Evaluating strategies to improve rotavirus vaccine impact during the second year of life in Malawi

• Type of Material: Article
• Authors: Virginia E. Pitzer, Yale University; Aisleen Bennett, University of Malawi; Naor Bar-Zeev, University of Malawi; Khuzwayo C. Jere, University of Malawi; Benjamin Lopman, Emory University; Joseph A. Lewnard, University of California Berkeley; Umesh D. Parashar, Centers for Disease Control and Prevention; Nigel A. Cunliffe, University of Liverpool
• Language: English
• Date: 2019-08-14
• Publisher: American Association for the Advancement of Science
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 American Association for the Advancement of Science. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1126/scitranslmed.aav6419
• Title of Journal or Parent Work: Science Translational Medicine
• Volume: 11
• Issue: 505
• Grant/Funding Information: This work was supported by grant R01AI112970 from the US National Institutes of Health/National Institute of Allergy and Infectious Diseases to V.E.P. Rotavirus surveillance in Blantyre, Malawi was supported by a Wellcome Trust Programme Grant to N.A.C. (number 091909/Z/10/Z).; K.C.J. was supported by a Wellcome Trust Public Health and Tropical Medicine Training Fellowship (number 201945/Z/16/Z).; A.B. was the recipient of a Wellcome Trust Clinical PhD Fellowship (number 102466/Z/13/A).
• Keywords: Life Sciences & Biomedicine; Children; Cell Biology; Infants; 1st two years; Gastroenteritis; Efficacy; Safety; Transmission; Medicine, Research & Experimental; Immunogenicity; Double-blind; Research & Experimental Medicine; Infection; Science & Technology
• Research Categories: Health Sciences, Epidemiology; Biology, Virology; Biology, Microbiology; Health Sciences, Public Health

Abstract

Rotavirus vaccination has substantially reduced the incidence of rotavirus-associated gastroenteritis (RVGE) in high-income countries, but vaccine impact and estimated effectiveness are lower in low-income countries for reasons that are poorly understood. We used mathematical modeling to quantify rotavirus vaccine impact and investigate reduced vaccine effectiveness, particularly during the second year of life, in Malawi, where vaccination was introduced in October 2012 with doses at 6 and 10 weeks. We fitted models to 12 years of prevaccination data and validated the models against postvaccination data to evaluate the magnitude and duration of vaccine protection. The observed rollout of vaccination in Malawi was predicted to lead to a 26 to 77% decrease in the overall incidence of moderate-to-severe RVGE in 2016, depending on assumptions about waning of vaccine-induced immunity and heterogeneity in vaccine response. Vaccine effectiveness estimates were predicted to be higher among 4- to 11-month-olds than 12- to 23-month-olds, even when vaccine-induced immunity did not wane, due to differences in the rate at which vaccinated and unvaccinated individuals acquire immunity from natural infection. We found that vaccine effectiveness during the first and second years of life could potentially be improved by increasing the proportion of infants who respond to vaccination or by lowering the rotavirus transmission rate. An additional dose of rotavirus vaccine at 9 months of age was predicted to lead to higher estimated vaccine effectiveness but to only modest (5 to 16%) reductions in RVGE incidence over the first 3 years after introduction, regardless of assumptions about waning of vaccine-induced immunity.