Mucosal immunity in severely malnourished gambian children

Abstract

Severe malnutrition continues to be a serious public health problem. Case fatality rates in resource-poor settings are high. The median case fatality rate for the 1990s is 23% (range 4%-49%). Several studies have shown that the mortality rate associated with those who have been rehabilitated and have gone back to the community can range from 8% to as high as 41%. There may be a combination of socioeconomic and biologic reasons for these high rates, but our work focuses on the biologic aspects of severe malnutrition. We suspect that enteropathy plays an important role in the pathogenesis of severe malnutrition and its sequelae. Studies in The Gambia have been instrumental in shaping our views on mucosal immunity in severe malnutrition. In rural areas, growth faltering is universal (reaching about −2 Z-scores for weight-for-age) and commences at around 3 months of age and has been associated with various intestinal infections, increased intestinal permeability and Helicobacter sp infection. There is an intense lymphocytic infiltration of the lamina propria and the epithelial layer of duodenal biopsy specimens of malnourished children. There also appears to be a bias toward production of T helper 1 cytokines in the gut, suggesting an imbalance. To further characterize immune responses in the most severely affected children, we describe a study that is designed to compare mucosal immunity in severely malnourished children and well-nourished hospital control subjects with cytometry, enzyme-linked immunospot (ELISPOT) assays, and quantitative polymerase chain reaction. Preliminary results suggest that interferon-gamma production in severely malnourished children is relatively unimpaired and that immune responses are modified by infection.