• 1

    Vandenplas Y, Salvatore S, Vieira M, Devreker T, Hauser B, 2007. Probiotics in infectious diarrhoea in children: are they indicated? Eur J Pediatr 166 :1211–1218.

    • Search Google Scholar
    • Export Citation
  • 2

    Buts JP, 2006. Example of a Medicinal Probiotic: Lyophilized Saccharomyces boulardii. Gut Microflora. London: John Libbey Eurotext Editions, 221–244.

  • 3

    Mar Mar Nyein T, Tsukamoto, Tin Aye, Myo Khin, Khin New Oo, Khin Maung U, Takeda Y, 1992. Detection of pathogenic bacteria in children with diarrhea. Myanmar Health Sci Res Journal 4 :45–51.

    • Search Google Scholar
    • Export Citation
  • 4

    Mar Mar Nyein, Tin Aye, Khin Mg U, Myo Khin, Phyu Phyu Win, Thane Toe, 1999. Seasonal pattern of enterotoxigenic Escherichia coli (ETEC) in children under 3 years of age. Myanmar Health Sci Res J 8 :7–13.

    • Search Google Scholar
    • Export Citation
  • 5

    Mar Mar Nyein, Mi Mi Htwe, Aye Aye Maw, War War Aung, Khin Aye Aye Tun, Khin Myat Tun, 2005. Isolation of bacterial pathogens from children with diarrhea from Yangon’s Children Hospital 1999–2003, Paper presented at the Myanmar Research Conference. January 2005.

  • 6

    Bhan MK, Mahalanabis D, Pierce NF, Rollins N, 2005. The Treatment of Diarrhea: A Manual for Physicians and other Senior Health Workers. Geneva: World Health Organization/Child and Adolescent Health and Development, 8–16.

  • 7

    Surawicz CM, Elmer GW, Speelman P, McFarland LV, Chinn J, van Belle G, 1989. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Gastroenterology 96 :981–988.

    • Search Google Scholar
    • Export Citation
  • 8

    Buts JP, Corthier G, Delmee M, 1993. Saccharomyces boulardii for Clostridium difficile-associated enteropathies in infants. J Pediatr Gastroenterol Nutr 16 :419–425.

    • Search Google Scholar
    • Export Citation
  • 9

    Castaneda Guillot C, Garcia Bacallao E, Santa Cruz Dominguez M, Fernandez Garcia M, Monterrey Glutierrez P. 1995 Effects of Saccharomyces boulardii in children with chronic diarrhea, especially cases of giardiasis. Rev Mex Puericultura Pediatria 2 :12.

    • Search Google Scholar
    • Export Citation
  • 10

    Besirbellioglu BA, Ulcay A, Can M, Erdem H, Tanyuksel M, Avci IY, Araz E, Pahsa A, 2006. Saccharomyces boulardii and infection due to Giardia lamblia. Scand J Infect Dis 38 :479–481.

    • Search Google Scholar
    • Export Citation
  • 11

    Mansour-Ghanaei F, Dehbashi N, Yazdanparast K, Shafaghi A, 2003. Efficacy of Saccharomyces boulardii with antibiotics in acute amoebiasis. World J Gastroenterol 9 :1832–1833.

    • Search Google Scholar
    • Export Citation
  • 12

    Kollaritsch H, Holst H, Grobara P, Wiedermann G, 1993. Prevention of travelers’ diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study. Fortsschr Med 111 :152–156.

    • Search Google Scholar
    • Export Citation
  • 13

    Bleichner G, Blehaut H, Mentec H, Moyse D, 1997. Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. Intensive Care Med 23 :517–523.

    • Search Google Scholar
    • Export Citation
  • 14

    Saint-Marc T, Blehaut H, Musial C, Touraine JL, 1995. AIDS-related diarrhea: a double blind trial of Saccharomyces boulardii. Sem Hop 71 :735–741.

    • Search Google Scholar
    • Export Citation
  • 15

    Cetina-Sauri G, Sierra Basto G, 1994. Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea. Ann Pediatr (Paris) 41 :397–400.

    • Search Google Scholar
    • Export Citation
  • 16

    Kurugol Z, Koturoglu G, 2005. Effects of Saccharomyces boulardii in children with acute diarrhoea. Acta Paediatr 94 :44–47.

  • 17

    Billoo AG, Memon MA, Khaskheli SA, Murtaza G, Iqbal K, Saeed Shekhani M, Siddiqi AQ, 2006. Role of a probiotic (Saccharomyces boulardii) in management and prevention of diarrhoea. World J Gastroenterol 12 :4557–4560.

    • Search Google Scholar
    • Export Citation
  • 18

    Villarruel G, Rubio DM, Lopez F, Cintioni J, Gurevech R, Romero G, Vandenplas Y, 2007. Saccharomyces boulardii in acute childhood diarrhoea: a randomized, placebo-controlled study. Acta Paediatr 96 :538–541.

    • Search Google Scholar
    • Export Citation
  • 19

    Hochter W, Chase D, Hagenhoff G, 1990. Saccharomyces boulardii in treatment of acute adult diarrhea. Efficacy and tolerance of treatment. Munch Med Wochenschr 132 :188–192.

    • Search Google Scholar
    • Export Citation
  • 20

    Szajewska H, Skórka A, Dylag M, 2007. Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. Aliment Pharmacol Ther 25 :257–264.

    • Search Google Scholar
    • Export Citation
  • 21

    Salvatore S, Hauser B, Devreker T, Vieira MC, Luini C, Arrigo S, Nespoli L, Vandenplas Y, 2007. Probiotics and zinc in acute infectious gastroenteritis in children: are they effective? Nutrition 23 :498–506.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Effect of Saccharomyces boulardii in the Treatment of Acute Watery Diarrhea in Myanmar Children: A Randomized Controlled Study

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  • 1 Department of Child Health, North Okkalapa General Hospital, University of Medicine, Yangon, Myanmar; Universitair Ziekenhuis Brussel Kinderen, Brussels, Belgium

This study was conducted to evaluate the efficacy of Saccharomyces boulardii in acute diarrhea. One hundred hospitalized children in Myanmar (age range = 3 months to 10 years) were included. Fifty were treated with S. boulardii for five days in addition to oral rehydration solution (ORS) and 50 were given ORS alone (control group) in an alternating order. The mean duration of diarrhea was 3.08 days in the S. boulardii group and 4.68 days (P < 0.05) in the control group. Stools had a normal consistency on day 3 in 38 (76%) of 50 patients in the S. boulardii group compared with only 12 (24%) of 50 in the control group (P = 0.019). On day 2, 27 (54%) of 50 had less than three stools per day in the S. boulardii group compared with only 15 (30%) of 50 in the control group (P = 0.019). Saccharomyces boulardii shortens the duration of diarrhea and normalizes stool consistency and frequency. The shortening of the duration of diarrhea results in a social and economic benefits.

INTRODUCTION

Rapid rehydration and realimentation remain the cornerstone of treatment of acute gastroenteritis. Probiotics administered as add-on medications are likely to decrease the duration of acute infectious gastroenteritis with approximately 24 hours. Studies show a statistically significant benefit, mainly in infants and young children, in the treatment of persons with acute watery diarrhea. Because of strain specificity, only those organisms that have been clinically tested can be recommended.1

Saccharomyces boulardii is a probiotic yeast that has a direct antagonistic effect on many pathogens. The efficacy of S. boulardii is attributed to a direct inhibitory effect on the growth of pathogenic strains, an anti-secretory effect by specifically binding toxins to intestinal receptors, and a trophic effect on enterocytes with stimulation of enzymatic activity and non-specific anti-infectious mechanisms, such as anti-inflammatory activity.2 The polyamine increase induced by S. boulardii in humans results in an increased secretion of brush border disaccharidases and enzymes (lactase, sucrase, maltase, and aminopeptidase).2 The increased secretion of polyamines enhances maturation of enterocytes. Polyamines increase the glucose carrier activity on the membrane of enterocytes, which is essential to achieve maximal glucose absorption.2

Few studies with S. boulardii have been performed in Asia. The aim of this prospective study was to determine the effect of S. boulardii on the clinical course of acute watery diarrhea in hospitalized children. This aim was assessed by measurement of the duration of diarrhea and the frequency and consistency of stools. Acute diarrhea in Myanmar is caused mainly by enteropathogenic and enterotoxigenic Escherichia coli.35 Patients were tested selectively for the presence of these pathogens.

MATERIALS AND METHODS

One hundred children 3 months to 10 years of age (89 were 3 months to 2 years of age and 11 were more than 2 years of age) with acute watery diarrhea with a duration of less than seven days before inclusion were recruited in the pediatric ward of the North Okkalapa General Hospital in Yangon, Myanmar. Exclusion criteria were a fever > 38.5°C, clinically severe dehydration, macroscopic blood in the stools, intake of anti-fungal drugs, or existing severe malnutrition (weight-to-height ratio < 70%).

Patients were alternately assigned to receive the active product (S. boulardii) in addition to oral rehydration solution (ORS) or ORS alone. One hundred patients were divided into two groups; 50 patients were treated with S. boulardii, 250 mg twice a day for 5 days in combination with ORS (S. boulardii group) and 50 patients were given ORS alone (control group). The ORS was administered according to World Health Organization guidelines for management of diarrhea.6 Informed consent was obtained verbally from the parents before starting the study.

The duration of diarrhea and consistency and frequency of stools were recorded according to the information provided by the mother or attendant every morning starting from day 1. On admission, stool samples were taken from all patients for E. coli culture (Because this study was performed without any involvement of the company commercializing S. boulardii, the budget was limited). Diarrhea was defined as passing three or more loose stools per day (loose stool is a stool that takes the shape of the container). Diarrhea was considered to have stopped when the child passed less than three stools per day or stools with a solid consistency only. Data analysis was performed using the SPSS software version 11 (SPSS Inc., Chicago, IL). The chi-square test was used and a P value < 0.05 was considered significant.

RESULTS

Patient characteristics at baseline did not differ between the two groups. The mean duration of diarrhea was 3.08 days in S. boulardii group and 4.68 days in the control group (P < 0.05). On day 2, the defecation frequency was less than three times a day in 27 (54%) of 50 in the S. boulardii group and 15 (30%) of 50 in the control group (P = 0.019) (Table 1). On day 3, S. boulardii and ORS was two times more likely to reduce the frequency of stools to less than three per day than ORS alone. On day 4, 48 (96%) of 50 in the S. boulardii group had less than three stools per day compared with 39 (78%) of 50 in the control group.

On day two, S. boulardii had no significant effect on the consistency of stools. However, after day 3, stool consistency was significantly more solid in the S. boulardii group (Table 2). On day 3, 38 (76%) of 50 patients in the S. boulardii group passed solid stools compared with only 12 (24%) of 50 in the control group (P < 0.005). On day 4, patients were 13 times more likely to pass solid stools after receiving S. boulardii plus ORS than patients who received only ORS. After day 5, no patients in the S. boulardii group had liquid stools.

In the subgroup with E. coli gastroenteritis, stool consistency also normalized more rapidly in the S. boulardii group. This finding resulted in a significant difference in stool consistency on day 3 and 4 (P = 0.004 and P = 0.025, respectively).

DISCUSSION

The efficacy of S. boulardii has been documented in various types of diarrhea such as the prevention of antibiotic-associated diarrhea,7 Clostridium difficile–associated enteropathies,8 chronic diarrhea caused by giardiasis9,10 and amebiasis,11 prevention of traveler’s diarrhea,12 prevention of diarrhea in critically ill tube-fed patients,13 and treatment of human immunodeficiency virus–associated diarrhea.14 However, the major indication is acute diarrhea in children and adults.1519

The results presented in this trial in children in Myanmar hospitalized because of acute watery diarrhea confirm previous studies on S. boulardii for this indication.20,21 Acute diarrhea in Myanmar is caused mostly by enteropathogenic and enterotoxigenic E. coli, Salmonella, Shigella, Vibrio cholerae, and to a lesser extent by other microorganisms.35 In this study, pathogenic E. coli was isolated from 21 of 100 patients. The cause of diarrhea in the remaining patients was not known. The present study showed some beneficial effects of S. boulardii in treatment of diarrhea caused by E. coli.

The overall assessment of the clinical response showed a significant difference in favor of the active treatment group compared with the group treated with ORS alone, which confirmed the beneficial effects of S. boulardii for acute diarrhea. Saccharomyces boulardii has been shown to reduce the duration of diarrhea and the duration of hospitalization by approximately 24 hours.16,18,20,21 Greater efficacy has been shown if the treatment is started early.18 No severe side effects were observed during the trial.

In conclusion, the result of this prospective randomized study confirms that S. boulardii in combination with ORS reduces the duration of acute non-specific watery diarrhea in children in Myanmar. This biotherapeutic agent showed an obvious therapeutic effect in acute watery diarrhea with regard to consistency of stools, frequency of stools, and duration of diarrhea. Shortening the duration of diarrhea and reducing hospital stay result in a social and economic benefits.

Table 1

Stool frequency in the study population*

ControlsSaccharomyces boulardii
Day< 3 times≥ 3 times< 3 times≥ 3 timesP
* NS = not significant.
1050050NS
2153527230.019
3282239110.019
43911482NS
5482500NS
6500500NS
7500500NS
Table 2

Stool consistency in the study population*

ControlsSaccharomyces boulardii
DaySolidLiquidSolidLiquidPOdds ratio (95% CI)
* CI = confidence interval.
1050050
21493470.307
312383812< 0.0053.167 (1.888–5.312)
43020491< 0.00513.17 (1.909–88.889)
540105000.00113.025 (1.909–88.889)
6482500
7500500

*

Address correspondence to Yvan Vandenplas, Universitair Ziekenhuis Brussel Kinderen, Laarbeeklaan 101, 1090 Brussels, Belgium. E-mail: yvan.vandenplas@uzbrussel.be

Authors’ addresses: Khin Htwe, Khin Saw Yee, and Marlar Tin, Department of Child Health, North Okkalapa General Hospital, University of Medicine, Yangon, Myanmar. Yvan Vandenplas, Universitair Ziekenhuis Brussel Kinderen, Laarbeeklaan 101, 1090 Brussels, Belgium, Telephone: 32–2–477–5780, Fax: 32–2–477–5783, E-mail: yvan.vandenplas@uzbrussel.be.

REFERENCES

  • 1

    Vandenplas Y, Salvatore S, Vieira M, Devreker T, Hauser B, 2007. Probiotics in infectious diarrhoea in children: are they indicated? Eur J Pediatr 166 :1211–1218.

    • Search Google Scholar
    • Export Citation
  • 2

    Buts JP, 2006. Example of a Medicinal Probiotic: Lyophilized Saccharomyces boulardii. Gut Microflora. London: John Libbey Eurotext Editions, 221–244.

  • 3

    Mar Mar Nyein T, Tsukamoto, Tin Aye, Myo Khin, Khin New Oo, Khin Maung U, Takeda Y, 1992. Detection of pathogenic bacteria in children with diarrhea. Myanmar Health Sci Res Journal 4 :45–51.

    • Search Google Scholar
    • Export Citation
  • 4

    Mar Mar Nyein, Tin Aye, Khin Mg U, Myo Khin, Phyu Phyu Win, Thane Toe, 1999. Seasonal pattern of enterotoxigenic Escherichia coli (ETEC) in children under 3 years of age. Myanmar Health Sci Res J 8 :7–13.

    • Search Google Scholar
    • Export Citation
  • 5

    Mar Mar Nyein, Mi Mi Htwe, Aye Aye Maw, War War Aung, Khin Aye Aye Tun, Khin Myat Tun, 2005. Isolation of bacterial pathogens from children with diarrhea from Yangon’s Children Hospital 1999–2003, Paper presented at the Myanmar Research Conference. January 2005.

  • 6

    Bhan MK, Mahalanabis D, Pierce NF, Rollins N, 2005. The Treatment of Diarrhea: A Manual for Physicians and other Senior Health Workers. Geneva: World Health Organization/Child and Adolescent Health and Development, 8–16.

  • 7

    Surawicz CM, Elmer GW, Speelman P, McFarland LV, Chinn J, van Belle G, 1989. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Gastroenterology 96 :981–988.

    • Search Google Scholar
    • Export Citation
  • 8

    Buts JP, Corthier G, Delmee M, 1993. Saccharomyces boulardii for Clostridium difficile-associated enteropathies in infants. J Pediatr Gastroenterol Nutr 16 :419–425.

    • Search Google Scholar
    • Export Citation
  • 9

    Castaneda Guillot C, Garcia Bacallao E, Santa Cruz Dominguez M, Fernandez Garcia M, Monterrey Glutierrez P. 1995 Effects of Saccharomyces boulardii in children with chronic diarrhea, especially cases of giardiasis. Rev Mex Puericultura Pediatria 2 :12.

    • Search Google Scholar
    • Export Citation
  • 10

    Besirbellioglu BA, Ulcay A, Can M, Erdem H, Tanyuksel M, Avci IY, Araz E, Pahsa A, 2006. Saccharomyces boulardii and infection due to Giardia lamblia. Scand J Infect Dis 38 :479–481.

    • Search Google Scholar
    • Export Citation
  • 11

    Mansour-Ghanaei F, Dehbashi N, Yazdanparast K, Shafaghi A, 2003. Efficacy of Saccharomyces boulardii with antibiotics in acute amoebiasis. World J Gastroenterol 9 :1832–1833.

    • Search Google Scholar
    • Export Citation
  • 12

    Kollaritsch H, Holst H, Grobara P, Wiedermann G, 1993. Prevention of travelers’ diarrhea with Saccharomyces boulardii. Results of a placebo controlled double-blind study. Fortsschr Med 111 :152–156.

    • Search Google Scholar
    • Export Citation
  • 13

    Bleichner G, Blehaut H, Mentec H, Moyse D, 1997. Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. Intensive Care Med 23 :517–523.

    • Search Google Scholar
    • Export Citation
  • 14

    Saint-Marc T, Blehaut H, Musial C, Touraine JL, 1995. AIDS-related diarrhea: a double blind trial of Saccharomyces boulardii. Sem Hop 71 :735–741.

    • Search Google Scholar
    • Export Citation
  • 15

    Cetina-Sauri G, Sierra Basto G, 1994. Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea. Ann Pediatr (Paris) 41 :397–400.

    • Search Google Scholar
    • Export Citation
  • 16

    Kurugol Z, Koturoglu G, 2005. Effects of Saccharomyces boulardii in children with acute diarrhoea. Acta Paediatr 94 :44–47.

  • 17

    Billoo AG, Memon MA, Khaskheli SA, Murtaza G, Iqbal K, Saeed Shekhani M, Siddiqi AQ, 2006. Role of a probiotic (Saccharomyces boulardii) in management and prevention of diarrhoea. World J Gastroenterol 12 :4557–4560.

    • Search Google Scholar
    • Export Citation
  • 18

    Villarruel G, Rubio DM, Lopez F, Cintioni J, Gurevech R, Romero G, Vandenplas Y, 2007. Saccharomyces boulardii in acute childhood diarrhoea: a randomized, placebo-controlled study. Acta Paediatr 96 :538–541.

    • Search Google Scholar
    • Export Citation
  • 19

    Hochter W, Chase D, Hagenhoff G, 1990. Saccharomyces boulardii in treatment of acute adult diarrhea. Efficacy and tolerance of treatment. Munch Med Wochenschr 132 :188–192.

    • Search Google Scholar
    • Export Citation
  • 20

    Szajewska H, Skórka A, Dylag M, 2007. Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. Aliment Pharmacol Ther 25 :257–264.

    • Search Google Scholar
    • Export Citation
  • 21

    Salvatore S, Hauser B, Devreker T, Vieira MC, Luini C, Arrigo S, Nespoli L, Vandenplas Y, 2007. Probiotics and zinc in acute infectious gastroenteritis in children: are they effective? Nutrition 23 :498–506.

    • Search Google Scholar
    • Export Citation
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