ArticlesProbiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi
Introduction
Severe acute malnutrition affects 13 million children globally, and causes 1 to 2 million child deaths every year.1 Mortality in some settings is especially high. Programme case fatality rates of 20–30%, sometimes 50–60%, have been reported.2 Advances have been made initially by improving treatment protocols,3 and recently with community-focused programmes.4 However, challenges persist, especially where HIV is prevalent,5, 6 and therapeutic innovations to improve severe acute malnutrition outcomes remain a public health priority.
Probiotic and prebiotic functional foods are claimed to provide health benefits beyond the provision of essential nutrients.7 For some conditions such as diarrhoea, evidence of effect is good.8, 9 Most functional-food research, however, focuses on high-income countries—where product sales are high (ie, US$16 billion per year for probiotics alone)10—whereas only a few studies are done in low-income nations, where severe acute malnutrition and preventable mortality are high.11
In some patients, probiotics and prebiotics reduce diarrhoea, promote healthy gut flora, reduce pathogenic gut bacteria, and directly or indirectly modulate the immune system.12 Therefore, they should also be beneficial in severe acute malnutrition when impaired gut function is a problem, manifested as diarrhoea and malabsorption,13, 14 small bowel overgrowth,15 increased intestinal permeability,16 enteropathy,17 gram-negative (enteric) bacteraemia,18, 19 and suboptimal immune response.20
International efforts to deal with severe acute malnutrition are currently focused on community-based management of acute malnutrition,21 which aims to mobilise communities, decentralise services, and facilitate early presentation to care. These measures ensure high programme coverage.22 With community-based management of acute malnutrition programmes now treating many children, improved foods with even modest benefits to individual patients mean large beneficial effects for public health.
However, probiotics have a small risk of causing invasive infection;23 therefore, caution is recommended in immune-compromised patients.24 Improved risk–benefit data are vital: the most vulnerable, most immunosupressed children with severe acute malnutrition25 and HIV26 are also those needing therapeutic improvements.
Ready-to-use therapeutic foods are high-energy, nutrient-dense paste, formulated to WHO standards for the treatment of severe acute malnutrition,27 and are used in almost all programmes of community-based management of acute malnutrition. As the product is manufactured in food-processing factories and packaged in sealed containers, inclusion of functional additives to the standard ready-to-use therapeutic foods recipe can be readily achieved, and can be used for large-scale rollout in feeding programmes.
Here, we report the findings of a randomised controlled trial that assessed the effect of probiotic28 and prebiotic29 functional food to improve existing treatments for severe acute malnutrition (the PRONUT study).
Section snippets
Setting
The PRONUT study was done at MOYO nutrition rehabilitation unit, Queen Elizabeth Central Hospital, Malawi. Set within the paediatric department of a large urban teaching and referral hospital, the MOYO unit is responsible for all children admitted with severe acute malnutrition. Over 40% admissions are HIV seropositive, whereas the national average is 24%.30
Participants
Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) were recruited between July 12, 2006, to March 7, 2007. We defined
Results
From July 12, 2006, to March 7, 2007, 1024 Malawian children were admitted to the child malnutrition ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) (figure 1). 399 were randomly assigned to Synbiotic-enriched ready-to-use therapeutic food and 396 to control ready-to-use therapeutic food. The most common reason for non-enrolment was early death while still on stabilisation phase.
Patient characteristics were similar in both groups at baseline (table 1). Severe acute malnutrition
Discussion
In our setting, Synbiotic2000 Forte, prescribed in ready-to-use therapeutic food at an average dose of at least 1010 lactic acid bacteria per day, did not improve prespecified nutritional or clinical outcomes from severe acute malnutrition. This is an important negative finding. PRONUT is a very large randomised trial on the effect of probiotics and prebiotics. It is also based in a low-income, high-mortality country.
A 2004 Cochrane review8 of probiotics for the treatment of diarrhoea included
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