The impact of vaccines for diarrhoea on antibiotic use among children in five low-resource settings: a comparative simulation study.

Abstract

Vaccines for diarrhoea could have the ancillary benefit of preventing antibiotic use. We aimed to quantify and compare the expected impact of enteric vaccines on antibiotic use via Monte Carlo simulations. We analysed data from a longitudinal birth cohort, which enrolled children from 2009 to 2012 from Bangladesh, India, Nepal, Pakistan, and Tanzania. We used Monte Carlo simulations to estimate hypothetical vaccine impact in nine vaccination scenarios (including six single vaccines and three combination vaccines) on antibiotic- treated diarrhoea, overall antibiotic courses, and antibiotic exposures to bystander pathogens. For each vaccine scenario, we randomly selected target pathogen-specific diarrhoea episodes to be prevented according to the specified vaccine efficacy and estimated the absolute and relative differences in incidence of antibiotic use outcomes between vaccine and no vaccine scenarios. Among 1119 children, there were 3029 (135·3 courses per 100 child-years) antibiotic-treated diarrhoea episodes. Based on simulated results, a Shigella vaccine would cause the greatest reductions compared with the other single pathogen vaccines in antibiotic courses for all-cause diarrhoea (6·1% relative reduction; -8·2 courses per 100 child-years [95% CI -9·4 to -7·2]), antibiotic courses overall (1·0% relative reduction; -8·2 courses per 100 child-years [-9·4 to -7·2]), and antibiotic exposures to bystander pathogens (1·2% relative reduction; -15·9 courses per 100 child-years [-18·5 to -13·8]). An adenovirus-norovirus-rotavirus vaccine would cause the greatest reductions in antibiotic use (12·2 courses per 100 child-years [-13·7 to -11·0]) compared with the other combination vaccines. However, projected vaccine effects on antibiotic use in 2021 were 45-74% smaller than those estimated in 2009-12 accounting for reductions in diarrhoea incidence in the past decade. Vaccines for enteric pathogens could result in up to 8-12 prevented courses of antibiotics per 100 vaccinated children per year. Combination vaccines will probably be necessary to achieve greater than 1% reductions in total antibiotic use among children in similar low-resource settings. Wellcome Trust and Bill & Melinda Gates Foundation.