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-ageā¤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.
Phase:
Phase 3
Details
Lead Sponsor:
International Centre for Diarrhoeal Disease Research, Bangladesh