Seroprevalence of hepatitis A in Indian children from 2-10

years old, according socio-economic status

Introduction and rationale
Over the last 20 years the epidemiology of Hepatitis A virus (HAV) has shown shifting
patterns in the prevalence of antibodies to HAV in most Asian and South American countries 1-3.
In the late 70s and 80s most areas were classified as areas of either high or intermediate
endemicity. Infection was more common in childhood, often mildly symptomatic or asymptomatic
and did not represent a public health problem. Most of the adults had developed life-long
immunity but acute HAV infection was progressively more severe with increasing age 3.
Transmission of HAV is feco-oral and as a result of socio-economic development, better
living condition and improved sanitation and hygiene, transmission of HAV has dramatically
declined 4. But on the other hand, an increasing number of adolescents and adults became
susceptible to HAV infection, resulting in sporadic symptomatic hepatitis A disease or outbreaks
all over 5, especially in communities such as high school children6, factory workers or people
working in health institutions. This changing epidemiology surely prompts to modify
recommendations for vaccination against HAV in these countries 1. However general
recommendations are difficult to propose, because of different epidemiological patterns from one
country to another 1,2, and also within countries, from urban to rural areas 4.
Thus in country like India, where overall age-specific antibody patterns has not changed
during the last few decades 1,8, their might be sub-groups of individuals from high socio-economic
level at particular risk of HAV infection in adolescence and beginning of adulthood. Identification
of susceptible adolescents and adults according to their residence and socio-economic status (SES)
could help us to determine the recommendations for vaccination in a given country.
Studies on age-specific seroprevalence of HAV antibodies according to residence and socioeconomic level are therefore being performed in India.
Seroepidemiology of HAV in India
With respect to other countries of Asia, India always remained a country of high
endemicity of HAV for a long time. Age-specific seroprevalence of anti-HAV antibodies did not
change in the 10-year period between 1982 to 1992 in Pune8. The majority (73-85%) of the
children seroconverted to HAV by the age of 3 years and virtually all of them by 10 years of age.
Similar results were obtained in Delhi where 77-80% of the children aged more than 5 years old
were seropositive 9. Recent analysis of 1612 subjects representing 5 cities from different parts of
India (Koltata, Cochin, Indore, Jaipur and Patna) 12 showed that anti-HAV positivity varied from
26.2 to 85.3 per cent. Almost 50% of children between the age group of 1-5 yr were found to be
susceptible to HAV.
Moreover, in the recent past, India underwent a contrasted economic development leading to
considerable differences in socio-economic level of sub-groups of the population. Based on recent
studies conducted in different parts of India (Pune, Mumbai, Dehli, Chennai) 8,10,7,11, it is apparent
that children from low socio-economic category continue to be almost universally exposed to
HAV. Based on age-stratified population surveys conducted in Pune in 1982, 1992 and 1998, a
distinct change in the degree of exposure to HAV was demonstrated in population belonging to
higher socio-economic status only 10. Based on a hospital based-survey a significantly lower
exposure (54.5%) of higher socio-economic group (defined as the level of monthly income)
compared with the lower socio-economic group (85%) was documented from Mumbai 7.
Therefore the shifting epidemiological pattern of HAV transmission might not be obvious
when one looks at the overall prevalence of anti-HAV antibodies, with majority of the population
still in the hyperendemic state. Thus, only few population-groups were concerned by this changing

epidemiological pattern in India and are particularly at risk to developed symptomatic hepatitis A
disease. Hence, Studies should be conducted to identify susceptible adolescents and adults.
Objectives
To compare the proportion of subjects at risk to be infected with HAV between subjects
with different levels of socio-economic status but living in the same geographic area. Specifically
study focuses on:
Comparing the age-specific pattern of prevalence of anti-HAV antibodies according to
Socio-Economic Strata (SES) of the subjects.
Calculating the proportion of subjects at risk to be infected with HAV in the studied areas,
in each age group, by residence and socio-economic level.
Methods
Study populations
The total study population was divided into two major metro cities of India viz. Delhi and
Mumbai. Three eminent Centers/Doctors from each metro (total of 6 centers) were selected in such
a manner as to cover the varied SES. The target age groups included were children between age
group of 2-5 yrs & 6-10 Yrs.
Design
Cross-sectional study
Sample size
Sample size was calculated in order to detect a 33% difference between prevalence rates from 60%
in the low SES group to 40% in the high SES group with a 95% confidence level and 80% power:
300 children (150 in each group). The study was performed with 300 children in each metro so that
the total number of subjects were 600. Sample size was calculated on the basis, that the numbers of
subjects to be enrolled in each metro were statistically sufficient and hence independent analysis
per metro could also be possible.
Procedures
A minimum number of subjects of each age group (150 in the 2-5 years old; 150 in the 6-10 years
old) were randomly selected from two study populations with low or high SES. They were
enrolled after taking informed consent from their parents or guardians.
A standardized questionnaire was provided to the accompanying parent of each subject. The
questionnaire enquired about demographic data, current and past residence, past history of
jaundice, markers of socio-economic level as defined by local investigators. Blood was drawn by
venous puncture. Serum was separated from blood and was stored at -20C. Sera was then tested
for qualitative detection of antibody to HAV using enzyme immunoassay (HAVAB; Abbott
Diagnostics, Illinois, USA).
Statistical analysis
Statistical methods
The study population was stratified according to study town, age and socio-economic group. A
descriptive statistical analysis was then performed. Characteristics of children coming from Delhi
were compared to those of children coming from Mumbai in terms of demographic data (e.g. sex
and age groups) socio-economic characteristics (e.g. class of income and ownership status),
parents education level and living conditions (sanitation level, number of people per household,
etc).

A bivariate analysis of data was then conducted. All collected variables were tested for an
association with HAV serological status. The difference in the proportion of children revealing
positivity of HAV antibody was tested using 2 test of significance (or Fischers exact test if
necessary) for categorical variables. The differences of means between the two groups of children
(those with anti-HAV antibodies and those without) were tested with an analysis of variance
(ANOVA) for numeric variables. The seroprevalence of IgG anti-HAV antibodies was estimated
for each study subgroup (town, age and socio-economic group).
The level of statistical significance was fixed at 0.05. Statistical analysis was performed
using SPSS 10.1 Software.
Analyzed population
Children whose hepatitis A serological status was known and whose age corresponded to the target
age groups (2-5 years and 6-10 years) were analyzed.
Collected and Analyzed variables
Household income status was collected in different ways. In order to harmonize this, investigators
were asked to classify them in three groups as follows:
Upper: > Rs. 20,000 (equivalent to more than 450 USD)
Middle: Rs. 10,000 to Rs. 20,000 (equivalent to 225-450 USD)
Lower: <Rs. 10,000 (equivalent to less than 225 USD).
Some variables were re-coded as follows:
Type of plumbing was re-coded in a binary variable: piped water (yes/no).
How many people are living in your house was divided into two groups with age less
than 5 years and between 5 to 14 years classes
Number of children in the house were taken as family members with age between 15 to
39 years
Similarly Number of adults in the house were taken as members with age of 40 years
and more
A crowdy score was then calculated by dividing total number of people who are living in the
house (parents and children) by the number of rooms in the house. [Number of children per
household + Number of adults per household / Number of rooms in household]. In order to
have a binary score i.e. low crowded house and high crowded house, we decided to take the
median as the threshold value between the two categories.
A people per salary score was also calculated by divided the total number of people in
the house by the number of people who are earning money. The score was also recoded in binary
variable by taking the median as the threshold value.
A composite socio-economic score was made from the eight most relevant and reliable variables
and was calculated by adding points related to these variables, thus making 0 to 10 values in total.
1. Crowded house: low crowded house: 1 point; high crowded house: no point.
2. Houses ownership: yes: 1 point; no: no point.
3. Type of house: flat: 2 points; bungalow: 1 point; and slum: no point.
4. Houses construction: concrete: 1 point and local materials: no point.
5. Number of people per salary: <=4: 1 point and >4: no point.
6. Classes of income: upper: 2 points; middle: 1 point and lower: no point.
7. Piped water: yes: 1 point and no: no point.
8. Sanitary facilities: inside: 1 point and outside: no point.