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.

Public Health Relevance

Tsetse fly transmitted African trypanosomiasis is one of the most neglected diseases of sub-Sahara Africa, including Kenya, which has plagued human and animal health for decades. As active case finding is not economically sustainable during periods of endemicity, it is imperative that Kenya develops and implements an epidemiologically appropriate control program to prevent re-emergence of epidemics. This interdisciplinary application will develop an efficient and environmentally acceptable strategy based on improved vector control tools and a soundly informed decision support system (DSS) to help Kenya maintain a HAT-free status and decrease AAT burden.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI115648-03
Application #
9197955
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2015-01-01
Project End
2019-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Kamidi, Christine M; Auma, Joanna; Mireji, Paul O et al. (2018) Differential virulence of camel Trypanosoma evansi isolates in mice. Parasitology 145:1235-1242
Okeyo, Winnie A; Saarman, Norah P; Bateta, Rosemary et al. (2018) Genetic Differentiation of Glossina pallidipes Tsetse Flies in Southern Kenya. Am J Trop Med Hyg 99:945-953
Griffith, Bridget C; Weiss, Brian L; Aksoy, Emre et al. (2018) Analysis of the gut-specific microbiome from field-captured tsetse flies, and its potential relevance to host trypanosome vector competence. BMC Microbiol 18:146
Kamidi, Christine M; Saarman, Norah P; Dion, Kirstin et al. (2017) Multiple evolutionary origins of Trypanosoma evansi in Kenya. PLoS Negl Trop Dis 11:e0005895
Richardson, Joshua Brian; Lee, Kuang-Yao; Mireji, Paul et al. (2017) Genomic analyses of African Trypanozoon strains to assess evolutionary relationships and identify markers for strain identification. PLoS Negl Trop Dis 11:e0005949
Okeyo, Winnie A; Saarman, Norah P; Mengual, Michael et al. (2017) Temporal genetic differentiation in Glossina pallidipes tsetse fly populations in Kenya. Parasit Vectors 10:471
Bateta, Rosemary; Wang, Jingwen; Wu, Yineng et al. (2017) Tsetse fly (Glossina pallidipes) midgut responses to Trypanosoma brucei challenge. Parasit Vectors 10:614
Wachira, Benson M; Mireji, Paul O; Okoth, Sylvance et al. (2016) Responses of Glossina pallidipes and Glossina morsitans morsitans tsetse flies to analogues of ?-octalactone and selected blends. Acta Trop 160:53-7
Gilbert, Jennifer A; Medlock, Jan; Townsend, Jeffrey P et al. (2016) Determinants of Human African Trypanosomiasis Elimination via Paratransgenesis. PLoS Negl Trop Dis 10:e0004465