Rotavirus is the leading cause of severe diarrhea in children, and a major source of morbidity and mortality in developing countries. Vaccination has proven to be a safe and effective means of controlling the burden of rotavirus-associated gastroenteritis in developed countries, but logistical constraints and concerns over the reduced efficacy of the vaccines in developing country settings have hindered their wider adoption. Better evidence is needed to support the expected impact of vaccination in developing countries to overcome the barriers to vaccine introduction. We seek to address these concerns using a combination of statistical and mathematical modeling to gain a better understanding of the factors affecting the direct and indirect effects of rotavirus vaccination in developing countries. First, we will reanalyze data from pivotal birth cohort studies conducted in Mexico and India to explore the hypothesis that higher rates of rotavirus transmission and the younger age at infection in India compared to Mexico may help to explain the differences in protection from natural infection in these settings. Second, we will use mathematical models to examine the important drivers of rotavirus transmission dynamics in Bangladesh, Malawi, and Ghana. We will use the models to predict the impact of rotavirus vaccination in these settings accounting for both the direct and indirect effects of vaccination. Finally, we will validate and refine model predictions by comparing to data collected as part of ongoing studies of the impact of vaccination in Blantyre, Malawi and Accra and Navrongo, Ghana. These projects will improve our understanding of how the underlying transmission dynamics of rotavirus affect the expected direct and indirect effects of vaccination in developing countries, and will provide a validated platform for extending the modeling analyses to other countries to provide evidence-based support for rotavirus vaccine introduction.

Public Health Relevance

Rotavirus is the leading cause of severe diarrhea in children, and continues to be a major source of morbidity and mortality in developing countries despite the recent development of safe and effective vaccines. We will use statistical and mathematical modeling to explore the drivers underlying the transmission dynamics of rotavirus and provide a validated platform for assessing the expected direct and indirect effects of rotavirus vaccination in developing countries.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Alarcon, Rodolfo M
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Yale University
Public Health & Prev Medicine
Schools of Medicine
New Haven
United States
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Lopman, Benjamin A; Pitzer, Virginia E (2018) Waxing Understanding of Waning Immunity. J Infect Dis 217:851-853
Bennett, A; Pollock, L; Jere, K C et al. (2018) Direct and possible indirect effects of vaccination on rotavirus hospitalisations among children in Malawi four years after programmatic introduction. Vaccine 36:7142-7148
Lopman, Ben; Dahl, Rebecca; Shah, Minesh et al. (2018) Timing of birth as an emergent risk factor for rotavirus hospitalization and vaccine performance in the post-vaccination era in the United States. Am J Epidemiol :
Phelps, Matthew; Perner, Mads Linnet; Pitzer, Virginia E et al. (2018) Cholera Epidemics of the Past Offer New Insights Into an Old Enemy. J Infect Dis 217:641-649
Kunkel, Amber; Lewnard, Joseph A; Pitzer, Virginia E et al. (2017) Antimicrobial Resistance Risks of Cholera Prophylaxis for United Nations Peacekeepers. Antimicrob Agents Chemother 61:
Lewnard, Joseph A; Lopman, Benjamin A; Parashar, Umesh D et al. (2017) Naturally Acquired Immunity Against Rotavirus Infection and Gastroenteritis in Children: Paired Reanalyses of Birth Cohort Studies. J Infect Dis 216:317-326
Metcalf, C Jessica E; Walter, Katharine S; Wesolowski, Amy et al. (2017) Identifying climate drivers of infectious disease dynamics: recent advances and challenges ahead. Proc Biol Sci 284:
Phelps, Matthew D; Azman, Andrew S; Lewnard, Joseph A et al. (2017) The importance of thinking beyond the water-supply in cholera epidemics: A historical urban case-study. PLoS Negl Trop Dis 11:e0006103
Lewnard, Joseph A; Antillón, Marina; Gonsalves, Gregg et al. (2016) Strategies to Prevent Cholera Introduction during International Personnel Deployments: A Computational Modeling Analysis Based on the 2010 Haiti Outbreak. PLoS Med 13:e1001947
Pitzer, Virginia E; Bilcke, Joke; Heylen, Elisabeth et al. (2015) Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium? Sci Rep 5:18585