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Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas

Background 
Environmental enteric dysfunction (EED) is commonly defined as an acquired subclinical disorder of the small intestine, characterized by villous atrophy and crypt hyperplasia. EED has been proposed to underlie stunted growth among children in developing countries. A collection of biomarkers, organized into distinct domains, has been used to measure different aspects of EED. Here, we examine whether these hypothesized relationships, among EED domains and between each domain and stunting, are supported by data from recent studies.


Methodology 
A systematic literature search was conducted using PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL between January 1, 2010 and April 20, 2017. Information on study objective, design, population, location, biomarkers, and results were recorded, as well as qualitative and quantitative definitions of EED. Biomarkers were organized into five EED domains, and the number of studies that support or do not support relationships among domains and between each domain with stunting were summarized.


Results 
There was little evidence to support the pathway from intestinal permeability to microbial translocation and from microbial translocation to stunting, but stronger support existed for the link between intestinal inflammation and systemic inflammation and for intestinal inflammation and stunting. There was conflicting evidence for the pathways from intestinal damage to intestinal permeability and intestinal damage to stunting.


Conclusions 
These results suggest that certain EED biomarkers may require reconsideration, particularly those most difficult to measure, such as microbial translocation and intestinal permeability. We discuss several issues with currently used biomarkers and recommend further analysis of pathogen-induced changes to the intestinal microbiota as a pathway leading to stunting.

/pdf/environmental-enteric-dysfunction-pathways-and-child-t0krrmgh6t.pdf

Environmental enteric dysfunction pathways and child stunting: A systematic review.

Background Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health p...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1916004

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy

Environmental enteric dysfunction (EED) is an acquired enteropathy of the small intestine, characterized by enteric inflammation, villus blunting and decreased crypt-to-villus ratio. EED has been associated with poor outcomes, including chronic malnutrition (stunting), wasting and reduced vaccine efficacy among children living in low-resource settings. As a result, EED may be a valuable interventional target for programs aiming to reduce childhood morbidity in low and middle-income countries. Several highly plausible mechanisms link the proposed pathophysiology underlying EED to adverse outcomes, but causal attribution of these pathways has proved challenging. We provide an overview of recent studies evaluating the causes and consequences of EED. These include studies of the role of subclinical enteric infection as a primary cause of EED, and efforts to understand how EED-associated systemic inflammation and malabsorption may result in long-term morbidity. Finally, we outline recently completed and upcoming clinical trials that test novel interventions to prevent or treat this highly prevalent condition. Significant strides have been made in linking environmental exposure to enteric pathogens and toxins with EED, and in understanding the multifactorial mechanisms underlying this complex condition. Further insights may come from several ongoing and upcoming interventional studies trialing a variety of novel management strategies.

/pdf/environmental-enteric-dysfunction-a-review-of-potential-2kqrfbv20p.pdf

Environmental enteric dysfunction: a review of potential mechanisms, consequences and management strategies.

Pediatric clinical gastroenterology

Background A major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity. Methods Duodenal endoscopic biopsies from two cohorts where EED is prevalent (Pakistan, Zambia) and North American children with and without gluten sensitive enteropathy (GSE) were processed for routine hematoxylin & eosin (H&E) staining, and scanned to produce whole slide images (WSIs) which we shared among study pathologists via a secure web browser-based platform. A semi-quantitative scoring index composed of 11 parameters encompassing tissue injury and response patterns commonly observed in routine clinical practice was constructed by three gastrointestinal pathologists, with input from EED experts. The pathologists then read the WSIs using the EED histology index, and inter-observer reliability was assessed. The histology index was further used to identify within- and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype. Results Eight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet's AC 0.93. Zambian and Pakistani tissues shared some histologic features with GSE, but most features were distinct, particularly abundance of intraepithelial lymphocytes in the Pakistani cohort, and marked villous destruction and loss of secretory cell lineages in the Zambian cohort. Conclusions We propose the first EED histology index for interpreting duodenal biopsies. This index should be useful in future clinical and translational studies of this widespread, poorly understood, and highly consequential disorder, which might be caused by multiple contributing processes, in different regions of the world.

/pdf/a-novel-histological-index-for-evaluation-of-environmental-15bdh0c3vi.pdf

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

Summary Objective: To assess anemia prevalence and identify associated parameters in children <3 years of age in a rural area of Ghana. Method: Univariate and multivariate logistic regression of cross-sectional survey results from 861 children aged <3 years attending routine immunization services in Berekum district. Results: Anemia prevalence was 73.1%; most were either mildly (31.2%) or moderately (38.7%) affected. Risk factors for anemia (hemoglobin < 11.0 g/dl) in multivariate analysis were malaria parasitemia and male sex; these factors and younger age were associated with anemia severity. A partial defect in glucose-6-phosphate dehydrogenase was associated with decreased severity. Height-for-age, but not weight-for-age, was associated with anemia and its severity. Conclusions: Malaria parasitemia was strongly associated with anemia and its severity, suggesting that malaria control may be the most effective way to reduce the burden of anemia in rural Ghanaian children.

/pdf/pediatric-anemia-in-rural-ghana-a-cross-sectional-study-of-3zgj5xc4c5.pdf

Pediatric anemia in rural Ghana: a cross-sectional study of prevalence and risk factors.

/pdf/environmental-enteric-dysfunction-advancing-current-358d5yc8uj.pdf

Environmental enteric dysfunction: Advancing current knowledge

/pdf/chapter-one-environmental-enteric-dysfunction-eed-background-442n8qle8l.pdf

Chapter One. Environmental enteric dysfunction (EED) background

when available) was reviewed by two analysts to determine inclusion status for the EED Library. Dual review reduces bias and inaccuracies in the systematic review process. The principal investigators (DMD and PIT) initially piloted the Library inclusion process, until 100% concordance was achieved upon independent review of 1,300 consecutive references. A series of training sessions to convey the goals of the project, along with a protocol with which to determine inclusion of a reference in the EED Library, were provided to the team of RAs. Verbal and written instructions were conveyed to the analysts (Table 4), and a schematic regarding articles to include, and under what category, was also provided (Figure 5).

/pdf/chapter-three-eed-library-as-a-basis-for-systematic-reviews-qv9rjshdgz.pdf

Chapter Three. EED library as a basis for systematic reviews

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