Co-trimoxazole prophylaxis among children with severe malnutrition. (360G-Wellcome-083579_Z_07_Z)

This project aims to test the hypothesis that mortality after initial stabilisation among Kenyan children with complicated severe malnutrition is due to ongoing vulnerability to infectious disease, and that co-trimoxazole prophylaxis will reduce mortality. It is postulated that the effects of co-trimoxazole will be direct, by preventing life threatening bacterial infections and malaria, and indirect, by preventing less severe infections hence permitting existing nutrient intake and stores to be used for growth and immunological recovery. The objective is therefore to conduct a randomised, double blind, placebo-controlled trial of daily co-trimoxazole prophylaxis among HIV-uninfected Kenyan children with complicated severe malnutrition following stabilization as inpatients and for 6 months after discharge. The primary outcome will be survival at one year. Secondary outcomes are toxicity, hospital admission, survival at two years and growth. A further objective is to investigate the e ffects of co-trimoxazole prophylaxis on microbial ecology and phenotypic and molecular markers of resistance. The study has 90% power to detect a hazard ratio of 0.66 at 5% significance from expected baseline 1 year mortality of 18%.