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

Abstract

<i>Shigella</i> 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. 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 <i>Shigella</i>-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. <i>Shigella</i> 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 <i>Shigella</i> and hospitalization or linear growth faltering. However, children with <i>Shigella</i> 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 <i>Cryptosporidium</i> (aRR: 2.33, 95% CI: 1.35-4.04) were associated with hospitalization, and <i>Cryptosporidium</i> was linked to subsequent stunting (aRR: 1.36, 95% CI: 1.01-1.84). <i>Shigella</i> contributes to prolonged and persistent diarrhoea and, when untreated, can contribute to linear growth faltering. Pathogen-specific diagnosis, antibiotic access, and <i>Shigella</i> vaccination could reduce prolonged illness and growth impairment, with meaningful population-level benefits in low- and middle-income settings. Gates Foundation.