Indian Pediatrics 2014;51:870-2 http://www.indianpediatrics.net/nov2014/870.pdf
Utility of Hepatitis B Vaccination in India
Global health interventions are being scrutinized more closely than previously. According to an article in Science, the Center for Global Development in Washington has begun looking for hard evidence in real-life field conditions, whether a large-scale interventions have directly led to lower numbers of cases or deaths and whether the improvements are sufficient to justify the costs.(1)
This issue of Indian Pediatrics has a limited evaluation of the effect of inclusion of hepatitis B vaccine in childhood immunization program in India.(2) The authors did 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.
The Study Findings
1. Importantly the authors found that vaccination did not reduce hepatitis B carrier rate, which is the primary aim of the immunization programme. The hepatitis B surface antigen positivity which is an indicator of chronic HBV infection (HBsAg), 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% (NNT=135). 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) Other studies quoted in the paper (references 10 – 14 in their paper) found 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. 33% of unvaccinated had developed antiHBsAg by 6 years of age. This suggests that transmission of the virus is 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 supports 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 looks a little farfetched because asymptomatic infection among the unvaccinated can easily explain the antiHBs levels.
Other factors that need to be considered
Two other factors must also be mentioned here when considering impact of Hepatitis B immunization in real-life-conditions in the field:
a) The Hepatitis B 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 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 – DLHS 4: 2012-13 (file:///C:/DOCUME~1/Admin/LOCALS~1/Temp/Tamilnadu%2520State%2520Factsheet.pdf) has noted a decline in immunization coverage across districts which were considered to be well-performing in the past (DLHS–3:2007-08). 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.(10) 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 programme of the country.
St Stephens Hospital
1. Cohen J. A hard look at global health measures. Science. 2014 Sep 12;345(6202):1260-5. Available at http://www.sciencemag.org/content/345/6202/1260.full. Accessed on 23/9/14
2. Aggarwal R, Babu JJ, Hamalatha R, Reddy AV, Sharma D, Kumar T. Effect of inclusion of Hepatitis B vaccine in childhood immunization programme in India. A retrospective cohort study.
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, de Perio MA, Reilly M, Byrd K, Ward JW; 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(RR-10):1-19. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6210a1.html. Accessed on 23/9/14.
5. Minutes of the Expert group meetings on Hepatitis B and Hib vaccines March 2010. Available at http://www.icmr.nic.in/minutes/Minutes%20Expert%20Group%20%20Hepatitis%20B%20and%20Hib%20vaccines.pdf. Accessed on 25/9/14
6. Liver Research Foundation. Hepatitis B: Out of the shadows. http://www.liver-research.org.uk/liver-research-files/Hepatitis-B---Out-of-the-Shadows.pdf
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 of Systematic Reviews 2010, Issue 9. Art. No.: CD008658. DOI: 10.1002/14651858.CD008658.
8. Pandey K. Are some states under-reporting pentavalent vaccine deaths? Down to Earth 17/2/2014. Available at http://www.downtoearth.org.in/content/are-some-states-under-reporting-pentavalent-vaccine-deaths Accessed on 29/9/14.
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; Page 203 to 212. Available at http://jacob.puliyel.com/paper.php?id=336 Accessed 25/9/14
10. Dasgupta R, Dasgupta P, Agrawal A. Decline in Immunization Coverage Across Well-performing Districts in India: An Urban Conundrum? Indian J Pediatr.