Timing and predictors of severe rotavirus gastroenteritis among unvaccinated infants in low- and middle-income countries

Abstract

Delays in rotavirus vaccine schedule could improve performance in low- and middle-income countries (LMICs). However, delaying the first dose could be detrimental if infants experience severe rotavirus gastroenteritis (RVGE) early in life. Our objective was to describe the timing and predictors of severe RVGE in unvaccinated children in LMICs. We analysed the placebo arms from two clinical trials (cohort 1: NCT00241644; cohort 2: NCT00362648). We estimated the rate, cumulative incidence (per 1000 infants) and age distribution of severe RVGE episodes. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between baseline factors and severe RVGE. Cumulative incidence at 6 months of age was 23/1000 (95% CI 15-30) in cohort 1 and 6/1000 (95% CI 3-8) in cohort 2. Early antibiotic use (compared with no use) was associated with 2.03 (95% CI 1.18-3.48) and 1.41 (95% CI 0.80-2.51) times the rate of severe RVGE in cohorts 1 and 2, respectively. The cumulative incidence of severe RVGE was low at 6 months of age, suggesting that a 4-week delay in the vaccination schedule may not result in a large number of severe RVGE episodes prior to vaccine receipt.

Keywords: Epidemiology; gastroenteritis; immunisation (vaccination); rotavirus.

Conflict of interest statement

Data for this manuscript were provided by GlaxoSmithKline (GSK), Rixensart, Belgium through a third party, ClinicalStudyDatarequest.com, and by Merck and Co., Inc., Kenilworth, NJ, USA. Neither company had involvement in this study design and analysis. Both Merck and Co., Inc., Kenilworth, NJ, USA and GSK, Rixensart, Belgium were given the opportunity to comment on this manuscript prior to publication. All decisions regarding the content of this manuscript were made by the authors. Dr Gruber was employed by Merck and Co., Inc., Kenilworth, NJ, USA as a graduate research assistant from January–December 2014 to work on research related to their rotavirus vaccine. Dr Jonsson Funk is a member of the Scientific Steering Committee (SSC) for a post-approval safety study of an unrelated drug class funded by GSK. All compensation for services provided on the SSC is invoiced by and paid to UNC Chapel Hill. Dr Jonsson Funk receives salary support from the Center for Pharmacoepidemiology in the Department of Epidemiology, Gillings School of Global Public Health (current members: GSK, UCB BioSciences, Merck and Co., Inc.). Dr Jonsson Funk does not accept personal compensation of any kind from any pharmaceutical company. Dr Brookhart has received investigator-initiated research funding from the NIH and through contracts with the AHRQ's DEcIDE program and the PCORI. Within the past three years, he has received research support from Amgen and AstraZeneca and has served as a scientific advisor for Amgen, Merck and Co., Inc., GSK, UCB BioSciences, and RxAnte. Within the past three years, Dr Brookhart has received research support from Amgen and AstraZeneca and has served as a scientific advisor for Amgen, Merck, GSK, Genentech, TargetPharma, and RxAnte. Dr Brookhart owns equity in NoviSci, LLC, a data sciences company.

Figures

Fig. 1.

Cumulative incidence of severe rotavirus gastroenteritis from 6 weeks of age in cohort 1 (a) and cohort 2 (b). Number at risk at the start of follow-up and at 6 months intervals is labelled at corresponding time points for each country below the x-axis.