Each year, about 1 million children around the world die from SAM (severe acute malnutrition). Deaths in children with SAM mostly occur because malnutrition increases children’s susceptibility to life-threatening infections. Community-based treatment programmes for SAM have massively expanded and if children can be identified and treated early then poor outcomes can be averted. However, for many children, SAM is only discovered when they are admitted to hospital because they are sick, usually with severe pneumonia, diarrhoea or sepsis.
Children admitted to hospital and have SAM have a much higher risk of death in hospital than children without SAM. However, studies have also shown that children with malnutrition continue to have a high risk of mortality after they are treated and discharged. Amongst these children, malnutrition is the strongest risk factor for deaths after discharge from hospital.
For children with a long-term risk of mortality because of HIV infection, taking an inexpensive antibiotic, co-trimoxazole, every day considerably reduces mortality and readmissions to hospital. Antibiotics have also been shown to benefit growth in children with and without HIV.
In 2009, Prof. Jay Berkley and colleagues began a large randomised clinical trial to determine if daily co-trimoxazole would prevent mortality, reduce infections and improve nutritional recovery amongst children with SAM who did not have HIV. The trial involved 1,778 children aged 2 to 59 months at four hospitals in Kenya. Children were enrolled during hospital admission and followed up for a year.
The results of the trial were surprising to the team of investigators. After enrolment, 15% of the children with SAM died during the year of follow up despite medical and nutritional care. But there was no reduction in mortality amongst those receiving co-trimoxazole, nor was there a difference in growth. Some infections were prevented, including malaria, urinary tract infections and skin or soft tissue infections. However, there was no reduction in pneumonia episodes and there was an increase in diarrhoea episodes. Mortality was especially high amongst infants with SAM.
These findings mean that co-trimoxazole prophylaxis should not be recommended for managing children with SAM, except for those with HIV. The high mortality despite the hospitals and trial teams having provided care according to current WHO guidelines means that other components of care need to be examined. Most of the participating children were stunted, indicating chronic malnutrition, and had a broader background of poverty and vulnerability. This suggests that future approaches will need to be multi-faceted, addressing unmet nutritional needs, tackling infection and the social context.
You can read a commentary on the trial, published in the LANCET Global Health here:
An important chapter in the infection–malnutrition story.
Additional information on mortality, growth, the types of illness episodes experienced by children during the study and microbiological results are in Supplementary Material to the article.
The trial was led from the Clinical Trials Facility (CTF) at the KEMRI/Wellcome Trust Research Programme in Kilifi.The CTF supported the trial with GCP training, clinical and laboratory monitoring and data management. You can find out about other research on malnutrition at the KEMRI/Wellcome Trust Research Programme here: Malnutrition.