Modelling the Public Health Burden of Herpes Zoster and the Impact of Adjuvanted Recombinant Zoster Vaccine in Five Selected Countries in Southeast Asia.

INTRODUCTION: Herpes zoster (HZ) can cause substantial patient morbidity and lead to large healthcare costs. However, the disease burden of HZ in Southeast Asia may be underestimated. This study aimed to estimate the public health burden of HZ and the impact of vaccinating adults aged ≥ 50 years old in five Southeast Asian countries (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination. METHODS: For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country. RESULTS: Without RZV, it was estimated that there would be a total of approximately 10 million HZ cases, 2.1 million PHN cases, and 1.4 million non-PHN complications in individuals aged ≥ 50 years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2 million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country. CONCLUSIONS: This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article.

Assessing the Underestimation of Adult Pertussis Disease in Five Latin American Countries.

INTRODUCTION: Pertussis, a contagious respiratory disease, is underreported in adults. The study objective was to quantify underestimation of pertussis cases in adults aged ≥ 50 years in five Latin American countries (Argentina, Brazil, Chile, Mexico, Peru). METHODS: A previously published probabilistic model was adapted to adjust the number of pertussis cases reported to national surveillance systems by successive multiplication steps (proportion of pertussis cases seeking healthcare; proportion with a specimen collected; proportion sent for confirmatory testing; proportion positive for pertussis; proportion reported to passive surveillance). The proportions at each step were added in a random effects model to produce a pooled overall proportion, and a final multiplier was calculated as the simple inverse of this proportion. This multiplier was applied to the number of cases reported to surveillance to estimate the number of pertussis cases. Monte Carlo simulation with 10,000 iterations estimated median as well as upper and lower 90% values. Input data were obtained from surveillance systems and published sources. RESULTS: The estimated median underestimation factor for pertussis cases in adults ranged from 104 (90% limits 40, 451) in Chile to 114 (90% limits 39, 419) in Argentina. In all five countries, the largest estimated number of cases was in the group aged 50-59 years. The highest number per 100,000 population was in the group aged ≥ 90 years in most countries. The estimated median underestimation factor for pertussis hospitalizations was 2.3 (90% limits 1.8, 3.3) in Brazil and 2.4 (90% limits 1.8, 3.2) in Chile (data not available for other countries). CONCLUSION: This analysis indicates that the number of pertussis cases in adults aged ≥ 50 years in five Latin American countries is approximately 100 times higher than the number captured in surveillance data. These results could support decision-making in the diagnosis, management, and prevention of pertussis disease in adults.

Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico.

Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer's perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

Rotavirus (RV) infection causes acute diarrhea in infants and can be life-threatening. Several safe and effective vaccines against RV and its complications exist. For many governments choosing vaccines for national immunization programs, total costs or savings and health gains are important factors in the selection process. We compared the costs and health benefits of three RV vaccines for Mexico: HRV, HBRV, and BRV-PV, that have different dosing schedules: two doses for HRV and three doses for HBRV and BRV-PV. HRV is currently part of the national immunization program in Mexico. HRV would result in more health benefits as it incurs fewer RV-related cases, medical visits, hospitalizations, and infant deaths than the other vaccines due to its early protection achieved after only two doses to complete its schedule. However, from a payer's perspective, the least expensive vaccine was BRV-PV, while HRV was less expensive than HBRV. From a societal perspective, also accounting for families' costs and loss in income due to an infant's RV disease, and the families' costs and loss in income when accompanying the infant to the vaccination center, the HRV vaccine was less expensive than HBRV and BRV-PV presented in a 1-dose vial, while more expensive than BRV-PV presented in a 2-dose vial. HRV and HBRV are both approved in Mexico, although HBRV requires a greater investment at lower health benefits than HRV, from both a payer's and a societal perspective. A 2-dose vaccination scheme is an important asset for the economic value of this vaccination program.

How large could the public health impact of introducing recombinant zoster vaccination for people aged ≥50 years in five Latin American countries be?

This study aimed to: (1) estimate the disease burden of herpes zoster (HZ) and (2) assess the potential public health impact of introducing adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination in adults aged ≥50 years in Argentina, Brazil, Mexico, Chile, and Colombia using the ZOster ecoNomic Analysis (ZONA) static multicohort Markov model. The model followed individuals aged ≥50 years from administration of RZV over their remaining lifetime. Inputs were based, most often, on local data. First dose coverage was assumed to be 35%, with 75% second dose compliance. It was predicted that without RZV, there would be 23,558,675 HZ cases, 6,115,981 post-herpetic neuralgia (PHN) cases, and 7,058,779 non-PHN complications in the five countries, but introducing RZV under assumed coverage could avoid 4,583,787 (19%) HZ cases, 1,130,751 (18%) PHN cases, and 1,373,419 (19%) non-PHN complications. Also, 10427,504 (20%) doctor's office visits and 1,630,201 (19%) days of hospitalization could be averted in the three countries (Argentina, Brazil, and Mexico) with available input data. The numbers needed to be vaccinated to avoid one case of HZ were 9-10 across countries, and to avoid one case of PHN, 35-40. One-way sensitivity analyses showed that the input parameters with the largest impact on the estimated number of HZ cases avoided were first dose coverage, initial HZ incidence, and vaccine efficacy waning. In conclusion, the introduction of RZV for older adults in Latin America could greatly reduce the public health burden of HZ and reduce the related doctor visits and hospitalization days.

Why was the study done?Herpes zoster (HZ), commonly known as shingles or "culebrilla," typically causes a painful, itchy rash on the trunk in older adults, and can result in long-term complications. It is difficult to study the lifetime burden of HZ due to follow-up time constraints. We therefore wanted to predict how many people could develop HZ as they age and how many cases of HZ could be avoided by introducing adjuvanted recombinant zoster vaccine (RZV) in people aged 50 years and older in five Latin American countries (Argentina, Brazil, Mexico, Chile, and Colombia).What did the researchers do and find?Using a mathematical model, we predicted that nearly 5 million of an estimated 24 million cases of HZ could be avoided by vaccinating 35% of older adults with RZV in the five countries. This vaccination approach would also avert various complications of HZ, including post-herpetic neuralgia (long-lasting pain at the rash site) and save doctor's office visits and hospitalizations for HZ.What do the results mean?Introducing RZV for older adults in Latin America ­ as is already the case in various other countries ­ could prevent a substantial proportion of HZ cases, leading to improved public health and less health care resource utilization.What is the objective influence on the wider field?In the absence of real-world data on the potential impact of RZV on HZ in Latin America, these predictions could help policymakers to assess the potential value of introducing RZV for older adults in Latin America.

Estimated public health impact of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) on child morbidity and mortality in Gavi-supported countries.

Vaccine impact models against rotavirus disease (RD) and pneumococcal disease (PD) in low- and middle-income countries assume vaccine coverage based on other vaccines. We propose to assess the impact on severe disease cases and deaths avoided based on vaccine doses delivered by one manufacturer to Gavi-supported countries. From the number of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) doses delivered, we estimated the averted burden of disease 1) in a specific year and 2) for all children vaccinated during the study period followed-up until 5 years (y) of age. Uncertainty of the estimated impact was assessed in a probabilistic sensitivity analysis using Monte-Carlo simulations to provide 95% confidence intervals. From 2009 to 2019, approximately 143 million children received HRV in 57 Gavi-supported countries, avoiding an estimated 18.7 million severe RD cases and 153,000, deaths. From 2011 to 2019, approximately 146 million children received PHiD-CV in 36 countries, avoiding an estimated 5.0 million severe PD cases and 587,000 deaths. The number of severe cases and deaths averted for all children vaccinated during the study period until 5 years of age were about 23.2 million and 190,000, respectively, for HRV, and 6.6 million and 749,000, respectively, for PHiD-CV. Models based on doses delivered help to assess the impact of vaccination, plan vaccination programs and understand public health benefits. In 2019, HRV and PHiD-CV doses delivered over a 5-y period may have, on average, averted nine severe disease cases every minute and one child death every 4 min.

What is the context?The WHO added the pneumococcal conjugate vaccine and the rotavirus vaccine in the recommended vaccination schedule of all countries in 2007 and 2009, respectively.Previous studies estimated the public health benefit of these vaccines by approximating the number of children who received them.What is new?We used an alternative approach to estimate the benefit based on actual number of doses of the vaccines, human rotavirus vaccine (HRV; Rotarix) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) delivered to each country considered.The study analyzed data from children under 5 years of age in 60 Gavi-supported countries by identifying the number of vaccine doses delivered, estimating the number of children fully covered, applying the country-specific disease epidemiology, estimating the number of severe disease cases and deaths avoided.From 2009 to 2019, approximately 143 million children were vaccinated with HRV avoiding an estimated 18.7 million severe rotavirus disease cases and 153,000 deaths.From 2011 to 2019, about 146 million children were vaccinated with pneumococcal vaccine avoiding an estimated 5.0 million severe pneumococcal disease cases and 587,000 deaths.What is the impact? The benefit of HRV and PHiD-CV in Gavi-supported countries is often estimated based on assumptions of vaccine coverage rates.A modeling approach based on doses delivered by the vaccine manufacturer can provide an additional view on the potential vaccine benefits and improve planning, contribution, and sustainability of the immunization programs at a country level.In 2019, HRV and PHiD-CV together averted nine cases of severe disease each minute and one child death every 4 minutes.

Economic burden of meningococcal disease in children and adolescents in Tijuana, Mexico.

Invasive meningococcal disease (IMD) is an uncommon but serious and potentially fatal condition mainly affecting children and adolescents. Active surveillance between 2005 and 2016 at Tijuana General Hospital, Mexico, indicated that the incidence of IMD in Tijuana was higher than previously thought, at 2.69 per 100,000 population aged <16 years. The objective of this study was to estimate the economic burden associated with 51 IMD cases in children aged <16 years identified over the 11 years of active surveillance at Tijuana General Hospital, Mexico. Healthcare resource usage for the IMD cases was obtained from the hospital database and combined with unit costs from the hospital purchasing department or national databases to estimate total healthcare costs over a follow-up period of 3 months. Societal costs were represented by the value of lost wages for parents or guardians. All costs were expressed in US$. Over the 11-year study period there were 51 IMD cases, of which 13 (25%) were fatal. The total cost for all 51 cases over the 11-year study period was US$1,054,499 (average per case US$20,676), of which direct healthcare costs comprised US$1,029,948 (average per case US$20,195) and societal costs US$24,551 (average per case US$481). Extrapolated to the population of Tijuana region aged <16 years, the estimated annual economic burden of IMD was US$268,794. The major cost driver was the cost of hospitalization. These data illustrate the significant economic burden associated with IMD in Tijuana, and will be useful in assessing optimal vaccination programs against meningococcal disease in Mexico.

Cost effectiveness and budget impact of universal varicella vaccination in Russia.

This economic evaluation assesses the cost-effectiveness and budget impact of introducing a two-dose varicella vaccine in the Russian national immunization program. A static Markov model followed a simulated 2019 Russian cohort over its lifetime and compared outcomes and costs of three varicella vaccination strategies: strategy I (doses given at 12 and 15 months of age), strategy II (doses given at 1 year and 6 years of age), and a no vaccination scenario. Inputs on age-dependent clinical pathways, associated costs, and related health outcomes were collected from national sources and published literature. Results are presented as incremental cost-effectiveness ratio (ICER) from the healthcare payer and societal perspective over the lifetime of the birth cohort and the budget impact over a 10 years' time horizon. Vaccination strategies I and II resulted in an ICER of approximately 1.7 million rubles per quality-adjusted life years gained from the healthcare payer perspective and were cost-saving from the societal perspective. From the healthcare payer perspective, the costs per varicella case averted were 5,989 and 7,140 rubles per case for strategies I and II, respectively. However, from the societal perspective, vaccination is a dominant strategy and the budget impact analysis shows significant healthcare savings over 10 years, with strategy I realizing savings of ~2 billion rubles more than strategy II. From a public health impact perspective, varicella vaccination of children at 12 and 15 months of age through the Russian NIP is expected to be cost-effective with an affordable budget impact compared to no vaccination.

A graphical version of the plain language summary can be found here: 10.6084/m9.figshare.19291463Focus on the patientWhat is the context? Varicella, or chickenpox, is a highly contagious infection. Though mild in children, complications can occur in older individuals, increasing the economic burden for society and public health institutions.In 2019, approximately 0.6% of the Russian population was impacted by varicella, a vaccine-preventable disease.In Russia, varicella vaccination is only implemented in some regions. These regions report a decreasing trend in infection rates in the groups covered by vaccination.What is new? This study assesses the public health and economic impact of implementing varicella vaccination in Russia through its National Immunization Program.We compared two vaccination strategies to a no vaccination scenario: º Strategy I: two doses at 12 and 15 months of ageº Strategy II: two doses at 1 and 6 years of age Over a 10-year period, we found that: º Strategy I prevented 607,682 cases, 2,388,659 general practitioner visits and 10,256 hospitalizations, and saved 6.2 million rublesº Strategy II prevented 491,084 cases, 1,805,668 general practitioner visits and 10,108 hospitalizations, and saved 4.2 million rubles Strategy I saves more direct (i.e., general practitioner visits, hospitalizations and treatment) and indirect (i.e., income loss, disability payments, and caregiving) costs to society than strategy II.What is the impact? Varicella vaccination, especially when introduced at 12 and 15 months (strategy I) in the National Immunization Program, provides public health and economic benefits.From the healthcare payer perspective: this is a cost-effective intervention. From the societal perspective: the budget impact analysis shows significant savings.

A Cross-Sectional Concept Elicitation Study to Understand the Impact of Herpes Zoster on Patients' Health-Related Quality of Life.

INTRODUCTION: After a chickenpox infection, the varicella zoster virus lies dormant in nerve cells and can be reactivated in later life to cause herpes zoster (HZ), also called shingles, a painful rash that may result in persistent postherpetic neuralgia (PHN). Treatment options are limited, and HZ/PHN may have substantial negative effects on health-related quality of life (HRQoL). This qualitative cross-sectional study explored the subjective patient experience and impact on HRQoL of HZ and PHN in adults aged ≥ 50 years in Canada. METHODS: Patients were eligible for the study if they were aged at least 50 years and had been diagnosed with HZ by a healthcare practitioner 7-60 days earlier for HZ patients and 90-365 days earlier for PHN patients. Eligible patients were invited to participate in concept elicitation interviews by telephone. Data from the interviews were transcribed and analyzed to identify key concepts related to symptoms and impacts on the patients' lives. RESULTS: A total of 32 patients participated, with a mean age of 61 years. Most (72%) were female. The most common symptoms reported were rash (n = 32), pain (n = 31), fatigue (n = 26), and itchiness (n = 20). The most commonly reported HRQoL domains affected were emotional functioning (n = 31), activities of daily living (n = 31), sleep (n = 29), physical functioning (n = 25) and hobbies (n = 21). A conceptual model was developed to summarize these symptoms and impacts. CONCLUSION: HZ negatively affected many dimensions of patients' HRQoL, particularly during the acute phase of illness. This qualitative study helps to broaden understanding of the subjective patient experience of HZ.

Meta-Regression of Herpes Zoster Incidence Worldwide.

INTRODUCTION: Many studies have been conducted worldwide to estimate herpes zoster (HZ) incidence rates. We synthesized studies of HZ incidence rates in the general population using meta-analysis models. METHODS: A random effects meta-analysis was conducted to estimate HZ incidence from a published worldwide systematic literature review (SLR) including only individuals aged 50 years and older. Meta-regression was used to explore whether variability in incidence rates could be explained by a combination of study-specific characteristics including age, gender, continent and year of study data. The impact of adding additional covariates-case detection method (general practitioner surveillance, healthcare database, sentinel network, etc.), case definition (medical record-based, self-reported), study design (retrospective passive surveillance, retrospective active surveillance, etc.), incidence type (cumulative incidence/1000 persons or incidence rate/1000 person-years), patient type (outpatients or in- and out-patients) and latitude to the base model-was also assessed. RESULTS: Sixty-one records from 59 studies were included in the analysis: 25, 20, 11 and 5 from Europe, North America, Asia and Oceania, respectively. There was variation in study methodology and outcomes. Heterogeneity of incidence rates was greatest among studies conducted in Asia. Meta-analysis showed that incidence increased with age, was lower in males compared to females, tended to be lower in Europe and North America compared to Asia and Oceania and increased with year of study data. The data-driven meta-regression model included continent, year of study data, gender, age and an age × gender interaction term. The difference in incidence between males and females was greater in younger ages (e.g., 50-59) compared to older age groups (e.g., 80+). None of the additional covariates contributed significantly to the model. CONCLUSION: Incidence rates were shown to vary by age, gender, continent and year of study data.

Long-term efficacy data for the recombinant zoster vaccine: impact on public health and cost effectiveness in Germany.

The aim of the study was to update previously published public health impact and cost-effectiveness analyses of the recombinant zoster vaccine (RZV), in the German population aged ≥50 years of age (YOA), with the latest vaccine efficacy (VE) estimates against herpes zoster (HZ). The updated estimates are derived from a long-term follow-up study. A previously published multi-cohort Markov model following age cohorts over their lifetime was used. Demographic, epidemiological, cost, and utility data were based on German specific sources. Vaccine coverage was assumed to be 40%, with a second dose compliance of 70%. The estimated VE at time 0 was 98.9% (95% C.I.: 94.0-100%) with an annual waning of 1.5% (95% CI: 0.0-3.4%) for the age group 50-69 YOA. Corresponding values were 95.4% (95% C.I.: 89.7-100%) and 2.3% (95% CI: 0.3-4.4%) for the age group ≥70 YOA. It was estimated that, over the remaining lifetime since vaccination, RZV would prevent approximately 884 thousand (K), 603 K, and 538 K HZ cases in three age cohorts 50-59, 60-69, and ≥70 YOA, respectively. The number needed to vaccinate to prevent one HZ and one postherpetic neuralgia case was 6 and 36 (50-59 YOA cohort), 6 and 34 (60-69 YOA cohort), 10 and 48 (≥70 YOA cohort). The incremental cost-effectiveness ratio of vaccination ranged from €26 K/quality-adjusted life year (QALY) in 60 YOA to €35 K/QALY in 70 YOA. Due to the higher, sustained, RZV VE, improved public health and cost-effectiveness results were observed compared to previous analyses.

PLAIN LANGUAGE SUMMARYWhat is the context?Shingles is a viral infection caused by the reactivation of the chickenpox virus. It causes a painful rash that lasts for several weeks.The incidence and severity of shingles increase with age. In Germany alone there are approximately 400,000 new cases annually.Vaccination can help prevent shingles.Previous studies, based on data collected up to four years post-vaccination, estimated the number of shingles cases prevented. What is new?Here, we use data from the same studies followed over a longer-term to update previous analyses in the German population.We found, based on data up to 8 years following vaccination, that:○ In adults 50-69 years: the vaccine initially prevents 98.9% of cases, with a reduction of 1.5% each year(for example, after one year, it would prevent 97.4% of cases).○ In adults over 70 years of age: the vaccine initially prevents 95.4% of cases, with a reduction of 2.3% each year (for example, after one year, it would prevent 93.1% of cases).○ Vaccination would reduce the number of shingles cases by 0.9 million in a cohort of adults aged 50-59 years, 0.6 million in adults 60-69 years, and 0.5 million in adults older than 70 years, over the remainder of their lifetime.What is the impact?The study provides more certainty regarding results as it is based on the most complete/up to date data. The results showed the potential of Shingrix to prevent shingles while at the same time providing good value for money.

Estimated Public Health Impact of the Recombinant Zoster Vaccine.

OBJECTIVE: To investigate the potential public health impact of adult herpes zoster (HZ) vaccination with the adjuvanted recombinant zoster vaccine (RZV) in the United States in the first 15 years after launch. METHODS: We used a publicly available model accounting for national population characteristics and HZ epidemiological data, vaccine characteristics from clinical studies, and anticipated vaccine coverage with RZV after launch in 2018. Two scenarios were modeled: a scenario with RZV implemented with 65% coverage after 15 years and a scenario continuing with zoster vaccine live (ZVL) with coverage increasing 10% over the same period. We estimated the numbers vaccinated, and the clinical outcomes and health care use avoided yearly, from January 1, 2018, to December 31, 2032. We varied RZV coverage and investigated the associated impact on HZ cases, complications, and health care resource use. RESULTS: With RZV adoption, the numbers of individuals affected by HZ was predicted to progressively decline with an additional 4.6 million cumulative cases avoided if 65% vaccination with RZV was reached within 15 years. In the year 2032, it was predicted that an additional 1.3 million physicians' visits and 14.4 thousand hospitalizations could be avoided, compared with continuing with ZVL alone. These numbers could be reached 2 to 5 years earlier with 15% higher RZV vaccination rates. CONCLUSION: Substantial personal and health care burden can be alleviated when vaccination with RZV is adopted. The predicted numbers of HZ cases, complications, physicians' visits, and hospitalizations avoided, compared with continued ZVL vaccination, depends upon the RZV vaccination coverage achieved.

A systematic literature review of herpes zoster incidence worldwide.

We conducted a systematic review to characterize the incidence rate of herpes zoster (HZ) in the general population, specifically in individuals ≥50 years of age. A total of 69 publications were included in the review. We found a cumulative incidence of HZ ranging from 2.9-19.5 cases per 1,000 population and an incidence rate of HZ ranging from 5.23-10.9 cases per 1,000 person-years. The cumulative incidence (3.22-11.2 versus 2.44-8.0 cases per 1,000 population) and incidence rates (6.05-12.8 versus 4.30-8.5 cases per 1,000 person-years) were higher in females than males. Studies revealed a trend of increasing incidence of HZ with increasing age and over time. Variations in incidence estimates can be attributed to the various study designs, case ascertainments, age distributions of the population and year of the study. HZ is associated with a substantial disease burden and is expected to increase due to population aging.

A systematic literature review to assess the burden of herpes zoster disease in China.

INTRODUCTION: Herpes zoster (HZ) or shingles occurs as a result of reactivation after a primary infection with varicella zoster virus (chickenpox). The burden of HZ in older adults in China is not well understood. We conducted a systematic literature review to understand the burden of disease related to HZ, its complications, and associated costs in China. AREAS COVERED: Using publications retrieved from Chinese and English literature databases, we described incidence and prevalence of HZ, occurrence of HZ-related complications, and costs associated with HZ in mainland China, Taiwan, and Hong Kong. EXPERT OPINION: The data, although limited, indicate that the burden of disease due to HZ is substantial in China, with incidence rates that are comparable to the rest of the world. Recently, an adjuvanted recombinant HZ vaccine was approved for use in China. Disease prevention is likely to reduce the burden of disease, with potentially significant economic benefits. However, understanding the public health impact of vaccination in China will require extensive baseline information about incidence, complication rates, and associated costs. This review gives an overview of available research, but also reveals existing gaps. Well-designed observational studies are needed to quantify the total burden of disease and potential impact of prevention through vaccination.

PLAIN LANGUAGE SUMMARY What is the context? Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described. 32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. What is new? We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China. The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. What is the impact? Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination. Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy.

Incremental clinical and economic impact of recombinant zoster vaccination: real-world data in a budget impact model.

BACKGROUND: In 2017, the FDA approved the adjuvanted recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in immunocompetent adults aged 50 years and older. RZV joined zoster vaccine live (ZVL) as U.S.-marketed vaccines against HZ. The Advisory Committee on Immunization Practices preferentially recommended use of RZV over ZVL. In order to inform population-based decision makers (PBDMs) about the incremental clinical and economic impact of RZV adoption, budget impact (BI) models may be used. Populating such models with national data can inform PBDMs about the incremental value of RZV adoption nationally; however, heterogeneity across health plans requires the inclusion of plan-specific data to ensure the relevance of modeling outcomes for plan-specific decision makers. OBJECTIVE: To investigate the clinical and economic outcomes associated with the adoption of RZV in nationally representative populations with commercial and Medicare coverage and to demonstrate the effect of the heterogeneity of health plans using real-world data from a large, integrated delivery network (IDN). METHODS: We used a publicly available BI model. The model accounts for national and IDN-collected population characteristics (size, age distribution) and epidemiological data (incidence of HZ and complications, HZ recurrence rate), vaccine characteristics from randomized controlled trials and observational studies (efficacy, waning, second dose compliance for RZV, adverse event rate), national costs (vaccine, direct medical for HZ, complications, and vaccine adverse events), and current and anticipated vaccine coverage. We assessed incremental clinical (HZ cases and complications) and economic (per-member-per-month [PMPM] costs) impact at 5-year to 15-year time horizons, comparing scenarios where RZV is solely implemented with one where only ZVL is utilized. RESULTS: Following the adoption of RZV, the incremental HZ cases avoided over 5 and 15 years were estimated to be 1,800 and 15,000 for a commercial plan, 3,800 and 21,000 for a Medicare plan, and 8,600 and 71,000 for a specific IDN. The incremental PMPM budget impact over the same time horizons was estimated to be $0.42 and $0.31, respectively, for a commercial plan, $0.35 and $0.10 for a Medicare plan, and $0.39 and $0.25 for a specific IDN. The differences in results across plans resulted from the population age distribution, the vaccine copay (applied in the Medicare scenario only), the vaccine coverage in the plan, and other plan-specific factors affecting disease epidemiology and costs per case of HZ. CONCLUSIONS: Model projections indicated that RZV adoption avoided HZ cases and related complications, with the PMPM budget impact dependent on plan-specific factors. As health gains increased over time, the incremental costs incurred were found to decrease as the shorter-term costs of adopting the new vaccine were increasingly offset by the longer-term benefits of vaccination. DISCLOSURES: GlaxoSmithKline Biologicals SA funded this study (GSK study identifier: HO-17-18378) and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also paid all costs associated with the development and publication of this manuscript. Patterson, Van Oorschot, and Curran are employees of the GSK group of companies and hold shares in the GSK group of companies. Herring, Carrico, and Zhang are employees of RTI Health Solutions, which received funding via a contractual agreement with the GSK group of companies to perform the work contributing to this research. Ackerson, Bruxvoort, Sy, and Tseng are employees of Kaiser Permanente Southern California, which was contracted by the GSK group of companies for the conduct of this study and were members of the KPSC study team. Ackerson, Bruxvoort, Sy, and Tseng report research contracts with the following pharmaceutical companies unrelated to this study: Dynavax (Ackerson, Bruxvoort, and Sy); the GSK group of companies (Ackerson, Bruxvoort, Sy, and Tseng); Novavax (Ackerson, Sy, and Tseng); and Seqirus (Ackerson, Bruxvoort, Sy, and Tseng). Tseng reports having served as a paid consultant for the GSK group of companies. The authors declare no other financial and nonfinancial relationships and activities. Findings from this study were presented at AMCP Nexus 2019; October 29-November 1, 2019; National Harbor, MD.

The potential public health impact of Herpes Zoster vaccination in the 65 years of age cohort in Italy.

Herpes Zoster (HZ) presents a considerable public health burden in Italy among people aged ≥50 years. This study aimed to assess the clinical and economic impact of HZ vaccination in the 65 years of age (YOA) cohort in Italy, by comparing the new Adjuvanted Recombinant Zoster Vaccine (RZV) with the currently available Zoster Vaccine Live (ZVL). A static Markov model was developed to follow all 65 YOA subjects from the year of vaccination over their lifetime by comparing three different HZ vaccination strategies: no vaccination, vaccination with ZVL and vaccination with RZV. In the base-case scenario, three 65 YOA cohorts were assumed to be vaccinated within three years, with a vaccine coverage rate of 20%, 35% and 50% at Year 1, 2 and 3 respectively, as recommended by the National Immunization Plan. The three 65 YOA Italian cohorts accounted altogether for 2,290,340 individuals. Of these, it was assumed that 564,178 subjects could be vaccinated with either RZV or ZVL in three years. The vaccination with RZV could prevent an additional total number of 35,834 HZ and 8,131 postherpetic neuralgia (PHN) cases over ZVL, leading to additional total savings of €12.4 million for the national healthcare and social systems. The introduction of RZV can be expected to have higher impact on the burden of HZ disease in the 65 YOA cohort in Italy. The avoided HZ and PHN cases can lead to an associated reduction in economic burden to the healthcare and social systems.

The Epidemiology of Herpes Zoster in Immunocompetent, Unvaccinated Adults ≥50 Years Old: Incidence, Complications, Hospitalization, Mortality, and Recurrence.

BACKGROUND: Data on the epidemiology of herpes zoster (HZ), particularly in the unvaccinated immunocompetent population, are needed to assess disease burden and the potential impact of vaccination. METHODS: The study at a large health care organization comprised: (1) incidence estimated from immunocompetent adults aged ≥50 years unvaccinated with zoster vaccine live who had incident HZ in 2011-2015; (2) proportion of HZ-related nonpain complications assessed by double abstraction of electronic health records (EHRs) of 600 incident patients 2011-2015; (3) HZ-related hospitalizations among HZ patients diagnosed in 2015; (4) HZ-related death determined from automated data and EHRs; and (5) recurrent HZ identified from a cohort initially diagnosed with HZ in 2007-2008 and followed through 2016. RESULTS: HZ incidence rate was 9.92/1000 person-years (95% confidence interval [CI], 9.82-10.01). Proportions of cutaneous, neurologic, and other complications were 6.40% (95% CI,1.73%-11.07%), 0.77% (95% CI, .00%-2.36%), and 1.01% (95% CI, .00%-2.93%), respectively. Only 0.86% of patients had an HZ-related hospitalization. The case-fatality rate was 0.04%. Recurrence rate was 10.96/1000 person-years (95% CI, 10.18-11.79) with 10-year recurrence risk of 10.26% (95% CI, 9.36%-11.23%). CONCLUSIONS: These recent HZ epidemiology data among an immunocompetent, unvaccinated population measure real-world disease burden.

Public Health Impact and Cost-Effectiveness of Non-live Adjuvanted Recombinant Zoster Vaccine in Canadian Adults.

OBJECTIVES: In Canada, incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN) are increasing, posing a significant burden on the healthcare system. This study aimed to determine the public health impact and cost effectiveness of an adjuvanted recombinant zoster vaccine (RZV) compared to no vaccination and to the live attenuated vaccine (ZVL) in Canadians aged 60 years and older. METHODS: A multi-cohort Markov model has been adapted to the Canadian context using recent demographic and epidemiologic data. Simulations consisted of age-cohorts annually transitioning between health states. Health outcomes and costs were discounted at 1.5% per year. The perspective of the Canadian healthcare payer was adopted. A coverage of 80% for the first RZV and ZVL dose and a compliance of 75% for the second RZV dose were assumed. RESULTS: RZV was estimated to be cost effective compared with no vaccination with an incremental cost-effectiveness ratio (ICER) of $28,360 (Canadian dollars) per quality-adjusted life-year (QALY) in persons aged ≥ 60 years, avoiding 554,504 HZ and 166,196 PHN cases. Compared with ZVL, RZV accrued more QALYs through the remaining lifetime and an increase in costs of approximately $50 million resulting in an average ICER of $2396. Results were robust under deterministic and probabilistic sensitivity analyses. HZ incidence rate and persistence of vaccine efficacy had the largest impact on cost effectiveness. CONCLUSIONS: The cost-utility analysis suggested that RZV would be cost effective in the Canadian population compared with no vaccination and vaccination with ZVL at a willingness-to-pay threshold of $50,000.

More than 95% of adults aged 50 are infected with varicella-zoster virus and are at risk of developing herpes zoster, also known as shingles. This risk is higher in older people and in people with a reduced immune system. Shingles causes a painful rash and may trigger persistent pain and other complications that greatly reduce quality of life. In Canada, Zostavax is the only existing approved vaccine against shingles. It has been offered in a publicly funded program in Ontario to those aged 65­70 years since September 2016. Shingrix, is a new shingles vaccine that has recently been approved by Health Canada for adults aged ≥ 50 years. The present model suggests that Shingrix confers higher protection against shingles compared to Zostavax, with a greater reduction in shingles episodes. The increase in vaccination costs would be partially offset by reduced healthcare visit and medication expenses. For these reasons, provincial health plans may consider offering Shingrix to people aged ≥ 50 years.

Public health impact model estimating the impact of introducing an adjuvanted recombinant zoster vaccine into the UK universal mass vaccination programme.

OBJECTIVES: In 2013, the herpes zoster (HZ) immunisation programme was introduced in the UK, recommending vaccination of adults 70 years of age (YOA) with the zoster vaccine live (ZVL), the only vaccine available at the time. The recently approved adjuvanted recombinant zoster vaccine (RZV) has a substantially different clinical profile that may offer additional benefits.This study aimed to 1) assess the public health impact (PHI) of introducing RZV in the UK compared with the current vaccination strategy and 2) explore via scenario analyses the optimal age group of vaccination in terms of PHI. DESIGN: A previously developed health economic model was adapted to the UK setting. SETTING: Calculations were based on efficacy data from pivotal clinical trials, HZ incidence and postherpetic neuralgia (PHN) probability from a UK study and HZ-associated complication rates from published literature. POPULATION: The base-case population considered a 2018-projected UK vaccination cohort of individuals 70 YOA. INTERVENTIONS: Vaccination with ZVL or RZV, assuming a first-dose coverage of 48.3% for both vaccines and 70% compliance for the second dose of RZV. OUTCOME MEASURES: Outcomes included reduction of HZ and PHN cases, complications and the use of healthcare resources over a life-time horizon. The impact of coverage and second-dose compliance was also explored. RESULTS: Compared with no vaccination, RZV would lead to a reduction of 30 262 HZ and 5409 PHN cases while ZVL would lead to a reduction of 7909 HZ and 3567 PHN cases. The number needed to vaccinate to prevent 1 HZ case is 12 with RZV and 45 with ZVL. The highest PHI with RZV could be achieved in individuals 60 or 65 YOA. CONCLUSION: Under the model assumptions, RZV is predicted to avert more HZ and PHN cases compared with ZVL. Results were robust under different scenario and sensitivity analyses.

Cost-Effectiveness of the Adjuvant Recombinant Zoster Vaccine in Japanese Adults Aged 65 Years and Older.

INTRODUCTION: The incidence of herpes zoster (HZ) rises steeply after the age of 50 years and the number of HZ cases and complications such as postherpetic neuralgia (PHN) is predicted to increase because of the ageing population. The objective of this study was to estimate the cost-effectiveness of recombinant zoster vaccine (RZV) compared with no vaccine for the Japanese population aged ≥ 65 years. METHODS: A multi-cohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of 1 million people aged ≥ 65 years over their remaining lifetime. Vaccination at ≥ 65 years was used in alignment with the influenza and pneumococcal vaccines recommended from 65 years. Japan-specific data inputs for the model were obtained from local data sources. Age-stratified vaccine efficacy and waning rates were based on published clinical trial data. In the base-case analysis, vaccine coverage was assumed to be 40% with a second dose compliance of 95%. Costs and outcomes were discounted at 2% annually and the incremental cost-effectiveness ratio (ICER) was calculated from both a payer's and the societal perspective. Sensitivity analyses were carried out to explore the overall uncertainty in the model. RESULTS: Vaccination with RZV was projected to prevent 48,943 HZ cases and 12,136 PHN cases per million people aged ≥ 65 years compared with no vaccination. The incremental costs and quality-adjusted life years (QALYs) gained were ¥9.99 billion and 2314 QALYs from a payer's perspective and ¥9.34 billion and 2314 QALYs from a societal perspective. The resulting ICERs were approximately ¥4,320,000 and ¥4,040,000 per QALY gained from a payer's and the societal perspective, respectively. The ICER remained below a willingness-to-pay threshold of ¥5,000,000 for most sensitivity analyses carried out. CONCLUSION: Vaccination against HZ with RZV would be cost-effective compared with no vaccination for the Japanese population aged ≥ 65 years. TRIAL REGISTRATION: GSK study identifier: HO-16-17837. FUNDING: GlaxoSmithKline Biologicals SA.

Cost-effectiveness of an adjuvanted recombinant zoster vaccine in older adults in the United States who have been previously vaccinated with zoster vaccine live.

Zoster Vaccine Live (ZVL) is marketed in the US since 2008, and a non-live adjuvanted Recombinant Zoster Vaccine (RZV) was approved in 2017. Literature suggests that waning of ZVL efficacy may necessitate additional vaccination. The Advisory Committee on Immunization Practices recommended vaccination with RZV in immunocompetent adults aged 50+ years old, including those previously vaccinated with ZVL. The objective of this study was to determine the cost-effectiveness of vaccinating US adults aged 60+ years old, previously vaccinated with ZVL. The ZOster ecoNomic Analysis (ZONA) model, a deterministic Markov model, was adapted to follow a hypothetical 1 million(M)-person cohort of US adults previously vaccinated with ZVL. Model inputs included demographics, epidemiology, vaccine characteristics, utilities and costs. Costs and quality-adjusted life-years (QALYs) were presented over the lifetimes of the cohort from the year of additional vaccination, discounted 3% annually. The model estimated that, vaccination with RZV 5 years after previous vaccination with ZVL, would reduce disease burden compared with no additional vaccination, resulting in a gain of 1,633 QALYs at a total societal cost of $96M (incremental cost-effectiveness ratio: $58,793/QALY saved). Compared with revaccinating with ZVL, vaccination with RZV would result in a gain of 1,187 QALYs and societal cost savings of almost $84M. Sensitivity, scenario, and threshold analyses demonstrated robustness of these findings. Vaccination with RZV is predicted to be cost-effective relative to no additional vaccination, assuming a threshold of $100,000/QALY, and cost-saving relative to ZVL revaccination of US adults aged 60+ years old who have been previously vaccinated with ZVL.