Control of Tsetse Fly Transmitted Diseases in Kenya

 描述(申请人提供)：本申请涉及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高度被忽视的热带病，几十年来一直困扰着人类和动物的健康。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子出没地区的数百万人的营养和经济繁荣，包括在肯尼亚。目前尚不存在哺乳动物疫苗，目前的杀锥虫药物治疗具有不良副作用，治疗失败的报告越来越多。由于疾病控制的积极监测活动在经济上将不再可持续，肯尼亚等疾病流行国家(DECs)必须在低流行时期制定和实施方案，以防止未来出现流行病。目前最有效的HAT/AAT控制方法包括减少采采集媒介种群。虽然媒介生物控制可以减少疾病，但除非能够提高传统工具(诱捕器和靶标)的效率，否则在采采蝇出没的广大地区实施媒介控制可能是不划算的。此外，必须制定战略计划，以确定控制目标单位及其在时间和空间上的动态，以防止来自邻近地点的苍蝇在开垦的土地上重新定居。耶鲁大学和肯尼亚农业研究所-锥虫病研究中心(KARI-TRC)的科学家一直在合作，在肯尼亚建设生物医学研究专长的能力，以解决寄生虫传播生物学、媒介能力遗传学、化学生态学、种群生物学和与采采虫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政策决策。该应用程序是成功合作开发两个研究项目的产物，该研究项目具有针对HAT控制的即时翻译应用程序。我们将：(1)扩展采采集种群控制的工具箱：这些研究将1)利用最新的基因组和功能遗传发现来了解采采集的化学传感生理，并识别和测试新的气味，以提高用于采采集种群控制的陷阱和靶标的效率，以及2)评估使用这些增强的控制工具来减少采采集种群的成本效益。(2)开发决策支持系统(DSS)以监测肯尼亚采采热传播疾病的风险。该项目将根据采采集媒介种群之间的遗传连通性水平、考虑采采集种群之间功能连通性的生境适宜性、循环寄生虫流行率和菌株多样性以及采采集微生物区系组成，开发具有流行病学意义的决策支持系统。将根据采采热的时空动态和获得的监测数据，开发一个数学疾病传播模型，以评估HAT在肯尼亚再次出现的可能性。

 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.