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.

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.

Two-dose varicella vaccine effectiveness in China: a meta-analysis and evidence quality assessment.

BACKGROUND: The objectives of this review were to evaluate the vaccine effectiveness (VE) of the two-dose varicella vaccine for healthy children in China and explore the application of the approach of Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in observational studies on VE. METHODS: We searched for observational studies on two-dose varicella VE for children in China aged 1-12 years that were published from 1997 to 2019, and assessed the quality of each study using the Newcastle Ottawa Scale (NOS). We used meta-analysis models to obtain the pooled two-dose VE, and the studies were divided into subgroups and analysed according to whether or not it was an outbreak investigation and its NOS score. The quality of evidence of VEs were rated by approach of the GRADE system. RESULTS: A total of 12 studies and 87,196 individuals were included. The pooled two-dose VE was 90% (95% confidence interval [CI]: 69-97%). The VE of outbreak studies (87% [95% CI: 76-93%]) was lower than non-outbreak studies (99% [95% CI: 98-99%]). There was no significant difference in VEs by different NOS quality. The quality of the evidence assessment of pooled two-dose VE was "low", which was rated down by one category in limitations and publication bias respectively and rated up by two category in large effect. The quality of evidence assessment in subgroup of NOS score ≥ 7 was "moderate". CONCLUSIONS: The VE of two-dose varicella vaccine is relatively high in preventing varicella, and is recommended for countries which need further control for varicella. However, higher quality evidence is needed as a supplement for stronger recommendations. The approach of GRADE could be applied for rating the quality of evidence in observational study.

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.

Varicella vaccination in Italy and Germany - different routes to success: a systematic review.

INTRODUCTION: Italy (in pilot regions) and Germany (nationwide) were the first European countries to introduce universal varicella vaccination (UVV) programs. AREAS COVERED: A systematic review was performed to assess varicella epidemiology before UVV programs and the impact of 1-dose and 2-dose UVV programs in Italy and Germany. EXPERT OPINION: Italy implemented 1- or 2-dose UVV programs successively in eight pilot regions between 2003 and 2011 and nationwide in 2017. Germany implemented 1- and 2-dose UVV programs in 2004 and 2009, respectively. While Italy had two nationwide surveillance systems in place for varicella in the pre-vaccination era, in Germany, a mandatory notification system for varicella was only introduced in the New Federal States 2 years before the 1-dose UVV implementation. Substantial reductions in moderate/severe varicella and varicella-related hospitalization incidence occurred during the 1-dose era. Further reductions were reported in Italy and Germany after the recommendation of a second dose in a long or short schedule, respectively. Different benefit-risk evaluations of a tetravalent varicella-containing vaccine (MMRV) used as a first dose led to different recommendations (MMRV versus MMR+V) in these countries. Vaccination strategies in both countries tailored to country-specific needs and goals led to a reduction in varicella-related health care hospitalization costs.

[Systematic reviews and evidence quality assessment on effectiveness of 1 dose varicella attenuated live vaccine for healthy children aged 1-12 years in China].

Objective: To assess the effectiveness of 1 dose varicella attenuated live vaccine (VarV) for healthy children aged 1-12 years in China and explore the application of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework in observational studies of vaccine effectiveness (VE). Methods: We searched studies about the VE of 1-dose VarV for children aged 1-12 years in China which published before 2019 and evaluated the quality of the studies by the Newcastle Ottawa Scale (NOS) table. We used Meta-analysis models to obtain the pooled 1-dose VE and that in subgroups by study design, outbreak or not, study quality and age of subjects. The evidences of VEs were rated by means of the GRADE system. Results: Thirty-two studies were included and the pooled 1-dose VE was 75% [95% confidence interval (CI): 68%-80%]. The VE of outbreak studies [VE=66% (95%CI: 57%-73%)] was lower than non-outbreak studies [VE=85% (95%CI: 78%-89%)], and the VE in <6 years old children [VE=84% (95%CI:77%-89%)] was higher than that in ≥6 years old children [VE=60% (95%CI: 51%-68%)]. There was no significant difference in VE among studies with different design and quality. The quality of the evidences of pooled 1-dose VE was"very low", which was downgraded in bias risk and inconsistency and not downgraded in indirectness, imprecision and publication bias. Conclusions: The 1-dose VarV can provide medium level protection for 1-12 years old children in China, but it will decrease significantly for ≥6 years old children, so it is suggested to implement the strategies of two-dose vaccination of VarV in children <6 years old. The GRADE framework can be used in the observational studies of VE and it is suggested that the technical guidelines of observational study should be worked out to improve the overall quality of evidence.

The impact of long-term moderate level of vaccination coverage for epidemiology of varicella in Lu'an, China: should we change immunisation strategy now?

As China implements the voluntary vaccination programme of one-dose of varicella vaccine (VarV) for decades, robust estimates of the impact of voluntary vaccination era on epidemiology of varicella are needed. We estimated the vaccination coverage (VC) of VarV by using surveillance data on immunisation. The descriptive epidemiological method was used to describe the changing epidemiology of varicella from 2007 to 2018. The screening method was used to estimate the vaccine effectiveness (VE) of VarV. The overall VC for VarV was 71.7%, ranged from 47.7% to 79.5% among 2008-2017 birth cohorts. In total, 16 660 varicella cases were reported during 2007-2018, the incidence increased from 10.0 cases per 100 000 population in 2007 to 65.2 cases per 100 000 population in 2018. A shift in age group of varicella was observed since 2012, with the age increased from 5-9 years to 10-14 years. The overall VE was 79.9%, and the VE increased from 60.1% in 2008 birth cohort to 96.2% in 2017 birth cohort. We found that the overall VE for VarV is moderate, but appears highly effective within 5 years after vaccination. In addition, a shift varicella infection to older ages has occurred at the long-term moderate level VC of one-dose VarV. Therefore, to contain the incidence of varicella and prevent any potential shift to older ages, the introduction of VarV into routine immunisation programme is likely needed in Lu'an.

Impact of a 2-dose voluntary vaccination strategy on varicella epidemiology in Beijing, 2011-2017.

BACKGROUND: One-dose voluntary varicella vaccination for children was introduced in Beijing since 1998. In Oct 2012, a second dose varicella vaccine (VarV) was recommended to further decrease varicella disease and the outbreaks. We describe the impact of the 2-dose voluntary vaccination strategy on varicella epidemiology in Beijing, China. METHODS: Varicella incidence rates and outbreak characteristics in 2011-2017 was examined using surveillance data. Varicella vaccination coverage among children born in 2007-2012 was estimated through Beijing children immunization registry system. Vaccine effectiveness (VE) for VarV2 was estimated by screening method. RESULTS: Overall varicella incidence decreased by 37.8% from 103.2 per 100,000 population in 2011 to 64.2 per 100,000 population in 2017. Incidence declines in children aged <15 years with most significantly decrease by 82.3% in children aged 5-9 years, while no significant change happened in adolescent and adults. A total of 251 outbreaks with 3239 outbreak-related cases were reported in 2011-2017, the number of outbreaks decreased significantly by 50.7% from 69 in 2011 to 34 in 2017. The VarV1 coverage ranged from 85.4% to 92.6% among children 4 year of age and the VarV2 coverage ranged from 40.1% to 72.9% among children 6 year of age in the 2007-2012 birth cohort. Overall VE estimates against all varicella disease was 94.4% (95% CI: 89.9-98.9%) for VarV2. CONCLUSIONS: Moderate VarV2 coverage has been achieved in Beijing resulting in remarkable declining of the incidence in children. Varicella outbreaks has not been eliminated suggested that measures such as including a 2-dose varicella vaccination in routine immunization program should be taken in the future.

Frequency and cost of live vaccines administered too soon after prior live vaccine in children aged 12 months through 6 years, 2014-2017.

OBJECTIVE: To identify number of children who received live vaccines outside recommended intervals between doses and calculate corrective revaccination costs. METHODS: We analyzed >1.6 million vaccination records for children aged 12 months through 6 years from six immunization information system (IIS) Sentinel Sites from 2014-15 when live attenuated influenza vaccine (LAIV, FluMist® Quadrivalent) was recommended for use, and from 2016-17, when not recommended for use. Depending on the vaccine, insufficient intervals between live vaccine doses are less than 24 or 28 days from a preceding live vaccine dose. Private and public purchase costs of vaccines were used to determine revaccination costs of live vaccine doses administered during the live vaccine conflict interval. Measles, mumps, rubella (MMR), varicella, combined MMRV, and LAIV were live vaccines evaluated in this study. RESULTS: Among 946,659 children who received at least one live vaccine dose from 2014-15, 4,873 (0.5%) received at least one dose too soon after a prior live vaccine (revaccination cost, $786,413) with a median conflict interval of 16 days. Among 704,591 children who received at least one live vaccine dose from 2016-17, 1,001 (0.1%) received at least one dose too soon after a prior live vaccine (revaccination cost, $181,565) with a median conflict interval of 14 days. The live vaccine most frequently administered outside of the recommended intervals was LAIV from 2014-15, and varicella from 2016-17. CONCLUSIONS: Live vaccine interval errors were rare (0.5%), indicating an adherence to recommendations. If all invalid doses were corrected by revaccination over the two time periods, the cost within the IIS Sentinel Sites would be nearly one million dollars. Provider awareness about live vaccine conflicts, especially with LAIV, could prevent errors, and utilization of clinical decision support functionality within IISs and Electronic Health Record Systems can facilitate better vaccination practices.

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.

Burden of varicella in Latin America and the Caribbean: findings from a systematic literature review.

BACKGROUND: Varicella is typically mild and self-limiting, but can be associated with complications and even death. The limited data available on varicella in Latin America and the Caribbean (LAC) indicate substantial burden in countries where varicella vaccine is not part of publicly funded childhood national immunization programs. METHODS: A systematic literature review of published studies was complemented by "gray" literature on varicella incidence, complications, mortality, and economic consequences, in the absence and presence of universal varicella vaccination (UVV) in LAC. RESULTS: Seroprevalence data indicate that varicella is usually a disease of childhood in LAC. Varicella incidence rates, while unreliable in the absence of mandatory reporting, show a trend to increased incidence due to greater urbanization and population density. The introduction of UVV in national immunization programs has led to significant reductions in varicella incidence in these areas. CONCLUSIONS: Varicella continues to pose a substantial healthcare burden in LAC. The future introduction of UVV in additional countries is predicted to provide substantial reductions in cases, with important economic benefits. For countries that have already implemented UVV, the challenge is to maintain high rates of coverage and, where relevant, consider inclusion of a second dose to reduce breakthrough cases. Given the significant proportion of the region now implementing UVV, a regional recommendation in order to prevent any potential for age-shifts in varicella infection might be considered.

Burden of varicella in Central and Eastern Europe: findings from a systematic literature review.

INTRODUCTION: Vaccination against varicella rapidly reduces disease incidence, resulting in reductions in both individual burden and societal costs. Despite these benefits, there is no standardization of varicella immunization policies in Europe, including countries in Central and Eastern Europe (CEE). AREAS COVERED: This systematic literature review identified publications on the epidemiology of varicella, its associated health and economic burden, and vaccination strategies within the CEE region, defined as Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, Slovakia, and Slovenia. Twenty-six studies were identified from a search of PubMed, Embase®, and MEDLINE® biomedical literature databases, supplemented by gray literature and country-specific/global websites. EXPERT COMMENTARY: Limited information exists in published studies on the burden of varicella in CEE. The wide variability in incidence rates between countries is likely explained by a lack of consistency in reporting systems. Funded universal varicella vaccination (UVV) in CEE is currently available only in Latvia as a one-dose schedule, but Hungary together with Latvia are introducing a two-dose strategy in 2019. For countries that do not provide UVV, introduction of vaccination is predicted to provide substantial reductions in cases and rates of associated complications, with important economic benefits.

Global impact of varicella vaccination programs.

Although varicella is usually a mild and self-limited disease, complications can occur. In 1998, the World Health Organization recommended varicella vaccination for countries where the disease has a significant public health burden. Nonetheless, concerns about a shift in the disease to older groups, an increase in herpes zoster in the elderly and cost-effectiveness led many countries to postpone universal varicella vaccine introduction. In this review, we summarize the accumulating evidence, available mostly from high and middle-income countries supporting a high impact of universal vaccination in reductions of the incidence of the disease and hospitalizations and its cost-effectiveness. We have also observed the effect of herd immunity and noted that there is no definitive and consistent association between vaccination and the increase in herpes zoster incidence in the elderly.

[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.

Varicella epidemiology in Latin America and the Caribbean.

INTRODUCTION: The Latin American Society of Pediatric Infectious Diseases (SLIPE), with the support of the Americas Health Foundation (AHF), has developed a position paper on varicella prevention in Latin America and Caribbean countries (LAC). This article summarizes the most relevant aspects of varicella in LAC, and emphasizes the need to include the varicella vaccine in the national immunization programs in the Region and evaluate its impact disease burden. AREAS COVERED: A systematic review was conducted of the medical evidence published and presented at various regional medical conferences on the disease burden in LAC, the advances made by prevention programs, the available vaccines in the Region, and their immunogenicity, efficacy, effectiveness, and safety. The different national varicella-prevention vaccination programs were reviewed, as was available information regarding the impact of these programs on the epidemiology of varicella in those countries implementing a varicella vaccine strategy. Following that initial publication, an update was conducted, including data from additional countries in the Region. EXPERT COMMENTARY: Varicella is a vaccine-preventable infectious disease, considered a 'benign disease' because of lower complication rates when compared with measles, pertussis. The incorporation of a two-dose varicella vaccine in national immunization schedules in all countries throughout LAC would be of great benefit to the health of the children.

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.

Assessing varicella vaccine effectiveness and its influencing factors using health insurance claims data, Germany, 2006 to 2015.

In Germany, routine childhood varicella vaccination was implemented in 2004 with two doses recommended since 2009. We used an immunisation information system based on countrywide health insurance claims data to analyse vaccine effectiveness (VE) and factors influencing VE. We applied proportional hazard models to estimate VE under various conditions and compared the risk of acquiring varicella among unvaccinated children in regions with high vs low vaccination coverage (VC). Among 1.4 million children we identified 29,404 varicella cases over a maximum follow-up of 8 years post-vaccination. One-dose VE was 81.9% (95% confidence interval (CI): 81.4-82.5), two-dose VE 94.4% (95% CI: 94.2-94.6). With dose one given 1-27 days after measles-containing vaccine (MCV), one-dose VE was 32.2% (95% CI: 10.4-48.6), two-dose VE 92.8% (95% CI: 84.8-96.6). VE was not associated with age at vaccination (11-14 vs ≥ 15 months), time since vaccination, or vaccine type. Unvaccinated children had a twofold higher risk of acquiring varicella in low VC regions. Our system generated valuable data, showing that two-dose varicella vaccination provides good protection for at least 8 years. Unvaccinated children benefit from herd effects. When the first varicella vaccine dose is given shortly after MCV, a second dose is essential.