Vaccinated Birth Cohorts Research Articles

Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Evidence-based impact projections of single-dose human papillomavirus vaccination in India: a modelling study.

Despite the high burden of cervical cancer, access to preventive measures remains low in India. A single-dose immunisation schedule could facilitate the scale-up of human papillomavirus (HPV) vaccination, contributing to global elimination of cervical cancer. We projected the effect of single-dose quadrivalent HPV vaccination in India in comparison with no vaccination or to a two-dose schedule. In this modelling study, we adapted an HPV transmission model (EpiMetHeos) to Indian data on sexual behaviour (from the Demographic and Health Survey and the Indian National AIDS Control Organisation), HPV prevalence data (from two local surveys, from the states of Tamil Nadu and West Bengal), and cervical cancer incidence data (from Cancer Incidence in Five Continents for the period 2008-12 [volume XI], and the Indian National Centre for Disease Informatics and Research for the period 2012-16). Using the model, we projected the nationwide and state-specific effect of HPV vaccination on HPV prevalence and cervical cancer incidence, and lifetime risk of cervical cancer, for 100 years after the introduction of vaccination or in the first 50 vaccinated birth cohorts. Projections were derived under a two-dose vaccination scenario assuming life-long protection and under a single-dose vaccination scenario with protection duration assumptions derived from International Agency for Research on Cancer (IARC) India vaccine trial data, in combination with different vaccination coverages and catch-up vaccination age ranges. We used two thresholds to define cervical cancer elimination: an age-standardised incidence rate of less than 4 cases per 100 000 woman-years, and standardised lifetime risk of less than 250 cases per 100 000 women born. Assuming vaccination in girls aged 10 years, with 90% coverage, and life-long protection by two-dose or single-dose schedule, HPV vaccination could reduce the prevalence of HPV16 and HPV18 infection by 97% (80% UI 96-99) in 50 years, and the lifetime risk of cervical cancer by 71-78% from 1067 cases per 100 000 women born under a no vaccination scenario to 311 (80% UI 284-339) cases per 100 000 women born in the short term and 233 (219-252) cases per 100 000 women born in the long term in vaccinated cohorts. Under this scenario, we projected that the age-standardised incidence rate threshold for elimination could be met across India (range across Indian states: 1·6 cases [80% UI 1·5-1·7] to 4·0 cases [3·8-4·4] per 100 000 woman-years), while the complementary threshold based on standardised lifetime risk was attainable in 17 (68%) of 25 states, but not nationwide (range across Indian states: 207 cases [80% UI 194-223] to 477 cases [447-514] per 100 000 women born). Under the considered assumptions of waning vaccine protection, single-dose vaccination was projected to have a 21-100% higher per-dose efficiency than two-dose vaccination. Single-dose vaccination with catch-up for girls and women aged 11-20 years was more impactful than two-dose vaccination without catch-up, with reduction of 39-65% versus 38% in lifetime risk of cervical cancer across the ten catch-up birth cohorts and the first ten routine vaccination birth cohorts. Our evidence-based projections suggest that scaling up cervical cancer prevention through single-dose HPV vaccination could substantially reduce cervical cancer burden in India. The Bill &amp; Melinda Gates Foundation.

Identifying a Single Optimal Integrated Cervical Cancer Prevention Policy in Norway: A Cost-Effectiveness Analysis.

Interventions targeting the same disease but at different points along the disease continuum (e.g., screening and vaccination to prevent cervical cancer [CC]) are often evaluated in isolation, which can affect cost-effectiveness profiles and policy conclusions. We evaluated nonavalent human papillomavirus (HPV) vaccine (9vHPV) compared with bivalent HPV vaccine (2vHPV) alongside deintensified screening intervals for a vaccinated birth cohort to inform a single optimal integrated CC prevention policy. Using a multimodeling approach, we evaluated the health and economic impacts of alternative CC screening strategies for a Norwegian birth cohort eligible for HPV vaccination in 2021 assuming they received 1) 2vHPV or 2) 9vHPV. We conducted 1) a restricted analysis that evaluated the optimal HPV vaccine under current screening guidelines; and 2) a comprehensive analysis including alternative screening and vaccination strategy combinations. We calculated incremental cost-effectiveness ratios (ICERs) and evaluated them according to different cost-effectiveness thresholds. Assuming a cost-effectiveness threshold of $40,000 per quality-adjusted life year (QALY) gained, we found that, while holding screening intensity fixed, switching the routine vaccination program in Norway from 2vHPV to 9vHPV would not be considered cost-effective (ICER of $132,700 per QALY gained). However, when allowing for varying intensities of CC screening, we found that switching to 9vHPV would be cost-effective compared with 2vHPV under an alternative threshold of $55,000 per QALY gained, if coupled with reductions in the number of lifetime screens. Our analysis highlights the importance of evaluating the full potential policy landscape for country-level decision makers considering policy adoption, including nonindependent primary and secondary prevention efforts, to draw appropriate conclusions and avoid sub-optimal outcomes. Without evaluating the full potential policy landscape, including primary and secondary prevention efforts, country-level decision makers may not be able to draw appropriate policy conclusions, resulting in suboptimal outcomes.An applied example from cervical cancer prevention in Norway compared a restricted analysis of current screening guidelines to a comprehensive analysis including alternative screening and vaccination strategy combinations.We found that a switch from bivalent to nonavalent human papillomavirus vaccine would be considered cost-effective in Norway if coupled with reductions in the number of lifetime screens compared with the current screening strategy.A comprehensive analysis that considers how different types of interventions along the disease continuum affect each other will be critical for decision makers interpreting cost-effectiveness analysis results.

Universal Infant Hepatitis B Virus (HBV) Vaccination for 35 Years: Moving Toward the Eradication of HBV.

A universal hepatitis B virus (HBV) vaccination program has been implemented in Taiwan since 1984. A total of 1611 individuals in Taipei were enrolled to monitor long-term efficacy. The prevalences of hepatitis B surface antigen (HBsAg) and hepatitis B core antibody in the vaccinated birth cohort were lower than in those born before 1984 (0.4% vs 7.7%, and 2.2% vs 50.8%, respectively; P < .0001). Three vaccine-failure carriers all were born to HBsAg-carrier mothers, probably due to no antiviral intervention during pregnancy. Occult HBV infection was rare in the postvaccination era. High vaccination coverage, comprehensive HBV screening, and antiviral agents for pregnant mothers will be essential to eliminate HBV transmission.

Hepatitis B virus prevalence in first-time blood donors in Flanders, Belgium: Impact of universal vaccination and migration.

Transfusion-transmissible infections such as hepatitis B virus (HBV) remain a major concern for the safety of blood transfusion. This cross-sectional study aimed to assess the trend of HBV prevalence and associated risk factors among a first-time donor population in a low endemic country. Between 2010 and 2018, blood samples were collected from first-time donors presented at donor collection sites of Belgian Red Cross-Flanders. They were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and HBV DNA, HIV and hepatitis virus C (HCV) antibodies and RNA, and syphilis antibodies. A total of 211,331 first-time blood donors (43.7% males, median age 25 years) were analyzed. HBsAg prevalence decreased from 0.06% in 2010 to 0.05% in 2018 (p= .004) and this declining trend was accompanied by an increased number of donors in the HBV vaccinated birth cohort (p< .001). HBsAg prevalence was 0.33% in foreign-born donors and 0.02% in Belgian natives (p< .001). Multivariate risk profiling showed that anti-HBc positivity was significantly associated with mainly foreign-born donors (odds ratio [OR]=9.24) but also with older age (OR=1.06), male gender (OR=1.32), year of blood donation (OR=0.94), and co-infections with HCV (OR=4.31) or syphilis (OR=4.91). The decreasing trend in HBV prevalence could mainly be explained by the introduction of the universal HBV vaccination. Being born in endemic areas was the most important predictor for HBV infection while the co-infections with syphilis suggest unreported sexual risk contacts.

Variable anti-HBs antibody titers in vaccinated birth cohorts – A cross-sectional population-based study

BackgroundAfter the introduction of hepatitis B (HB) vaccination in 1995 in newborns, two catch-up campaigns targeted unvaccinated 9 year old in 2000–2003 (born 1991–1994) and the 18 year old in 2004–2008 (born 1986–1990), resulting in several birth-cohorts. Our objective was to assess the anti-HBs titers in each birth-cohort. MethodsWe included all outpatients (78.5%) and hospitalized patients with measured anti-HBs antibody titers in the Teaching Hospital of Infectious Diseases, Cluj-Napoca, Romania, during April 2014 – December 2018 (without HB history). We compared the anti-HBs titers in all birth-cohorts using the Lexis surfaces (titers by age, time period and cohort patterns). We also evaluated the number of acute HB in the corresponding inpatient birth-cohorts and special groups. ResultsWe included 2963 participants, mean age = 31.0 ± 14.2, 64.1% women. The birth-cohort 1995–2006, vaccinated after delivery (n = 424, 3-dose HB vaccine coverage > 90%), had significantly lower protective titers (41.3% >10 mIU/mL) compared to the other birth-cohorts: born after 2007 (also vaccinated at birth, 67.0%, n = 106), 1991–1994 (age 9, 74.3%, n = 847), 1986–1990 (age 18, 71.3%, n = 543). In the unvaccinated cohort (n = 1043, mean age = 45.5 ± 12.4) protective titers were found in 44.8%, probably after self-limited HB infection.Concordant results were found using the proportion of patients with detectable or robust titers, and median or geometric mean titers.Four breakthrough acute HB infections were hospitalized of the corresponding vaccinated cohorts (birth years 1988, 1990, 1995, 1996). Data on a few tested infants (n = 47, not included in the main study) demonstrated good protection, 88.9%. ConclusionsOur study demonstrated the long-term evidence of protection of HBV vaccine at two decades following the primary immunization and a booster seems unsupported. Further studies should be done to assess the need of a booster dose within the general population and special groups.

Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women.

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial. A total of 9,482 female trial participants received HPV16/18-vaccination in 2007-2009 at age of 13-15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014-2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high-risk HPV types were: 0.5% (53/1,000 follow-up years, 104 ) and 25% (2,530/104 ) in the frequently screened Arm 1; 0.2% (23/104 ) and 24% (2,413/104 ) in the infrequently screened Arm 2; and 3.1% (304/104 ) and 23% (2,284/104 ) in the safety Arm 3. Corresponding prevalence of HSIL/ASC-H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former.

Impact of rotavirus vaccination on rotavirus genotype distribution and diversity in England, September 2006 to August 2016.

IntroductionRotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence.AimWe assessed the vaccine’s impact on rotavirus genotype distribution and diversity 3 years post-vaccine introduction.MethodsEpidemiological and microbiological data on genotyped rotavirus-positive samples between September 2006 and August 2016 were supplied by EuroRotaNet and Public Health England. Multinomial multivariable logistic regression adjusting for year, season and age was used to quantify changes in genotype prevalence in the vaccine period. Genotype diversity was measured using the Shannon’s index (H′) and Simpson’s index of diversity (D).ResultsWe analysed genotypes from 8,044 faecal samples. In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year. In the vaccine era, G1P[8] prevalence declined each season (35%, 231/654; 12%, 154/1,257; 5%, 34/726) and genotype diversity increased significantly in 6–59 months old children (H’ p < 0.001: D p < 0.001). In multinomial analysis, G2P[4] (adjusted multinomial odds ratio (aMOR): 9.51; 95% confidence interval (CI): 7.02–12.90), G3P[8] (aMOR: 2.83; 95% CI: 2.17–3.81), G12P[8] (aMOR: 2.46; 95% CI: 1.62–3.73) and G4P[8] (aMOR: 1.42; 95% CI: 1.02–1.96) significantly increased relative to G1P[8].ConclusionsIn the context of reduced rotavirus disease incidence, genotype diversity has increased, with a relative change in the dominant genotype from G1P[8] to G2P[4] after vaccine introduction. These changes will need continued surveillance as the number and age of vaccinated birth cohorts increase in the future.

Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol

IntroductionThe first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated...

Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer

The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P < .001 and 1986-1992 vs 1984-1986; P<.002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC. Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer.

Cost-effectiveness of rotavirus vaccination in Albania

BackgroundRotavirus vaccines have been introduced in several European countries but can represent a considerable cost, particularly for countries that do not qualify for any external financial support. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into Albania's national immunization program and to inform national decision-making by improving national capacity to conduct economic evaluations of new vaccines. MethodsThe TRIVAC model was used to assess vaccine impact and cost-effectiveness. The model estimated health and economic outcomes attributed to 10 successive vaccinated birth cohorts (2013–2022) from a government and societal perspective. Epidemiological and economic data used in the model were based on national cost studies, and surveillance data, as well as estimates from the scientific literature. Cost-effectiveness was estimated for both the monovalent (RV1) and pentavalent vaccines (RV5). A multivariate scenario analysis (SA) was performed to evaluate the uncertainty around the incremental cost-effectiveness ratios (ICERs). ResultsWith 3% discounting of costs and health benefits over the period 2013–2022, rotavirus vaccination in Albania could avert 51,172 outpatient visits, 14,200 hospitalizations, 27 deaths, 950 disability-adjusted life-years (DALYs), and gain 801 life-years. When both vaccines were compared to no vaccination, the discounted cost per DALY averted was US$ 2008 for RV1 and US$ 5047 for RV5 from a government perspective. From the societal perspective the values were US$ 517 and US$ 3556, respectively. ConclusionFrom both the perspectives, the introduction of rotavirus vaccine to the Albanian immunization schedule is either cost-effective or highly cost-effective for a range of plausible scenarios. In most scenarios, including the base-case scenario, the discounted cost per DALY averted was less than three times the gross domestic product (GDP) per capita. However, rotavirus vaccination was not cost-effective when rotavirus cases and deaths were based on plausible minimum estimates. Introduction of RV1 would yield similar benefits at lower cost.

Potential impact of vaccination against Neisseria meningitidis on Neisseria gonorrhoeae in the United States: Results from a decision-analysis model

Components in 4CMenB vaccine against Neisseria meningitidis serogroup B have shown to potentially cross-react with Neisseria gonorrhoeae. We modeled the theoretical impact of a US 4CMenB vaccination program on gonorrhea outcomes. A decision-analysis model was populated using published healthcare utilization and cost data. A two-dose adolescent vaccination campaign was assumed, with protective immunity starting at age 15 years and a base-case efficacy against gonorrhea of 20%. The 20%-efficacy level is an assumption since no clinical data have yet quantified the efficacy of 4CMenB against Neisseria gonorrhoea. Key outcome measures were reductions in gonorrhea and HIV infections, reduction in quality-adjusted life-years (QALYs) lost, and the economically justifiable price assuming a willingness-to-pay threshold of $75,000 per QALY gained. Adolescent vaccination with 4CMenB would prevent 83,167 (95% credible interval [CrI], 44,600–134,600) gonorrhea infections and decrease the number of HIV infections by 55 (95% CrI, 2–129) per vaccinated birth cohort in the USA. Excluding vaccination costs, direct medical costs for gonorrhea would reduce by $28.7 million (95% CrI, $6.8–$70.0 million), and income and productivity losses would reduce by $40.0 million (95% CrI, $8.2–$91.7 million). Approximately 83% of the reduction in lost productivity is generated by avoiding HIV infections. At a cost of $75,000 per QALY gained, and incremental to the vaccine's effect on meningococcal disease, a price of $26.10 (95% CrI, $9.10–$57.20) per dose, incremental to the price of the meningococcal vaccine, would be justified from the societal perspective. At this price, the net cost per infection averted would be $1,677 (95% CrI, $404–$2,564). Even if the cross-immunity of 4CMenB vaccine and gonorrhea is only 20%, the reduction in gonorrhea infections and associated costs would be substantial.

Modeling the impact of the 7-valent pneumococcal conjugate vaccine in Chinese infants: an economic analysis of a compulsory vaccination

BackgroundThe purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule.MethodsA decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2 + 1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio.ResultsIn a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively.ConclusionsCompulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization.

Respiratory syncytial virus immunization program for the United States: Impact of performance determinants of a theoretical vaccine

ObjectivesTo inform strategic decisions on respiratory syncytial virus (RSV) vaccine development and identify critical endpoints likely to drive the vaccine's medical and economic impact. DesignA decision-analysis model populated using healthcare utilization data and costs from the literature; vaccine efficacy and duration based on assumptions. SettingVaccination in the physician office setting in the USA. ParticipantsA hypothetical cohort of newborn infants. InterventionVaccination of children at low and high risk of respiratory sequelae with a theoretical RSV vaccine vs palivizumab prophylaxis for children at high risk. Outcome measuresMedical and economic value of RSV vaccination, including cost per quality adjusted life-year (QALY) gained. ResultsUsing base-case assumptions (efficacy 50% at birth; half-life 12months), RSV vaccination would prevent 23,069 hospitalizations and 66 deaths per vaccinated birth cohort in the USA. Excluding vaccination costs, direct medical costs for RSV would reduce by $236 million, and income and productivity losses by $134 million. Assuming a vaccine cost per course similar to Rotarix® in the USA ($232 including administration fees), the cost per QALY gained would be $93,401 (95% CI: $65,815-$126,060) from the healthcare system perspective and $65,115 (95% CI: $41,003–$93,679) from the societal perspective. The net cost (healthcare system perspective) per life-year saved would be $216,120 (95% CI: $161,184–$263,981); the cost per hospitalization averted would be $19,172 (95% CI: $14,679–$22,093). Aside from efficacy, the vaccine's impact is sensitive to the start of protective immunity and the duration of protection. ConclusionsDevelopment of an RSV vaccine would substantially reduce inpatient hospitalizations and outpatient visits. It would also have an impact on infant mortality. To demonstrate the full medical and economic value of the vaccine, appropriate endpoints or endpoint surrogates for hospitalization, mortality, and total case reductions should be collected during vaccine development.

Economic evaluation of universal 7-valent pneumococcal conjugate vaccination in Taiwan: A cost-effectiveness analysis

Pneumococcal diseases caused by Streptococcus pneumoniae can lead to significant morbidity and mortality in young infants and the elderly. The seven-valent pneumococcal conjugate vaccine (PCV7) has been available on the private market in Taiwan since October 2005. To date, there has not been any cost-effectiveness analysis (CEA) of PCV7 in Taiwan. A pharmacoeconomic model populated with local parameters is needed for vaccine decision-making. The aim of the study was to provide a CEA of PCV7 in Taiwan and explore the impact of herd effect and indirect cost on the findings of CEA. A decision analytic model was populated with local epidemiological and economic data to simulate the expected clinical and economic outcomes from a hypothetical vaccinated birth cohort of 191,310 infants compared to no vaccination over a 10-year time horizon. To explore the impact of herd effect, results were presented with and without herd effect. Moreover, the study was conducted from both payer and societal perspectives to examine the impact of indirect cost. One-way sensitivity analyses were performed to evaluate model robustness. The cost-effectiveness of a reduced three-dose schedule was also estimated. PCV7 vaccination could prevent 1281 cases of invasive pneumococcal diseases, 178,145 cases of all-cause hospitalized pneumonia, 69,962 cases of all-cause acute otitis media, and 981 deaths over a 10-year time horizon. The vaccination program with an annual cost of NT$1,950.5 million could lead to 15.4% reduction in direct medical costs of NT$6,010 million and 64.1% reduction in indirect costs of NT$9,467 million. The vaccination with a four-dose schedule would lead to an incremental cost of NT$1,183,028 per life-year gained from the payer perspective and NT$619,862 per life-year gained from the societal perspective. Taking herd effect and indirect costs into account, PCV7 vaccination is cost-effective in Taiwan. Further pharmacoeconomic model should include herd effect in CEA of infectious disease research.

Effect of Age on the Incidence of Acute Hepatitis B After 25 Years of a Universal Newborn Hepatitis B Immunization Program in Taiwan

Raising concerns about the waning immunity of cohorts receiving hepatitis B virus (HBV) vaccination in infancy persuaded us to identify the changing incidence of acute hepatitis B (AHB) in children and young adults. Data on AHB surveillance through the National Notifiable Disease Surveillance System from July 2001 to June 2009 were collected and described. Cases were divided into 2 cohorts according to their birth year: before or after the universal newborn HBV vaccination program. Age-specific incidence was compared for the 2 birth cohorts with diagnosis at age 15-24 years. In total, 2226 patients with AHB were identified. AHB rates varied by age; the highest rates occurred among unvaccinated individuals aged 25-39 years (2.33/100 000). Due to breakthrough HBV infection from mother-to-infant transmission, vaccinated infants (0.78/100 000) had higher rates than those aged 1-14 years (0.04/100 000), who had the lowest rates. The incidence in vaccinated birth cohorts was significantly lower than in unvaccinated birth cohorts among patients 15-24 years old, with an adjusted-relative risk of 0.42. Implementation of universal-at-birth HBV immunization programs has effectively reduced the occurrence of AHB among adolescents and young adults in Taiwan for >25 years, making infants and the 25-39-year-old cohort additional targets for preventing AHB.

More Lessons From the Taiwanese Hepatitis B Virus Vaccine Program

In this issue of The Journal of Infectious Diseases, the Taiwan National Children’s Hospital group, under the capable leadership of Dr Mei-Hwei Chang, has once again used carefully constructed national surveillance data to teach us something about hepatitis B virus (HBV) infection in young subjects who received neonatal HBV vaccine. As one would predict, the highest rates for acute HBV infection were in unvaccinated individuals. Also, as expected, rates of acute HBV infection were lower in vaccinated birth cohorts aged 15–24 years than in unvaccinated birth cohorts, demonstrating once again the efficacy of the universal newborn vaccination program. The biggest disappointment was that, due to breakthrough HBV infection from mother-to-infant transmission, vaccinated infants (0.78 per 100 000) had higher rates than those aged 1–14 years (0.04 per 100 000), who had the lowest rates. It is disconcerting that the 8 infants who were born to mothers with hepatitis B e antigen, and who developed acute HBV infection in the first year of life, were not given neonatal hepatitis B immunoglobulin (in accordance with Taiwan national vaccine policy). Although the authors discuss this problem and acknowledge that the combination of active and passive vaccination for all infants born to hepatitis B surface antigen (HbsAg)–positive women is 85%–95% effective in preventing transmission, it is puzzling that the authors do not recommend a change in the Taiwan national vaccine policy to that effect. The authors also do not comment on the fact that the infants were given the first dose of recombinant HBV vaccine at 2–43 days of life instead of within 12 hours of birth, as per the recommendation of the American Academy of Pediatrics. It is also unfortunate that there is no clinical information available to inform us whether the cases of acute HBV in vaccinated subjects differed phenotypically from cases in unvaccinated subjects. Likewise, with somewhat incomplete information, it is difficult to know if reporting physicians could be 100% accurate in differentiating acute HBV from acute on chronic HBV infection, because a liver biopsy and previous serology were necessary for that distinction but not always available. Although the success of the aggressive universal infant vaccine program was mentioned only in passing, it is important to acknowledge the tremendous achievement this program (95% vaccine coverage beginning in 2001) has already demonstrated by its efficacy in reducing rates of chronic HBV, fulminant HBV, and hepatocellular carcinoma in children. Certainly, the decline in acute HBV cases in Taiwan from 2001 to 2008 is a remarkable success. The most useful and cost-effective conclusions from this careful study are that energetic follow-up during the first 12 months of life should be focused on infants born to HbsAg-positive mothers and that, in a country like Taiwan where HBV is endemic, vaccine efforts could be focused on subjects $25 years of age who have not benefited from the universal newborn vaccination program. Given the cost in terms of both human suffering from chronic HBV liver disease and hepatocellular carcinoma and related public health expenditures, we should all continue to admire the Taiwan National Children’s Group for their efforts to analyze how best to reduce those costs, and to learn from them.

Abstract CN01-04: HBV vaccination to prevent hepatocellular carcinoma

Abstract Chronic HBV infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HCC is one of the five major cancers in the world population. Hepatitis B virus (HBV) is the most important etiologic agent of liver cancer in the world population, particularly in areas highly prevalent for liver cancer. Taiwan has launched the world's first universal HBV vaccination program in July 1984. The prevalence of HBV infection in vaccinated birth cohorts have been reduced remarkably to approximately one-tenth of the original prevalence. Furthermore, reduction of the HCC incidence in the vaccinated birth cohorts aged 6-14 years have been demonstrated. Recently, we have further provided evidence that the effect of HCC prevention by HBV vaccination has been extended from childhood to adolescent and gradually into early adulthood. The incidence of HCC was significantly lower among children and adolescents aged 6-19 years in the vaccinated than unvaccinated birth cohorts, showing an age- and sex-adjusted relative risk of 0.31 for the population vaccinated since birth. Failure to prevent HCC results mostly from unsuccessful control of HBV infection by highly infectious mothers. The risk of developing HCC for vaccinated cohorts was statistically significantly associated with prenatal maternal HBsAg and HBeAg seropositivity; lack of administration of hepatitis B immunoglobulin at birth, and incomplete HBV vaccination. Future strategies to interrupt mother-to-infant transmission and to increase the global coverage rate of HBV immunization may enhance the cancer prevention effect of HBV immunization. In conclusion, prevention of chronic HBV infection can successfully reduce the incidence of liver cancer. This is the first example of cancer preventive vaccine in human, which proves that prevention of the infection of an infectious agent can prevent its related cancer. This example has been extended to the prevention of cervical cancers, and hopefully into other infection-related cancers in the near future. Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN01-04.

No association between tuberculin skin test and atopy in a bacillus Calmette‐Guérin vaccinated birth cohort

Previously, an inverse association was suggested between mycobacterial infection and atopy. We aimed to determine the association between tuberculin skin test (TST) and allergic manifestations in a birth cohort where all infants were vaccinated with bacillus Calmette-Guérin (BCG) at birth. Newborns were enrolled randomly and prospectively followed up for a period of 5 yr. Information on family history and environmental factors was obtained at birth, International Study of Asthma and Allergies in Childhood asthma questionnaire, physical examination, skin prick test to common inhalant and food allergens and TST were performed at 2 and 5 yr of age. Positive TST reactivity was defined as an induration of > or = 10 mm. A total of 399 newborns were enrolled, 293 and 125 were available for a followup visit at 2 and 5 yr of age respectively. The prevalence of ever asthma, rhinitis and allergen sensitization tended to increase while eczema decreased with time. No significant association was found between TST reactivity and ever and current wheeze, doctor diagnosed asthma or atopic sensitization both at 2 and 5 yr of age. This prospectively designed birth cohort study did not confirm the previously suggested inverse correlation between TST reactivity and atopic sensitization or any allergic manifestations in Turkish children vaccinated with BCG at birth.

Cost-effectiveness of three different vaccination strategies against measles in Zambian children

The vaccination program in Zambia includes one dose of measles vaccine at 9 months of age. The objective of this study was to compare the cost-effectiveness of the current one-dose measles vaccination program with an immunization schedule in which a second dose is provided either through routine health services or through supplemental immunization activities (SIAs). We simulated the expected cost and impact of the vaccination strategies for an annual cohort of 400,000 children, assuming 80% vaccination coverage in both routine and SIAs and an analytic horizon of 15 years. A vaccination program which includes SIAs reaching children not previously vaccinated would prevent on additional 29,242 measles cases and 1462 deaths for each vaccinated birth cohort when compared with a one-dose program. Given the parameters established for this analysis, such a program would be cost-saving and the most cost-effective vaccination strategy for Zambia.