Cohort Studies of Dengue Virus Infection

登革热病毒感染的队列研究

• 批准号: 8702985
• 负责人: Timothy Paul Endy
• 金额: $ 47.94万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8702985
• 关键词: Address; Adult; Affect; Antibodies; Arbovirus Infections; Area; Blood Circulation; Child; Clinical; Cohort Studies; Country; Dengue; Dengue Hemorrhagic Fever; Dengue Virus; Development; Disease; Elderly; Epidemic; Epidemiology; Family; Family Study; Family member; Fever; Flavivirus Infections; Frequencies; Herd Immunity; Household; Immune; Immune response; Immunity; Immunologic Memory; Immunologics; Incidence; Individual; Infection; Instruction; Intervention; Life; Methods; Modeling; Morbidity - disease rate; Mothers; Nature; Neighborhoods; Newborn Infant; Outcome; Pathogenesis; Patients; Population; Predisposition; Prevention; Process; Public Health; Recording of previous events; Research; Research Design; Risk; Role; Seasons; Secondary to; Sentinel; Serotyping; Severity of illness; Site; Source; Sterility; Sum; T-Lymphocyte; Thailand; Vaccines; Virus; Virus Diseases; cohort; experience; global health; immunosenescence; insight; member; neutralizing antibody; novel; placental transfer; prevent; primary outcome; programs; prospective; therapeutic vaccine; transmission process; vector control; virus host interaction

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.

该项目的总体目标是定义DENV在存在疾病的家庭中的传播， 登革热病毒血症家族成员。这项前瞻性家庭队列研究可以确定以下免疫相关性： 保护、疾病和宿主从原发到继发DENV感染的全谱反应。 这项研究还将确定成人之间的感染和影响感染力的群体免疫。 登革病毒是一种重要的虫媒病毒感染，引起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 相互作用导致轻微或严重的登革热感染。关于登革热的传播和 发病机理包括定义保护或疾病的免疫相关性，定义力的群体免疫 感染和成人疾病以及免疫力下降的后果。我们以前的研究指出， DENV病毒血症患者家庭是DENV传播和最终登革热的潜在来源 传播可根据家庭成员及其感染风险或防护程度来确定。 在这项新的研究设计中，我们将前瞻性地跟踪家庭队列，并能够发现疾病 病毒血症家庭成员成为家庭内额外传播的哨点病例， 小区这项研究将能够确定家庭群体免疫和家庭内的感染力 和对邻近区域的风险，表征和定义保护性免疫的相关性（T细胞， 中和抗体滴度）， 疾病，并通过连续感染和病毒定义病毒-宿主反应谱 血清型。这项建议将是第一项此类研究，其结果对我们的 了解病毒宿主发病机制，定义疾病严重程度从亚临床到 严重的登革病毒感染和有效的登革病毒疫苗的开发。