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.

Public Health Relevance

Helen Y. Chu, MD MPH, is an Acting Instructor in the Division of Allergy and Infectious Diseases at the University of Washington. For this K23 award entitled Prospective Community-Based Study of RSV Risk Factors in Nepalese Children, the career development plan and proposed patient-oriented research will allow the candidate mentored learning in epidemiology, immunology, and virology while investigating the host and virologic factors associated with respiratory syncytial virus (RSV) disease in a prospective community-based study of mothers and children in rural Nepal. The research findings will define the disease burden and risk factors for RSV disease for future preventive interventions and will form the basis for the candidate's independent career conducting patient-oriented research to improve the health of children in the developing world.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI103105-02
Application #
8688142
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Kim, Sonnie
Project Start
2013-06-24
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$177,347
Indirect Cost
$13,137
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Uddin, S M Iftekhar; Englund, Janet A; Kuypers, Jane Y et al. (2018) Burden and Risk Factors for Coronavirus Infections in Infants in Rural Nepal. Clin Infect Dis 67:1507-1514
Katz, Joanne; Englund, Janet A; Steinhoff, Mark C et al. (2018) Impact of Timing of Influenza Vaccination in Pregnancy on Transplacental Antibody Transfer, Influenza Incidence, and Birth Outcomes: A Randomized Trial in Rural Nepal. Clin Infect Dis 67:334-340
Philpott, Erin K; Englund, Janet A; Katz, Joanne et al. (2017) Febrile Rhinovirus Illness During Pregnancy Is Associated With Low Birth Weight in Nepal. Open Forum Infect Dis 4:ofx073
Englund, Janet A; Chu, Helen Y (2017) Vaccines Against Respiratory Syncytial Virus: The Time Has Come. J Infect Dis 215:4-7
Katz, Joanne; Englund, Janet A; Steinhoff, Mark C et al. (2017) Nutritional status of infants at six months of age following maternal influenza immunization: A randomized placebo-controlled trial in rural Nepal. Vaccine 35:6743-6750
Steinhoff, Mark C; Katz, Joanne; Englund, Janet A et al. (2017) Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis 17:981-989
Lenahan, Jennifer L; Englund, Janet A; Katz, Joanne et al. (2017) Human Metapneumovirus and Other Respiratory Viral Infections during Pregnancy and Birth, Nepal. Emerg Infect Dis 23:
Chu, Helen Y; Englund, Janet A (2017) Maternal immunization. Birth Defects Res 109:379-386
Chu, Helen Y; Tielsch, James; Katz, Joanne et al. (2017) Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal. J Clin Virol 95:90-95
Chu, Helen Y; Katz, Joanne; Tielsch, James et al. (2016) Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy. PLoS One 11:e0152015

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