Paediatrica Indonesiana

VOLUME 52 NUMBER 2 March 2O12

Original Article
Paediatr Indones, Vol. 52, No. 2, March 2012 91
Effect of adding tyndallized probiotics to the World
Health Organization standard therapy for acute
diarrhea in children
Kesatrianita Mawarni Fanny, Wahyu Damayanti, Mohammad Juffrie
Abstract
Background Diarrhea is the major cause of morbiditv and mortalitv
in children. Probiotics can decrease the frequencv and duration
of diarrhea. 1here are two tvpes of probiotics, live and tvndallized.
1vndallized probiotics have been sterilized, so thev are unable to produce
active metabolites, but mav have an effect on human immunitv.
Objective 1o evaluate the effectiveness of supplementin, WH
standard therapv with tvndallized probiotics in children with
acute, waterv diarrhea.
Methods We performed a randomized, sin,le-blind, controlled
trial in children a,ed 3-6O months who were dia,nosed with acute,
waterv diarrhea at Ounun,sitoli Oeneral Hospital, Nias, North
Sumatera. Subjects were collected bv consecutive samplin, bv
wav of parent interviews.
Results ne hundred subjects with acute, waterv diarrhea were
divided into 2 ,roups of 5O. ne ,roup was treated with onlv
WH standard therapv for acute, waterv diarrhea. 1he other
,roup was treated bv WH standard therapv with the addition
of tvndallized probiotics. 1here were no si,nificant differences in
basic characteristics between the two ,roups. Diarrheal duration
for the ,roup receivin, WH standard therapv onlv was 3.95
1.3 davs, while that of the ,roup receivin, both WH standard
therapv and tvndallized probiotics was 1.6 2.3 davs (P > O.O5).
Diarrheal frequencv on the fifth dav in the WH standard therapv
,roup was 1.9O O.99 times per dav, while that of the tvndallized
probiotic ,roup was 1.56 O.67 times per dav (P > O.O5).
Conclusion 1here were no si,nificant differences between WH
standard therapv alone and WH standard therapv with the addition
of tvndallized probiotics for decreasin, the duration and frequencv of
diarrhea in children. [Paediatr Indones. 2012;52:91-4].
Keywords: tyndallized probiotic, acute diarrhea,
WHO standard therapy
lrom the Department of Child Health, Medical School, Oadjah Mada
Universitv, Yo,vakarta, lndonesia.
Reprint requests to: Kesatrianita Mawarni lannv, Department of Child
Health, Oadjah Mada Universitv Medical School, Jalan Kesehatan No. 1
Sekip Yo,vakarta 552o1, lndonesia. 1el 62-271-561616. lax 62-271-
5o3715. lmail: fannyhondro@gmail.com
D
iarrhea is the major cause of morbiditv
and mortalitv in children. ln lndonesia,
based on National Basic Health Research
(Riskesdas) 2OO7 results, diarrhea was
the major cause of death in infants (12'), followed
bv pneumonia (21'). ln children a,ed 1-1 vears,
it caused 25.2' of deaths, followed bv pneumonia
(15.5').
1,2
Currentlv, the five steps for diarrhea treatment
used, known as the five pillars of rehvdration,
nutritional support, zinc supplementation, selective
antibiotic use and parental education. 1hese
pillars are in a,reement with the WH standards
of mana,ement for acute diarrhea, consistin, of
rehvdration, administration of zinc and continued
feedin,.
3,1
Probiotics are food and drinks that contain
live microor,anisms which mav provide beneficial
phvsiolo,ical effects for the host throu,h microbial
action.
5
Previous studies have reported that live
Kesatrianita MF et al: lffect of addin, tvndallized probiotics to the WH standard therapv for acute diarrhea in children
92 Paediatr Indones, Vol. 52, No. 2, March 2012
probiotics mav reduce the duration and frequencv of
diarrhea.
5,6,7
ln addition to live probiotics, tvndallized
probiotics have also been used. 1vndallization
sterilizes the probiotics, so that active metabolites
are not produced. However, this form of probiotic
mav still have an effect on human immunitv. Since
micoror,anisms in tvndallized probiotics are unable to
reproduce, tvndallized probiotics have an advanta,e
over the live form, in that ,ene resistance cannot be
inherited and there is no possibilitv of it causin, sepsis.
A number of studies on tvndallized probiotics have
shown that thev stimulate 1h1 cvtokines and suppress
the production of immuno,lobulin l, enhancin, the
svstemic and mucosal immune responses, particularv
the production of immuno,lobulin A.
o,9
Since
there have been few studies on the effectiveness of
tvndallized probiotics on acute waterv diarrhea in
children, we aimed to evaluate their effect on diarrhea
duration and frequencv.
Methods
lrom Au,ust to ctober 2OO9, we performed a
randomized, sin,le-blind, controlled trial comparin,
two ,roups of subjects with acute waterv diarrhea.
ne ,roup received WH standard therapv and the
other ,roup received WH standard therapv with
tvndallized probiotics. Subjects were children a,ed
3-6O months livin, in Ounun,sitoli, Nias who suffered
from waterv stool 3 or more times per dav for less than
11 davs and whose parents ,ave written informed
consent. We excluded children sufferin, from acute
diarrhea accompanied bv a severe disease and/or with
malnutrition (Figure 1).
1he estimated required sample size was 1OO,
calculated bv unpaired cate,orical analvsis formula,
with D ~ O.O5 and E ~ O.2O. Bv consecutive samplin,,
subjects were divided into two ,roups of 5O subjects each.
WH standard treatment consisted of rehvdration,
Figure 1. Study ow chart
Assessed for eligibility (n = 105 )
Randomized (n = 100)
Allocated to control group
(n = 50)
WHO standard therapy
only
Lost to follow-up (n = 0)
Analyzed (n = 50)
Excluded
Did not meet the
inclusion criteria (n = 5)
Allocated to treatment group
(n =50)
WHO standard therapy +
tyndallized probiotic
Lost to follow-up (n = 0)
Analyzed (n = 50)
Kesatrianita MF et al: lffect of addin, tvndallized probiotics to the WH standard therapv for acute diarrhea in children
Paediatr Indones, Vol. 52, No. 2, March 2012 93
oral zinc and continued feedin,. 1he treatment ,roup
received tvndallized probiotic (Dialac

1 sachet twice
dailv, _ 31O m, tvndallized probiotics per dose) for
five davs in addition to the WH standard treatment.
1he control ,roup received onlv the WH standard
treatment. We confirmed that outpatient subjects
received treatment bv telephonin, their parents. Nurses
confirmed administration of therapv for the inpatient
subjects. lrequencv of diarrhea and the side effects of
the therapv were recorded bv parents or nurses on a
standardized form. 1he outcomes of the studv were
the duration and frequencv of diarrhea.
1his studv was approved bv the Commission on
Medical Research lthics and Health, Oadjah Mada
Universitv Medical School. All subjects' parents
provided written informed consent.
Data was analvzed with SPSS for Windows
16.O. 1he effect of tvndallized probiotics with WH
standard therapv was analvzed bv independent
t-test and Chi-square test. Results were considered
statisticallv si,nificant if P < O.O5 with a 95'
confidence interval (Cl).
Results
1here were 1OO subjects divided into two ,roups.
Characteristics of subjects are shown in Table 1.
1here were no si,nificant differences in the
duration or frequencv of diarrhea between the two
,roups as shown in Table 2. Mean duration of diarrhea
in the probiotic ,roup was 1.6 2.3 davs, while that
of the WH standard therapv ,roup was 3.95 1.3
davs (P ~ O.9o). 1he frequencv of diarrhea after the
fifth dav of treatment was 1.56 (SD O.67) times/dav
in the probiotic ,roup, and 1.9 (SD O.99) times/dav
in the WH standard therapv ,roup (P ~ O.1O6). ln
this studv, no side effects, such as sepsis or bacteremia
due to the use of tvndallized probiotics, were observed.
Accordin, to parents' and nurses' reports, all subjects
received their therapv with a 1OO' compliance.
Discussion
1he addition of tvndallized probiotics did not
shorten the duration or reduce the frequencv of
acute diarrhea. Several meta-analvsis studies have
concluded that the addition of probiotics can reduce
the duration of diarrhea, however, these studies used
live probiotics.
5,6,7
Results similar to ours were obtained bv Khanna
et al
1O
in lndia and Pramono et al
11
in lndonesia.
Accordin, to Khanna et al, to observe a therapeutic
effect from probiotics, microbial colonization
should have occurred before their administration.
Table 1. Baseline characteristics of subjects
Characteristics
WHO standard therapy
+ tyndallized probiotic
n = 50
WHO standard therapy
alone
n = 50
Male gender, n (%)
Mean age, months (SD)
Dehydration status
Not dehydrated, n (%)
Dehydrated, n (%)
Mean diarrhea frequency, n (SD)
Nutritional status
Well-nourished, n (%)
Undernourished, n (%)
29(58.0)
17.46 (15.82)
36 (72)
14(28)
7.20 ( 2.16)
30 (60)
20 (40)
25(50)
12.74 (9.84)
30 (60)
20(40)
7.26(2.0)
30(60)
20(40)
Table 2. Diarrhea duration and frequency
Results
WHO standard therapy
+ tyndallized probiotics
WHO standard
therapy alone
P*
Mean duration of diarrhea, days (SD)
Mean frequency of diarrhea on 5th day, times/day (SD)
4.60 (2.3)
1.56 (0.67)
3.95 (1.3)
1.90 (0.99)
0.98
0.11
*t-test
Kesatrianita MF et al: lffect of addin, tvndallized probiotics to the WH standard therapv for acute diarrhea in children
94 Paediatr Indones, Vol. 52, No. 2, March 2012
However, microbial colonization means the duration
of diarrhea would be lon,er. ln acute diarrhea,
colonization mav not vet have taken place, so the
addition of tvndallized probiotics would not provide
the optimal effect.
12
Since stool cultures were not examined, we do
not know the microbial patho,ens causin, diarrhea
in our studv. lrom past stool examination studies,
probiotics were reported to provide ,ood therapeutic
effect on rotavirus diarrhea.
9
A limitation of our studv was the lack of
intensive supervision after treatment administration
to each ,roup. As such, co-intervention mav have
occurred bevond our monitorin, efforts due to the
exchan,e of information between studv ,roups.
lurthermore, with the sin,le-blind studv desi,n, studv
contamination between ,roups mav have occurred if
parents or relatives ,ave other dru,s to the subjects,
influencin, the outcome of the studv. 1herefore,
further research mav be needed, usin, a lar,er sample
size and more intensive monitorin, for each subject.
Nevertheless, our results were similar to previous
research, concludin, that tvndallized probiotics did
not reduce the duration and frequencv of acute
diarrhea in children.
1here were no si,nificant differences in
duration and frequencv of diarrhea between the
WH standard therapv ,roup and the WH
standard therapv with tvndallized probiotics
,roup.
References
1. Juffrie M, Mulvani NS. Diare cair akut dan diare berdarah.
Jakarta: Badan Penerbit lDAl, 2OO9. p.1-11.
2. Badan penelitian dan pen,emban,an kesehatan-Depkes Rl.
National Basic Health reaserch (Riskesdas) 2OO7. Jakarta:
National report, 2OO7. p.1O6-o.
3. Departemen Kesehatan Rl. Policv of Health Minister
(Kepmenkes) of Rl (No.1216/Menkes/SK/Xl/2OO1), ,uidelines
for the eradication of diarrheal diseases. Jakarta, 2OO5.
1. World Health r,anization. 1he clinical mana,ement of
diarrhea: implementin, the new recommendation. Oeneva:
WH Document Production Services, 2OO6. p. 2-5.
5. Van Niel CW, leutdner C, Oarisson MM, Christakis DA.
lactobacillus therapv for acute infectious diarrhea in
children: a meta-analvsis. Pediatrics. 2OO2,1O9:67o-o1.
6. Huan, JS, Bousvaros A, Lee JW, Diaz A, Davidson lJ.
lfficacv of probiotics use in acute diarrhea in children: a
meta-analvsis. Di, Dis Sci. 2OO2,17:2625-31.
7. Sjazewska H, Mrukowicz Jz. Probiotics in the treatment and
prevention of acute infectious diarrhea in infants and children:
a svstematic review of published randomized, double-blind,
placebo-controlled trials. J Pediatr Oastroenterol Nutr.
2OO1,33:S17-25.
o. lshibashi N, Yamazaki S. Probiotics and safetv. Am J Clin
Nutr. 2OO1,73:S165-7O.
9. Delcenserie V, Martel D, lamoereux M, Amiot J, Boutin
Y, Rov D. lmmunomodulatorv effect of probiotics in the
intestinal tract. Curr lssues Mol Biol. 2OOo,1O:37-51.
1O. Khanna V, Alam S, Malik A, Malik A. lfficacv of tvndalized
Lactobacillus acidophilus in acute diarrhea. lndian J Pediatrics.
2OO5,72:935-o.
11. Pramono B, Sudarmo RM, Ranuh RO, Athivah Al, Budiono.
Pen,aruh pemberian heat-killed probiotic complex pada usia
6-21 bulan terhadap perjalanan dan kesembuhan diare akut
|master's thesis]. |Surabava]: Universitas Airlan,,a, 2OO9.
12. Ribeiro H, Ribeiro TC, Mattos AP, Valois SS, Neri DA,
Vanderhoof JA, et al. limitations of probiotic therapv in
acute, severe dehvdratin, diarrhea. J Pediatr Oastroenterol
Nutr. 2OO3,36:112-5.