Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (
Author summary Shigella is the second leading cause of diarrhea morbidity and mortality among children in low and middle-income countries. We characterized the epidemiology of Shigella using highly sensitive diagnostic methods in 41,405 diarrheal and monthly non-diarrheal stools from the first two years of life in a multisite birth cohort. The prevalence of Shigella varied from 4.9%-17.8% across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age, unimproved sanitation, low maternal education, initiating complementary foods before 3 months, and malnutrition were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase, a marker of intestinal inflammation, which suggests a potential mechanism for the impact of Shigella on child growth. Because culture missed most clinically relevant cases of severe diarrhea and dysentery, molecular diagnostics may be important tools in upcoming Shigella vaccine trials.