Control of Tsetse Fly Transmitted Diseases in Kenya

 描述（由申请人提供）：本申请旨在制定可持续控制采采蝇传播的非洲锥虫病的战略，这是撒哈拉以南非洲地区高度被忽视的热带病（NTD），数十年来一直困扰着人类和动物健康。由非洲锥虫寄生虫引起的人类疾病（HAT）是致命的，而由相关寄生虫引起的动物疾病（AAT）阻碍了农业发展，并限制了生活在采采蝇出没地区（包括肯尼亚）的数百万人的营养和经济繁荣。没有哺乳动物疫苗存在，目前的杀锥虫药物治疗具有不期望的副作用，治疗失败的报道越来越多。由于积极的疾病控制监测活动将不再具有经济可持续性，疾病流行国家（DEC），如肯尼亚，必须在低流行期制定和实施计划，以防止未来流行病的出现。目前最有效的HAT/AAT控制方法涉及减少采采蝇媒介种群。虽然病媒控制可以减少疾病，但在舌蝇出没的大片地区实施控制可能会带来成本限制，除非可以提高所使用的传统工具（陷阱和目标）的效率。此外，必须制定战略计划来识别控制目标单元及其动态。随着时间和空间的推移，以防止来自邻近地点的苍蝇重新定居已清理的土地。耶鲁大学和肯尼亚农业研究所-锥虫研究中心的科学家一直在合作，在肯尼亚建设生物医学研究专门知识方面的能力，以解决寄生虫传播生物学、病媒能力遗传学、化学生态学、种群生物学和与采采蝇病媒和锥虫寄生虫有关的生物信息学问题，并促进以科学证据为导向的公共卫生决策。该应用程序是这一成功合作的产物，开发了两个研究项目，用于HAT控制的即时翻译应用。我们将：（1）扩大可用于舌蝇种群控制的工具箱：这些研究将1）利用最近的基因组和功能遗传学发现来了解舌蝇的化学感觉生理学，并识别和测试新的气味，以提高用于舌蝇种群控制的陷阱和目标的效率，以及2）评估使用这些增强的控制工具减少舌蝇种群的成本效益。(2)建立一个决策支持系统，以监测肯尼亚采采蝇传播疾病的风险。该项目将根据采采蝇病媒种群之间的遗传连接水平、解释采采蝇种群之间功能连接的生境适宜性、循环寄生虫流行率和菌株多样性以及采采蝇微生物群组成，开发一个流行病学相关的DSS。将根据采采蝇的时空动态和获得的监测数据，开发一个疾病传播数学模型，以评估肯尼亚HAT重新出现的概率。

 DESCRIPTION (provided by applicant): This application addresses the development of strategies for the sustainable control of tsetse fly-transmitted African trypanosomiasis, which is highly Neglected Tropical Disease (NTD) in sub-Sahara Africa that has plagued human and animal health for decades. Human disease (HAT) caused by African trypanosome parasites are fatal, while the animal disease (AAT) caused by related parasites impede agricultural development and restrict nutrition and economic prosperity for millions of people living in tsetse-infested areas, including in Kenya. No mammalian vaccines exist, and current trypanocidal drug treatments have undesirable side effects with growing reports of treatment failures. As active surveillance campaigns for disease control will no longer be economically sustainable, disease endemic countries (DECs), such as Kenya, must develop and implement programs during periods of low endemicity to prevent the emergence of future epidemics. The most effective current HAT/AAT control methods involve reduction of tsetse vector populations. While vector control can reduce disease, its implementation over vast areas infested by tsetse can be cost prohibiting unless the efficiency of the traditional tools used (traps and targets) can be improved Additionally, a strategic plan must be developed to identify the control target units and their dynamics over time and space to prevent recolonization of cleared lands with flies from neighboring sites. Yale University and the Kenyan Agricultural Research Institute-Trypanosomiasis Research Center (KARI-TRC) scientists have been collaborating to build capacity in Kenya on biomedical research expertise to address parasite transmission biology, genetics of vector competence, chemical ecology, population biology and bioinformatics related to tsetse vectors and trypanosome parasites, and to promote scientific evidence-driven public health policy decisions. This application is a product of this successful collaboration to develop two research projects with immediate translational applications for HAT control. We will: (1) Expand the toolbox available for tsetse population control: These studies will 1) exploit recent genomic and functional genetic discoveries to understand tsetse's chemosensory physiology and identify and test new odors to improve the efficiency of traps and targets used for tsetse population control, and 2) evaluate the cost-effectiveness of using these enhanced control tools for tsetse population reduction. (2) Develop a Decision Support System (DSS) to monitor tsetse transmitted disease risk in Kenya. This project will develop an epidemiologically relevant DSS based on levels of genetic connectivity among tsetse vector populations, habitat suitability that accounts for the functional connectivity between tsetse populations, circulating parasite prevalence and strain diversity as well as tsetse microbiota composition. A mathematical disease transmission model will be developed to evaluate the probability of HAT re-emergence in Kenya based on spatiotemporal dynamics of tsetse and surveillance data obtained.