A SEHGAL ET AL.
Use of Hepatitis B Vaccine Alone or in Combination with Hepatitis B Immunoglobulin for Immunoprophylaxis of Perinatal Hepatitis B Infection by A. Sehgal,* R. Sehgal,** I. Gupta,* O. N. Bhakoo,*** and N. K. Gangulyf Departments of'Obstetrics and Gynaecology, **Parasitology, ***Paediatrics, and ^Experimental Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160012
Introduction Infection with hepatitis B virus can lead to various complications like cirrhosis, glomerulonephritis, and hepatocellular carcinoma. 1 ' 2 Infection may be acquired during the perinatal period from mothers who are carriers of the virus.3-4 The risk of the baby getting infected varies with the serological status of the mother; 70-100 per cent infants becoming infected if the mother is both HBsAg and HBeAg positive, while the risk is low (12-20 per cent) if the mother is HBsAg and anti-HBe positive. s ~ 7 A vaccine to prevent HBV infection was licensed in 1981. To date, millions of doses have been administered. It has been observed from various regions of the world that perinatal infection can be prevented with the use of either HBV vaccine alone or in combination with hepatitis B immunoglobulin (HBIG). 3 Recently, the World Health Organization has recommended that HBV vaccine should be included in the expanded programme of immunization (EPI). 8 Hepatitis B prevalence in India is about 2-10 per cent and there is a wide prevalence of antibody to Acknowledgement The study was funded by the department of Science and Technology, Chandigarh (U.T.). Correspondence: Dr Indu Gupta, Department of Obstetrics and Gynaecology, Pgimer, Chandigarh-160012, India. Journal of Tropical Pediatrics
Vol.38
October 1992
hepatitis B virus. It is estimated that more than 100000 babies in India acquire the infection during their perinatal period from carrier mothers. 9 Hence, it is important that preventive measures are taken to prevent transmission to the neonates by use of vaccine. To date, to the best of our knowledge, no study is available from our country which has used the HBV vaccine as a prophylactic measure for prevention of perinatal HBV infection. It is also not clear whether vaccine alone in multiple doses or a combination of vaccine with immunoglobulin will be better for immunoprophylaxis. The addition of a single dose of HBIG increases the cost of the vaccination programme. The present study was designed to check the immunogenicity, safety and efficacy of the HBV vaccine alone or in combination with HBIG. Materials and Methods Subjects The study was conducted in a total of 4137 pregnant women admitted in the labour wards of Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh from January 1987 to December 1989. A detailed history was taken regarding the past and present pregnancy with special reference to any episode ofjaundice or liver disease. A thorough clinical examination was performed in each case. Collection of © Oxford University Press 1992
247
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
Summary The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates bora to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0,1,2 months) of the vaccine alone, while 27 infants were given hepatitis B imnninoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels S10 IU/I) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 P. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies bora to anti-HBe positive mothers.
A SEHGAL ET AL.
blood samples from all the pregnant mothers was done after obtaining an informed written consent, at the time of delivery. The sera were separated and stored in aliquots at - 7 0 ° C for further use.
Vaccination of neonates born of HBsAg positive mothers The neonates born to HBsAg positive mothers, irrespective of mothers' HBe antigen status, were vaccinated and allocated randomly to two groups. Group I. This group consisted of neonates who were given 10 /ig of plasma derived vaccine (Korea Green Cross Corporation, South Korea) within 24 hours of birth intramuscularly into the thigh muscle. Second and third dose of vaccine was given at 4 and 8 weeks. Group II. This group consisted of neonates who were given HBV vaccine along with hepatitis B specific immunoglobulin (HBTG). The dose and route of the vaccine was the same as in Group I along with 0.5 ml of HBIG in the contralateral thigh (Hepabig, Green Cross Corporation, South Korea). Vaccine and HBIG were given within 24 hours of birth. Subsequent doses of vaccine were given as in the case of Group I patients. Group III. Consisted of neonates who were not vaccinated. Initially, the vaccine was not available (until April 1988); hence, these babies were taken in the control group. The mothers were explained the purpose and scope of vaccination; however, some of the mothers did not give consent for the vaccination, but agreed to come for follow-up and, hence, served as controls. Follow-up of mothers and neonates All the three groups were called for follow-up at 3 and 6 months after the birth of the child. Blood samples were collected from all the mothers and infants during the follow-up. The sera were separated and stored at - 7 0 ° C until use. All the HBsAg positive samples (positive by RPHA), and subsequent samples of the mothers and neonates were checked for HBsAg, HBeAg, anti-HBe, and antiHBsAG antibodies with the use of ELISA tests. HBsAg was checked by ELISA using the kit obtained 248
Results Out of the 4137 pregnant women screened, 109 (2.63 per cent) were positive for HBsAg. Twenty-four and 27 neonates were enrolled in groups I and II, respectively, and 58 subjects (mothers) who did not agree to vaccination of their children, were considered as group III subjects. Table 1 shows the results obtained in the case of group I and II subjects. Three babies of group I were positive at birth for HBsAg and were excluded from the evaluation. The seroprotection rate (anti-HBs litres ^ 10 IU/1) at 3 and 6 months was 66 and 81 per cent, respectively. The overall protective efficacy of the vaccine in group I was 95 per cent. Only one baby (5 per cent) was positive for HBsAg by 6 months in group I. In group II subjects, three neonates were positive for HBsAg at birth. Two babies (8 per cent) became positive for HBsAg by 6 months of follow-up. The seroprotection rate at 3 and 6 months was 68 and 76 per cent, respectively, which is almost similar to that of group I infants. The protective efficacy of the vaccine at 6 months was 88 per cent in group II. Seroconversion rates with the two schedules of the vaccine were almost similar at 3 and 6 months (Table 1). The mean anti-HBs titres in both group I and II at 3 and 6 months was almost similar, though in group I (vaccine alone) the titres were somewhat higher (29.18 + 11.37) than group II (vaccine plus HBIG; 25 ± 14.2) at 6 months of follow-up (Table 1). Table 2 shows the results of the vaccination in group I and group II subjects according to the maternal serological status at time of vaccination. If the mother was HBeAg positive then the number of infants with titres of anti-HBs Js 10 IU/1 at 6 months was 57 and 71 per cent in groups I and II, respectively. In cases of babies whose mothers were only HBsAG positive the seroprotection rate was 83 and 57 per cent in groups I and II, respectively. Seroprotection rates of babies with mothers positive for anti-HBe antibodies were 100 and 90 per cent in groups I and II, respectively. The number of infants who became carriers was almost similar in both the groups. None of the infants became carriers in mothers who were anti-HBe positive in both the groups. Journal of Tropical Pediatrics
Vol.38
October 1992
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
Screening of maternal blood for HBsAg The maternal samples were screened daily for HBsAg by reverse passive haemagglutination assay (RPHA, Cellognost, Hoechst India Ltd.) so that the babies born to HBsAg positive mothers could be vaccinated within 24 hours. All the sera of the HBsAg positive mothers and their respective babies were tested with ELISA also. These sera were also tested for HBeAg by ELISA, which was put up periodically as and when required number of samples were available. Serum samples were stored in aliquots at -70°C.
from Biotest Diagnostics, West Germany and the test was performed according to the manufacturer's instructions. HBeAg and anti-HBe antibodies were detected with the help of ELISA kit obtained from Hoechst Diagnostics (India) Ltd. The tests were performed according to the manufacturer's instructions. Anti-HBs antibodies were detected with the help of ELISA kit obtained from Hoechst Diagnostics (India) Ltd. The standard curve was drawn from the dilution of the WHO anti-HBs antibody standard and the results expressed as IU/1 of anti-HBs.
A. SEHGAL ET AL.
Table 3 shows the results in group III subjects. By 6 months, 67 per cent of the babies born to HBsAg and HBeAg positive mothers had become positive for HBsAg. Whereas 17 per cent of babies became positive when the mothers were HBsAg positive only, while 9 per cent of babies acquired the infection when the mothers were HBsAg and anti-HBeAg positive.
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Vol.38
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249
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
o.
Discussion It is well documented that 70-100 per cent of HBeAg positive carrier mothers are likely to transmit the infection to their babies at or after birth. 5 " 7 ' 10 In the present study it was observed that 67 per cent of the unvaccinated babies born to HBeAg + mothers became infected. In two randomly allocated groups, three doses of vaccine with or without HBIG were used to immunize babies of HBsAg positive mothers. It was observed that the protective efficacy and seroconversion rates in both the groups were almost similar (Table 1). About 20 per cent of the babies in each group had titres below 10 IU/leven6 months after the immunization. Perhaps these babies belonged to the category who could be labelled as non-respondents. There may be one or several mechanism responsible for this. For example, they may have become infected in utero, but the antigen may not have reached detectable levels at birth and would have become positive during the first few months of life;10 prematurity and genetic differences may be responsible for a low response to the vaccine; or HBIG may to some extent interfere with active immunity. 12 Serological status of the mother may affect the protective efficacy of the vaccine. It was observed that the percentage of infants with anti-HBs titres of ;> 10 IU/1 at 6 months was much lower in both the groups if the mother was HBeAg positive. This was more obvious in infants vaccinated with three doses of vaccine alone (57 per cent) compared to the groups given HBIG along with the vaccine (71 percent). This is similar to reports by other workers, who have shown that babies born to HBeAg positive mothers were found to be better protected at all intervals if given HBIG and vaccine compared to those given vaccine alone. 1 0 1 3 Hence, the present study shows that both HBIG and vaccine together or vaccine alone are effective in the prophylaxis of perinatal transmission of HBV infection. Both the schedules appear to induce similar seroconversion rates, though seroprotective rates were lower with vaccine alone at 3 months, but are similar at 6 months' follow-up. In infants born to HBeAg positive carrier mothers, the protective efficacy of vaccine alone is much lower, and these groups of patients may require the use of HBIG along with vaccine to prevent the transmission of HBV. 13 On the other hand, the babies who did not receive any immunoprophylaxis showed that by 6 months 67 per
A. SEHGAL ET AL.
TABLE 2
Correlation of maternal viral markers and seroprotection rates in babies at 6 months follow-up, with two schedules of vaccination Mother's serological status HBsAg + ve HBeAg + ve
HBsAg + only
HBsAg + ve Anti-HBe + ve
HBsAg + ve HBeAg + ve
Vaccine+ HBIG
Vaccine alone
Markers
HBsAg + ve Anti-HBe + ve
HBsAg + ve
n=7
n=>6
n=8
n=7
n=7
n=10
Number immune at 6 months Anti-HBS 10IU/1
4 (57.1%)
5 (83.3%)
8 (100%)
5 (71.4%)
4 (57.7%)
9 (90%)
Number who become HBsAg
1 (14.3%)
1 (16.6%)
0
1 (14.2%)
1 (14.2%)
0
carriers
TABLE 3
Viral markers in follow-up study in unvaccinated babies and their mothers (Group III) No. HBsAg positive during subsequent follow-up Antigen status of mother at parturition
No. of infants available for follow-up*
Mothers
Babies
3 months
6 months
3 months
6 months
HBsAg + only
23
20 (86.9)
18 (78.0)
4 (17.4)
3 (13.0)
HBsAg + and HBeAg +
15
14 (93.0)
14 (93.0)
8 (53.3)
10 (66.6)
HBsAg + and anti-HBeAg +
11
7 (63.3)
6 (54.5)
1 (9.0)
1 (9.0)
Total
49
* Figures in parentheses represent percentages. Six babies were positive for HBsAg at birth. They were excluded from the study. Two mothers and babies did not come for follow-up while one baby died at 2 months of age due to gastroenteritis.
cent of babies born to HBsAg and HBeAg positive mothers had become positive for HBsAg, thereby adding to the HBV carrier reservoir of the country. They may also suffer from the adverse and fatal effects of being HBsAg carriers. Therefore, it is important to decide if such babies need to be protected as a routine. The subjects included in this study are being further followed up to see the long-term protective efficacy of the vaccination schedules. References 1. Bcasley RR. Hepatitis B virus as the etiologic agent in hepatocellular carcinoma. Epidemiologic consideration. Hepatology 1982; 2 (Suppl.): 215-65. 2. Rustigi V. Epidemiology of hepatocellular carcinoma. 250
3. 4.
5. 6. 7.
In: EH Bisceglie AM. Moderator. Hepatocellular carcinoma. Ann Intern Med 1988; 108: 390-401. Smego RA, Halsey NA. The case for routine hepatitis B immunization in infancy for population at increased risk. Paediat Infect Dis J 1987; 6: 11-19. Biswas SC, Gupta I, Ganguly NK, Chawla Y, Dilawari JB. Prevalence of hepatitis B surface antigen in pregnant mothers and its perinatal transmission. Trans Roy Soc Trop Med Hyg. 1989; 83: 698-700. Centre for Disease Control. Postexposure prophylaxis for hepatitis B. Morbid Mortal Wkly Rep 1984; 33: 285-90. Gerety RJ, Tabor, E. Epidemiology of hepatitis B In: Hepatitis B. Gerety RJ. (ed.) Academic Press, New York, 1985; 77-92. Nayak NC. The status and impact of viral hepatitis—a view of the global and Indian scene. Ann Nat Acad Med Sci, India 1985; 21: 195-206.
Journal of Tropical Pediatrics
Vol.38
October 1992
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
Number of neonates enrolled
A. SEHGAL ET A L
8. World Health Organization. Progress in the control of viral Hepatitis: Memorandum from a WHO meeting. Bull Wld Hlth Org 1988; 66: 443-55. 9. 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: 137-45. 10. Wheeley SM, et al. Hepatitis B vaccine in the prevention of perinatally transmitted hepatitis B virus infection: Final report on a West Midlands pilot study. J Med Virol 1990; 30: 113-16.
11. Ganesca J, Esteban JE, Esteban R. Hepatitis B immuno prophylaxis of low birth weight infants. (Letter). Paediatrics 1985; 76: 1020. 12. PolakoffS, Vandervelde EM. Immunization of neonates at high risk of hepatitis B in England and Wales, National surveillance. Br Med J 1985; 297: 249-53. 13, Ip AMH, Lelie PN, Wong VCW, Kuhns MC, Reesink HW. Prevention of hepatitis B virus carrier state in infants according to maternal serum levels of HBV DNA. Lancet 1989; i: 406-10.
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
Journal of Tropical Pediatrics
Vol.38
October 1992
251
Use of Hepatitis B Vaccine Alone or in Combination with Hepatitis B Immunoglobulin for Immunoprophylaxis of Perinatal Hepatitis B Infection by A. Sehgal,* R. Sehgal,** I. Gupta,* O. N. Bhakoo,*** and N. K. Gangulyf Departments of'Obstetrics and Gynaecology, **Parasitology, ***Paediatrics, and ^Experimental Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160012
Introduction Infection with hepatitis B virus can lead to various complications like cirrhosis, glomerulonephritis, and hepatocellular carcinoma. 1 ' 2 Infection may be acquired during the perinatal period from mothers who are carriers of the virus.3-4 The risk of the baby getting infected varies with the serological status of the mother; 70-100 per cent infants becoming infected if the mother is both HBsAg and HBeAg positive, while the risk is low (12-20 per cent) if the mother is HBsAg and anti-HBe positive. s ~ 7 A vaccine to prevent HBV infection was licensed in 1981. To date, millions of doses have been administered. It has been observed from various regions of the world that perinatal infection can be prevented with the use of either HBV vaccine alone or in combination with hepatitis B immunoglobulin (HBIG). 3 Recently, the World Health Organization has recommended that HBV vaccine should be included in the expanded programme of immunization (EPI). 8 Hepatitis B prevalence in India is about 2-10 per cent and there is a wide prevalence of antibody to Acknowledgement The study was funded by the department of Science and Technology, Chandigarh (U.T.). Correspondence: Dr Indu Gupta, Department of Obstetrics and Gynaecology, Pgimer, Chandigarh-160012, India. Journal of Tropical Pediatrics
Vol.38
October 1992
hepatitis B virus. It is estimated that more than 100000 babies in India acquire the infection during their perinatal period from carrier mothers. 9 Hence, it is important that preventive measures are taken to prevent transmission to the neonates by use of vaccine. To date, to the best of our knowledge, no study is available from our country which has used the HBV vaccine as a prophylactic measure for prevention of perinatal HBV infection. It is also not clear whether vaccine alone in multiple doses or a combination of vaccine with immunoglobulin will be better for immunoprophylaxis. The addition of a single dose of HBIG increases the cost of the vaccination programme. The present study was designed to check the immunogenicity, safety and efficacy of the HBV vaccine alone or in combination with HBIG. Materials and Methods Subjects The study was conducted in a total of 4137 pregnant women admitted in the labour wards of Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh from January 1987 to December 1989. A detailed history was taken regarding the past and present pregnancy with special reference to any episode ofjaundice or liver disease. A thorough clinical examination was performed in each case. Collection of © Oxford University Press 1992
247
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
Summary The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates bora to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0,1,2 months) of the vaccine alone, while 27 infants were given hepatitis B imnninoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels S10 IU/I) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 P. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies bora to anti-HBe positive mothers.
A SEHGAL ET AL.
blood samples from all the pregnant mothers was done after obtaining an informed written consent, at the time of delivery. The sera were separated and stored in aliquots at - 7 0 ° C for further use.
Vaccination of neonates born of HBsAg positive mothers The neonates born to HBsAg positive mothers, irrespective of mothers' HBe antigen status, were vaccinated and allocated randomly to two groups. Group I. This group consisted of neonates who were given 10 /ig of plasma derived vaccine (Korea Green Cross Corporation, South Korea) within 24 hours of birth intramuscularly into the thigh muscle. Second and third dose of vaccine was given at 4 and 8 weeks. Group II. This group consisted of neonates who were given HBV vaccine along with hepatitis B specific immunoglobulin (HBTG). The dose and route of the vaccine was the same as in Group I along with 0.5 ml of HBIG in the contralateral thigh (Hepabig, Green Cross Corporation, South Korea). Vaccine and HBIG were given within 24 hours of birth. Subsequent doses of vaccine were given as in the case of Group I patients. Group III. Consisted of neonates who were not vaccinated. Initially, the vaccine was not available (until April 1988); hence, these babies were taken in the control group. The mothers were explained the purpose and scope of vaccination; however, some of the mothers did not give consent for the vaccination, but agreed to come for follow-up and, hence, served as controls. Follow-up of mothers and neonates All the three groups were called for follow-up at 3 and 6 months after the birth of the child. Blood samples were collected from all the mothers and infants during the follow-up. The sera were separated and stored at - 7 0 ° C until use. All the HBsAg positive samples (positive by RPHA), and subsequent samples of the mothers and neonates were checked for HBsAg, HBeAg, anti-HBe, and antiHBsAG antibodies with the use of ELISA tests. HBsAg was checked by ELISA using the kit obtained 248
Results Out of the 4137 pregnant women screened, 109 (2.63 per cent) were positive for HBsAg. Twenty-four and 27 neonates were enrolled in groups I and II, respectively, and 58 subjects (mothers) who did not agree to vaccination of their children, were considered as group III subjects. Table 1 shows the results obtained in the case of group I and II subjects. Three babies of group I were positive at birth for HBsAg and were excluded from the evaluation. The seroprotection rate (anti-HBs litres ^ 10 IU/1) at 3 and 6 months was 66 and 81 per cent, respectively. The overall protective efficacy of the vaccine in group I was 95 per cent. Only one baby (5 per cent) was positive for HBsAg by 6 months in group I. In group II subjects, three neonates were positive for HBsAg at birth. Two babies (8 per cent) became positive for HBsAg by 6 months of follow-up. The seroprotection rate at 3 and 6 months was 68 and 76 per cent, respectively, which is almost similar to that of group I infants. The protective efficacy of the vaccine at 6 months was 88 per cent in group II. Seroconversion rates with the two schedules of the vaccine were almost similar at 3 and 6 months (Table 1). The mean anti-HBs titres in both group I and II at 3 and 6 months was almost similar, though in group I (vaccine alone) the titres were somewhat higher (29.18 + 11.37) than group II (vaccine plus HBIG; 25 ± 14.2) at 6 months of follow-up (Table 1). Table 2 shows the results of the vaccination in group I and group II subjects according to the maternal serological status at time of vaccination. If the mother was HBeAg positive then the number of infants with titres of anti-HBs Js 10 IU/1 at 6 months was 57 and 71 per cent in groups I and II, respectively. In cases of babies whose mothers were only HBsAG positive the seroprotection rate was 83 and 57 per cent in groups I and II, respectively. Seroprotection rates of babies with mothers positive for anti-HBe antibodies were 100 and 90 per cent in groups I and II, respectively. The number of infants who became carriers was almost similar in both the groups. None of the infants became carriers in mothers who were anti-HBe positive in both the groups. Journal of Tropical Pediatrics
Vol.38
October 1992
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
Screening of maternal blood for HBsAg The maternal samples were screened daily for HBsAg by reverse passive haemagglutination assay (RPHA, Cellognost, Hoechst India Ltd.) so that the babies born to HBsAg positive mothers could be vaccinated within 24 hours. All the sera of the HBsAg positive mothers and their respective babies were tested with ELISA also. These sera were also tested for HBeAg by ELISA, which was put up periodically as and when required number of samples were available. Serum samples were stored in aliquots at -70°C.
from Biotest Diagnostics, West Germany and the test was performed according to the manufacturer's instructions. HBeAg and anti-HBe antibodies were detected with the help of ELISA kit obtained from Hoechst Diagnostics (India) Ltd. The tests were performed according to the manufacturer's instructions. Anti-HBs antibodies were detected with the help of ELISA kit obtained from Hoechst Diagnostics (India) Ltd. The standard curve was drawn from the dilution of the WHO anti-HBs antibody standard and the results expressed as IU/1 of anti-HBs.
A. SEHGAL ET AL.
Table 3 shows the results in group III subjects. By 6 months, 67 per cent of the babies born to HBsAg and HBeAg positive mothers had become positive for HBsAg. Whereas 17 per cent of babies became positive when the mothers were HBsAg positive only, while 9 per cent of babies acquired the infection when the mothers were HBsAg and anti-HBeAg positive.
2 3
S
2 -H
=i o
oI Al °
c 5 o >-
i:
fi s£
o »1
ll ° 9 o a a. > o. u 3 + 3
I 2 o£ Journal of Tropical Pediatrics
Vol.38
Sf 2|
I? October 1992
249
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
o.
Discussion It is well documented that 70-100 per cent of HBeAg positive carrier mothers are likely to transmit the infection to their babies at or after birth. 5 " 7 ' 10 In the present study it was observed that 67 per cent of the unvaccinated babies born to HBeAg + mothers became infected. In two randomly allocated groups, three doses of vaccine with or without HBIG were used to immunize babies of HBsAg positive mothers. It was observed that the protective efficacy and seroconversion rates in both the groups were almost similar (Table 1). About 20 per cent of the babies in each group had titres below 10 IU/leven6 months after the immunization. Perhaps these babies belonged to the category who could be labelled as non-respondents. There may be one or several mechanism responsible for this. For example, they may have become infected in utero, but the antigen may not have reached detectable levels at birth and would have become positive during the first few months of life;10 prematurity and genetic differences may be responsible for a low response to the vaccine; or HBIG may to some extent interfere with active immunity. 12 Serological status of the mother may affect the protective efficacy of the vaccine. It was observed that the percentage of infants with anti-HBs titres of ;> 10 IU/1 at 6 months was much lower in both the groups if the mother was HBeAg positive. This was more obvious in infants vaccinated with three doses of vaccine alone (57 per cent) compared to the groups given HBIG along with the vaccine (71 percent). This is similar to reports by other workers, who have shown that babies born to HBeAg positive mothers were found to be better protected at all intervals if given HBIG and vaccine compared to those given vaccine alone. 1 0 1 3 Hence, the present study shows that both HBIG and vaccine together or vaccine alone are effective in the prophylaxis of perinatal transmission of HBV infection. Both the schedules appear to induce similar seroconversion rates, though seroprotective rates were lower with vaccine alone at 3 months, but are similar at 6 months' follow-up. In infants born to HBeAg positive carrier mothers, the protective efficacy of vaccine alone is much lower, and these groups of patients may require the use of HBIG along with vaccine to prevent the transmission of HBV. 13 On the other hand, the babies who did not receive any immunoprophylaxis showed that by 6 months 67 per
A. SEHGAL ET AL.
TABLE 2
Correlation of maternal viral markers and seroprotection rates in babies at 6 months follow-up, with two schedules of vaccination Mother's serological status HBsAg + ve HBeAg + ve
HBsAg + only
HBsAg + ve Anti-HBe + ve
HBsAg + ve HBeAg + ve
Vaccine+ HBIG
Vaccine alone
Markers
HBsAg + ve Anti-HBe + ve
HBsAg + ve
n=7
n=>6
n=8
n=7
n=7
n=10
Number immune at 6 months Anti-HBS 10IU/1
4 (57.1%)
5 (83.3%)
8 (100%)
5 (71.4%)
4 (57.7%)
9 (90%)
Number who become HBsAg
1 (14.3%)
1 (16.6%)
0
1 (14.2%)
1 (14.2%)
0
carriers
TABLE 3
Viral markers in follow-up study in unvaccinated babies and their mothers (Group III) No. HBsAg positive during subsequent follow-up Antigen status of mother at parturition
No. of infants available for follow-up*
Mothers
Babies
3 months
6 months
3 months
6 months
HBsAg + only
23
20 (86.9)
18 (78.0)
4 (17.4)
3 (13.0)
HBsAg + and HBeAg +
15
14 (93.0)
14 (93.0)
8 (53.3)
10 (66.6)
HBsAg + and anti-HBeAg +
11
7 (63.3)
6 (54.5)
1 (9.0)
1 (9.0)
Total
49
* Figures in parentheses represent percentages. Six babies were positive for HBsAg at birth. They were excluded from the study. Two mothers and babies did not come for follow-up while one baby died at 2 months of age due to gastroenteritis.
cent of babies born to HBsAg and HBeAg positive mothers had become positive for HBsAg, thereby adding to the HBV carrier reservoir of the country. They may also suffer from the adverse and fatal effects of being HBsAg carriers. Therefore, it is important to decide if such babies need to be protected as a routine. The subjects included in this study are being further followed up to see the long-term protective efficacy of the vaccination schedules. References 1. Bcasley RR. Hepatitis B virus as the etiologic agent in hepatocellular carcinoma. Epidemiologic consideration. Hepatology 1982; 2 (Suppl.): 215-65. 2. Rustigi V. Epidemiology of hepatocellular carcinoma. 250
3. 4.
5. 6. 7.
In: EH Bisceglie AM. Moderator. Hepatocellular carcinoma. Ann Intern Med 1988; 108: 390-401. Smego RA, Halsey NA. The case for routine hepatitis B immunization in infancy for population at increased risk. Paediat Infect Dis J 1987; 6: 11-19. Biswas SC, Gupta I, Ganguly NK, Chawla Y, Dilawari JB. Prevalence of hepatitis B surface antigen in pregnant mothers and its perinatal transmission. Trans Roy Soc Trop Med Hyg. 1989; 83: 698-700. Centre for Disease Control. Postexposure prophylaxis for hepatitis B. Morbid Mortal Wkly Rep 1984; 33: 285-90. Gerety RJ, Tabor, E. Epidemiology of hepatitis B In: Hepatitis B. Gerety RJ. (ed.) Academic Press, New York, 1985; 77-92. Nayak NC. The status and impact of viral hepatitis—a view of the global and Indian scene. Ann Nat Acad Med Sci, India 1985; 21: 195-206.
Journal of Tropical Pediatrics
Vol.38
October 1992
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on June 6, 2015
Number of neonates enrolled
A. SEHGAL ET A L
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Journal of Tropical Pediatrics
Vol.38
October 1992
251
