Saccharomyces boulardii in Acute Gastroenteritis in Children

Transcription

1 Article ID: WMC ISSN Saccharomyces boulardii in Acute Gastroenteritis in Children Corresponding Author: Dr. Yvan Vandenplas, Brussels, Pediatrics, UZ Brussel, Laarbeeklaan 101, Belgium Submitting Author: Dr. Yvan Vandenplas, Brussels, Pediatrics, UZ Brussel, Laarbeeklaan 101, Belgium Article ID: WMC Article Type: Research articles Submitted on:13-nov-2011, 02:08:31 PM GMT Article URL: Subject Categories:PAEDIATRICS Keywords:Diarrhea, Gastroenteritis, Saccharomyces boulardii Published on: 14-Nov-2011, 03:00:25 PM GMT How to cite the article:amorissani Folquet M, Saizonou R, Guedehoussou T, Vandenplas Y. Saccharomyces boulardii in Acute Gastroenteritis in Children. WebmedCentral PAEDIATRICS 2011;2(11):WMC Source(s) of Funding: No funding Competing Interests: M. Amorissani Folquet and Y. Vandenplashave received travel and unrestricted research grants from Biocodex. Webmedcentral > Research articles Page 1 of 11

2 Saccharomyces boulardii in Acute Gastroenteritis in Children Author(s): Amorissani Folquet M, Saizonou R, Guedehoussou T, Vandenplas Y Abstract Objective: To evaluate Saccharomyces boulardii in the management of gastroenteritis in children in Togo, Benin and Côte d Ivoire. Methods: Prospective descriptive study, conducted by healthcare personnel in the 3 West African countries between May and December Well-nourished, (1 month -15 years old) children without chronic disease presenting with acute diarrhea (defined as more than 3 loose or liquid stools per 24-hour period, which started < 4 days before enrolment) were included. Stool frequency, consistency, and tolerance of treatment were evaluated at each visit. Results: 66 investigators recruited 331 patients. The patients were predominantly male; 81% were less than 3 years old (mean age 25.6 months). The mean duration of the diarrhea before enrolment was 1.6 days. The average number of stools returned to normal (2.43 stools per day) from day 2. S. boulardii was well tolerated in 93% of cases. The treatment was shown to be effective in close to 98% of the children. Conclusion: 81% of the children recruited were less than 3 years old. A daily dose of 500 mg S. boulardii was well tolerated, confirming the value of S. boulardii in diarrhea in children, in combination with oral rehydration therapy and early feeding. Introduction The aim of the recommended treatment options, oral rehydration therapy (ORT) and early feeding, is to treat and prevent the consequences of diarrhea, i.e. dehydration and malnutrition. However, these have no effect on the duration of diarrhea (1). In Togo, Benin and Côte d Ivoire, acute diarrhea is the fourth-ranking cause of death in children under the age of 5 years, after neonatal causes, malaria, and acute respiratory infections (2). Many studies with probiotics in addition to ORT and rapid realimentation have been conducted to evaluate the efficacy of probiotics in childhood gastroenteritis (3). Two probiotic strains, Lactobacillus GG and Saccharomyces boulardii (S. boulardii) (4,5) have been best documented. The efficacy of S. boulardii in the management of gastroenteritis has been shown in several clinical trials in developing countries (6). However, the use of S. boulardii has not yet been evaluated in this part of Africa. The aim of this prospective study was therefore to evaluate the use of S. boulardii in acute gastroenteritis in children in Africa. Although the data presented result from an open, observational study, they are relevant because they represent the first systematically obtained data on acute diarrhea using S. boulardii in this part of the world. Methods This prospective study was conducted simultaneously in the 3 West African countries Togo, Benin and Côte d Ivoire between May and December, Patient recruitment and follow-up were performed by healthcare personnel (doctors, nurses, medical assistants or midwives). The recruitment criteria were: children aged between 1 month and 15 years old, presenting with acute diarrhea, which was defined as at least 3 loose or liquid stools in a 24-hour period, which started less than 4 days before enrolment. Breastfed infants were considered to have diarrhea if the mother reported a significant increase in the number of stools per day and symptoms of dehydration were present. Since the etiology could not be explored in this setting, the origin of the diarrhea remains unknown. Only children with a normal baseline nutritional status and no severe signs of dehydration were included. Children presenting with fever above 38.5 C, bloody and/or purulent stools suggesting an invasive pathogen, and diarrhea lasting for more than 4 days were excluded. Additional exclusion criteria were antifungal therapy during 48 hours prior to enrolment or antibiotic therapy during the 4 weeks prior to enrolment. Rehydration and resumption of appropriate feeding, according to the WHO protocol (7) were recommended in all children. In addition, S. boulardii at a dose of 250 mg, morning and evening, for 5 days, was administered. The study was approved by the local ethical committees. Parents had to give their informed consent before participating. During S. boulardii treatment, a data sheet was completed, including demographic data (age, body weight, height, and sex), stool characteristics (number, Webmedcentral > Research articles Page 2 of 11

3 consistency), associated symptoms and dose administered. An adequate amount of S. boulardii (500 mg/day for 5 days) was given free to the parents. The efficacy of the treatment was evaluated by the duration of the diarrhea, defined as the time from enrolment to the first stool of normal consistency, identical to the pre-diarrhea consistency (Bristol score) Results Sixty-six investigators participated in the study, and recruited 331 patients over a 7-month period. Table 1 shows the distribution of the involved healthcare personnel according to country and category. The demographic and clinical characteristics of the children are presented in Table 2. The patients were predominantly male, with a sex ratio of Figure 1 shows the age distribution of the children. The mean age of the patients was 25.6 months, ranging from 1 month to 168 months. The vast majority (81%) of patients were under the age of 3 years. The mean duration of diarrhea prior to enrolment was 1.6 days (SD: 1.01). The requested data were adequately reported in 94% (n:292) of all included patients. The mean duration of the diarrhea after enrolment was 2.46 days (SD: 1.09). In all but 5 patients, duration of diarrhea was less than 5 days. In other words, according to the definitions, there was a treatment failure (no normal stool before day 5 of S. boulardii treatment) in 5/292 patients (1.7 %). The mean daily number of stools on day 2 was 2.43 stools per day. S. boulardii was well tolerated (excellent or good tolerability) in 93% of cases. The questionnaire did not provide information on symptoms of intolerance. Information was reported on only one case: 1 child developed mild transient constipation; it did not require discontinuation of the treatment. The recommended dose was administered in 89% of the patients. Lower doses were administered mainly in relation to the patient s age. Discussion Childhood diarrhea is a public health problem in developing countries, with children under the age of 2 years being more frequently and more severely affected (8,9). Great effort has been made to improve the prognosis of this condition, such as oral rehydration therapy and encouraging exclusive breastfeeding. Although diarrhea is very frequent in these countries, healthcare professionals are rapidly contacted since the mean duration of diarrhea was less than 2 days. Previous campaigns to raise awareness about the impact of diarrhea in young children can be credited for this. As a consequence, the use of rehydration solutions is becoming more widespread in these countries. Although the presence of signs of diarrhea-related complications was an exclusion criterion for the study, it is interesting to observe that no case of dehydration or malnutrition was reported. This observation suggests the necessity to set-up a prospective controlled study to evaluate the hypothesis if early administration of S. boulardii may prevent the development of dehydration and chronic diarrhea also in African countries S. boulardii is well tolerated in African children. The duration of diarrhea and stool frequency is in line with the results from previous studies in other developing countries (Table 3). Diarrhea persisted for more than 5 days in only 1.7 % of patients. Villaruel et al. demonstrated a mean difference of 1.37 days in duration of diarrhea in a group of 88 children from Salta (Argentina) treated with S. boulardi compared to placebo (10). Also, the number of children with prolonged diarrhea (> 7 days) was significantly higher in the placebo groyp (52.2 % versus 20.4 %; RR 0.39 ( ) (10). Kurugol and corworkers studied 200 Turkish children with acute diarrhea, and showed a decreased duration of diarrhea ( versus days; p = 0.03) and shorter hospital stay ( versus days; p < 0.001) (11). An open study by Billoo et al. in Pakistan resulted in similar conclusions (12). Interesting, this study suggested a smaller incidence of new episodes of diarrhea during a period of two months after treatment with S. boulardii during 5 days (13). Hafeez confirmed a decrease of duration of diarrhea with one day (3.6 versus 4.5 days) (14). Htwe showed a 1.5 days benefit in Myanmar children (3.08 versus 4.68 days). The mean duration of diarrhea in children treated with S. boulardi in this study was slightly shorter, 2.5 days. Probiotics can be used as add-on treatment to ORT and rapid re-alimentation in children and infants with acute diarrhea. S. boulardii was well tolerated, as no side effects were observed. Conclusion(s) This study involved a large number of patients. The patients recruited were mainly young children in whom diarrhea is a major issue. S. boulardii, at a dose of 500 mg/day during 5 days, produced results in line with those obtained in clinical studies published to date. These are the first data on the use of S. boulardii acute gastroenteritis coming from Togo, Benin and Webmedcentral > Research articles Page 3 of 11

4 Côte d Ivoire. The data suggest that epidemiology and natural evolution of acute diarrhea in this part of the world is similar to other developing countries. The dose of 500 mg/day produced results in line with those obtained in the clinical studies published to date, being fast-acting and well tolerated. Acknowledgements M. Amorissani Folquet and Y. Vandenplashave received travel and unrestricted research grants from Biocodex. References 1. Vandenplas Y, Salvatore S, Vieira M, Devreker T, Hauser B. Probiotics in infectious diarrhoea in children: are they indicated? Eur J Pediatr. 2007;166: WHO. Part 2: Causes of death (2004) GBD_report_2004update_part2.pdf 3. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr Oct;33 Suppl 2:S Guarino A, Albano F, Ashkenazi S, Gendrel D, Hoekstra JH, Shamir R, Szajewska H; ESPGHAN/ESPID Evidence-Based Guidelines for the Management of Acute Gastroenteritis in Children in Europe Expert Working Group. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: executive summary. J Pediatr Gastroenterol Nutr. 2008;46: Vandenplas Y, Brunser O, Szajewska H. Saccharomyces boulardii in childhood. Eur J Pediatr 2009;168: Szajewska H, Skórka A, Dylag M. Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. Aliment Pharmacol Ther. 2007; 25: WHO. The Treatment of Diarrhoea. A Manual for Physicians and other Senior Health Workers; WHO/CDR/95.3. Geneva: World Health Organization, Imboua C, Assamoi B. Prise en charge de l enfant diarrhéique. Abidjan : MSP /PNSI/PMD ; P. 9. Konde-Lule JK, Elasu S, Musonge DL. Knowledge, attitudes, and practices and their policy implications in childhood diarrhoea in Uganda. J Diarrhoeal Dis Res 1992;10: Villarruel G, Rubio DM, Lopez F, Cintioni J, Gurevech R, Romero G, Vandenplas Y. Saccharomyces boulardii in acute childhood diarrhoea: a randomized, placebo-controlled study. Acta Paediatr. 2007;96: Kurugöl Z, Koturoglu G. Effects of Saccharomyces boulardii in children with acute diarrhoea. Acta Paediatr. 2005;94: Billoo AG, Memon MA, Khaskheli SA, Murtaza G, Iqbal K, Saeed Shekhani M, Siddiqi AQ. Role of a probiotic (Saccharomyces boulardii) in management and prevention of diarrhoea. World J Gastroenterol. 2006;12: Hafeez A, Tariq P, Ali S, Kundi ZU, Khan A, Hassan M. The efficacy of Saccharomyces boulardii in the treatment of acute watery diarrhoea in children: a multicentre randomized controlled trial. J Coll Phys Surg Pakist 2002; 12: Htwe K, Yee KS, Tin M, Vandenplas Y. Effect of Saccharomyces boulardii in the treatment of acute watery diarrhea in Myanmar children: a randomized controlled study. Am J Trop Med Hyg. 2008;78: Webmedcentral > Research articles Page 4 of 11

5 Illustrations Illustration 1 Table 1: Distribution by category of healthcare personnel Investigators TOGO BENIN Côte d'ivoire N = 19 N= 14 N=39 Doctors 68% 86% 39% Nurses 5% 14% 55% Medical assistants 26% 0% 0% Midwives 0% 0% 6% Webmedcentral > Research articles Page 5 of 11

6 Illustration 2 Table 2: Distribution of the children according to demographic characteristics Age (months) Mean age Maximum age 168 Minimum age 1 % boys: 57% Weight (g) Mean weight Maximum weight Minimum weight Duration of the diarrhea before enrolment (days) Mean 1.6 Minimum 0 Maximum 4 Webmedcentral > Research articles Page 6 of 11

7 Illustration 3 Table 3: Clinical study data on the duration of diarrhea [6] Study Diarrhea duration (days) Control Sb Villarruel Kurugol Billoo Hafeez Htwe This study Webmedcentral > Research articles Page 7 of 11

8 Disclaimer This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party. Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website. Webmedcentral > Research articles Page 8 of 11

9 Reviews Review 1 Review Title: Faculty Review: Use of Saccharomyces boulardii in African children with acute diarrhoea Posted by Lead Faculty Dr. Prashanth GP on 13 Jan :19:54 AM GMT 1 Is the subject of the article within the scope of the subject category? Yes 2 Are the interpretations / conclusions sound and justified by the data? Partly 3 Is this a new and original contribution? Yes 4 Does this paper exemplify an awareness of other research on the topic? Yes 5 Are structure and length satisfactory? Yes 6 Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? 7 Can you suggest any reductions in the paper, or deletions of parts? Yes 8 Is the quality of the diction satisfactory? Yes 9 Are the illustrations and tables necessary and acceptable? No 10 Are the references adequate and are they all necessary? Yes 11 Are the keywords and abstract or summary informative? Yes Rating: 4 Comment: At the outset, I congratulate the authors for reporting the first systematically obtained data from three African countries concerning the use of S. boulardii in acute gastroenteritis among children. However, there are areas of concern in the present study, including the methodology and presentation of the scientific data, which need both clarification and improvisation. I would suggest authors to take the help of a qualified statistician to further refine the data presentation. Some of the specific comments are as follows. Yes 1. Definition of diarrhea in breastfed infants is subjective and not clear why are symptoms of dehydration considered for patient inclusion only in this age group?? 2. Were all recruited children previously healthy? Whether children with chronic diseases, including HIV, excluded? 3. The term normal nutritional status needs qualification. 4. Whether a written consent obtained in the local language? Ethical approval was provided by what body in these set-ups? A statement addressing these issues needs to be included. 5. It is important to let the reviewer know the names of the Hospitals where the study was conducted. 6. It is not clear whether the study was community-based or hospital -based (primary care or referral centre??) (26% of the investigators were medical assistants in Togo, whereas only doctors and nurses recruited children in Benin) 7. It s essential, at the submission stage, to reveal the affiliations of all the co-authors. A statement mentioning the contributions of each co-author is desirable. 8. It is stated in Methods that patient recruitment and follow-up were performed by health personnel of different cadre. Was any kind of training provided for health assistants/midwives? A statement clarifying who supervised the data collection process is warranted. Was the data entry verified by a second investigator? 9. Statistical method section is untouched upon It needs mention as limitations of the study in the discussion part 10. Since the primary objective of the study was to evaluate the use of Saccharomyces boulardii in the absence of a planned control-group, collecting the information on symptoms of intolerance could have added more value to this descriptive study. Also, vomited and/or skipped doses are not reported 11. The trial medication: whether the storage, quality control, and distribution-related expenses handled by the local governments or pharma companies, or the authors themselves? Discussion 1. The sentence previous campaigns to raise.. (paragraph1, line 10 in Discussion section) is not related to the study. I would vomit this sentence.. 2. The discussion section needs to be written analytically rather than mere reporting of the statistical numbers from other studies. Majority of the studies quoted by the authors are RCTs where we have control groups to compare the results. It is important to Webmedcentral > Research articles Page 9 of 11

10 quote descriptive epidemiological studies for comparing the results of the present study.. I would suggest the authors to restructure whole of the 2 nd paragraph in discussion section. 3. The age group studied here is broad (1-15 yrs) and etiology of diarrhea not looked into These need mention under limitations of the study. Competing interests: No Invited by the author to make a review on this article? : No Experience and credentials in the specific area of science: Trained at a tertiary care center in a developining-country set up for three years; involved in the sample and data collection process in an institutional study of acute diarrhea in children. Publications in the same or a related area of science: No How to cite: J K.Faculty Review: Use of Saccharomyces boulardii in African children with acute diarrhoea[review of the article 'Saccharomyces boulardii in Acute Gastroenteritis in Children ' by ].WebmedCentral 1970;3(1):WMCRW Webmedcentral > Research articles Page 10 of 11

11 Disclaimer This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party. Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website. Webmedcentral > Research articles Page 11 of 11