The epidemiologic and economic impact of varicella and herpes zoster vaccination in South Korea: A mathematical modelling study.

BACKGROUND: In South Korea, the National Immunization Program has included one-dose varicella vaccination for 1-year-olds since 2005. This study examines the potential impact of introducing a two-dose varicella vaccination for children, along with zoster vaccination for adults, using either the zoster vaccine live (ZVL) or recombinant zoster vaccine (RZV). METHODS: The investigation considered four strategies in a base case scenario. The first involved introducing zoster vaccination for 60-year-olds, with a 60 % coverage. The second strategy combined zoster vaccination with a second-dose varicella vaccination for 4-year-olds, with a 90 % coverage. An age-structured model spanning 50 years was employed, assuming a zoster vaccine catch-up campaign over the initial 5 years. Cost-effectiveness analyses were conducted, assessing incremental cost-effectiveness ratios (ICERs), incremental net monetary benefits (INMBs), and net loss under different ages at zoster vaccination (50, 60, 65, and 70 years) and varying willingness-to-pay (WTP) levels from ₩40 million ($34,998) to ₩84 million ($74,000). RESULTS: All strategies were cost-effective and significantly reduced herpes zoster (HZ) incidence, preventing approximately 3,077,000 to 7,609,000 cases, depending on the chosen strategy. The combined strategy prevented around 4,950,000 varicella and 653,000 HZ cases additionally. RZV outperformed ZVL by preventing twice as many HZ cases and offering greater QALY gains. However, ZVL was more cost-effective due to its lower cost. Probabilistic sensitivity analyses revealed that RZV became more cost-effective at higher WTP thresholds, exceeding ₩60.9 million ($53,193) in terms of ICER and ₩62.5 million ($54,591) for INMBs and net loss. The optimal age for zoster vaccination was 60 years concerning ICER but 50 years regarding INMB. CONCLUSIONS: Combining RZV with a two-dose varicella vaccination strategy reduced the disease burden and improved QALY more effectively, though ZVL remained more cost-effective at lower WTP levels. Decisions regarding vaccination policies should be balanced between the public health needs and WTP levels.

The clinical and economic costs associated with regional disparities in varicella vaccine coverage in Italy over 50 years (2020-2070).

Italy implemented two-dose universal varicella vaccination (UVV) regionally from 2003 to 2013 and nationally from 2017 onwards. Our objective was to analyze regional disparities in varicella outcomes resulting from disparities in vaccine coverage rates (VCRs) projected over a 50-year time-horizon (2020-2070). A previously published dynamic transmission model was updated to quantify the potential public health impact of the UVV program in Italy at the national and regional levels. Four 2-dose vaccine strategies utilizing monovalent (V) and quadrivalent (MMRV) vaccines were evaluated for each region: (A) MMRV-MSD/MMRV-MSD, (B) MMRV-GSK/MMRV-GSK, (C) V-MSD/MMRV-MSD, and (D) V-GSK/MMRV-GSK. Costs were reported in 2022 Euros. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually. Under strategy A, the three regions with the lowest first-dose VCR reported increased varicella cases (+ 34.3%), hospitalizations (+ 20.0%), QALYs lost (+ 5.9%), payer costs (+ 22.2%), and societal costs (+ 14.6%) over the 50-year time-horizon compared to the three regions with highest first-dose VCR. Regions with low first-dose VCR were more sensitive to changes in VCR than high first-dose VCR regions. Results with respect to second-dose VCR were qualitatively similar, although smaller in magnitude. Results were similar across all vaccine strategies.

An economic evaluation and incremental analysis of the cost effectiveness of three universal childhood varicella vaccination strategies for Ireland.

BACKGROUND: The cost effectiveness of childhood varicella vaccination is uncertain, as evidenced by variation in national health policies. Within the European Economic Area (EEA), only 10 of 30 countries offer universally funded childhood varicella vaccination. This study estimates the cost effectiveness of universal childhood varicella vaccination for one EEA country (Ireland), highlighting the difference in cost effectiveness between alternative vaccination strategies. METHODS: An age-structured dynamic transmission model, simulating varicella zoster virus transmission, was developed to analyse the impact of three vaccination strategies; one-dose at 12 months old, two-dose at 12 and 15 months old (short-interval), and two-dose at 12 months and five years old (long-interval). The analysis adopted an 80-year time horizon and considered payer and societal perspectives. Clinical effectiveness was based on cases of varicella and subsequently herpes zoster and post-herpetic neuralgia avoided, and outcomes were expressed in quality-adjusted life-years (QALYs). Costs were presented in 2022 Irish Euro and cost effectiveness was interpreted with reference to a willingness-to-pay threshold of €20,000 per QALY gained. RESULTS: From the payer perspective, the incremental cost-effectiveness ratio (ICER) for a one-dose strategy, compared with no vaccination, was estimated at €8,712 per QALY gained. The ICER for the next least expensive strategy, two-dose long-interval, compared with one-dose, was estimated at €45,090 per QALY gained. From a societal perspective, all three strategies were cost-saving compared with no vaccination; the two-dose short-interval strategy dominated, yielding the largest cost savings and health benefits. Results were stable across a range of sensitivity and scenario analyses. CONCLUSION: A one-dose strategy was highly cost effective from the payer perspective, driven by a reduction in hospitalisations. Two-dose strategies were cost saving from the societal perspective. These results should be considered alongside other factors such as acceptability of a new vaccine within the overall childhood immunisation schedule, programme objectives and budget impact.

Clinical and economic impact of universal varicella vaccination in Norway: A modeling study.

BACKGROUND: Norway has not implemented universal varicella vaccination, despite the considerable clinical and economic burden of varicella disease. METHODS: An existing dynamic transmission model of varicella infection was calibrated to age-specific seroprevalence rates in Norway. Six two-dose vaccination strategies were considered, consisting of combinations of two formulations each of a monovalent varicella vaccine (Varivax® or Varilrix®) and a quadrivalent vaccine against measles-mumps-rubella-varicella (ProQuad® or PriorixTetra®), with the first dose given with a monovalent vaccine at age 15 months, and the second dose with either a monovalent or quadrivalent vaccine at either 18 months, 7 or 11 years. Costs were considered from the perspectives of both the health care system and society. Quality-adjusted life-years saved and incremental cost-effectiveness ratios relative to no vaccination were calculated. A one-way sensitivity analysis was conducted to assess the impact of vaccine efficacy, price, the costs of a lost workday and of inpatient and outpatient care, vaccination coverage, and discount rate. RESULTS: In the absence of varicella vaccination, the annual incidence of natural varicella is estimated to be 1,359 per 100,000 population, and the cumulative numbers of varicella outpatient cases, hospitalizations, and deaths over 50 years are projected to be 1.81 million, 10,161, and 61, respectively. Universal varicella vaccination is projected to reduce the natural varicella incidence rate to 48-59 per 100,000 population, depending on the vaccination strategy, and to reduce varicella outpatient cases, hospitalizations, and deaths by 75-85%, 67-79%, and 75-79%, respectively. All strategies were cost-saving, with the most cost-saving as two doses of Varivax® at 15 months and 7 years (payer perspective) and two doses of Varivax® at 15 months and 18 months (societal perspective). CONCLUSIONS: All modeled two-dose varicella vaccination strategies are projected to lead to substantial reductions in varicella disease and to be cost saving compared to no vaccination in Norway.

Cost-effectiveness of varicella and herpes zoster vaccination in Sweden: An economic evaluation using a dynamic transmission model.

OBJECTIVES: Comprehensive cost-effectiveness analyses of introducing varicella and/or herpes zoster vaccination in the Swedish national vaccination programme. DESIGN: Cost-effectiveness analyses based on epidemiological results from a specifically developed transmission model. SETTING: National vaccination programme in Sweden, over an 85- or 20-year time horizon depending on the vaccination strategy. PARTICIPANTS: Hypothetical cohorts of people aged 12 months and 65-years at baseline. INTERVENTIONS: Four alternative vaccination strategies; 1, not to vaccinate; 2, varicella vaccination with one dose of the live attenuated vaccine at age 12 months and a second dose at age 18 months; 3, herpes zoster vaccination with one dose of the live attenuated vaccine at 65 years of age; and 4, both vaccine against varicella and herpes zoster with the before-mentioned strategies. MAIN OUTCOME MEASURES: Accumulated cost and quality-adjusted life years (QALY) for each strategy, and incremental cost-effectiveness ratios (ICER). RESULTS: It would be cost-effective to vaccinate against varicella (dominant), but not to vaccinate against herpes zoster (ICER of EUR 200,000), assuming a cost-effectiveness threshold of EUR 50,000 per QALY. The incremental analysis between varicella vaccination only and the combined programme results in a cost per gained QALY of almost EUR 1.6 million. CONCLUSIONS: The results from this study are central components for policy-relevant decision-making, and suggest that it was cost-effective to introduce varicella vaccination in Sweden, whereas herpes zoster vaccination with the live attenuated vaccine for the elderly was not cost-effective-the health effects of the latter vaccination cannot be considered reasonable in relation to its costs. Future observational and surveillance studies are needed to make reasonable predictions on how boosting affects the herpes zoster incidence in the population, and thus the cost-effectiveness of a vaccination programme against varicella. Also, the link between herpes zoster and sequelae need to be studied in more detail to include it suitably in health economic evaluations.

Health Impact and Cost-effectiveness Assessment for the Introduction of Universal Varicella Vaccination in Switzerland.

BACKGROUND: Varicella, caused by the varicella-zoster virus, is a highly contagious infectious disease with substantial health and economic burden to society. Universal varicella vaccination (UVV) is not yet recommended by the Swiss National Immunization Program, which instead recommends catch-up immunization for children, adolescents and adults 11-40 years of age who have no reliable history of varicella or are varicella-zoster virus-IgG seronegative. The objective of this study was to perform an assessment of health impact and cost-effectiveness comparing UVV with current practice and recommendations in Switzerland. METHODS: A dynamic transmission model for varicella was adapted to Switzerland comparing 2 base-case schedules (no infant vaccination and 10% coverage with infant vaccination) to 3 different UVV schedules using quadrivalent (varicella vaccine combined with measles-mumps-rubella) and standalone varicella vaccines administered at different ages. Modeled UVV coverage rates were based on current measles-mumps-rubella coverage of approximately 95% (first dose) and 90% (second dose). Direct medical costs and societal perspectives were considered, with cost and outcomes discounted and calculated over a 50-year time horizon. RESULTS: UVV would reduce the number of varicella cases by 88%-90%, hospitalizations by 62%-69% and deaths by 75%-77%. UVV would increase direct medical costs by Swiss Franc (CHF) 39-49 (US $43-54) per capita and costs from a societal perspective by CHF 32-40 (US $35-44). Incremental quality-adjusted life-years per capita increased by 0.0012-0.0014. Incremental cost-effectiveness ratios for the UVV schedules versus the base-case were CHF 31,194-35,403 (US $34,452-39,100) per quality-adjusted life-year from the direct medical cost perspective and CHF 25,245-29,552 (US $27,881-32,638) from the societal perspective. CONCLUSIONS: UVV appears highly effective and cost-effective when compared with current clinical practice and recommendations in Switzerland from both a direct medical costs perspective and societal perspective.

What We Know Now: An Economic Evaluation of Chickenpox Vaccination and Dose Timing Using an Agent-Based Model.

OBJECTIVES: The value of chickenpox vaccination is still debated in the literature and by jurisdictions worldwide. This uncertainty is reflected in the inconsistent uptake of the vaccine, where some countries offer routine childhood immunization programs, others have targeted programs, and in many the vaccine is only privately available. Even across the countries that have universal funding for the vaccine, there is a diversity of schedules and dosing intervals. Using an agent-based model of chickenpox and shingles, we conducted an economic evaluation of chickenpox vaccination in Alberta, Canada. METHODS: We compared the cost-effectiveness of 2 common chickenpox vaccination schedules, specifically a long dosing interval (first dose: 12 months; second dose: 4-6 years) and a short dosing interval (first dose: 12 months; second dose: 18 months). RESULTS: The economic evaluation demonstrated a shorter dosing interval may be marginally preferred, although it consistently led to higher costs from both the societal and healthcare perspectives. We found that chickenpox vaccination would be cost-saving and highly cost-effective from the societal and healthcare perspective, assuming there was no impact on shingles. CONCLUSION: Chickenpox vaccine was cost-effective when not considering shingles and remained so even if there was a minor increase in shingles following vaccination. However, if chickenpox vaccination did lead to a substantial increase in shingles, then chickenpox vaccination was not cost-effective from the healthcare perspective.

Cost-effectiveness analysis of universal varicella vaccination in Turkey using a dynamic transmission model.

BACKGROUND: In 2013, Turkey introduced one-dose universal varicella vaccination (UVV) at 12 months of age. Inclusion of a second dose is being considered. METHODS: We developed a dynamic transmission model to evaluate three vaccination strategies: single dose at 12 months (1D) or second dose at either 18 months (2D-short) or 6 years of age (2D-long). Costs and utilization were age-stratified and separated into inpatient and outpatient costs for varicella and herpes zoster (HZ). We ran the model including and excluding HZ-related costs and impact of exogenous boosting. RESULTS: Five years post-introduction of UVV (1D), the projected varicella incidence rate decreases from 1,674 cases pre-vaccine to 80 cases/100,000 person-years. By 25 years, varicella incidence equilibrates at 39, 12, and 16 cases/100,000 person-years for 1D, 2D-short, and 2D-long strategies, respectively, using a highly effective vaccine. With or without including exogenous boosting impact and/or HZ-related costs and health benefits, the 1D strategy is least costly, but 2-dose strategies are cost-effective considering a willingness-to-pay threshold equivalent to the gross domestic product. The model predicted a modest increase in HZ burden during the first 20-30 years, after which time HZ incidence equilibrates at a lower rate than pre-vaccine. CONCLUSIONS: Our findings support adding a second varicella vaccine dose in Turkey, as doing so is highly cost-effective across a wide range of assumptions regarding the burden associated with varicella and HZ disease.

Cost-effectiveness of Recombinant Zoster Vaccine (RZV) and Varicella Vaccine Live (VVL) against herpes zoster and post-herpetic neuralgia among adults aged 65 and over in Japan.

BACKGROUND: The approval of the extended use of 1-dose varicella vaccine (VVL) in adults aged 50 and older against herpes zoster (HZ) in 2016 and the 2-dose recombinant zoster vaccine (RZV) in 2018 raised the need to evaluate the value for money between these two vaccines. METHODS: We conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of the immunisation programmes from payer's perspective. Eight strategies with different ages to receive VVL or RZV were set, namely: 65-84 year old (y.o.), 70-84 y.o., 75-84 y.o., and 80-84 y.o. VVL- or RZV-strategy. Incremental cost-effectiveness ratios (ICERs) compared with curative care scenario were calculated. The health statuses following the target cohort were as follows: acute HZ followed by recovery, post-herpetic neuralgia followed by recovery, post HZ/PHN, recurrence of HZ, and general death. RESULTS: At the vaccination cost ¥8000 (US$73) for 1-dose ZVL and ¥30,000 (US$273) for 2-dose RZV, ICERs ranged from ¥2,633,587/US$23,942 (age 80-84 y.o.) to ¥3,434,267 or US$31,221 (age 65-84 y.o.)/QALY gained for VVL-strategies; from ¥5,262,227 or US$47,838 (age 80-84 y.o.) to ¥6,278,557 or US$57,078/QALY gained (age 65-84 y.o.) for RZV-strategies. Cost-effectiveness acceptability curves derived from probabilistic sensitivity analyses showed that if the cost-effective threshold was at ¥3,000,000 or US$27,273/QALY, the acceptability was 90.7% and 8.8% for 65-84 VVL-strategy and 65-84 RZV-strategy, respectively; if at ¥5,000,000 or US$45,455/QALY, 56.2% and 43.8%, and if at ¥10,000,000 or US$90,909/QALY 11.9% and 88.1%, respectively. CONCLUSION: Vaccinating individuals aged 65-84 y.o., 70-84 y.o., 75-84 y.o., 80-84 y.o. with VVL or RZV to prevent HZ-associated disease in Japan can be cost-effective from payer's perspective, with vaccination costs at ¥8,000 per shot for VVL, ¥30,000 for 2-dose RZV. While the results suggesting that only 65-84 VVL-strategy and 65-84 RZV strategy should be considered when introducing HZ immunisation programme. The optimal strategy varies depending on the willingness-to-pay threshold.

The impact of demographic changes, exogenous boosting and new vaccination policies on varicella and herpes zoster in Italy: a modelling and cost-effectiveness study.

BACKGROUND: The present study aims to evaluate the cost-effectiveness of the newly introduced varicella and herpes zoster (HZ) vaccination programmes in Italy. The appropriateness of the introduction of the varicella vaccine is highly debated because of concerns about the consequences on HZ epidemiology and the expected increase in the number of severe cases in case of suboptimal coverage levels. METHODS: We performed a cost-utility analysis based on a stochastic individual-based model that considers realistic demographic processes and two different underlying mechanisms of exogenous boosting (temporary and progressive immunity). Routine varicella vaccination is given with a two-dose schedule (15 months, 5-6 years). The HZ vaccine is offered to the elderly (65 years), either alone or in combination with an initial catch-up campaign (66-75 years). The main outcome measures are averted cases and deaths, costs per quality-adjusted life years gained, incremental cost-effectiveness ratios, and net monetary benefits associated with the different vaccination policies. RESULTS: Demographic processes have contributed to shaping varicella and HZ epidemiology over the years, decreasing varicella circulation and increasing the incidence of HZ. The recent introduction of varicella vaccination in Italy is expected to produce an enduring reduction in varicella incidence and, indirectly, a further increase of HZ incidence in the first decades, followed by a significant reduction in the long term. However, the concurrent introduction of routine HZ vaccination at 65 years of age is expected to mitigate this increase and, in the longer run, to reduce HZ burden to its minimum. From an economic perspective, all the considered policies are cost-effective, with the exception of varicella vaccination alone when considering a time horizon of 50 years. These results are robust to parameter uncertainties, to the two different hypotheses on the mechanism driving exogenous boosting, and to different demographic projection scenarios. CONCLUSIONS: The recent introduction of a combined varicella and HZ vaccination programme in Italy will produce significant reductions in the burden of both diseases and is found to be a cost-effective policy. This programme will counterbalance the increasing trend of zoster incidence purely due to demographic processes.

[Varicella vaccination: scientific reasons for a different strategic approach]. / Vaccinazione antivaricella: argomenti scientifici per possibili strategie diverse dalle attuali.

The Italian Parliament has recently introduced 10 mandatory immunisations, including the one against varicella. For this vaccination, the obligation starts with the birth cohort of 2017, but it is offered free of charge to subjects with a negative history and not previously vaccinated. This paper presents up-to-date evidence on this issue and illustrates a number of critical arguments that may question the opportunity of this choice. Particularly, while the disease is relatively mild in children aged between 1 and 9 years, the risk of worsening its consequences is progressive with age, becoming worst in the elderly, so the vaccination of children may increase the age of the cases. Some vaccine side effects are not trivial and the duration of protection is still uncertain, as well as the cost-effectiveness of mass vaccination and its long-term effects, referring to virus reactivation and to the incidence of Herpes zoster in the general population, which could be increased and anticipated in the long run. Varicella vaccination is not included in international eradication goals and very few Europeans Countries have considered it as a public health priority. A different rational choice could have been to offer a selective vaccination only to adolescents with a negative history of chickenpox; or at least to delay the beginning of the universal campaign in the Italian regions that had not started the mass vaccination yet, evaluating the results over time. Lastly, this paper lists a number of preventive interventions of proven effectiveness and cost-effectiveness, with extraordinary margins of improvement, whose mandatory introduction in the population have never been considered, even as a matter of debate.

Estudio coste-beneficio de la vacunación contra varicela en Aragón / A cost-benefit analysis of varicella vaccination in Aragón

Fundamento. La varicela, enfermedad infecto-contagiosa que afecta a la infancia de forma benigna, puede complicarse en adultos y niños vulnerables y ser mortal. Existen vacunas eficaces. Se estudiaron retrospectivamente los costes que supuso esta enfermedad en la población aragonesa en el período 2004-2014 y las hospitalizaciones generadas. Se compararon con los gastos que supondría haber vacunado a esas personas y también los gastos de vacunar a la población de 1 año de edad durante todo ese período. Mediante un análisis coste-beneficio, se evaluó el impacto económico de la vacunación. Método. Se utilizaron datos de la Autonomía de Aragón (España) de estos 11 años (incidencia anual de varicela, altas hospitalarias por este motivo, precio de la consulta de atención primaria y de hospitalización de cada año, así como el coste de días de trabajo según el salario mínimo anual y medicaciones utilizadas). Se calcularon los costes capitalizados, se compararon con los gastos capitalizados de vacunación y se realizó un análisis de sensibilidad. Resultados. Se obtuvo un índice beneficio-coste de 1,6 vacunando y revacunando a todos los niños que se enfermaron. Resultó un índice beneficio-coste de 1,24 al vacunar a toda la población de 12 meses con vacuna de 28,59€. En estos 11 años, el 53% de las hospitalizaciones fueron niños menores de 5 años. Conclusiones. Las campañas públicas de vacunación con 2 dosis a población menor de 4 años suponen ahorro y rentabilidad porque el precio de la vacuna permite un índice beneficio-coste superior a 1. Es esperable una gran disminución de hospitalizaciones en la población de 3-4 años.

Background. Varicella, a contagious and infectious disease that is usually benign in children, may become complicated among adults and vulnerable children and may even be life-threatening. There are effective vaccines. A retrospective study was conducted about costs and resulting hospitalizations related to this disease in the population of Aragón in the 2004-2014 period. Costs were compared to the expenses that would have been incurred if those people had received the vaccine and also to the expenses of vaccinating the 1-year-old population over the entire period. A cost-benefit analysis was done to assess the economic impact of varicella vaccination. Method. Data for the 11-year period were provided by the Autonomous Community of Aragón (Spain) and included annual varicella incidence, hospital discharges of varicella cases, costs of primary health care visits and hospitalizations for each year, costs of each workday as per the minimum annual salary and of drugs used). Capitalized costs were estimated and compared to capitalized expenses of vaccination, and a sensitivity analysis was performed. Results. A benefit-cost ratio of 1.6 was obtained considering that all children who had varicella had been vaccinated and had received a booster dose. A benefit-cost ratio of 1.24 was obtained considering that the vaccine had been administered to every 1-year-old individual at a price of EUR 28.59 per vaccine. Over the 11-year period, 53% of hospitalizations corresponded to children younger than 5 years old. Conclusions. Public campaigns for the immunization of children younger than 4 years old with 2 doses lead to cost savings and are cost-effective because the vaccine price results in a benefit-cost ratio greater than 1. A major reduction is expected in the number of hospitalizations among children aged 3-4 years.

A cost-benefit analysis of varicella vaccination in Aragón. / Estudio coste-beneficio de la vacunación contra varicela en Aragón.

BACKGROUND: Varicella, a contagious and infectious disease that is usually benign in children, may become complicated among adults and vulnerable children and may even be life-threatening. There are effective vaccines. A retrospective study was conducted about costs and resulting hospitalizations related to this disease in the population of Aragón in the 2004-2014 period. Costs were compared to the expenses that would have been incurred if those people had received the vaccine and also to the expenses of vaccinating the 1-year-old population over the entire period. A cost-benefit analysis was done to assess the economic impact of varicella vaccination. METHOD: Data for the 11-year period were provided by the Autonomous Community of Aragón (Spain) and included annual varicella incidence, hospital discharges of varicella cases, costs of primary health care visits and hospitalizations for each year, costs of each workday as per the minimum annual salary and of drugs used). Capitalized costs were estimated and compared to capitalized expenses of vaccination, and a sensitivity analysis was performed. RESULTS: A benefit-cost ratio of 1.6 was obtained considering that all children who had varicella had been vaccinated and had received a booster dose. A benefit-cost ratio of 1.24 was obtained considering that the vaccine had been administered to every 1-year-old individual at a price of EUR 28.59 per vaccine. Over the 11-year period, 53% of hospitalizations corresponded to children younger than 5 years old. CONCLUSIONS: Public campaigns for the immunization of children younger than 4 years old with 2 doses lead to cost savings and are cost-effective because the vaccine price results in a benefit-cost ratio greater than 1. A major reduction is expected in the number of hospitalizations among children aged 3-4 years.

FUNDAMENTOS: La varicela, enfermedad infecto-contagiosa que afecta a la infancia de forma benigna, puede complicarse en adultos y niños vulnerables y ser mortal. Existen vacunas eficaces. Se estudiaron retrospectivamente los costes que supuso esta enfermedad en la población aragonesa en el período 2004-2014 y las hospitalizaciones generadas. Se compararon con los gastos que supondría haber vacunado a esas personas y también los gastos de vacunar a la población de 1 año de edad durante todo ese período. Mediante un análisis coste-beneficio, se evaluó el impacto económico de la vacunación. MÉTODO: Se utilizaron datos de la Autonomía de Aragón (España) de estos 11 años (incidencia anual de varicela, altas hospitalarias por este motivo, precio de la consulta de atención primaria y de hospitalización de cada año, así como el coste de días de trabajo según el salario mínimo anual y medicaciones utilizadas). Se calcularon los costes capitalizados, se compararon con los gastos capitalizados de vacunación y se realizó un análisis de sensibilidad. RESULTADOS: Se obtuvo un índice beneficio-coste de 1,6 vacunando y revacunando a todos los niños que se enfermaron. Resultó un índice beneficio-coste de 1,24 al vacunar a toda la población de 12 meses con vacuna de 28,59€. En estos 11 años, el 53% de las hospitalizaciones fueron niños menores de 5 años. CONCLUSIONES: Las campañas públicas de vacunación con 2 dosis a población menor de 4 años suponen ahorro y rentabilidad porque el precio de la vacuna permite un índice beneficio-coste superior a 1. Es esperable una gran disminución de hospitalizaciones en la población de 3-4 años.

Economic burden of varicella in children 1-12 Years of age in Hungary, 2011-2015.

BACKGROUND: Although live-attenuated varicella-zoster virus (VZV) vaccines have been proven to be safe and effective in preventing varicella and real-word evidence shows routine childhood immunization programs are effective in dramatically reducing varicella associated morbidity and mortality, varicella vaccine is not included in the National Immunization Program (NIP) in Hungary. The purpose of this study was to evaluate the clinical and economic burden associated with varicella in Hungary. METHODS: This was a multicenter, retrospective, chart review study of patients aged 1-12 years with a primary varicella diagnosis between 2011 and 2015. Healthcare resource utilization (HCRU) associated with varicella, unit costs, and work loss were used to estimate direct and indirect costs. All costs are presented in 2015 HUF / Euros (€). RESULTS: 156 children with varicella were included (75 outpatients, 81 inpatients), with a mean age of 4.4 (SD: 2.0) and 3.7 (SD: 2.1) years, respectively. One or more complications were reported by 12.0% of outpatients and 92.6% of inpatients, the most common being dehydration, skin and soft tissue infections, pneumonia, keratoconjunctivitis, and cerebellitis. HCRU estimates included use of over-the-counter (OTC) medications (96.0% outpatients, 53.1% inpatients), prescription medications (9.3% outpatients, 70.4% inpatients), tests/procedures (4.0% outpatients, 97.5% inpatients), and consultation with allied health professionals (2.7% outpatients, 30.9% inpatients). The average duration of hospital stay (inpatients) was 3.6 (95% CI: 3.2, 4.1) days. The total combined direct and indirect cost per varicella case was 228,146.7 Hungarian Forint (HUF)/€ 736.0 for inpatients and 49,790.6 HUF/€ 106.6 for outpatients. The overall annual cost of varicella in Hungary for children aged <15 years in 2015 was estimated at 1,903,332,524.3 HUF/ € 6,139,980.4. CONCLUSION: Varicella is associated with substantial clinical burden in Hungary, resulting in the utilization of a significant amount of healthcare resources. These results support the need for routine vaccination of all healthy children to reduce the varicella-associated disease burden.

Cost-effectiveness of varicella vaccine against herpes zoster and post-herpetic neuralgia for elderly in Japan.

BACKGROUND: The extended use of varicella vaccine in adults aged 50 and older against herpes zoster (HZ) was recently approved in Japan, which has raised the need to evaluate its value for money. METHODS: We conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of varicella vaccine immunisation programme for the elderly in Japan. Four strategies with different ages to receive a shot of vaccine were set, namely: (1) 65-84, (2) 70-84, (3) 75-84 and (4) 80-84years old (y.o.). Incremental cost-effectiveness ratios (ICERs) compared with no programme from societal perspective were calculated. The health statuses following the target cohort are as follows: without any HZ-related disease, acute HZ followed by recovery, post-herpetic neuralgia (PHN) followed by recovery, post HZ/PHN, and general death. The transition probabilities, utility weights to estimate quality-adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Costs of per course of vaccination were assumed at ¥10,000 (US$91). The model with one-year cycle runs until the surviving individual reached 100 y.o. RESULTS: ICERs ranged from ¥2,812,000/US$25,680 to ¥3,644,000/US$33,279 per QALY gained, with 65-84 y.o. strategy having the lowest ICER and 80-84 y.o. strategy the highest. None of the alternatives was strongly dominated by the other, while 80-84 y.o. and 70-84 y.o. strategy were extendedly dominated by 65-84 y.o. STRATEGY: Probabilistic sensitivity analyses showed that the probabilities that ICER is under ¥5,000,000/US$45,662 per QALY gained was at 100% for 65-84 y.o., 70-84 y.o., 75-84 y.o. strategy, respectively, and at 98.4% for 80-84 y.o. CONCLUSION: We found that vaccinating individuals aged 65-84, 70-84, 75-84, and 80-84 with varicella vaccine to prevent HZ-associated disease in Japan can be cost-effective from societal perspective, with 65-84 y.o. strategy as the optimal alternative. Results are supported by one-way sensitivity analyses and probabilistic sensitivity analyses.

Coverage, efficacy or dosing interval: which factor predominantly influences the impact of routine childhood vaccination for the prevention of varicella? A model-based study for Italy.

BACKGROUND: Varicella is a highly infectious disease with a significant public health and economic burden, which can be prevented with childhood routine varicella vaccination. Vaccination strategies differ by country. Some factors are known to play an important role (number of doses, coverage, dosing interval, efficacy and catch-up programmes), however, their relative impact on the reduction of varicella in the population remains unclear. This paper aims to help policy makers prioritise the critical factors to achieve the most successful vaccination programme with the available budget. METHODS: Scenarios assessed the impact of different vaccination strategies on reduction of varicella disease in the population. A dynamic transmission model was used and adapted to fit Italian demographics and population mixing patterns. Inputs included coverage, number of doses, dosing intervals, first-dose efficacy and availability of catch-up programmes, based on strategies currently used or likely to be used in different countries. The time horizon was 30 years. RESULTS: Both one- and two-dose routine varicella vaccination strategies prevented a comparable number of varicella cases with complications, but two-doses provided broader protection due to prevention of a higher number of milder varicella cases. A catch-up programme in susceptible adolescents aged 10-14 years old reduced varicella cases by 27-43 % in older children, which are often more severe than in younger children. Coverage, for all strategies, sustained at high levels achieved the largest reduction in varicella. In general, a 20 % increase in coverage resulted in a further 27-31 % reduction in varicella cases. When high coverage is reached, the impact of dosing interval and first-dose vaccine efficacy had a relatively lower impact on disease prevention in the population. Compared to the long (11 years) dosing interval, the short (5 months) and medium (5 years) interval schedules reduced varicella cases by a further 5-13 % and 2-5 %, respectively. Similarly, a 10 % increase in first-dose efficacy (from 65 to 75 % efficacy) prevented 2-5 % more varicella cases, suggesting it is the least influential factor when considering routine varicella vaccination. CONCLUSIONS: Vaccination strategies can be implemented differently in each country depending on their needs, infrastructure and healthcare budget. However, ensuring high coverage remains the critical success factor for significant prevention of varicella when introducing varicella vaccination in the national immunisation programme.

Varicella-zoster virus susceptibility and primary healthcare consultations in Norway.

BACKGROUND: Currently Norway does not recommend universal varicella vaccination for healthy children. This study assessed susceptibility to varicella-zoster virus (VZV) in the Norwegian population for the first time. METHODS: A national convenience sample of residual sera was tested for anti-VZV IgG by ELISA. We estimated age-specific seropositivity to VZV, controlling for sex and geographical distribution. We assessed differences between the proportions using the chi-square test and multivariable logistic regression. Seroprevalence data were compared to the varicella and herpes zoster-associated consultation rates in patients attending primary healthcare. RESULTS: Although 73.2 % (n = 1,540) of all samples were positive for VZV, only 11.2 % of samples collected from 1-year-olds were seropositive. There was a sharp increase in the proportion of seropositive in 3- and 5-year-olds (40.2 % and 65.4 %, respectively). By the school entry age of 6 years, 69.8 % of children were seropositive. The age-specific annual consultation rate for varicella in primary healthcare peaked in 1-year-olds, with 2,627 cases per 100,000 population. The profile of varicella-related consultations in primary healthcare mirrored the VZV seropositivity profile. The herpes zoster-related consultations in primary healthcare peaked in people over 70 years of age (702 cases per 100,000 population). CONCLUSIONS: VZV seroprevalence in Norway was somewhat lower than in some other European countries. The age-specific varicella-related consultation rates in primary healthcare mirrored the age profile of VZV seroprevalence.

The Cost-effectiveness of Varicella Zoster Virus Vaccination Considering Late Onset Asthma.

BACKGROUND: Recent studies reported that infection by varicella zoster virus (VZV) may lead to delayed onset of asthma in children/adolescents. This information will likely alter the cost-effectiveness of the US. VZV vaccination program. We created a decision analysis model to estimate the costs and health-related effects of VZV 2-dose vaccination, assuming VZV infection delays asthma onset. METHODS: The Markov model considered a birth cohort of 3,957,577 individuals entering the population from a societal perspective. We predicted the number of asthma/VZV cases, asthma-/VZV-related mortality and costs associated with asthma/VZV. Comparison arms included (1) VZV vaccination program without delayed asthma onset, (2) VZV vaccination program with delayed asthma onset and (3) no VZV vaccination program with delayed asthma onset. We considered delayed onset ranging from 3 to 12 years. RESULTS: The vaccination program proved cost-effective without an assumed delay in asthma onset. When the vaccination and no-vaccination arms were compared assuming delayed asthma onset, vaccination remained less costly despite increased savings related to asthma without vaccination. With delayed asthma onset of 9 years post VZV infection, cost savings due to vaccination were $914.09 million, with 9984 cases of asthma averted and 9 greater overall deaths with vaccination. CONCLUSION: VZV vaccination program was less costly than the "no-vaccination" scenario, despite delayed onset of asthma post VZV infection. However, vaccination resulted in increased asthma morbidity and mortality. This adds to current evidence that VZV vaccination is cost-effective, and may alter asthma-related health-care outcomes. VZV's effect on asthma symptoms still needs further evaluation before firm conclusions can be reached.

Economic evaluation of pediatric influenza immunization program compared with other pediatric immunization programs: A systematic review.

This study compared the economic value of pediatric immunisation programmes for influenza to those for rotavirus (RV), meningococcal disease (MD), pneumococcal disease (PD), human papillomavirus (HPV), hepatitis B (Hep B), and varicella reported in recent (2000 onwards) cost-effectiveness (CE) studies identified in a systematic review of PubMed, health technology, and vaccination databases. The systematic review yielded 51 economic evaluation studies of pediatric immunisation - 10 (20%) for influenza and 41 (80%) for the other selected diseases. The quality of the eligible articles was assessed using Drummond's checklist. Although inherent challenges and limitations exist when comparing economic evaluations of immunisation programmes, an overall comparison of the included studies demonstrated cost-effectiveness/cost saving for influenza from a European-Union-Five (EU5) and United States (US) perspective; point estimates for cost/quality-adjusted life-years (QALY) from dominance (cost-saving with more effect) to ≤45,444 were reported. The economic value of influenza programmes was comparable to the other vaccines of interest, with cost/QALY in general considerably lower than RV, Hep B, MD and PD. Independent of the perspective and type of analysis, the economic impact of a pediatric influenza immunisation program was influenced by vaccine efficacy, immunisation coverage, costs, and most significantly by herd immunity. This review suggests that pediatric influenza immunisation may offer a cost effective strategy when compared with HPV and varicella and possibly more value compared with other childhood vaccines (RV, Hep B, MD and PD).