Universal Infant Hepatitis Research Articles

The analysis of "a" dominant mutation of hepatitis B virus in community-based population of Shandong Province, China

To determine the rate and type of "a" dominant mutation of hepatitis B virus (HBV) in community-based population of Shandong province and the possible effect of hepatitis B vaccination upon "a" dominant mutation. The anticipants aged 1-59 years were selected by multi-stage random sampling from the general population of Shandong province. Hepatitis B vaccination status was obtained by inquisition (for those over 15 years old) or immunization record (for those under 14 years old). The blood samples were collected and detected for HBsAg by ELISA. HBV DNA was extracted from the sera with positive HBsAg and S gene was amplified by nested-PCR. The PCR produce was sequenced and compared with the standard sequence. Overall, 7601 anticipants were investigated. HBV DNA was successfully amplified and sequenced in 102 of 239 samples with positive HBsAg. 14.70% sera samples mutated in HBV "a" determinant region and 13 mutation types were detected. There were no statistically differences in the mutation rate by age groups (born before or after national universal infant hepatitis B vaccination) and hepatitis B vaccination status. The "a" determinant mutation seemed to be uncommon in community-based population of Shandong province and the mutation sites were relatively scattered. Hepatitis B vaccination has no effect on "a" dominant mutation of hepatitis B virus.

Challenge with hepatitis B vaccine in children previously vaccinated with a hepatitis B-containing combination vaccine

The World Health Organization (WHO) recommends universal infant hepatitis B virus (HBV) vaccination as the most effective preventive measure against HBV-induced disease in endemic areas. More than 160 countries have followed the WHO recommendations to incorporate HBV vaccination in their national infant immunization programs. While antibodies to hepatitis B surface antigen (anti-HBs) concentrations progressively decrease following vaccination in infancy, protection persists, probably due to lasting immune memory. Hence, it is thought that future exposure to wild-type virus or HBV vaccine will induce a protective secondary immune response. Children aged 7-8 years old who had been vaccinated in infancy with a hexavalent DTacP-IPV-HB-Hib vaccine (Hexavac(R); Sanofi Pasteur MSD, Lyon, France) and children aged 7-9 years vaccinated in infancy with a DT-HB vaccine (Primavax(R); Sanofi Pasteur MSD), whose anti-HBs concentrations had fallen below the seroprotective threshold of 10 mIU/mL at age 4.5-6 years, received a challenge dose of monovalent HBV vaccine (HBVAXPRO(R); Sanofi Pasteur MSD) to assess persistence of protection. One month postchallenge, 54 of 61 (88.5%) Hexavac-primed seronegative children and 34 of 40 (85.0%) Primavax-primed seronegative children had anti-HBs concentrations > or =10 mIU/mL. The percentage of protected children would have been even higher if the children who still had protective antibody levels (who were not included in this challenge study) had been assessed (42.1% with Hexavac, 55.4% with Primavax). Vaccination with a HBV-containing multivalent vaccine during infancy induces a lasting immune memory that can be boosted, even in children with a decline in anti-HBs concentrations. The present results confirm that the full primary vaccination schedule in infancy seems to confer long-term protection via immune memory and that an additional HBV dose is not generally required.

A significant reduction in hepatitis B virus infection among the children of Shandong Province, China: the effect of 15 years of universal infant hepatitis B vaccination

Objective To evaluate the effect of the universal infant hepatitis B vaccination program on hepatitis B infection in China. Methods In 2006, a survey was conducted in Shandong Province, China, among children aged 1–14 years, 15 years after the introduction of universal infant hepatitis B vaccination. The subjects were selected by stratified, multi-stage sampling. Vaccination history was obtained by immunization certificate (when available) or parent recall. Hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc) were detected by ELISA. Hepatitis B infection was defined as the presence of HBsAg and/or anti-HBc. The prevalence rates of HBsAg, anti-HBs and hepatitis B infection obtained in this survey were compared with the results of a survey conducted in 1992 (prior to universal vaccination). Results A total of 3738 children aged 1–14 years were included in the final analysis. A vaccination coverage rate of 93% was achieved in 2006. The prevalence rates of HBsAg and hepatitis B infection decreased from 8% and 46% in the 1992 survey to 1% and 4%, respectively, in the 2006 survey. Conclusions Universal hepatitis B vaccination in infants can result in a 90.47% reduction in hepatitis B infection in children aged 1–14 years.

Reduction in hepatitis B virus seroprevalence among U.S.-born children of foreign-born Asian parents—Benefit of universal infant hepatitis B vaccination

We demonstrate that after implementation of recommendations for universal infant hepatitis B vaccination, HBV infection prevalence among children of foreign-born Asian parents in Georgia declined dramatically; horizontal transmission of infection within households has occurred infrequently; and the vast majority of infants and children have received the recommended hepatitis B vaccinations. These results provide evidence of the success of the hepatitis B infant vaccination program and highlight its potential impact on reducing chronic HBV infection morbidity and mortality among U.S. populations at high risk.

Seroepidemiology of hepatitis A among Greek children indicates that the virus is still prevalent: Implications for universal vaccination

A national cross-sectional seroprevalence survey was conducted in order to evaluate the current seroepidemiology of hepatitis A among 1,383 children, aged 0-14 years, residing in Greece. Stratification of the study population was conducted according to age and area of residence. Sera from study participants were tested for the presence of anti-HAV IgG antibodies. Immigrant children, as well as children residing in rural areas, had lower immunization rates. Among unvaccinated children, the seroprevalence rate of anti-HAV was 17.1%. Nationality was shown to have a marginally significant effect since non-immunized immigrant children had a higher seroprevalence rate (22.4% vs. 15.9%, OR = 1.52, P = 0.064). Significant differences between geographic areas for both vaccination coverage and natural immunity were observed. The study findings indicate that hepatitis A is prevalent in Greece and therefore universal infant hepatitis A immunization should be implemented.

Cost effectiveness of hepatitis B vaccination strategies in Ireland: an economic evaluation

In accordance with World Health Organization recommendations, many European countries have introduced universal hepatitis B vaccination policies. The UK and Ireland are exceptions. In this study, we conducted an economic evaluation of a universal infant hepatitis B vaccination programme, using a six-component vaccine, compared with the current selective strategy of vaccinating high-risk infants with a monovalent hepatitis B vaccine. A cost effectiveness analysis was conducted using a Markov model. The perspective of the analysis was the Irish Health Service Executive. Unit cost and resource utilization data were derived from expert clinical opinion, published sources, diagnosis-related group costs for hospital admissions and local cost estimates for medical fees and laboratory investigations. A full probabilistic sensitivity analysis was undertaken. Both costs and outcomes were modelled over a period of 80 years and discounted at 3.5%. Assuming an incidence of acute hepatitis B virus (HBV) infection in Ireland of 8.4 per 100,000 population, the incremental cost effectiveness ratio ranged from euro10,992/life years gained (LYG) to euro67 200/LYG, at the lowest and highest price estimates for the six-component vaccine, respectively. The cost effectiveness of universal versus selective hepatitis B vaccination was sensitive to the risk of acute HBV infection, the cost of the universal infant vaccination programme and the discount rate. At a cost of euro29.00 per dose of the six-component vaccine, universal infant hepatitis B vaccination is cost effective at euro37 018/LYG. This compares favourably with other preventive programmes in Ireland.

The impact of a new universal infant and school-based adolescent hepatitis B vaccination program in Australia

We compared the results of two national serosurveys in Australia to evaluate the impact of universal infant vaccination and school-based programs for adolescents. Immunity improved significantly overall, especially in 1-year-olds (40.0% versus 86%; p < 0.0001); in adolescents it was significantly higher in regions with established school-based programs (56.6% versus 38.8%; p = 0.0008). 6.1% of 1–59-year-olds were positive for HBcAb and 0.7% for HBsAg. We have demonstrated successful implementation of universal infant hepatitis B vaccination in Australia and that school-based programs for adolescents are effective. This experience should be applicable to low prevalence countries in northern Europe which have not implemented universal hepatitis B immunisation.

Should hepatitis B vaccine be used for infants?

Chronic hepatitis B virus infection causes nearly all the deaths from this virus. As the initial infection occurs without symptoms and decades prior to the onset of cirrhosis and liver cancer, these consequences are rarely recognized as being caused by the virus. Consequently, its public health importance is under-recognized. Safe and effective vaccines have now been available for over 20 years. Concerns have been raised regarding the mercury preservative in vaccines leading to potential toxicity. But the evidence to date does not support any association of hepatitis B vaccine with serious adverse consequences. Protecting infants through immunization is the most effective control strategy. By 2005, over 80% of countries had implemented routine infant immunization. In countries with relatively low rates of hepatitis B virus infection, some have argued to defer immunization until later life. However, these arguments focus on the more visible acute infection. The possible future cost from a single infant infection argues for universal infant hepatitis B immunization – given the very high costs of treating its consequences (e.g., liver transplant) and the very low price of the vaccine.

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

BACKGROUNDThe impact of the universal infant hepatitis B (HB) immunization program initiated in 1991 in Mongolia is still unclear.METHODSA 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).RESULTSSerology 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.CONCLUSIONSPrevalence 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.

Near Elimination of Hepatitis B Virus Infections Among Hawaii Elementary School Children After Universal Infant Hepatitis B Vaccination

Hawaii implemented routine infant hepatitis B vaccination in 1992 and required it for school entry in 1997. Previously, in 1989, a serologic survey among Hawaii school children in grades 1 to 3 indicated that 1.6% had chronic hepatitis B virus infection, and 2.1% had resolved infection. We conducted a follow-up survey to examine changes in hepatitis B virus infection rates. This study was performed in Oahu, Hawaii, during the 2001-2002 school year among children in grades 2 and 3. Consenting parents/guardians provided demographic information including place of birth. Participants were tested for serologic evidence of hepatitis B virus infection and their vaccination status was determined by reviewing school records. Rates of symptomatic acute hepatitis B among persons aged < or = 19 years were calculated from cases reported from Hawaii to the Centers for Disease Control and Prevention between 1990 and 2004. Completed hepatitis B vaccination series were documented for 83% of the 2469 participants by age 18 months and for 97% by age 5 years. Past or present hepatitis B virus infection was detected among 6 participants (0.24%), including 1 (0.04%) with chronic infection and 5 (0.20%) with resolved infections. Compared with the 1989 survey, these prevalences represent declines of 97% and 90% in chronic and resolved hepatitis B virus infections, respectively. The incidence of symptomatic acute hepatitis B in Hawaii children and adolescents aged < or = 19 years decreased from 4.5 cases per 100,000 in 1990 to 0.0 during 2002-2004. To date, the last reported case in a child aged < 15 years in Hawaii occurred in 1996. Hepatitis B virus infection has nearly been eliminated in Hawaii children born after universal infant hepatitis B vaccination was implemented. These findings suggest that hepatitis B prevention goals are being met through routine immunization and related prevention programs among US children.

Uptake and Behavioural and Attitudinal Determinants of Immunization in an Expanded Routine Infant Hepatitis B Vaccination Program in British Columbia

British Columbia (BC) implemented a universal infant hepatitis B (HB) immunization program in 2001. The study objective was to evaluate HB immunization coverage among the first six-month cohort of eligible infants in the province outside of the Vancouver-Richmond health region and to assess parent/guardian behavioural and attitudinal determinants of HB immunization. A cross-sectional survey of HB immunization was conducted using a random sample of eligible infants born between 1 January-30 June 2001. HB immunization coverage data were obtained from the provincial Public Health Information System, and through a telephone survey of 487 of eligible infants' parents/guardians that was conducted between October 2002-January 2003. At this time, parents/guardians were also asked about behaviours and attitudes towards immunization, based on the Immunization Health Belief Model Scale. HB immunization coverage with at least one dose of HB vaccine was 89% and uptake of 3 doses of HB vaccine was 78%. HB immunization was significantly associated (p<0.001) with a recommendation for HB immunization from a health care professional. The main reason for non-HB immunization was parental concern about side effects. Seventy-eight percent of infants completed the 3-dose HB vaccination schedule. Parental behaviour regarding HB immunization of their children was strongly influenced by a supportive recommendation from either a nurse or doctor.

Acute Hepatitis B Among Children and Adolescents—United States, 1990-2002

Since the 1991 adoption of a comprehensive strategy to eliminate hepatitis B virus (HBV) transmission in the United States, the incidence of acute hepatitis B cases has declined steadily. Declines have been greatest among children born after the 1991 recommendations for universal infant hepatitis B vaccination were implemented. In 1995, the elimination strategy was expanded to include routine vaccination of all adolescents aged 11-12 years and, in 1999, to include children aged < or =18 years who had not been vaccinated previously. To describe the epidemiology of acute hepatitis B in children and adolescents in the United States, CDC analyzed notifiable disease surveillance data collected during 1990-2002 and data collected during 2001-2002 through enhanced surveillance of reported cases of acute hepatitis B in children born after 1990. This report summarizes the results of that analysis, which indicated that the rate of acute hepatitis B in children and adolescents decreased 89% during 1990-2002 and that racial disparities in hepatitis B incidence have narrowed. Many confirmed cases in persons born after 1990 occurred among international adoptees and other children born outside the United States. Continued implementation of the hepatitis B elimination strategy and accurate surveillance data to monitor the impact of vaccination are necessary to sustain the decline of acute hepatitis B among children.

Measuring Hepatitis B Uptake in a New Universal Infant Program

Vancouver-Richmond Health Board has the highest reported rate of hepatitis B in Canada, including an annual average of 25 cases in children under 12 years of age, based on reports from 1994-1997 inclusive. The current provincial adolescent grade-six hepatitis B immunization program does not protect against childhood infection. The regional health board implemented universal infant hepatitis B immunization in September 1998. Immunization coverage data were obtained on a random sample of 191 infants born in March 1999 one year after initiation of the program. By eight months of age, 97.9% of children had received some vaccinations. 73.8% of infants had received three doses of hepatitis B vaccine and 12.6% had received two doses. In comparison, 89% had received three doses and 7.9% two doses of DPTP-Hib vaccine. 13.1% of infants had not received any hepatitis B vaccine. For a majority (67%) of these children, their physician's lack of awareness or lack of acceptance of the program constituted the reason for no hepatitis B vaccine uptake. Only one parent cited adverse publicity as the reason for refusing vaccination. This survey reveals a successful first year of the program without harm to the pre-existing childhood vaccination programs. Hepatitis B vaccine uptake can be improved by increased awareness among physicians and parents.

Fragmentation of scheduled visits and missed doses among infants receiving multiple injected vaccines.

A retrospective cohort study was used to determine the extent to which immunisation visits due in the first year of life are split into separate visits. A one-month birth cohort of infants registered in early childhood health centres in the former Eastern Sydney Health Area was followed up when the infants were 8 to 11 months of age. A telephone questionnaire sought documented dates of each dose in the primary series of diphtheria-tetanus-pertussis (DTP), Haemophilus influenzae type b (Hib) and hepatitis B (HBV) vaccination. Of the 141 subjects, 130 had received all due doses of DTP and Hib vaccines and 63 (45 per cent) had been enrolled in the neonatal hepatitis B program. Infants in the latter group received the first DTP-Hib dose on average one week later than did those not in the hepatitis B program (DTP, P = 0.016; Hib, P = 0.047). The greatest percentage of missed DTP or Hib doses occurred in infants not receiving HBV vaccination (7.1 per cent of doses) or those high-risk infants enrolled in the neonatal hepatitis B program (2.9 per cent). Overall, 12 infants had 28 (6.9 per cent) of the 404 possible scheduled visits fragmented into two separate visits. In all cases, parents reported that this was at the suggestion of the general practitioner. We found no greater likelihood of fragmentation for infants who had also received hepatitis B vaccine. Only 17 infants (29 per cent) had received the third hepatitis B vaccine and DTP doses at the same visit, as recommended. These findings confirm anecdotal reports of fragmentation of scheduled visits and missed doses for infants due to receive multiple injections, and some delay in uptake among those receiving hepatitis B vaccine. Universal infant hepatitis B immunisation should not be considered until combination vaccines (which should also include a Hib component) become available in Australia.

Hepatitis B immunisation rates among infants in ethnic groups with high prevalences of hepatitis B surface antigen carriers.

To determine hepatitis B immunisation rates in infants from ethnic groups with hepatitis B surface antigen chronic carrier prevalence over 5 per cent, a questionnaire was sent to all Maternal and Child Health Centres in Victoria, requesting information on the hepatitis B and diphtheria-tetanus-pertussis (DTP) or combined diphtheria-tetanus (CDT) immunisation status for all infants born between 1 July 1992 and 30 June 1993 and at risk of hepatitis B infection because of maternal ethnicity. We received data on 3611 of 5744 infants (62.9 per cent) in targeted ethnic groups. Of these, 12.8 per cent had not received hepatitis B vaccine, and 81.6 per cent, 76.8 per cent and 64.0 per cent had received at least one, two and three doses respectively, while 84 per cent had received at least three doses of DTP vaccine and/or CDT vaccine. Coverage with DTP or CDT was higher than for hepatitis B vaccine (P < 0.001), and coverage was better in areas with a higher percentage of infants in high-prevalence ethnic groups (P < 0.001). Changes in the program in Victoria in terms of timing of the first dose of vaccine plus greater attention to follow-up may lead to improved hepatitis B immunisation rates among infants in targeted ethnic groups. Adoption of universal infant hepatitis B immunisation, by increasing familiarity with hepatitis B vaccine, is likely to be the best way to increase immunisation coverage for these infants.

Why should Australia adopt universal infant hepatitis B vaccination?

Why should Australia adopt universal infant hepatitis B vaccination?

California Pediatricians' Knowledge of and Response to Recommendations for Universal Infant Hepatitis B Immunization

To assess California pediatricians' level of agreement with and implementation of universal infant hepatitis B immunization. Mailed questionnaire in the summer and fall of 1993 to a random sample of 1030 California pediatricians to determine whether they universally immunize infants with hepatitis B vaccine. The response rate was 71%. More than 81% said they universally immunize infants against hepatitis B infection; however, 18.3% stated that they do not. Pediatricians were more likely to immunize infants universally against hepatitis B if they (1) agreed with the recommendations (90% vs 54%, P < .01), (2) practiced in a health maintenance organization setting vs private group practice (92% vs 79%, P < .05), or (3) practiced in settings with predominantly low-income patients (89% vs 78%, P = .01). Pediatricians who universally immunize infants against hepatitis B virus were in practice an average of 1.7 years longer than those who do not (13.3 years vs 11.6 years, P = .01). In multivariate analyses, the most powerful predictor of universal immunization was agreement with the recommendations. Among those who disagreed with the recommendations, the most common reasons for disagreement included the following: (1) the long-term efficacy of hepatitis B vaccine is not proved--54%; (2) an additional immunization would make the visits too costly--53%; and (3) three shots would be too much at one visit--53%. A majority (81.6%) of our sample of California pediatricians universally immunize infants against hepatitis B; however, a significant minority (18.4%) do not agree with the recommendations and do not plan to implement them. Many of their objections are being addressed through combination vaccine development and ongoing research; however, alternative policies and additional research should also be considered.

Evaluation of universal hepatitis B immunization practices of Illinois pediatricians.

To characterize universal hepatitis B immunization practices of pediatricians who routinely provide childhood immunizations in Illinois. Survey of 522 randomly chosen Illinois pediatricians. Student's t test, chi 2 analysis, and multivariate logistic regression were used to identify relationships between physician demographics and outcomes of interest. Physician agreement with the new Centers for Disease Control and Prevention Immunization Practices Advisory Committee and the American Academy of Pediatrics universal infant hepatitis B immunization guidelines, incorporation of the recommendations, routine hepatitis B immunization of older children (aged 6 months to 11 years), and routine hepatitis B immunization of adolescents. The survey response rate was 71.5%. Of those pediatricians routinely providing immunizations (N = 323), 72.8% agreed with and 90.1% have incorporated universal hepatitis B immunization; 36.5% and 53.0% routinely immunized older children and adolescents, respectively. Pediatricians practicing in medium-sized practices were half as likely to agree with the recommendations (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.31 to 0.84). Cost and a belief that universal immunization of infants is not medically necessary were the two most commonly listed reasons for not incorporating the new guidelines. Percent reimbursement from public aid was negatively related to the routine immunization of older children (OR, 0.34; 95% CI, 0.12 to 0.95). Both percent reimbursement from self-pay (OR, 5.62; 95% CI, 2.25 to 14.05) and a rural location (OR, 0.16; 95% CI, 0.04 to 0.56) were related to routine hepatitis B immunization of adolescents. Gender and number of years in practice were not associated with physician response. The majority of Illinois pediatricians who routinely provide pediatric immunizations have incorporated the new universal hepatitis B immunization guidelines into their practices. Continued efforts to address financial barriers and to educate physicians may hasten the time when the transmission of the hepatitis B virus will no longer occur.

Physician attitudes and practices regarding universal infant vaccination against hepatitis B infection in Minnesota: implications for public health policy

Physician attitudes and practices regarding universal infant vaccination against hepatitis B virus infection in Minnesota were assessed approximately 1 year after publication of the Immunization Practices Advisory Committee recommendations. Four-hundred eighteen Minnesota family physicians and pediatricians were sent self-administered questionnaires, with follow-up by telephone. Among physicians who provide care to infants, 67 (29%) of 234 family physicians and 29 (50%) of 58 pediatricians routinely offered hepatitis B vaccine to all infants (overall 33%) (P = 0.002). The recommendations of the Immunization Practices Advisory Committee, the American Academy of Pediatrics and the American Academy of Family Physicians had the greatest positive influence on physicians' opinions regarding routine hepatitis B vaccination. The factors with the greatest negative influence on their opinions were the low prevalence of hepatitis B virus infection in Minnesota and the addition of three injections to the current childhood immunization schedule. Universal infant hepatitis B vaccination remains controversial among Minnesota family physicians and pediatricians. We believe, given the variability in hepatitis B virus incidence and prevalence in the United States and the relatively low risk of most infants, that a single national policy based solely on universal infant immunization may be difficult to implement.

Discussion of Immunization Practices Advisory Committee/American Academy of Pediatrics recommendations for universal infant hepatitis B vaccination

The Committee on Infectious Diseases of the American Academy of Pediatrics and the Advisory Committee on Immunization Practices of the United States Public Health Service have revised the recommendations for hepatitis B control to include universal immunization of infants. Previous selective strategies targeting high risk groups for immunization have failed to prevent the significant morbidity and mortality associated with hepatitis B virus infection. The committees considered several alternative policy options before selecting universal immunization of infants as the most effective strategy for preventing the disease and its sequelae in the United States. More than 30 other countries have also adopted universal infant immunization programs. All children should receive three doses of vaccine by the time they are 18 months of age. Scheduling of the three doses is flexible. Two hepatitis B vaccines are currently available in the United States, and both are highly effective and safe. Dosage depends on several factors, including manufacturer, age at vaccination, maternal serologic status for hepatitis B surface antigen and presence of underlying disease. The committees continue to recommend immunization of high risk older children and adults, and immunization of adolescents is encouraged where resources are available.