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

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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.