Immunization Against Hepatitis A in Migrant Children: Three Vaccination Strategies, A Retrospective Study.

BACKGROUND: Hepatitis A is endemic in many countries. Swiss guidelines recommend vaccinating patients native from endemic areas. In Geneva's Children's hospital, migrant children are screened and vaccinated if seronegative. Because hepatitis A's prevalence is decreasing worldwide, more children are seronegative at arrival, highlighting the need for immunization in medical centers and refugee camps and questioning the benefits of systematic serology. Other Swiss hospitals vaccinate regardless of serostatus. This study's aim is to assess migrant children's immunity according to origin and age, and the cost-effectiveness of different immunization strategies. METHODS: We retrospectively analyzed 329 children's serostatus (1-16 years of age) between 2012 and 2015, using enzyme-linked fluorescent assay method. Serology and vaccine costs were based on local prices. Groups were compared with χ test and the age-seropositivity relationship was studied with linear regression. RESULTS: The predominant regions were the Eastern Mediterranean and European Regions with mostly negative serologies (71% and 83%) and the African Region with mostly positive serologies (79%). Immunity varied depending on birth country. Regardless of region, seropositivity increased with age (P < 0.001). The most cost-effective vaccination strategy was an individualized approach based on age and origin, reducing costs by 2% compared with serology-guided immunization and by 17% compared with systematic vaccination. CONCLUSIONS: Many migrant children >5 years old are seronegative and at risk of clinical infection. They need to be immunized. New guidelines according to age and origin should be defined to reduce immunization costs. We recommend systematic vaccination for patients <5 years old or native from low endemicity areas (≤25.7% of seropositivity). For the others, we propose serology-based vaccination.

Economic evaluation of a publicly funded hepatitis A travel vaccination program in Ontario, Canada.

BACKGROUND: Hepatitis A virus (HAV) causes acute liver infection and is spread through the fecal-oral route. Travel to countries in HAV-endemic regions (e.g., Asia and Latin America) is a well-described risk factor for infection. Currently, Ontario publicly funds hepatitis A vaccination for some populations at high risk of HAV infection but not for all travellers to endemic countries. The objective of this study was to determine the cost-effectiveness of expanding publicly funded HAV vaccination to people planning travel to HAV-endemic regions, from the Ontario healthcare payer perspective. METHODS: We conducted a cost-utility analysis comparing an expanded high-risk publicly-funded hepatitis A vaccination program including funded vaccine for travellers to endemic regions to the current high risk program in Ontario. A Markov state transition model was developed, including six possible health states. Model parameters were informed through targeted literature searches and included hepatitis A disease probabilities, utilities associated with health states, health system expenditures, and vaccine costs. Future costs and health outcomes were discounted at 1.5%. Primary outcomes included cost, incremental cost-effectiveness ratio (ICER) and quality adjusted life years (QALYs) over a lifetime time horizon. We conducted one-way, two-way, and probabilistic sensitivity analysis. RESULTS: The expanded high risk HAV vaccine program provided few incremental health gains in the travel population (mean 0.000037 QALYs/person), at an incremental cost of $124.31. The ICER of the expanded program compared to status quo is $3,391,504/QALY gained. The conclusion of the model was robust to changes in key parameters across reasonable ranges. CONCLUSIONS: The expanded vaccination program substantially exceeds commonly accepted cost-effectiveness thresholds. Further research concerning possible cost-effective implementation of high-risk travel hepatitis A vaccination should focus on a more integrated understanding of the risk of acquiring hepatitis A during travel to endemic regions (e.g., purpose, length of stay).

High prevalence of anti-hepatitis A IgG in a cohort of UK HIV-negative men who have sex with men: implications for local hepatitis A vaccine policy.

BASHH guidelines recommend that 'the hepatitis A virus total antibody test can be offered to at-risk patients whose immune status is unknown … depending on local funding arrangements'. We sought to measure the local prevalence of anti-hepatitis A (HAV) IgG in HIV-negative men who have sex with men (MSM), to inform the utility of pre-vaccination screening. We assessed the prevalence of anti-HAV IgG in HIV-negative MSM who attended sexual health services in County Durham and Darlington, UK, from March to August 2017. Data were extracted from electronic patient records and analysed in Excel. Our study was granted local Caldicott approval. Seventy four per cent of 244 HIV-negative MSM who attended for review were screened. Anti-HAV IgG was detected in 42% who did not report definite previous infection or vaccination; not detected in 57.4%; and was equivocal in 0.6%. Vaccine was administered to 48% of eligible patients. The estimated financial costs of universal vaccination of MSM (£4235.40) and pre-vaccination screening with vaccination of susceptible patients (£4188.13) are similar. Pre-vaccination screening and vaccination of susceptible patients does not save resources compared to a policy of universal vaccination of MSM in our setting. Universal vaccination of MSM attending genitourinary medicine clinics may improve vaccine uptake.

The Financial Burden of Public Health Responses to Hepatitis A Cases Among Food Handlers, 2012-2014.

When food handlers become ill with hepatitis A virus (HAV) infection, state and local health departments must assess the risk of HAV transmission through prepared food and recommend or provide postexposure prophylaxis (PEP) for those at risk for HAV infection. Providing PEP (eg, hepatitis A [HepA] vaccine or immunoglobulin), however, is costly. To describe the burden of these responses on state and local health departments, we determined the number of public health responses to HAV infections among food handlers by reviewing public internet sources of media articles. We then contacted each health department to collect data on whether PEP was recommended to food handlers or restaurant patrons, the number of PEP doses given, the number of HepA vaccine or immunoglobulin doses given as PEP, and the mean number of health department person-hours required for the response. Of 32 public health responses identified from Twitter, HealthMap, and Google alerts from January 1, 2012, to December 31, 2014, a total of 27 (84%) recommended PEP for other food handlers or restaurant patrons or both. Per public health response, the mean cost per dose of the HepA vaccine or immunoglobulin was $34 139; the mean personnel cost per response was $7329; and the total mean cost of each response was $41 468. PEP is expensive. Less aggressive approaches to PEP, such as limiting PEP to fellow food handlers in nonoutbreak situations, should be considered in the postvaccination era. HepA vaccine for PEP provides long-term immunity and can be used when immunoglobulin is unavailable or cannot be administered within 14 days of exposure to HAV.

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis.

Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2-98.6) for HAV vaccine and 98.3% (95% CI 91.3-99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases.

The impact of assumptions regarding vaccine-induced immunity on the public health and cost-effectiveness of hepatitis A vaccination: Is one dose sufficient?

Hepatitis A vaccination stimulates memory cells to produce an anamnestic response. In this study, we used a mathematical model to examine how long-term immune memory might convey additional protection against clinical/icteric infections. Dynamic and decision models were used to estimate the expected number of cases, and the costs and quality-adjusted life-years (QALYs), respectively. Several scenarios were explored by assuming: (1) varying duration of vaccine-induced immune memory, (2) and/or varying levels of vaccine-induced immune memory protection (IMP), (3) and/or varying levels of infectiousness in vaccinated individuals with IMP. The base case analysis assumed a time horizon of 25 y (2012 - 2036), with additional analyses over 50 and 75 y. The analyses were conducted in the Mexican public health system perspective. In the base case that assumed no vaccine-induced IMP, the 2-dose hepatitis A vaccination strategy was cost-effective compared with the 1-dose strategy over the 3 time horizons. However, it was not cost-effective if we assumed additional IMP durations of at least 10 y in the 25-y horizon. In the 50- and 75-y horizons, the 2-dose strategy was always cost-effective, except when 100% reduction in the probability of icteric Infections, 75% reduction in infectiousness, and mean durations of IMP of at least 50 y were assumed. This analysis indicates that routine vaccination of toddlers against hepatitis A virus would be cost-effective in Mexico using a single-dose vaccination strategy. However, the cost-effectiveness of a second dose depends on the assumptions of additional protection by IMP and the time horizon over which the analysis is performed.

Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children.

BACKGROUND: Since 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12-23months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective. METHODS: We developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention. RESULTS: Over the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained. CONCLUSIONS: Given the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population.

Health economic assessment of universal immunization of toddlers against Hepatitis A Virus (HAV) in Mexico.

Hepatitis A virus (HAV) has shifted from high to intermediate endemicity in Mexico, which may increase the risk of clinically significant HAV infections in older children, adolescents and adults. The objective of this study was to evaluate the cost-utility of single-dose or 2-dose universal infant HAV vaccination strategy in Mexico, compared with no vaccination. A previously published dynamic model estimated the expected number of HAV cases with each strategy, and a decision model was used to estimate the costs and quality-adjusted life-years (QALYs) expected with each strategy. The time horizon was 25 years (2012-2036) and the base case analysis was conducted from the perspective of the Mexican public health system. Costs and QALYs after the first year were discounted at 5% annually. Input data were taken from national databases and published sources where available. The single-dose HAV vaccination strategy had an incremental cost-utility ratio (ICUR) of Mexican peso (MXN) 2,270 per QALY gained, compared with no vaccination. The two-dose strategy had an ICUR of MXN 14,961/QALY compared with no vaccination, and an ICUR of MXN 78,280/QALY compared with the single-dose strategy. The estimated ICURs were below the threshold of 1 x Mexican gross domestic product per capita. When indirect costs were included (societal perspective), the single-dose HAV vaccination strategy would be expected to improve health outcomes and to be cost-saving. This analysis indicates that routine vaccination of toddlers against HAV would be cost-effective in Mexico using either a single-dose or a 2-dose vaccination strategy. GSK study identifier: HO-12-12877.

Public Health Impact and Cost-Effectiveness of Hepatitis A Vaccination in the United States: A Disease Transmission Dynamic Modeling Approach.

OBJECTIVE: To assess the population-level impact and cost-effectiveness of hepatitis A vaccination programs in the United States. METHODS: We developed an age-structured population model of hepatitis A transmission dynamics to evaluate two policies of administering a two-dose hepatitis A vaccine to children aged 12 to 18 months: 1) universal routine vaccination as recommended by the Advisory Committee on Immunization Practices in 2006 and 2) Advisory Committee on Immunization Practices's previous regional policy of routine vaccination of children living in states with high hepatitis A incidence. Inputs were obtained from the published literature, public sources, and clinical trial data. The model was fitted to hepatitis A seroprevalence (National Health and Nutrition Examination Survey II and III) and reported incidence from the National Notifiable Diseases Surveillance System (1980-1995). We used a societal perspective and projected costs (in 2013 US $), quality-adjusted life-years, incremental cost-effectiveness ratio, and other outcomes over the period 2006 to 2106. RESULTS: On average, universal routine hepatitis A vaccination prevented 259,776 additional infections, 167,094 outpatient visits, 4781 hospitalizations, and 228 deaths annually. Compared with the regional vaccination policy, universal routine hepatitis A vaccination was cost saving. In scenario analysis, universal vaccination prevented 94,957 infections, 46,179 outpatient visits, 1286 hospitalizations, and 15 deaths annually and had an incremental cost-effectiveness ratio of $21,223/quality-adjusted life-year when herd protection was ignored. CONCLUSIONS: Our model predicted that universal childhood hepatitis A vaccination led to significant reductions in hepatitis A mortality and morbidity. Consequently, universal vaccination was cost saving compared with a regional vaccination policy. Herd protection effects of hepatitis A vaccination programs had a significant impact on hepatitis A mortality, morbidity, and cost-effectiveness ratios.

Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

BACKGROUND: Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. METHODS: A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000-2004 versus 2006-2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. RESULTS: Total HA and unspecified hepatitis cases decreased from 157,871 in 2000-2004 to 17,784 in 2006-2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006-2010 than in the previous period, respectively. CONCLUSION: After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the standard two-dose scheme, can be a good alternative for future vaccination policies in other countries where HA is endemic.

Cost-effectiveness of hepatitis A vaccination in Indonesia.

OBJECTIVE: This study aims to assess the cost-effectiveness of hepatitis A immunization in Indonesia, including an explicit comparison between one-dose and two-dose vaccines. METHODS: An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involved a 70-year time horizon with 1-month cycles for children less than 2 years old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination. RESULTS: Vaccination would save US$ 3,795,148 and US$ 2,892,920 from the societal perspective, for the two-dose and one-dose vaccine schedules, respectively, in the context of hepatitis A treatment. It also would save 8917 and 6614 discounted quality-adjusted-life-years (QALYs), respectively. With the vaccine price of US$ 3.21 per dose, the implementation of single dose vaccine would yield an incremental cost-effectiveness ratio (ICER) of US$ 4933 per QALY gained versus no vaccination, whereas the two-dose versus one-dose schedule would cost US$ 14 568 per QALY gained. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules in isolation, but two-dose vaccination would no longer be cost-effective if one-dose vaccination is a feasible option. Vaccination would be 100% affordable at budgets of US$ 71,408 000 and US$ 37,690,000 for the implementation of the two-dose and one-dose vaccine schedules, respectively. CONCLUSIONS: The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine price. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose schedule. The vaccine price, mortality rate and discount rate were the most influential parameters impacting the ICERs.

Public acceptance and willingness to hepatitis a vaccination in children aged 7-18 years in Republic of Korea.

Hepatitis A can cause serious illness among adolescents and adults with low vaccination coverage. Even though hepatitis A vaccine is one of the strong candidates for Korean national immunization program, adolescents aged older than 12 yr would not benefit. Our purpose was to assess the willingness and analyze the correlates of Korean mothers for hepatitis A (HepA) vaccination to develop strategies for HepA vaccination. A national telephone survey on 800 mothers with children aged 7-18 yr was conducted with random-digit dialing method. Sixty-two percent and 92% of the mothers reported that they were willing to HepA vaccination at current cost and at half of the current cost, respectively. However, at current cost, only 79% wished to vaccinate their child in an epidemic and 32% wished to vaccinate promptly. Having two or more children, not having future plans to send the child overseas, and low family income were significantly associated with not willing to HepA vaccination. Low perception of the susceptibility for hepatitis A and perception of the current cost as barrier increased the odds of unwillingness to vaccination at current cost and to prompt vaccination. The mothers' willingness to HepA vaccination for the children aged 7-18 yr in Korea was not very high at current cost and associated socioeconomic status and health-belief. Targeted intervention or strategies are needed to increase the HepA vaccination rate among children in Korea.

Public Acceptance and Willingness to Hepatitis A Vaccination in Children Aged 7-18 Years in Republic of Korea

Hepatitis A can cause serious illness among adolescents and adults with low vaccination coverage. Even though hepatitis A vaccine is one of the strong candidates for Korean national immunization program, adolescents aged older than 12 yr would not benefit. Our purpose was to assess the willingness and analyze the correlates of Korean mothers for hepatitis A (HepA) vaccination to develop strategies for HepA vaccination. A national telephone survey on 800 mothers with children aged 7-18 yr was conducted with random-digit dialing method. Sixty-two percent and 92% of the mothers reported that they were willing to HepA vaccination at current cost and at half of the current cost, respectively. However, at current cost, only 79% wished to vaccinate their child in an epidemic and 32% wished to vaccinate promptly. Having two or more children, not having future plans to send the child overseas, and low family income were significantly associated with not willing to HepA vaccination. Low perception of the susceptibility for hepatitis A and perception of the current cost as barrier increased the odds of unwillingness to vaccination at current cost and to prompt vaccination. The mothers' willingness to HepA vaccination for the children aged 7-18 yr in Korea was not very high at current cost and associated socioeconomic status and health-belief. Targeted intervention or strategies are needed to increase the HepA vaccination rate among children in Korea.

Economic evaluations of hepatitis A vaccination in middle-income countries.

Economic evaluations of hepatitis A vaccination are important to assist national and international policy makers in different jurisdictions on making effective decisions. Up to now, a comprehensive review of the potential health and economic benefits on hepatitis A vaccination in middle-income countries (MICs) has not been performed yet. In this study, we reviewed the literature on the cost-effectiveness of hepatitis A vaccination in MICs. Most of the studies confirmed that hepatitis A vaccination was cost effective or even cost saving under certain conditions. We found that vaccine price, medical costs, incidence and discount rate were the most influential parameters on the sensitivity analyses. Vaccine price has been shown as a barrier for MICs in implementing universal vaccination of hepatitis A. Given their relatively limited financial resources, implementation of single-dose vaccination could be considered. Despite our findings, we argue that further economic evaluations in MICs are still required in the near future.

Seroprevalence of hepatitis A virus in a cross-sectional study in Mexico: Implications for hepatitis A vaccination.

Hepatitis A virus (HAV) remains a public health concern worldwide contributing to significant morbidity in developed and developing countries. This cross-sectional database study estimated the overall HAV seroprevalence and the seroprevalence by gender, age, region and socioeconomic status in Mexico. Between January and October 2010, serum samples collected during the National Health and Nutrition survey (ENSANUT 2006) were obtained from subjects aged 1-95 y. Subjects' gender, age, geographical region and socioeconomic status were extracted from the survey and compiled into a subset database by the Mexican National Institute of Public Health. Anti-HAV antibodies were measured using a chemiluminescent immunoassay. A total of 3658 subjects were included in the according-to-protocol cohort. Overall, the HAV seroprevalence was 84.2%. The HAV seroprevalence rates were similar between females (86.1%) and males (82.2%). The percentage of subjects seropositive for anti-HAV antibodies was highest in adults aged ≥ 20 y (96.9%), followed by adolescents aged 10-19 y (80.1%) and lowest in children aged 1-9 y (45.0%) (p < 0.0001). Regionally, the highest HAV seroprevalence rate was observed in the South (88.8%) followed by Central and Northern Mexico and Mexico City (p = 0.02). The HAV seroprevalence was similar between subjects of high socioeconomic (90.1%) status and of low socioeconomic status (86.6%). This study confirms the intermediate HAV endemicity in Mexico. Cost-effectiveness studies are necessary to evaluate the inclusion of an effective hepatitis A vaccine from a population-based perspective in addition to continuous efforts to improve hygiene and sanitation that have a substantial impact on the disease burden.

Cost-effectiveness analysis of universal childhood hepatitis A vaccination in Brazil: regional analyses according to the endemic context.

OBJECTIVE: To conduct a cost-effectiveness analysis of a universal childhood hepatitis A vaccination program in Brazil. METHODS: An age and time-dependent dynamic model was developed to estimate the incidence of hepatitis A for 24 years. The analysis was run separately according to the pattern of regional endemicity, one for South+Southeast (low endemicity) and one for the North+Northeast+Midwest (intermediate endemicity). The decision analysis model compared universal childhood vaccination with current program of vaccinating high risk individuals. Epidemiologic and cost estimates were based on data from a nationwide seroprevalence survey of viral hepatitis, primary data collection, National Health Information Systems and literature. The analysis was conducted from both the health system and societal perspectives. Costs are expressed in 2008 Brazilian currency (Real). RESULTS: A universal immunization program would have a significant impact on disease epidemiology in all regions, resulting in 64% reduction in the number of cases of icteric hepatitis, 59% reduction in deaths for the disease and a 62% decrease of life years lost, in a national perspective. With a vaccine price of R$16.89 (US$7.23) per dose, vaccination against hepatitis A was a cost-saving strategy in the low and intermediate endemicity regions and in Brazil as a whole from both health system and society perspective. Results were most sensitive to the frequency of icteric hepatitis, ambulatory care and vaccine costs. CONCLUSIONS: Universal childhood vaccination program against hepatitis A could be a cost-saving strategy in all regions of Brazil. These results are useful for the Brazilian government for vaccine related decisions and for monitoring population impact if the vaccine is included in the National Immunization Program.

[Cost-utility analysis on universal childhood hepatitis A vaccination in regions with different anti-HAV prevalence rates of China].

OBJECTIVE: To explore the inputs and outputs of areas with different anti-HAV prevalence rates on universal childhood vaccination, and to provide a scientific basis for the formulation of the immunization strategy. METHODS: Since hepatitis A vaccination was scheduled at 12 and 18 months of age for all the healthy children, a single cohort including 1 000 000 individuals was formed in 2009, using the Chinese inactivated vaccine. Decision analysis was used to build Markov-decision tree model. The universal childhood hepatitis A vaccination was compared with non-vaccination group to evaluate the number of symptomatic infection, hospitalization, death, quality-adjusted life years (QALYs) lost, and the incremental cost-utility from the health system and the societal perspectives. Outcomes of the vaccination for the next 70 years were also predicted. The process of analysis was run separately in five regions defined by the anti-HAV prevalence rates (around 50%, 50% - 69%, 70% - 79%, 80% - 89% and > 90%). Sensitivity analysis was performed to test the stability or reliability of the results, and to identify sensitive variables. RESULTS: The study projected that, in the lowest, lower, and intermediate infection regions, the cost and output indicators of universal childhood hepatitis A vaccination were all lower than non-vaccinated group. Universal vaccination could gain QALYs and save both costs from the health system or the society. In the regions with higher infection rate, the output indicators of universal childhood hepatitis A vaccination were lower than in those non-vaccinated groups, except for the number of death due to hepatitis A, which had a 20 cases of increase. The model also predicted that in the highest infected region, universal vaccination would increase 4 560 814 and 5 840 430 RMB Yuan in the total costs from both the health system and the societies, respectively, when compared to the non-vaccination groups. Universal vaccination would also decrease the numbers of symptomatic infection, hospitalization, and QALYs lost, but would increase 51 deaths due to hepatitis A, and 1507, 1929 more RMB Yuan for each QALY gained from the health system and societal respectively, in the regions with highest infection rate. Sensitivity analyses discovered that the infection rate among those susceptible population and the proportion of those who initially under protection but subsequently lost their immunity every year, were the two main sensitive variables in the model. CONCLUSION: Our research discovered that the universal vaccination strategy should be based on the protective period of the vaccine and the anti-HAV prevalence in different endemic areas.

Cost-effectiveness of hepatitis A vaccination for adults in Belgium.

Hepatitis A vaccination targeting adults (or adult risk-groups like e.g. travellers, health care workers, soldiers or teachers) could be considered an alternative to a universal infant or adolescent vaccination program in low endemic countries. We estimated the current disease burden of hepatitis A in Belgium, and evaluated whether adult vaccination is cost-effective. We used a Markov cohort model to simulate the costs and effects of (1) vaccination of adults and (2) serological screening of adults and vaccination of susceptibles and compared these with the current situation. The results indicated that these expanded vaccination strategies are not cost-effective in the epidemiological circumstances of a typical low-endemic western country. In order to gain 1 quality-adjusted life year the health care payer would have to pay 185,000€ for vaccination and 223,000€ for screening and vaccination of seronegatives. For adult vaccination to be cost-effective, risk-groups would need to be exposed to a force of infection that is 3.5-4 times higher than currently estimated in the general population; or the total costs of vaccination would have to drop with approximately 75%.

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

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