Defining Severe Shigellosis in the Enterics for Global Health Study: A Comparison of Leading Diarrhea Severity Definitions Among Children With Shigella Diarrhea

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Abstract
Background: Shigella vaccine development is a critical priority due to high burden and long-term outcomes among children. Choosing a clinical efficacy endpoint for Shigella vaccine trials requires comparing existing diarrhea severity definitions among children with Shigella. Methods: Six- to 35-month-old children presenting with diarrhea were enrolled at 7 EFGH study sites. Among children with Shigella, 6 diarrhea severity definitions (Global Enteric Multicenter Study [GEMS] moderate-to-severe diarrhea [MSD], modified Vesikari score [MVS], MVS +/− dysentery, Clark score, MAL-ED score, and Shigella mortality score) were examined against 2 outcomes: change in length/height-for-age z-score (ΔLAZ/HAZ) over 3 months and death or hospitalization within 14 days. We compared the performance of each severity score to predict outcomes using linear regression and measures of diagnostic accuracy. Results: Moderate or severe diarrhea was negatively associated with ΔLAZ/HAZ by MVS (−0.07 z-score, 95% CI −0.10 to −0.03), MVS +/− dysentery (−0.05, 95% CI −0.09 to −0.02), and MAL-ED score (−0.04, 95% CI −0.07 to 0.00). GEMS MSD (93.6%), MAL-ED (87.2%), MVS +/− dysentery (85.1%), and MVS (80.9%) had high sensitivity in predicting death or hospitalization. Conclusions: MVS, MVS +/− dysentery, and MAL-ED score identified adverse outcomes following Shigella diarrhea and are viable options for a vaccine trial case definition.
Funding Information
  • Bill & Melinda Gates Foundation (INV-028721)
  • Bill & Melinda Gates Foundation (INV-041730)
  • Bill & Melinda Gates Foundation (INV-016650)
  • Bill & Melinda Gates Foundation (INV-031791)
  • Bill & Melinda Gates Foundation (INV-036891)
  • Bill & Melinda Gates Foundation (INV-036892)

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