Risk factors associated with Shigella diarrhea in 6-35-month-olds: A cross-sectional study, Malawi, 2022-2024

Diarrhea due to Shigella causes 60,000 deaths annually among children under five in low- and middle-income countries. This Enterics for Global Health sub-study examined host, clinical, and environmental factors linked to Shigella-attributable diarrhea in Malawian children and assessed seasonal variations. Data from 1,399 children aged 6-35 months presenting with diarrhea at a health centre in Blantyre, Southern Malawi from August 3, 2022, through August 2, 2024, were analyzed. Prevalence ratios of risk factors for Shigella-attributable diarrhea were estimated using modified Poisson regression. A Shigella case was defined by culture positivity or infection attributable to Shigella via quantitative polymerase chain reaction (qPCR). Multivariate analyses adjusted for age, wealth index quintile, and vaccination status. Effect modification by season (rainy vs. dry) was assessed for each predictor. Sensitivity analyses compared cases identified by culture or qPCR. Shigella-attributable diarrhea was found in 12.4% of children. Older age (12-35 months), dysentery, and diarrhea severity were positively associated with Shigella-attributed diarrhea in unadjusted and adjusted models; stunting and age-appropriate vaccination were significant only in unadjusted models. Seasonal effect modification occurred for wasting and Shigella infection in the dry season but not rainy season. Longer diarrhea duration was marginally linked to increased Shigella risk in the dry season only. Conversely, open defaecation/unimproved sanitation increased Shigella risk during the rainy season but not the dry season. Sensitivity analyses showed consistent risk patterns for culture- and qPCR-diagnosed cases. This study identified age, dysentery, and diarrhea severity as key factors for Shigella-attributed diarrhea. Seasonal effects influenced the relationships between Shigella infection and wasting, diarrhea duration, and sanitation. Policies prioritizing vulnerable populations and accounting for seasonal variations can help reduce the Shigella burden in children.