Paediatrica Indonesiana

VOLUME 52 NUMBER 1 January º 2O12
Original Article
22 º Paediatr Indones, Vol. 52, No. 1, January 2012
Surveillance of rotavirus diarrhea
Titis Widowati
1
, Achirul Bakrie
2
, Hera Nirwati
3
, Yati Soenarto
1
Abstract
Background Rotavirus is a major cause of severe diarrhea and
dehvdration in children worldwide. Data on the burden of disease
in Indonesia is limited.
Objective 1o provide an epidemiolo,ical profile of rotavirus
infection among children hospitalized for diarrhea in Mohammad
Hoesin Hospital, Palemban,.
Methods ln Januarv - December 2OO6, a prospective, hospital-
based surveillance was carried out in children a,ed less than
five vears, presentin, with diarrhea. Stool samples were
examined for rotavirus usin, enzvme immunoassav (llA).
O- and P-tvpin, were performed on specimens confirmed to
be positive bv llA.
Results A total of 513 fecal specimens from 531 children were
tested for rotavirus. Rotavirus was detected in 61' of the
specimens, mostlv of the O9 tvpe (62.5'). lncidence of rotavirus
diarrhea was hi,hest in the 6 month to 2 vears a,e ,roup (6O.1').
Children with rotavirus diarrhea were more likelv to present with
dehvdration, compared to those with non-rotavirus diarrhea (91'
vs 7O', respectivelv, P~O.O3).
Conclusion Rotavirus was the most common patho,en found
in children with diarrhea. Rotavirus was detected in 61' of
pediatric diarrheal specimens tested in our study. This finding
warrants the use of a lar,e-scale pro,ram to prevent disease,
such as vaccination a,ainst rotavirus. [Paediatr Indones.
2012;52:22-7].
Keywords: rotavirus, diarrhea, dehydration, G9
strain
lrom the Department of Child Health, Oadjah Mada Universitv Medical
School, DR Sardjito Hospital, Yo,vakarta
1
, and Sriwijava Universitv,
Mohammad Hoesin Hospital, Palemban,
2
, and the Department of
Microbiolo,v, Oadjah Mada Universitv Medical School, Yo,vakarta
3
,
Indonesia.
Reprint requests to: 1itis Widowati, Department of Child Health, Medical
School, Oadjah Mada Universitv, DR Sardjito Hospital, Yo,vakarta, Jl
Kesehatan no 1, Sekip Utara, Yo,vakarta, 55o21, lndonesia. 1el. ÷62-271-
5o7333. lax. ÷62-271-5o3715. l-mail: titis_widowati@yahoo.com
R
otavirus is the most common cause of severe
diarrhea in infants and young children
in both industrialized and developin,
countries. 1he severitv of rotavirus diarrhea,
in particular, is associated with life-threathening
dehvdration. ln developin, countries where diarrhea
is estimated to cause 2 million deaths per year,
more than 6OO,OOO children under five vears of a,e
die annuallv from rotavirus infection. 1his fi,ure
represents about 5' of all deaths in children voun,er
than five vears.
1-3
Indonesia is one of the countries with greatest
number of rotavirus related deaths which accounted
for 9,97O per 1OO,OOO children under 5 vears a,e
in 2OOo (2' of the worldwide total) accordin, to
the results of svstematic reviews and meta-analvsis
research on the estimation of worldwide rotavirus
associated mortality in children younger than 5
years.
4
While most deaths are in children from
developin, countries, industrialized nations also
have a substantial disease burden. More than
Titis Widowati et al: Surveillance of rotavirus diarrhea
Paediatr Indones, Vol. 52, No. 1, January 2012 º 23
9O' of children have been reported to be infected
with rotavirus bv the a,e of 3 vears, re,ardless of
nationalitv, level of hv,iene, sanitation or access to
clean water.
5,6
Oood hv,iene practice and oral rehvdration
pro,rams have not controlled the disease, and
vaccination seems to be the onlv option to prevent
rotavirus infection. Vaccines have been estimated
to prevent oO' of severe disease. ln addition to
studvin, vaccine safetv and efficacv, the decision
on whether to introduce rotavirus vaccine into the
state immunization program should be supported by
information on disease burden, health benefits, and
impact on ,overnmental bud,ets.
7,o
ln lndonesia, studies on rotavirus have been
conducted since 197o. Past research revealed that
rotavirus was responsible for 25'-5O' of pediatric
hospitalizations for diarrhea in both industrialized and
developin, countries.
9
To date, only a few studies on
rotavirus strain prevalence in lndonesia have been
done. Òur studv, conducted in Palemban,, Sumatra,
Indonesia, was performed to further elucidate the
prevalence of rotavirus infection and characterize
infecting strains.
Methods
Children under 5 years of age who were hospitalized
for acute diarrhea in Januarv to December 2OO6
were enrolled into our studv. Diarrhea was defined
as passing watery and/or bloody stools, as well as
mucous stool.
The diagnosis of diarrhea was made by the
admitting physician. The study coordinator or
research assistant then evaluated subjects for
eligibility. Informed consent was obtained from
parents of all eli,ible subjects. Data on demo,raphic,
clinical and laboratory characteristics were completed
bv a trained studv assistant. All patients received
the standard treatment protocol, regardless of their
enrollment status.
After a subject enrolled, a ward nurse collected
a stool sample within the first 48 hours of hospital
admission. Specimens were stored in a dedicated
refrigerator at 4
o
C. Study assistants filled forms on
stool sample collections. All stool samples and forms
were then sent to Bio Farma Laboratory, Bandung,
for rotavirus identification. All stool samples were
tested for the presence of ,roup A rotavirus bv llA
usin, lDllA
TM
Rotavirus (Dako Cvtomation, ltd.,
Cambridgeshire, UK) at the Bio Farma Laboratory.
O- and P-tvpin, were performed on specimens
confirmed to be positive bv llA in the Microbiolo,v
laboratorv, Oadjah Mada Universitv Medical School,
Yo,vakarta. Rotavirus RNA specimens were analvzed
to determine the VP1 and VP7 ,enotvpes usin, the
method described bv Oentsch et al.
1O
All data were entered into a pre-designed data
set by a data entry operator in the hospital and sent to
Oadjah Mada Universitv Medical School for analvsis.
lthical approval was issued bv the lthics Review
Committee, Oadjah Mada Universitv Medical School,
Yogyakarta. Written informed consent was obtained
from all subjects’ parents.
Results
ln the 12 month studv period, a total of 531
children under 5 years of age who were admitted
and hospitalized at Mohammad Hoesin Hospital,
Palemban, with acute diarrhea, were enrolled.
lrom these subjects, 513 stool specimens were
tested. 1here were more bovs (59') than ,irls
(11') enrolled. Òverall, rotavirus was detected in
61' of the specimens tested. 1he detection rate for
rotavirus was hi,her for males than for females, 65'
vs. 62', respectivelv, althou,h the difference was not
statisticallv si,nificant (P~O.1o) (Figure 1).
We plotted the total number of diarrhea cases,
number of specimens tested and number of rotavirus-
positive cases bv month (Januarv - December 2OO6).
Rotavirus diarrhea occurred vear-round, with the
highest rate occurring between June and August
(Figure 2).
Figure 3 shows the distribution of rotavirus
diarrhea bv a,e ,roups. li,htv-five percent of
rotavirus diarrhea cases occurred before the a,e
of 2 years, with the highest incidence occurring in
subjects a,ed 6 months to 2 vears. We found 5'
of rotavirus cases in subjects < 3 months old, and
51' of rotavirus cases were hospitalized bv the a,e
1 year.
1he major si,ns and svmptoms observed in
children with rotavirus diarrhea were dehvdration,
Titis Widowati et al: Surveillance of rotavirus diarrhea
24 º Paediatr Indones, Vol. 52, No. 1, January 2012
vomitin,, mucous stool and fever (Table 1).
Dehvdration occurred more frequentlv in children
with rotavirus diarrhea compared to those with
non-rotavirus diarrhea, 91' vs. o9', respectivelv.
However, vomitin, occurred at hi,her frequencv
in the rotavirus ,roup, oo' vs. 7O', respectivelv.
Converselv, children with rotavirus diarrhea were
less likelv to have bloodv stools than those with
non-rotavirus diarrhea (3' vs. 9', respectivelv).
Dehvdration was the main reason for hospitalization
in children with rotavirus diarrhea. Moderate
dehvdration occurred more frequentlv than severe
dehvdration (77' vs. 17') in rotavirus-positive
subjects (Figure 4).
Figure 1. Rotavirus infection by gender
350
300
250
200
150
100
50
0
Male Female
Sex
N
o
.

o
f

s
p
e
c
i
m
e
n
s

t
e
s
t
e
d
No. of specimens tested
No. of rotavirus diarrhea
Figure 2. Number of subjects with diarrhea, number of specimens tested and num-
ber of rotavirus-positive (RTV pos) cases by month (January – December 2006)
80
70
60
50
40
30
20
10
0
J
a
n
F
e
b
M
a
r
A
p
r
M
a
y
J
u
n
J
u
l
y
A
u
g
S
e
p
t
O
c
t
N
o
v
D
e
c
No. of cases
No. of specimens tested
RTV pos
Titis Widowati et al: Surveillance of rotavirus diarrhea
Paediatr Indones, Vol. 52, No. 1, January 2012 º 25
O- and P-tvpin, was performed on 1O specimens.
1he most common O-serotvpe rotaviruses present were
O9 (62.5'), followed bv O1 (1O') and O2 (5'). Mixed
infections were observed in 15' of cases. 1he majoritv
of P-serotvpes detected were P|6] (72.5') and P|1]
(5'). Mixed infections were observed in the remainin,
specimens (12.5'). Untvpeable strains were detected in
7.5' of the O strains and 1O' of the P strains.
Figure 4. Dehydration levels in children with rotavirus diarrhea compared to those
with non-rotavirus diarrhea
300
250
200
150
100
50
0
N
o
.

o
f

s
p
e
c
i
m
e
n
s

t
e
s
t
e
d
No. of rotavirus positive
diarrhea
No. of negative diarrhea
No
dehydration
Moderate
dehydration
Severe
dehydration
Level of dehydration
Figure 3. Age distribution of rotavirus (RTV) diarrhea
200
180
160
140
120
100
80
60
40
20
0
Month group
No. of cases
No. of specimens tested
RTV pos
0
0
-
0
2
0
3
-
0
5
0
6
-
1
1
1
2
-
2
3
2
4
-
3
5
3
6
-
4
7
4
8
-
5
9
Titis Widowati et al: Surveillance of rotavirus diarrhea
26 º Paediatr Indones, Vol. 52, No. 1, January 2012
Discussion
We observed a lar,e percenta,e (61') of diarrheal
cases in children aged under 5 years to be infected with
rotavirus. 1he peak incidence of rotavirus diarrhea
occurred in subjects under 2 vears of a,e (o5'), with the
highest incidence in children aged between 6 months
to 2 years. This finding is consistent with a number of
epidemiological studies from other countries.
6,o,9,11
1his studv revealed that in the Mohammad
Hoesin Hospital, Palemban,, rotavirus diarrhea
occurred year-round, similar to that found in other
developin, tropical countries.
12,13
The peak incidence
of rotavirus diarrhea occurred from Julv to Au,ust,
when the rainfall was low. However, it is difficult to
demonstrate a seasonal pattern of rotavirus diarrhea
in Palemban, because the studv period was less than
2 years in duration.
Children with rotavirus infection were more
likelv to have dehvdration and vomitin, compared
to those with non-rotavirus diarrhea. We observed
the major clinical si,n of rotavirus diarrhea in
Palemban, to be dehvdration (91' of rotavirus cases),
thus, children with rotavirus diarhea often required
hospitalization.
Due to the prominence of frequent vomitin,, oral
rehvdration solution was not effective for replenishin,
lost bodv fluid, therefore, intravenous fluid therapv
was usuallv ,iven. 1he use of intravenous therapv
implies that rotavirus diarrhea causes not onlv
significant clinical impact, but also economic impact,
since intravenous rehvdration is more expensive than
oral rehydration. A study in Yogyakarta and Central
Java showed that rotavirus diarrhea was more likelv
to increase cost bv 25'.
14
1here have been few studies investi,atin, the
strains of rotavirus in lndonesia. 1he first studv
conducted in Yo,vakarta in the 197Os showed the
prevailin, strains to be O1, O2, O3, and O1, with O3
(53') the most common. O1 was onlv found in 2'
of rotavirus cases at the time.
15
A study conducted
in Central Java and Yo,vakarta in 2OO1 reported that
O1 was the most common strain, accountin, for 6O'
of identified cases. O3 was not identified.
16
We found O9 to be the predominant strain in
Palemban,, constitutin, 62.5' of the rotavirus identified.
Serotvpe O9 was documented as an emer,in, strain
worldwide and was also recently identified in Indonesia
bv Putnam et al.
17
lindin,s in five other hospitals
also showed diversitv in rotavirus strains. O1 and O9
were also the predominant strains in other hospitals,
but O3 and O1 were onlv observed in Yo,vakarta.
lnterestin,lv, P|6] which was uncommon ,loballv, was
found to be predominant in our study. Similarly, a study
in Ban,ladesh reported that P|6] was the major strain
found in neonates.
18
Òverall, our findin, supports the
idea that strains of rotavirus differ bv location and time.
Continuous monitorin, of rotavirus strains is, therefore,
highly important to determine the circulating strains and
provide steps for vaccine implementation.
We found the burden of rotavirus in Palemban,
to be hi,h. Rotavirus is, indeed, a common patho,en
and an important cause of hospitalization in children
with diarrhea|1, 9].
1,4
As such, a bold attempt must
be made to reduce the disease burden.
Rotavirus vaccine is currentlv recommended
bv WHÒ as the best method to prevent rotavirus
infection.
19
1he decision to implement a rotavirus
vaccine pro,ram in lndonesia has been hindered bv
the lack of awareness of the true disease burden of
Table 1. Clinical manifestations in children with rotavirus diarrhea hospitalized at Mohammad Hoesin
Hospital, Palembang
Clinical symptoms
Rotavirus (+) cases
n = 326
Rotavirus (-) cases
n = 187
RR
(95% CI)
P
value
Dehydration, n (%)
- Severe, n (%)
- Moderate, n (%)
- None, n (%)
Vomiting, n (%)
Mucous stool, n (%)
Bloody stool, n (%)
Fever (%)
307 (94.2)
55 (16.9)
252 (77.3)
19 (5.8)
287 (88.0)
146 (44.8)
10 (3.1)
147 (45.1)
166 (88.8)
31 (16.6)
135 (72.2)
21 (11.2)
130 (69.5)
97 (51.9)
16 (8.6)
73 (39.0)
1.06 (1.0 to 1.12)
1.25 (0.96 to 1.62)
1.07 (1.00 to 1.15)
Reference
1.27 (1.14 to 1.40)
0.86 (0.72 to 1.04)
0.36 (0.17 to 0.77)
1.16 (0.93 to 1.43)
0.03*
0.08
0.03
<0.001
0.12
0.006
0.18
* compared to no dehydration as the reference
Titis Widowati et al: Surveillance of rotavirus diarrhea
Paediatr Indones, Vol. 52, No. 1, January 2012 º 27
rotavirus and the importance of rotavirus vaccines.
2O
An assessment of rotavirus vaccine rationale and
potential barriers should be undertaken prior to vaccine
program implementation.
21
Òur results provide support
for one of the key steps for policy-makers in assessing the
importance of rotavirus vaccine implementation.
Acknowledgments
We thank l.P. Sukanto (P1 Bio larma) for laboratorv work, Abdul
Wahab and Althaf Setyawan (Community Health and Nutrition
Research laboratorv, Oadjah Mada Universitv Medical School)
for data analvsis, as well as the doctors, nurses and administrative
staff at the Pelemban, sites, for help with this studv. We are ,rateful
to all research assistants in the Child Health Department, Oadjah
Mada Universitv Medical School: A.W. lrlin Mulvadi, lra A,ustin,
Muhammad Bavu Sason,ko, Dara Rosmaillina Pabittei, Retno Palupi
and Mava lndriati for their valuable contributions to this work.
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