• Mortality [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  

• Frequency and causes of hospital re-admission [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  
• Growth [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Microbial population and antimicrobial resistance [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  
• Immune activation and inflammatory markers; markers of immune function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  

Malnutrition is the most important underlying risk factor for childhood death in developing countries. Severely malnourished children are at greatly increased risk of death from infectious diseases in the community, in hospital and following discharge. Malnutrition and infection are synergistic, in part because malnutrition causes secondary immune deficiency, whilst infections cause losses and diversion of nutrients. This synergy is exacerbated by a high level of exposure to pathogens. Among children treated for severe malnutrition in Africa, mortality following discharge from hospitals ranges between 8% and 41%.

Cotrimoxazole is a synthetic antibacterial combination that blocks two steps of folate metabolism involved in the biosynthesis of nucleic acids and proteins essential to many bacteria and some parasites, including Plasmodium falciparum. It is cheap, widely available and has an established safety profile in African populations. Cotrimoxazole prophylaxis dramatically reduces mortality among children with HIV, irrespective of the degree of immune suppression. The primary effect is in reducing bacterial infection, especially pneumonia. the effect has been demonstrated in areas with high levels of cotrimoxazole resistance bacteria. It is also widely used in developed countries among children with other immune deficiencies to prevent infection. Children with severe malnutrition are immune deficient, as evidenced by their susceptibility to infectious diseases, and may therefore benefit from daily antimicrobial prophylaxis.

The objective is to conduct a randomized, double blind, placebo-controlled trial of co-trimoxazole prophylaxis for 6 months among HIV-uninfected children with severe malnutrition following stabilization. The primary outcome will be survival at one year. Secondary outcomes are toxicity, survival at two years, growth, hospitalisation and microbial resistance and ecology.