Zinc Supplementation in Shigella Patients

Shigellosis is a major cause of morbidity and mortality in young children in Bangladesh and other developing countries. Further, the increasing emergence of resistance to a wide range of antibiotics is of great concern. Another major public health problem in Bangladesh is malnutrition, which is closely linked with shigellosis and with a high mortality. In Shigellosis, a heavy nutritional burden is placed on children and vital micronutrients such as vitamin A is lost in the urine. We recently found that the immune response in S. Flexneri infection was lower in children who were severely malnourished (weight-for-age≤65% as a percentage of the National Centre for Health Statistics median) when compared to children with weight-for-age from >65-75%. T cell responses were primarily affected with lowered CD4/CD8 ratios, lowered proliferative responses to T cell mitogens, Conconavalin A (ConA) and phytohaemagglutinin (PHA). However, proliferation of pheripheral blood mononuclear cells (PBMs) was lowered only in the presence of autologous plasma suggesting that a factor(s) in plasma, probably nutritional, rather than a defect in cells themselves was responsible. In children with S. dysenteriae 1 infection, proliferative responses to PHA were similarly lowered in the presence of autologous plasma but inhibition correlated to lowered transferring levels in plasma and not to the weight-for-age of the children. Also severely malnourished children with either S. flexneri or S. dysenteriae 1 infection were more severely ill. These findingings show that immunity in malnourishrd children with shigella infection is impaired which may lead to more severe illness. As zinc has profound effects on immunity as well as clinical outcome in diarrhoeal diseases, it is possible that zinc deficiency may be a factor in reducing immunity and increasing severity of acute illness in malnourished children with shigellosis. In this study, we will investigate the effect of zinc supplementation, in a double blind placebo controlled trial, on inflammatory responses, outcome of acute illness and growth following recovery from acute illness with S. flexneri infection.