Prospective Community-Based Study of RSV Risk Factors in Nepalese Children

描述（由申请人提供）： 该提案描述了一个5年的培训和研究计划，将使候选人实现成为一个独立的面向患者的研究人员的目标。她将利用她在国际研究、流行病学和分子病毒学方面的背景，在国际社区环境中确定导致尼泊尔儿童呼吸道合胞病毒（RSV）疾病的宿主和病毒学因素。培训计划将使候选人获得试验设计、纵向数据统计分析以及免疫学和分子病毒学技术方面的额外技能。她将利用尼泊尔一个完善的研究基地的研究基础设施来进行这些研究，并获得研究人员的密切指导，这些研究人员拥有20多年的研究创新干预措施的经验，以降低尼泊尔的孕产妇和婴儿死亡率。利用这些资源，她将发展专业知识，在资源有限的环境中进行以患者为导向的RSV疾病治疗和预防干预研究。研究计划：RSV的疾病负担不成比例地影响发展中国家的儿童。该人群的疾病风险因素特征不明确。候选人将使用正在进行的基于社区的前瞻性随机临床试验的研究基础设施，在尼泊尔南部农村地区进行孕产妇流感免疫接种，以表征导致尼泊尔儿童RSV疾病负担的宿主和病毒学因素。目的1：确定保护0至6个月婴儿免于RSV疾病所需的母婴对中RSV特异性抗体水平。候选人将使用从500对母婴中前瞻性收集的鼻咽、母体血清和母乳以及婴儿脐带血样本，确定RSV特异性母源抗体在保护婴儿免受实验室确认的RSV疾病中的作用。目的2：确定病毒载量、亚型和其他呼吸道病毒感染对RSV疾病严重程度和传播的作用。候选人将确定较高的RSV病毒载量、A亚型病毒和呼吸道病毒合并感染的存在是否会增加尼泊尔婴儿中RSV疾病的严重程度。她将描述病毒载量、亚型和呼吸道病毒合并感染对尼泊尔家庭和村庄内RSV传播的影响。这些研究的结果将为资源有限环境下的母婴疫苗接种试验和感染控制策略提供关键数据。最终，该提案将允许候选人制定一个更大的 改善发展中国家儿童健康的研究项目。

DESCRIPTION (provided by applicant): This proposal describes a 5-year training and research plan that will allow the candidate to achieve her goal of becoming an independent patient-oriented researcher. She will use her background in international research, epidemiology and molecular virology to identify the host and virologic factors that lead to respiratory syncytial virus (RSV) disease in Nepalese children in an international community-based setting. The training plan will allow the candidate to acquire additional skills in trial design, statistical analysis of longitudinal data, and immunology and molecular virology techniques. She will use the research infrastructure of a well-established study site in Nepal to perform these studies and receive close mentorship from researchers with over 20 years of experience examining innovative interventions to reduce maternal and infant mortality in Nepal. Using these resources, she will develop the expertise to perform patient-oriented research on therapeutic and preventive interventions against RSV disease in resource-limited settings. Research Plan: The disease burden of RSV disproportionately affects children in the developing world. The risk factors for disease in this population are poorly characterized. The candidate will use the research infrastructure of an ongoing prospective community-based randomized clinical trial of maternal influenza immunization in rural southern Nepal to characterize the host and virologic factors that contribute to RSV disease burden among children in Nepal. Aim 1: Determine the level of RSV-specific antibody in mother- infant pairs required to protect infants age 0 to 6 months from RSV disease. The candidate will determine the role of RSV-specific maternal antibody in protection of infants from laboratory-confirmed RSV disease using prospectively collected nasopharyngeal, maternal serum and breast milk, and infant cord blood samples from 500 mother-infant pairs. Aim 2: Determine the role of viral load, subtype, and infection with other respiratory viruses on RSV disease severity and transmission. The candidate will determine if higher RSV viral load, subtype A virus, and presence of respiratory viral co-infections increases RSV disease severity among infants in Nepal. She will describe the influence of viral load, subtype, and respiratory viral coinfections o transmission of RSV within Nepalese households and villages. The results from these studies will provide critical data for maternal and infant vaccination trials and infection control strateges in resource-limited settings. Ultimately, the proposal will allow the candidate to develop a larger research program to improve the health of children in the developing world.