Nutritional Enteric Failure: Neglected Tropical Diseases and Childhood Stunting.

Chronic malnutrition, defined by linear growth failure, or stunting, affects over 165 million children globally [1]. In many areas of the world with a high prevalence of stunting, children experience frequent and recurrent exposure to pathogens, including neglected tropical diseases (NTDs). These infections appear to have detrimental effects on linear growth [2–6], but interventions to promote linear growth have demonstrated limited benefit. Difficulty in establishing effective growth-promoting interventions is not unique to NTDs; even the optimal delivery of all interventions known to improve nutritional status is estimated to be able to reverse less than a quarter of all stunting [7]. The failure to identify effective interventions to reverse stunting offers the opportunity to develop a new conceptual model of chronic malnutrition that furthers our understanding of the mechanism linking pathogen and environmental exposures to linear growth failure. Such a conceptual model may guide the identification of new targets for intervention to reduce the substantial morbidity and mortality associated with chronic malnutrition [1]. The current definition of chronic malnutrition is based on anthropometric indicators suggesting previous or ongoing stunting. However, stunting and its associated cognitive and immunologic sequelae represent the end stage of a complex series of pathophysiologic events. Fundamentally, it is the failure of the enteric system to meet the metabolic demands of the growing and developing child, as a direct result of either inadequate dietary intake, poor absorption of energy and nutrients, chronic inflammation, or interactions between these etiologies [2]. The failure of the gut as an organ system to meet the metabolic and immunological demands of the growing child can be classified as “nutritional enteric failure,” characterized by linear growth failure, decreased cognitive development, and susceptibility to infection. All of these insults directly relate to the failure of the enteric system to meet the specific needs of tissues with high metabolic demand, including bone, the brain, and the immune system. Furthermore, the gut may also fail in its two key immune functions: firstly as a barrier to infection and secondly as an important antigen-processing organ. Reclassifying the stunting syndrome as nutritional enteric failure would shift focus away from decreased height and highlight the underlying mechanisms linking postnatal environmental influences to linear growth failure and its associated morbidity, and it would enable the identification of additional interventional targets to prevent substantial childhood morbidity and mortality. Organ failure is defined as a condition in which a system cannot maintain normal homeostasis, resulting from either insufficient supply or inadequate excretion of a substrate in relation to a patient’s metabolic requirements. For example, heart failure is defined as a state in which the cardiac output is unable to meet the body’s circulatory demands without external support