Probiotics and ORS

Dear Camilla, The only clinical trial on the use of pre / probiotics in SAM I am aware of is : Kerac M, Bunn J, Seal A, Thindwa M, Tomkins A, Sadler K, Bahwere P, Collins S. Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi. Lancet. 2009 Jul 11;374(9684):136-44. See abstract below. Not really convincing. BACKGROUND: Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS: We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS: Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION: In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies.

Dear Kiran, Thanks for asking this question. As lead author of the trial Andre has already highlighted, I fully agree that the evidence for probiotics in SAM is not at all persuasive at present. In case you’re interested in further details of the Lancet study (including what I feel is a much more interesting long term follow up of the patients 1-2 years following their initial episode of SAM) please see my PhD write-up here. The full Lancet article is also free if you register on their website. Some other thoughts on probiotics: i) There is good evidence that probiotics/prebiotics do have beneficial health effects. See for example the excellent 2010 Cochrane review by Prof Steve Allen and colleagues, who conclude that: “Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea." HOWEVER.. ii) Effects are often very organism and patient/condition specific. This is one of several possible reasons why the Synbiotic preparation we used in Malawi, though proven effective for other patient groups, did not seem to work in our children with SAM. iii) Probiotic efficacy is not the only issue that matters Even had our study shown a positive result, there would have been cost, cost-effectiveness and feasibility/logistics (e.g. organism stability over prolonged periods at high tropical temperatures) to consider before any large scale roll-out and meaningful population-level health impact would have been possible. Opportunity costs are particularly critical. It's easy to get carried away with novel and exciting technologies and treatments. But whilst (other) probiotics still have the potential to be of help, in the short to medium term, it’s arguably much more important to focus on delivering existing treatments well and ensuring high population coverage. This includes promoting breastfeeding for older infants, not just those under six months - breastmilk itself having (cheap and freely available) probiotic/prebiotic properites Will be interesting to see how this field evolves. Here are some useful references for anybody who’s interested in following up further: • Steve Allen et al. Probiotics for treating acute infectious diarrhea. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD003048. • Marc Monachese et al, Probiotics and prebiotics to combat enteric infections and HIV in the developing world: a consensus report. Gut Microbes Vol 2, issue 3 May/June 2011. • Neerja Haiela et al. Are probiotics a feasible intervention for prevention of diarrhoea in the developing world? Gut Pathog 2010 Aug 29;2(1):10 • Gregor Reid et al. Probiotics for the developing world Jnl Clinical Gastroenterology 2005 Jul;39(6):485-8