The Burden of Hepatitis A Outbreaks in the United States: Health Outcomes, Economic Costs, and Management Strategies.

BACKGROUND: Hepatitis A (HepA) vaccines are recommended for US adults at risk of HepA. Ongoing United States (US) HepA outbreaks since 2016 have primarily spread person-to-person, especially among at-risk groups. We investigated the health outcomes, economic burden, and outbreak management considerations associated with HepA outbreaks from 2016 onwards. METHODS: A systematic literature review was conducted to assess HepA outbreak-associated health outcomes, health care resource utilization (HCRU), and economic burden. A targeted literature review evaluated HepA outbreak management considerations. RESULTS: Across 33 studies reporting on HepA outbreak-associated health outcomes/HCRU, frequently reported HepA-related morbidities included acute liver failure/injury (n = 6 studies of 33 studies) and liver transplantation (n = 5 of 33); reported case fatality rates ranged from 0% to 10.8%. Hospitalization rates reported in studies investigating person-to-person outbreaks ranged from 41.6% to 84.8%. Ten studies reported on outbreak-associated economic burden, with a national study reporting an average cost of over $16 000 per hospitalization. Thirty-four studies reported on outbreak management; challenges included difficulty reaching at-risk groups and vaccination distrust. Successes included targeted interventions and increasing public awareness. CONCLUSIONS: This review indicates a considerable clinical and economic burden of ongoing US HepA outbreaks. Targeted prevention strategies and increased public awareness and vaccination coverage are needed to reduce HepA burden and prevent future outbreaks.

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.

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.

Cost-effective analysis of hepatitis A vaccination in Kerala state, India.

Several hepatitis A outbreaks have recently been reported in Kerala state, India. To inform coverage decision of hepatitis A vaccine in Kerala, this study aimed to examine the cost-effectiveness of 1) hepatitis A vaccination among children aged 1 year and individuals aged 15 years, and 2) serological screening of individuals aged 15 years and vaccination of susceptible as compared to no vaccination or vaccination without serological screening. Both live attenuated hepatitis A vaccine and inactivated hepatitis A vaccine were considered in the analysis. A combination of decision tree and Markov models with a cycle length of one year was employed to estimate costs and benefits of different vaccination strategies. Analysis were based on both societal and payer perspectives. The lifetime costs and outcomes were discounted by 3%. Our findings indicated that all strategies were cost-saving for both societal and payer perspectives. Moreover, budget impact analysis revealed that vaccination without screening among individuals aged 15 years could save the government's budget by reducing treatment cost of hepatitis A. Our cost-effectiveness evidence supports the inclusion of hepatitis A vaccination into the vaccination program for children aged 1 year and individuals aged 15 years in Kerala state, India.

Hepatitis A virus vaccination in persons with hepatitis C virus infection: consequences of quality measure implementation.

UNLABELLED: Hepatitis A virus (HAV) superinfection in persons with hepatitis C virus (HCV) infection has been associated with a high mortality rate, and vaccination is recommended. The incidence of HAV is low, and the aim of this study was to determine the mortality risk of HAV superinfection and the consequences of routine vaccination in persons with HCV infection. To determine the mortality risk of HAV superinfection, a meta-analysis including studies reporting mortality in HCV-infected persons was performed. Data were extracted independently by two investigators and recorded on a standardized spreadsheet. The pooled mortality estimate was used to determine the number needed to vaccinate (NNV) to prevent mortality from HAV superinfection. The total vaccine cost was also calculated. A total of 239 studies were identified using a defined search strategy. Of these, 11 appeared to be relevant, and of these, 10 were suitable for inclusion in the meta-analysis. The pooled odds ratio (OR) for mortality risk in HAV superinfection of HCV-infected persons was 7.23 (95% confidence interval: 1.24-42.12) with significant heterogeneity (I(2) = 56%; P = 0.03) between studies. Using the pooled OR for mortality, this translates to 1.4 deaths per 1,000,000 susceptible persons with HCV per year. The NNV to prevent one death per year is therefore 814,849, assuming 90% vaccine uptake and 94.3% vaccine efficiency. The vaccine cost for this totals $162 million, or $80.1 million per death prevented per year. CONCLUSION: These data challenge the use of routine HAV vaccination in HCV-infected persons and its incorporation into clinical practice guidelines. HAV vaccination of all HCV-infected persons is costly and likely to expose many individuals to an intervention that is of no direct benefit.

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.

Should Brazilian patients with chronic hepatitis C virus infection be vaccinated against hepatitis A virus?

BACKGROUND AND AIM: Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with hepatitis C virus (HCV) infection. The aim of this study was to investigate the presence of serological and molecular HAV markers in a population of HCV-infected patients in order to determine a cost-effective strategy to vaccinate against HAV. METHODS: The presence of total and immunoglobulin (Ig)M anti-HAV antibodies was investigated in 399 patients (median age, 50 years; range, 4-81) referred to the Public Health Central Laboratory of Pernambuco State who tested positive for anti-HCV antibodies and HCV RNA. HAV RNA was investigated by reverse transcription-nested polymerase chain reaction in these patients. RESULTS: Three hundred and eighty-four (96%) patients were positive for anti-HAV total and negative for IgM anti-HAV antibodies (immune patients). Three patients had IgM (and total) anti-HAV antibodies, showing an acute infection, and two of them had HAV RNA detected in serum samples. HAV RNA was also found in another patient in the absence of detectable anti-HAV antibodies. By nucleotide sequencing, it was demonstrated that the HAV isolates infecting these patients belonged to subgenotype 1B. CONCLUSION: This study provides valuable new data on anti-HAV prevalence among HCV carriers in Brazil. In the present study, we found a high proportion of patients with anti-HAV positivity, indicating that anti-HAV testing of HCV-infected patients is a cost-effective strategy and should be carried out before vaccination against HAV in these patients, particularly in regions such as our geographical area with high total anti-HAV prevalence.

Comparison of two vaccination strategies against hepatitis A and B in patients with chronic hepatitis C.

OBJECTIVE: although the vaccination against hepatitis A (VAH) and hepatitis B (VBH) is recommended in patients with HCV, the most cost-effective strategy has not been established. Our objective was to compare the cost-effectiveness of universal strategy (vaccination all patients) with selective strategy (vaccination only patients against virus they lack immunity to) in patients with HCV. PATIENTS AND METHODS: we compared the direct medical costs of the two vaccination strategies against both viruses in 313 patients with HC. Serological markers for HAV (anti-HAV) and HBV (HbsAg, anti HBs, anti HBc) were determined in the 313 patients and the costs of the vaccines and the blood tests necessary to determinate the immunity state in our care system were considered. RESULTS: the prevalence of anti-HAV was 81,2% and of anti-HBc was 24,6%. The prevalence of anti-HAV increases with age. HAV vaccination with universal strategy has a cost of 19.806,64 euro and with selective one of 9.899,62 euro. HBV vaccination with universal strategy rose to 18.780 euro and to 20.385,57 euro with selective one (employing anti-HBc). Costs were analysed in different groups of age and several hepatitis HBV risk factors. CONCLUSIONS: the selective vaccination strategy against HAV was most cost-effective in our patients with HCV. However, when the prevalence of the anti-HAV decreased to less than 20% universal strategy will be the best option. Difference of cost-effective between the two vaccination strategies against HBV was small, on behalf of universal one, so in groups with higher anti-HBc prevalence, like parenteral drugs users and tattoos, the selective strategy could be the best option.

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).

The need for an evidence-based decision-making process with regard to control of hepatitis A.

Universal hepatitis A (HA) vaccination was implemented by the Argentinean Ministry of Health in June 2005 with a single dose at age 12 months. The decision was made taking into account the following factors. (1) Disease burden: The incidence rate for the disease increased from 2003 to 2004; the northern and western regions of the country were the most affected. Sero-prevalence data for children 1-15 years old was 54% for the whole country, with differences per region and age. From May 1982 to September 2002, 210 patients were recruited with acute hepatic failure; HA was the aetiology in 61% of them. (2) Cost-effectiveness: Compared with no vaccination, the one-dose schedule would save US$15.3 millions, with regional variations. (3) Vaccine features: Immunization with one-dose schedule HA vaccine confers good immunogenicity and effectiveness. (4) Programmatic feasibility: The National Immunizations Program has appropriate distribution system for vaccines, with adequate cold chain. (5) Social acceptance and political compromise: The population largely accepts HA vaccination and the national authorities should be committed to providing it regularly. The main global issue is that hepatitis A virus infection remains the most commonly reported vaccine-preventable disease in many parts of the world despite the availability of vaccines.

Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to explore the effect of methodological quality on the economic attractiveness of vaccination strategies.

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature.Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection.Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.

Seroprevalence of hepatitis A virus antibodies among a sample of Egyptian children.

We determined the seroprevalence of hepatitis A virus antibodies (HAV Ab) among 296 Egyptian children aged 2.5-18 years of different social classes to ascertain whether to give HAV vaccine early in life or to leave children to acquire natural immunity. Overall 61.4% were seropositive for HAV Ab. There was a significant increase in the seroprevalence of HAV Ab with higher age and lower social class; in children aged < 6 years, 72.7% of high and 19.0% of low social class were seronegative for HAV Ab. A national vaccination programme for HAV is not a priority. We recommend vaccination against hepatitis A for high social class children at the preschool period without testing for HAV. Vaccination for middle social class children can be done, but only after testing for HAV.

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 cost-effectiveness of universal vaccination of children against hepatitis A in Argentina: results of a dynamic health-economic analysis.

BACKGROUND: Socioeconomic improvements can reduce levels of endemic hepatitis A, but conversely increase the burden of disease. Routine childhood vaccination can rapidly control hepatitis A infection rates through the induction of herd immunity, although such programs can be costly. METHODS: We evaluated the healthcare benefits and cost-effectiveness of a routine childhood vaccination program against hepatitis A in Argentina, using a dynamic model that incorporated the changing epidemiology of infection and the impact of vaccine-induced herd immunity. Demographic, disease, and economic data from Argentina were used where available. RESULTS: At 95% coverage, the program would reduce the number of hepatitis A infections by 352,405 annually, avoiding 121,587 symptomatic cases and 428 deaths. Substantial healthcare benefits were also observed with vaccination coverage as low as 70%, which would prevent 295,826 infections. Economically, the program would save 23,989,963 US$ annually at 95% coverage, equivalent to 3,429 US$ per life-year gained. The program remained cost-saving in response to variation in factors, including disease-related costs, discount rate, herd immunity level, and rate of decrease of force of infection. The break-even cost per vaccine dose for the society was 25 US$ in the base-case, more than three times the current public cost of 7 US$ per dose. CONCLUSIONS: Routine childhood vaccination against hepatitis A showed both health benefits and robust economic benefits in this analysis, supporting the recent decision of the Argentine government to implement such a program.

Exploration of cost effectiveness of active vaccination in the control of a school outbreak of hepatitis A in a deprived community in the United Kingdom.

In January 2006, an outbreak of hepatitis A occurred in a socio-economically deprived area of Liverpool, in the United Kingdom (UK), where extensive community outbreaks of hepatitis had previously occurred. A total of nine cases were confirmed. Five of these were linked within a primary school. The outbreak initially occurred among a close social contact group, but there was evidence of subsequent person-to-person transmission within a local primary school. The school was attended by 221 pupils (age range 4-12 years) with a total of 37 teaching and other staff (age range 22-71 years). Following local risk assessment, mass hepatitis A virus (HAV) vaccination was offered to all staff and pupils, as all were judged to be likely to have been in close contact with the affected pupils. A total of 188 of 217 eligible children (87%), and 33 of 37 staff (89%) were vaccinated. A salivary seroprevalence survey was conducted at the same time as vaccination to assess the benefit of this intervention in the school population. The survey confirmed high levels of susceptibility to hepatitis A in this setting (97.8%, 95% CI 91.6 to 99.62). The direct costs of intervention were estimated as euro5,000. The cost effectiveness of intervention varies widely (euro60.50 to euro2,099 per case avoided) depending on the expected attack rate, which is difficult to estimate due to heterogeneity in published studies.

Geographic analysis of vaccine uptake in a cluster-randomized controlled trial in Hue, Vietnam.

This paper identifies spatial patterns and predictors of vaccine uptake in a cluster-randomized controlled trial in Hue, Vietnam. Data for this study result from the integration of demographic surveillance, vaccine record, and geographic data of the study area. A multi-level cross-classified (non-hierarchical) model was used for analyzing the non-nested nature of individual's ecological data. Vaccine uptake was unevenly distributed in space and there was spatial variability among predictors of vaccine uptake. Vaccine uptake was higher among students with younger, male, or not literate family heads. Students from households with higher per-capita income were less likely to participate in the trial. Residency south of the river or further from a hospital/polyclinic was associated with higher vaccine uptake. Younger students were more likely to be vaccinated than older students in high- or low-risk areas, but not in the entire study area. The findings are important for the management of vaccine campaigns during a trial and for interpretation of disease patterns during vaccine-efficacy evaluation.

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.

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.

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.