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.     

Prevention of perinatal hepatitis B virus transmission in the Netherlands, 2003-2007: children of Chinese mothers are at increased risk of breakthrough infection

Background

In the Netherlands, different hepatitis B vaccination schedules have been used for children born to HBV-infected mothers. All schedules included a birth dose of hepatitis B immunoglobuline (HBIg). We assessed determinants of perinatal HBV transmission and determinants of anti-HBs titers in infants born to HBsAg positive mothers.

Methods

We included infants born to HBV infected mothers between 1.1.2003 and 30.6.2007, using national databases and a separate database for Amsterdam. Risk factors for perinatal transmission and determinants of the anti-HBs titer were studied using logistic and linear regression, respectively.

Results

Of 2657 infants registered in the national database, 91% were registered to have received HBIg and at least three hepatitis B vaccinations. In Amsterdam, this coverage among 413 children at risk was higher (96%, p < 0.01). Serological test results for 2121 infants (80%) indicated that 13 (0.6%) were HBsAg positive. A mother of Chinese descent was the only risk factor for perinatal HBV infection identified (RR 9.1, 95% CI 3.1–26.8). Receiving a birth dose of hepatitis B vaccine later than in the first week of life was not associated with an increased risk of perinatal HBV infection. A shorter period between last vaccination and testing, and having received more doses of hepatitis B vaccine were independently associated with a higher anti-HBs titer.

Conclusions

Infants born to Chinese mothers were at increased risk of perinatal HBV infection. All HBsAg positive pregnant women of Chinese origin should be assessed to determine whether there is an indication for anti-viral treatment during pregnancy. Among infants who received HBIg at birth, we did not detect an increased risk of perinatal HBV infection when the first dose of hepatitis B vaccine was administered after the first week of life.     

Hepatitis B vaccine alone may be enough for preventing hepatitis B virus transmission in neonates of HBsAg (+)/HBeAg (−) mothers

Background and aimTo prospectively evaluate the efficacy of vaccine alone compared with vaccine plus HBIG for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (−) mothers.MethodsCombined immunization is currently recommended for neonates of HBsAg (+) mothers in China. As a result, a randomized design is infeasible due to ethical reasons. In practice, Guangxi Zhuang Autonomous Region and Jiangsu Province implement vaccine alone and vaccine plus HBIG strategies for neonates born to HBsAg (+)/HBeAg (−) mothers, respectively. We alternatively enrolled neonates of HBsAg (+)/HBeAg (−) mothers from these two regions. Three doses of a recombinant yeast-derived hepatitis B vaccine were given at 0, 1 and 6 months with or without HBIG at birth.ResultsAt 7 months, sera were collected from 132 neonates in Guangxi Zhuang Autonomous Region and 752 neonates in Jiangsu Province. Baseline characteristics of both mothers and neonates were comparable in the two regions. No differences were revealed regarding the occurrence of perinatal HBV transmission with or without HBIG at birth [0.1% (1/752) vs. 0.0% (0/132), p = 1.000]. The anti-HBs response rates were 97.7% (129/132) and 98.5% (740/751) for the neonates with vaccine alone and with HBIG (p = 0.758), respectively. Vaccine alone induced a significantly higher anti-HBs GMC as compared to vaccine plus HBIG at 7 months of age (1555.3 mIU/mL vs. 654.9 mIU/mL, p < 0.0001). At 12 months of age, protective levels of anti-HBs remained in 97.4% (596/612) and 98.3% (118/120) of the neonates receiving and not receiving HBIG, respectively (p = 0.771). The neonates receiving combined prophylaxis had a markedly lower anti-HBs GMC (210.7 mIU/mL vs. 297.0 mIU/mL, p = 0.011). Horizontal HBV transmission occurred in none of the successfully immunized neonates for both compared groups at 12 months of age.ConclusionsVaccine alone may be enough for preventing HBV transmission in neonates of HBsAg (+)/HBeAg (−) mothers.     

乙型肝炎表面抗原和e抗原阳性产妇所生新生儿乙型肝炎母婴传播阻断效果的影响因素

目的探讨乙型肝炎(乙肝)表面抗原(HBsAg)和e抗原(HBeAg)阳性产妇所生新生儿在出生后乙肝疫苗(HepB)和乙肝免疫球蛋白(HBIG)联合免疫以及完成HepB全程免疫后乙肝病毒(HBV)突破性感染的影响因素。方法2016年6月-2017年5月在南昌市2个县(区)选择HBsAg和HBeAg阳性产妇所生新生儿,在联合免疫和HepB全程免疫完成后1-2个月检测血清HBsAg和乙肝表面抗体(HBsAb),分析儿童母婴传播阻断失败率(HBsAg阳性率)。结果本研究共纳入278名婴儿,母婴传播阻断失败率为2.52%(7/278),HBsAb阳性率为96.8%(269/278)。产妇HBsAg阳性时间在2年以上是阻断失败的危险因素,而分娩方式、喂养方式、母亲和婴儿HBIG的使用情况和婴儿性别等与HBV阻断失败率无相关性。结论HepB和HBIG联合免疫对HBsAg和HBeAg阳性产妇所生新生儿具有较好的乙肝母婴传播阻断效果,建议加强育龄妇女HBsAg和HBeAg筛查。     

Post-vaccination serological test results of infants at risk of perinatal transmission of hepatitis B using an intensified follow-up programme in a London centre

Immunisation of infants born to hepatitis B virus (HBV) infected mothers is an important public health measure to prevent mother-to-child transmission of HBV. Post-vaccination serological tests (PVST) inform the success of the infant HBV immunisation programme and identify infected infants. Previous studies suggested that the rates of PVST in the UK programme were unsatisfactory. We introduced an intensified local follow-up programme and offered an earlier PVST 2–3 months after the third vaccination at age 4–5 months. Of 219 infants born between 2009 and 2011, 193 infants (88.1%) had at least one PVST: 145 (66.2%) early; 94 (42.9%) standard; 46 (21.0%) both and 26 (11.9%) never tested. Twenty-four infants were identified as high risk for mother-to-child transmission according to national criteria and received both hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine at birth. These infants had a significantly lower hepatitis B surface antibody (anti-HBs) levels at early PVST compared to the lower risk group who received hepatitis B vaccine only (median of 59 vs. 376 mIU/ml, P = 0.006). None of the infants tested were infected with hepatitis B. This study illustrates that the rate of PVST can be improved by using an intensified follow-up programme offering an early PVST. The significantly lower anti-HBs levels in the HBIG subgroup is of concern as this group of infants is already at higher risk for acquiring HBV infection. Infants with poor antibody responses can be identified by an early PVST and offered a timely extra booster dose.     

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.     

乙型肝炎母婴传播阻断成功儿童乙型肝炎病毒突破性感染的特征

目的了解乙型肝炎(乙肝)母婴传播阻断成功儿童乙肝病毒(HBV)突破性感染及其影响因素。方法选取江苏省淮安市淮安区2009年9月-2011年1月乙肝表面抗原(HBsAg)阳性母亲所生儿童,且乙肝母婴传播阻断成功。阻断成功定义为儿童按国家免疫程序在完成出生时乙肝疫苗(HepB)和乙肝免疫球蛋白以及1、6月龄HepB接种后7-12月龄HBsAg阴性,HBV突破性感染定义为阻断成功儿童在12月龄后HBsAg阳性或24月龄后乙肝核心抗体(HBcAb)阳性。至2019年9月进行5次随访并检测HBV血清标志物,分析HBV突破性感染及其影响因素。结果本研究共纳入儿童390名,其中12名29-117月龄儿童发生HBV突破性感染,发生率为3.08%(12/390),均为乙肝核心抗体(HBcAb)阳性和HBsAg阴性。乙肝疫苗(HepB)初次免疫无、低、正常、高应答儿童HBV突破性感染率分别为25.00%、6.67%、2.61%、0.95%;母亲HBeAg阳性、阴性的儿童分别为9.76%、0.00%;母亲高、低HBV病毒载量的儿童分别为11.96%、0.34%。儿童HBV突破性感染发生密度为0.36/100人年;多因素Cox回归分析显示,HepB初次免疫低或无应答、母亲高病毒载量是儿童HBV突破性感染的危险因素(HR=5.91,95%CI:1.87-18.71;HR=45.81,95%CI:5.88-356.96)。结论乙肝母婴传播阻断成功儿童的HBV突破性感染发生率较低;母亲HBeAg阳性、母亲高HBV病毒载量、HepB初次免疫低或无应答的儿童更易发生突破性感染。     

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.     

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.     

中国2014年HBsAg阳性母亲所生1～14岁儿童乙型肝炎血清流行病学特征分析

目的 分析HBsAg阳性母亲所生1～14岁儿童乙肝血清流行病学特征。方法 以2014年全国乙型肝炎（乙肝）血清流行病学调查中母亲HBsAg阳性的1～14岁儿童作为研究对象,采用SPSS 18.0软件分析不同性别、年龄、民族、出生地点、城乡、地区的儿童HBsAg、抗-HBs、抗-HBc阳性率以及HBsAg、抗-HBs影响因素等。结果 共分析HBsAg阳性母亲所生的1～14岁儿童645人,HBsAg、抗-HBs、抗-HBc阳性率分别为3.41%（22/645）、71.94%（464/645）、7.60%（49/645）。其中,1～、3～、5～、10～14岁组HBsAg阳性率分别为1.27%（3/236）、3.23%（6/186）、5.71%（8/140）、6.02%（5/83）,抗-HBs阳性率分别为85.17%（201/236）、69.35%（129/186）、56.43%（79/140）、66.27%（55/83）,抗-HBc阳性率分别为4.66%（11/236）、5.38%（10/186）、11.43%（16/140）、14.46%（12/83）。多因素logistic分析结果显示,出生地点、首针乙型肝炎疫苗（HepB）接种时间是影响HBsAg阳性母亲所生儿童HBsAg阳性率的主要因素,在医院外出生儿童HBsAg阳性率高于在医院内出生者（OR=7.47,95%CI：1.50～37.25）,首针HepB出生后> 24 h接种儿童HBsAg阳性率高于出生后≤24 h接种者（OR=6.21,95%CI：2.15～17.99）。结论 我国乙肝母婴阻断取得一定成效。住院分娩和首针HepB及时接种仍是新生儿乙型肝炎母婴阻断工作的重点。     

Assessing the impact of the routine childhood hepatitis B immunization program and the need for hepatitis B vaccine birth dose in Sierra Leone, 2018

Sierra Leone is highly endemic for hepatitis B virus (HBV) infection and thus recommends three doses of hepatitis B vaccine (HepB3) from 6 weeks of age but does not recommend a birth dose (HepB-BD) to prevent mother-to-child transmission (MTCT). We evaluated impact of the existing HepB3 schedule and risk for MTCT of HBV. We conducted a community-based serosurvey among 4–30-month-olds, their mothers, and 5–9-year-olds in three districts in Sierra Leone. Participants had an HBV surface antigen (HBsAg) rapid test; all HBsAg-positive and one HBsAg-negative mother per cluster were tested for HBV markers. We collected children’s HepB3 vaccination history. Among 1889 children aged 4–30 months, HepB3 coverage was 85% and 20 (1·3% [95% CI 0·8–2·0]) were HBsAg-positive, of whom 70% had received HepB3. Among 2025 children aged 5–9 years, HepB3 coverage was 77% and 32 (1·6% [1·1–2·3]) were HBsAg-positive, of whom 56% had received HepB3. Of 1776 mothers, 169 (9·8% [8·1–11·7]) were HBsAg-positive. HBsAg prevalence was 5·9% among children of HBsAg-positive mothers compared to 0·7% among children of HBsAg-negative mothers (adjusted OR = 10·6 [2·8–40·8]). HBsAg positivity in children was associated with maternal HBsAg (p = 0·026), HBV e antigen (p < 0·001), and HBV DNA levels ≥ 200 000 IU/mL (p < 0·001). HBsAg prevalence was lower among children than mothers, for whom HepB was not available, suggesting routine infant HepB vaccination has lowered HBV burden. Since HBsAg positivity in children was strongly associated with maternal HBV infection and most of the HBsAg-positive children in the survey received HepB3, HepB-BD may prevent MTCT and chronic HBV infection.     

江苏省农村地区儿童乙型肝炎疫苗免疫效果及其影响因素研究

目的探讨江苏省农村地区儿童接种乙型肝炎(乙肝)疫苗后免疫效果及其影响因素。方法采用多阶段分层随机整群抽样方法,抽取江苏省农村地区在实施乙肝疫苗计划免疫后出生的农村儿童为研究对象,检测HBsAg、抗-HBs标志,对抗-HBs阴转儿童进行不同种类疫苗的加强免疫,并分析HBsAg阳性儿童乙肝病毒(HBV)感染的危险因素。结果2522名1～7岁儿童中HBsAg阳性率在0．28%～1．28%之间,抗-HBs随年龄增加而逐渐下降,由1岁时的76．7%降至7岁时的45．5%;出生时未及时接种乙肝疫苗的儿童的HBV感染率显著高于及时接种儿童(1．4%:0．5%, P=0．031);应用不同剂量疫苗加强免疫后,抗-HBs阳转率均为90%以上。结论江苏省农村地区计划免疫适龄儿童人群的HBsAg阳性率为0．28%～1．28%,平均为0．8%,儿童中HBV感染主要为母婴传播,并与未及时接种乙肝疫苗有关。     

江西省两个地区乙型肝炎表面抗原阳性母亲所生新生儿乙型肝炎病毒母婴传播阻断效果和影响因素

目的探讨乙型肝炎(乙肝)表面抗原(HBsAg)阳性母亲所生新生儿乙肝疫苗(HepB)和乙肝免疫球蛋白(HBIG)联合免疫后的乙肝母婴传播阻断效果和影响因素。方法2016年6月-2019年1月在江西省两个区县选择HBsAg阳性母亲所生新生儿,实施首剂HepB(HepB1)和HBIG联合免疫以及HepB全程免疫,全程免疫后1-2个月检测血清HBsAg和乙肝表面抗体(HBsAb),分析HBsAg阳性率和影响因素。结果本研究共纳入HBsAg阳性母亲所生新生儿2281名,HepB1、HepB1联合HBIG、HepB全程及时接种率分别为99.43%、94.83%、30.47%;全程免疫后HBsAg阳性率为0.61%,HBsAb阳性率为98.47%;乙肝e抗原(HBeAg)同时阳性、阴性母亲的婴儿HBsAg阳性率分别为2.08%、0.12%(Fisher确切概率法,P=0.000)。结论HepB和HBIG联合免疫可有效阻断乙肝母婴传播;需探讨HBsAg和HBeAg同时阳性孕妇所生新生儿的乙肝母婴传播阻断措施。     

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.     

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.     

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.     

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.     

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.     

Adolescent booster with hepatitis B virus vaccines decreases HBV infection in high-risk adults

BackgroundNeutralizing antibodies (anti-HBs) after immunization with hepatitis B virus (HBV) vaccines against HBV surface antigen (HBsAg) wane after 10–15 years. We analyzed the effect of an adolescent booster given to vaccination-protected children born to mothers with different HBsAg-carrying status against HBV infection in their mature adulthood.MethodsA total of 9793 individuals, who were HBsAg-negative at childhood (baseline) and donated blood samples, both during childhood and adulthood, from the vaccination group in “Qidong Hepatitis B Intervention Study”, were enrolled. Among them 7414 received a one-dose, 10 μg-recombinant HBV vaccine booster at 10–14 years of age. At endpoint (23–28 years of age), we determined the HBV serological markers and quantified their serum HBV-DNA in each of the chronic HBV-infected adults.ResultsFifty-seven adults were identified as chronic HBV infection, indicated by HBsAg(+)&anti-HBc(+) for more than 6 months. The individuals who were born to HBsAg-positive mothers (high-risk adults) had significantly increased risk of developing chronic HBV infections in adulthood compared with those who were born to HBsAg-negative mothers; the adjusted odds ratio (OR) was 12.56, 95%CI:7.14–22.08. The seronegative status of anti-HBs at 10–11 years of age significantly increased the risk of HBV infections among the high-risk adults. When HBsAg(−)&anti-HBc(+) children who were born to HBsAg-positive mothers 70% of them remained as the status and 10% of them developed HBsAg(+)&anti-HBc(+). While when they were born to HBsAg-negative mothers 1.05% HBsAg(−)&anti-HBc(+) children developed HBsAg(+)&anti-HBc(+) and 24.74% of them remained as the status in 12–18 years. One dose of adolescent booster showed significant protection on high-risk adults from chronic HBV infection; P for trend was 0.015.ConclusionsMaternal HBsAg-positive status was an independent risk factor for vaccination-protected children to develop HBV breakthrough infection in adulthood. Adolescent boosters might be appropriate for high-risk individuals who were born to HBsAg-positive mothers when their serum anti-HBs < 10 mIU/ml.     

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.