The consequences of Shigella medically-attended diarrhoea and other leading pathogens among young children living in high-burden settings: a multi-country prospective cohort study

Background: Shigella is a leading cause of diarrheal illness in children in low- and middle-income countries, with evidence of contribution to prolonged diarrhoea, hospitalization, and impaired growth. Methods: In this prospective cohort study, we analysed data from 8756 children aged 6–35 months with acute (onset within the last seven days after at least two diarrhoea-free days) medically attended diarrhoea (defined as three or more abnormally loose or watery stools with or without blood in the previous 24 h) enrolled between June 2022–August 2024 from health facilities in Bangladesh (1341 children from 3 health facilities), Kenya (1390 children from 6 health facilities), Malawi (1325, 1), Mali (1341, 4), Pakistan (1365, 6), Peru (1058, 5), and The Gambia (937, 2). Eligible children resided in the pre-defined catchment area and were accompanied by a consenting caregiver. We evaluated associations between Shigella-attributed diarrhoea (compared to controls with no detected diarrheagenic pathogen) and three primary outcomes: prolonged/persistent diarrhoea, hospitalization, and linear growth faltering assessed at 4 weeks and 3 month follow-up visits. Pathogen attribution was based on culture or pathogen-specific quantitative PCR thresholds. Poisson regression and linear regression with generalised estimating equations were used to assess associations, stratified by antibiotic treatment and adjusted for sociodemographic and clinical variables. Findings: Shigella was the most prevalent attributed pathogen (20.6%). It was the only pathogen associated with both prolonged (≥seven days, adjusted Prevalence Ratio (aPR): 1.56, 95% CI: 1.34–1.82) and persistent (≥14 days, aPR: 1.66, 95% CI:1.03–2.68) diarrhoea. No associations were identified between Shigella and hospitalization or linear growth faltering. However, children with Shigella who did not receive effective antibiotics experienced greater decrements in linear growth (length-for-age z-score (LAZ)/height-for-Age Z-score (HAZ): −0.05, 95% CI: −0.09, −0.01) in the three months following infection compared to those without any pathogen detected. Rotavirus (adjusted Risk Ratio (aRR): 2.40, 95% CI: 1.53–3.76) and Cryptosporidium (aRR: 2.33, 95% CI: 1.35–4.04) were associated with hospitalization, and Cryptosporidium was linked to subsequent stunting (aRR: 1.36, 95% CI: 1.01–1.84). Interpretation: Shigella contributes to prolonged and persistent diarrhoea and, when untreated, can contribute to linear growth faltering. Pathogen-specific diagnosis, antibiotic access, and Shigella vaccination could reduce prolonged illness and growth impairment, with meaningful population-level benefits in low- and middle-income settings. Funding: Gates Foundation.