Highly prevalent conditions with multiple and complex underlying etiologies are a challenge to public health. Undernutrition, for example, affects 20% of children in the developing world. The cause and consequence of poor nutrition are multifaceted. Undernutrition has been associated with half of all deaths worldwide in children aged <5 years; in addition, its pernicious long-term effects in early childhood have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Study, led by the Fogarty International Center of the National Institutes of Health and the Foundation for the National Institutes of Health, has been established at sites in 8 countries with historically high incidence of diarrheal disease and undernutrition. Central to the study is the hypothesis that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. It is further postulated that this leads to growth faltering and deficits in cognitive development. The effects of repeated enteric infection and undernutrition on the immune response to childhood vaccines is also being examined in the study. MAL-ED uses a prospective longitudinal design that offers a unique opportunity to directly address a complex system of exposures and health outcomes in the community-rather than the relatively rarer circumstances that lead to hospitalization-during the critical period of development of the first 2 years of life. Among the factors being evaluated are enteric infections (with or without diarrhea) and other illness indicators, micronutrient levels, diet, socioeconomic status, gut function, and the environment. MAL-ED aims to describe these factors, their interrelationships, and their overall impact on health outcomes in unprecedented detail, and to make individual, site-specific, and generalized recommendations regarding the nature and timing of possible interventions aimed at improving child health and development in these resource-poor settings.

HighlightsChildren living in these settings had a high prevalence of enteropathogens, high levels of intestinal inflammation, abnormal intestinal permeability, high markers of systemic inflammation, and postnatal acquired linear growth deficits when compared to children living in the US or EuropeThis study contributes empiric evidence to demonstrate that enteric infection alters both fecal markers of inflammation and permeabilityCurrent markers of enteropathy fail to account for a large portion of the observed shortfalls in linear growth in these populations, and markers of systemic inflammation appear as the most promising predictive biomarkers for identifying linear growth failure in childrenEnvironmental enteropathy (EE) is hypothesized as a mediator of growth faltering, but few prospective studies have evaluated pathways linking enteropathogen exposure, intestinal inflammation and permeability, and growth. The MAL-ED study represents a novel analytical framework and explicitly evaluates multiple putative EE pathways in combination and using an unprecedented quantity of data. Despite evidence that gut inflammation and altered gut permeability are frequently present and that associations between enteropathogen exposure and gut dysfunction exist, the observed attributable effects of EE on growth faltering in young children were small.

Childhood malnutrition is not just due to lack of nutrients, it can also be caused by enteric infections leading to intestinal inflammation and malabsorption of nutrients. Human genetic polymorphisms can alter host genes that affect nutrient absorption and metabolism. Changes in intestinal microbial ecology and the microbiome (the collective genome of the intestinal microbiota) can also affect the harvest of nutrients from the diet. A substantial proportion of malnourished children fail to recover due to inappropriate treatment. However, there may be other causes for treatment failure, including changes in the microbiome and infection with an enteropathogen, and a genetic predisposition to malnutrition may exist. It is, therefore, logical to undertake the following: 1) investigate genetic predisposition to malnutrition, 2) determine the genetic markers and biomarkers that can help identify children at risk of malnutrition, and 3) look for new treatment modalities that can improve the clinical management of children with malnutrition.

Bangladesh is a country with a high burden of micronutrient malnutrition. Stunting affects 41 % of children aged under 5 years. Zn is one of the key micronutrients that is associated with stunting. The present study, as part of the national micronutrient survey 2011–2012, revealed for the first time the nationally representative prevalence of Zn deficiency and determined the associations of the condition. A cross-sectional ‘nationwide’ survey was conducted in pre-school-age children (6–59 months; PSAC) and non-pregnant non-lactating women (15–49 years; NPNLW). Multistage random sampling was done in 150 clusters; fifty in each of the rural, urban and slum strata. Data were analysed on 662 PSAC and 1073 NPNLW. Serum Zn was assayed by atomic absorption spectrophotometry. Zn deficiency was defined as serum Zn of <9·9 and <10·1 µmol/l in PSAC and NPNLW, respectively. The national prevalence of Zn deficiency was 44·6 and 57·3 % in PSAC and NPNLW, respectively. In PSAC, it was 29·5, 48·6 and 51·7 %, respectively, in urban, rural and slum strata. Household expenses (β = 0·13; P = 0·007), Hb (β = 0·10; P = 0·005), intake of animal-source Zn (β = 0·096; P = 0·02) and asset score (β = 0·11; P = 0·03) were positively associated with serum Zn in NPNLW. Residence in an urban area (β = 0·33; P = 0·03) and intake of plant-origin Zn (β = −0·13; P = 0·038) determined higher and lower status of Zn in PSAC, respectively. Zn deficiency was highly prevalent in Bangladesh, and it was principally related to inadequate quality of diet. To improve Zn nutrition, Bangladesh needs to strengthen research and programmes related to Zn biofortification, fortification and phytate-reducing technologies in the food system in the short and medium term. In addition, promotion of animal-source Zn for all is important in the long run.