{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:20:55Z","timestamp":1789554055851,"version":"build-2803163510"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T00:00:00Z","timestamp":1602460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1019093"],"award-info":[{"award-number":["OPP1019093"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1197861"],"award-info":[{"award-number":["OPP1197861"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold &amp;lt;27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared to culture-positive Shigella MSD cases (n\u2005=\u2005745), culture-negative\/qPCR-attributable Shigella cases (n\u2005=\u2005852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age\u2005&amp;lt;12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaa1545","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T04:00:23Z","timestamp":1602216023000},"page":"e569-e579","source":"Crossref","is-referenced-by-count":32,"title":["The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a <i>Shigella<\/i> Severity Score: Implications for Pediatric <i>Shigella<\/i> Vaccine Trials"],"prefix":"10.1093","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0051-9131","authenticated-orcid":false,"given":"Patricia B","family":"Pavlinac","sequence":"first","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, Washington,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A","family":"Platts-Mills","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirkby D","family":"Tickell","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of Washington, Seattle, Washington,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Juma","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Kenya Medical Research Institute (KEMRI), Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furqan","family":"Kabir","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Aga Khan University, Karachi,Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Nkeze","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Okoi","sequence":"additional","affiliation":[{"name":"Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul,The Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darwin J","family":"Operario","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, 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