乙型肝炎高效价免疫球蛋白联合乙型肝炎疫苗免疫母亲和婴幼儿的随访研究

目的探讨乙型肝炎(乙肝)病毒(HBV)表面抗原(HBsAg)阳性母亲所产婴幼儿经乙肝高效价免疫球蛋白(HBIG)和乙肝疫苗联合免疫后的免疫效果。方法对184例HBsAg阳性母亲所产婴幼儿进行随访调查,于婴幼儿7、24、36月龄应用酶联免疫吸附试验检测血清HBV主要标志物。结果184例婴幼儿出生时HBsAg阳性者7例,HBV宫内感染率为3．80％(7／184)。分娩时HBsAg、HBeAg双阳性母亲所产婴幼儿HBV宫内感染率为11．63％(5／43);而单阳性母亲感染率约为1．42％(2／141)。7月龄随访到125例要幼儿,24、36月龄随访到108例婴幼儿,仅2例出生于双阳性母亲的婴幼儿HBsAg仍持续阳性,其余在7月龄随访时均已阴转,HBV慢性感染率为28．57％。婴幼儿出生时抗-HBs阳性率为7．02％,经HBIG和乙肝疫苗联合免疫,7月龄时抗-HBs阳性率达92％,24月龄降为72．04％。而婴幼儿抗-HBs产生与母亲双阳性无关,与其出生时HBsAg阳性呈显著相关。双阳性39例母亲所产婴幼儿出生时25例HBeAg阳性,随访时除2例HBsAg为阳性的婴幼儿HBeAg仍持续阳性外,余均转阴。随访中未见婴幼儿出现HBsAg或HBeAg阳转。结论HBsAg阳性母亲所产婴幼儿经HBIG和乙肝疫苗联合免疫后免疫效果良好,母亲双阳性可能并不影响婴幼儿联合免疫后抗-HBs的产生。     

Long-term efficacy of 10-12 years after being immunized with Chinese hamster ovary cell derived hepatitis B vaccine in Chinese Rural Communities

Objective

To evaluate the long-term efficacy of Chinese hamster ovary (CHO) cell derived hepatitis B vaccine in country community in China.

Methods

A cross-sectional investigation was carried out. Children who were born between 1997 and 1999 and vaccinated with the three doses of CHO-derived hepatitis B vaccine were selected as study objects. Their serum samples were taken to test for hepatitis B virus (HBV) markers, and the results were compared to that before vaccination. In addition, for HBsAg positive children, their mothers were visited.

Results

1254 Children were enrolled in the study. The prevalence of HBsAg was 0.24% and the vaccine efficacy was 97.0%, similar to that of yeast derived hepatitis vaccines. Among 3 mothers of HBsAg positive children, 2 were HBsAg positive, indicating maternal HBV transmissions.

Conclusion

The long-term efficacy of the CHO-derived hepatitis B vaccine is good and after vaccination maternal transmission is the most important route of spreading HBV.     

Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women

Purpose

Annually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of vaccine series and post-vaccination serologic testing (PVST). In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated.

Methods

Data were from HBsAg-negative infants born to HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with antibody to hepatitis B surface antigen (anti-HBs) <10 mIU/mL at PVST after receiving ≥3 vaccine doses. Multivariable analyses modeled statistically significant predictor variables associated with non-response.

Results

A total of 17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to HBsAg-positive mothers received ≥3 doses of vaccine with anti-HBs results. 8199 (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second series. Factors associated with anti-HBs <10 mIU/mL included gestational age <37 weeks, vaccine birth dose >12 h after birth, timing of final vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccine dose in bivariate analysis. PVST interval >6 months from final vaccine dose (OR = 2.7, CI = 2.0, 3.6) was significantly associated with anti-HBs <10 mIU/mL; the proportion increased from 2% at 1–2 months to 21.6% at 15–16 months after the final dose. Receipt of a 4th dose improved the response rate (OR = 0.5, CI = 0.3, 0.8).

Conclusions

Ninety-five percent of a large cohort of uninfected infants born to HBsAg-positive mothers in the United States responded to primary HepB vaccine series. The proportion of infants with anti-HBs <10 mIU/mL increased with longer interval between the final vaccine dose and PVST. Optimal timing of PVST is within 1–2 months of final vaccine dose to avoid unnecessary revaccination.     

Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal

Background

In Nepal, an estimated 2–4% of the population has chronic hepatitis B virus (HBV) infection. To combat this problem, from 2002 to 2004, a national three dose hepatitis B vaccination program was implemented to decrease infection rates among children. The program does not currently include a birth dose to prevent perinatal HBV transmission. In 2012, to assess the impact of the program, we conducted a serosurvey among children born before and after vaccine introduction.

Methods

In 2012, a cross-sectional nationally representative stratified cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children born from 2006 to 2007 (post-vaccine cohort) and among children born from 2000 to 2002 (pre-vaccine cohort). Demographic data, as well as written and oral vaccination history were collected. All children were tested for HBsAg; mothers of HBsAg positive children were also tested. Furthermore, we evaluated the field sensitivity and specificity of the SD Bioline HBsAg rapid diagnostic test by comparing results with an enzyme immunoassay.

Results

Among 2181 post-vaccination cohort children with vaccination data by either card or recall, 86% (95% confidence interval [CI] 77–95%) received ≥3 hepatitis B vaccine doses. Of 1200 children born in the pre-vaccination cohort, 0.28% (95% CI 0.09–0.85%) were positive for HBsAg; of 2187 children born in the post-vaccination cohort, 0.13% (95% CI 0.04–0.39%) were positive for HBsAg (p = 0.39). Of the six children who tested positive for HBsAg, two had mothers who were positive for HBsAg. Finally, we found the SD Bioline HBsAg rapid diagnostic test to have a sensitivity of 100% and a specificity of 100%.

Conclusions

This is the first nationally representative hepatitis B serosurvey conducted in Nepal. Overall, a low burden of chronic HBV infection was found in children born in both the pre and post-vaccination cohorts. Current vaccination strategies should be continued.     

Seroprotection after recombinant hepatitis B vaccination among newborn infants: A review

Introduction

Hepatitis B vaccination starting at birth provides a safety net for infants exposed to hepatitis B virus (HBV) during delivery or in early life. Hepatitis B vaccine is recommended in the United States for infants prior to birthing facility discharge, and within the first 12 h of life for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We performed a literature review and summarized the response to recombinant hepatitis B vaccine among infants.

Methods

Studies published between 1987 and 2011 assessing seroprotection from recombinant hepatitis B vaccine starting within the first 30 days of life were eligible. Seroprotection was defined using an antibody to hepatitis B surface antigen (anti-HBs) threshold of 10 mIU/mL at series completion. Infant seroprotection was compared in trial arms varying by maternal hepatitis B antigen status (e antigen [HBeAg], HBsAg), hepatitis B immune globulin (HBIG) administration, birth weight, vaccine dosage, schedule, and age at first dose.

Results

Forty-three studies were included. The median seroprotection proportion overall was 98% (range 52%, 100%). The final median seroprotection proportions did not vary appreciably by maternal HBsAg status, HBIG administration, or schedule. Higher compared to lower dosage resulted in earlier increases in anti-HBs but not in final seroprotection proportions. Infants with birth weights <2000 g compared to ≥2000 g had lower median seroprotection proportions (93% and 98%, respectively). Median seroprotection proportions were also lower when infants with birth weights <2000 g were vaccinated at 0–3 days of age compared to 1 month of age or older (68% versus 95%, respectively).

Conclusion

High levels of protection from recombinant hepatitis B vaccine are achieved in term infants vaccinated at birth, effectively preventing transmission of HBV and resultant morbidity and mortality. Implications, if any, for long-term protection are unknown for differences in responses among infants vaccinated at birth compared to ages older than 1 month.     

Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine

Background

Combined immunization with hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine (HB vaccine) can effectively prevent perinatal transmission of hepatitis B virus (HBV). With the universal administration of HB vaccine, anti-HBs conferred by HB vaccine can be found increasingly in pregnant women, and maternal anti-HBs can be passed through the placenta. This study was designed to evaluate the effect of hepatitis B immunization on preventing mother-to-infant transmission of HBV and on the immune response of infants towards HB vaccine.

Method

From 2008 to 2013, a prospective study was conducted in 15 centers in China. HBsAg-positive pregnant women and their infants aged 8–12 months who completed immunoprophylaxis were enrolled in the study and tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). Antepartum administration of HBIG to HBsAg-positive women was based on individual preference. HBsAg-negative pregnant women and their infants of 7–24 months old who received HB vaccines series were enrolled and tests of their HBV markers were performed.

Results

1202 HBsAg-positive mothers and their infants aged 8–12 months were studied and 40 infants were found to be HBsAg positive with the immunoprophylaxis failure rate of 3.3%. Infants with immunoprophylaxis failure were all born to HBeAg-positive mothers of HBV-DNA ≥ 6 log₁₀ copies/ml. Among infants of HBeAg-positive mothers, immunoprophylaxis failure rate in vaccine plus HBIG group, 7.9% (29/367), was significantly lower than the vaccine-only group, 16.9% (11/65), p = 0.021; there was no significant difference in the immunoprophylaxis failure rate whether or not antepartum HBIG was given to the pregnant woman, 10.3% (10/97) vs 9.0% (30/335), p = 0.685. Anti-HBs positive rate was 56.3% (3883/6899) among HBsAg-negative pregnant women and anti-HBs positive rate was 94.2% in cord blood of anti-HBs-positive mothers. After completing the HB vaccine series, anti-HBs positive rate among infants with maternal anti-HBs titers of <10 IU/L, 10–500 IU/L and ≥500 IU/L was 90.3% (168/186), 90.5% (219/242) and 80.2% (89/111) respectively, p = 0.011. Median titers of anti-HBs (IU/L) among infants in the three groups was 344.2, 231.9 and 161.1 respectively, p = 0.020.

Conclusions

HBIG plus HB vaccine can effectively prevent mother-to-infant transmission of HBV, but no HBV breakthrough infection was observed in infants born to HBeAg-negative mothers who received HB vaccine with or without HBIG after birth. Antepartum injection of HBIG has no effect on preventing HBV mother-to-infant transmission. High maternal titer of anti-HBs can transplacentally impair immune response of infants towards HB vaccine.     

Significance and anamnestic response in isolated hepatitis B core antibody-positive individuals 18 years after neonatal hepatitis B virus vaccination in Taiwan

Aim

To investigate the significance of isolated hepatitis B core antibody (anti-HBc) and to analyze the response to hepatitis B virus (HBV) booster vaccination in young adults with isolated anti-HBc who had been fully vaccinated with HBV vaccine as infants.

Materials and methods

We screened 1734 new university entrants who had been fully vaccinated against HBV in infancy for the presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and anti-HBc upon university entry. Results positive for isolated anti-HBc were reconfirmed by testing for the presence of HBsAg and anti-HBc once more, and further evaluated for anti-HCV, anti-HIV, and HBV DNA status 6 months later. Students were also offered HBV booster vaccinations at that time. Geometric mean titers (GMT) of anti-HBs after one booster dose of HBV were compared between students with isolated anti-HBc and students with HBV naïve status.

Results

The overall prevalence of isolated anti-HBc in our student cohort was 1.2% (21 of 1734). No evidence of occult HBV infection was observed. A “booster” anamnestic response (anti-HBs titer ≥10 mIU/mL) was noted in 95% (20 of 21) of subjects with isolated anti-HBc. After re-measurement of anti-HBc, 13 (62%) of the 21 subjects with isolated anti-HBc were reclassified as having resolved HBV infection with a loss of anti-HBs. In the remaining 8 subjects (38%), isolated anti-HBc was determined to be false positive. The HBV status of these 8 subjects was HBV naïve due to the waning-off effect of anti-HBs of the neonatal HBV vaccination. There was no significant difference in anamnestic response to a single HBV booster dose of vaccine between students with isolated anti-HBc (n = 13) and those with HBV naïve (n = 323) status (GMT 50.6 vs 47.7 mIU/mL, P = 0.90).

Conclusion

The presence of isolated anti-HBc 18 years after HBV vaccination can be attributed to post-HBV infection with a loss of anti-HBs and to a decline in anti-HBs elicited by vaccine. A single HBV booster dose of vaccine is recommended for subjects with isolated anti-HBc who were fully vaccinated with HBV vaccine as infants. This finding needs to be replicated in further studies with larger cohorts.     

A reduction in chronic hepatitis B virus infection prevalence among children in Vietnam demonstrates the importance of vaccination

Background

Vietnam has high endemic hepatitis B virus infection with >8% of adults estimated to have chronic infection. Hepatitis B vaccine was first introduced in the national childhood immunization program in 1997 in high-risk areas, expanded nationwide in 2002, and included birth dose vaccination in 2003. This survey aimed to assess the impact of Vietnam's vaccination programme by estimating the prevalence of hepatitis B surface antigen (HBsAg) among children born during 2000–2008.

Methods

This nationally representative cross-sectional survey sampled children based on a stratified three-stage cluster design. Demographic and vaccination data were collected along with a whole blood specimen that was collected and interpreted in the field with a point-of-care HBsAg test.

Results

A total of 6,949 children were included in the survey analyses. The overall HBsAg prevalence among surveyed children was 2.70% (95% confidence interval (CI): 2.20–3.30). However, HBsAg prevalence was significantly higher among children born in 2000–2003 (3.64%) compared to children born 2007–2008 (1.64%) (prevalence ratio (PR: 2.22, CI 1.55–3.18)). Among all children included in the survey, unadjusted HBsAg prevalence among children with ≥3 doses of hepatitis B vaccine including a birth dose (1.75%) was significantly lower than among children with ≥3 doses of hepatitis B vaccine but lacked a birth dose (2.98%) (PR: 1.71, CI: 1.00–2.91) and significantly lower than among unvaccinated children (3.47%) (PR: 1.99, CI: 1.15–3.45). Infants receiving hepatitis B vaccine >7 days after birth had significantly higher HBsAg prevalence (3.20%) than those vaccinated 0-1 day after birth (1.52%) (PR: 2.09, CI: 1.27–3.46).

Conclusion

Childhood chronic HBV infection prevalence has been markedly reduced in Vietnam due to vaccination. Further strengthening of timely birth dose vaccination will be important for reducing chronic HBV infection prevalence of under 5 children to <1%, a national and Western Pacific regional hepatitis B control goal.     

Efficacy of yeast-derived recombinant hepatitis B vaccine after being used for 12 years in highly endemic areas in China

Objective

To evaluate the long-term efficacy and duration of yeast-derived recombinant hepatitis B vaccine in hepatitis B virus (HBV)-endemic areas.

Method

A cross-sectional investigation was carried out in five HBV-endemic areas. Children who were born between 1997 and 2008 and vaccinated with yeast-derived recombinant hepatitis B vaccine were selected. Serum samples were taken to test HBV infection markers by microparticle enzyme immunoassay, and the results were compared to those before vaccination.

Results

7066 subjects were enrolled. The average adjusted hepatitis B surface antigen (HBsAg) prevalence was 1.02%. HBV core antibody (anti-HBc) prevalence was 3.54%. The overall percentage of HBsAg(−)&Anti-HBc(−)&Anti-HBs(+) was 61.34%. With time after immunization, the percentage annually decreases from 86.11% in 2008 to 49.80% in 1997. Geometric mean concentration (GMC) of anti-HBs decreased significantly annually. The portion of GMC = 100–999.9 mIU/ml was 48.0% in 2008, and decreased to 16.7% in 1997.

Conclusion

HBsAg prevalence decreased dramatically. This shows that the yeast-derived recombinant hepatitis B vaccine is effective and stable after being used for 12 years in HBV-endemic areas. It is not suggested to carry out booster immunization.     

Post-vaccination serologic testing of infants born to hepatitis B surface antigen positive mothers in 4 provinces of China

ObjectiveTo evaluate prenatal maternal hepatitis B virus (HBV) screening and post-vaccination hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs) status and titers of babies born to HBsAg positive mothers, and to provide evidence for development of standard postvaccination serologic testing (PVST) strategies for babies born to HBsAg positive mothers in China.MethodsIn 2014, we conducted a baseline survey of HBV mother to child transmission (MTCT) interruption strategy implementation and PVST for babies born to HBsAg positive mothers after received 3 doses of hepatitis B vaccine (HepB) in 8 counties in 4 Provinces. Bivariate analysis and multivariable analyses modeled statistically significant predictor variables associated with infant HBsAg, anti-HBs positive, anti-HBs titer.ResultsAmong the 1563 infants born to HBsAg positive mothers, 1025 (65.6%) maternal-infant pairs were enrolled in PVST after receiving 3 doses of HepB. 38 infants tested HBsAg positive for an HBsAg positive rate of 3.7%. Maternal hepatitis B e antigen (HBeAg) status and age of infant were significantly associated with infant HBsAg positivity. A total of 932 infants were anti-HBs positive when tested at 7–24 months of age, yielding an anti-HBs positivity rate of 90.9%. Maternal HBeAg status was the factor associated with infant anti-HBs status. Amount of antigen of HepB and infant’s age were most associated with anti-HBs titers. PVST performed 1–2 months after the 3rd dose of HepB was associated with the highest anti-HBs level and the anti-HBs Geometric Mean Concentration (GMC) decreased as the PVST intervals prolonged.ConclusionsIn China, perinatal HBV transmission is approaching the theoretical minimum possible with the current strategy of HepB coupled with HBIG administration for HBV-exposed newborns. PVST of infants born to an HBsAg positive mother is an essential strategy to ensure full protection for vaccine non-responders and appropriate medical care for those infected.     

Epidemiological serosurvey of Hepatitis B in China—Declining HBV prevalence due to Hepatitis B vaccination

Objective

To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants.

Methods

National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA.

Findings

The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1–59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age <15 years compared to that found in the 1992 national serosurvey, and among children age <5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other).

Conclusions

China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16–20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.     

Effectiveness of a Chinese hamster ovary cell derived hepatitis B vaccine in Chinese rural communities

Objective

To evaluate the effectiveness of a Chinese hamster ovary cell derived hepatitis B vaccine in a country community in Hebei Province, PR China.

Method

A cross-sectional investigation was carried out in 4 of 7 randomly selected country communities in Zhengding County in 2005. All of the children who were born between 1997 and 1999 were selected as study objects. Their serum samples were taken to test for HBV markers, and HBsAg prevalence was compared to that of the same age group before hepatitis B vaccination in 1983. In addition, for HBsAg positive children, their mothers were visited and tested for serum HBV markers, in order to distinguish maternal HBV transmissions.

Results

Among the 2205 children of the selected birth cohort, 1696 (76.9%) were visited. The prevalence of HBsAg was 0.53%, and by comparing to that of before hepatitis B vaccination, the effectiveness was 95.3%, similar to that of yeast derived hepatitis B vaccines. Among 7 mothers of HBsAg positive children, 5 were HBsAg positive, indicating maternal HBV transmissions; and although one mother was HBsAg negative, her kid was not vaccinated, which indicates a horizontal transmission. As for the other kid, he was adopted and the HBV infection status of his birth mother was unknown.

Conclusion

The effectiveness of the CHO derived hepatitis B vaccine is comparable to yeast derived ones, and after the hepatitis B vaccination maternal transmission is the most important route of spreading HBV.     

Stable seroepidemiology of hepatitis B after universal immunization in Taiwan: A 3-year study of national surveillance of primary school students

Background

This study is aimed to investigate if there was increased risk of HBV acquisition among first graders in Taiwan during a 3-year follow-up period.

Methods

A total of 1545 healthy first graders, who were vaccinated against HBV in infancy, were recruited in 2005. All subjects were checked for hepatitis B surface antigens (HBsAg), antibodies to HBsAg (anti-HBs), and to the hepatitis B core antigen (anti-HBc). Nucleotide sequence of the “a” determinant of HBsAg was determined by polymerase chain reaction and direct sequencing in the HBsAg carriers.

Results

Among 1545 subjects, 0.78% were HBsAg seropositive, 54.30% were anti-HBs seropositive, and 1.68% anti-HBc seropositive. Three of the 10 HBV carriers (30%), whose HBV DNA were sequenced for the S gene, had surface antigen mutants at the “a” determinant.

Conclusion

There were no new chronic HBV infections in this cohort of children for two consecutive years. HBV S gene vaccine escape mutants did exist in the vaccine-failure population, but they may not have made a major health impact.     

Factors associated with effectiveness of the first dose of hepatitis B vaccine in China: 1992–2005

Background

In China, the prevalence of chronic hepatitis B infection was high because of perinatal and early childhood transmission. A three-dose hepatitis B vaccine schedule with a first dose as soon as possible after birth was introduced in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI). In 2006, a serological survey evaluated the effectiveness of vaccination.

Methods

We conducted a restricted analysis of the national serological survey that sampled children and collected information on demographic characteristics, birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg) status as determined by ELISA testing. We compared children who received the first dose in a timely way (i.e., within 24 h of birth) with others in terms of HBsAg status, stratified by birth cohort and place of birth.

Results

Three-dose hepatitis B vaccine coverage increased from 60.8% for children born in 1992–1997 to 93.2% for children born in 2002–2005. Meanwhile, timely birth dose coverage increased from 38.7% to 74.4%. Among 29,410 children born in 1992–2005 who had received three vaccine doses and no hepatitis B immune globulin, factors associated with being HBsAg-negative in multivariate analysis included receiving a timely birth dose (p = 0.04), birth after 1998 (p < 0.001), living in an urban setting (p = 0.008) and hospital birth (p = 0.001). The relative prevalence of HBsAg among children receiving the timely birth dose was lower for children born in county or larger hospitals (0.39), intermediate in township hospitals (0.73) and highest at home (0.87).

Conclusions

Hospital birth and receiving a timely birth dose are the main determinants of the field effectiveness of the first dose of hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries are key to increasing timely birth dose coverage and its effectiveness.     

Long-term efficacy of plasma-derived and recombinant hepatitis B vaccines in a rural township of Central Taiwan

Aims

To assess the differences of long-term efficacy between plasma-derived and recombinant hepatitis B virus (HBV) vaccines and the effectiveness of catch-up vaccination in adolescents with undetectable anti-HBs.

Methods

Before 1992, infants born in Taiwan were immunized using plasma-derived HB vaccine, and thereafter, by using recombinant HB vaccine. From the only junior middle school of a rural township in central–southern Taiwan, 1788 (93.7%) students from five cross-sectional screenings, grouping into three birth cohorts (Group I: born during 1984–1986, II: 1986–1992 and III: 1992–1995), were enrolled for checking HBsAg, anti-HBs and anti-HBc. Students with undetectable HBsAg and anti-HBs underwent a booster dose (2.5 ug) of recombinant HB vaccine (Engerix-B; GlaxoSmithKline, Rixensart, Belgium) and had anti-HBs re-checked 3 weeks later. Individuals who had remained undetectable for anti-HBs completed the other two doses of HB vaccines at 1 and 6 months later.

Results

The prevalence of HBsAg (11.4, 5.4 and 1.2%), anti-HBs (64.5, 44.1 and 36.0%) and anti-HBc (29.5, 12.5 and 4.4%) decreased from Group I to III (P < 0.001 for trends). After a booster dose, the positive rates of anti-HBs increased up to 80.5% (16% increase) in Group I, 81.0% (36.9% increase) in Group II, and 94.4% (58.4% increase) in Group III. The percentages of anamnestic response increased with a trend (P < 0.001). A total of 110 non-responders completed 3 doses of catch-up HB vaccination, but 3 cases (2.7%) of Group II, evoked primary vaccination response.

Conclusion

Recombinant vaccine showed predominant disappearance rate (62.7%) of anti-HBs 12–15 years after vaccination, but provided better anamnestic response after a booster dose. It also showed high success rate (97.3%) in catch-up vaccination in adolescents.     

Using data to guide policy: Next steps for preventing perinatal hepatitis B virus transmission in Cambodia

Background

Cambodia is highly endemic for hepatitis B virus (HBV) infection. Preventing perinatal HBV transmission should be prioritized in health facilities by providing hepatitis B vaccination to all infants within 24 h of birth (timely birth dose coverage).

Methods

Teams assessed birth dose policy, practices and coverage in hospitals and health facilities in 10 provinces in Cambodia.

Results

Fifty-one sites were assessed. Median (interquartile range) timely birth dose coverage was 66% (48–92%); coverage was 88% (range = 60–96%) in facilities vaccinating on-site and 48% (range = 20–52%) in those referring off-site (p < 0.0001). Overall, 5 (29%) of 16 hospitals that referred vaccination off-site did not tell mothers vaccination should take place within 24 h of birth, and 6 (35%) discharged mothers when no vaccination services were available for infants to receive the birth dose.

Conclusions

Newborns can miss a time-sensitive opportunity to be protected against perinatal HBV infection when they are referred for vaccination off-site rather than being vaccinated in the delivery facility. These data support the case to strengthen policies and practices to provide hepatitis B birth dose vaccination in the delivery facility.     

Quantitative evaluation of the effect of the hepatitis B vaccine based on the HBsAg- and anti-HBs-positive rates in the Chinese population over the last 33 years

Objective

The purpose of the study was to quantitatively evaluate the effect of the hepatitis B vaccine based on 33 years of data published on the HBsAg- and anti-HBs-positive rates.

Methods

All data were obtained from studies in published Chinese scientific journals from 1977 to 2009. The HBsAg- or anti-HBs-positive rate over a certain observation period was presented.

Results

When the anti-HBs-positive rate was low, the ability of anti-HBs to control the HBsAg-positive rate is not apparent. When the anti-HBs level is high, the ability of anti-HBs to control the HBsAg-positive rate increases gradually, and a linear relationship was observed between the HBsAg-positive rate and the anti-HBs-positive rate. However, the rate of decrease of HBsAg positivity was markedly higher than the theoretical rate.

Conclusion

The effect of other known or unknown factors, in addition to the vaccination campaign, could have contributed to the decrease in the prevalence of HBV infection.     

Immunogenicity and safety in newborns of a new recombinant hepatitis B vaccine containing the S and pre-S2 antigens.

A study to evaluate the safety and immunogenicity of a recombinant hepatitis B vaccine containing the S and pre-S2 antigens (GenHevac B Pasteur) was conducted in healthy newborn infants. All infants received 20 micrograms of vaccine within 24 h of birth and at 1 and 2 months with a booster injection at month 12. The vaccine was administered alone in 19 infants born to low risk mothers, i.e. surface antigen (HBsAg)-negative and antibody to the core antigen (Anti-HBc)-positive mothers. The vaccine was administered in combination with 100 IU hepatitis B immune globulin (HBIg) at birth and 1 month in 18 infants born to high risk mothers, i.e. HBsAg positive mothers. In the group not receiving HBIg, the anti-HBs seroconversion rate at the 10 mIU ml-1 threshold was 50% 1 month after the first injection. In both groups, the anti-HBs seroconversion rates were 100% 1 month after the third injection and greater than 85% 1 month after the second injection. After the booster injection greater than 90% of the infants had an anti-HBs titre greater than 1000 mIU ml-1 which will probably provide them with adequate protection for several years. The kinetics of the anti-pre-S2 response was similar to that of the anti-HBs response and 100% of infants in both groups had seroconverted 1 month after the second injection of the vaccine. The side effects were scarce, all mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of needle length for response to hepatitis B vaccine in macrosomic neonates: a prospective randomized study

Objectives

The objective of this study was to determine whether use of a longer (1 in.) rather than a standard (5/8 in.) needle used for macrosomic neonates (birthweight over 4000 g) may affect antibody titers after immunization against hepatitis B virus (HBV).

Methods

Fifty nine healthy infants were vaccinated at birth, 1, and 6 months of age with hepatitis B vaccine, with follow up to 7 months of age. Infants were randomized into two groups according to needle length of first vaccine at birth. First group vaccinated with standart needle length and other group received vaccine by longer needle length.

Results

Macrosomic infants who were immunized with a longer needle achieved significantly higher antibody titers to hepatitis B surface antigen than standart needle length (median, 3890.2 vs 1311.7 mIU/mL, respectively; p = 0.001).

Conclusions

Macrosomic neonates benefit from longer needle length with higher levels of antibody titers after HBV vaccination.     

A predictive value of quantitative HBsAg for serum HBV DNA level among HBeAg-positive pregnant women

Background

The high maternal HBV DNA level is the most important factor contributing to HBV perinatal transmission. This study is to explore whether HBsAg can be used as a surrogate marker of serum HBV DNA for HBsAg-positive pregnant women.

Methods

A total of 975 HBsAg-positive pregnant women and their infants were enrolled in this study. All infants received three doses of a yeast-derived recombinant Hepatitis B vaccine at 0, 1 and 6 months. They were also given Hepatitis B immunoglobulin (HBIG) at birth. HBsAg and HBeAg were determined using Abbott Architect assays while serum HBV DNA level was detected by the Abbott Real Time HBV DNA assay.

Results

Of the 975 subjects, 367 (37.6%) were HBeAg-positive and 608 (62.4%) were HBeAg-negative. Among the HBeAg-positive group, the samples with HBV DNA levels of ≥7.0 log IU/mL were 76.6% (281/367), and it was only 0.7% (4/608) for the HBeAg-negative group. HBV DNA level was positively correlated with HBsAg in HBeAg-positive group (r = 0.786, p < 0.001) but not in HBeAg-negative group (r = 0.022, p = 0.593). Among HBeAg-positive group, the area under the receiver–operator curve (ROC) of HBsAg titer for high HBV DNA level (≥7.0 log IU/mL) was 0.961 (95% CI, 0.940–0.983, p < 0.001). The optimum cut-off point HBsAg titer above 4.1 log IU/mL had a sensitivity of 85.1%, specificity of 96.5%, and accuracy of 87.5% to predict HBV DNA levels of ≥7.0 log IU/mL. Of 367 infants born to mothers with HBeAg-positive, perinatal transmission was detected in 24 infants (6.5%, 24/367). Their mothers all had serum HBV DNA levels of ≥7.0 log IU/mL, 23 (95.8%) had HBsAg titers of ≥4.1 log IU/mL and the other mother had HBsAg titer of 3.9 log IU/mL. Of 608 infants born to mothers with HBeAg-negative, only one (0.2%, 1/608) became HBsAg-positive at the age of 7 months, and the mother of the infant had serum HBV DNA level of 3.4 log IU/mL and HBsAg titer of 1.8 log IU/mL, respectively.

Conclusion

Serum HBsAg titer may be used as a surrogate marker of serum HBV DNA for HBeAg-positive pregnant women.