Dengue epidemiology in Thailand and implications for vaccine development

描述(申请人提供)：登革热是一个重要的全球卫生问题，其地理范围和流行严重程度每年都在增加。这项研究项目将解决我们在了解登革热疾病的流行病学和发病机制方面的重大差距。明确的目标。这项研究的主要目的将是：(1)评估先前的黄病毒免疫与登革热的相关性，以及感染登革热血清型与初次和继发性感染结局的相关性；(2)更好地确定登革热的临床表现谱，并制定和测试更敏感和更具体的病例定义；(3)利用以医院为基础的数据来评估进展为登革热和登革热休克综合征(DSS)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结构和分布随时间发生变化的方式和原因。研究设计。这项研究将涉及泰国曼谷的现有数据集和初步数据收集，以及AFRIMS在泰国Kamphaeng Phet省(KPP)的登革热现场。曼谷收集了30年来登革出血热住院的被动监测数据，以及曼谷西里吉王后国立儿童医院登革热住院儿童12年的更详细的临床数据。KPP的一项前瞻性研究收集了自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换的数据，并增加了2003-2008年期间病毒感染病例的集群部分。方法：研究方法。先前黄病毒免疫的效果将使用KPP队列数据进行评估，这些数据包括登记时有无日本脑炎抗体、登革热事件的临床严重性以及感染是初级、继发性还是继发性感染的信息。将通过将现有数据纳入预测模型来测试和修改病例定义，并评估灵敏度、特异度和接受者操作特征曲线。将根据实验室标记和入院时的临床特征来评估进展为DHF的预测因素。然后将对病例定义和进展到DHF的预测因素的“最佳匹配”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，包括登革热平均年龄是否增加以及如何增加。意义重大。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.