Environmental Enteric Dysfunction in Children

Abstract

Diarrheal diseases are a major cause of childhood death in resource-poor countries, killing approximately 760,000 children younger than 5 years each year. Although deaths due to diarrhea have declined dramatically, high rates of stunting and malnutrition have persisted. Environmental enteric dysfunction (EED) is a subclinical condition caused by constant fecal-oral contamination with resultant intestinal inflammation and villous blunting. These histological changes were first described in the 1960s, but the clinical effect of EED is only just being recognized in the context of failure of nutritional interventions and oral vaccines in resource-poor countries. We review the existing literature regarding the underlying causes of and potential interventions for EED in children, highlighting the epidemiology, clinical and histologic classification of the entity, and discussing novel biomarkers and possible therapies. Future research priorities are also discussed.

Figure 1

Proposed schematic progression of Environmental Enteric Dysfunction resulting from a hyper-stimulated enteric immune system: i) chronic recurrent exposure to abnormally high concentrations of ingested enteropathogens in the small-intestinal lumen, ii) mucosal inflammation with infiltration of the lamina propria by plasma cells and lymphocytes, iii) spectrum of villous blunting, altered barrier integrity, and reduced intestinal absorptive capacity (e.g. malabsorption of small sugars such as lactulose). The bidirectional arrow points out the fact that the lesion may improve or worsen over time (Illustration © 2015 Haderer & Muller Biomedical Art).

Figure 2

a) & b) Duodenal biopsies typical histo-pathological features of Environmental Enteric Dysfunction (villus atrophy, crypt hyperplasia and lamina propria infiltration by inflammatory cells) (Histopathology images courtesy of Dr. A Ali)