The hepatitis B immunization programme in Singapore

A voluntary immunization programme to prevent perinatal transmission of hepatitis B virus (HBV) infection in Singapore was implemented on 1 October 1985 as an integral component of the national childhood immunization programme. Up to April 1988, a total of 68,845 mothers who attended government maternal and child health clinics were screened for the disease. Of these, 2432 (3.5%) were positive for hepatitis B surface antigen (HBsAg) and 904 (1.3%) for hepatitis B e antigen (HBeAg). Virtually all the babies born to carrier mothers completed the full immunization schedule; and in addition, those of HBeAg-positive mothers were given a dose of hepatitis B immunoglobulin at birth. The hepatitis B immunization programme was extended on 1 September 1987 to cover all newborns. About 90% of the 15,943 babies delivered in government institutions from September 1987 to April 1988 were immunized at birth, with the subsequent doses being administered at maternal and child health clinics at 4-6 weeks and 5 months later. More than 85% of the children given the full course of plasma-derived and yeast-derived hepatitis B vaccine from birth continued to have protective antibody to HBV two years after immunization. The programme is being closely monitored to assess the duration of immunity and the need for booster doses, while seronegative adults are also being encouraged to be vaccinated.     

乙型肝炎疫苗预防接种与疑似不良反应

乙型肝炎(乙肝)是严重危害我国人群健康的传染病,按照2006年全国乙肝血清流行病学调查结果估算,我国总人群中有34％的人感染过HBV,其中HBsAg携带者约为9 300万,每年有大约26万人由于感染HBV导致肝硬化和原发性肝癌死亡?。HBV可通过母婴、血液和性接触三种途径传播,目前尚无有效治愈乙肝的药物,因此接种疫苗成为控制乙肝的关键。     

国产酵母重组乙肝疫苗不同免疫程序免疫的效果观察

应用２批国产酵母重组乙肝疫苗，分别按０、１、２、和０、１、６免疫程序对３９３名小学生进行１年免疫效果观察。所有接种的小学生中未发现严重副反应者。结果表明，免疫程序对抗体阳转率影响较小，第１针免疫后３个月（Ｔ３）时，接种各疫苗组的抗体阳转率均达或接近９０％，第１针免疫后７个月（Ｔ７）时，接种各疫苗组的抗体阳转率均达高峰（９０．００％～９８．２８％），其后开始缓慢下降，而抗体ＧＭＴ与免疫程序有关，０、１、２免疫程序组抗体ＧＭＴ上升快，而０、１、６组抗体峰值高。     

对我国乙型肝炎疫苗扩大免疫的看法

我国血源性乙肝疫苗于1985年底问世,1995年酿酒酵母重组和中国仓鼠卵巢细胞（CliO）重组乙肝疫苗也相继投产,投产前后都进行了以新生儿为主的临床观察,证明是安全有效的。10μg／mL血源性乙肝疫苗以0、1、6月程序免疫出生于表面抗原（HBsAg）、e抗原（HBeAg）双阳性母亲的新生儿,母婴围产期传播阻断率为42．9％;200μg／mL 3针免疫后阻断率为67．4％;第一针30μg／mL,第二、三针100μg／mL免疫后阻断率为75．6％;三针均用30μg／mL免疫的阻断率为82．3％,剂量效应明显（P〈0．05）。     

昆明市甲肝、乙肝和伤寒疫苗接种效益分析

目的对昆明市乙型病毒性肝炎（乙肝）、甲型病毒性肝炎（甲肝）、伤寒等疫苗接种进行成本效益分析,为昆明市针对不同疫苗、不同人群制定免疫接种策略提供科学依据。方法通过调查问卷收集昆明市近年来甲肝、乙肝、伤寒疫苗可预防传染病患者医疗费用资料,进行疫苗接种成本效益比值（BCR）分析。结果本研究共调查样本12563例,其中甲肝1337例、乙肝1881例、伤寒941例。根据疫苗接种的成本效益分析,接种甲肝疫苗的BCR=1.79,每年可避免1827人发病,每年产生净效益1578.98万元;接种乙肝疫苗的BCR=1.80,每年可避免3546人成为乙肝病毒感染者,减少77877.74个工作日的损失,每年产生净效益3002.40万元;接种伤寒疫苗的BCR=1.2,每年可减少1238人发病,减少19468.85个工作日损失,每年产生净效益1141.16万元。结论在人群中实施甲肝、乙肝、伤寒疫苗预防接种能产生巨大的经济效益和社会效益。     

乙肝疫苗扩免策略实施效果评价

目的:评价乙肝疫苗扩免策略实施效果。方法:分析烟台市新生儿乙肝疫苗接种及影响因素,整群随机检测1 543名7～12月龄儿童乙肝表面抗体(Anti-HBs)水平;描述分析15岁以下儿童乙肝发病状况。结果:烟台市新生儿乙肝疫苗接种率、及时率保持在97%以上,阳性母亲的新生儿77.35%采用乙肝免疫球蛋白(HBIG)联合阻断;5μg啤酒酵母扩免乙肝疫苗具有较高的免疫原性,80.75%儿童能够产生保护性应答,接种医院级别及父母乙肝感染状况是影响免疫应答的因素;扩免策略实施后儿童乙肝发病率大幅下降,5年降低了78.99%。结论:烟台市新生儿乙肝疫苗免疫策略效果显著,强化产科培训,正确把握接种禁忌,普及孕妇HBV检测,完善低/无应答者免疫将进一步降低乙肝发病率。     

One year evaluation of immunogenicity conferred by a Chinese hamster ovary cell recombinant hepatitis B vaccine in a French Polynesian newborn immunization programme.

In 1988, a hepatitis immunization programme, using a Chinese hamster ovary (CHO) cell recombinant vaccine, was implemented for newborn children in the Austral archipelago (French Polynesia). Three different schedules were used: (i) 4 vaccine doses at months (M) 0, M1, M2 and M12; (ii) 3 vaccine doses at M0, M1, M6; and (iii) 3 vaccine doses at M0, M1, M2. Results at the one year follow-up may be summarized as follows. Of 197 infants who received one or more doses of CHO-recombinant vaccine, (i) none was an HBsAg carrier; (ii) 89.5% had anti-HBs-antibody titres greater than 10 miu/ml; and (iii) 95.9% had seroconverted for at least one of the 2 antibodies studied (anti-HBs or anti-pre-S2). After 2 doses (M0, M1), anti-HBs seroconversion rate and geometric mean titre were, respectively, 82.6% and 98.47 miu/ml. After 3 doses, seroconversion rates and geometric mean titres were, respectively, 91.1% and 200.59 miu/ml using schedule M0, M1, M2, and 100% and 1253.4 miu/ml using the M0, M1, M6 schedule. None of the 7 vaccinated neonates born to HBsAg/HBeAg positive mothers was found to be an HBsAg carrier. These preliminary results indicate that, in field conditions, vaccination with a CHO-recombinant vaccine resulted in high immunogenicity.     

Efficacy of a mass hepatitis B immunization program after switching to recombinant hepatitis B vaccine: a population-based study in Taiwan

To study the efficacy of immunization against hepatitis B after plasma-derived vaccine was replaced by recombinant vaccine, 2-year-old Taiwanese children were recruited by stratification random sampling and tested for hepatitis B markers. They were grouped according to maternal infectivity and children's immunization status. Of 2010 children, 2.5% had hepatitis B surface antigen (HBsAg), 94.1% had its antibody (anti-HBs), 6.8% had core antibody, and 3.3% were seronegative. Children of highly infectious mothers immunized with hepatitis B immunoglobulin and vaccine on schedule had a lower HBsAg-positive rate and a higher anti-HBs-positive rate than those with vaccine only and off-schedule. The efficacy of the Taiwanese mass hepatitis B immunization was maintained after switching to recombinant hepatitis B vaccine.     

A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine

A randomised trial was conducted in 285 adults not immune to hepatitis B (HB) to compare the safety and immunogenicity of a commercial aluminium-adjuvanted HB vaccine with and without an additional new adjuvant (AgB/RC-210-04 or AgB study groups, respectively). The additional adjuvant RC-529 is a fully synthetic monosaccharide mimetic of monophosphoryl lipid A. Subjects in the AgB/RC-210-04 (n=136) and AgB (n=149) groups were vaccinated intramuscularly on days 0, 30, and 180, according to the standard vaccination schedule for hepatitis B vaccines. Serum levels of anti-HBs were measured on days 30, 60, 90, 180, and 210. Standard safety assessments were made throughout the study period. The rates of seroprotection (anti-HBs > or =10.0 mIU/ml) were significantly greater for the AgB/RC-210-04 group at all time points: at day 90, the seroprotection rate, the primary endpoint of the trial, was 99% for AgB/RC-210-04 compared with 84% for AgB (p<0.0001). Similarly, geometric mean anti-HBs titres were significantly higher at all time points for the AgB/RC-210-04 group. There were more local reactions in the AgB/RC-210-04 group, however they were transient and this double-adjuvanted formulation was well tolerated. We conclude that the addition of a synthetic adjuvant to the AgB vaccine significantly enhanced the immunogenicity of the commercial vaccine AgB. The results indicate furthermore that a two-dose regime of the double-adjuvanted vaccine (schedule: 0-1 month) may be sufficient to achieve seroprotection in nearly 100% of individuals.     

1 500名儿童重组乙型肝炎疫苗免疫效果观察

目的 评价临沂市儿童重组酵母乙型肝炎疫苗接种8年后的免疫效果。方法 采取随机整群抽样法，采用固相放射免疫法（SPRIA）检测血清HBsAg、抗-HBs和抗-HBc水平，并对免疫后HBsAg阳性原因进行分析。结果 1500名3～8岁儿童中HBsAg阳性率为0.47%，疫苗免疫保护率为89.00%，抗-HBc阳性率为2.07%，各年龄组比较差异无统计学意义。抗-HBs阳性率为44.47%，但随年龄增大抗体阳性率下降。几何平均滴度为58.03mIU/mL，各年龄组比较差异无统计学意义。在7例HBsAg阳性儿童中，57.14%儿童的母亲HBsAg阳性。结论 重组酵母乙型肝炎疫苗接种3～8年后，免疫人群保护效果理想，HBsAg阳性率未随免疫时间延长而明显增加。重组酵母乙型肝炎疫苗接种后抗-HBs阳性率随年龄增大而下降，应加强血清学监测。     

北京市1992—2013年乙肝疫苗免疫规划对急性乙肝成本效果分析

目的 评价北京市1992—2013年急性乙肝报告发病率指标与乙肝疫苗免疫规划总成本之间的成本效果关系。 方法 以乙肝疫苗免疫规划总成本为成本指标,对急性乙肝发病率进行成本效果分析,主要包括成本分析、增量成本效果比以及边际效果分析。 结果 1992—2013年间北京市乙肝疫苗接种的总成本增加,人力成本占比上升;随着乙肝疫苗免疫规划总成本的增长,急性乙肝发病率先增长后下降,由1992年的3.58/10万人下降到2013年的1.34/10万人;多期间增量成本效果比方面,1999—2005年这一期间的增量成本效果比较好。 结论 乙肝疫苗成本变化符合实际发展规律;急性乙肝发病率的变化可能与流动人口中乙肝病毒携带者数量增加、传染病报告规定变化、乙肝诊断标准变化以及机构投入优化有关;急性乙肝的发病率随成本投入的增加而下降,但是最优组合尚未出现,可进行乙肝疫苗免疫规划的跟踪评估并结合实际调整防控策略。     

An evaluation of the efficacy of the national immunization programme for hepatitis B

We report an evaluation of the Israeli national immunization programme for hepatitis B in the Haifa subdistrict. We used a convenience sample of blood tests reported positive for HBsAg over a 6-year period from children who were born after routine immunization began in 1992. We identified 11 children with presumed chronic hepatitis B virus infection who were residents of the Haifa subdistrict, three of whom were born in Israel. All three were immunized at the appropriate age and are thus considered vaccination failures rather than failure to vaccinate. The remaining eight were born abroad, had emigrated to Israel as children and were not immunized at birth. We estimate the rate of chronic hepatitis B virus infection for children born since 1998 to be 0.24/10,000 births. For all children resident in the subdistrict under the age of 12 years, the period prevalence is estimated to be 1.26/10,000. The rate of chronic infection in children younger than 12 years was significantly less than that of older cohorts and less than that of historical controls before the start of immunization. Although the reported rates are probable underestimates of actual rates, the fact that they are based on testing carried out in clinical settings increases the likelihood of positive findings and thus reduces the degree of error. The fact that most young carriers are foreign born points to the importance of timely catch-up programmes. In countries with low and intermediate rates of chronic infection, serosurveys of immunized children need to be large and are therefore costly. Monitoring HBsAg positive tests from routine testing carried out in clinical settings is an inexpensive way to monitor chronic infection rates.     

Efficiency of the incorporation of the hepatitis A vaccine as a combined A+B vaccine to the hepatitis B vaccination programme of preadolescents in schools

In 1998, the Department of Health of Catalonia (Spain) began universal vaccination of preadolescents against hepatitis A by replacing the simple hepatitis B vaccine with a combined hepatitis A+B vaccine. Economic analyses were made of the two alternative strategies: to continue with the simple hepatitis B vaccination or to replace the simple vaccine with a combined hepatitis A+B vaccine. The analysis was made from the societal perspective and the time horizon considered was 25 years. In the base case, (estimated annual hepatitis A incidence of 15 per 100,000 and incremental price of the hepatitis A+B vaccine over the simple hepatitis B vaccine of 1.98) the net present value of the programme was positive (+533,708) and the benefit-cost ratio was 2.58. If the estimated disease incidence were reduced by half, the programme would still be efficient.     

Assessment of vaccine wastage during a pulse polio immunization programme in India

A study to assess the wastage factor of oral polio vaccine (OPV) in the Pulse Polio Immunization (PPI) programme of the Government of India was undertaken by the Indian Council of Medical Research (ICMR) at approximately 31,000 immunization booths all over the country. The study was conducted through the network of 31 Human Reproduction Research Centres (HRRCs) and other ICMR institutes. Wastage at the point of administration of OPV was estimated to be 14.5% with a wastage factor of 1.17 which is well below the assumed wastage of 33% and the corresponding wastage factor of 1.5 in the PPI programme. The wastage and wastage factor as estimated in the present study were also less than the wastage of 25% and the wastage factor of 1.33 recommended by the World Health Organization. Minimum wastage (6.3%) at Kanchipuram and maximum wastage (22.1%) at Kanpur were observed. Further, the wastage of unopened vials and vials during use was also observed following colour changes on the vaccine vial monitor (VVM), indicating poor cold-chain maintenance at the immunization site. In total, 13 booths reported wastage of nine or more unopened vials, whereas 19 booths reported wastage of nine or more vials during use because of colour changes on VVM. Other reasons for wastage of vaccine were also observed from a sample of booths. The technology of introducing VVM on OPV vials for monitoring the cold-chain proved useful in situations in which mass vaccination programmes such as PPI are carried out.     

广东省实施新生儿乙肝疫苗接种后免疫效果评价

目的评价实施新生儿乙肝疫苗接种后的免疫效果。方法采用多阶段随机抽样方法,于2006年9月在广州市越秀区、云浮市云城区、汕尾市城区、肇庆四会市、韶关南雄县、梅州五华县等6个国家疾病监测点,抽取1～14岁儿童进行调查,用酶联免疫吸附试验方法检测HBV血清标志物[乙肝病毒表面抗原(HBsAg)、乙肝病毒表面抗体(抗-HBs)、乙肝病毒核心抗体(抗-HBc)],并与1992年同年龄段儿童的HBV流行情况进行比较。结果共调查1951名1～14岁儿童,其乙肝疫苗全程接种率为59.7%(1165/1951),其中1～4岁为88.8%(649/731),5￣14岁为42.3%(516/1220);1￣14岁儿童中免疫组HBsAg阳性率(2.3%,28/1211)低于未免疫组(10.8%,18/167)和免疫史不详组(7.5%,43/573),差异有统计学意义(P<0.01);乙肝疫苗首针在出生后当天或第2天接种儿童的HBsAg阳性率为1.4%(10/734),低于第3天以后才接种者(3.8%,18/477),差异有统计学意义(P<0.05);1￣14岁儿童HBsAg阳性率为4.6%(89/1951),其中1￣4岁儿童HBsAg阳性率为1.9%(14/731),与1992年比较分别下降了76.9%、88.6%(P<0.01)。结论实施新生儿乙肝疫苗接种取得良好免疫效果,出生后及时接种免疫效果更好。     

The cost-effectiveness of introducing hepatitis B vaccine into infant immunization services in Mozambique

OBJECTIVE: To estimate the cost-effectiveness of introducing hepatitis B vaccine into routine infant immunization services in Mozambique, which took place in the year 2001. METHODS: A decision analytic model was used to estimate the impact of hepatitis B vaccination. This model was developed for the WHO to estimate the global burden of disease from hepatitis B. Cost data of vaccine delivery and medical treatment related to hepatitis B infection were collected for the analysis. FINDINGS: The introduction of hepatitis B vaccine has increased the annual budget for immunization services by approximately 56%. It is predicted that more than 4000 future deaths are averted annually by the intervention. In the base case scenario, the incremental costs per undiscounted deaths averted amount to US$436, and the costs per undiscounted DALY averted amount to US$36. Since the major impact of hepatitis B vaccination will not start to be evident for at least another 40 years (deaths from hepatitis B mainly occur between 40-60 years of age), the cost per DALY averted rises to US$47, when using a discount rate of 3% on health effects. We found that the monovalent hepatitis B vaccine was considerably more cost-effective than the hepatitis B vaccine in combination with DTP. INTERPRETATION: If policy makers value future health benefits equal to current benefits, the cost-effectiveness of infant hepatitis B vaccination is in the range of other primary health care interventions for which similar analysis has been undertaken.     

黎平县儿童乙肝疫苗接种率调查分析

目的了解黎平县乙肝疫苗接种率水平及其影响因素,为今后的乙肝预防控制工作提供依据。方法采用分层多阶段随机抽样方法调查30个行政村的目标儿童,同时对儿童家长及各级单位的计划免疫基层接种人员进行相关知识的问卷调查。结果共调查190名儿童,乙肝疫苗首针及时接种率为35.26%(67/190),乡镇所在地村和非乡镇所在地村出生儿童24 h内及时接种率分别为55.17%(32/58)和26.52%(35/132),两率比较差异有统计学意义(P<0.05);在县级医院、乡医院或村卫生室及家中分娩婴儿分别为12、70和108人,首针及时接种率分别为83.33%(10/12)、55.71%(39/70)和16.67%(18/108),各率比较差异有统计学意义(P<0.01))。乙肝疫苗全程及时接种率为33.68%(64/190),乡所在地村和非乡所在地村全程及时接种率分别为55.17%(32/58)和24.24%(32/132),其差异有统计学意义(P<0.01);各级计划免疫工作人员对乙肝疫苗接种知识正确回答率为13.11%(8/61)。结论黎平县儿童乙肝疫苗首针及全程及时接种率较低,应加强首针及时接种工作,提高全程及时接种率,同时应加强计划免疫宣传和健康教育活动,对计划免疫工作人员进行专业知识的系统培训。     

贵州省实施乙型肝炎疫苗免疫策略的成本-效果分析

目的 分析贵州省实施乙型肝炎疫苗(Hepatitis B vaccine,HepB)免疫策略的成本-效果。方法 根据贵州省HepB接种情况,1992年、2006年、2014年贵州省乙肝血清流行病学调查结果,计算全省不同时期HepB接种投入以及接种HepB的成本效果比值(Cost-Effectiveness Ratio,CER)。结果 贵州省1999-2016年共接种HepB 25951786剂次。全省推广使用HepB、纳入免疫规划并联合查漏补种免疫策略18年,共减少HBsAg携带者3195730例,减少慢性乙肝319573例,减少肝硬化31957例,减少肝癌3196例。1999-2016年贵州省实施HepB免疫策略总投入成本675亿元,18年间接种HepB每减少1例HBsAg携带者、慢性乙肝、肝硬化及肝癌病例需投入的成本为19013元,其中,推广使用HepB疫苗时期(1999-2002年)、纳入免疫规划并联合HepB查漏补种时期(2003-2010年)以及后HepB常规免疫时期(2011-2016年)接种HepB每减少1例HBsAg携带者、慢性乙肝、肝硬化及肝癌病例需投入的成本分别为57979元、7809元和35912元。结论 接种HepB对降低贵州省接种人群乙肝发病水平具有良好的成本-效果,2003-2010年将HepB纳入免疫规划并联合查漏补种免疫策略的成本效果最好。     

Prevalence of hepatitis B virus infection in Tonga: identifying high risk groups for immunization with hepatitis B vaccine

A serological survey for evidence of hepatitis B virus (HBV) infection was conducted in the Kingdom of Tonga as the first step in developing a strategy for an immunization programme. There were 414 individuals from the general population plus 137 pregnant women included in the survey. HBsAg was found in 20% of the general population and 88% had one or more serologic markers of HBV infection. In the 5-9 year age group, 80% of the children had one or more markers of HBV, and in the 10-19 year age group, the prevalence was 96.4%, indicating that most transmission of HBV in the Tongans studied occurs in the young. Of the pregnant women studied, 15% were positive for HBsAg, and 57% of those positive for HBsAg were also positive for HBeAg. Evidence of delta virus infection was not found in any of 82 HBsAg positive sera tested. Surveillance data suggested that significant serious sequelae to HBV infection (cirrhosis and primary hepatocellular carcinoma) also occur in Tonga. Immunization of infants and children is the most effective strategy for reducing or eliminating HBV infection and its sequelae in developing countries like Tonga.