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Ten-year neonatal hepatitis B vaccination program, The Netherlands, 1982-1992: protective efficacy and long-term
R del Canho1, P M Grosheide, J A Mazel
1Department of Internal Medicine II, University Hospital Dijkzigt, Rotterdam, Netherlands.
Insights
Hepatitis B vaccination in infants is highly effective, with protective efficacy mainly influenced by maternal HBV DNA levels. Long-term immunity is enhanced when hepatitis B vaccination is given with DKTP vaccine.
Area of Science:
- Immunology
- Vaccinology
- Public Health
Background:
- Hepatitis B virus (HBV) infection in neonates can lead to chronic infection.
- Passive-active immunization strategies aim to prevent perinatal HBV transmission.
- Optimizing neonatal hepatitis B vaccination schedules is crucial for long-term protection.
Purpose of the Study:
- To evaluate factors influencing the protective efficacy and long-term immunogenicity of neonatal passive-active hepatitis B immunization.
- To compare different vaccination schedules, including timing, vaccine types, and immunoglobulin doses.
- To assess the impact of concomitant DKTP vaccination on hepatitis B vaccine effectiveness.
Main Methods:
- Meta-analysis of individual patient data from three randomized controlled trials involving 705 infants.
- Multivariate logistic regression analysis to identify predictive factors for protective efficacy and immunogenicity.
- Long-term follow-up (up to 5 years) to assess sustained seroprotection.
Main Results:
- Overall protective efficacy against HBsAg carriage at 12 months was 92%.
- Maternal HBV DNA level was the sole significant factor influencing protective efficacy (100% efficacy if <150 pg/mL vs. 68% if >150 pg/mL).
- Starting active immunization at 3 months, concomitant with DKTP vaccination, enhanced long-term seroprotection compared to starting at birth.
Conclusions:
- Passive-active hepatitis B immunization is highly effective, primarily dependent on maternal HBV DNA levels.
- The timing of active immunization (birth vs. 3 months) did not significantly impact initial protective efficacy.
- Concomitant administration with DKTP vaccine improves long-term immunity, supporting integration into standard infant immunization programs.
Abstract:
From 1982 to 1989, 705 infants born to HBsAg-positive mothers entered the Dutch neonatal hepatitis B vaccination program and received passive-active hepatitis B immunization in three randomized controlled trials testing variations in time of starting active vaccination, dose and type of vaccine, and number of hepatitis B immunoglobulin (HBIg) injections. A meta-analysis of individual patient data of the three randomized trials was performed to determine which independent host and vaccination related factors influence protective efficacy and long-term immunogenicity, and to assess whether hepatitis B vaccination concomitant with standard DKTP vaccination provides optimal protection. Statistical methodology included multivariate logistic regression analysis. Eight infants (1.1%), all born to HBeAg-positive mothers, became HBsAg carriers within the first year of life. The protective efficacy rate (PER) of passive-active immunization at 12 months follow-up was 92% for the total group of children from 114 HBeAg-positive mothers with no significant differences between children starting active immunization at birth or at 3 months of age, between infants starting at 3 months of age receiving one or two doses of HBIg or between those receiving plasma derived or recombinant vaccine. The only factor that affected the PER significantly was the level of maternal HBV DNA; PER was 100% if maternal HBV DNA was < 150 pg ml-1 and 68% for HBV DNA levels > 150 pg ml-1. After 5 years of follow-up, the group that started active immunization at birth had significantly more infants with loss of seroprotection (anti-HBs levels < 10 IU l-1, 15%) than the corresponding group starting at 3 months of age (anti-HBs < 10 IU l-2, 2%). One of 35 children with loss of seroprotection at 2 years became a HBsAg carrier in the fifth year of follow-up. This meta-analysis shows that the protective efficacy of passive-active hepatitis B vaccination is mainly influenced by material HBV DNA levels, and independent of the time of starting active vaccination at birth or at 3 months of age; long-term immunity was enhanced by starting active vaccination concomitant with DKTP vaccination. These findings allow incorporation of hepatitis B vaccine into the standard infant immunization programs for countries with a passive-active immunization strategy for the control of hepatitis B. Additional measures are needed to protect neonates of highly viremic women.