Burden of diarrhea and antibiotic use among children in low-resource settings preventable by Shigella vaccination: a simulation study

BackgroundShigella is a leading cause of diarrhea and dysentery in children in low resource settings, which is frequently treated with antibiotics. The primary goal of a Shigella vaccine would be to reduce mortality and morbidity associated with Shigella diarrhea. However, ancillary benefits could include reducing antibiotic use and antibiotic exposures for bystander pathogens carried at the time of treatment, specifically for fluoroquinolones and macrolides (F/M), which are the recommended drug classes to treat dysentery. MethodsWe used data from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to estimate the impact of two one-dose (6 or 9 months) and three two-dose (6 & 9 months, 9 & 12 months, and 12 & 15 months) Shigella vaccines on diarrheal episodes, overall antibiotic use, and F/M use. Further, we considered additional protection through indirect and boosting effects. To estimate the absolute and relative reductions in the incidence of diarrhea and antibiotic use under each vaccination scenario, Monte Carlo simulations with random sampling were performed. FindingsWe analyzed 9392 diarrhea episodes and 15697 antibiotic courses among 1715 children in the MAL-ED birth cohort study. There were 273.8 diarrhea episodes, 30.6 shigellosis episodes, and 457.6 antibiotic courses per 100-child years. A Shigella vaccine given at 9 & 12 months prevented 1.7 (95% CI: 1.3, 2.1) severe Shigella diarrhea episodes (46.5% reduction), 11.0 (95% CI: 10.0, 11.9) Shigella diarrhea episodes of any severity (35.9% reduction), 3.1 (95% CI: 2.6, 3.7) F/M courses (2.9% reduction overall), 5.8 (95% CI: 5.2, 6.6) antibiotic courses (1.0% reduction overall), and 6.3 (95% CI: 5.2, 7.5) F/M (3.2% reduction) and 11.2 (95% CI: 9.7, 12.9) antibiotic (1.2% reduction) exposures to bystander pathogens, respectively, per 100-child years. InterpretationA Shigella vaccine could make substantial reductions in Shigella diarrhea, antibiotic use to treat shigellosis, and bystander exposures due to shigellosis treatment. However, the reductions in overall diarrhea episodes and antibiotic use would be modest. FundingWellcome Trust, Bill & Melinda Gates Foundation