Update on Probiotic Use in Children with Diarrhoea

Transcription

1 Update on Probiotic Use in Children with Diarrhoea Ahmed Laving Paediatric Gastroenterologist and Senior Lecturer, University of Nairobi KPA Annual Scientific Meeting, Kisumu 2017

2 Outline Physiology of normal gut flora Probiotics: definition and types Efficacy in different settings

3 Gastrointestinal (GI) tract Surface area: 250 m2 (2nd largest organ in body) Main entry site of pathogenic micro-organisms therefore first-line of defence Sophisticated ecosystem whose balance is ensured by the subtle interaction between: Microflora GI-associated mucosal immune system These considerations underline the importance of the part played by beneficial bacteria in the gut Guarner F et al. Lancet 2003; 361:

4 Gut microflora: Composition Initial colonisation of GI tract begins at BIRTH and is affected by: type of delivery (normal vs. caesarean) Type of diet (breast vs. formula feeding) Some bacteria create a favourable habitat for themselves & prevent growth of other bacteria introduced later into the GI ecosystem Initial colonisation relevant to final composition of permanent flora in adults Composition of individual s flora usually constant but may alter with: acute diarrhoeal illnesses antibiotic treatment sometimes dietary interventions Guarner F et al. Lancet 2003; 361:

5 Gut microflora: Colonisation Commensal bacterial flora ( species) colonise the whole GI <103 CFU/mL CFU/mL CFU/mL CFU: Colony Forming Unit 5

6 Gut microflora: Functions Metabolic fermentation of non-digestible dietary residue salvage of energy (as short-chain fatty acids) and absorbable nutrients source of vitamin K Trophic control of epithelial cell proliferation and differentiation development and homeostasis of the immune system Protective Protection against pathogens (the barrier effect) Guarner F et al. Lancet 2003; 361:

7 Probiotics The term probiotic is derived from Greek and it means for life FAO/WHO defined the term probiotics as live microorganisms administered in an adequate amount which confer a health benefit on the host. 1 1.Food and Agriculture Organization/World Health Organization. Joint FAO/WHO Expert Consultation on Evaluation of Health a nd Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. 2001

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9 History of Probiotics Persian version of Old Testament (Genesis 18:8) states Abraham owed his longevity to the consumption of sour milk In 76 BC, Roman historian Plinius recommended fermented milk products to treat gastroenteritis Metchnikof, Nobel laureate in 20th century: Bulgarians on fermented milk lived longer Tissier, Pasteur Institute: discovered Bifidobacter in breastmilk

10 Probiotics: Mechanism of action It is unlikely that there is only one mechanism of action Probably work by multiple mechanisms: Production of antimicrobial substances (i.e. bacteriocins) Immunomodulation Stimulation of the cellular and humoral immune systems Reduction of the inflammatory response»via modulation of cytokines Bacterial-epithelial crosstalk Each agent may have a unique action Each probiotic should be evaluated on its own merits Borruel N et al. Am J Gastroenterol 2003; 98: Urdaci MC et al. J Clin Gastroenterol 2004; 38(Suppl 2):S86 S90 Marteau Ph,Best Pract & Res Clin Gastroent; (5)

11 Probiotics: Clinical Evidence Diarrhoea Infantile Colic

12 Areas of investigation of Probiotics in Childhood Diarhoea Prevention of Acute infectious diarrhoea Antibiotic- associated diarrhoea Nosocomial diarrhoea Treatment of Acute infectious diarrhoea Persistent infectious diarrhoea

13 Probiotics in treatment of acute infectious diarrhoea

14 Probiotics: Acute Diarrhoea A 9 RCT meta-analysis suggests probiotic treatment of children with acute diarrhoea: Reduces duration of diarrhoea by 0.7 days Reduces the frequency of diarrhoea by 1.6 stools on second day of treatment Van Niel CW et al, Pediatrics 2002; 109:

15 Probiotics: Acute Diarrhoea A meta-analysis of 6 studies including 707 patients with diarrhoea suggests a high benefit of probiotics versus placebo Bradley CJ, et al CMAJl 2006;175:

16 Probiotics: Acute Diarrhoea Cochrane review Sixty-three studies met the inclusion criteria with a total of 8014 participants Reduced mean duration of diarrhoea by 24.7 hrs Reduced stool frequency on day 2 by 1.7 episodes Reduced risk of diarrhoea lasting >4 days by 59% Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database of Systematic Reviews 2010, Issue 11.

17 Probiotics in prevention of acute infectious diarrhoea

18 Probiotics: Prevention of acute diarrhoea Role of probiotic in preventing acute diarrhoea in children A double-blind, randomized, controlled field trial involving 4000 children aged between 1 and 5 years in an impoverished urban slum of Kolkata, India. Sur et al Epidemiol. Infect. (2011), 139,

19 Probiotics: Kolkata study Sur et al Epidemiol. Infect. (2011), 139,

20 Probiotics in Prevention of Antibiotic Associated Diarrhoea

21 Antibiotic Associated Diarrhea Unexplained diarrhea between 2 hours to 2 weeks after starting antibiotics Associated with: penicillins, especially amoxycillin-clavulanate cephalosporins macrolides trimethoprim-sulphamethoxazole erythromycin Prevalence 10-25%% of children on antibiotics as outpatients Most commonly due to C. dif f icil e (10-20%) Alam S, Mushtaq M. Antibiotic Associated Diarrhea in Children. Indian Paediatrics 2009; 491 (46)

22 Antibiotic-Associated Diarrhoea (AAD) Amoxicillin +clavulanate 10 to 25 % Ampicillin 5 to 10% Clostridium difficile 10 to 20 percent of AAD The majority of cases of colitis associated with antibiotic therapy Cefixime 15 to 20 Other cephalosporines, fluoroquinolones, azithromycin, clarithromycin, erythromycin, and tetracycline Others 2 to 5 Bartlett J G, NEJM, 2002; 346:

23 Probiotics: AAD A meta-analysis of 9 clinical trials suggests: Probiotics could be used in the prevention of AAD Data are in favour of the probiotic group in AAD prevention Odds ratio: 0.37 ( ), p<0.001 versus placebo D Souza AL BMJ 2002; 324:

24 Probiotics: Prevention of AAD Favours treatment Favours tcontrol Johnston BC, Goldenberg JZ, Vandvik PO, Sun X, Guyatt GH. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database of Systematic Reviews 2011,

25 Probiotics: Prevention of AAD Cochrane review 2011 Sixteen studies (3432 participants) met the inclusion criteria in the meta- analysis. The incidence of AAD in the probiotic group was 9% compared to 18% in the control group (2874 participants; RR 0.52; 95%CI 0.38 to 0.72) The overall evidence suggests a protective effect of probiotics in preventing AAD. Johnston BC, Goldenberg JZ, Vandvik PO, Sun X, Guyatt GH. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database of Systematic Reviews 2011,

26 Probiotics in Prevention of Nosocomial Diarrhoea

27 Prevention of Nosocomial Diarrhoea Children admitted to hospital for other causes often acquire diarrhea during hospitalization The most common agent is rotavirus and, less commonly, C. difficile

28 Probiotics: Nosocomial Diarrhoea Hojsak et al (2010)

29 Probiotics: Nosocomial Diarrhoea Hojsak et al (2010)

30 Probiotics in Treatment of Persistent Diarrhoea

31 Probiotics: Persistent Diarrhoea Bernaola Aponte G, Bada Mancilla CA, Carreazo Pariasca NY, Rojas Galarza RA. Probiotics for treating persistent diarrhoea in children. Cochrane Database of Systematic Reviews 2010,

32 Infections in Child Care Centers

33 In summary The efficacy of probiotics on persistent diarrhea remains uncertain. The purpose of this study was to evaluate the effect of Lactobacillus sp and Saccharomyces boulardii on persistent diarrhea in children. In a doubleblind trial eighty-nine children, aged 6-24 months were randomly distributed to receive pasteurized cow milk containing 2 viable lyophilized strains Lactobacillus casei and Lactobacillus acidophillus strains CERELA, (10(10)10(12) colony-forming units per g) (n = 30), or lyophilized S. boulardii, (10(10)-10(12) colony forming units per g) (n = 30) or pasteurized cow milk as placebo (n = 29); on each diet 175 g was given twice a day for a 5 day period. Number of depositions, duration of illness and frequency of vomiting were considered. Enteric pathogens were isolated from stools in 40% of the patients, 27% had rotavirus. Lactobacillus and S. boulardii significantly reduced the number of depositions (p < 0.001) and diarrheal duration (p < 0.005). Similarly both significantly (p < 0.002) reduced vomiting as compared with placebo. There was no difference between treatments depending on rotavirus status. In conclusion, L. casei and L. acidophillus strains CERELA and S. boulardii are useful in the management of persistent diarrhea in children.

34 Probiotics and Infantile Colic

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