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Defining severe shigellosis in the Enterics for Global Health study: A comparison of leading diarrhea severity definitions among children with Shigella diarrhea

Article scientifique 2025 Anglais

Résumé

Abstract Background Shigella has high global burden and serious long-term outcomes among young children. Increasing antibiotic resistance makes Shigella vaccine development a critical priority. Choosing the optimal 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 to a clinic with diarrhea were enrolled in Bangladesh, Kenya, Malawi, Mali, Pakistan, Peru, and The Gambia. Among children with Shigella , six dichotomized diarrhea severity definitions (GEMS moderate-to-severe diarrhea (MSD), Modified Vesikari Score (MVS), MVS +/− dysentery, Clark score, MAL-ED score, and Shigella mortality score) were examined against two outcomes: change in length/height-for-age z-score (ΔLAZ/HAZ) from enrollment to three-month follow-up and death or hospitalization within fourteen days of enrollment. We compared the performance of each severity score to predict outcomes using linear regression, measures of diagnostic accuracy, and Receiver Operating Characteristic (ROC) curves. Results Among 1,968 children with Shigella , moderate or severe diarrhea was negatively associated with ΔLAZ/HAZ by three definitions: 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, while Shigella mortality had the largest area under the curve (91.0). Conclusions MVS, MVS +/− dysentery, and the MAL-ED score identified adverse outcomes following Shigella diarrhea, indicating that they are viable options for a Shigella vaccine trial case definition. 40-word summary We compared six diarrhea severity definitions among children 6-35 months with Shigella . Moderate-to-severe diarrhea as measured by Modified Vesikari Score (MVS), MVS +/− dysentery, and MAL-ED score was associated with reduced length/height-for-age z-score and hospitalization or mortality.

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Schultes, O., Hotwani, A., Pavlinac, P., Hossain, M., Nasrin, D., Omore, R., Khanam, F., Kawonga, F., Bardales, P., Atlas, H., Awuor, A., Badji, H., Conteh, B., Cornick, J., Feutz, E., Galagan, S., Gitteh, E., Houpt, E., Iqbal, J., Islam, S., Kabir, F., Keita, A., Liu, J., Mategula, D., Mhango, C., Mosharraf, M., Ogwel, B., Okonji, C., Onwuchekwa, U., Raz, S., Romaina-Cachique, L., Schiaffino, F., Vasquez, T., Yousafzai, M., Tapia, M., Tennant, S., Jere, K., Kosek, M., Sow, S., Platts-Mills, J., Qamar, F., McQuade, E., Kotloff, K., Ochieng, J., Qadri, F. (2025). Defining severe shigellosis in the Enterics for Global Health study: A comparison of leading diarrhea severity definitions among children with Shigella diarrhea. https://doi.org/10.1101/2025.07.30.25331602

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Auteur(s)

Olívia Lang Schultes Aneeta Hotwani Patricia B. Pavlinac Mohammed 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 L. 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 U. Onwuchekwa Saifa Raz Lucero A. Romaina-Cachique Francesca Schiaffino Tackeshy Pinedo Vasquez Mohammad Tahir Yousafzai Milagritos D. Tapia Sharon M. Tennant Khuzwayo C. Jere Margaret Kosek Samba O. Sow James A Platts-Mills Farah Naz Qamar Elizabeth T. Rogawski McQuade Karen L. Kotloff John B. Ochieng Firdausi Qadri

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