Impact of Shigella, rotavirus, and other enteric vaccines on etiology-specific diarrhea, antibiotic use, and exposure of subclinical infections to antibiotics among children in low-resource settings (360G-Wellcome-219741_Z_19_Z)

Diarrhoeal disease, caused by leading aetiologies of Shigella and rotavirus, is a major contributor to antimicrobial resistance (AMR) due to increasing incidence of drug-resistant episodes and frequent treatment with antibiotics. We propose to quantify the comprehensive impact of enteric vaccines in combating AMR by preventing drug-resistant diarrhoea episodes and reducing antibiotic use using data from the MAL-ED study, a longitudinal birth cohort conducted in 8 low-resource sites. Specifically, we will: 1) quantify the incidence of antibiotic use and of antibiotic exposure to subclinical enteric infections that is attributable to the treatment of aetiology-specific diarrhoea episodes, 2) estimate reductions in the incidence of aetiology-specific diarrhoea and antibiotic exposure achievable by vaccines against Shigella, rotavirus, and other enteric pathogens, and 3) estimate the worldwide impact of enteric vaccine introduction on aetiology-specific diarrhoea, antibiotic use, and antibiotic exposure to subclinical infections using data from Demographic Health Surveys and Multiple Indicator Cluster Surveys. These results will generate precise estimates of enteric vaccine impact, most importantly for Shigella vaccines, which have been prioritized for development, and for rotavirus vaccines, which continue to be adopted globally. These quantitative estimates will inform advocacy efforts for continued support and provide relevant data for comprehensive analyses of cost-effectiveness.