{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T09:10:01Z","timestamp":1780650601527,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010837","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health - Tropical Medicine Research Centers","award":["AI098507"],"award-info":[{"award-number":["AI098507"]}]},{"name":"Brazil Initiative at the Brown University Watson Institute for International and Public Affairs"},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Minas Gerais"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Studies have implicated schistosomiasis as a cause of intestinal barrier disruption, a salient feature of environmental enteric dysfunction (EED), as eggs translocate from the sterile bloodstream through the gut wall. We examined the longitudinal impact of praziquantel (PZQ) treatment on a) EED biomarkers and b) Insulin growth factor I (IGF-1), a key driver of childhood linear growth, since EED has been implicated in linear growth stunting.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methodology<\/jats:title><jats:p>290 children infected with<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>in Brazil were treated with PZQ at baseline. EED biomarkers lipopolysaccharide (LPS) and intestinal fatty acid binding-protein (I-FABP) were measured, as well as IGF-1 at baseline, 6 and 12-months. Multivariate regression analysis was applied to assess associations between<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>intensity and plasma biomarkers (LPS, I-FABP, and IGF-1), controlling for potential confounding variables.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Principal findings<\/jats:title><jats:p>At baseline,<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>infection intensities were 27.2% light, 46.9% moderate, and 25.9% heavy. LPS concentrations were significantly reduced at the 12-month visit compared to baseline (p = 0.0002). No longitudinal changes were observed for I-FABP or IGF-1 in the 6- or 12-month periods following baseline treatment. After 6-months, I-FABP concentration was significantly higher in high vs low intensity (p = 0.0017). IGF-1 concentrations were significantly lower among children with high and moderate vs low intensity infections at each study visit.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions\/significance<\/jats:title><jats:p>We report that<jats:italic>S<\/jats:italic>.<jats:italic>mansoni<\/jats:italic>infection impacts LPS, I-FABP and IGF-1. These findings suggest a mechanistic role for EED in schistosomiasis-related morbidities, particularly linear growth.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pntd.0010837","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T17:40:19Z","timestamp":1664991619000},"page":"e0010837","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of environmental enteric dysfunction in the pathogenesis of Schistosoma mansoni-associated morbidity in school-aged children"],"prefix":"10.1371","volume":"16","author":[{"given":"Jacqueline","family":"Ara\u00fajo 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Cadernos de Aten\u00e7\u00e3o B\u00e1sica n\u00b0 21. 2nd ed 2008. p. 48\u201365."},{"key":"pntd.0010837.ref039","first-page":"2002","volume-title":"Prevention and control of schistosomiasis and soil-transmitted helminthiasis: report of a WHO expert committee","author":"World Health Organization"},{"key":"pntd.0010837.ref040","volume-title":"Socio-economic differences in health, nutrition, and population in Brazil","author":"DR Gwatkin","year":"2000"},{"issue":"1 Pt 1","key":"pntd.0010837.ref041","first-page":"E33","article-title":"Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin","volume":"269","author":"J Fan","year":"1995","journal-title":"Am J Physiol"},{"issue":"4","key":"pntd.0010837.ref042","first-page":"R956","article-title":"Role of central IL-1 in regulating peripheral IGF-I during endotoxemia and sepsis","volume":"274","author":"CH Lang","year":"1998","journal-title":"Am J Physiol"},{"key":"pntd.0010837.ref043","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ghir.2019.08.004","article-title":"Role of ghrelin on growth hormone\/insulin-like growth factor-1 axis during endotoxemia","volume":"48\u201349","author":"F Faim","year":"2019","journal-title":"Growth Horm IGF Res"},{"issue":"1","key":"pntd.0010837.ref044","doi-asserted-by":"crossref","first-page":"E50","DOI":"10.1152\/ajpendo.00149.2003","article-title":"NO plays a role in LPS-induced decreases in circulating IGF-I and IGFBP-3 and their gene expression in the liver","volume":"286","author":"T Priego","year":"2004","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"6","key":"pntd.0010837.ref045","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.4269\/ajtmh.19-0875","article-title":"Plasma Endotoxin Levels Are Not Increased in Schistosoma mansoni-Infected Women without Signs or Symptoms of Hepatosplenic Disease","volume":"102","author":"KM Klemperer","year":"2020","journal-title":"Am J Trop Med Hyg"},{"issue":"2","key":"pntd.0010837.ref046","doi-asserted-by":"crossref","first-page":"495","DOI":"10.4269\/ajtmh.17-0949","article-title":"Endotoxin at the Maternal-Fetal Interface in a Resource-Constrained Setting: Risk Factors and Associated Birth Outcomes","volume":"99","author":"EA McDonald","year":"2018","journal-title":"Am J Trop Med Hyg"},{"issue":"4","key":"pntd.0010837.ref047","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/apt.12194","article-title":"Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies","volume":"37","author":"MP Adriaanse","year":"2013","journal-title":"Aliment Pharmacol Ther"},{"issue":"12","key":"pntd.0010837.ref048","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.3109\/00365521.2011.627447","article-title":"Additional value of serum I-FABP levels for evaluating celiac disease activity in children","volume":"46","author":"AC Vreugdenhil","year":"2011","journal-title":"Scand J Gastroenterol"},{"issue":"8","key":"pntd.0010837.ref049","doi-asserted-by":"crossref","first-page":"e0006710","DOI":"10.1371\/journal.pntd.0006710","article-title":"Aberrant plasma MMP and TIMP dynamics in Schistosoma\u2014Immune reconstitution inflammatory syndrome (IRIS)","volume":"12","author":"O Goovaerts","year":"2018","journal-title":"PLoS neglected tropical diseases"},{"issue":"9541","key":"pntd.0010837.ref050","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S0140-6736(06)69440-3","article-title":"Human schistosomiasis","volume":"368","author":"B Gryseels","year":"2006","journal-title":"The Lancet"},{"key":"pntd.0010837.ref051","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.3389\/fimmu.2018.03042","article-title":"Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses","volume":"9","author":"AH Costain","year":"2018","journal-title":"Frontiers in immunology"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0010837","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:04:55Z","timestamp":1677035095000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010837"}},"subtitle":[],"editor":[{"given":"W. 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