Ni Y-H, Chen D-S
Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.
Pathol Biol (Paris). 2010 Aug;58(4):296-300. doi: 10.1016/j.patbio.2009.11.002. Epub 2010 Jan 29.
The world's first nationwide hepatitis B virus (HBV) universal vaccination program for infants was launched in Taiwan in July, 1984. All infants received three to four doses plasma or recombinant HBV vaccines. In addition, infants of HBeAg-positive mothers received 0.5ml of hepatitis B immunoglobulin within 24hours after birth. The vaccination coverage rate is as high as 97%. Seroprevalence of hepatitis B surface antigen (HBsAg) declined from 9.8% (prevaccination period) to 0.6% in children in Taipei City after 20years of mass vaccination. The seropositive rates for HBsAg, antibody to HBsAg, and antibody to hepatitis B core antigen were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (<20years old) in 2004. In line with the decrease of chronic HBV infection, the incidence of hepatocellular carcinoma (HCC) also decreased in children in Taiwan. From 1981 to 1994, the incidence of HCC in 6- to 9-year-olds declined from 0.52/100,000 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (p<0.001). We extended the observation to 2000, the incidence of HCC per 100,000 children declined from 0.54 to 0.20. The prevalence of a determinant mutants (amino acids 121-149 of HBsAg) in Taiwanese carrier children was 7.8% (eight out of 103) in 1984, increased to 19.6% (10 out of 51) in 1989, peaked at 28.1% (nince out of 32) in 1994, and remained stationary at 23.1% (three out of 13) and about 25% in 1999 and 2004, respectively; it was higher in those fully vaccinated compared with those not vaccinated. The other group of subjects who are susceptible to vaccine failure is the immunocompromized hosts. We observed some de novo HBV infection in children after liver transplantation. Despite of the success of hepatitis B immunization, childhood chronic HBV infection and HCC were not eliminated by the universal vaccination program. Among those HBsAg carriers born after the vaccination program, 89% of their mothers were found to be positive for HBsAg, indicating the importance of maternal transmission. This was also true in the mothers of children with HCC, of them 96% were HBsAg positive. After two decades of universal infant HBV vaccination, we found this program provides long-term protection for up to more than 20years, and a universal booster is not required for the primary HBV vaccinees before adulthood. Mother-to-child transmission, although largely diminished, is still the main cause for immunoprophylaxis failure. The emergence of escape mutant did not impose increased risk of chronic infection at present. Nevertheless, development of new vaccines may overcome the vaccine failure.
1984年7月,台湾启动了全球首个针对婴儿的全国性乙肝病毒(HBV)普遍疫苗接种计划。所有婴儿都接种了三到四剂血浆或重组乙肝疫苗。此外,乙肝e抗原(HBeAg)阳性母亲的婴儿在出生后24小时内接种了0.5毫升乙肝免疫球蛋白。疫苗接种覆盖率高达97%。经过20年的大规模疫苗接种,台北市儿童乙肝表面抗原(HBsAg)的血清流行率从9.8%(接种疫苗前)降至0.6%。在2004年接种疫苗计划后出生的人群(<20岁)中,HBsAg、乙肝表面抗体(抗-HBs)和乙肝核心抗体(抗-HBc)的血清阳性率分别为1.2%、50.5%和3.7%。随着慢性乙肝病毒感染率的下降,台湾儿童肝细胞癌(HCC)的发病率也有所下降。1981年至1994年,6至9岁儿童的肝细胞癌发病率从1974年至1984年出生人群的0.52/10万降至1984年至1986年出生人群的0.13(p<0.001)。我们将观察期延长至2000年,每10万名儿童的肝细胞癌发病率从0.54降至0.20。1984年,台湾乙肝病毒携带者儿童中决定簇突变体(HBsAg氨基酸121-149)的流行率为7.8%(103例中有8例),1989年增至19.6%(51例中有10例),1994年达到峰值28.1%(32例中有9例),1999年和2004年分别稳定在23.1%(13例中有3例)和约25%;与未接种疫苗的儿童相比,完全接种疫苗的儿童中该突变体流行率更高。另一组易出现疫苗接种失败的人群是免疫功能低下的宿主。我们观察到肝移植后儿童出现了一些新发乙肝病毒感染。尽管乙肝疫苗接种取得了成功,但普遍疫苗接种计划并未消除儿童慢性乙肝病毒感染和肝细胞癌。在接种疫苗计划后出生的HBsAg携带者中,89%的母亲HBsAg呈阳性,这表明母婴传播的重要性。肝细胞癌患儿的母亲中也是如此,其中96%的母亲HBsAg呈阳性。经过二十年的婴儿乙肝病毒普遍疫苗接种,我们发现该计划可提供长达20多年的长期保护,并且在成年前,初次接种乙肝疫苗的人群无需普遍加强接种。母婴传播虽然在很大程度上减少了,但仍然是免疫预防失败的主要原因。目前,逃逸突变体的出现并未增加慢性感染的风险。然而,开发新疫苗可能会克服疫苗接种失败问题。