{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:00:34Z","timestamp":1789192834762,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010722","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000}}],"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"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":["OPP1131125"],"award-info":[{"award-number":["OPP1131125"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K01AI130326"],"award-info":[{"award-number":["K01AI130326"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic>Shigella<\/jats:italic> infections cause inflammation, which has been hypothesized to mediate the associations between <jats:italic>Shigella<\/jats:italic> and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and <jats:italic>Shigella<\/jats:italic> infections affect school-aged growth and cognitive outcomes from 6\u20138 years of age.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/principal findings<\/jats:title>\n<jats:p>We conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6\u20138 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study. We estimated the associations between <jats:italic>Shigella<\/jats:italic> burden and inflammation with linear growth at 2, 5, and 6\u20138 years of age, and with the cognitive test scores using linear regression and adjusting for potential confounding variables. We also assessed whether inflammation mediated the associations between <jats:italic>Shigella<\/jats:italic> and school-aged outcomes using a regression-based approach to mediation analysis. A high prevalence of <jats:italic>Shigella<\/jats:italic> was associated with a 0.32 (95% CI: 0.08, 0.56) z-score lower height-for-age z-score (HAZ) at 6\u20138 years compared to a low prevalence of <jats:italic>Shigella<\/jats:italic>. Intestinal inflammation had a smaller association with HAZ at 6\u20138 years. <jats:italic>Shigella<\/jats:italic> burden had small and consistently negative associations with cognitive outcomes in Brazil and Tanzania, but not South Africa, and the estimates were not statistically significant. Systemic inflammation was strongly associated with lower verbal fluency scores in Brazil (semantic fluency z-score difference: -0.57, 95% CI: -1.05, -0.10; phonemic fluency z-score difference: -0.48, 95% CI: -0.93, -0.03). There was no evidence that intestinal inflammation mediated the association between <jats:italic>Shigella<\/jats:italic> and HAZ or cognitive outcomes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/significance<\/jats:title>\n<jats:p>While <jats:italic>Shigella<\/jats:italic> infections were consistently associated with long-term deficits in linear growth, the estimates of the negative associations between <jats:italic>Shigella<\/jats:italic> and cognitive outcomes were imprecise and only observed in the Brazil and Tanzania sites. Systemic inflammation was strongly associated with lower semantic and phonemic fluency scores in Brazil only, highlighting the site-specificity of effects.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0010722","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T18:32:58Z","timestamp":1663957978000},"page":"e0010722","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Impact of Shigella infections and inflammation early in life on child growth and school-aged cognitive outcomes: Findings from three birth cohorts over eight years"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4942-3747","authenticated-orcid":true,"given":"Elizabeth T.","family":"Rogawski McQuade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Scharf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erling","family":"Svensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Huggins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Maphula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliwaza","family":"Bayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislaus","family":"Blacy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Pamplona E. de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric R.","family":"Houpt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal O.","family":"Bessong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estomih R.","family":"Mduma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo A. 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