Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials

Andrew Clark*, Kevin van Zandvoort, Stefan Flasche, Colin Sanderson, Julie Bines, Jacqueline Tate, Umesh Parashar, Mark Jit

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Background: The duration of protection offered by rotavirus vaccines varies across the world, and this variation is important to understanding and predicting the effects of the vaccines. There is now a large body of evidence on the efficacy of live oral rotavirus vaccines in different settings, but these data have never been synthesised to obtain robust estimates of efficacy by duration of follow-up. Our aim is to estimate the efficacy of live oral rotavirus vaccines at each point during follow-up and by mortality stratum. Methods: In our meta-regression study, we identified all randomised controlled trials of rotavirus vaccines published until April 4, 2018, using the results of a Cochrane systematic review, and cross checked these studies against those identified by another systematic review. We excluded trials that were based on special populations, trials without an infant schedule, and trials without clear reporting of numbers of enrolled infants and events in different periods of follow-up. For all reported periods of follow-up, we extracted the mean duration of follow-up (time since administration of the final dose of rotavirus vaccination), the number of enrolled infants, and case counts for rotavirus-positive severe gastroenteritis in both non-vaccinated and vaccinated groups. We used a Bayesian hierarchical Poisson meta-regression model to estimate the pooled cumulative vaccine efficacy (VE) and its waning with time for three mortality strata. We then converted these VE estimates into instantaneous VE (iVE). Findings: In settings with low mortality (15 observations), iVE pooled for infant schedules of Rotarix and RotaTeq was 98% (95% credibility interval 93–100) 2 weeks following the final dose of vaccination and 94% (87–98) after 12 months. In medium-mortality settings (11 observations), equivalent estimates were 82% (74–92) after 2 weeks and 77% (67–84) after 12 months. In settings with high mortality (24 observations), there were five different vaccines with observation points for infant schedules. The pooled iVE was 66% (48–81) after 2 weeks of follow-up and 44% (27–59) after 12 months. Interpretation: Rotavirus vaccine efficacy is lower and wanes more rapidly in high-mortality settings than in low-mortality settings, but the earlier peak age of disease in high-mortality settings means that live oral rotavirus vaccines are still likely to provide substantial benefit. Funding: Bill & Melinda Gates Foundation.

Original languageEnglish
Pages (from-to)717-727
Number of pages11
JournalThe Lancet Infectious Diseases
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 2019

Bibliographical note

Funding Information:
This work was supported by the Bill & Melinda Gates Foundation (grant number OPP1147721 ) and the Vaccine Impact Modelling Consortium (grant number OPP1157270 ). The views expressed are those of the authors and not necessarily those of the Consortium or its funders. SF is funded through a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 208812/Z/17/Z ). We would like to acknowledge the WHO Immunization and Vaccines Related Implementation Research Advisory Committee for providing useful feedback on the analysis. We also thank Cochrane Response (Hanna Bergman, Nicholas Henschke, and Karla Soares-Weiser) for sharing the list of RCTs identified in their updated systematic review. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Funding Information:
JB reports project grants from the Bill & Melinda Gates Foundation and the National Health and Medical Research Council for the conduct of clinical trials of the RV3-BB rotavirus vaccine at MCRI, and other support from the Victorian Government Operational Infrastructure Support Program. All other authors declare no competing interests.

Publisher Copyright:
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

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