，沃尔巴克氏体- 受感染的蚊子或转基因蚊子。与现有蚊子大规模饲养相结合 项目可以加速ADAM技术的应用。成年ADAM雄性用昆虫生长 调节剂（IGR），然后释放以将致死剂量的IGR递送到产卵部位。第一阶段工作 包括：1）实验室开发，2）监管工作，例如，研究授权的批准 加州农药法规部，3）在肯塔基州对Ae.白纹伊蚊，和4）在 与联合清真寺消除区（CMAD）合作，测试ADAM方法， AE.埃及人。实验结果表明，Ae. albopictus，Ae.埃及库蚊和尖音库蚊雄性可以：1） 耐受IGR，对雄性携带者的成本可以忽略不计，2）直接将杀幼虫剂递送到繁殖地点，以及3） 用IGR剂量交叉污染雌性，随后对幼虫致命。现场试验与两个AE。 埃及伊蚊和埃及伊蚊。白纹伊蚊表现出ADAM方法引起显著幼虫死亡率和显著 与未处理部位相比，成年人群减少。第一阶段的工作还包括 改进大规模生产成年雄蚊的方法。 在拟议的第二阶段工作中，我们将开展工作，复制和扩大对Ae的田间试验。 埃及伊蚊和埃及伊蚊。白纹伊蚊，从原理验证试验到足以供操作使用的规模， 灭蚊区。通过对来自不同州的多个减排区进行实地试验， 我们建议的第二阶段工作将满足EPA对商业注册的要求，即，疗效和 在多种生态环境中证明安全性。除了环保署，数据将提交给 世界卫生组织（世卫组织）病媒控制咨询小组，作为一个咨询机构 新的病媒控制方式世卫组织的批准预计将增加国际上对自动协调机制的接受 技术.额外的第二阶段工作将扩展第一阶段与Cx的工作。pipiens，一个重要的载体西方 尼罗河病毒。具体而言，一项或多项田间试验将提供针对这种额外的， 这是防治蚊患工作的另一个重点。