{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:08:29Z","timestamp":1790068109894,"version":"4.0.1"},"reference-count":34,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,6]]},"abstract":"<jats:p>Despite nutrition interventions, stunting thought to be secondary to underlying environmental enteropathy (EE) remains pervasive among infants residing in resource-poor countries and remains poorly characterized. From a birth cohort of 380 children, 65 malnourished infants received 12 weeks of nutritional supplementation with ready-to-use therapeutic food (RUTF). Eleven children with insufficient response to RUTF underwent upper endoscopy with duodenal biopsies, which were compared with U.S., age-matched specimens for healthy, celiac disease, non-celiac villous atrophy, non-celiac intraepithelial lymphocytosis, and graft-versus-host disease patients. Of the 11 children biopsied, EE was found in 10 (91%) with one subject with celiac disease. Morphometry demonstrated decreased villus-to-crypt (V:C) ratios in EE relative to healthy and non-celiac lymphocytosis patients. Environmental enteropathy villus volumes were significantly decreased relative to healthy controls. In EE, average CD3<jats:sup>+<\/jats:sup> cells per 100 epithelial cells and per 1,000 \u00b5m<jats:sup>2<\/jats:sup> of lamina propria and the number of lamina propria CD20<jats:sup>+<\/jats:sup> B-cell aggregates were increased relative to all other groups. Our results indicate that V:C ratios are reduced in EE but are less severe than in celiac disease. Environmental enteropathy intraepithelial and lamina propria T lymphocytosis is of greater magnitude than that in celiac disease. The increases in lamina propria B and T lymphocytes suggest that non-cytolytic lymphocytic activation may be a more prominent feature of EE relative to celiac disease. These results provide new insights into shared yet distinct histological and immunological features of EE and celiac disease in children.<\/jats:p>","DOI":"10.4269\/ajtmh.17-0306","type":"journal-article","created":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T07:00:36Z","timestamp":1522738836000},"page":"1577-1584","source":"Crossref","is-referenced-by-count":26,"title":["Environmental Enteropathy in Undernourished Pakistani Children: Clinical and Histomorphometric Analyses"],"prefix":"10.4269","volume":"98","author":[{"given":"Sana","family":"Syed","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan;"},{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia;"},{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Yeruva","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Sailer","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Sadiq","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najeeha","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan;"}],"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":"Kumail","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahida","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerrold","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Pathology, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Asad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"J Pediatr Gastroenterol Nutr","first-page":"6","article-title":"Environmental enteric dysfunction in children","volume":"63","author":"Syed","year":"2016"},{"key":"b2","series-title":"Lancet","first-page":"1032","article-title":"Child undernutrition, tropical enteropathy, toilets, and handwashing","volume":"374","author":"Humphrey","year":"2009"},{"key":"b3","series-title":"Clin Infect Dis","first-page":"S207","article-title":"Environmental enteric dysfunction: pathogenesis, diagnosis, and clinical consequences","volume":"59","author":"Keusch","year":"2014"},{"key":"b4","series-title":"Food Nutr Bull","first-page":"357","article-title":"Implications of acquired environmental enteric dysfunction for growth and stunting in infants and children living in low- and middle-income countries","volume":"34","author":"Keusch","year":"2013"},{"key":"b5","series-title":"Trends Mol Med","first-page":"328","article-title":"Environmental enteropathy: critical implications of a poorly understood condition","volume":"18","author":"Korpe","year":"2012"},{"key":"b6","series-title":"Am J Trop Med Hyg","first-page":"756","article-title":"Enteropathies in the developing world: neglected effects on global health","volume":"86","author":"Prendergast","year":"2012"},{"key":"b7","series-title":"Curr Opin Gastroenterol","first-page":"12","article-title":"Environmental enteropathy","volume":"32","author":"Ali","year":"2016"},{"key":"b8","series-title":"J Pathol","first-page":"146","article-title":"The villus architecture of the small intestine in the tropics: a necropsy study","volume":"98","author":"Chacko","year":"1969"},{"key":"b9","series-title":"Ann Intern Med","first-page":"218","article-title":"Recovery of small-intestinal structure and function after residence in the tropics. I. Studies in Peace Corps volunteers","volume":"74","author":"Lindenbaum","year":"1971"},{"key":"b10","series-title":"Am J Clin Nutr","first-page":"1062","article-title":"Subclinical malabsorption in Thailand. I. Intestinal absorption in Thai children","volume":"25","author":"Keusch","year":"1972"},{"key":"b11","series-title":"Am J Clin Nutr","first-page":"1040","article-title":"Effect of Lactobacillus GG on intestinal integrity in Malawian children at risk of tropical enteropathy","volume":"82","author":"Galpin","year":"2005"},{"key":"b12","series-title":"J Infect Dis","first-page":"S23","article-title":"Innate immunity, gut integrity, and vitamin A in Gambian and Indian infants","volume":"182","author":"Thurnham","year":"2000"},{"key":"b13","series-title":"Br J Nutr","first-page":"141","article-title":"Poor intestinal permeability in mildly stunted Nepali children: associations with weaning practices and Giardia lamblia infection","volume":"88","author":"Goto","year":"2002"},{"key":"b14","series-title":"J Am Coll Nutr","first-page":"51","article-title":"Asymptomatic environmental enteropathy among slum-dwelling infants","volume":"13","author":"Fagundes Neto","year":"1994"},{"key":"b15","series-title":"Vaccine","first-page":"452","article-title":"Immune responses and protection in children in developing countries induced by oral vaccines","volume":"31","author":"Qadri","year":"2013"},{"key":"b16","series-title":"J Nutr","first-page":"1332","article-title":"Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation","volume":"133","author":"Campbell","year":"2003"},{"key":"b17","series-title":"J Nutr","first-page":"1237","article-title":"Environmental contamination and chronic inflammation influence human growth potential","volume":"133","author":"Solomons","year":"2003"},{"key":"b18","series-title":"Pediatr Res","first-page":"306","article-title":"Chronic T cell-mediated enteropathy in rural west African children: relationship with nutritional status and small bowel function","volume":"54","author":"Campbell","year":"2003"},{"key":"b19","series-title":"Nat Commun","first-page":"7806","article-title":"Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model","volume":"6","author":"Brown","year":"2015"},{"key":"b20","series-title":"PLoS Negl Trop Dis","first-page":"e0004820","article-title":"Cryptosporidium priming is more effective than vaccine for protection against cryptosporidiosis in a murine protein malnutrition model","volume":"10","author":"Bartelt","year":"2016"},{"key":"b21","author":"WHO","year":"2013"},{"key":"b22","series-title":"Public Health Nutr","first-page":"444","article-title":"Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993\u20132005","volume":"12","author":"McLean","year":"2009"},{"key":"b23","author":"World Health Organization","year":"2011"},{"key":"b24","series-title":"Am Fam Physician","first-page":"1425","article-title":"Update on vitamin B12 deficiency","volume":"83","author":"Langan","year":"2011"},{"key":"b25","author":"WHO","year":"2012"},{"key":"b26","series-title":"J Clin Endocrinol Metab","first-page":"1911","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011"},{"key":"b27","series-title":"J Clin Microbiol","first-page":"472","article-title":"A laboratory-developed TaqMan Array Card for simultaneous detection of 19 enteropathogens","volume":"51","author":"Liu","year":"2013"},{"key":"b28","series-title":"Lancet Infect Dis","first-page":"716","article-title":"Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea: a multicentre study","volume":"14","author":"Liu","year":"2014"},{"key":"b29","series-title":"J Pediatr Gastroenterol Nutr","first-page":"195","article-title":"Chronic diarrhea and malnutrition\u2013histology of the small intestinal lesion","volume":"12","author":"Sullivan","year":"1991"},{"key":"b30","series-title":"Postgrad Med J","first-page":"779","article-title":"Tropical malabsorption","volume":"82","author":"Ramakrishna","year":"2006"},{"key":"b31","author":"Syed","year":"2016"},{"key":"b32","series-title":"Sci Transl Med","first-page":"276ra24","article-title":"Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy","volume":"7","author":"Kau","year":"2015"},{"key":"b33","series-title":"J Pediatr Gastroenterol Nutr","first-page":"153","article-title":"Crypt fission peaks early during infancy and crypt hyperplasia broadly peaks during infancy and childhood in the small intestine of humans","volume":"47","author":"Cummins","year":"2008"},{"key":"b34","series-title":"J Pediatr Gastroenterol Nutr","first-page":"506","article-title":"Epithelial growth of the small intestine in human 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