Impact of hepatitis B immunisation as part of the EPI

Since 1992, hepatitis B vaccine has been an integrated part of Thailand's expanded programme on immunisation (EPI). Based on the data from five representative provinces, we have evaluated its impact on the countrywide prevalence of HBV infection and carrier rate. The population studied comprised 400-488 healthy and immuno-competent, subjects per area. The subjects' ages ranged from 6 months to 18 years. We examined their sera for viral hepatitis markers using commercially available test kits and established the coverage rate of hepatitis B vaccination after its inclusion into the EPI to be 71.2-94.3%. The number of individuals undergoing the complete course of vaccinations had increased four-fold. Consequently, only 0.7% of the children born after the implementation of this the novel EPI strategy were HBV carriers.     

Evaluation of a prison-based hepatitis B immunisation pilot project

This paper describes the evaluation findings of a hepatitis B immunisation pilot project, which aimed to increase the uptake and compliance of hepatitis B vaccinations among female prisoners in Victoria. The evaluation used a mixed methods approach including in-depth interviews, focus group discussions and an analysis of quantitative data. Fifty-five per cent of potential participants (391/712) were offered hepatitis B immunisation. Of those offered immunisation, 204 were eligible for immunisation and 169 (83%) received the first dose. Ninety-three per cent of eligible women received two doses and 84% completed the three-dose series. Lessons learnt from the pilot led to the revision of key prison hepatitis B immunisation policies and practices to ensure uniformity across Victorian prisons.     

Early immunisation with hepatitis B vaccine: a five-year study

We evaluated the response to the recombinant Hepatitis B vaccine using an accelerated schedule versus the traditional schedule by studying the immunologic memory induced in 200 children with HBs-Ag negative mothers. At seroconversion, the traditional schedule presented a higher percentage of children with serum HBs-Ag concentrations over 100 mIU/ml than the accelerated schedule. After five years this difference was no longer statistically significant and children who presented anti-HBsAg concentrations below 10 mUI/ml received an additional booster dose which stimulated the antibody concentration to exceed 100 mIU/ml in all cases. Recombinant HBV vaccine induced better long term immunologic memory when it was administered earlier.     

Impact of a targeted hepatitis B vaccination program in Amsterdam, The Netherlands

To evaluate hepatitis B virus (HBV) risk group vaccination in Amsterdam, which started in 1998, we examined 342 reported acute HBV-cases and sequenced 85 DNA isolates. The reported number of cases declined from 214 in 1992-1997 to 128 in 1998-2003, due to a decline in injecting drug users (IDU) and their heterosexual partners. Phylogenetic analyses showed that after 1998, the IDU cluster nearly disappeared, probably due to a decline in injecting. Acute HBV remained stable among men having sex with men; given their increased sexual risk behavior, vaccination has probably prevented an increase in their acute infections. Currently, 48-72% of the people who should be included in the program are still susceptible to HBV.     

The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu

The aims of this project were: (1) to determine the extent to which infant hepatitis B immunisation is preventing chronic hepatitis B infection in children living in a sample of Pacific Island countries; and (2) to identify factors associated with the successful prevention of hepatitis B infection in these populations. A regional hepatitis B immunisation project which supplied hepatitis B vaccine to 10 Pacific Island countries began in 1995. Seroepidemiological surveys were conducted in Fiji, Kiribati, Tonga and Vanuatu in early 1998. These included immunised pre-school children and their biological mothers, and a historical control group of unimmunised students. Prevalence rates for hepatitis B surface antigen (HBsAg) in the populations of students, mothers and their pre-school children were respectively: Fiji: 6.9, 6.6, 0.7%; Kiribati: 27.4, 15.1, 3.8%; Tonga: 11.1, 18.6, 3.8%; Vanuatu: 16.3, 12.3, 3.0%; and for all four countries: 13.2, 12.5, 2.6%. Compared to the historical control group of students, the pre-school population had a much lower probability of HBsAg positivity (relative risk [RR]=0.19 [95%CI: 0.12-0.31]). Statistically significant differences in risk were apparent for all the countries: Fiji: RR=0.10; Kiribati: RR=0.14; Tonga: RR=0.34; Vanuatu: RR=0.19. This is equivalent to an overall program effectiveness of 81% (95%CI: 69-88%) in reducing chronic carriage. Also, the overall protective effectiveness against vertical hepatitis B transmission resulting in HBsAg positivity among children exposed to HBeAg positive and negative carrier mothers, was estimated to be 70%. By age 6 months, when all children should have had three vaccine doses, completed immunisation rates ranged from 22 (Fiji) to 84% (Vanuatu). Coverage of the first dose being given within 2 days of birth varied from 43% in Kiribati to 92% in Tonga. In conclusion hepatitis B immunisation of infants in these four countries is having a substantial beneficial effect in preventing chronic hepatitis B infection. Nevertheless, there is significant scope for further improving the timeliness of immunisation.     

At-birth immunisation against hepatitis B using a novel pre-filled immunisation device stored outside the cold chain.

We evaluated the immunogenicity of hepatitis B (HB) vaccine in UniJect, a pre-filled, non-reusable injection device, stored at tropical temperatures for up to one month and used to give the first dose of HB vaccine to newborns. Infants in Tabanan district, Bali, Indonesia, were given their first dose of HB vaccine with UniJect stored out of the cold chain, UniJect stored in the cold chain; or standard syringe, needle and multidose vial stored in the cold chain. Subsequent doses were given by usual means and blood samples drawn 4-6 weeks after the third dose. No significant differences were found in seroconversion rates or geometric mean titres of HB surface antibody between the three groups.     

Epidemiology of hepatitis B infection in Finland: Implications for immunisation policy

ObjectivesWe describe the current epidemiology of acute and chronic hepatitis B infections in Finland. We estimate the total incidence of chronic hepatitis B following from the current incidence of acute infections and the influx of chronic carriers of hepatitis B associated with net immigration. We evaluate the incidence of hepatitis B infections preventable by a universal vaccination programme among infants.MethodsWe analysed hepatitis B cases reported to the National Infectious Disease Register during 2004–2012 and used pre-developed methods to adjust for acute asymptomatic infections. We estimated the projected incidence of chronic infection by applying age-specific risks of chronic infection to the estimated incidence of acute infection. We estimated the influx of chronic carriers associated with immigration by utilising data on immigration during 2004–2012 and the WHO regional estimates of carriage prevalence.ResultsThe estimated incidence of acute hepatitis B infection in Finland, adjusted for asymptomatic infections, was 1.67 per 100,000 per year (95% Crl 1.43–1.94) which is 4.2-fold to the register-based incidence. The estimated lifetime risks of acute and chronic hepatitis B infections were 0.13% and 0.01%, respectively. We estimated that annually seven new chronic infections would result from infections acquired in Finland. These new chronic infections accounted for 1.2% of the total incidence of chronic infections. We estimated that eventually three chronic infections per year would be potentially preventable by a universal infant vaccination programme.ConclusionsPartly due to the fact that hepatitis B infections in neonates and in children are rare, a very limited number of chronic hepatitis B infections resulted from infection acquired within the country. A vast majority of chronic hepatitis B infections occurred among foreign-born persons and were therefore not preventable by a universal infant immunisation programme in Finland. Even with a targeted immunisation programme, the incidence of hepatitis B infection has remained low.     

Targeted hepatitis B vaccination--a cost effective immunisation strategy for the UK?

OBJECTIVE: To compare the potential cost effectiveness of vaccination against hepatitis B virus (HBV) targeted at genitourinary clinic (GU) attendees with that of universal infant vaccination. DESIGN: A mathematical model of sexual and perinatal transmission of HBV was used to compare the effectiveness among heterosexual and homosexual populations of programmes of mass infant vaccination and targeted immunisation of genitourinary medicine (GU) clinic attendees. Each was applied to 90% of the eligible population with differing assumptions about rates of compliance and seroconversion - problems of delivery (obtaining high compliance) was considered a significant drawback of targeted vaccination. Observed relationships between GU clinic attendance and sex partner change rates for heterosexuals and for homosexuals were used to define the rates of vaccination uptake within sexual activity risk groups. SETTING: England and Wales. RESULTS: Model results showed that for heterosexuals universal infant vaccination became more effective than clinic based vaccination only approximately 40 years after the start of the programme and that the predicted cost effectiveness of GU clinic vaccination was greater at all times. For homosexuals, clinic vaccination was always more effective over the time frame considered, but by 50 years if it were carried out without prior screening it had become appreciably less cost effective than a mass infant programme. With prior screening in GU clinics this cost effectiveness deficit was only marginal. CONCLUSIONS: Targeted vaccination might have a much greater potential than is realised at present, particularly if it were possible to improve compliance of clinic attendees. A fuller comparison between mass infant and targeted vaccination must await the specific inclusion in the model of other risk groups such as intravenous drug users. An important determinant of the relative merits of the two approaches is the relationship between rates of attendance and of changing sexual partners. Further research on this is required.     

Antibody response after hepatitis B immunisation in a group of health care workers

Hepatitis B immunisation has been offered to staff of Hampstead Health Authority since 1982 and is now offered to all staff with clinical contact. Three doses of 20 micrograms of vaccine are given at zero, one, and six months and the antibody response is measured three months later. Results were analysed to seek for associations with the antibody response. At the time of analysis, 2739 people had started vaccination and 1067 had completed the course and had a measurement of antibody response. Vaccine injections were initially into the buttock and later into the arm; measurement of antibody levels was initially by radioimmunoassay (RIA) and later by enzyme immunoassay (EIA). A positive antibody response was defined as a positive/negative ratio of greater than 10 for RIA or a level of greater than 10 mIU/ml for EIA. Associations between antibody response and other variables were tested by chi 2 and a multiple logistic regression analysis was undertaken to examine the effects of variables in combination. The overall antibody response rate was 95%. Men and women did not respond differently but there were significantly more positive responses with the EIA testing method and a tendency for more positive responses with arm injections. The responders were significantly younger than the non-responders and had significantly lower values of body mass index (wt/ht2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of conventional and accelerated hepatitis B immunisation schedules for homeless drug users

This historical control study examines the uptake of two hepatitis B immunisation schedules at an inner city primary care centre for homeless people in Northern England. Originally homeless patients disclosing current or past illicit drug use were offered hepatitis B immunisation. In 1999 a conventional hepatitis B vaccine schedule was offered (immunisations at 0, 1, and 6 months) whereas in 2000 an accelerated schedule was introduced (immunisations at 0, 7 and 21 days). There was an increase in the uptake of hepatitis B vaccination by homeless drug users once the accelerated schedule was introduced. Furthermore, the completion rates for the accelerated vaccination regimen were almost seven times higher than for the conventional one. This indicates that the accelerated hepatitis B schedule should be the regime of choice for patients with a current or past history of drug use.     

Genetic immunisation against hepatitis B using whole bacteriophage lambda particles

Mice and rabbits have been vaccinated with whole bacteriophage lambda particles containing a DNA vaccine expression cassette under the control of the CMV promoter (enhanced green fluorescent protein [lambda-EGFP] or hepatitis B surface antigen [lambda-HBsAg]). Mice were vaccinated twice intramuscularly (i.m.) with 5x10(9) of lambda-EGFP phage (containing 250 ng DNA) and exhibited specific anti-EGFP responses 28 days post-vaccination. Rabbits were vaccinated i.m. with 4x10(10) of lambda-HBsAg phage (2 microg DNA) or recombinant HBsAg protein. Following two vaccinations with lambda-HBsAg, one out of four rabbits exhibited high level anti-HBsAg responses (comparable to those seen using the recombinant HBsAg protein). Following a third vaccination with lambda-HBsAg, all four rabbits showed similar high level responses which have not decreased after more than 6 months. High anti-phage responses were observed in all animals following the first immunization with lambda-HBsAg, indicating that a high antibody titre against the phage carrier did not prevent a subsequent immune response against the DNA vaccine component. Compared to results in mice using equivalent lambda-HBsAg doses, anti-HBsAg responses were much higher in rabbits, which could indicate a swamping effect in mice. Since phage lambda DNA is approximately 50 kb in size (tenfold larger than most plasmid vectors used for naked DNA immunisation), a comparable dose of phage lambda DNA given as intact phage particles actually delivers tenfold less vaccine DNA on a per gene copy (molar) basis. Thus the efficiency of the technique may be even higher than the data at first suggests.     

Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine

BackgroundThe exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence.MethodsSubjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12–15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11–15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: <15 mIU/mL; anti-HBs: <10 mIU/mL).Results209 subjects returned for follow-up at Year 15 of whom 162 were included in the long-term according-to-protocol immunogenicity cohort. All subjects remained seropositive for anti-HAV antibodies, while 81.1% and 81.8% still had anti-HBs antibodies ≥10 mIU/mL in the 2- and 3-dose groups, respectively. Following hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience.ConclusionImmunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination.Trial registrationhttp://www.clinicaltrials.gov NCT00875485.     

Antibody response after hepatitis B immunisation in a group of health care workers.

Hepatitis B immunisation has been offered to staff of Hampstead Health Authority since 1982 and is now offered to all staff with clinical contact. Three doses of 20 micrograms of vaccine are given at zero, one, and six months and the antibody response is measured three months later. Results were analysed to seek for associations with the antibody response. At the time of analysis, 2739 people had started vaccination and 1067 had completed the course and had a measurement of antibody response. Vaccine injections were initially into the buttock and later into the arm; measurement of antibody levels was initially by radioimmunoassay (RIA) and later by enzyme immunoassay (EIA). A positive antibody response was defined as a positive/negative ratio of greater than 10 for RIA or a level of greater than 10 mIU/ml for EIA. Associations between antibody response and other variables were tested by chi 2 and a multiple logistic regression analysis was undertaken to examine the effects of variables in combination. The overall antibody response rate was 95%. Men and women did not respond differently but there were significantly more positive responses with the EIA testing method and a tendency for more positive responses with arm injections. The responders were significantly younger than the non-responders and had significantly lower values of body mass index (wt/ht2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethical issues in preventing mother-to-child transmission of hepatitis B by immunisation

Without intervention, a pregnant woman who is a chronic hepatitis B carrier is at risk of transmitting hepatitis B and of her infant becoming a chronic carrier and having a significantly increased lifetime risk of developing liver cancer or cirrhosis. Hepatitis B vaccine and immunoglobulin reduce the risk of the baby becoming a carrier, but with only a short window period after birth to deliver this potentially life-saving intervention. We reviewed the evidence on the magnitude of the risk. If the carrier mother is e antigen positive (highly infective), the calculated risk to the infant without intervention is 75.2%, reduced to 6.0% by giving vaccine and immunoglobulin at birth. If the mother is surface antigen positive but e antigen negative, the risk to the infant without intervention is 10.3%, reduced to 1.0% by giving vaccine and immunoglobulin. If vaccine is accepted but immunoglobulin refused, as for example by some Jehovah's Witnesses, the risk to babies of e antigen positive mothers is reduced to 21.0% and to babies of e antigen negative mothers to 2.6%. These figures can be used to inform parents and as a possible basis for child protection proceedings if parents decline vaccine and/or immunoglobulin. We argue from the perspective of the best interests of the child that the severity of the condition justifies initiating child protection proceedings whenever a baby is born to a hepatitis B carrier mother and, despite concerted attempts to persuade them, the parents refuse vaccine and/or immunoglobulin.     

Cost-effectiveness of a pneumococcal conjugate immunisation program for infants in Switzerland

OBJECTIVE: To compare projected economic costs and health benefits associated with using pneumococcal conjugate heptavalent vaccine as routine immunisation in healthy children in Switzerland.DESIGN: A cost-utility analysis was performed from both the societal as well as the sickness funds' perspective.SETTING: Simulated birth cohorts of 80,000 children (the approximate size of a birth cohort in Switzerland) were followed from birth up to age of 5.MAIN OUTCOME MEASURES: Reduction in disease burden, costs of vaccination, cost-utility ratio (cost per quality-adjusted life year (QALY)).RESULTS: With a vaccine coverage of 70% vaccination of newborns only would avert 4 deaths, 8 cases of meningitis, 37 cases of other invasive pneumococcal disease, 150 cases of pneumococcal pneumonia and about 2700 cases of otitis media (OM) per year. The net cost of the vaccination program would be 22 Mio. CHF per year for society and about 19 Mio. CHF for the sickness funds. This results in a cost-utility ratio of 35,700 CHF (approximately 26,300 USD (1)) per QALY from the societal perspective and 39,300 CHF (28,900 USD) per QALY from the sickness funds' perspective. Additional catch-up vaccination of all infants <24 months in the years after vaccine introduction would result in additional benefits at a cost of 33,600 CHF per additional QALY gained. However, if the catch-up vaccination should include all children <60 months, each additional QALY would be gained at a very high cost (162,000 CHF per additional QALY).CONCLUSIONS: Routine vaccination of healthy infants <2 years in Switzerland can reduce mortality and long term neurologic impairment resulting from invasive pneumococcal disease at a reasonable cost-utility ratio.     

Impact of the universal hepatitis B immunization program in Mongolia: achievements and challenges

BACKGROUND: The impact of the universal infant hepatitis B (HB) immunization program initiated in 1991 in Mongolia is still unclear. METHODS: A nationwide school-based cross-sectional serosurvey was conducted in 2004, with stratified, multistage, random cluster sampling from all public elementary schools (n=593) in Mongolia. All children were tested for serological markers of hepatitis B virus (HBV). RESULTS: Serology results were available for 1,145 children (592 boys and 553 girls) aged 7-12 years (survey response rate: 93%). Immunization card was available for 702 (61.3%) children. The coverage of complete HB vaccination was 60.1% and it was increased by birth cohort from 44% to 76%. Significantly higher proportion of children in Metropolitan cities (75.2%) was completely vaccinated with HB compared to those in Province centers (55.7%) and rural areas (59.1%). HBV infection occurred in 5.9%, 13.2%, and 20.8% of complete vaccinees living in Metropolitan, Province centers, and rural areas, respectively; of whom 1.2%, 2.9%, and 8.6% were HB surface antigen (HBsAg) carriers, respectively. Only 17.0% of the children had protective anti-HBs which decreased from 31.1% to 16.3% among 7 to 12-year-olds indicating its decay with time. CONCLUSIONS: Prevalence of HBV infection and carriage among young generation meaningfully declined compared with those of previous studies in Mongolia. The coverage of birth dose and complete HB vaccination was significantly low in Province centers and rural areas which should be taken into consideration.     

Impact of a breastfeeding promotion program for Hmong women at selected WIC sites in Northern California

The very low rate of breastfeeding among Hmong immigrants to the U.S. is of concern to the Special Supplemental Food Program for Women, Infants, and Children (WIC). The objective of this intervention was to increase breastfeeding initiation by specifically targeting attitudes towards infant feeding among Hmong WIC participants. The intervention group (n = 63) was compared with a control group (n = 349) of women who had delivered infants within the previous 8 months. The intervention consisted of a prenatal class and individual meeting, immediate support within 3 days postpartum, and a final interview 3 to 6 weeks postpartum. In the intervention group, 24 women (38.1%) initiated breastfeeding and 11 (17.5%) were still breastfeeding at the final interview, whereas in the control group, 19 women (5.4%) reported breastfeeding at their first postpartum WIC interview at 3 to 6 weeks postpartum (17.5% vs. 5.4%; p = .002). Older mothers were more likely to breastfeed. Primary reasons for choosing formula included the availability of WIC vouchers and the perception that formula feeding was more convenient. Barriers to breastfeeding initiation included delayed first breastfeed (mean = 20 hours postpartum), separation of infant and mother, provision of supplements in the hospital, and gifts of formula at discharge. This study illustrates that a short-term, targeted intervention can have a positive effect on the initiation of breastfeeding.