Defining severe shigellosis in the Enterics for Global Health study: A comparison of leading diarrhea severity definitions among children with Shigella diarrhea.
Olivia Lang Schultes, Aneeta Hotwani , Patricia B Pavlinac , M Jahangir Hossain , Dilruba Nasrin , Richard Omore , Farhana Khanam , Flywell Kawonga , Paul F Garcia Bardales , Hannah E Atlas , Alex O Awuor , Henry Badji , Bakary Conteh , Jennifer Cornick , Erika Feutz , Sean R Galagan , Ensa Gitteh , Eric R Houpt , Junaid Iqbal , Sadia Islam , Furqan Kabir , Adama Mamby Keita , Jie Liu , Donnie Mategula , Chimwemwe Mhango , Md Parvej Mosharraf , Billy Ogwel , Caleb Okonji , Uduma Uma Onwuchekwa , Tackeshy Pinedo Vasquez , S M Azadul Alam Raz , Lucero Romaina-Cachique , Francesca Schiaffino , Milagritos D Tapia , Sharon M Tennant , Mohammad Tahir Yousafzai , Khuzwayo C Jere , Margaret N Kosek , Samba O Sow , James A Platts-Mills , Farah Naz Qamar , Elizabeth T Rogawski McQuade , Karen L Kotloff , John Benjamin Ochieng , Firdausi Qadri , EFGH Consortium
Date:
2025-08
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.
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