Effects of Shigella diarrhea with and without antibiotic treatment on linear growth: an individual patient data meta-analysis of five multisite studies among children in low-resource settings
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Background
Quantifying the effect of Shigella diarrhea with and without antibiotic treatment on linear growth faltering is critical to understanding the potential impact of Shigella vaccines.
Methods
Using individual-level data from five multisite studies, we estimated the effect of Shigella diarrhea on length/height-for-age z-score (HAZ) 60-90 days after the episode compared to diarrhea episodes with no etiology identified and non-diarrheal controls. Effects were estimated under treatment with and without antibiotics using augmented inverse probability weighted estimators with ensemble machine learning.
Findings
Among 26,752 diarrhea episodes, 5,503 (20.6%) were attributed to Shigella and of those, 2,567 (46.6%) were treated with guideline recommended antibiotics. Compared to other diarrhea episodes, Shigella diarrhea without treatment with guideline recommended antibiotics was associated with small reductions in HAZ (HAZ difference: -0.03, 95% CI: -0.05, -0.01), but not when treated with guideline recommended antibiotics (HAZ difference: -0.01, 95% CI: -0.02, 0.01). Compared to non-diarrheal controls, Shigella diarrhea was associated with decrements in HAZ in the following 60-90 days regardless of antibiotic treatment (HAZ difference overall: -0.08, 95% CI: -0.10, -0.07). A larger impact of Shigella diarrhea was observed among younger children.
Interpretation
Shigella diarrhea was associated with short-term decrements in height. Treatment with guideline recommended antibiotics prevented the impact of Shigella on linear growth compared to other diarrhea episodes but not compared to non-diarrheal controls. These results suggest that improved recognition and treatment or prevention of Shigella could improve child growth.
Funding
This work was supported by the Gates Foundation (INV-071320 to ERM and DB) and NIH/NIAID (R01AI185140 to ERM).
Research in context
Evidence before this study
We searched PubMed on June 1, 2026 for articles published in any language since Jan 1, 1990, using the search terms (shigell*)) AND ((pediatric OR paediatric OR infant* OR child*))) AND ((grow* OR linear OR height OR length OR stunt*)). We identified 436 publications, of which 8 research articles and two systematic reviews investigated the association between Shigella diarrhea and child growth. The studies were of different designs and employed a wide range of statistical analyses. Only one study considered the impact of antibiotic treatment on the association between Shigella and linear growth, and none appropriately accounted for antibiotic treatment as a mediator of the effect of Shigella on growth. No pooled estimates derived from a meta-analysis of the evidence were available.
Added value of this study
This study leverages harmonized diagnostic and covariate data from more than 26,000 episodes of diarrhea to conduct an individual patient data meta-analysis of the effect of Shigella diarrhea on short-term linear growth. The analysis appropriately accounts for antibiotic treatment as a mediator of the effect and considers comparisons to other diarrhea episodes and to non-diarrheal controls. Flexible modeling methods using machine learning and doubly robust estimators minimize bias and maximize the precision of estimates. Shigella -attributed diarrhea was associated with small but significant decrements in HAZ in the short-term, with larger effects observed among younger children. Treatment with guideline recommended antibiotics reduced the impact of Shigella compared to other diarrhea episodes, but did not prevent effects on HAZ compared to non-diarrheal controls.
Implications of all the available evidence
The impact of Shigella on growth faltering increases the value proposition for Shigella- targeted interventions. Appropriate antibiotic treatment may mitigate but will not fully prevent the effects of Shigella on child growth, suggesting detection and treatment of shigellosis is not sufficient to prevent growth faltering. Vaccination and other interventions for disease prevention are needed and could improve linear growth even in settings with frequent appropriate antibiotic treatment.
