Evidence map›Paper›PMID 39300660›Full record

ArticleThe American journal of clinical nutrition2024

Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children.

Paul Kelly, Kelley VanBuskirk, David Coomes, Samer Mouksassi, Gerald Smith, Zehra Jamil, Md Shabab Hossain, Sana Syed, Chelsea Marie, Phillip I Tarr and 14 more

Abstract readComparative Study
In one paragraph

Article in The American journal of clinical nutrition, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Mild Duodenal Mucosal Injury and Increased Type I Interferon Signaling Are Preludes to Celiac Disease.Laboratory investigation; a journal of technical methods and pathology · 2025
    Article
  8. Review
  9. Article
  10. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Paul KellyBlizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, United Kingdom. Electronic address: m.p.kelly@qmul.ac.uk.
Kelley VanBuskirkDepartment of Global Health, University of Washington School of Public Health, Seattle, WA, United States.
David CoomesDepartment of Epidemiology, University of Washington School of Public Health, Seattle, WA, United States.
Samer MouksassiCertara, Princeton, NJ, United States.
Gerald SmithCytel, Vancouver, British Columbia, Canada.
Zehra JamilDepartment of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Md Shabab HossainNutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Sana SyedDepartment of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, United States.
Chelsea MarieDepartment of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Phillip I TarrDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
Peter B SullivanDepartment of Paediatrics, Children's Hospital, University of Oxford, Oxford, United Kingdom.
William A PetriDepartment of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Donna M DennoDepartment of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States.
Tahmeed AhmedNutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Mustafa MahfuzNutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
S Asad AliDepartment of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Sean R MooreDepartment of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, United States.
I Malick NdaoDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
Guillermo J TearneyDepartment of Pathology, Harvard Medical School, Boston, MA, United States.
Ömer H YilmazDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United States.
Shyam S RaghavanDepartment of Pathology, University of Virginia School of Medicine, Charlottesville, VA, United States.
Christopher A MoskalukDepartment of Pathology, University of Virginia School of Medicine, Charlottesville, VA, United States.
Ta-Chiang LiuDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States.
EEDBI Consortium

Funding

Washington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Jeffrey Wade Brown · 2000 to 2026
$30.8M
NIDDK NIH HHS P30 DK052574
6 · The paper itself

Abstract

backgroundEnvironmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses.

objectivesWe set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia ("EED") with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as "normal") or celiac disease.

methodsFive gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner's glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value.

resultsBiopsies from the duodenal bulb showed higher intramucosal Brunner's gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner's glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan.

conclusionsThis scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED.

Indexed as

DuodenumBangladeshBiopsyCeliac DiseaseChildChild Nutrition DisordersChild, PreschoolCohort StudiesFemaleGoblet CellsHumansInfantIntestinal DiseasesIntestinal MucosaMalePakistanchild healthcryptsenteropathyglobal healthgoblet cellsintestinemalnutritionPaneth cellsstuntingvilli

Identifiers

PMID39300660
PMCPMC13168970

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.