The Burden of Chikungunya and Dengue Transmission, Infection and Disease in Kenya

描述（由申请人提供）：节肢动物传播的病毒，如登革热（DENV）和基孔肯雅（CHIKV）病毒的暴发表明，这些新出现/再出现的健康威胁对发展中国家和发达国家造成了巨大的成本和健康负担。在撒哈拉以南非洲，由于误诊的可能性很高，而且在不同地区和不同易感人群中传播的程度未知，对这些疾病的常规被动监测只能检测到其影响的一小部分。已知和未知的昆虫学、环境和行为因素在不同生境中导致传播的差异。我们假设，DENV和CHIKV造成的重大人类疾病负担在临床环境中未被发现，导致错过了预防机会，并增加了大规模暴发的风险。初步数据表明，肯尼亚儿童和成人在已知暴发之间和期间经常暴露于DENV和CHIKV，尽管在这种情况下很少诊断出急性虫媒病毒感染。我们的目标是评估与肯尼亚DENV 1-4毒株和CHIKV有关的人类疾病的真正负担，然后确定病毒传播的驱动因素，估计爆发开始的阈值，并提供改进的爆发风险评估。我们将调查CHIKV和DENV1-4在肯尼亚两个地区的传播情况，这两个地区代表了不同程度的城市化，具有不同的景观、气候和人口。采用几种新方法，我们实现了以下目标：1)量化由CHIKV和DENV1-4引起的人类感染和疾病的发生率，并确定它们对急性发热性疾病的相对贡献；2)测量肯尼亚境内伊蚊媒介中CHIKV和DENV1- 4的传播水平，并估计人类媒介接触量；3)通过将人类传播数据（目标1）和媒介传播数据（目标2）与现场和使用卫星图像收集的环境和天气/气候数据相结合，检测和预测农村和城市环境中CHIKV和DENV传播的时空格局。这项研究涉及全年存在虫媒病毒传播的肯尼亚Msambweni（沿海）和Kisumu（西部）及其附近的队列，并以10年的纵向合作研究为基础。方法包括分析定义明确的昆虫学、临床、流行病学和气候学发现与病毒和蚊子暴露的免疫生物标志物之间的关系。这些研究将填补关于CHIKV和DENV在当地栖息地持续存在的知识空白，以及在流行间期导致持续存在和在流行期间造成区域差异的因素。这些数据还将回答有关高危人群重症发热综合征虫媒病毒病因学的基本问题，同时更好地估计相关疾病负担和长期后遗症。

DESCRIPTION (provided by applicant): 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 the developing and developed world. In sub-Saharan Africa, routine passive surveillance for these diseases detects only a fraction of their impact, given the high probability of misdiagnosis and unknown levels of transmission across different landscapes and within different susceptible populations. Known and unknown entomologic, environmental, and behavioral factors differentially drive transmission in different habitats. We hypothesize that a significant burden of human disease due to DENV and CHIKV is undetected in the 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 to DENV and CHIKV, both between and during known outbreaks, although acute arboviral infections are rarely diagnosed in this setting. Our objectives are to assess the true burden of human disease related to DENV strains 1-4 and for CHIKV across Kenya, and then to determine the drivers of viral circulation, estimate the thresholds for outbreak initiation, and provide improved outbreak risk assessment. We will investigate transmission of CHIKV and DENV1-4 in two regions of Kenya that represent heterogeneous degrees of urbanization with varied landscape, climate, and populations. Using several novel approaches, we address the following aims: 1) Quantify the incidence of human infection and disease due to CHIKV and DENV1-4 and determine their relative contribution to acute febrile illness; 2) Measure the level of CHIKV and DENV1- 4 circulation in Aedes mosquito vectors and estimate the amount of human-vector contact in Kenya; and 3) Detect and predict spatial and temporal patterns of CHIKV and DENV transmission in rural and urban settings by integrating data on circulation in humans (Aim 1) and vectors (Aim 2) with environmental and weather/climate data collected both in situ and using satellite imagery. 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 collaborative longitudinal 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 the factors that contribute to persistence during inter- epidemic periods and to regional variation during epidemic periods. The data will also answer fundamental questions about arboviral etiologies in severe fever syndromes among at-risk populations while providing better estimates of related disease burden and long-term sequelae.