Economic evaluation of infant and adolescent hepatitis B vaccination in the UK

A Markov model of hepatitis B virus (HBV) disease progression in the UK estimated that 81% of predicted HBV-associated morbidity and mortality could be prevented by universal infant vaccination at a cost of approximately £260,000 per QALY gained.Universal adolescent vaccination would be less effective (45% prevented) and less cost-effective (£493,000 per QALY gained). Higher HBV incidence rates in males and intermediate/high risk ethnic populations meant it was approximately 3 times more cost-effective to vaccinate these groups. At current vaccine costs a selective infant vaccination programme, based on vaccinating intermediate/high risk ethnic populations would not be considered cost effective.The threshold cost per vaccinated child at which the programme would be considered cost-effective was investigated. Universal infant vaccination would be cost-effective if the average cost of vaccinating each child against HBV, including vaccine and administration costs of all doses, was less than £4.09. Given the low cost of vaccination required to make a universal programme cost-effective the most feasible policy in the UK would be to use a suitably priced combined vaccine that included the other antigens in the current infant vaccination schedule.     

Hepatitis B vaccination strategies tailored to different endemicity levels: Some considerations

Hepatitis B is a serious public health problem. Worldwide three different levels of hepatitis B endemicity (high, intermediate and low) can be distinguished. Areas with different levels of endemicity require tailored vaccination strategies to fit the needs for individuals at risk and/or countries, depending on the infection risk per age group, vaccination rate, duration of protection after vaccination, cost effectiveness of vaccination strategies and ease of implementation in the national immunization schedules.This opinion paper evaluates these factors and proposes a combination of infant risk group and universal adolescent vaccination for low endemic countries thus targeting the different groups at risk. A universal infant vaccination schedule starting with a newborn vaccination within 24 h after birth is more appropriate in intermediate- and high-endemic regions.     

城、郊新生儿乙型肝炎疫苗免疫情况调查

目的　了解乙型肝炎疫苗的免疫后效果。方法　于 1997年 9～ 12月在北京、武汉、哈尔滨、上海、成都、兰州和长春 7个城市 ,采用整群随机抽样方法抽取 3～ 4岁年龄组儿童 2 180人进行调查。结果　 1993～ 1994年新生儿乙型肝炎疫苗全程接种率城区为 91.10 % ,明显高于郊区的 84.71%。HBsAg阳性率降至1.5 6% ,抗 -HBs阳性率平均为 70 .5 0 %。城区儿童HBsAg阳性率0 .2 8% ,郊区儿童HBsAg阳性率为2 .17% ,说明免疫儿童中HBsAg阳性者的主要来源在郊区。 结论　上述表明 ,我国乙型肝炎疫苗免疫效果显著 ,但在郊区 ,疫苗免疫效果还不够理想。     

中国乙型肝炎不同流行区最佳免疫策略研究

目的比较在乙型肝炎不同流行区接种乙型肝炎疫苗的成本效益,探讨最佳免疫策略。方法采用成本效益分析方法和综合权重评分法,筛选高中低流行区最佳免疫策略。结果隆安、上海和济南三地接种乙型肝炎疫苗均获明显的经济效益;定义的不同流行区均以低剂量免疫策略（１０μｇ×３方案）的效益成本比值最大,高、中、低流行区分别为４９．９１、５４．５３、３７．６８;具有较高免疫保护率的高剂量免疫策略可获最大净效益;权重综合评分分析显示,低剂量免疫策略为最佳乙型肝炎免疫策略。结论建议经济较落后地区实行低剂量免疫策略,期望获得较大效益成本比;经济发达地区实施高剂量免疫策略,以获较大净效益并明显降低人群ＨＢｓＡｇ阳性率     

Investigation of memory B cell responses to hepatitis B surface antigen in health care workers considered as non-responders to vaccination

Up to 20% of health care workers are considered as non-responders to hepatitis B vaccination (anti-HBs < 10 mUI/ml in serum). We have explored memory B cells differentiated in vitro into anti-HBs antibody-secreting cells (anti-HBs-SCs) by ELISPOT assay. Anti-HBs-SCs were detected in vaccinated responders (n = 11) and non-responders (n = 10) but IgG anti-HBs-SCs were significantly lower in the non-responder group (p < 0.001). Low amounts of HBs antibodies were also quantified by ELISA in non-responders’ sera. These results indicate that a suboptimal B cell response exists in non-responders to HBV vaccination. This B cell response may mediate a protection against clinically significant breakthrough hepatitis B infection.     

乙型肝炎感染危险因素的多因素分析

目的了解不同人群乙肝病毒感染现状,分析乙肝病毒感染的相关危险因素。方法按照全国疾病监测点总体调查抽样方案的要求,进行入户个案调查乙肝感染相关行为危险因素,并采血检测HBV感染情况。调查数据用SPSS 13.0软件进行分析。结果口腔诊疗史（OR=1.498）、输血史（OR=1.434）和创伤性美容史（OR=2.132）是本次调查所得乙肝感染的主要危险因素。不同职业人群存在统计学差异（χ2=364.69,P〈0.001）,工人感染率最高,达到74.14%,不同文化程度人群中以高中（中专）感染率（63.33%）为最高（χ2=221.74,P〈0.001）。乙肝疫苗接种具有良好的保护效果（χ2=318.93,P〈0.001）。结论在重点人群中开展健康教育、改变不正确的行为、掌握正确的防治方法、实施免疫接种是预防控制乙肝的重要措施。     

中国乙型肝炎疫苗免疫预防效果和现行策略的经济学和决策学评估

目的 对中国儿童乙型肝炎(乙肝)疫苗免疫预防14年(1992-2005年)效果评估和对现行的乙肝疫苗接种方案进行优化.方法 构建适合中国乙肝疫苗免疫预防实际效果评估和方案优化决策树模型,模型中参数根据相关研究文献或由专业机构提供.主要分析指标为成本效果比(CER)和效益成本比(BCR),用敏感度分析和阈值分析对各参数影响大小进行评估. 结果 14年间,中国直接和间接地用于新生儿乙肝疫苗接种总投入约为53.48亿元,而获得的总效益达2728.25亿元,即乙肝疫苗接种的净效益为2674.77亿元;同期由于疫苗接种避免发生HBV感染约6523万人,每预防一例HBV感染的费用为81.99元,但每投入1元获得的收益为51.01元.中国现行乙肝疫苗接种采用新生儿3剂5 μg,并于出生24 h内完成第一针;对孕妇筛检HBsAg,阳性者新生儿加注一剂乙肝免疫球蛋白(HBIG)均为最优方案.而新生儿以外的1～60岁人群乙肝疫苗接种仍町以获得正效益,尤其是在20岁以前接种效益更明显;但"筛检后再接种"均优于"直接接种". 结论 中国既往14年间在新生儿中实行的乙肝疫苗接种策略,从实际的预防效果和投资的经济效益看都是值得的;现行的新生儿优先接种并保持高覆盖率的策略仍为合理方案.     

Baseline hepatitis B vaccination coverage among persons with diabetes before implementing a U.S. recommendation for vaccination

Background

Recent data suggest that adults with diabetes are at increased risk of incident hepatitis B infection and may suffer increased morbidity or mortality from chronic hepatitis B infection. In October 2011, the Advisory Committee on Immunization Practices (ACIP) recommended hepatitis B vaccination (HepB) for persons with diabetes aged 19–59 years and stated that persons with diabetes aged 60 years and older should be considered for vaccination.

Objective

To determine HepB coverage among persons with diabetes aged ≥19 years prior to implementation of the new ACIP recommendation and to determine predictors for vaccination.

Methods

We used the 2009 National Health Interview Survey to determine weighted proportions of self-reported HepB coverage (≥1 and ≥3 doses) among persons with diabetes aged ≥19 years. A multivariable logistic regression analysis was performed to determine factors independently associated with vaccination.

Results

Overall, 19.5% (95% CI: 17.4–21.6%) and 16.6% (14.7–18.6%) of persons with diabetes, aged ≥19 years, reported receiving ≥1 and ≥3 doses of HepB, respectively, compared with 30.3% (29.4–31.3%) and 26.5% (25.5–27.4%) among persons without diabetes. While unadjusted HepB coverage was higher among persons without diabetes, diabetes status was not associated with ≥1 or ≥3 dose vaccination. Among persons with diabetes, being a healthcare provider (OR 4.2, 2.5–7.0), ever tested for HIV (OR 2.6, 1.8–3.6), high-risk behaviors (OR 1.8, 1.0–3.4, P-value = 0.053) and having some college education (OR 1.7, 1.2–2.4) were all independently associated with vaccination.

Conclusion

HepB coverage among persons with diabetes is low. These data can be used to provide a baseline for measuring future progress toward vaccination of persons with diabetes.     

Factors predicting response to hepatitis B vaccination in patients with inflammatory bowel disease

Hepatitis-B-seronegative patients with inflammatory bowel disease (IBD) should be vaccinated. However, response to vaccination in this population seems to be poorer than in healthy people. The aim of this study is to assess which clinical, analytical and immunosuppressive therapy parameters affect the response to hepatitis B vaccination in patients with IBD. A follow-up including monitoring of the immunosuppressive therapy of a cohort of 123 patients with IBD was carried out after each round of vaccination against hepatitis B virus. The recombinant HBsAg vaccine (20 μg) was administered using the standard regimen (0, 1 and 6 months). Anti-HBs values >10 IU/L after 1–3 months post-vaccination were considered as a successful response to vaccination. One hundred and five patients (85.5%) completed the programme and response to vaccination was observed in 50 (47.6%) patients. Multivariate analysis showed an independent relationship, with weaker response to vaccination, for IBD duration equal to or longer than 110 months [adjusted OR (95% CI): 0.282 (0.114–0.701)], serum albumin levels below 3.6 mg/dl at the beginning of vaccination [adjusted OR (95% CI): 0.336 (0.112–1.009)], and corticosteroid therapy in more than one vaccination dose [adjusted OR (95% CI): 0.333 (0.135–0.820)]. This study confirms the poor response to hepatitis B vaccination in patients with IBD, being particularly weak in individuals with long-term IBD progression, low serum albumin levels and those on corticosteroid therapy.     

Duration of hepatitis B antibody response in children immunised with hepatitis B and compulsory vaccines

Twenty four subjects were simultaneously administered DT toxoids, OPV and HBV vaccines at the age of 3, 4–5 and 11 months and then followed up for 2 and 4 years in order to evaluate the duration of the immune response and the need and the timing of HBV revaccination. A fall in anti-HBs titre below 10 mIU/ml was observed at the follow up in 4/24 (16.7%) of the subjects. In other 5 children (20.8%) anti-HBs titre was found to be just above 10 mIU/ml. This would suggest that a revaccination is indicated and it could be performed at the age of 5–6 years when children enter school. This schedule is simple, effective and money saving since it reduces the cost/benefit ratio and the number of visits for immunisations, and it is expected to improve the compliance for the vaccination.     

Hepatitis B vaccination of relatives of hepatitis B virus DNA positive carriers: An experience with plasma-derived vaccine

We assessed in a western population the efficacy of a plasma-derived hepatitis B vaccine in relatives of highly infectious hepatitis B virus (HBV) carriers. A consecutive group of 103 HbsAg, anti-HBs and anti-HBc negative household relatives of 45 HBV-DNA positive chronic carriers received a 5 pg dose of plasma-derived vaccine at 0, 1, 2 and 12 months. Protective levels of immunity developed in 101 subjects (97.8%) 3 months after boosting. Low responders to the vaccine were mostly found among parents and spouses of carriers, whilst offspring and siblings were usually high responders. The main discriminant in predicting a good response was age below 12 years. Hyporesponsiveness did not occur in family clusters. No major HBV events occurred among immunized relatives patients. Hepatitis B vaccine is safe and effective in immunizing relatives of HBV carriers while no genetic conditioning of the immune response is evident among them.Corresponding author.     

Hepatitis B vaccination of susceptible elderly residents of long term care facilities during a hepatitis B outbreak

Protection of older persons, particularly those with diabetes, against hepatitis B virus (HBV) infection is of growing concern because of increased reports of outbreaks among long-term care facility residents receiving assisted blood glucose monitoring. We evaluated hepatitis B vaccine immunogenicity among residents immunized in response to two such outbreaks in skilled nursing facilities during June 2009–July 2010. One hundred forty-eight (71%) of 209 residents were found to be susceptible to HBV infection. Of 105 patients who began a vaccination series with Twinrix^® (0-, 1-, 6-month dosing), 86 (82%) completed the series and postvaccination testing. Of these, most were elderly (median age 79.5 years; range 45–101), female (56%), and African-American (51%). Twenty-nine (34%) vaccinated residents had post-vaccination hepatitis B surface antibody levels ≥10 mIU/ml. There were no significant differences in vaccine response by age, gender, race, diabetes status, body mass index, or current smoking status. Our findings indicate that a low proportion of skilled nursing facility residents achieved a seroprotective response after hepatitis B vaccination.     

黑龙江和甘肃省成人乙型肝炎疫苗接种现状和影响因素

目的了解成人乙型肝炎疫苗(HepB)接种率和影响因素。方法采用便利抽样法在黑龙江和甘肃省抽取4个调查点18-59岁常住人口进行问卷调查,分析HepB接种率、全程(≥3剂次)接种率及其影响因素。结果调查对象HepB接种率、全程接种率分别为55.38%(528/1051)、36.73%(386/1051)。HepB接种率和全程接种率均甘肃低于黑龙江(OR=0.37,95%CI:0.26-0.52;OR=0.31,95%CI:0.23-0.43);农民低于政府/事业单位或企业职员(OR=0.25,95%CI:0.15-0.41;OR=0.27,95%CI:0.16-0.47);家庭成员无HBV感染者高于有感染者(OR=0.56,95%CI:0.35-0.91;OR=0.42,95%CI:0.27-0.65);乙肝知识得分>10分者高于得分≤10分者(OR=2.14,95%CI:1.56-2.94;OR=1.97,95%CI:1.42-2.73)。HepB接种率还以40-49岁和50-59岁低于18-27岁(OR=0.59,95%CI:0.36-0.95;OR=0.24,95%CI:0.14-0.41);农村低于城镇(OR=0.40,95%CI:0.27-0.59)。HepB全程接种率还以初中及以下文化程度者低于大学及以上者(OR=0.46,95%CI:0.28-0.75);有医疗保险者高于无保险者(OR=2.26,95%CI:1.27-4.01)。结论成人HepB接种率和全程接种率较低。需加强成人(特别是农村、农民、文化程度较低人群)乙肝防控知识宣传,提高成人HepB接种和全程接种率。     

新生儿乙型肝炎疫苗免疫接种效果分析

目的 观察新生儿应用乙型肝炎疫苗接种的免疫效果,为该地区儿童乙型肝炎预防提供参考.方法 选取2009年5月-2012年8月进行乙型肝炎疫苗接种的0～3岁婴幼儿1187例,根据年龄分为＜1岁组276例、1～2岁组302例、2～3岁组298例和＞3岁组311例,采用ELISA法检测4组新生儿血清中乙型肝炎病毒表面抗原(HBsAg)和乙型肝炎病毒表面抗体(抗-HBs)两项指标,比较不同年龄阶段新生儿免疫情况.结果 1187例婴幼儿抗-HBs阳性率为84.08％,其中＜1岁组为94.57％、1～2岁组为87.75％、2～3岁组为81.54％、＞3岁组为73.63％,4组的抗-HBs阳性率差异有统计学意义(P＜0.05);1187例婴幼儿HBsAg阳性率为0.34％,＜1岁组和1～2岁组均为0、2～3岁组为0.34％、＞3岁组0.96％,4组的HBsAg阳性率差异无统计学意义.结论 接种过乙型肝炎疫苗的新生儿免疫水平随年龄增长开始降低,有必要对≥3周岁儿童再次进行乙型肝炎血清标志物检测,及时采取乙型肝炎预防措施.     

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.     

Assessing potential introduction of universal or targeted hepatitis A vaccination in the Netherlands

In many industrialized countries, hepatitis A incidence rates have declined steadily in the past decades. Since future cohorts of non-vaccinated elderly will lack protection against disease and the burden of hepatitis A is higher with increasing age, this could be an argument in favour of taking preventive measures such as including hepatitis A vaccine into the National Immunisation Program, or offering hepatitis A vaccine to the elderly only. Using a vaccination evaluation scheme, we assessed the potential benefits and drawbacks of introducing hepatitis A vaccine in the National Immunisation Program in the Netherlands. The average number of annual hepatitis A notifications is declining, from 957 in the period 1991 to 1995 to 211 over the period 2006 to 2010. The direct health care costs and costs due to productivity losses per patient are rising, because the age at infection increases and older patients require a relatively higher number of hospitalizations. Initiating a vaccination program would most likely not be cost-effective yet. The annual costs of mass-vaccination are large: about €10 million for infants and €13 million for older people (and only in the first year €210 million), based on current retail prices. The annual effects of mass-vaccination are small: the cost-of-illness in recent years attributed to hepatitis A infection is estimated to be €650,000 per year, and the disease burden is on average 17 DALYs. Given the current low hepatitis A incidence, and the continuing decline in incidence, targeted preventive measures such as vaccinating travellers and other high-risk groups and timely vaccination of close contacts of hepatitis A patients are adequate. However, because susceptibility to hepatitis A is increasing in the group with the highest risk of developing severe complications upon infections, careful monitoring of the epidemiology of hepatitis A remains important.     

乙型肝炎疫苗接种预防乙型肝炎和肝癌效果

目的 评价乙型肝炎(乙肝)疫苗预防乙肝和原发性肝细胞癌(肝癌)的保护效果。方法采用出生队列调查、横断面血清流行病学调查以及乙肝发病和肝癌死亡监测,对乙肝疫苗的预防效果进行评价。结果 婴儿乙肝疫苗普种后14年,接种人群HBsAg阳性率为0.7％～2.9％(平均为1.5％),保护率为83.5％～96.6％;HBV感染率为1.1％～5.1％(平均为2.2％),保护率为93.5％～98.4％。乙肝疫苗普种后15年,1～14岁年龄组乙肝发病率为1.4/10万,下降92.4％;0～19岁组肝癌死亡率为0.17/10万,下降19.23倍。结论 婴儿乙肝疫苗普种可降低急性乙肝发病率和肝癌死亡率。     

Impact of hepatitis B immunization strategies on infection rates in Italy: A deterministic computer simulation

The impact of different immunization strategies on hepatitis B infection rates in Italy oveR a 20 year period is simulated by the means of a simple deterministic mathematical model. The anticipated effect of vaccination of health workers only, of newborns from HBsAg+ mothers, of all newborns, of the entire population are simulated. Immunization of newborns from hbSaG+ mothers is by far the strategy with the greater effectiveness per unit cost.     

乙型肝炎疫苗接种前不筛查是安全的

本文对乙型肝炎疫苗接种前不筛查是否安全问题进行了讨论,从乙型肝炎疫苗的成分、感染和未感染过乙型肝炎病毒者接种乙型肝炎疫苗的结果表明,乙型肝炎疫苗接种前不进行筛查是安全的。