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

描述(由申请人提供)：由节肢动物传播的病毒，如登革热(DENV)和基孔肯雅(CHIKV)病毒的爆发，表明这些新出现/重新出现的健康威胁对发展中国家和发达国家造成的巨大成本和健康负担。在撒哈拉以南非洲，这些疾病的常规被动监测只能检测到其影响的一小部分，因为误诊的可能性很高，而且在不同的地貌和不同的易感人群中传播的程度未知。已知和未知的昆虫学、环境和行为因素在不同的生境中以不同的方式驱动传播。我们假设，在临床环境中没有发现DENV和CHIKV对人类疾病造成的重大负担，从而导致错失了预防机会，并增加了大规模爆发的风险。初步数据表明，肯尼亚儿童和成人经常在已知疫情期间和期间接触DENV和CHIKV，尽管在这种情况下很少诊断出急性虫媒病毒感染。我们的目标是评估肯尼亚境内与DENV毒株1-4和CHIKV有关的人类疾病的真实负担，然后确定病毒传播的驱动因素，估计暴发开始的阈值，并提供改进的暴发风险评估。我们将调查CHIKV和DENV1-4在肯尼亚两个地区的传播情况，这两个地区代表着不同程度的城市化，具有不同的景观、气候和人口。我们使用几种新的方法解决以下目标：1)量化CHIKV和DENV1-4引起的人类感染和疾病的发病率，并确定它们对急性发烧疾病的相对贡献；2)测量伊蚊媒介中CHIKV和DENV1-4的循环水平，估计肯尼亚人与媒介接触的数量；以及3)通过将关于CHIKV和DENV在农村和城市环境中的传播数据整合(目标1)和媒介(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CHIKV和DENV在农村和城市传播的空间和时间模式。这项研究涉及肯尼亚Msambweni(沿海)和Kisumu(西部)及其附近的队列，那里全年都有虫媒病毒的传播，并基于10年的纵向合作研究。方法包括分析明确的昆虫学、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记物之间的关系。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，以及有助于在流行期间持续存在的因素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中严重发热综合征的虫媒病毒病原学的基本问题，同时提供对相关疾病负担和长期后遗症的更好估计。

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.