lobal health interventions are
being scrutinized more closely than previously. According to an article
published recently, the Center for Global Development in Washington is
looking for evidence in real-life field conditions to ascertain whether
large-scale health interventions have actually led to lower numbers of
cases or deaths, and whether these improvements are sufficient to
justify the costs [1]. This issue of Indian Pediatrics includes a
paper on limited evaluation of the effect of inclusion of hepatitis B
(HB) vaccine in childhood immunization program in India [2]. The authors
carried out a serological survey of children aged 5 to 11 years in rural
Andhra Pradesh; 2674 of those surveyed had received HB immunization and
2350 had not received such immunization. Babies who get infected with
the hepatitis B virus (HBV) either develop antibodies to HBV [Anti-hepatititis
B antibody to core antigen (AntiHBc) and Anti-hepatititis B antibody to
surface antigen (AntiHBs)] and clear the organism from their system or
else they become chronic carriers of hepatitis B antigen (HBsAg).
Vaccination is meant to reduce the numbers who become chronic carriers.
Three salient points emerge from their study:
1. Authors found that vaccination did not reduce
hepatitis B carrier rate, which is the primary aim of the
immunization program. The hepatitis B surface antigen positivity,
which is an indicator of chronic HBV infection, was 0.15% among the
vaccinated compared to 0.17% in those not vaccinated (P=0.855).
2. AntiHBc was present in 1.79% of the
unvaccinated but also in 1.05% of the vaccinated. The absolute risk
reduction (ARR) was 0.74%; 135 babies need to be vaccinated to
prevent 1 child from getting infected with hepatitis B using this
criterion. The authors note that this is a statistically significant
reduction (Risk ratio 0.59, 95%CI 0.36-0.94). However, the clinical
significance and utility of decreasing asymptomatic infection from
1.79% to 1.05% is questionable.
3. Vaccine-induced seroprotection (AntiHBs) is
another useful surrogate of vaccine efficacy [3]. At 6 years of age,
protective levels of anti-HBs antibody (10 mlU/mL) were present only
in about 59% of those immunized. By 11 years, only 13% had
protective levels. This is in stark contrast to reports from other
countries where 95% of those vaccinated have protective levels and
it drops to 92% at 40 years [4]. As also mentioned in this paper,
few other studies have reported protective levels of 90% to 76% on
follow up, 5 to 10 years later. The low antibody response in the
present study correlates with low ARR against hepatitis described
above.
Reasons for Low Vaccine Efficacy
The authors point out that the low antiHBc positivity
rate among the unvaccinated indicates HBV transmission was low in the
area, and it may be the reason they failed to find a reduction in
hepatitis B carrier rate among the vaccinated. One-third of unvaccinated
had developed antiHBsAg by 6 years of age which suggests that
transmission of HB virus was not low in the area. It is comparable to
world literature, that without vaccination, a third of the population
get infected and the vast majority clear the infection [5]. The findings
of the present study support the contention that Hepatitis B is
widespread but it is a benign disease in India, possibly because of
characteristics of the circulating virus strain and the genetic makeup
of the population [6].
Viewing the same data of 33% antiHBs positivity among
the unvaccinated, the authors speculate that these rural people may be
getting Hepatitis B immunization surreptitiously, without entering it in
their records. This seems a bit far-fetched and it seems more plausible
that asymptomatic infection among the unvaccinated resulted in antiHBs
positivity.
Other Issues
Two other factors must also be mentioned here when
considering impact of Hepatitis B immunization in real-life conditions
in the field:
a) The vaccine administered to babies in this
study was a stand-alone Hepatitis B vaccine. It is known that this
vaccine provokes a better antibody response than the combination
Pentavalent vaccine, that is being administered currently. The
efficacy with Pentavalent vaccine is likely to be even less than
that reported in this paper [7].
b) The other factor that will impact outcomes
in the field is the uptake of immunization. According to information
obtained under the Right to Information Act, states with good
surveillance systems like Goa and Kerala are reporting one death as
adverse events following immunization (AEFI) per 4000 to 12000
babies immunized with the hepatitis B containing Pentavalent vaccine
[8,9]. The District Level Household Survey in Tamil Nadu in 2012-13
has noted a decline in immunization coverage across districts which
were considered to be well-performing in 2007-08 [10]. The number of
fully immunized children has fallen in Tamil Nadu by as much as 25%.
Adverse impact of the polio eradication campaign and social
resistance in some states such as Tamil Nadu and Kerala due to
reports of AEFI deaths following Pentavalent vaccine are being
considered as possible explanations for this phenomenon [11]. Low
uptake of vaccine will further erode the benefits.
If the findings of this study are replicated in other
areas, it should prompt a re-evaluation of the need for this vaccine in
the immunization program of the country.
1. Cohen J. A hard look at global health measures.
Science. 2014;345:1260-5.
2. Aggarwal R, Babu JJ, Hamalatha R, Reddy AV, Sharma
D, Kumar T. Effect of inclusion of Hepatitis B vaccine in childhood
immunization program in India. A retrospective cohort study. Indian
Pediatr. 2014;51:875-9.
3. Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC.
What level of hepatitis B antibody is protective? J Infect Dis.
1999;179:489-92.
4. Schillie S, Murphy TV, Sawyer M, Ly K, Hughes E,
Jiles R, et al; Centers for Disease Control and Prevention (CDC).
CDC guidance for evaluating health-care personnel for hepatitis B virus
protection and for administering postexposure management. MMWR Recomm
Rep. 2013;62:1-19.
5. Indian Council of Medical Research. Minutes of the
Expert Group Meetings on Hepatitis B and Hib Vaccines. March 2010.
Available from:
http://www.icmr.nic.in/minutes/Minutes%20Expert%20Group%20%20Hepatitis%20B%20
and%20Hib%20vaccines.pdf. Accessed September 25, 2014.
6. Liver Research Foundation. Hepatitis B: Out of the
Shadows. Available from:
http://www.liver-research.org.uk/liver-research-files/Hepatitis-B—Out-of-the-Shadows.pdf.
Accessed September 29, 2014.
7. Kapoor AN, Tharyan P, Kant L, Balraj V, Shemilt I.
Combined DTP-HBV vaccine versus separately administered DTP and HBV
vaccines for primary prevention of diphtheria, tetanus, pertussis, and
hepatitis B (Protocol). Cochrane Database Syst Rev. 2010;9:CD008658.
8. Pandey K. Are Some States Under-reporting
Pentavalent Vaccine Deaths? Down to Earth 17/2/2014. Available from:
http://www.downtoearth.org.in/content/are-some-states-under-reporting-pentavalent-vaccine-deaths.
Accessed September 29, 2014.
9. Puliyel J. New models for public-private
partnerships in health promotion. In: IDFC 12th India
Infrastructure Report 2013-14: Road to Universal Health Coverage. New
Delhi: Orient BlackSwan; 2014; p. 203-12.
10. Ministry of Health and Family Welfare.
District Level Household and Facility Survey-4. State Fact Sheet: Tamil
Nadu. Available from:
http://www.iipsindia.org/pdf/pre%20bid%20conference%20combine%20PP.pdf.
Accessed October 6, 2014.
11 Dasgupta R, Dasgupta P, Agrawal A. Decline in
immunization coverage across well-performing districts in India: An
urban conundrum? Indian J Pediatr. 2014;81:847-9.
