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Environmental enteric dysfunction (EED) is an asymptomatic acquired disorder characterized by upper small bowel inflammation, villus blunting, and gut permeability. It is a major contributor to poor growth in childhood as well as other highly consequential outcomes such as delayed neuorcognitive development. After decades of intermittent interest in this entity, we are now seeing a resurgence in the field of EED. However, recent studies have been hampered by a lack of investigation of the target tissue-the upper small bowel. In 2016, the EEDBI (Environmental Enteric Dysfunction Biopsy Initiative) Consortium was established as a common scientific platform across 3 independent EED biopsy cohort studies in Bangladesh, Pakistan, and Zambia. Two centers in the United States recruited comparison groups of children undergoing endoscopy for clinical indications. The EEDBI Consortium goal was to augment the contributions of the individual centers and answer high-level questions amenable to analysis and interpretation across the studies. Here, we describe the Consortium and its cohorts and recruitment procedures across studies. We also offer details applicable to all papers in this supplement, which describe EED mucosal histology, morphometry, immunohistochemistry, and transcriptomics as well as histology relationship to pathogens and biomarkers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses., Objectives: We 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., Methods: Five 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., Results: Biopsies 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., Conclusions: This 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Acute respiratory infections (ARI) play a major role in hospitalizations in the Middle East, but the specific viral causes are unknown. We conducted prospective viral surveillance in children <5 y of age admitted with ARI and/or fever at 2 dissimilar hospitals in Amman, Jordan during peak respiratory syncytial virus (RSV) season. We collected prospective clinical and demographic data and obtained nose/throat swabs for testing for RSV by real-time polymerase chain reaction (RT-PCR). We obtained clinical and laboratory data for 728/743 (98%) subjects enrolled. The children's median age was 4.3 months, 58.4% were males, 87% were breastfed, 4% attended day care, 67% were exposed to smokers, 7% were admitted to the intensive care unit, and 0.7% died (n = 5). Out of 728 subjects, 467 (64%) tested positive by RT-PCR for RSV. Comparing RSV-positive with RSV-negative subjects, the RSV-positive subjects had lower median age (3.6 vs 6.4 months, p < 0.001) and fewer males (55% vs 64%, p = 0.02). RSV-positive children had higher rates of oxygen use (72% vs 42%, p < 0.001), a longer hospital stay (5 vs 4 days, p = 0.001), and higher hospital charges (US$538 vs US$431, p < 0.001) than RSV-negative children. In young hospitalized Jordanian infants, the medical and financial burden of RSV was found to be high. Effective preventive measures, such as an RSV vaccine, would have a significant beneficial impact.