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

项目摘要 节肢动物传播病毒的暴发，如登革热(DENV)和基孔肯雅(CHIKV)病毒， 展示这些新出现/重新出现的健康威胁对 发展中国家和发达国家。在撒哈拉以南非洲，对这些疾病的常规被动监测 仅检测到其影响的一小部分，因为误诊的可能性很高，并且未知级别的 在不同的地貌和不同的易感人群中传播。已知和未知 昆虫学、环境和行为因素在不同的栖息地以不同的方式驱动传播。我们 假设由DENV和CHIKV引起的人类疾病的重大负担在 临床环境，导致错失预防机会，并增加大型- 大规模暴发。初步数据显示，肯尼亚儿童和成年人经常接触到 DENV和CHIKV，在已知暴发之间和期间，尽管急性虫媒病毒感染很少 在这种情况下被诊断出来。我们的目标是评估与DENV有关的人类疾病的真正负担 1-4株和肯尼亚境内的CHIKV，然后确定病毒传播的驱动因素，估计 疫情启动的阈值，并提供改进的疫情风险评估。我们会调查的 CHIKV和DENV1-4在肯尼亚两个地区的传播代表了不同程度的 景观、气候和人口多种多样的城市化。使用几种新的方法，我们解决了 以下目标：1)量化CHIKV和DENV1-4引起的人类感染和疾病的发生率 并确定其对急性热病的相对贡献；2)测定CHIKV和DENV1水平- 4伊蚊媒介和非人类灵长类动物宿主中的循环，并估计 肯尼亚的人-媒介接触；以及3)检测和预测CHIKV和 农村和城市环境中登革热病毒的传播，综合人体内传播的数据(目标1)和 向量(目标2)，包括现场和使用卫星收集的环境和天气/气候数据 想象。这项研究涉及肯尼亚Msambweni(沿海)和Kisumu(西部)及其附近的队列， 那里有全年传播的虫媒病毒，并基于10年的合作 纵向研究。方法论包括分析明确定义的昆虫学、 病毒和蚊子暴露的临床、流行病学和气候学结果以及免疫生物标志物。 这些研究将填补有关CHIKV和DENV在当地栖息地和 造成疫情间期持续性和疫情期间区域差异的因素 句号。这些数据还将回答有关严重发烧的虫媒病毒病因的基本问题。 高危人群中的症状，同时提供更好的相关疾病负担和长期 长期后遗症。

PROJECT ABSTRACT 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 non-human primate reservoirs 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.