Outbreaks of arthropod-borne viruses, such as dengue (DENV) and chikungunya (CHIKV) viruses,demonstrate the substantial cost and health burden of these emerging/re-emerging health threats to thedeveloping and developed world. In sub-Saharan Africa, routine passive surveillance for these diseasesdetects only a fraction of their impact, given the high probability of misdiagnosis and unknown levels oftransmission across different landscapes and within different susceptible populations. Known and unknownentomologic, environmental, and behavioral factors differentially drive transmission in different habitats. Wehypothesize that a significant burden of human disease due to DENV and CHIKV is undetected inthe clinical setting, leading to missed opportunities for prevention and heightened risk for large-scale outbreaks. Preliminary data demonstrate that Kenyan children and adults are frequently exposed toDENV and CHIKV, both between and during known outbreaks, although acute arboviral infections are rarelydiagnosed in this setting. Our objectives are to assess the true burden of human disease related to DENVstrains 1-4 and for CHIKV across Kenya, and then to determine the drivers of viral circulation, estimate thethresholds for outbreak initiation, and provide improved outbreak risk assessment. We will investigatetransmission of CHIKV and DENV1-4 in two regions of Kenya that represent heterogeneous degrees ofurbanization with varied landscape, climate, and populations. Using several novel approaches, we addressthe following aims: 1) Quantify the incidence of human infection and disease due to CHIKV and DENV1-4and determine their relative contribution to acute febrile illness; 2) Measure the level of CHIKV and DENV1-4 circulation in Aedes mosquito vectors and non-human primate reservoirs and estimate the amount ofhuman-vector contact in Kenya; and 3) Detect and predict spatial and temporal patterns of CHIKV andDENV transmission in rural and urban settings by integrating data on circulation in humans (Aim 1) andvectors (Aim 2) with environmental and weather/climate data collected both in situ and using satelliteimagery. This research involves cohorts in and near Msambweni (coastal) and Kisumu (western), Kenya,where there is year-round transmission of arboviruses, and is based on 10 years of collaborativelongitudinal studies. Methodologies include analyses of the relationship between well-defined entomologic,clinical, epidemiologic, and climatologic findings and immune biomarkers of virus and mosquito exposure.These studies will fill knowledge gaps about the persistence of CHIKV and DENV in local habitats and thefactors that contribute to persistence during inter-epidemic periods and to regional variation during epidemicperiods. The data will also answer fundamental questions about arboviral etiologies in severe feversyndromes among at-risk populations while providing better estimates of related disease burden and long-term sequelae.
Worldwide transmission of arthropod-borne viral (arboviral) infections; such as dengueand chikungunya viruses; poses a significant threat to human health that can quickly overwhelmboth local and international public health resources. The proposed studies will assess the trueburden of related human disease of dengue and chikungunya in Kenya; determine the drivers ofviral circulation; identify the thresholds for outbreak initiation; and provide optimized outbreakprediction for more effective disease control. As dengue and chikungunya viruses emerge innew habitats; these studies are relevant not only to current Kenya Ministry of Health publichealth and mosquito control programs; but also to developed country public health and controlprograms and to future dengue and chikungunya vaccine trials.!
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