From the Departments of Pediatrics, *Microbiology and **Laboratory Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi 110 095, India.
Reprint requests: Prof. Sunil Gomber, F-4A, Vijay Nagar, Delhi 110 009. Fax: 91-11-229 0495.

Manuscript received: June 21, 1999;
Initial review completed: July 26, 1999;
Revision accepted: September 22, 1999

Hepatitis B infection continues to be the single most important cause of viral hepatitis in developing countries and is a formidable cause of chronic liver disease and primary carcinoma of liver(1,2). The World Health Organization has recommended immunization of all children with three doses of 10 mg each of hepatitis B vaccine intramuscularly(3,4). The conventional 3 dose schedule of 0,1 and 6 months suggested by various workers does not coincide with the schedule of other vaccines under Expanded Program of Immunization (EPI)(5,6). As a consequence, it results in more visits of children to the immunization clinics causing burden on patients which results in poor compliance and non adherence to immunization program. In order to improve compliance and to effectively control the disease, the present study was carried out to look for the immunogenicity and feasibility of administration of hepatitis B vaccine with DPT and OPV vaccines.

Eighty eight term infants who were being exclusively breast fed had been included into the study. These infants were randomly selected at 6 weeks of age while attending the immunization clinic of the hospital from July 1998 to Jan 1999. An informed consent was obtained from the parents or guardian of the children. These infants were administered 10 mg of international DNA recombinant hepatitis B vaccine intramuscularly into the antero-latreal part of thigh. The dosing schedule was 6,10 and 14 weeks and the vaccine was administered along with DPT and OPV at two different sites. The status of hepatitis B surface antigen (HBsAg) of each child was evaluated by ELISA method (Omega Diagnostic Ltd., U.K.) and children negative for HBsAg were only included into the study. Antibodies to hepatitis B surface antigen in human serum (Anti HBs) were estimated by ELISA test (Biokit S.A., Spain). The antibodies were estimated after administration of two doses (14 wks) and one month after three doses of the vaccine (18 wks). The estimations could be carried out on 35 infants who could complete all three doses in time.

Anti HBs titers ³10 mIu/ml were considered as seroprotective levels(7). The geometric mean titers were estimated by multiplying all the values and taking 1/nth power of net value. Calculations were done by taking log values and then antilog of these values estimated geometric mean titers (GMT).

Estimation of antiHBs titers at 14 weeks and 18 weeks revealed seroprotection in 94.4% (33/35) and 97.1% (34/35) cases, respectively. The difference was not statistically significant (p = 1.00). However, the GMTs attained after 3 doses were much higher as compared to titers attained after 2 doses (Table I). No adverse effects were documented.

Table I - Anti HBs Titers Following Two and Three Doses of Hepatitis B Vaccine.

 The conventional vaccination schedule of 2 doses at 1 month interval followed by a third dose 6 months after the first (0-1-6) does not coincide with the EPI immunization program of Government of India. The extra budren due to increased number of visits to health facilities, apprehension of achieving good immuno-genicity when administered simultaneously with other vaccines and its exhorbitant cost have been the main limiting factors of putting it into the existing National Program of Immunization. The present study documents that 94.4% had seroconverted to protective levels even after 2 doses of intramuscular administration 4 weeks apart. The third dose helped in increased seroconversion with attainment of increased titers significantly higher than those achieved after 2 doses. The results are in conformity with earlier studies on infants and children of simultaneous administration of hepatitis B vaccine with other EPI vaccines (8–10). The GMT of Anti HBs obtained in infants using 2,4 and 6 months(11) and 0,1 and 6 months(12) schedules were however higher (Table II). The significance of post vaccination titers in providing long term protection is unclear but some of the workers suggest that infants who achieved higher Anti HBs titers were likely to be protected better in later years than infants with low titers(13,14).

Table II -  Geometric Mean Titers in Infants Vaccinated Against Hepatitis 
B by Different Vaccination Schedules

To conclude, Hepatitis B vaccination at 6,10 and 14 weeks along with other EPI vaccines produces a high seroconversion rate but substantially lower antibody level than at 0, 1 and 6 months schedule. The implications of this as far as long term protection is concerned requires further study.

1. Kane M. Global Program for control of hepatitis B infection. Vaccine 1995; 13: S47-S49.

2. Nayak NC, Panda SK, Zuckerman AJ, Bhan MK, Guha DK. Dynamics and impact of perinatal transmission of Hepatitis B virus in North India. J Med Virol 1987; 21: 137-145.

3. World Health Organization. Immunization Policy WHO/EPI/GEN/95.3, 1995.

4. John TJ. Hepatitis B immunization. Indian Pediatr 1995; 32: 609-613.

5. Brunell PA. Hepatitis. In: Nelson Textbook of Pediatrics, 14th edn. Eds. Behrman RE, Kleigman RM, Nelson WE, Vaughan VC III. Philadelphia, W.B. Saunders Co., 1992; pp 818-822.

6. Greenberg DP, Vadheim CM, Marcy SM, Partridge S, Jing J, Chiu CY, et al. Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. Vaccine 1996; 14: 811-816.

7. Canvo RD, Grosheide PM, Voogd M, Huisman WM, Heijtink RA, Schalm SW. Immunogenicity of 20 mg of recombinant DNA hepatitis B vaccine in healthy neonates: A comparison of three different vaccination schemes. J Med Virol 1993; 41: 30-34.

8. Mittal SK, Rao S, Kumar S, Aggarwal V, Prakash C, Thiruparam S. Simultaneous administration of hepatitis B vaccine with other EPI vaccines. Indian J Pediatr 1994; 61: 183-188.

9. Villa GD, Picciotto L, Ribera G, Bencivenga M, Cotugno M, Hartmann P. Effective antibody response in newborn babies living in Maldives to simultaneous vaccination against hepatitis B, poliomyelitis, diphtheria and tetanus. Vaccine 1995; 13: 795-798.

10. Coursaget P, Yvonnet B, Relyveld EH, Barres JL, Dipo-Mar I, Chiron JP. Simultaneous administration of Diphtheria-Tetanus-Pertussis-Polio and Hepatitis B vaccines in a simplified immunization program. Infection and Immunity 1985; 51: 784-787.

11. Giammanco G, Moiraghi A, Zotti C, Pignato S, Volti Li S, Giammanco A, et al. Safety and immunogenicity of a combined diphteria-tetanus-acellular pertusis-hepatitis B vaccine administered according to two different primary vaccination schedules. Vaccine 1998; 16: 722-726.

12. Safary A. Hepatitis B vaccination - Now and in the future. In: Hepatitis-B in India: Problems and Prevention. Eds. Sarin SK, Singhal AK. New Delhi, CBS Publishers, 1996; pp 132-151.

13. Coberly JS, Townsend T, Repke J, Fields H, Margolis H, Halsey NA. Suboptimal response following intradermal hepatitis B vaccine in infants. Vaccine 1994; 12: 984-987.

14. Stevens CE, Toy PT, Taylor PE, Lee T, YipH. Prospects for control of hepatitis B virus infection: Implications of childhood vaccination and longterm protection. Pediatrics 1992; 90: 170-173