Intestinal infections and environmental enteropathy: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition

Intestinal infections continue to exact an unacceptable toll on childhood well-being. This is particularly true in the developing world where diarrheal disease has significant morbidity and mortality, especially when accompanied by malnutrition. A wide range of viral, bacterial, nd parasitic pathogens cause protean illnesses, including acute watery diarrhea, bloody diarrhea, persistent diarrhea, chronic diarrhea, and asymptomatic infection. Gastrointestinal infections and overgrowth of enteric flora may also be related to functional abdominal disorders, either directly or as postinfectious phenomena Such as irritable bowel syndrome (1,2). In addition, animal studies suggest that commensal organisms may precipitate or perpetuate inflammatory bowel disease and even contribute to extraintestinal manifestations such as arthritis (3,4). Intestinal infections pose multiple challenges. First, origins are often geography specific, requiring investigation strategies that are location appropriate. Second, accurate diagnoses are often thwarted by the polymicrobial nature of stool and limitations of diagnostic tools. Third, host-microbe interactions show great variability. Enteric infections in people with the acquired immunodeficiency syndrome, transplants, and other immune disorders also require unique approaches. In this report, we argue that high-quality research and education have the potential to help find solutions. On the treatment side, oral rehydration is a cheap, effective, widely available treatment for dehydration, acidosis, and potassium depletion caused by acute watery diarrhea and has reduced much of the mortality resulting from this condition. Morbidity continues to burden communities where oral rehydration is under-utilized and communities that lack clean water, safe food, and acceptable hygiene standards. These underlying problems are often inextricably linked to development. economic, and political issues, which are difficult for the medical community to address effectively. Globally, poor growth is the most important risk factor for childhood morbidity and mortality. An estimated 168 million children (27% of all under 5 years of age) are moderately to severely underweight (Z scores below -2). Weight changes significantly affect child mortality, independently of socioeconomic and secular factors. Approximately 56% of child deaths are attributed to malnutrition, although most cases are not severe (5). Environmental enteropathy poses a different, but related. set of challenges. Probably all children living in poor tropical regions have abnormal small bowel structure and function, including crypt hyperplasia, villous stunting, hypercellularity of the lamina propria, decreased mucosal surface area, and increased intestinal permeability. These changes seem to be secondary to environmental exposure to food and water contaminated with bacteria of presumably fecal origin (6). Subclinical malabsorption was not initially believed to be an important contributor to childhood malnutrition, but it is now believed that environmental enteropathy may contribute up to 40% of growth faltering in the developing world (7). However, the relative contributions of enteropathy, anorexia, a monotonous diet of low energy density, and micronutrient deficiencies to poor,growth are still unclear. It is also unknown how environmental contamination actually contributes to enteropathy. Biopsies demonstrate T-cell activation and an exaggerated local Thl cellular response similar to food-sensitive enteropathy (eg, celiac disease, but the role of cytokines such as tumor necrosis factor-a and interfon-gamma is still poorly delineated because there appear to be multiple mechanisms leading to T-cell-mediated enteropathy (8). The gut inflammation in this disorder is unlikely to be an allergic response because these children are rarely atopic. The relative contribution to environmental enteropathy of factors such as specific pathogens (e.g., Helicobacter pylori, Salmonella species, Giardia lamblia, Cryptosporidium parvum, and pathogenic Escherichia coli), nonspecific colonization or small bowel bacterial overgrowth, recurrent or persistent diarrhea, contaminated weaning, foods, overcrowding, and malnutrition remains to be established. What is clear, however, is that the enteropathies of kwashiorkor, cow's milk alergy, autoimmunity, and HIV infection are distinct and symptomatic, in contrast to environmental enteropathy, which is asymptomatic. Because environmental enteropathy Occurs after the introduction of weaning foods. gastrointestinal tract maturation is likely to have a more important bearing on this enteropathy In early childhood than in adulthood. Although environmental enteropathy is usually asymptomatic, it probably acts synergistically with malnutrition and specific diarrhea pathogens to increase the burden of diarrheal disease and to exacerbate poor nutritional status by diminishing the potential for catch-up Growth between episodes. Thus. environmental enteropathy may be the missing link in the disputed Vicious cycle of diarrhea-malnutrition.