Dengue epidemiology in Thailand and implications for vaccine development

描述（由申请人提供）：登革热是一种重要的全球健康问题，其地理范围和流行严重程度每年都在增加。该研究项目将解决我们对登革热疾病的流行病学和发病机制的理解中的关键空白。具体的目标。本研究的主要目的是：(1)评估既往黄病毒免疫与登革出血热的关系，以及感染登革热血清型与原发性和继发性感染结果的关系；(2)更好地定义登革热疾病的临床表现谱，并制定和测试更敏感和具体的病例定义；使用基于医院的数据来评估DHF和登革休克综合征（DSS）进展的预测因素，以指导早期干预；(3)评估泰国登革热病毒的人口统计和分布如何以及为何随时间而变化。研究Desiqn。该研究将涉及泰国曼谷的现有数据集和原始数据收集，以及AFRIMS在泰国坎彭彭省（KPP）的登革热现场。在曼谷收集了30年的登革热住院被动监测数据，在曼谷诗丽吉王后国立儿童医院收集了12年更详细的登革热住院儿童临床数据。KPP的一项前瞻性研究收集了1998年以来学龄儿童队列中有症状的登革热疾病和无症状血清转化的数据，并在2003-2008年期间增加了病毒病例的聚集性组成部分。方法。既往黄病毒免疫的影响将使用KPP队列数据进行评估，这些数据包括入组时日本脑炎抗体的存在/缺失、登革热疾病的临床严重程度以及感染是否为原发性、继发性或继发性感染。病例定义将通过将现有数据纳入预测模型进行测试和修改，并评估敏感性、特异性和接受者工作特征曲线。发展为DHF的预测因素将根据入院时的实验室标记物和临床特征进行评估。然后将对病例定义和发展为登革出血热的预测因素的“最佳拟合”模型进行前瞻性测试。将评估登革热感染的人口统计和传播模式的变化，包括登革出血热的平均年龄是否增加以及如何增加。Siqnificance。登革热是一个重要的全球卫生问题。这项研究将解决登革热病毒和登革热疾病的流行病学、病毒学和免疫学方面的关键问题。

DESCRIPTION (provided by applicant): Dengue is an important global health problem that is increasing in geographic range and epidemic severity each year. This research project will address critical gaps in our understanding of the epidemiology and pathogenesis of dengue illnesses. Specific aims. The major aims of this research will be: (1) to evaluate the association of prior flavivirus immunity with DHF, as well as the association of infecting dengue serotype and the outcome of primary and secondary infections; (2) to better define the spectrum of clinical presentations in dengue illness and to develop and test more sensitive and specific case definitions; to use hospital-based data to evaluate predictors of progression to DHF and dengue shock syndrome (DSS) to guide early intervention; (3) to evaluate how and why the demographics and distribution of dengue viruses have changed over time in Thailand. Research Desiqn. The research will involve both existing datasets and primary data collection in Bangkok, Thailand, and AFRIMS' dengue field site in Kamphaeng Phet Province (KPP), Thailand. 30 years of passive surveillance data on DHF hospitalizations have been collected in Bangkok, with 12 years of more detailed clinical data from children hospitalized with dengue at Queen Sirikit National Children's Hospital in Bangkok. A prospective study in KPP has collected data on symptomatic dengue illnesses and asymptomatic seroconversion in cohorts of school-aged children since 1998, with a cluster component for viremic cases added for the period 2003-2008. Methods. The effects of prior flavivirus immunity will be evaluated using the KPP cohort data which include information on the presence/absence of antibodies to Japanese Encephalitis at enrollment, the clinical severity of incident dengue illnesses, and whether the infection represented a primary, secondary, or post-secondary infection. Case definitions will be tested and modified by incorporating existing data into predictive models, with evaluation of sensitivity, specificity and Receiver Operating Characteristic curves. Predictors for progression to DHF will be assessed based upon laboratory markers and clinical characteristics on admission to the hospital. "Best fit" models for case definitions and predictors of progression to DHF will then be tested prospectively. Changes in the demographics and transmission patterns of dengue infections will be assessed, including whether and how the mean age of DHF has increased. Siqnificance. Dengue is an important global health problem. This research will address key questions in the epidemiology, virology, and immunology of dengue viruses and dengue illness.