Timing of rotavirus vaccination and incidence of severe rotavirus gastroenteritis among infants in low- and middle-income countries

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  • March 19, 2019
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  • Gruber, Joann
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Rotavirus vaccines effectiveness is much lower in low- and middle-income countries (LMICs) than high-income countries. Some factors associated with decreased immune response, including interference by transplacental antibodies and the microbiota, may be mitigated by altering vaccine schedules. The purpose of this dissertation was to investigate when children in LMICs experienced severe rotavirus gastroenteritis (RVGE) and if the timing of rotavirus vaccine doses was associated with severe RVGE. We analyzed data from two clinical trials in LMICs. To understand the timing and predictors of severe RVGE, we estimated the rate, cumulative incidence, and age distribution of severe RVGE among unvaccinated infants. Cox proportional hazards models were used to estimate associations between baseline factors and severe RVGE. To estimate the association between rotavirus vaccine dose timing and severe RVGE incidence, we compared different schedules using the complement of the Kaplan-Meier estimator to estimate differences and ratios of cumulative severe RVGE risk at 6, 12, and 18 months of age and also used a Cox proportional hazards model to estimate hazard ratios. To obtain adjusted estimates, we used the associations observed in the placebo group, which should only differ from the null due to confounding, to calibrate the estimates within the rotavirus vaccinated groups. The cumulative incidence of severe RVGE was 6 – 8 % at 20 months of age. The cumulative incidence increased steadily over the first two years of life and was low at 6 months of age. Antibiotic use was associated with about 1.4 to 2 times the rate of severe RVGE. There was a dose-response relationship between age at first pentavalent vaccine (RV5) dose and severe RVGE. Earlier administration of first RV5 dose was associated with an increased severe RVGE risk and that risk declined with increased age of first dose until approximately 8 – 9 weeks of age. An interval of 4 versus 6 weeks between monovalent vaccine (RV1) doses was associated with increased risk of severe RVGE when RV1 was administered on an approximately 10/14 week schedule. This dissertation, in conjunction with previous scientific literature, indicates severe RVGE episodes may be prevented by altering rotavirus vaccine schedules in LMICs.
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  • In Copyright
Advisor
  • Hudgens, Michael
  • Brookhart, M. Alan
  • Becker-Dreps, Sylvia
  • Thomas, James C.
  • Jonsson Funk, Michele
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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