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Bangladesh Journal of Medical Science Vol. 14 No. 01 January’15

65

Original article

Hepatitis A virus vaccination strategy and pre-immunization screening of Bangladeshi children
Mahmud S1, Karim ASMB2, Alam J3, Islam MMZ1, Sarker NK1,  Munshi AS1, Sarker S1

Introduction
Hepatitis A virus (HAV) infection occurs throughout
the world but most common in developing coun-
tries.1 In these countries with high endemicity, 90%
of the population is infected by 10 years of age.2
Here children are continuously exposed to the virus,
which confers lifelong immunity.3 In many develop-
ing countries like India,   Pakistan, Nepal several
sero-prevalence studies have shown high rates of
sero-positivity among child by sub-clinical infec-
tion4-9. Therefore, mass vaccination against HAV
has not been recommended in endemic countries.10
Furthermore, Hepatitis-A vaccine is expensive. In

Bangladeshi children, limited data are available
regarding the sero-prevalence of HAV antibody.11
In this context, the present study was designed to see
the prevalence of HAV antibody (IgG & IgM)
among children of different age group and to per-
form a cost benefit analysis study before formulating
a vaccination strategy for the children of
Bangladesh.
Materials & Methods
A cross sectional observational study was conducted
from July 2008 to June 2009. Blood was collected at
blood collection centers of Bangabandhu Sheikh
Mujib Medical University (BSMMU) Hospital &
Dhaka Shishu (Children) Hospital (DSH). A total of

Corresponds to: Dr. Salahuddin Mahmud, Assistant Professor, Dhaka Shishu (Children) Hospital, Dhaka,
E-mail: drsmbablu@gmail.com

Abstract:
Background: HAV infection is endemic in many developing countries like India, Pakistan, 
Nepal etc. Several seroprevalence studies show high rates of sero-positivity among children by 
sub-clinical infection. Therefore mass vaccination against HAV has not been recommended in 
endemic countries. Objective: To determine whether routine hepatitis A vaccination is indicated 
for all Bangladeshi children & also to know whether pre-vaccination screening is necessary. 
Materials & Methods: Serum samples from 254 children aged between 1-15 years were tested 
for antibody (IgM & IgG) against hepatitis A virus (HAV) to determine the seroprevalence of 
HAV antibody and do a cost-benefit analysis for decision making about vaccination against 
HAV among the children of Bangladesh. Results: Hepatitis A virus antibody was positive in 141 
(55.5%) of 254 children. Age-specific sero-prevalence was 13 (23.2%) of 56 in 1-3 year,64 
(55.2%) of 116 in 3-5 year, 39 (70.9%) of 55 in 5-10 year & 25 (92.6%) of 27 in 10-15 year age 
group. Cost benefit analysis showed that the total cost of screening followed by vaccination was 
almost 1.8 times less than the total cost of vaccination of all children without screening. 
Conclusions: Majority of the children were found sero-positive against HAV around 15 year of 
age. Therefore mass vaccination against HAV may not be required for Bangladeshi children.
Key words: Hepatitis A virus (HAV); HAV seroprevalence; HAV vaccine

1. Salahuddin Mahmud,  Assistant Professor, Bangladesh Institute of Child Health, Dhaka Shishu Hospital
2. A.S.M. Bazlul Karim, Professor, Paediatric Gastroenterology & Nutrition, BSMMU
3. Jahangir Alam, Professor, Bangladesh Institute of Child Health, Dhaka Shishu Hospital
4. M.M. Ziaul Islam, Assistant Professor, Bangladesh Institute of Child Health, Dhaka Shishu Hospital.
5. N.K. Sarker, Assistant Professor, Bangladesh Institute of Child Health, Dhaka Shishu Hospital.
6. A.S. Munshi, Assistant Professor, Bangladesh Institute of Child Health, Dhaka Shishu Hospital.
7. Shaoli Sarker, Assistant Professor, Bangladesh Institute of Child Health, Dhaka Shishu Hospital.

DOI: http://dx.doi.org/10.3329/bjms.v14i1.21561 
Bangladesh Journal of Medical Science Vol. 14 No. 01 January'15. Page: 65-69



254 children aged 1-15 years (boys=139 &
girls=115), who had no previous history of jaundice
or hepatitis or Hepatitis A vaccination but attended
OPD of these two hospitals for other illnesses were
included in this study. The sample size was deter-
mined by the prevalence rates of neighburing coun-
tries with a similar socioeconomic condition (e.g.,
India & Pakistan) as there are no previous data on
HAV prevalence particularly in the  children of
Bangladesh. With prior written consent, clinical his-
tory and relevant data were recorded and 2 ml of
blood was collected from each of the study cases.
Serum was separated, stored at -20°C and were test-
ed for HAV antibody (IgG & IgM) by ELISA using
the ELISA kit (DiaSorin Italy, ETI-AB-HAVK
PLUS, no136, 01/2009) at the Department of
Virology laboratory of BSMMU, Dhaka. The cut-off
value was determined by the mean absorbance of the
calibrator values. The presence or absence of anti-
HAV was determined by comparing the absorbance
values of unknown samples with the absorbance val-
ues below/above the cut-off values of the controls.
For cost benefit analysis, pre-vaccination screening
price was 2$ for each child & vaccine price along
with vaccination charge was 15$ (Per dose).
A preformed semi structured data collecting form
was used as a data collection instrument. Data were
collected by researcher and analyzed by Statistical
Package for social Science (SPSS) version 11.5 pro-
gram. P value of <0.05 was considered as statistical-
ly significant.
Results
Hepatitis A virus antibody (total) was found positive
in 141 (55.5%) of 254 children (Fig:I)

Fig: I Anti-HAV positivity among all children

Total 172 children from 1-5 year age group, 55 chil-
dren from 5-10 year age group and 27 children from
10-15 year age group were taken. Boys were 139 &

girls 115 so male:female ratio was 1.2: 1. Age distri-
bution of the children positive for HAV antibody
shows that with the advancement of age, anti-HAV
positivity increases. Anti-HAV of 1-5 year age group
was found to be 44.7%, it gradually increased to
70.9% in 5-10 year age group and finally to 92.6%
in 10-15 year age group. Anti-HAV positivity of 5-
10 year age group was significantly higher than that
of 1-5 year age group (p=0.001) and antibody posi-
tivity of 10-15 year age group was significantly
higher than that of 5-10 year age group (p=0.026).
(Table 1.1).

Table 1.2 shows anti-HAV positivity in children
aged 1-5 year. Anti-HAV was found 18.9% in 1-2
year age group, 31.6% in 2-3 year age group, 53.1%
in 3-4 year age group & 56.7% in 4-5 year age
group.

Pre-immunization screening of Bangladeshi Children

66

HAV antibody 
  Age

 (yrs)  n Positive Negative χ2 p-value 

1 – 5  172 77 (44.7) 95 (55.3) 

5 – 10  55 39 (70.9) 16 (29.1) 
11.397 

4.970 

0.001 

     0.026 
10 – 15  27 25 (92.6) 2 (7.4) 

Table 1.1 Anti-HAV positivity with age 

#Data were analysed using Chi-square (X2) Test 
Figures in the parentheses denote corresponding 
percentage

Table 1.2 Seroprevalence of antibodies
in children aged 1-5 year

# Data were analysed using Chi-square (X2) Test;

Figures in the parentheses denote corresponding 
percentage

HAV antibody
  Age

 (yrs)
 

n Positive Negative χχ2 p-value 

1 – 2  37 7 (18.9) 30 (81.1) 

2 – 3  19 6 (31.6) 13 (68.4) 
1.129 0.467 

3 – 4  49 26 (53.1) 23 (46.9) 
2.536 0.111 

4 – 5  67 38 (56.7) 29 (43.3) 
0.153 0.696 



Table 1.3 shows, total number of subjects were 254.
Current cost of 2 doses of vaccine is 15$×2=30$.
Anti-HAV assay by ELISA costs 2$ per test. Total
cost of vaccination of all the 254 children without
screening is (30$×254) 7620$. On the other hand
total cost of screening all the children is (2$×254)
508$. After screening of all the 254 children, 113
were found anti-HAV negative, who needed vaccina-
tion. Cost of vaccination of these 113 children is
(30$×113) 3390$. Thus, total cost of vaccination
after prior screening is (508$+3390$) 3898$.
Therefore the cost of vaccination without screening
is almost 2 (1.95) times more than the cost of vacci-
nation after screening (Table 1.3). Therefore, it is
worthwhile to screen the individuals before recom-
mending hepatitis A vaccine.

Discussion
Acute viral hepatitis caused by HAV is an acute,
self-limiting infection.12 Hepatitis A virus infection
is very common in early childhood and most of the
infections are asymptomatic or mildly sympto-
matic.13 Immunity that develops following natural
infection is stronger and persists longer than that
develops following vaccination.14
Three epidemiological patterns of endemicity (low,
intermediate and high) are observed worldwide.
Each pattern has a different rate of infection, prevail-
ing age of infection, and transmission model. HAV
epidemiological pattern are highly dependent on age
and level of hygiene. The distribution of HAV sero-
prevalence by age group may reflect current hepati-
tis A endemicity in countries and regions. The coun-
tries with low endemicity include Japan, Singapore,
Hongkong and Taiwan whereas those with moderate
endemicity include Thailand, Malaysia and Sri
Lanka. Countries with high endemicity for HAV
infections include India, China, Nepal, Bangladesh,

Pakistan, Myanmar and Philippines.15 In many
developing countries of Africa, Asia and Latin
America, most infections occur by 5 years of age
where seroprevalence approach 90-100% by 10-15
years of age.1 In Africa, Hendricks et al.16 showed
anti-HAV positivity of >90% among the 5-10 year
age group among lower class black children. 
India, China, Nepal, Pakistan and Bangladesh are
included in high endemic zone15 and a large number of
populations acquire immunity through subclinical
infections in early life.17 During the last 5 years sever-
al reports from countries in southern Asia, Latin
America and Europe showed a decreasing seropreva-
lence of protective antibody against hepatitis A virus.18

In the present study the average prevalence of anti-
HAV was 55.5%. Only 44.7% individuals were pos-
itive at the age range of 1-5 years. Anti-HAV sero-
prevalence increased with age from 44.7% in 1-5
year age group to 92.6% in the 10-15 year age group.
It was also observed that in 1-5 year age group
(younger children), about one third of children were
anti-HAV positive by 2-3 year of age and more than
half by 3 years of age. Similar results were also
observed in other studies in Bangladesh. Ahmed et
al.19 found a high prevalence (74.8%) of anti-HAV
among Bangladeshi children and adult. He also
reported anti-HAV positivity of 38% in 1-5 year age
group, 75.2% in 5-10 year age group, 80.4% in 11-
15 year age group and 98.5% in 15-20 year age
group. Saha et al.11 also reported anti-HAV positiv-
ity of 40.4% in 1-5 year age group which gradually
increased to 98.4% in >30 year age group. Another
study by Sheikh et al.20 reported anti-HAV positivi-
ty of 100% in 15-20 year age group. These findings
are similar to the findings of our neighbouring coun-

Mahmud S, Karim ASMB, Alam J, Islam MMZ, Sarker NK,  Munshi AS, Sarker S

67

Vaccine 
strategy 

Total 254 
children 

Number of 
ELISA 

tests 

Cost of 
ELISA 

2$ per test 

Number of 
vaccinees 

Cost of 
vaccine 
15$ per 
dose × 2 

Total cost 

Without 
screening 

254 0 0 254 7620$ 7620$

With 
screening 

254       254 508$ *113 3390$ 3898$ 

Table 1.3: The cost benefit analysis of hepatitis A virus vaccination strategies

*113 were found negative for anti-HAV



Pre-immunization screening of Bangladeshi Children

68

tries. Mall et al.2 from India (Calcutta) reported 40%
anti-HAV positivity in 1-5 year age group and
through gradual increase in age the prevalence
reached to 97% in the >16 year age group. 
A recent study by Kamath et al.5 reported anti-HAV
positivity of 61.6% in 5-10 year age group and 97%
in 11-15 year age group in Chennai, India.
Agboatwalla et al.8 & Sawayama et al.21 also
reported similar results from Pakistan (94.1%
seropositive by the age of 5 years) and Nepal (91.1%
seropositive) respectively. Anti-HAV positivity was
found 94.1% in 1-5 year age group at Rawalpindi
and 99% in two rural villages in Nepal. In Africa,
Raharimanga et al.14 reported that the overall sero-
prevalence of anti-HAV was 92.2%. In 8-10 year age
group it was 83.7% and in 10-24 year age group it
was 95.5%.
In the present study, it was evident that the cost of
vaccination with screening is more than 2 times
cheaper (3898$) than the cost of vaccination without
screening (7620$). As such, these findings suggest to
screen the individuals before recommending hepati-
tis A vaccination. Ahmed et al. 19 also observed that
the cost of vaccination with screening was almost
three times cheaper (US$3418) than the cost of vac-
cination without screening (US$8928). It is to be
economically worthwhile, the cost of vaccinating a
group of people must be equal to or less than the cost
of testing the entire group plus the cost of vaccinat-
ing the non-immune group22. In India also reported
that, if anti-HAV positivity is >50% in a particular
age group, then it is advisable to screen the individ-
ual before HAV vaccination. On the other hand,
when the chance of positivity is <50% in a particu-
lar age group, then vaccination can be offered with-
out screening for antibodies. 13 It is evaluated that in
India, selective vaccination of high risk populations,
based on their serological evidence of HAV anti-

body, could be a rational and cost effective
approach. 23 In a developed country like Argentina
reported that universal vaccination against HAV was
cost effective. 24
Conclusions
In the studied children anti-HAV positivity was more
than 50% after 3 years of age and finally increased
to more than 90% after 10 years of age. So, high pro-
portion of children in the present study acquired
HAV antibody since early childhood and anti HAV
positivity increased with increase in age. On cost
benefit analysis, the cost of vaccination with screen-
ing was almost 2 times cheaper than the cost of vac-
cination without screening. Therefore mass vaccina-
tion or vaccination without prior knowledge regard-
ing the serostatus could be an unnecessary immuno-
logical assult & may not be a suitable strategy for
Bangladesh in lieu of the present socioeconomic
condition. Assult
Recommendations
Based on the present study, it may be recommended
that in children less than 3 years of age vaccination
without prior screening can be done. However in
children of ?3 years of age, pre-vaccination screen-
ing should be done prior to vaccination as this is cost
effective, safe and more rational.
Further community based studies with larger sample
size are required before giving a final recommenda-
tion for routine HAV vaccine to children of
Bangladesh.
Limitations of study
Small sample size, selection biasness and absence of
socio-economic status are the three limitations of
this study.
Acknowledgement
Prof. C. A. Kawser, PhD, Chairman of Pediatrics,
BSMMU.
Prof. Samir K. Saha, PhD, Head, Dept. of
Microbiology, BICH, DSH.



Mahmud S, Karim ASMB, Alam J, Islam MMZ, Sarker NK,  Munshi AS, Sarker S

69

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