Cohort Studies of Dengue Virus Infection

该项目的总体目标是在有病人在场的情况下定义DENV在家庭中的传播， 登革热病毒症家庭成员。这项前瞻性的家庭队列研究确定了 从最初的DENV感染到继发性DENV感染，保护、疾病和宿主反应的全谱。 这项研究还将确定成人中的感染和影响感染力的群体免疫。 DENV是一种重要的虫媒病毒感染，导致严重的发热性疾病及其更严重的表现， 登革出血热(DHF)我们先前关于登革热发病机制和疾病的前瞻性队列研究 流行病学有助于了解登革热病毒的传播和病毒宿主 导致轻微或严重登革热感染的相互作用。关于登革热传播和 病机包括定义保护或疾病的免疫相关因素，定义力量的群体免疫 成人的感染和疾病以及免疫力减弱的后果。我们之前的研究指出 一名DENV病毒症患者的家庭是DENV传播和最终登革热的潜在来源 传播可由家庭单位成员及其不受感染的风险或保护程度来界定。 在这项建议的新颖研究设计中，我们将前瞻性地跟踪家庭队列，并能够发现疾病 病毒症家庭成员，成为家庭内额外传播的哨兵病例 邻里关系。这项研究将能够确定家族性群体免疫和家庭内的感染力。 和对邻居的风险，表征和定义保护性免疫的相关因素(T细胞， 中和抗体滴度)在免受感染或亚临床疾病的家庭成员中 疾病，并定义通过顺序感染和病毒的病毒宿主反应的谱 血清型。这项建议将是此类研究的第一次，其结果将对我们的 对病毒-宿主致病机制的理解，该致病机制定义了疾病严重程度从亚临床到 严重的DENV感染和有效的DENV疫苗的开发。

The overall objective of this project is to define DENV transmission vi/ithin a family in the presence of an ill, dengue viremic family member. This prospective family cohort study m\\ identify immunologic correlates of protection, disease and the full spectrum ofthe host response from primary to secondary DENV infection. This study will also define infection among adults and herd immunity that influences the force of infection. DENV is an important arboviral infection causing a severe febrile illness and its more serious manifestation, dengue hemorrhagic fever (DHF). Our previous prospective cohort studies on dengue pathogenesis and epidemiology has contributed to the understanding of dengue virus transmission and the virus-host interactions leading to mild or severe dengue infection. What is unknown about dengue transmission and pathogenesis include correlates of immunity that define protection or illness, herd immunity defining the force of infection, and illness in adults and the consequences of fading immunity. Our previous studies point to the household of a DENV viremic patient as a potential source of DENV transmission and ultimately dengue transmission may be defined by the family unit members and their degree of risk or protection from infection. In this proposal's novel study design, we will prospectively follow family cohorts and be able to detect the ill viremic family member who becomes the sentinel case for additional transmission within the family and neighborhood. This study will be able to define familial herd immunity and force of infection within a family and risk to the neighborhood, characterize and define the correlates of protective immunity (T-cell, neutralizing antibody titer) among family members who are protected from infection or develop subclinical disease, and define the spectrum ofthe virus-host response through sequential infections and virus serotypes. This proposal will be the first study of its kind with its findings having implications on our understanding of the virus-host pathogenesis that defines the gradient of disease severity from subclinical to severe DENV infection and the development of effective DENV vaccines.