Assessment of Environmental Enteropathy in the MAL-ED Cohort Study: Theoretical and Analytic Framework

Abstract

Individuals in the developing world live in conditions of intense exposure to enteric pathogens due to suboptimal water and sanitation. These environmental conditions lead to alterations in intestinal structure, function, and local and systemic immune activation that are collectively referred to as environmental enteropathy (EE). This condition, although poorly defined, is likely to be exacerbated by undernutrition as well as being responsible for permanent growth deficits acquired in early childhood, vaccine failure, and loss of human potential. This article addresses the underlying theoretical and analytical frameworks informing the methodology proposed by the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study to define and quantify the burden of disease caused by EE within a multisite cohort. Additionally, we will discuss efforts to improve, standardize, and harmonize laboratory practices within the MAL-ED Network. These efforts will address current limitations in the understanding of EE and its burden on children in the developing world.

Desnutrição infantil em um dos municípios de maior risco nutricional do Brasil: estudo de base populacional na Amazônia Ocidental Brasileira

“…The maintenance of the vaccination schedule shows the importance of access to primary health care and assists in the prevention of infectious episodes, another important factor for the development of a stunting 41 . The role of infectious diseases on height deficits has been well documented and attributed, among other factors, to a shift in energy expenditure to combat the infectious process to the detriment of growth 42 . The introduction of cow's milk was premature and inadequate, being statistically associated with stunting.…”

Giardia: a pathogen or commensal for children in high-prevalence settings?

“…The current working model of enteropathogen-associated growth shortfalls in children links nutrient deficiencies with microbial-driven intestinal inflammation, gut dysfunction, and increased intestinal permeability, termed environmental enteropathy (EE)[27, 28**]. Chronic Giardia infection has been associated with altered intestinal architecture and chronic lymphocytic inflammation in humans and some experimental models [4, 29, 30].…”

Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh

“…The lactulose mannitol ratio (L:M) test of intestinal permeability is widely used but suffers from several limitations: it measures permeability but not intestinal or systemic inflammation (2); it lacks formal validation studies (18, 19); and it is burdensome to implement in field settings. Proposed alternate markers of EED measured in serum and stool could address these shortcomings (2, 4, 13), but limited data exist to support their use for this purpose. Several proposed fecal markers, such as myeloperoxidase, neopterin, lactoferrin and calprotectin, markers of inflammation, and α-1 antitrypsin, a marker of protein-losing enteropathy, come from the study of inflammatory bowel disease (20–22).…”