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Year : 2004  |  Volume : 1  |  Issue : 1  |  Page : 60-71
Universal neonatal hepatitis B virus vaccination in India: Why?

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India

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How to cite this article:
Aggarwal R. Universal neonatal hepatitis B virus vaccination in India: Why?. Hep B Annual 2004;1:60-71

How to cite this URL:
Aggarwal R. Universal neonatal hepatitis B virus vaccination in India: Why?. Hep B Annual [serial online] 2004 [cited 2023 Sep 26];1:60-71. Available from: https://www.hepatitisbannual.org/text.asp?2004/1/1/60/27919

Hepatitis B virus

Hepatitis B virus (HBV) was first discovered in 1966. It belongs to a family of closely related DNA viruses called the hepadnaviruses. The viral particles, also called as the Dane particles, are 42-nm sized spheres that contain a core, enclosing the DNA, which is surrounded by a capsid.[1] A peculiar feature of HBV is that a large excess of viral envelope protein, also known as hepatitis B surface antigen (HBsAg), is present in the circulation; this provides an easy tool for the diagnosis of HBV infection and forms the basis of the currently available HBV vaccines.

Routes of acquisition of HBV infection

HBV infection is acquired primarily by parenteral routes. These include: (a) transfusion of blood or blood products infected with HBV; (b) needle prick by infected syringe(s) or needle(s); (c) sexual contact with an HBV-infected person; and, (d) transmission from an infected mother to her newborn child at birth.[2] Of these, the first three modes are important in adults. In contrast, children can acquire HBV infection either from their mothers at the time of birth (vertical transmission) or by inapparent spread from family members and other children (horizontal spread).[2] All over the world, spread of HBV from child to child accounts for most HBV infections.[2],[3],[4],[5],[6],[7] Such transmission usually happens in household settings but may also occur in child day care centres and in schools. The most probable mechanisms of child-to-child spread involve contact of skin sores, small breaks in the skin, or mucous membranes with blood or skin sore secretions. HBV may also spread through contact of saliva through bites or other breaks in the skin. In addition, the virus may spread through shared towels or toothbrushes, since it can persist on such objects for long periods in high titres, even in the absence of visible blood.

The risk of transmission of HBV infection from a pregnant women to her newborn infant is quite variable, and correlates well with the rate of viral replication in the mother, as assessed by presence of a viral protein named as hepatitis B e antigen (HBeAg) in her serum. Thus, infants born to HBeAg-positive mothers carry a nearly 90% risk of perinatal acquisition of HBV infection, whereas those born to HBeAg-negative mothers carry a much lower risk of around 15%-20%.[8],[9]

Natural history of HBV infection

The consequences of HBV infection depend in a large measure on the age at the time of acquisition of infection.[2],[10] Infection acquired in adult life may be symptomatic in the form of typical acute viral hepatitis or may be clinically inapparent. The rate of development of severe liver disease or of death among persons with acute HBV infection is very low. Importantly, most adult individuals who acquire HBV infection recover completely from this infection and clear the virus from their bodies. However, in about 2%-5% of HBV-infected adults, the virus persists in the body for more than 6 months; this condition is known as chronic HBV infection.[2]

In contrast, HBV infection acquired at birth and during infancy is associated with a milder illness, if any. However, in this age group, the infection is rarely cleared and more than 90% of infected infants develop chronic infection;[10] this phenomenon is related to immaturity of the immune system in neonates and infants. The risk of HBV infection becoming chronic declines with increasing age and reaches the adult level by the age of around 6 years.

In persons who fail to clear HBV infection, the virus persists for several years and often life-long. These individuals with chronic HBV infection are at an increased risk of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.[1],[2] These long-term sequelae are responsible for most of the mortality and morbidity due to HBV infection; in comparison, acute effects of HBV infection are relatively minor and are only rarely associated with death.

Magnitude of problem

More than a third of the world's population has been infected with HBV at some time. It is estimated that worldwide there are 350 million persistent carriers of HBV; these constitute roughly 5% of the world's population. It is estimated that nearly 25% of chronic HBV carriers would develop chronic liver disease and cirrhosis, which could progress to hepatocellular carcinoma. It is thus estimated that annual mortality from HBV infection and its sequelae worldwide is roughly 1 million.[1],[11],[12]

Based on the rate of HBV carriage rate, regions of the world are classified as high (HBsAg positivity rate in general population >8%), intermediate (2%-8%) and low (<2%) endemicity regions.[2]

Prevention of HBV infection

Prevention of HBV infection assumes importance in view of the high frequency of this infection and its long-term health consequences. This can be achieved either through reducing the opportunities of contact between infective and susceptible persons, or through specific protection of susceptible individuals through vaccination. The former is achieved through screening of transfused blood and blood products for HBV infection, and use of safe practices for handling of needles and other sharp objects. However, these avoidance measures have limited efficacy since it is not easy to identify the infective individuals. It is thus clear that vaccination is the mainstay of prevention of HBV infection.

Hepatitis B vaccines have been available for nearly three decades, and are highly safe and effective in preventing HBV infection and the development of its serious consequences.[13] Two types of hepatitis B vaccines are available, plasma-derived and recombinant. The plasma-derived vaccines are prepared from purified HBsAg from the plasma of persons with chronic HBV infection. Recombinant hepatitis B vaccines are made using HBsAg synthesized by genetic engineering techniques. There are no significant differences in safety, immunogenicity, or efficacy between the two types of hepatitis B vaccines; the choice of type of vaccine used is thus based on considerations of cost and availability. Significantly, hepatitis B vaccines do not interfere with immune response to other childhood vaccines, whether live or inactivated.

Hepatitis B vaccines are administered intramuscularly, typically in a three-dose schedule. These induce protective antibody titers in nearly 95% of healthy vaccine recipients and provide lasting immunity. Even though antibody titers may become undetectable a few years after vaccination, the immunological memory provided by the vaccine ensures that the individual is still protected from chronic HBV infection.[14] It is currently believed that the vaccine provides a life-long protection.

Strategies for HBV vaccination

Most of the serious health consequences of HBV infection, namely liver cirrhosis and hepatocellular carcinoma, occur among persons who are chronically infected. Further, the chronically infected persons form the principal reservoir of HBV and act as the main source of infection in a community. Therefore, the principal objective of hepatitis B immunization strategies is, to prevent chronic HBV infections. Since chronic persistence of HBV infection is much more frequent when the infection is acquired in early life, the most effective preventive strategy is one of preventing infection in neonatal period and early childhood. This fact forms the cornerstone of prevention of HBV infection.

Routine vaccination of all infants (universal vaccination strategy) as an integral part of national immunization schedules is the most effective strategy for prevention of hepatitis B.[2],[15] This strategy induces protection against HBV at an early age, thus preventing a majority of chronic infections, which are acquired during early childhood.

An alternative approach (selective vaccination strategy) involves identification of HBV carrier pregnant women and administration of vaccine selectively to their infants. This strategy reduces the amount of vaccine needed and may therefore appear cheaper. However, this approach is much less effective because a large proportion of children who acquire chronic HBV infection have mothers who are not infected with HBV; infections in them would not be prevented by the selective vaccination strategy.

Further, since the effect of HBV vaccination is life-long, the universal immunization strategy also prevents infections acquired during adolescence and adult hood. These late infections cannot be prevented adequately by other strategies since (a) a large proportion of these occur among persons with no identifiable risk factors, and (b) it is difficult to reach groups who are at a high risk of acquiring HBV infection. Selective immunization of children born only to HBV-infected mothers would not be expected to prevent these infections.

In view of these arguments, in 1992, the World Health Assembly recommended universal neonatal hepatitis B immunization for all countries in the world, irrespective of the HBV endemicity rate.[16] By the end of 2000, 129 countries had included HB vaccine into their national immunization systems;[17] currently, 151 countries have done so.[15]

Effect of hepatitis B vaccination

Impact of introduction of hepatitis B vaccination in a community can be measured in several ways. Firstly, hepatitis B vaccination may be expected to lead to a reduction in the number of patients with acute HBV infection, similar to reduction in burden of acute disease observed with vaccines against other infections. However, since HBV infection is only rarely associated with symptomatic disease among children, the main target group for vaccination, surveillance for acute hepatitis B is unlikely to show any impact. However, reduction in acute hepatitis B may become manifest as the vaccinated cohort grows older. Similarly, reduction in long-term consequences of HBV infection like cirrhosis and hepatocellular carcinoma is also likely to be delayed by several decades. The effect of vaccination is thus measured much more effectively in terms of reduction in hepatitis B carrier rate in the vaccinated population, either in comparison to an unvaccinated cohort or to historical carrier rates in the population.[2]

Hepatitis B: magnitude of problem in India

Data on burden of HBV infection in India come primarily from studies on HBsAg seroprevalence.[18],[19],[20],[21],[22],[23] Of the studies among various groups, those among pregnant women and voluntary blood donors are most closely representative of the rates in the general population. Though these studies have used laboratory tests with different sensitivity and specificity rates, they provide a good estimate of HBV burden in the country. In these studies, HBsAg prevalence among general population groups has ranged from 0.1% to 11.7%, being between 2% to 8% in most studies, and among pregnant women 0.6% to 11.2%. The HBsAg prevalence among blood donors ranged from 1% to 4.7%. Based on these data, most workers in the field believe that the true hepatitis B carrier rate in the Indian population is between 3% to 5%.

Assuming an HBsAg carrier rate of 4%, the total number of HBV carriers in the country is estimated to be about 40 millions. This constitutes nearly 12%-15% of the entire HBV carrier pool in the world.

Among patients with acute viral hepatitis in India, HBV infection is the second most common cause (after hepatitis E) being responsible for nearly one-third of patients. It is also the causative factor in 30%-40% of patients with liver cirrhosis and a large proportion of patients with hepatocellular carcinoma.

HBV vaccination strategy for India

To decide on the most appropriate vaccination strategy for prevention of HBV infection, we need to take into account the most important mode of transmission of infection in the population.

As indicated previously, HBeAg positivity rate among HBsAg positive pregnant women is an important determinant of the risk of vertical transmission of HBV infection to newborn infants. This rate in various Indian studies has ranged between 8% and 47%, with most studies showing a rate of 18% or less.[18],[19],[20],[21],[22],[23] Consensus opinion suggests that the HBeAg prevalence in India among HBsAg carriers is in general more similar to that in Africa (10%) than that in East Asia (30%-50%). Therefore, the potential for perinatal HBV transmission in India is possibly lower than that in East Asia.

Using the data from a large study of 8575 pregnant women in northern India, we have shown that only about 14% of chronic HBV infections in India are accounted for by perinatal transmission from HBV infected mothers.[18]

In India, some workers initially recommended the use of selective hepatitis B immunization.[24],[25] Our calculations showed that horizontal infection during early years of life was the major contributor to HBV carrier pool in India rather than perinatal transmission. This has led to the realization that selective vaccination strategy was unlikely to make any dent in the problem of chronic HB in our country.[26] Our calculations showed that universal HB immunization was a much more cost-effective approach, primarily because effectiveness of selective immunization approach was quite limited. Thereafter, several professional bodies in India have recommended the universal HB vaccination strategy.[27],[28] In fact, recently the Government of India has taken the decision to implement universal neonatal hepatitis B immunization in the country in a phased manner beginning with 30 districts and some urban slum areas.[29] However, the program implementation has slipped and the targets appear not to have been achieved.

Likely consequences of hepatitis B virus vaccination in India

The best method to determine the effects of an HBV vaccination program at a community level is to actually introduce such a program in a section of the population and to follow the vaccinated cohort. The results in this group can be compared either to an unvaccinated cohort or to the available historical data. Such data are not available from India.

However, sufficient data are available from other countries where hepatitis B vaccination has been in vogue for several years. In these countries, routine immunization of infants against hepatitis B has led to a significant reduction in the prevalence of chronic HBV infection.[30],[31],[32],[33],[34] The demonstration of this effect in a wide variety of countries and epidemiological settings indicates that this effect is independent of geographical and social factors. In addition, such vaccination has been effective in reducing the incidence of liver cancer in children too.[35]

Based on data from other countries, it is possible using mathematical modeling techniques to calculate the likely effects of a universal neonatal immunization program on the health status and survival of the Indian population. We had recently undertaken such a study.[36] In our analysis, we assumed two cohorts of newborn, one unimmunized against hepatitis B and the other receiving hepatitis B vaccine. Both the groups were considered as exposed to the currently prevalent rates of hepatitis B exposure in our community. The baseline hepatitis B carrier rate in the Indian population was assumed as four percent. The vaccine coverage rate was assumed as equal to that for three doses of diphtheria-pertussis-tetanus vaccine, and the vaccine efficacy rate as 95%. Both the cohorts were followed up over the entire life span using a Markov transition model. The results of our modeling showed that, even with current vaccine coverage rates, a universal hepatitis B immunization program would lead to a reduction in HBsAg positivity rate from 4.0% to 1.15%, a major change. Further, we found that this intervention will lead to an increase in average life expectancy of the Indian population through 0.173 years (slightly more than 2 months) and 0.213 quality-adjusted life-years. These major gains can be achieved at a small cost i.e. US$ 16.27 for each year of life gained and US$ 13.22 for each quality-adjusted life-year gained. These values need to be compared to India's per capita gross national product of US$ 440 per year. In general, it is believed that any intervention that leads to a gain of one year of life at a cost less than the country's GNP is worth paying for from public funds. Using this criterion, hepatitis B vaccination is eminently suitable as a public health measure. However, we need to remember that it will be several years before the beneficial effects on health are apparent.


It is clear from the aforesaid that HBV infection is a significant public health problem in India. A safe and effective vaccine is available for preventing this infection. The best strategy for the use of this vaccine is universal immunization of all newborns, irrespective of whether their mother has evidence of HBV infection or not. Several countries in the world have already adopted this strategy, resulting in a marked reduction in HBV related disease. We in India should adopt this public health measure at the earliest possible. This should lead to a marked reduction in HBV carrier rate, incidence of HBV related chronic liver diseases and an increase in average life expectancy of our population.

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36.Aggarwal R, Ghoshal UC, Naik SR. Assessment of cost-effectiveness of universal hepatitis B immunization in a low-income country with intermediate endemicity using a Markov model. J Hepatol 2003;38:215-22.  Back to cited text no. 36  [PUBMED]  [FULLTEXT]

Correspondence Address:
Rakesh Aggarwal
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014
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Source of Support: None, Conflict of Interest: None

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