Hepatitis B vaccination in children: The Taiwan experience

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 0.5 ml of hepatitis B immunoglobulin within 24 hours 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 20 years 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 (< 20 years 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 20 years, 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.     

Impact of universal vaccination on intrafamilial transmission of hepatitis B virus

To control hepatitis B virus (HBV) infection, a nationwide vaccination program was launched in 1984 and resulted in a significant reduction in the rate of persistent infection of children. However, the relative contribution of vaccination to the intrafamilial clustering of HBV infection remains unclear. The rate of intrafamilial HBV transmission in vaccinated children was investigated. Eighty-four sera from vaccinated children were enrolled and HBV serum markers were determined. The modes of intrafamilial HBV transmission were investigated by history taking and serological assay, and confirmed by genotyping and phylogenetic analysis. The results showed 66 (78.6%) vaccinated children born to hepatitis B surface antigen (HBsAg)-negative parents were HBsAg-negative. Eighteen vaccinees were born to HBsAg-positive parents; four (21.4%) of the children were HBsAg-positive. According to the parents' HBsAg status, three patterns of HBsAg-positive parents were identified. Serological analysis showed that three of 15 children born to HBsAg-positive mother (pattern I) and one of two children born to HBsAg-positive father became infected (pattern II). The remaining one child was HBsAg negative with both parents positive for HBsAg (pattern III). Genotyping and phyogenetic analysis confirmed the mode of intrafamilial transmissions. Sequence analysis of S and pre-S genes showed that HBV isolates of HBsAg-positive vaccinees were variants; no G145R but G145A and other substitutions were found. In conclusion, this small study showed that both maternal and paternal transmissions are important of the intrafamilial spread of HBV infection. In addition, the introduction of HBV vaccination has resulted in a reduction of intrafamilial transmission, but a study of a large population is needed.     

Impact of the Expanded Program of Immunization against hepatitis B infection in school children in Malaysia

The implementation of the Expanded Program of Immunization (EPI) in 1989 has dramatic impact on hepatitis B virus (HBV) infection in school children in Malaysia. A cross-sectional seroprevalence study of HBV infection in 190,077 school children aged 7–12 years from 1997 to 2003 showed a steady decline of HBV surfacce antigen (HBsAg) prevalence rate from 2.5% for children born in 1985 to 0.4% among school children born in 1996. The overall prevalence of HBsAg was 0.6%, 0.7% in males and 0.6% in females. Over 92.7% of school children had been vaccinated with HBV vaccine, in which 93.7% were vaccinated under the EPI and 6.3% on voluntary basis. The school children vaccinated under EPI had a 0.4% HBsAg carrier rate, which was significantly lower than school children vaccinated on a voluntary basis (HBsAg carrier rate 1.3%) and non-vaccinated school children (HBsAg carrier rate 2.7%), suggesting that HBV vaccination of infants was the most effective measure in preventing vertical transmission of HBV in the hyperendemic region.     

Prevalence of HBsAg carriers in native and immigrant pregnant female populations in Israel and passive/active vaccination against HBV of newborns at risk.

Israel has no official prevention policy at present against perinatal and horizontal transmission of hepatitis B virus (HBV) infection in newborns and children at risk. The present study was designed to assess the prevalence of HBV carrier state in a population of 11,123 pregnant women at term. Among this population (mean age 29.7 +/- 5.9), 98 women (0.88%) were found to be asymptomatic HBsAg+ carriers, and 97% of these carriers were anti-HBe+. Evidence for HBV replication, as determined by serum HBV-DNA, was established in 6.6% of the HBsAg+/anti-HBe+ population. The HBsAg carrier rate was strongly influenced by religion, continent, and country of birth of the carrier mothers. The highest relative carrier rate was found among women of Moslem origin (4.3%), as compared to Jewish women (0.67%). Most carrier women were born in Israel (56.1%) to mothers who had emigrated from regions with intermediate or high endemicity of HBV, such as North Africa or the Middle East. In these groups, the HBsAg carrier rate ranged between 1.2 and 3.0%. Ninety-three percent of newborns receiving passive/active vaccination against HBV developed protective levels of anti-HBs. Finally, evidence for horizontal transmission of HBV was found in 19.3% of 83 non-vaccinated children in families of HBsAg carriers. The present study therefore establishes HBsAg prevalence rates in specific risk groups of women at term and confirms the need for an official policy on immunization against HBV in Israel. Since over 50% of women at term belong to the defined risk groups, universal active vaccination of the entire newborn population each year is suggested as the most rational and needed policy in Israel.     

Seroprevalence of hepatitis B virus infection in children in Taipei, 1989: five years after a mass hepatitis B vaccination program

A nationwide hepatitis B vaccination program was launched in Taiwan in 1984. To study the impact of this ongoing program on hepatitis B virus (HBV) infection, a follow-up seroepidemiologic study was carried out in 1989 in a Taipei district where pre-vaccination seroepidemiology had been studied. HBV markers were studied in 1134 apparently healthy children (619 boys and 515 girls) under 13 years of age between March and July 1989. The prevalence of hepatitis B surface antigen (HBsAg) in children under 5 years of age decreased from 9.3% in 1984 to approximately 2% in 1989. A significant decrease in HBsAg prevalence and hepatitis B core antibody in 5- to 8-year-old children who were not immunized against HBV showed that horizontal infection among the older children had also decreased. Thus, this program not only protected vaccinated subjects; the reduction in numbers of highly infectious young HBV carriers also contributed to a lower prevalence of hepatitis B infection and carrier rates in some older children. This study demonstrates that hepatitis B vaccination is effective in protecting the majority of children in hyperendemic areas from HBV infection and from becoming chronic carriers.     

Trend of hepatitis B virus infection in freshmen classes at two high schools in Hualien,Taiwan from 1991 to 1999

Taiwan is an endemic area of hepatitis B virus (HBV) infection. A nationwide mass vaccination program to prevent HBV infection was started in 1985. Perinatal and horizontal transmission of HBV decreased substantially after the launching of this program. However, the influence of this program on children born before 1985 has not been studied. From 1991 to 1999, annual surveys of hepatitis B virus surface antigen (HBsAg) and antibody (anti-HBs) were carried out in freshmen at two high schools in Hualien, Taiwan. The average age was 16 years old. Although these students were born 2-10 years after the start of the national HBV vaccination program, there is a significant trend of decreasing HBsAg carrier rate (from 21.0% to 10.5% in males and 14.3% to 4.7% in females) and increasing anti-HBs rate (from 56.6% to 67.8% in males and 70.3% to 75.9% in females) over the 9 years. With yearly comparison, the carrier rate of HBsAg started to show significant decrease since 1994, while the anti-HBs began to rise significantly after 1996, especially in male students. The HBsAg carrier rate in male students was significantly higher, while the anti-HBs rate was significantly lower, than that in female students in most of the years. It is concluded that the effect of HBV vaccination also reduced horizontal transmission of HBV to children born up to 7 years before the start of the program.     

Multiple intra-familial transmission patterns of hepatitis B virus genotype D in north-eastern Egypt

The transmission rate of intra‐familial hepatitis B virus (HBV) and mode of transmission were investigated in north eastern Egypt. HBV infection was investigated serologically and confirmed by molecular evolutionary analysis in family members (N = 230) of 55 chronic hepatitis B carriers (index cases). Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti‐HBc) prevalence was 12.2% and 23% among family members, respectively. HBsAg carriers were prevalent in the age groups; <10 (16.2%) and 21–30 years (23.3%). The prevalence of HBsAg was significantly higher in the family members of females (19.2%) than males (8.6%) index cases (P = 0.031). HBsAg and anti‐HBc seropositive rates were higher significantly in the offspring of females (23%, 29.8%) than those of the males index cases (4.3%, 9.8%) (P = 0.001, 0.003), as well as higher in the offspring of an infected mother (26.5, 31.8%) than those of an infected father (4.7%, 10.5%) (P = 0.0006, 0.009). No significant difference was found in HBsAg seropositive rates between vaccinated (10.6%) and unvaccinated family members (14.8%). Phylogenetic analysis of the preS2 and S regions of HBV genome showed that the HBV isolates were of subgenotype D1 in nine index cases and 14 family members. HBV familial transmission was confirmed in five of six families with three transmission patterns; maternal, paternal, and sexual. It is concluded that multiple intra‐familial transmission routes of HBV genotype D were determined; including maternal, paternal and horizontal. Universal HBV vaccination should be modified by including the first dose at birth with (HBIG) administration to the newborn of mothers infected with HBV. J. Med. Virol. 84:587–595, 2012. © 2011 Wiley Periodicals, Inc.     

Molecular evidence of father-to-child transmission of hepatitis B virus

At present in Japan, only high-risk infants born to chronic hepatitis B virus (HBV)-infected mothers are given HBV vaccine. However, children can contract the virus from other HBV-infected family members, including fathers. The aim of this study is to present substantial and unequivocal evidence of father-to-child transmission of HBV infection using techniques including homology analysis and phylogenetic analysis. Thirteen chronic HBV-infected members of five families that included eight children and their respective fathers were enrolled in this study. Homology analysis and phylogenetic analyses of 2 coding region, the S gene and X gene, from the HBV genome were performed comparing the 13 nucleotide sequences from the 13 subjects. The nucleotide homology among the five sets of fathers and children was quite high (99.3-100%). A phylogenetic tree constructed on the 13 nucleotide sequences showed that all 5 sets of fathers and children were grouped into the same cluster with high bootstrap values. These results strongly indicate that father-to-child transmission is an important route of HBV infection in Japan and it is recommend that universal vaccination against HBV infection be instituted immediately in Japan for all children, in accordance with the WHO recommendation of 1997.     

乙型肝炎病毒母婴阻断长期效果的随访研究

目的观察乙型肝炎病毒母婴阻断长期效果,探讨HBsAg阳性孕妇生产儿童发生慢性HBV感染的相关影响因素。方法随访和收集于2004--2006年在北京地坛医院出生的HBsAg阳性母亲所生,并在出生时进行200单位乙肝免疫球蛋白（HBIG）注射和经过乙肝疫苗10μg,0、1和6个月的完整免疫接种程序的儿童静脉血,采用Abbott微粒子化学发光法检测其HBsAg、抗-HBs抗体、抗-HBc抗体,分析母婴阻断和乙肝疫苗接种的长期效果及其影响因素。结果收集和调查306名儿童年龄3—6（4．84）岁,其母亲生产时HBeAg阳性198人,HBeAg阴性92人。10（3．27％）名儿童发生慢性HBV感染。除慢性HBV感染者外,其余296名儿童,20．27％抗-HBs〈10mlU／ml;44．26％抗-HBs≥10—100mlU／ml;27．03％抗-HBs≥100～1000mlU／ml和8．45％抗-HBs≥1000mlU／m,抗-HBs保护率为79．73％（236／296）。抗-HBc阳性率为7．43％（22／296）。10例感染儿童的母亲生产时HBeAg均为阳性,HBVDNA均在10。拷贝／ml以上,其中8例超过10^8拷贝／ml。结论在进行乙肝疫苗加HBIG注射的HBV母婴传播阻断措施下,HBV母婴阻断失败和慢性H13V感染发生在HBeAg阳性和高病毒载量产妇所生婴儿,在有效阻断后仍需进行抗HBs监测并加强免疫接种。     

广州市应用乙型肝炎疫苗免疫22年人群血清学效果研究

目的评价广州市长期应用乙型肝炎疫苗（hepatitis B vaccine,HepB）对乙型肝炎（乙肝）免疫防病效果。方法在广州市全市12个区、县级市按照多阶段分层整群抽样法,以家庭为单位对1～59岁人群进行横断面调查分析,包括检测HBsAg、抗-HBs,对HepB接种史及主要乙肝感染危险因素进行问卷调查,评估人群HepB接种率,分析和比较不同年龄组、不同家庭感染状况下接种与未接种HepB人群乙型肝炎病毒感染指标,评价HepB免疫防病效果。结果 1～16岁年龄组乙肝疫苗全程接种率为88.11%（2535/2877）,17～59岁人群有乙肝疫苗免疫史为20.75%（470/2113）。在推行新生儿HepB接种纳入计划免疫管理后出生的1～16岁人群,HBsAg阳性率为1.29%,而出生时尚未开展HepB接种的20～59岁人群HBsAg阳性率为13.72%。1～16岁人群中有HepB接种史人群HBsAg阳性率0.99%,无接种史人群为5.56%,疫苗保护率为82.19%。20～59岁人群接种HepB,基本都不是在新生儿时期,疫苗保护率为52.01%。新生儿接种HepB,母婴乙肝传播阻断率为94.16%,并能有效阻断家庭内水平传播。结论长期实施新生儿接种HepB能控制、消除受种人群乙肝病毒感染,非新生儿人群接种HepB也能显著降低乙肝病毒感染率。     

Decline of hepatitis B carrier rate in vaccinated and unvaccinated subjects: sixteen years after newborn vaccination program in Taiwan

Taiwan was an endemic area for hepatitis B virus (HBV) infection, and related liver diseases cause a significant drain of public resources. To control the endemic, a nation-wide newborn vaccination program was started in 1985. We reviewed the results of the annual survey for HBV surface antigen (HBsAg) performed in freshmen class of two high schools in Hualien, eastern Taiwan, from 1991 to 2001. A total of 10,194 students, most of them 15 years old, were tested for serum HBsAg using enzyme immunoassays. There is a significant trend (P < 0.0001) of decreasing HBsAg carrier rate from 20.3 to 4.4% in males and 14.3% to 2.4% in females, respectively, over 11 years. The HBsAg carrier rate was 16.0-20.3% in students surveyed during 1991-1993 (born more than 6 years before the start of the national vaccination program), which decreased to 7.7-11.9% during 1994-1999 (born 1-6 years before the program). It further declined to 4.7% and 3.4% in 2000 and 2001 (born after the start of the program). The HBsAg carrier rate in male students was significantly higher than that in female students in most of the years. The HBV newborn vaccination program not only successfully prevented most of the perinatal transmission of HBV but also reduced horizontal transmission of HBV to children born up to 6 years before the start of the program. Also, the protection persisted for at least 15 years.     

Hepatitis B virus surface gene mutants in immunoprophylaxis-failed infants from Southern China

Hepatitis B virus (HBV) vaccination was considered the most powerful tool for prevention of HBV transmission from mother to infant. In 1992, a universal HBV vaccination program for infants was launched in China. The aim of this study was to investigate the HBV surface antigen (HBsAg) variations in immunoprophylaxis-failed infants, vaccine free infant patients and adult chronic hepatitis B (CHB) patients (without nucleoside analog treatment). Immunoprophylaxis-failed infants were recruited from two centers (Guangdong and Chongqing, representing Southern China). HBV serum markers, including HBsAg, hepatitis e antigen (HBeAg), and core antigen, were detected by the enzyme-linked immunosorbent assay. HBV DNA load was detected by quantitative polymerase chain reaction. Nucleotide sequences encoding HBsAg were amplified and analyzed. Frequencies of amino acid substitutions within the second loop of “a” determinant (region with greater local hydrophilicity) in immunoprophylaxis-failed infants were clearly higher than the unvaccinated infant patients and adult CHB patients (9.6% vs 0% vs 3.8%; χ ² = 7.454; P = 0.024). More than 50% (52.8%) aa substitutions in immunoprophylaxis-failed infants were located in B cell epitopes, while 64.6% aa substitutions in adult CHB patients were located in CTL cell epitopes. HBeAg negative patients had higher substitution frequency in CTL and Th cell epitopes, and in immunoprophylaxis-failed infant patients with substitution in major hydrophilic region region had a higher alanine aminotransferase level (68.6 ± 111.5 vs 62.1 ± 132.2; P = 0.026), and lower DNA load (7.03 ± 1.72 vs 7.82 ± 1.73; P < 0.001). In conclusion, our results observed vaccine-induced immune selection pressure in vaccine failed infants, substitutions in “a” determinant, especially the G145 substitution was still the most stable and remarkable site of vaccine escape.     

A study on the perinatal transmission of the hepatitis B virus

The purpose of this study was to determine the age wise prevalence of Hepatitis B virus (HBV) in children under five years and to analyze the relative importance of horizontal or vertical transmission. This study included 400 children in the age group of less than five years attending the outpatient department of pediatrics with minor complaints. History of HBV immunization was taken as the exclusion criteria. All the samples were tested for Hepatitis B surface antigen (HBsAg) and anti HBs using commercial ELISA kits. Liver function tests were performed on all the HBsAg positive patients. Hepatits B nucleocapsid antigen (HBeAg) was detected in few HBsAg positive mothers. Overall HBsAg positivity in children below five years was 2.25%. There was no statistically significant difference in HBsAg positivity in the different age groups by chi square test. HBsAg positivity in mothers was 4.25%. However only in three cases the pair of mother and child were both positive for HBsAg. The mean anti HBs positivity in children was 23.75%. There was no statistically significant difference in the anti HBs positivity in different age groups of children. The observation that there is no statistically significant difference in the prevalence of HBV infection (HBsAg and HBs) amongst different age groups of children below five years signifies that a large proportion of HBV infection in children of this age is acquired via vertical transmission. It is also indicated that this mode of disease transmission is responsible for the majority of chronic carriers. Universal immunization of all infants is desirable to decrease the carrier pool and it is inferred from the present study that Hepatitis B immunization should begin at birth to have greater impact.     

Prevention and control of hepatitis B in China

About 170 million Chinese are infected chronically with HBV and 10% suffer from chronic hepatitis. Around half a million Chinese die from hepatitis B caused hepatocellular carcinoma and endstage cirrhosis each year. From 1983 to the present, a controlled clinical trial involving 80,000 children on a universal hepatitis B vaccination programme to prevent chronic hepatitis, hepatocellular carcinoma, and endstage cirrhosis was implemented in Qidong, China. A pilot study demonstrated that the HBsAg rate reached the adult level before the fifth year of age, and neonatal vaccination with either plasma-derived or recombinant hepatitis B vaccines provided a similar 75% protective efficacy against HBV infection. The high rate of follow-up and blood tests coverage of the cohorts provided data to show 75% protection at the tenth to eleventh years of age against serum HBsAg and also against prolonged hepatic dysfunction. The strategy of controlling hepatitis B nationwide was based on the universal immunisation of newborns, beginning in cities and then the rural areas. The large-scale vaccine source was provided by domestic plants through technology transfer, first providing plasma-derived vaccine replaced completely by recombinant DNA vaccine in 1997. An official survey in 1999 using a cluster sampling of 25,878 children from 31 provinces reported an average coverage rate of three dose of hepatitis B vaccination of 70.7%, being higher in urban areas. The Ministry of Public Health of China has planned to integrate hepatitis B vaccination into the nationwide EPI program with Government-provided vaccines starting January 1, 2002.     

Screening,characterisation and prevention of Hepatitis B virus (HBV) co-infection in HIV-positive children in South Africa

BackgroundIn South Africa, the first HBV vaccine dose is administered at age 6 weeks, leaving a potential window for vertical transmission. Insights into HBV seroprevalence in the vulnerable HIV-infected group are important to drive improvements in surveillance, treatment and prevention.ObjectivesWe set out to implement a screening program for HBV among HIV-infected children and adolescents in Kimberley, South Africa. Our aims were to demonstrate that screening is feasible and sustainable, to establish the prevalence of HBV, to characterise the HBV cases we identified, and to inform discussion about the infant vaccination schedule.Study designWe tested all HIV positive children (age 0–16) for Hepatitis B surface antigen (HBsAg), delivering this testing as part of routine state-funded care. We followed up HBsAg-positive cases with an extended panel of HBV serology tests, and HBV DNA viral load quantification.ResultsOur screening campaign was successfully incorporated into routine out-patient care. Among 625 patients tested, we found five positive for HBsAg (0.8%), of whom three were Hepatitis B e-antigen positive. Two additional children initially tested HBsAg-positive but were negative on repeat testing. Antiviral therapy in the HBsAg children was reviewed and adjusted if required.ConclusionsThe results testify to the overall success of the HBV vaccine campaign. However, we have demonstrated that ongoing vigilance is required to detect cases and prevent transmission events. Further evaluation of the optimum timing of the first vaccine HBV vaccine dose is required; a vaccine dose at birth could reduce prevalence further.     

Clinical characteristics of hepatitis B virus infection in middle school students born after the universal infant vaccination program in Shanghai,China

The aim of this study was to investigate the prevalence of hepatitis B surface antigen (HBsAg) and clinical characteristics of middle school students infected with hepatitis B virus (HBV) after initiation of the HBV immunization program in China. A total of 82,156 serum samples were collected from students in 33 junior schools and 25 senior schools. HBsAg was tested by ELISA. Samples from HBsAg-positive students were collected and analyzed for HBV serum markers, alanine aminotransferase (ALT), HBV DNA levels, and HBV genotypes. The overall prevalence of HBsAg was 1.11% in middle school students in Shanghai, China. The prevalence of HBsAg in students born during the immunization program to HBsAg-positive mothers was significantly higher than that in students born during the universal vaccination program (1.47% vs 0.78%, P < 0.01). Only HBV genotypes B and C were found in these infections, and genotype C was the dominant one. Twenty-one (13.0%) of 162 HBsAg-positive students had active hepatitis B, and 18 were hepatitis B e antigen (HBeAg) positive. The universal infant vaccination program has reduced the prevalence of HBsAg significantly. HBeAg-positive hepatitis B, however, needs to be monitored among the students in whom vaccination failed.     

Seroprevalence of Hepatitis-B infection amongst Taiwanese university students 18 years following the commencement of a national Hepatitis-B vaccination program

In Taiwan, the nation-wide Hepatitis-B virus (HB) vaccination program was first launched in July 1984 and was directed to those infants born to hepatitis B surface antigen (HBsAg) carrier mothers in Taiwan. From July 1986 onwards, all infants born in Taiwan were immunized against HB. This study examined the HB-infection status amongst students at a Taiwanese university 18 years subsequent to the implementation of universal HB vaccination. A total of 1,969 new university entrants in 2005 were grouped into 1 of 3 distinct birth cohorts according to their HB-vaccination schedule (cohort-1 students born prior to July 1, 1984; cohort-3 students born subsequent to June 30, 1986) and were examined for their serum HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) status. Immunity arising from vaccination was defined as an anti-HBs level 10 mIU/ml. We observed a trend toward a decreasing anti-HBc-positive rate and a decreasing HBsAg carrier rate from, respectively, 26.5 and 8.7% for cohort-1 to 4.7 and 1.7% for cohort-3 students. The prevalence of students featuring seronegativity for all three HB markers increased from 12.3% for cohort-1 to 48.8% for cohort-3 individuals. Amongst the 1,695 subjects revealing seronegativity for HBsAg and anti-HBc, their anti-HBs level was analyzed according to their birth year. The prevalence of students featuring a non-protective anti-HBs level increased from 11.9% for birth-year 1984 individuals to 48.2% for birth-year 1987 students. The introduction of HB vaccine has effectively reduced the transmission of HBV infection in Taiwan, 18 years subsequent to the commencement of the universal HB-vaccination program. A "waning-off" effect of anti-HBs seropositivity acquired from the HB vaccination program has also been observed.     

Asymptomatic hepatitis B carriers who were vaccinated at birth

The long-term persistence of immunity following universal infant immunization against hepatitis B virus (HBV) and the need for a subsequent booster dose in adolescence remain under debate. With data derived from Long'an County, Guangxi, China, we reported previously that the prevalence of hepatitis B surface antigen (HBsAg) among adults born from 1987 to 1993 increases with age, although these individuals had received a first dose of the vaccine within 24 hours of birth. Here, we sought the source of transmission by comparison of genotypes among their family members using phylogenetic analysis of complete HBV S gene sequences. For comparison, we screened 2199 vaccinated individuals aged 5 to 17 in Cang Wu County and 1592 vaccinated individuals aged 3 to 7 in Ling Shan County in Guangxi for HBsAg carriers and investigate their family members. In total, 50 asymptomatic HBsAg carriers who were vaccinated at birth and 152 family members were analyzed. The results showed that 25% (95% CI: 6.0-44.0) of the HBsAg-positive children had not acquired their HBV infection from their mothers. This phenomenon showed a trend that increases with age. Antibody escape mutations were detected in 22.9% (95% CI: 11.0-34.8) of the isolates. In conclusion, a booster dose may be necessary for adolescence who were vaccinated at birth in highly endemic countries.     

HBsAg阳性儿童和健康儿童对国产甲型肝炎灭活疫苗免疫原性和安全性的观察

目的：观察HBsAg阳性儿童对国产甲型肝炎灭活疫苗的免疫原性和安全性。方法：随机选取121名1－10岁健康儿童和10名同龄的HBsAg阳性儿童，抗－HAV均阴性，接种唐山怡安生物工程有限公司研制的甲型肝炎灭活疫苗。接种剂量为500U／剂和1000U／剂两组，免疫程序为0和6个月，并在初免后30d，第二针后30和180d用ELISA方法检测抗－HAV。结果：HBsAg阳性儿童和健康儿童接种500U／剂和1000U／剂甲型肝炎灭活疫苗后抗体阳转率均为100％。第二针免疫后30d抗体平均几何滴度500U／剂组分别为4684．9mIU和4535．6mIU；1000U／剂组分别为5399．8mIU和7347．1mIU。二者比较差异无显著性，免疫后亦未见异常反应，初免后1年抗体水平仍然很高。结论：HBsAg阳性儿童接种国产甲型肝炎灭活疫苗具有良好的免疫应答，同时也是安全的。     

A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China

The emergence of mutations in the hepatitis B virus (HBV) S gene has threatened the long‐term success of vaccination programs since the worldwide introduction of effective vaccines against hepatitis B. This study was conducted on 5,407 children (0–8 years old) in eastern China in 2007. We analyzed the prevalence of HBsAg, anti‐HBs, and “a”‐determinant mutations in the HBV S gene by microparticle enzyme immunoassays, PCR, and DNASTAR software. The total HBsAg prevalence was 1.52% (82/5,407) in the children and increased with age. In contrast, the positive rate (65.42%, 2,374/3,629) and the titers of anti‐HBs decreased with age. The predominant infection was HBV of genotype C and serotype adr (45/51; 88% of cases). Mutations of I126T, amino acid 137 (nt553T deletion mutation), G145A, G145R, and F158S were found in the children; the mutations of amino acid 137 and F158S have not been reported previously. The total prevalence of mutant strains was 14% (7/51). To investigate whether the infection resulted from maternal transmission, we compared the S gene sequences in 16 mother–child pairs. Fourteen mother–child pairs exhibited the same HBV genotype, with 99.5–100% sequence homology in the S gene, while two pairs exhibited different genotypes. This study suggested that the hepatitis B vaccination strategies in eastern China have been successful. Although the emergence of “a”‐determinant mutations in the HBV S gene have resulted in HBV infection in immunized children, this does not pose a threat to the vaccination strategies. The HBV‐infected children had contracted the infection via vertical transmission. J. Med. Virol. 81:1517–1524, 2009. © 2009 Wiley‐Liss, Inc.