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167

TRANSACTIONSOF THE ROYAL SOCIETYOF TROPICAL MEDICINE AND HYGIENE (1995) 89,167-170

Prevalence

of hepatitis

B and C viruses in healthy

Indonesian

blood donors

Medical
Faculty, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; Directorate General, Communicable
Disease Control and Environmental Health Ministry of Health, Jakarta, Indonesia; 3US Naval Medical Research Unit No. 2,
Jakarta, Indonesia; 41ndonesian Blood Bank Service, Jakarta, Indonesia

H. A. Sulaiman, Julitasari2, Annie Sie3, Masri Rustam4, W. Melani4, A. Co&n3 and G. B. Jennings3

Abstract
Blood samples were collected from 7572 healthy volunteer blood donors from 21 of the 27 Indonesian provinces, and tested for antibodies to hepatitis C virus (anti-HCV) using the new second-generationenzyme immunosorbent assay,and also tested for hepatitis B surface antigen (HBsAg). We detected anti-HCV in 2.1% of
the blood donors. No statistically significant difference was found between males and females or between locations, but there was a statistically significant increasing likelihood of anti-HCV prevalence with increasing
age. HBsAg was found in 8.8% of the 3839 tested donors. There was no statistically significant difference
between sexesor age groups, but there was a statistically significant higher prevalence in the islands of Sulawesi and eastern Indonesia. Only 7 individuals, from 5 locations, were both anti-HCV and HBsAg positive. Based on responsesto a questionnaire, a history of surgery, blood transfusion, intravenous medication,
and acupuncture were identified as risk factors for the presenceof anti-HCV. No such risk factor was identified for HBsAg prevalence. The combined data suggest separatemodes of transmission for the 2 viruses,
and indicate the need for continued surveillance for these agentsin Indonesian blood banks.
Keywords: hepatitis B, hepatitis C, prevalence in blood donors, Indonesia

Introduction
Hepatitis B virus (HBV) causesacute and chronic hepatitis and hepatocellular carcinoma (ROBINSON, 1985).
Hepatitis C virus (HCV) has been associatedwith acute
hepatitis and hepatic cirrhosis (CHEN et al., 1990), and
may be a cause of hepatocellular carcinoma (DAZZA et
al., 1993). These agents therefore pose a serious threat to
the safe collection of blood for blood bank systems.
Numerous studies have documented the prevalence of
these viruses in developed countries (KUHNL et al.,
1989; STEVENS et al., 1990), but less is known about developing countries where cost is a major factor in determining which assaysare available for blood bank screening programmes. The obvious value of such testing is a
decreasedprevalence of associateddiseasein blood recipients (ALTER et al., 1986).
A previous assessmentof HBV prevalence in Indonesia, conducted in 1981, was limited to Jakarta, the national capital, and found 10% of the blood donors positive for hepatitis B surface antigen (HBsAg) (MBOI et al.,
1981). A more recent report, limited to the provincial
capital of South Sulawesi, identified 7.1% of the blood
donors as HBsAg seropositive (AMIRUDIN et al., 1991).
The samereport detected HCV antibodies (anti-HCV) in
3.1% of the blood donors, a much higher proportion
than that in other countries (DAWSON et al., 1991;
JANOT et al., 1989). The importance of these agents in
Indonesia was shown recently by SULAIMAN et al. (1991).
Among acute hepatitis cases, 6.4% were associatedwith
HBV and 2.8% had anti-HCV. However, HBsAg was detected in 36.5% of liver cirrhosis cases and anti-HCV

in

73.9%, while 58.6% of hepatocellular carcinoma cases


were positive for HBsAg and 34.2% for anti-HCV.
Both of these Indonesian HCV studies were performed
using the anti-HCV first-generation enzyme immunoassay (EIA) which tested for a single HCV antigen. A
newer, second generation HCV EIA has been developed,

and incorporates antigens from 3 separateHCV proteins


~LAI et al., 1992). This new assavhas imoroved sensitivity and specificity (ALTER, 1992j and its&useshould provide more accurate data on HCV prevalence.
Indonesia is the fourth most populous country in the
world, comprising over 13 000 islands stretching nearly
5000 km along the equator. The major islands are
Java/Bali, Sumatra, Kalimantan, Sulawesi, and Eastern
Indonesia, including Irian Jaya. The blood bank service
is responsible for the safe collection of blood throughout
the archipelago. This study was conducted to determine
the risk to the blood bank system of blood-borne paAddress for correspondence: Dr A. L. Corwin, US
Box 3, Unit 8132, APO Al96520-8132, USA.

NAMRU-2,

thogens from donors, and to identify any risk factor(s)


associated with seropositivity. The assessmentrevealed
HCV and HBsAg to be potential threats, especially in
certain areasof the archipelago.
Materials and Methods
Subjects

Seven thousand, five hundred and seventy-two blood


donors (6732 male, 755 female, and 85 unknown) were
sequentially surveyed at 24 blood bank services in 21 of
the 27 Indonesian provinces, from November 1992 to
February 1993. Blood donations in Indonesia are entirely
voluntary, with no commercial gain. The number of
samples collected at each site was proportional to the
population of the province. Ages of the study population
ranged from 11 to 76 years (meankstandard deviation
32.91+10.02 years). The mean ageof males (33.04k9.97
years) was significantly higher than that of females
(31.79+ 10.48 years) (P<O.OOl). No donor reported any
ailment at the time of blood collection.
Data and specimens were collected blind, without
knowledge of the subjects identity. A standardized questionnaire, completed for all subjects by a trained blood
bank service interviewer, provided an epidemiological
orofile and medical historv with emnhasis on the
presence or absence of suspected risk fa&ors associated
with HCV transmission.

Data and specimen collection

procedures were approved by the Naval Medical Research Unit No. 2 Committee for the Protection of
Human Subjects.
Laboratory assays

Serum samples were sent on ice to Jakarta and stored


at -20C until assayed. All sam les were assayed for
anti-HCV according to the manuPacturers instructions,
using the Abbott HCV EIA second generation (Abbott
Laboratories, North Chicago, Illinois, USA). In addition
to the antigen of the first generation assay, this EIA de-

tects antibodies to the NS3 and core proteins of HCV.


Sampleswere considered positive if they were repeatedly
reactive in at least 2 EIAs. Due to the limited number of
available assays,only someof the sampleswere tested for
HBsAg (Table l), using the Auzyme@ monoclonal EIA
(Abbott) according to the manufacturers instructions.
Statistical tests

The proportional hypothesis test was used to determine the statistical significance of differences between 2
proportions from onegroup (overlapping categoriesfrom
a single sample). In addition, 95% confidence intervals
(CI) were calculated for proportions from a single sample

168
Table 1. Age distribution
of hepatitis C virus and
HBsAg positive blood donors screened throughout
Indonesia, November 1992-February
1993

Age group
(years)a

Anti-hepatitis C
positive
HBsAg positive

1l-20
21-30
31-40
41-50
5 l-70

61597 (1.0%) 231316 (7.3%)


3312944 (1.1%) 14111467(9.6%)
22/2087 (1.1%) 8811092(8.1%)
55/1351 (4.1%) 511626 (8.0%)
451436 (10.3%) 191241 (7.9%)
x2=3*37
x>;o904~4
P=O.5030

aRespondents not revealing their age or sex were not


included in calculations.
by the exact and normal methods. x2 tests with Yatess
correction were performed when comparing multiple
proportions from mutually exclusive sample groups. Students t test and analysis of variance were used to determine the significance of differences between mean
values.
Table 2. Prevalence of hepatitis C virus aad HBsAg among blood
donors in Indonesia, by location, November KM-February 1993

Location
Java/Bali
Sumatra
Kalimantan
Sulawesi
Eastern
Indonesia

Anti-hepatitis C virus
No. positive/
No. of
no. tested
cities
9
5

:
3

No. of
cities

11214487 (25%)
2011186 (1.7%)

3
2

121800 (1.5%)
131700 (1.8%)
41399 (1.0%)
x2=8.2, P=O.O8

3
3

HBsAg
No. positive/
no. tested
9911793
271382
281597
871694

(55%)
(7.0%)
(4.7%)
(12.5%)

97/373 (26%)
3
x2=187.6, P<O,OOOl

the prevalence of anti-HCV in males (2.2%) and that in


females (1.7%) (the 95% CI for the difference between
the proportions was -0.05 to 1.5%). Similarly, HBsAg
antigen prevalence for males (8.8%) did not differ significantly from that of females (8.1%) (the 95% CI for the
difference between the proportions was -2.3 to 3.7%).
The mean ages of HCV antibody positive males (42
years) and females (46 years) did not differ significantly
(P>O.O5) (the 95% CI for the difference between the
means was -11.1 to 2.33). In contrast, the mean age of
HBsAg positive males (33 years) was significantly
(P<O.O5) higher than that of similar females (29 years)
(the 95% CI for the difference between the means was
0.315-8.13).
As shown in Table 1, the proportion of HCV reactive
positives >40 years of age (5.6%) was significantly higher
(P<O.OOl) than for younger blood donors (1.1%).
HBsAg prevalence ranged 7.3 to 9.6%, with no evidence
of trend with increasing age.
A geographical profile of HCV antibody and HBsAg
prevalence is presented in Table 2. Intra-island variability of HCV prevalence was significant in Java/Bali
and Sulawesi, ranging from 1.0 to 3.4% (P<O.Ol) and
I.0 to 3.0% (P<O.O5) respectively. However, interisland HCV prevalence values did not differ significantly.
This was also true when location-specific age differences
were controlled for in the analysis (<41 years, x2=4.152,
P=O.3858 vs. ~40 years, x2=6.865, P=O.1432). There
were significant differences between the proportions of
HBsAg reactors within Kalimantan (P<O.O5), Sulawesi
(PcO.05) and Eastern Indonesia (P<O.Ol). Inter-island
prevalence of HBsAg ranged from 4.7% in Kalimantan
to 26% in Eastern Indonesia, a significant difference
(P<0~0001).
There was no evidence of differences in HCV or

Table 3. Risk factors associated with the presence and absence of hepatitis C virus and HBsAg among blood donors
in Indonesia, November 1992-February
1993

Historya
Jaundice
Family member with
jaundice
Surgery
Blood transfusion
Circumcision
Tattoo
Acupuncture
Intravenous
medication

Anti-hepatitis C virus
Pre(e;i posltlveino. tested)
Absent

.I+&
Prei~;i pontlve/no. tested).
Absent

5/158 (9.5%)

62416949(9.0%)

261313(8.3%)

30513285(9.3%)

5/157 (3.2%)
36/161 (224%))::
141158(8.9%)
138068 (86.2%)
9061 (5.6%)
21/161 (13%)

315/7178 (4.4%)
940/7311 (12.8%)
23417284(3.2%)
6050/7200 (83.8%)
319/7321 (5.8%)
42317238(5.8%)

151328(4.5%)
30/333 (9*0%)**
1l/330 (3.3%)
2391329(72.6%)
16/334 (4.7%)
23/238 (7.0%)

159/3398 (4.7%)
501/3444 (14.5%)
loo/3417 (2.9%)
2704/3405 (79.4%)
15613456(4.5%)
23313426(6.8%)

211158(13.3%)

491/7138 (6.9%)

18/333 (5.4%)

246/3454 (7.1%)

Respondents answering not known were not included in calculations. Statistically significant results are indicated thus:
lzJ<o*o1, l *P<o*ool, **P<o*ooo1.
HBsAg prevalences when the archipelago was divided
Analysis of age and sex data was restricted to 7415
into East and West Indonesia. There were, however, sigcases; 157 cases (2.1% of total samples) were excluded
nificant differences when locations were grouped by size,
becauseof incomplete demographic data.
regardless of age of the subjects. Anti-HCV was detected
in 1.6% (4912984) of subjects living in locations with
Results
populations < 1 million and in 2.4% (11214588)of subThe overall prevalences of HCV antibody and HBsAg
jects living in locations with populations 21 million
antigen were 2.1% (95% CI 1.8-2.5%) (16117572)and
(x2=4.82, PcO.05). In contrast, prevalence of HBsAg
8.8% (95% CI 7+-9.7%) (338/3839), respectively (Table
was significantly higher (x2=44.86, P<O.OOOl) in cities
1). The mean age of donors positive for anti-HCV (42.0
or provinces with smaller populations (13.3%) than in
years) was significantly higher (P<O.OOl) than that of
those with 21 million (6.6%).
those without this antibody (32.7 years) (the 95% CI for
Risk factors associatedwith HCV and HBsAg positivthe difference between the means was -10.9 to 7.8
ity differed overall (Table 3). HCV reactors were more
years). However, there was no statistically significant diflikely to have reported a medical history of blood transfuference (P>O.O5) between the mean ages of those who
were HBsAg antibody positive (32.5 years) and those
sions, surgery, acupuncture and intravenous medication.
who were negative (32.9 years) (the 95% CI for the difHowever, surgery and circumcision were significantly asference between the meanswas -0.7 to 1.6 years).
sociated with absenceof HBsAg. There was no apparent
association (P>O+OS)between the presence or absenceof
No significant difference (P>O.O5) was found between

169
HBsAg and the risk of HCV infection.
Discussion

These findings show the risk to the Indonesian blood


bank system of blood-borne pathogens from their volunteer donors. Our findings of a 2.1% anti-HCV prevalence
in Indonesian blood donors is much higher than that reported from western countries (using a first generation
EIA), 0.42%-0.9% (KUHNL et al., 1989; STEVENSet al.,
1990). A report from Japan documented a similar prevalence (0.56%) (TANAKA et al., 1992). However, developing south-east Asian countries have a higher prevalence. Thai blood donors had an anti-HCV prevalence
of 2.3% in a small number of samples tested (POOVORAWANet al.. 1991). while a studv of healthv subiects in
Singapore found 1.70/oto be positive for an&HCV (YAP
et al., 1991). Cultural differences or cross reactivity with
region-specific anti ens might explain this observed variation between devei:oped and developing countries; however, such common agents as dengue and Japaneseencephalitis virus have not been shown to cross-react with
HCV (DAWSONet al., 1991). The finding of higher HCV
prevalence in areas with ~1 million population suggests
that the new urban lifestyle of a developing nation may
expose city dwellers to risk factors associatedwith HCV
infection. Further studies are needed to explain the
underlying reason for the higher prevalence.
ALLAIN et al. (1992) have reported the need for confirmatory testing of samples found to be positive for antiHCV by EIA. Unfortunately, we did not perform confirmatory recombinant immunoblot testing, a technique
commonly used for this purpose. DAWSONet al. (1991)
and ALBERTI et al. (1991) reported that this additional
testing confirmed 26O/0to 47% of samples positive by
EIA samnles as true HCV infections. However. both of
those stuhies used a first generation anti-HCV EIA. Our
study used the second generation assayand thus should
have found fewer false oositives (AACH et al.. 1991). Regardless of this, our finding of 2.1% anti-H& irevalence is significant, and warrants continued screening
by the Indonesian blood bank system.
Only 7 of 3839 (0.18%) individuals screened for both
HBV and HCV markers were positive for both; thus it
seems unlikely that the 2 viruses are transmitted to Indonesian blood donors in an identical manner. HBV is
transmitted sexually and vertically (ROBINSON, 1985),
and both agents can be transmitted by blood, but uncertainties remain regarding the transmission of HCV
(EVERHARTet al., 1990; REESINK et al., 1990; KAO et
at., 1992). In our study, anti-HCV and HBsAg prevalence was essentially equal in the 2 sexes,but there was
a difference in prevalence between age groups (Table 1).
Anti-HCV was more prevalent in the older age groups, a
finding similar to that in other studies (SCOTT et al.,
1992; TANAKA et al., 1992). This is compatible with exposure later in life, perhaps via one of the risk factors
identified in Table 3. Alternatively,
repeated exposure
during the course of life may be necessary to elicit an

antibody response detectable by the EIA. HBsAg prevalence, on the other hand, was constant throughout the
5 age groups. This may indicate that the prevalence of

HBsAg is due to exposure early in life, i.e. through vertical transmission. These conclusions are consistent with
there being different means of transmission of the 2
viruses.
The prevalence of HBsAg in the blood donors, though
lower than previously reported for Jakarta (MBOI et al.,

1981), was alarmingly high in many areasof the Indone-

sian archipelago.

A significantly

higher prevalence of

HBsAg was detected among blood donors from Sulawesi


and Eastern Indonesia than in the rest of the Indonesian
archipelago. Whether some cultural difference exists be-

tween these areas and the remainder of Indonesia which


might cause the higher prevalence is unknown; however,
the data suggest that factors associated with a less intensively urban lifestyle (populations <l million) may have

some effect. A study of the general population is needed


to determine the importance of vertical and sexual HBV
transmission. This geographical difference in prevalence
was not found with anti-HCV, which again is in agreement with the idea of there being different routes of
transmission of the 2 viruses.
Our results underline the importance of screening programmes in identifying blood-borne pathogens which
posea threat to potential recipients. Both HBV and HCV
were identified as significant threats and continued surveillance is required by the Indonesian blood bank system, and perhaps also in other south-east Asian countries.
Acknowledgements
This study was supported by the Naval Medical Research and
Develoument Command. Navv Deoartment for Work Unit
62787A-OOlOl.ENX2414 (NAM&J-~) and 62787A-OOl.OlEAX
1288 (NMRI), and USCINPAC N0003893MPLAOSl. The opinions and assertions contained herein are those of the authors
and do not urport to reflect those of the US Navy, US Department of DePense, or the Indonesian Ministry of Health.
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Received 6June 1994; revised 16 August 1994; accepted for


publication 25 August 1994

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