Human African trypanosomiasis (HAT) kills thousands of people each year in sub-Saharan Africa. The disease is caused by African trypanosomes transmitted by the tsetse fly. HAT transmission is complex;it requires mammalian and invertebrate hosts and involves domestic and wild reservoirs. No mammalian vaccines exist and therapeutic drugs have serious side effects with increasing resistance seen in patients. In contrast, reduction of tsetse populations is highly efficacious for disease control. However, the implementation of the tsetse control programs, which rely on traps and targets, have been difficult to sustain because they are not practical and require extensive community participation. A paratransgenic strategy has been developed which exploits the unique biology of tsetse and its maternally inherited bacterial symbionts. In this strategy, tsetse's mutualist symbiont Sodalis is harnessed to express trypanosome inhibitory molecules in tsetse's midgut to impair trypanosome transmission. Transgenic Sodalis bacterium conferring refractoriness may be driven into natural tsetse populations by cytoplasmic incompatibility phenomenon mediated by tsetse's symbiont, Wolbachia. We propose to investigate the biogeography of the human disease vector species, Glossina fuscipes fuscipes, its Trypanosoma parasite(s), and its Wolbachia and Sodalis symbionts. Using a combination of laboratory and field experiments, we will investigate the potential for a Wolbachia mediated gene-drive mechanism to aid in the application of paratransgenic flies. In addition, we will elucidate the basic genetic structure of this human disease vector population, for which no information exists. This information is necessary for the efficacious implementation and monitoring of either the traditional or novel control strategies. Knowledge obtained on symbiont biology, maternal linkage of tsetse's multiple symbionts, Wolbachia infection phenotype, potential strength of Wolbachia mediated drive, population genetics and epidemiological dynamics will provide the parameters needed to develop a mathematically based model framework. This model will allow us to test the predictive nature of the empirical data, design the optimal strategies for population control, and predict feasibility and robustness for the success of the replacement strategy. This interdisciplinary application will combine epidemiology, population genetics and modeling with model parameterization and verification from laboratory and field research.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IDM-M (02))
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Costero, Adriana
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Yale University
Public Health & Prev Medicine
Schools of Medicine
New Haven
United States
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Kamidi, Christine M; Auma, Joanna; Mireji, Paul O et al. (2018) Differential virulence of camel Trypanosoma evansi isolates in mice. Parasitology 145:1235-1242
Saarman, Norah; Burak, Mary; Opiro, Robert et al. (2018) A spatial genetics approach to inform vector control of tsetse flies (Glossina fuscipes fuscipes) in Northern Uganda. Ecol Evol 8:5336-5354
Gloria-Soria, Andrea; Dunn, W Augustine; Yu, Xiaoqing et al. (2018) Uncovering Genomic Regions Associated with Trypanosoma Infections in Wild Populations of the Tsetse Fly Glossina fuscipes. G3 (Bethesda) 8:887-897
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
Manangwa, Oliver; Nkwengulila, Gamba; Ouma, Johnson O et al. (2017) Genetic diversity of Glossina fuscipes fuscipes along the shores of Lake Victoria in Tanzania and Kenya: implications for management. Parasit Vectors 10:268
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
Opiro, Robert; Saarman, Norah P; Echodu, Richard et al. (2017) Genetic diversity and population structure of the tsetse fly Glossina fuscipes fuscipes (Diptera: Glossinidae) in Northern Uganda: Implications for vector control. PLoS Negl Trop Dis 11:e0005485
Gloria-Soria, Andrea; Dunn, W Augustine; Telleria, Erich L et al. (2016) Patterns of Genome-Wide Variation in Glossina fuscipes fuscipes Tsetse Flies from Uganda. G3 (Bethesda) 6:1573-84
Aksoy, Emre; Vigneron, Aurélien; Bing, XiaoLi et al. (2016) Mammalian African trypanosome VSG coat enhances tsetse's vector competence. Proc Natl Acad Sci U S A 113:6961-6

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