A central goal of our research is to understand the mechanisms that enable arthropod-borne viruses (arboviruses) to emerge from sylvatic, zoonotic cycles into circulation among humans, thereby causing endemic or epidemic disease. In this project, we will investigate the mechanisms by which 2 arboviruses with important public health impacts, dengue (DENV) and chikungunya viruses (CHIKV), emerge from sylvatic cycles in non-human primates in Senegal to circulate among humans. The results will be critical for assessing the feasibility of strategies to control or eradicate these pathogens when vaccines become available. DENV and CHIKV are ideal viruses to study in tandem in this region because they share vectors and reservoir hosts, their history of emergence has been investigated through extensive genetic studies, and they have been under continuous surveillance in Senegal by the Institut Pasteur since 1972. Endemic/epidemic DENV infects 100 million people per year in over 100 countries, causing classical dengue fever as well as dengue hemorrhagic fever and dengue shock syndrome, while CHIKV has caused recent epidemics involving over 2 million persons with severe arthritic disease. Our previous studies indicate that DENV-1, -2 and -4 evolved independently from ancestral, sylvatic DENV strains that circulate in West Africa and Malaysia, where they are transmitted among nonhuman primate reservoir hosts by arboreal Aedes spp. mosquitoes. Moreover, we have generated phylogenetic evidence that CHIKV originated in Africa, where it persists in a sylvatic cycle, and subsequently spread to Asia where it circulates among humans in urban settings. However the mechanisms involved in generating the endemic/epidemic cycles of each of these viruses are unknown. In the proposed research, we will investigate prospectively the degree and nature of contact between humans and the sylvatic transmission cycles of DENV and CHIKV, and the potential for this contact to lead to emergence. We hypothesize that 3 factors determine the probability of emergence of a sylvatic arbovirus: (i) the temporal and spatial dynamics of the virus in its sylvatic cycle, (ii) the degree of contact between humans and the sylvatic cycle, and (iii) the magnitude of genetic change required for the sylvatic strains to circulate among humans. We will integrate modeling and field studies to generate tools that can be used to predict the risk of human infection and emergence. The results of this multidisciplinary project will improve our understanding of emergence mechanisms of DENV, CHIKV and other zoonotic, sylvatic arboviral pathogens including Zika virus, another arbovirus enzootic in eastern Senegal that recently emerged in Micronesia to cause a DEN-like epidemic. Other major benefits include (i) characterization of a wide variety of arboviral febrile disease etiologies in West Africa, where there is little known about their disease burden;(ii) improved clinical diagnostics in eastern Senegal, (iii) identification of risk factors for arboviral infections, and (iv) training of young American and Senegalese scientists in both field and laboratory approaches to studying emerging arboviral diseases.

Public Health Relevance

We will investigate the mechanisms by which 2 arboviruses with important public health impacts, dengue (DENV) and chikungunya viruses (CHIKV), emerge from a sylvatic cycle in non-human primates in Senegal to circulate among humans. We will investigate prospectively the degree and nature of contact between humans and their sylvatic transmission cycles, and the potential for this contact to lead to emergence. The results will improve our understanding of emergence mechanisms of DENV, CHIKV and other zoonotic, sylvatic arboviral pathogens including Zika virus, another arbovirus enzootic in eastern Senegal that recently emerged in Micronesia to cause a DEN-like epidemic.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI069145-04
Application #
8134774
Study Section
Vector Biology Study Section (VB)
Program Officer
Cassetti, Cristina
Project Start
2008-09-22
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$616,880
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Pathology
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Tsetsarkin, Konstantin A; Chen, Rubing; Weaver, Scott C (2016) Interspecies transmission and chikungunya virus emergence. Curr Opin Virol 16:143-150
Hyde, Jennifer L; Chen, Rubing; Trobaugh, Derek W et al. (2015) The 5' and 3' ends of alphavirus RNAs--Non-coding is not non-functional. Virus Res 206:99-107
Diagne, Cheikh Tidiane; Diallo, Diawo; Faye, Oumar et al. (2015) Potential of selected Senegalese Aedes spp. mosquitoes (Diptera: Culicidae) to transmit Zika virus. BMC Infect Dis 15:492
Althouse, Benjamin M; Hanley, Kathryn A; Diallo, Mawlouth et al. (2015) Impact of climate and mosquito vector abundance on sylvatic arbovirus circulation dynamics in Senegal. Am J Trop Med Hyg 92:88-97
Althouse, Benjamin M; Durbin, Anna P; Hanley, Kathryn A et al. (2014) Viral kinetics of primary dengue virus infection in non-human primates: a systematic review and individual pooled analysis. Virology 452-453:237-46
Faye, Ousmane; Ba, Yamar; Faye, Oumar et al. (2014) Urban epidemic of dengue virus serotype 3 infection, Senegal, 2009. Emerg Infect Dis 20:456-9
Diallo, Diawo; Sall, Amadou A; Diagne, Cheikh T et al. (2014) Patterns of a sylvatic yellow fever virus amplification in southeastern Senegal, 2010. Am J Trop Med Hyg 90:1003-13
Tsetsarkin, Konstantin A; Chen, Rubing; Yun, Ruimei et al. (2014) Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes albopictus mosquitoes. Nat Commun 5:4084
Diagne, Cheikh T; Faye, Oumar; Guerbois, Mathilde et al. (2014) Vector competence of Aedes aegypti and Aedes vittatus (Diptera: Culicidae) from Senegal and Cape Verde archipelago for West African lineages of chikungunya virus. Am J Trop Med Hyg 91:635-41
Diallo, Diawo; Sall, Amadou A; Diagne, Cheikh T et al. (2014) Zika virus emergence in mosquitoes in southeastern Senegal, 2011. PLoS One 9:e109442

Showing the most recent 10 out of 38 publications