African trypanosomiasis impacts both human and animal health in Sub-Saharan Africa. Uganda is the only country that has both forms of the human African trypanosomiasis (HAT): Trypanosoma brucei gambiense (Tbg) in the north-west and Trypanosoma brucei rhodesiense (Tbr) in the south-east. Tbr cases have been migrating from their traditional foci in the south to central Uganda, with the two disease belts feared to merge in northern Uganda. This interdisciplinary project focuses on northern Uganda to understand HAT transmission dynamics and risk of Tbr and Tbg disease merger. Our findings will provide fundamental knowledge on the role of the vector in HAT epidemiology, and provide practical information to inform the development and implementation of effective control strategies. We propose five integrated aims to: 1) Analyze the genomic variation in Gff, its associated microbiome and parasite (Trypanosoma) using a multispecies SNP chip, 2) Characterize the expression and genetic variations of the Trypanosoma-resistance candidate genes in different Gff population groups, 3) Discover gene-environment associations and impacts of climate change on Ugandan Gff, 4) Understand genetic as well as microbiome contributions for differentiation of Gff populations and 5) Assess the impact of Gff dispersal on the effectiveness and cost-effectiveness of vector control for reducing trypanosomiasis burden. Our studies will produce 1) fundamental information on host-parasite interactions that will predict the potential risk of disease merger and its epidemiological consequences, 2) suitability maps for Gff based on genetic and environmental data to better plan and operate vector control activities, 3) candidate genes on parasite-resistance, environmental adaptations that can be used in downstream genetic control methods and 4) predictions on the most effective and cost-effective control methods for HAT.

Public Health Relevance

Uganda is the only country that has both forms of the human African trypanosomiasis (HAT): Trypanosoma brucei gambiense (Tbg) in the north-west and Trypanosoma brucei rhodesiense (Tbr) in the south-east. The two disease belts feared to merge in northern Uganda, which would exacerbate the public health HAT burden. This interdisciplinary study will provide knowledge on the vector population dynamics and vector-parasite interactions, on the genetic and environmental parameters most fundamental to disease spread, and on the most appropriate and cost-effective methods for control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI068932-10
Application #
9415457
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2008-01-15
Project End
2019-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
10
Fiscal Year
2018
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
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Opiro, Robert; Saarman, Norah P; Echodu, Richard et al. (2016) Evidence of temporal stability in allelic and mitochondrial haplotype diversity in populations of Glossina fuscipes fuscipes (Diptera: Glossinidae) in northern Uganda. Parasit Vectors 9:258
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
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

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