Community-Based Cross-Sectional Assessment Survey On Herpes Zoster Vaccination Practices.

Background: Herpes Zoster (HZ), also known as Shingles, is a commonly occurring infection especially among the elderly. It is due to the reactivation of the dormant virus in the sensory ends that were present since the primary infection with the virus. Objective: Our study aims at assessing the knowledge, attitudes practices beliefs and current barriers towards the Shingrix vaccine to fully understand where we stand and come up with proper recommendations to services these at-risk individuals and ultimately have a positive impact on the healthcare system. Methods: Questionnaire based cross sectional study using a translated version of a previously developed and tested questionnaire. Results: more than 8000 participants responded to the survey. The vast majority had chicken pox before and did hear about the vaccine from different sources. Most of the participants had minimal knowledge regarding the vaccine and were willing to take it regardless of some safety concerns. Conclusion: more efforts need to be conducted to enhance vaccine uptake in at risk populations in Saudi Arabia.

Maternal varicella antibodies in children aged less than one year: Assessment of antibody decay.

OBJECTIVES: To investigate maternal antibody levels to varicella in infants <12 months of age in Ontario, Canada. STUDY DESIGN: In this study, we included specimens from infants <12 months of age, born at ≥37 weeks gestational age, who had sera collected at The Hospital for Sick Children (Toronto, Canada) between 2014-2016. We tested sera using a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). We measured varicella susceptibility (antibody concentration <150mIU/mL) and mean varicella antibody concentration, and assessed the probability of susceptibility and concentration between one and 11 months of age using multivariable logistic regression and Poisson regression. RESULTS: We found that 32% of 196 included specimens represented infants susceptible to varicella at one month of age, increasing to nearly 80% at three months of age. At six months of age, all infants were susceptible to varicella and the predicted mean varicella antibody concentration declined to 62 mIU/mL (95% confidence interval 40, 84), well below the threshold of protection. CONCLUSIONS: We found that varicella maternal antibody levels wane rapidly in infants, leaving most infants susceptible by four months of age. Our findings have implications for the timing of first dose of varicella-containing vaccine, infection control measures, and infant post-exposure prophylaxis recommendations.

Characteristics and economic burden of hospitalized patients with herpes zoster in China, before vaccination.

Herpes zoster (HZ) brings a significant economic burden. The HZ vaccine was introduced in China for the first time in 2020, and there is a lack of up-to-date information on the hospitalization costs and characteristics prior to vaccination. This study aimed to describe the characteristics and economic burden of HZ inpatients in Hunan Province, China, and analyze the factors influencing the length of stay (LOS) and costs. This was a retrospective study and we extracted information from the Chinese National Health Statistics Network Reporting System on HZ inpatients in Hunan Province, China from 2017 to 2019. Spatial join tools and Global or Local Moran's Index were used for the geographic analysis of hospitalized HZ incidence. Multivariate linear regression models were used to analyze the factors influencing LOS and costs. There were 44,311 HZ inpatients included in this study, incurring a total of $31,857,734 medical costs. These patients had a median LOS of 8 days and a median expenditure of $573.47. Older age, more comorbidities, and the presence of complications with nervous system involved were all significantly associated with longer LOS and higher costs. HZ infection resulted in a large direct medical cost and heavy disease burden, especially in patients with advanced age or underlying medical conditions. The HZ vaccine has the potential to effectively reduce the disease burden and should be widely popularized especially among high-risk groups.

Healthcare resource use and costs of varicella and its complications: A systematic literature review.

Varicella is a highly contagious disease caused by the varicella zoster virus (VZV). While the disease is usually mild, severe complications can occur requiring costly hospitalization. A thorough understanding of the healthcare resource use (HCRU) and costs of varicella is needed to inform health-economic models of preventive strategies. A systematic literature review was carried out to retrieve relevant publications between 1999 and 2021, reporting HCRU and cost outcomes for varicella and its complications. Data were extracted and stratified according to pre-specified age groups and complication categories. Costs were re-based to a $US2020 footing using both purchasing power parity and the medical component of consumer price indexes. Data were summarized descriptively due to high heterogeneity in study design and outcome reporting. Forty-four publications fulfilled the inclusion and exclusion criteria of which 28 were conducted in Europe, 6 in Middle East and Asia, 5 in South America, 3 in North America, and 2 in multiple regions. Primary healthcare visits accounted for 30% to 85% of total direct costs. Hospitalization costs varied between $1,308 and $38,268 per episode depending on country, complication type, and length of stay, contributing between 2% and 60% to total direct costs. Indirect costs, mostly driven by workdays lost, accounted for approximately two-thirds of total costs due to varicella. The management of varicella and related complications can lead to substantial HCRU and costs for patients and the healthcare system. Additional research is needed to further characterize the varicella-associated economic burden and its broader impact from a societal standpoint.

Varicella, also known as chickenpox, is a highly contagious infectious disease which affects mostly children. Indeed, >90% of children will have had chickenpox by the age of 12 years. The symptoms are usually mild, but in some cases, serious complications can occur such as pneumonia, bacterial superinfection of the skin and encephalitis. A clear understanding of the complications of chickenpox for patients and the healthcare system would be helpful so that countries can assess the true health and economic burden of the disease.In this study, we have summarized existing published data from around the world. We have included studies that reported on the number of varicella cases, doctor visits, hospitalizations, and costs due to varicella and associated complications.These data showed that varicella causes high costs to the healthcare system. Even though less than 1% of varicella patients need to be hospitalized, costs remain high because varicella is so common. Furthermore, if the number of workdays lost are counted as well, then varicella-related costs are even higher.

The potential impact of increased recombinant zoster vaccine coverage on the burden of herpes zoster among adults aged 50-59 years.

INTRODUCTION: Recombinant zoster vaccine (RZV) is recommended in the US for prevention of herpes zoster (HZ) in adults aged ≥50 years. Vaccination rates remain suboptimal for adults 50-59 years compared with adults ≥50 years overall. The objective of this study was to model changes in outcomes associated with improved RZV vaccination coverage in US adults 50-59 years. METHODS: A multicohort Markov model compared a scenario using real-world vaccination coverage for US adults 50-59 years in 2020 versus scenarios assuming higher coverage. Outcomes, based on a lifetime horizon, included HZ cases and complications avoided, quality-adjusted life-years (QALY), and costs. Model inputs included HZ epidemiology, RZV vaccine efficacy, coverage, adverse events, and costs, based on published literature and US sources. Some inputs were updated from previous models, including real-world estimates of RZV coverage, series completion, and reflecting longer-term data on waning of vaccine efficacy. The model utilized a cohort size of 42,756,488 individuals based on the 2020 US population census. RESULTS: The model projected that increasing RZV coverage in adults 50-59 years from 7.3 % to 14.6 % (to coverage for adults 60-64 years in 2020) would avoid an additional 504,468 HZ cases, 42,077 postherpetic neuralgia cases, and 56,247 cases of other HZ-associated complications. The increase in vaccine coverage would result in higher vaccination-related costs of $1,172,411,566, but the avoided HZ cases and complications would be expected to result in direct cost savings of $721,973,386 and indirect cost savings of $593,497,480 from avoided productivity loss. Overall, a gain of 5,230 discounted QALYs and cost savings of $143,059,299 from a societal perspective would be realized. CONCLUSION: Modestly higher RZV coverage in US adults 50-59 years could reduce the clinical burden associated with HZ and may result in societal cost savings. These findings demonstrate the potential value of increasing RZV vaccination in this population.

Evolving etiologies, comorbidities, survival, and costs of care in adult encephalitis.

Encephalitis is a central nervous system disorder, often caused by infectious agents or aberrant immune responses. We investigated causes, comorbidities, costs, and outcomes of encephalitis in a population-based cohort. ICD-10 codes corresponding to encephalitis were used to identify health services records for all adults from 2004 to 2019. Data were cross-validated for identified diagnoses based on laboratory confirmation using univariate and multivariate statistical analyses. We identified persons with a diagnosis of encephalitis and abnormal cerebrospinal fluid (CSF) results (n = 581) in whom viral genome was detected (n = 315) in a population of 3.2 million adults from 2004 to 2019. Viral genome-positive CSF samples included HSV-1 (n = 133), VZV (n = 116), HSV-2 (n = 34), enterovirus (n = 4), EBV (n = 5), and CMV (n = 3) with the remaining viruses included JCV (n = 12) and HHV-6 (n = 1). The mean Charlson Comorbidity Index (2.0) and mortality rate (37.6%) were significantly higher in the CSF viral genome-negative encephalitis group although the mean costs of care were significantly higher for the CSF viral genome-positive group. Cumulative incidence rates showed increased CSF VZV detection in persons with encephalitis, which predominated in persons over 65 years with a higher mean Charlson index. We detected HSV-2 and VZV more frequently in CSF from encephalitis cases with greater material-social deprivation. The mean costs of care were significantly greater for HSV-1 encephalitis group. Encephalitis remains an important cause of neurological disability and death with a viral etiology in 54.2% of affected adults accompanied by substantial costs of care and mortality. Virus-associated encephalitis is evolving with increased VZV detection, especially in older persons.

The incidence of herpes zoster in China: A meta-analysis and evidence quality assessment.

This review aimed to estimate the disease burden of herpes zoster (HZ) in China and explore the application of the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach in studies of disease burden. We searched for the literature of observational studies analyzing HZ incidence in populations of all ages in China. Meta-analysis models were constructed to calculate the pooled incidence of HZ and pooled risks of postherpetic neuralgia (PHN), HZ recurrence, and hospitalization. Subgroup analysis was performed according to gender, age, and quality assessment score. The quality of evidence for incidence was rated using the GRADE system. Twelve studies with a total of 25,928,408 participants were included in this review. The pooled incidence for all ages was 4.28/1000 person years (95% CI 1.22-7.35). It increased with the increasing in age especially for individuals aged ≥60 y, which was 11.69/1000 person years (95% CI 6.56-16.81). The pooled risks of PHN, recurrence, and hospitalization were 12.6% (95% CI 10.1-15.1), 9.7% (95% CI 3.2-16.2), and 6.0/100,000 population (95% CI 2.3-14.2), respectively. The quality of the evidence assessment of the pooled incidence by the GRADE for all ages was 'low'; however, it was 'moderate' for the ≥60 yold subgroup. HZ is a serious public health problem in China and is more significant in individuals older than 60 y. Therefore, an immunization strategy for the zoster vaccine should be considered. The evidence quality assessment by the GRADE approach indicated that we had more confidence in the estimation of aged population.

Proceedings of the expert consensus group meeting on herpes zoster disease burden and prevention in India: An opinion paper.

Herpes zoster (HZ) is a debilitating viral infection causing a dermatomal vesicular rash. Many known risk factors exist in India and adults >50 years of age may be especially susceptible to HZ. However, HZ is not a notifiable disease in India and data on incidence and disease burden is lacking. An Expert Consensus Group meeting was conducted with experts from relevant specialties to discuss HZ disease, its local epidemiology, and suggestions for implementing HZ vaccination in the Indian healthcare system. Currently, there is lack of patient awareness, poor reporting practices and general negligence in the treatment of the disease. HZ patients generally approach their general physicians or specialists for diagnosis, which is usually based on patient history and clinical symptoms. Recombinant zoster vaccine (RZV) has >90% efficacy and is recommended in adults ≥50 years of age to prevent HZ in the United States. Despite RZV being approved for use, it is not yet available in India. India has a growing elderly population with known risk factors for HZ like immunosuppression, and co-morbidities like diabetes and cardiovascular disease. This indicates the need for a targeted immunization program in India. Meeting also emphasized adult vaccine availability and accessibility in the country.

Laboratory assessment of a multi-target assay for the rapid detection of viruses causing vesicular diseases.

BACKGROUND: The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common causes of vesicular disease include Monkeypox virus (MPXV), clades I and II, Herpes simplex viruses Type 1 and Type 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Varicella-zoster virus (VZV) and Enteroviruses (EVs). Here, we assessed a syndromic viral vesicular panel for rapid and simultaneous detection of these 7 targets in a single cartridge. OBJECTIVE: The aim of this study was to evaluate the QIAStat-Dx ® viral vesicular (VV) panel and compare with laboratory developed tests (LDTs). Limit of detection, inter-run variability, cross-reactivity and specificity were assessed. Positive and negative percent agreement, and correlation between assays was determined using 124 clinical samples from multiple anatomical sites. RESULTS: The overall concordance between the QIAstat and LDTs was 96%. Positive percent agreement was 82% for HHV-6, 89% for HSV-1 and 100% for MPXV, HSV-2, EV and VZV. Negative percent agreement was 100% for all targets assessed. There was no cross-reactivity with Vaccinia, Orf, Molluscum contagiosum viruses, and a pooled respiratory panel. CONCLUSION: The QIAstat VV multi-target syndromic panel combine ease of use, rapid turnaround, good sensitivity and specificity for enhanced diagnosis, clinical care and public health responses.

Recombinant zoster vaccine coverage in the United States: An analysis of claims-based data.

Recombinant zoster vaccine (RZV) is recommended for individuals ≥ 50 years of age for protection against herpes zoster (HZ). This study quantifies RZV coverage and assesses predictors for RZV vaccination using a U.S. claims database. Univariate linear regression provided annual prevalence of RZV vaccination and multivariable logistic regression provided ORs and 95% CIs for associations between predictors and RZV vaccination. A total of 4,124,315 individuals (19,080,914 person-years) were included in this study. Since receiving FDA approval for the prevention of HZ, RZV coverage (of at least one dose) has reached approximately 17% within the eligible U.S. population by January 2021, although significant disparities between demographic groups were noted. Our findings suggest that HZ vaccine coverage may be reduced below goal in the U.S. and highlights the importance of continuing to monitor RZV vaccination. Additionally, as our study found disparities in vaccine coverage, attention towards marginalized and medically underserved populations is needed.

The necessity for popularizing varicella-zoster virus vaccine programs worldwide: An age-period-cohort analysis for the Global Burden of Disease study 2019.

BACKGROUND: Varicella-zoster virus (VZV) causes varicella and herpes zoster (VHZ), which is endemic worldwide. Although infection with VZV represents a considerable health threat, the global, regional and national burden of VZV infection, especially the probable relationship between VZV vaccines and the epidemiology of VZV infection, is poorly known. We sought to estimate the global spatial patterns and temporal trends of VHZ burden in 204 countries and territories from 1990 to 2019. METHODS: Numbers and age-standardized rates (ASR) of VHZ incidence, and disability-adjusted life years (DALYs) were estimated using data from the Global Burden of Diseases Study (GBD) 2019. Spatiotemporal trends in ASR were evaluated by estimated annual percentage change (EAPC). RESULTS: Worldwide, in 2019, there were approximately 84.0 million incidence and 0.9 million DALYs due to VHZ. The corresponding ASIR (age-standardized incidence rate) and ASDR (age-standardized DALY rate) drastically decreased in children (aged <20 years old), while the ASIR and ASDR of VHZ significantly increased in middle- and old-aged adults (aged >50 years old), with highest ASIR and ASDR in the High-income Asia Pacific and Western Sub-Saharan Africa, respectively. From 1990-2019, the corresponding EAPC in ASIR were 0.03 (95% uncertainty interval [UI]: 0.02-0.04). Whereas the global EAPC in ASDR decreased in all regions (-1.59, 95% UI: -1.64 to -1.55), expect for Australasia (0.46, [0.05, 0.88]). Notably, in 2019, age-specific rates of VHZ DALYs presented a rapid growth trend after 70 years old. CONCLUSION: The spatiotemporal trends of VHZ were heterogeneous across countries from 1990 to 2019. The spatiotemporal trend in ASIR is highest in the High sociodemographic index (SDI) region, however the EAPC in ASDR is lowest, in part probably due to VHZ vaccination. Therefore, reducing morbidity and burden strategies such as vaccines programs for the prevention of VHZ should be promoted in those regions with high growth incidence and/or burden, especially for the population after 70 years old.

Public health impact of recombinant zoster vaccine for prevention of herpes zoster in US adults immunocompromised due to cancer.

Individuals who are immunocompromised (IC) due to therapy or underlying disease are at increased risk of herpes zoster (HZ). This study evaluates the public health impact of recombinant zoster vaccine (RZV) relative to no HZ vaccination for the prevention of HZ among adults aged ≥18 years diagnosed with selected cancers in the United States (US). A static Markov model was used to simulate three cohorts of individuals who are IC with cancer (time horizon of 30 years; one-year cycle length): hematopoietic stem cell transplant (HSCT) recipients, patients with breast cancer (BC; a solid tumor example), and patients with Hodgkin's lymphoma (HL; a hematological malignancy example). Cohort sizes reflect the estimated annual incidence of each condition in the US population (19,671 HSCT recipients, 279,100 patients with BC, and 8,480 patients with HL). Vaccination with RZV resulted in 2,297; 38,068; and 848 fewer HZ cases for HSCT recipients, patients with BC, and patients with HL, respectively (each versus no vaccine). Vaccination with RZV also resulted in 422; 3,184; and 93 fewer postherpetic neuralgia cases for HSCT, BC, and HL, respectively. Analyses estimated the quality-adjusted life years gained to be 109, 506, and 17 for HSCT, BC, and HL, respectively. To prevent one HZ case, the number needed to vaccinate was 9, 8, and 10, for HSCT, BC, and HL, respectively. These results suggest RZV vaccination may be an effective option to significantly reduce HZ disease burden among patients diagnosed with selected cancers in the US.

Shingles cases can be prevented by recombinant zoster vaccine (RZV). People who have a weakened immune system (immunocompromised) due to disease or therapy are more likely to develop shingles. For example, shingles occurs in nearly a quarter of patients receiving immunosuppressive treatment for blood cancers. To estimate the public health impact of vaccination against shingles in people who are immunocompromised due to cancer in the United States (US), we used a model to simulate groups with selected types of cancer. The results indicate vaccination with RZV can significantly reduce shingles cases and related complications among these groups in the US.

Cost-effectiveness of the recombinant zoster vaccine (RZV) against herpes zoster: An updated critical review.

The objective of this study was to critically review the cost-effectiveness (CE) of the recombinant zoster vaccine (RZV) against herpes zoster (HZ). A literature review was conducted in PubMed, Embase, and Cochrane between January 1, 2017, and February 28, 2022, and on select public healthcare agency websites to identify and collect data from CE studies comparing RZV to zoster vaccine live (ZVL) or to no vaccination. Study characteristics, inputs, and outputs were collected. The overall CE of RZV was assessed. RZV vaccination against HZ is cost-effective in 15 out of 18 studies included in the present review. Varying incremental cost-effectiveness ratios (ICERs) observed may be associated with different assumptions on the duration of protection of RZV, as well as different combinations of structural and disease-related study (model) inputs driving the estimation of ICERs.

What is the context?• Herpes zoster, also known as shingles, may cause painful rashes and skin alterations.• Chronic pain, also referred to as post-herpetic neuralgia, may persist for months or even years after the initial rash.• The disease is caused by reactivation of the varicella zoster virus.• The recombinant zoster vaccine (RZV) and the zoster vaccine live (ZVL) are approved for the prevention of herpes zoster and post-herpetic neuralgia.• We reviewed published evidence from the past 5 years on RZV.What is new?• Out of 18 selected studies, RZV vaccination against herpes zoster and post-herpetic neuralgia is cost-effective in 15.• In the 15 studies establishing RZV cost-effectiveness, RZV is always cost-effective or frequently cost-saving in direct comparisons to ZVL, when applicable.• RZV was found cost-saving in several immune-compromised populations.What is the impact?• The overview of the currently available body of evidence related to cost-effectiveness of RZV may help informing decision makers about the value of vaccination against herpes zoster.

Systematic review of economic evaluations of varicella vaccination programmes.

OBJECTIVES: This study carried out a systematic literature review of economic evaluations of varicella vaccination programmes from the earliest publication to the present day, including programmes in the workplace and in special risk groups as well as universal childhood vaccination and catch up programmes. METHODS: Articles published from 1985 until 2022 were sourced from PubMed/Medline, Embase, Web of Science, NHSEED and Econlit. Eligible economic evaluations, which included posters and conference abstracts, were identified by two reviewers who scrutinised each other's selections at both title and abstract and full report stages. The studies are described in terms of their methodological characteristics. Their results are aggregated by type of vaccination programme and the nature of the economic outcome. RESULTS: A total of 2575 articles were identified of which 79 qualified as economic evaluations. A total of 55 studies focused on universal childhood vaccination, 10 on the workplace and 14 on high risk groups. Twenty-seven studies reported estimates of incremental cost per quality-adjusted life year (QALY) gained, 16 reported benefit-cost ratios, 20 reported cost-effectiveness outcomes in terms of incremental cost per event or life saved and 16 reported cost-cost offset results. Most studies of universal childhood vaccination reported an increase in overall costs to health services, but often a reduction in cost from a societal perspective. CONCLUSIONS: The evidence surrounding the cost-effectiveness of varicella vaccination programmes remains sparse with contrasting conclusions in some areas. Future research should particularly aim to encompass the impact of universal childhood vaccination programmes on herpes zoster among adults.

Incidence of Herpes Zoster in Patients With Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

OBJECTIVE: To estimate the incidence of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) compared with the general population in the USA. METHODS: This retrospective, longitudinal cohort study used data from an administrative claims database containing both commercial and Medicare Advantage Part D data, with a data period from October 2015 to February 2020. Patients were aged ≥ 18 years and divided into 2 cohorts: patients with RA and patients without RA. Diagnosis and procedure codes were used to identify HZ cases and calculate incidence rates (IRs) of HZ in the 2 cohorts. Data were stratified by age group (ie, 18-49, 18-29, 30-39, 40-49, 50-64, and ≥ 65 yrs) and RA therapy type. IR ratios (IRRs), adjusted by cohort baseline characteristics, were estimated using generalized linear models to compare the incidence of HZ between cohorts. RESULTS: The overall IR of HZ was higher in the RA cohort (21.5 per 1000 person-years [PY]; N = 67,650) than in the non-RA cohort (7.6 per 1000 PY; N = 11,401,743). The highest IRs in both cohorts were observed in the age group of ≥ 65 yrs (23.4 and 11.4 per 1000 PY in the RA cohort and non-RA cohort, respectively). The overall adjusted IRR of HZ was 1.93 (95% CI 1.87-1.99, P < 0.001) for the RA cohort compared with the non-RA cohort. In the RA cohort, the highest IRs by medication class were observed in patients using corticosteroids and those using Janus kinase inhibitors. CONCLUSION: These results highlight the increased incidence of HZ in patients with RA.

Public health impact of herpes zoster vaccination on older adults in Hong Kong.

The growing burden of herpes zoster (HZ) in Hong Kong, due to an aging population with increasing life expectancy, may be reduced by vaccination. This study aimed to estimate public health impact of HZ vaccination in Hong Kong. The ZOster ecoNomic Analysis (ZONA) model was adapted with Hong Kong-specific key model inputs/assumptions, where available. Base case analysis involved adults ≥50 years of age (YOA), exploring three vaccination strategies (no vaccination/recombinant zoster vaccine [RZV]/zoster vaccine live [ZVL]) under private market (5% coverage) and mass vaccination (40% coverage) settings. Scenario and sensitivity analyses were performed. In the base case population (3.13 million), without vaccination, 891,024 HZ (28.4%), 156,097 post-herpetic neuralgia (PHN) (5.0%), and 38,755 (1.2%) HZ ophthalmicus (HZO) were projected over their remaining lifetime. Mass RZV vaccination reduced HZ, PHN, and HZO cases by 204,875 (-23.0%), 31,949 (-20.5%), and 8,471 (-21.9%), respectively, which was 4-5 times that reduced with ZVL. RZV was more efficient than ZVL, with lower number needed to vaccinate to prevent one HZ/PHN/HZO case (RZV: 7/40/148; ZVL: 27/163/709). Among all age cohorts, the greatest reduction in cases was projected for RZV (versus no vaccination/ZVL) in the youngest cohort, 50-59 YOA. Results were robust under scenario and sensitivity analyses. HZ burden in Hong Kong is substantial. Mass RZV vaccination is expected to considerably reduce public health burden of HZ among individuals ≥50 YOA, compared with no vaccination/ZVL. Results may support value assessment and decision-making regarding vaccination strategies for HZ prevention in Hong Kong.

In Hong Kong, the burden of shingles is increasing due to an aging population with increasing life expectancy. Vaccination can prevent shingles and reduce disease burden. Since 2021, two shingles vaccines are available in Hong Kong: zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). Using mathematical modeling, this study compared the public health impact (the number of cases of disease that would occur) of different shingles vaccination strategies, in a hypothetical population of 3.13 million Hong Kong adults aged ≥50 years in their remaining lifetime. The three strategies compared were no vaccination versus vaccination with ZVL or RZV. With no vaccination, public health burden of shingles would remain high, where an estimated 2 in 7 will have shingles, 1 in 20 will have shingles-related nerve pain, and 1 in 100 will have shingles around the eye. Vaccination (versus no vaccination) was predicted to reduce these cases by 47,477 (shingles), 7,701 (nerve pain), and 1,769 (shingles around the eye) for ZVL; and 204,875 (shingles), 31,949 (nerve pain), and 8,471 (shingles around the eye) for RZV. RZV avoided 4­5 times the number of cases compared with ZVL. Earlier RZV vaccination, from age 50 years, would have a greater public health impact than vaccination at a later age as the percentage of cases avoided with RZV (versus no vaccination) was highest in people aged 50­59 years compared with other age groups. These results may support value assessment and decision-making on public health vaccination strategies for shingles prevention in Hong Kong.

Assessment of attenuation of varicella-zoster virus vaccines based on genomic comparison.

Live attenuated varicella-zoster virus (VZV) vaccines are used to prevent chickenpox and shingles. Single nucleotide polymorphisms (SNPs) that occur during the attenuation of parental strains are critical indicators of vaccine safety. To assess the attenuation of commercial VZV vaccines, genetic variants were comprehensively examined through high-throughput sequencing of viral DNA isolated from four VZV vaccines (Barycela, VarilRix, VariVax, and SKY Varicella). Whole-genome comparison of the four vaccines with the wild-type strain (Dumas) revealed that the sequences are highly conserved on a genome-wide scale. Among the 196 common variants across the four vaccines, 195 were already present in the genome of the parental strain (pOka), indicating that the variants occurred during the generation of the parental strain from the Dumas strain. Compared to the pOka genome, the vaccines exhibited distinct variant frequencies on a genome-wide and within an attenuation-related open reading frame. In particular, attenuation-associated 42 SNPs showed that Barycela, VarilRix, VariVax, and SKY Varicella are in ascending order regarding similarity with pOka-like genotypes, which in turn, might provide genomic evidence for the levels of attenuation. Finally, the phylogenetic network analysis demonstrated that genetic distances from the parental strain correlated with the attenuation levels of the vaccines.

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.

Assessment of Safety and Efficacy of Tofacitinib, Stratified by Age, in Patients from the Ulcerative Colitis Clinical Program.

BACKGROUND: In patients with ulcerative colitis (UC), risks of infection and malignancies increase with age. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. This analysis assessed age as a risk factor for adverse events of special interest (AESI) in the tofacitinib UC clinical program. METHODS: Data were from phase 2 and 3 induction studies, a phase 3 maintenance study, and an open-label, long-term extension study. Efficacy and/or safety outcomes were analyzed in the Induction, Maintenance, and Overall Cohorts (patients who received ≥ 1 dose of tofacitinib), stratified by age. The effects of baseline demographic and disease-related factors on AESI incidence were assessed by Cox proportional-hazards regression analysis. RESULTS: In the Overall Cohort (1157 patients with ≤ 6.8 years' tofacitinib treatment), age was a statistically significant predictor of herpes zoster (HZ), malignancies excluding nonmelanoma skin cancer (NMSC), and NMSC. Other statistically significant predictors included prior tumor necrosis factor inhibitor failure for HZ, NMSC, and opportunistic infection events, and prior duration of UC for malignancies excluding NMSC. In the Induction and Maintenance Cohorts, a higher proportion of tofacitinib-treated than placebo-treated patients (numerical difference) achieved the efficacy endpoints (endoscopic improvement, clinical remission, clinical response) across all age groups. CONCLUSIONS: Older individuals receiving tofacitinib as induction and maintenance therapy to treat UC may have an increased risk of HZ, malignancies (excluding NMSC), and NMSC versus similarly treated younger patients, consistent with findings from the general population. Across all age groups, tofacitinib demonstrated greater efficacy than placebo as an induction and maintenance therapy. CLINICALTRIALS.GOV REGISTRATION NUMBERS: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.

Age was assessed as a risk factor for adverse events of special interest in the tofacitinib ulcerative colitis clinical program. Older individuals receiving tofacitinib may have an increased risk of herpes zoster, malignancies (excluding nonmelanoma skin cancer), and nonmelanoma skin cancer versus similarly treated younger patients.

Economic burden of herpes zoster in Latin America: A systematic review and meta-analysis.

This systematic review describes herpes zoster (HZ) economic burden in terms of healthcare resource use and cost outcomes in the Latin America and Caribbean (LAC) region. We searched online databases from 1 January 2000 to 20 February 2020 to identify eligible publications. We identified 23 publications that reported direct costs, indirect costs, and resources associated with HZ and its complications. The primary direct medical resources reported in the different studies were visits to doctors, transportation, days in the hospital, nursing, medication schedules, and physical therapy. Direct total costs per patient ranged from $99.99 to $4177.91. The highest cost was found in Brazil. Direct costs are, in average, 81.39% higher than indirect costs. The cost per patient that includes postherpetic neuralgia treatment is 115% higher on average for the directs and 73% for the indirect costs. Brazil reported a higher total cost per patient than Argentina and Mexico, while for indirect costs per patient, Brazil and Argentina had higher costs than Mexico, respectively. A meta-analysis on the number of days due to HZ hospitalization, performed on non-immunosuppressed patients over 65 years of age from three studies, resulted in a cumulative measure of 4.5 days of hospitalization. In the LAC region, the economic burden of HZ and associated complications is high, particularly among high-risk populations and older age groups. Preventative strategies such as vaccination could help avoid or reduce the HZ-associated disease economic burden in the LAC region.