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Defining Severe Shigellosis in the Enterics for Global Health Study: A Comparison of Leading Diarrhea Severity

Olivia Lang Schultes1, Aneeta Hotwani2, Patricia B Pavlinac1

  • 1Department of Global Health, University of Washington, Seattle, USA.

The Journal of Infectious Diseases
|December 11, 2025
PubMed

Insights

The Modified Vesikari Score (MVS), MVS with dysentery, and MAL-ED score effectively identify severe Shigella infections in children, aiding vaccine development. These scores predict adverse outcomes, crucial for clinical trials of Shigella vaccines.

Area of Science:

  • Infectious Diseases
  • Pediatrics
  • Vaccinology

Background:

  • Shigella infections pose a significant global health burden, particularly in young children, with severe long-term consequences.
  • Rising antibiotic resistance in Shigella necessitates the urgent development of effective vaccines.
  • Selecting appropriate clinical efficacy endpoints for Shigella vaccine trials is crucial and requires evaluating existing diarrhea severity definitions.

Purpose of the Study:

  • To compare the performance of six different diarrhea severity definitions in children with Shigella infections.
  • To evaluate these definitions' ability to predict key adverse outcomes, including growth faltering and mortality/hospitalization.
  • To identify the most suitable case definition for Shigella vaccine efficacy trials.

Main Methods:

  • A cohort of 6- to 35-month-old children with diarrhea was enrolled across seven countries.
  • Six diarrhea severity scores (GEMS MSD, MVS, MVS +/- dysentery, Clark, MAL-ED, Shigella mortality) were assessed.
  • Performance was evaluated against change in length/height-for-age z-score (ΔLAZ/HAZ) and 14-day death or hospitalization using regression, diagnostic accuracy, and ROC curves.

Main Results:

  • Three definitions (MVS, MVS +/- dysentery, MAL-ED) showed a significant negative association between moderate/severe diarrhea and ΔLAZ/HAZ.
  • GEMS MSD, MAL-ED, MVS +/- dysentery, and MVS demonstrated high sensitivity in predicting death or hospitalization.
  • The Shigella mortality score exhibited the largest area under the curve (91.0) for predicting adverse outcomes.

Conclusions:

  • The Modified Vesikari Score (MVS), MVS with dysentery, and the MAL-ED score are effective in identifying adverse outcomes in children with Shigella diarrhea.
  • These validated scores represent viable options for establishing case definitions in future Shigella vaccine efficacy trials.
  • This research provides critical data for optimizing Shigella vaccine trial design and endpoint selection.
Abstract

Keywords:
Shigellaclinical definitiondiarrhea severityvaccine

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