The effect of chronically elevated levels of cachectin/tumor necrosis factor (TNFalpha) on growth and nutritional status is unknown in humans. An acute elevation of this cytokine is associated with a severe life- threatening response characterized by fever and shock. This response is similar to what is seen in septic shock and severe complicated malaria. Morbidity from septic shock can even be prevented by pre-treatment with a monoclonal antibody against TNF. By contrast, chronic, low levels of TNFalpha are associated with anorexia, weight loss, anemia, net protein and net lipid catabolism. These responses are similar to the chronic wasting observed in infections with schistosomes and other parasitic diseases where moderate elevations in TNFalpha levels are observed. A large field study in Brazil has been designed to determine the relationship of growth and development in children who are moderately or lightly infected with S. mansoni. Children with low or moderate in that study will be randomized to treatment and placebo groups for 1 year after which all children will receive chemotherapy. Growth and body composition will be assessed in that study using anthropometric measurements. The present proposal takes advantage of that field research opportunity to determine if growth, development and nutritional status in these children with a chronic infection correlate with TNFalpha levels. Stool examinations for schistosomiasis will be performed on all children (3,000) in a small urban area in the Brazilian state of Bahia. Anthropometric measurements will be made on all children twice per year. Blood will be collected from all willing children for a hematocrit determination TNFalpha, Zn, Fe, ferritin and transferrin receptor once per year and at the end of the study. Twelve months after the first treatment, all the children in the placebo or treatment groups still found to be positive will be treated. Growth and serologic data will also be collected during the second year comparing growth reinfection rates, anemia and TNFalpha levels. Anthropometric and serologic data from the randomized treatment groups will be analyzed to determine if a correlation exists between S. mansoni infection growth indices, nutritional status and TNF levels.
| Assis, A M; Barreto, M L; Prado, M S et al. (1998) Schistosoma mansoni infection and nutritional status in schoolchildren: a randomized, double-blind trial in northeastern Brazil. Am J Clin Nutr 68:1247-53 |
| Parraga, I M; Assis, A M; Prado, M S et al. (1996) Gender differences in growth of school-aged children with schistosomiasis and geohelminth infection. Am J Trop Med Hyg 55:150-6 |
