Am. J. Trop. Med. Hyg., 78(2), 2008, pp.
214–216
Copyright © 2008 by The American Society of Tropical Medicine and Hygiene
            Effect of Saccharomyces boulardii in the Treatment of Acute Watery Diarrhea in
                          Myanmar Children: A Randomized Controlled Study
                                            Khin Htwe, Khin Saw Yee, Marlar Tin, and Yvan Vandenplas*
       Department of Child Health, North Okkalapa General Hospital, University of Medicine, Yangon, Myanmar; Universitair Ziekenhuis
                                                   Brussel Kinderen, Brussels, Belgium
         Abstract. 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                                          age) with acute watery diarrhea with a duration of less than
                                                                                  seven days before inclusion were recruited in the pediatric
   Rapid rehydration and realimentation remain the corner-
                                                                                  ward of the North Okkalapa General Hospital in Yangon,
stone of treatment of acute gastroenteritis. Probiotics admin-
                                                                                  Myanmar. Exclusion criteria were a fever > 38.5°C, clinically
istered as add-on medications are likely to decrease the du-
                                                                                  severe dehydration, macroscopic blood in the stools, intake of
ration of acute infectious gastroenteritis with approximately
                                                                                  anti-fungal drugs, or existing severe malnutrition (weight-to-
24 hours. Studies show a statistically significant benefit,
                                                                                  height ratio < 70%).
mainly in infants and young children, in the treatment of
                                                                                     Patients were alternately assigned to receive the active
persons with acute watery diarrhea. Because of strain speci-
                                                                                  product (S. boulardii) in addition to oral rehydration solution
ficity, only those organisms that have been clinically tested
                                                                                  (ORS) or ORS alone. One hundred patients were divided
can be recommended.1
                                                                                  into two groups; 50 patients were treated with S. boulardii,
   Saccharomyces boulardii is a probiotic yeast that has a di-
                                                                                  250 mg twice a day for 5 days in combination with ORS (S.
rect antagonistic effect on many pathogens. The efficacy of S.
                                                                                  boulardii group) and 50 patients were given ORS alone (con-
boulardii is attributed to a direct inhibitory effect on the
                                                                                  trol group). The ORS was administered according to World
growth of pathogenic strains, an anti-secretory effect by spe-
                                                                                  Health Organization guidelines for management of diarrhea.6
cifically binding toxins to intestinal receptors, and a trophic
                                                                                  Informed consent was obtained verbally from the parents be-
effect on enterocytes with stimulation of enzymatic activity
                                                                                  fore starting the study.
and non-specific anti-infectious mechanisms, such as anti-
                                                                                     The duration of diarrhea and consistency and frequency of
inflammatory activity.2 The polyamine increase induced by S.
                                                                                  stools were recorded according to the information provided
boulardii in humans results in an increased secretion of brush
                                                                                  by the mother or attendant every morning starting from day
border disaccharidases and enzymes (lactase, sucrase, mal-
                                                                                  1. On admission, stool samples were taken from all patients
tase, and aminopeptidase).2 The increased secretion of
                                                                                  for E. coli culture (Because this study was performed without
polyamines enhances maturation of enterocytes. Polyamines
                                                                                  any involvement of the company commercializing S. boular-
increase the glucose carrier activity on the membrane of en-
                                                                                  dii, the budget was limited). Diarrhea was defined as passing
terocytes, which is essential to achieve maximal glucose ab-
                                                                                  three or more loose stools per day (loose stool is a stool that
sorption.2
                                                                                  takes the shape of the container). Diarrhea was considered to
   Few studies with S. boulardii have been performed in Asia.
                                                                                  have stopped when the child passed less than three stools per
The aim of this prospective study was to determine the effect
                                                                                  day or stools with a solid consistency only. Data analysis was
of S. boulardii on the clinical course of acute watery diarrhea
                                                                                  performed using the SPSS software version 11 (SPSS Inc.,
in hospitalized children. This aim was assessed by measure-
                                                                                  Chicago, IL). The chi-square test was used and a P value
ment of the duration of diarrhea and the frequency and con-
                                                                                  < 0.05 was considered significant.
sistency of stools. Acute diarrhea in Myanmar is caused
mainly by enteropathogenic and enterotoxigenic Escherichia
coli.3–5 Patients were tested selectively for the presence of                                              RESULTS
these pathogens.
                                                                                     Patient characteristics at baseline did not differ between
                  MATERIALS AND METHODS                                           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 <
  One hundred children 3 months to 10 years of age (89 were
                                                                                  0.05). On day 2, the defecation frequency was less than three
3 months to 2 years of age and 11 were more than 2 years of
                                                                                  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
* Address correspondence to Yvan Vandenplas, Universitair Ziek-
                                                                                  day 3, S. boulardii and ORS was two times more likely to
enhuis Brussel Kinderen, Laarbeeklaan 101, 1090 Brussels, Belgium.                reduce the frequency of stools to less than three per day than
E-mail: yvan.vandenplas@uzbrussel.be                                              ORS alone. On day 4, 48 (96%) of 50 in the S. boulardii group
                                                                            214
                                                                 S. BOULARDII AND DIARRHEA IN MYANMAR                                                        215
                                  TABLE 1                                                  The cause of diarrhea in the remaining patients was not
                  Stool frequency in the study population*                                 known. The present study showed some beneficial effects of
                    Controls                        Saccharomyces boulardii                S. boulardii in treatment of diarrhea caused by E. coli.
Day        < 3 times          ⱖ 3 times            < 3 times       ⱖ 3 times         P        The overall assessment of the clinical response showed a
 1             0                   50                  0              50            NS
                                                                                           significant difference in favor of the active treatment group
 2            15                   35                 27              23           0.019   compared with the group treated with ORS alone, which con-
 3            28                   22                 39              11           0.019   firmed the beneficial effects of S. boulardii for acute diarrhea.
 4            39                   11                 48               2            NS     Saccharomyces boulardii has been shown to reduce the dura-
 5            48                    2                 50               0            NS     tion of diarrhea and the duration of hospitalization by ap-
 6            50                    0                 50               0            NS
 7            50                    0                 50               0            NS     proximately 24 hours.16,18,20,21 Greater efficacy has been
 * NS ⳱ not significant.
                                                                                           shown if the treatment is started early.18 No severe side ef-
                                                                                           fects were observed during the trial.
                                                                                              In conclusion, the result of this prospective randomized
had less than three stools per day compared with 39 (78%) of                               study confirms that S. boulardii in combination with ORS
50 in the control group.                                                                   reduces the duration of acute non-specific watery diarrhea in
   On day two, S. boulardii had no significant effect on the                               children in Myanmar. This biotherapeutic agent showed an
consistency of stools. However, after day 3, stool consistency                             obvious therapeutic effect in acute watery diarrhea with re-
was significantly more solid in the S. boulardii group (Table                              gard to consistency of stools, frequency of stools, and dura-
2). On day 3, 38 (76%) of 50 patients in the S. boulardii group                            tion of diarrhea. Shortening the duration of diarrhea and re-
passed solid stools compared with only 12 (24%) of 50 in the                               ducing hospital stay result in a social and economic benefits.
control group (P < 0.005). On day 4, patients were 13 times
more likely to pass solid stools after receiving S. boulardii                              Received July 6, 2007. Accepted for publication October 23, 2007.
plus ORS than patients who received only ORS. After day 5,                                 Authors’ addresses: Khin Htwe, Khin Saw Yee, and Marlar Tin, De-
no patients in the S. boulardii group had liquid stools.                                   partment of Child Health, North Okkalapa General Hospital, Uni-
   In the subgroup with E. coli gastroenteritis, stool consis-                             versity of Medicine, Yangon, Myanmar. Yvan Vandenplas, Univer-
                                                                                           sitair Ziekenhuis Brussel Kinderen, Laarbeeklaan 101, 1090 Brussels,
tency also normalized more rapidly in the S. boulardii group.                              Belgium, Telephone: 32-2-477-5780, Fax: 32-2-477-5783, E-mail:
This finding resulted in a significant difference in stool con-                            yvan.vandenplas@uzbrussel.be.
sistency on day 3 and 4 (P ⳱ 0.004 and P ⳱ 0.025, respec-
tively).
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