Risk of Herpes Zoster Ophthalmicus Recurrence After Recombinant Zoster Vaccination.

Importance: The recombinant zoster vaccine (RZV) is currently recommended for immunocompetent adults aged 50 years or older and immunocompromised adults aged 19 years or older and is effective in preventing herpes zoster ophthalmicus (HZO). However, questions about the safety of RZV in patients with a history of HZO remain. Objective: To evaluate whether there is an increased risk of HZO recurrence after RZV in patients with a history of HZO. Design, Setting, and Participants: This retrospective cohort study used medical and outpatient pharmacy claims data for commercial and Medicare Advantage enrollees from the Optum Labs Data Warehouse. Patients with incident HZO from January 1, 2010, to December 31, 2021, were identified; the study period ended on March 31, 2022. The vaccinated group consisted of patients with at least 1 dose of RZV more than 90 days following the initial HZO diagnosis. The unvaccinated group consisted of patients without any record of RZV in the study period. Vaccinated and unvaccinated patients were matched using exact k:1 matching without replacement. Exposure: Recombinant zoster vaccination. Main Outcomes and Measures: The main outcome was the number of HZO recurrences with and without RZV exposure. Results: A total of 16 408 patients were included in the matched analysis, of whom 12 762 were unvaccinated (7806 [61.2%] female; mean [SD] age at diagnosis, 68.8 [10.3] years) and 3646 were vaccinated (2268 [62.2%] female; mean [SD] age at diagnosis, 67.4 [9.8] years). Within the primary risk period of 56 days after the index date (ie, the start of follow-up for the outcome), the incidence of HZO recurrence after any RZV exposure was 37.7 per 1000 person-years compared with 26.2 per 1000 person-years in the unexposed group. After controlling for race and ethnicity, inpatient stays, emergency department visits, concomitant vaccines, and eye care practitioner visits, the association between vaccination status and HZO exacerbation in the primary risk period had an adjusted hazard ratio for any RZV exposure of 1.64 (95% CI, 1.01-2.67; P = .04). Conclusions and Relevance: In this study, RZV exposure was associated with a higher likelihood of HZO recurrence in patients with a history of HZO compared with no RZV exposure. These findings support consideration that patients with a history of HZO may benefit from monitoring after receiving RZV in case of HZO recurrence.

Factors associated with shingles and pneumococcal vaccination among older Canadians.

Background: Immunization against vaccine-preventable diseases such as shingles and pneumococcal disease is especially pertinent among older Canadians. However, vaccine uptake remains low. Data and methods: Data from the Canadian Health Survey on Seniors (CHSS) - 2019/2020 were used to examine receipt of shingles and pneumococcal vaccines among Canadians aged 65 and older living in the community. Multivariable logistic regression was used to identify individual predisposing, enabling and needs-related factors associated with receipt of each type of vaccination. Reasons reported for not getting vaccinated were also examined. Results: Based on the 2019/2020 CHSS, an estimated 36.3% of Canadians aged 65 and older (2.3 million people) had received the shingles vaccine, while 51.1% (3.1 million) had received the pneumococcal vaccine. Being a woman, having higher socioeconomic status, having had the flu shot and having a regular health care provider were associated with increased odds of vaccination. Being an immigrant, living outside large population centres, and belonging to South Asian or Chinese population groups were associated with lower odds of vaccination. Over one-third of unvaccinated people did not think the shingles vaccine (39.7%) or the pneumococcal vaccine (36.6%) was necessary. Other frequently reported reasons for non-vaccination were not having heard of the vaccine or the doctor not mentioning it; for the shingles vaccine, 12% cited cost as a reason. Interpretation: Understanding factors associated with uptake of vaccines and reasons for not obtaining them among older Canadians will help to inform policy and programs aimed at preventing the burden of these diseases.

Varicella Zoster vaccination in hemodialysis patients: The state of the art.

Varicella Zoster Virus (VZV) infection is a common childhood exanthematous disease, which in adults and immunocompromised people may result in severe neurologic complications. Up to one-third of infected subjects may have VZV clinical reactivation particularly if immunocompromised. Patients affected by end-stage renal disease on hemodialysis present immunodepression that contributes to their higher incidence of VZV infections and reactivation. While antiviral treatment in these patients shows low efficacy, the prevention of VZV through vaccination avoids the primary infection and the risk of reactivation. Two VZV vaccines are currently available: the live attenuate Zoster Vaccine (LZV) and a Recombinant Zoster Vaccine (RZV), with the latter appearing to provide greater efficacy. Given the higher incidence of VZV infection and reactivation, the lesser response to antivirals and the lower impact of VZ vaccine in hemodialysis patients in terms of side effects, a higher diffusion of VZV vaccination should be promoted by nephrologists in these patients in particular in those with future transplant opportunities.

ATAGI Targeted Review 2022: Vaccination for prevention of herpes zoster in Australia.

Abstract: In November 2016, herpes zoster (HZ) vaccination for older adults, using the live-attenuated zoster vaccine (Zostavax; ZVL) was added to the Australian National Immunisation Program (NIP) with the aim of reducing morbidity from HZ and its complications, particularly for people at increased risk. Prior to the program, there were on average 5.6 cases of HZ per 1,000 persons annually in Australia, with highest risk of disease in older and in immunocompromised people. The burden of complications of HZ, such as post-herpetic neuralgia (PHN), was also highest in older and immunocompromised groups. No formal comprehensive program evaluation has been undertaken since program commencement. This review examined published literature and available vaccine administration data to summarise the evidence and considerations underpinning current use of HZ vaccines and potential future program directions in Australia. There have been modest reductions in the incidence of HZ and its complications since program introduction. However, five years into the program, challenges remain, including suboptimal vaccine coverage and significant safety concerns arising from inadvertent use of ZVL in immunocompromised people, who are contraindicated to receive this vaccine. This reduces opportunities to offset the burden of HZ-related disease. The recombinant subunit zoster vaccine (Shingrix; RZV), first registered in Australia in 2018, became available on the Australian market in June 2021. This vaccine has higher efficacy than ZVL and, as a non-live vaccine, can be used in both immunocompetent and immunocompromised people. RZV has potential to address the unmet needs of at-risk population groups. However, it has not yet demonstrated cost-effectiveness for inclusion as a funded vaccine under the NIP. The Australian HZ vaccination program has had limited effectiveness in meeting its aim in highest risk groups. Future options and challenges anticipated in using vaccination to reduce the burden of HZ and its complications are discussed in this review.

A randomized trial assessing the efficacy, immunogenicity, and safety of vaccination with live attenuated varicella zoster virus-containing vaccines: ten-year follow-up in Russian children.

In Russia, a universal varicella vaccination (UVV) program has not been implemented, and varicella vaccination coverage is low. We assessed the efficacy, antibody persistence, and safety of one- and two-dose varicella vaccination schedules in Russian children with a ten-year follow-up period, as part of an international phase IIIB, observer-blind, randomized, controlled trial (NCT00226499). Children aged 12-22 months were randomized (3:3:1) to receive two doses of tetravalent measles-mumps-rubella-varicella vaccine (V2 group), one dose trivalent measles-mumps-rubella (MMR) vaccine and one dose of varicella vaccine (V1 group), or two doses of MMR vaccine (V0 [control] group), 42 days apart. Main study outcomes were: vaccine efficacy (VE) against confirmed varicella cases, anti-varicella zoster virus (VZV) seropositivity rates and geometric mean concentrations, and reporting of (serious) adverse events ([S]AEs). The total vaccinated cohort in Russia comprised 1000 children; 900 were followed up until study end (year [Y] 10). VE estimates against confirmed varicella (Y10) were 92.4% in the V2 group and 74.7% in the V1 group. Anti-VZV seropositivity rates remained ≥99.4% in the V2 group and ≥89.7% in the V1 group from day 42 post-vaccination 2 until Y10. Occurrence of (un)solicited AEs and SAEs was similar across groups and confirmed the safety profile of the vaccines. No vaccination-related SAEs or deaths were reported. These results are consistent with the global trial results, i.e., the highest VE estimates observed following the two-dose schedule compared to the one-dose schedule. These data may inform decision-making related to potential implementation of a UVV program.

What is the context?Varicella is a common childhood disease caused by the highly contagious varicella zoster virus.Varicella vaccines have been used for more than three decades.A large clinical trial conducted in ten countries assessed the efficacy and safety of one dose of monovalent varicella vaccine or two doses of combined varicella vaccine (MMRV). The enrolled children were also followed up for a ten-year period to evaluate the persistence of the immune response and the long-term efficacy of the vaccine.What is new?Here, we present the long-term efficacy, immunogenicity, and safety results in the cohort of children enrolled in Russia, as part of the global ten-year follow-up study. We found that:The monovalent and combined vaccines reduced the number of varicella cases.The MMRV two-dose regimen displayed higher efficacy in preventing varicella of all severities compared to the one-dose regimen.The immune response conferred by the vaccine persisted up to ten years post-vaccination.No vaccination-related deaths occurred, and no safety concerns were raised.What is the impact?Vaccination against varicella resulted in long-term protective efficacy and antibody persistence over ten years post-vaccination in Russian children.Although one-dose varicella vaccination was effective at protecting against varicella, a two-dose schedule provided a more complete protection. This could inform health policy decisions regarding the implementation of varicella vaccination in routine immunization program in Russia.

Influenza Vaccine Uptake in the Year After Concurrent vs Separate Influenza and Zoster Immunization.

Importance: Fewer than half of US adults receive the influenza vaccine each year; many cite concerns about side effects, which occur infrequently. By contrast, the recombinant zoster vaccine causes systemic side effects in a large proportion of patients. Objective: To determine whether concurrent administration of the influenza and zoster vaccines was associated with a reduced likelihood of influenza vaccination in the subsequent year. Design, Setting, and Participants: This cohort study included patients aged 50 years or older who received the influenza vaccine between August 1, 2018, and March 31, 2019, and received the zoster vaccine on the same day or separately (within the prior 180 days). Data were gathered from a national claims database of patients with commercial insurance and Medicare Advantage plans. Logistic regression analysis was used to adjust for baseline demographic characteristics, comorbidities, influenza vaccine month and location (pharmacy vs medical office), and health care use (including influenza vaccination in the prior year). Exposures: Concurrent vs separate influenza and zoster vaccine administration. Main Outcomes and Measures: Receipt of the influenza vaccine in the subsequent year (August 1, 2019, to March 31, 2020). Results: Among 89 237 individuals included in this study, the median age was 72 years (IQR, 67-77 years), 58.3% were women, 70.1% were White, and 85.7% had at least 1 comorbidity. Influenza vaccine uptake in 2019-2020 was lower among 27 161 individuals who received concurrent influenza and zoster vaccines compared with the 62 076 individuals who received the vaccines on separate days (87.3% vs 91.3%; adjusted odds ratio, 0.74; 95% CI, 0.71-0.78; P < .001). Results were similar across subgroups. Conclusions and Relevance: Results of this cohort study suggest that concurrent administration of influenza and zoster vaccines was associated with a reduction in receipt of the influenza vaccine the following year. One possible explanation is that some patients could have misattributed systemic side effects caused by the zoster vaccine to the influenza vaccine. It may be preferable to administer these 2 vaccines separately or enhance patient counseling about expected vaccine side effects.

Herpes Zoster Vaccines.

Herpes zoster (HZ) affects approximately 1 in 3 persons in their lifetime, and the risk of HZ increases with increasing age. The most common, debilitating complication of HZ is the chronic neuropathic pain of postherpetic neuralgia (PHN). Two herpes zoster vaccines, a live-attenuated varicella-zoster virus (VZV) vaccine (zoster vaccine live [ZVL]; ZOSTAVAX [Merck]) and an adjuvanted VZV glycoprotein E (gE) subunit vaccine (recombinant zoster vaccine [RZV]; SHINGRIX [GlaxoSmithKline]) are licensed for the prevention of HZ and PHN in healthy older adults. The safety and efficacy of both vaccines has been demonstrated in clinical trials in immunocompetent adults and in selected immunocompromised persons and persons with immune-mediated diseases. Numerous real-world effectiveness studies have confirmed the safety and effectiveness of both ZVL and RZV. Recombinant zoster vaccine (RZV) is more effective for prevention of HZ than ZVL. Recombinant zoster vaccine is nonreplicating and is thus safe in immunocompromised persons. Additional zoster vaccines are in different stages of development. Wider distribution of safe and effective zoster vaccines will improve the health and well being of the rapidly growing population of older adults around the world.

Live Attenuated Varicella Vaccine: Prevention of Varicella and of Zoster.

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate.

Healthcare workers' perceptions and experiences of communicating with people over 50 years of age about vaccination: a qualitative evidence synthesis.

BACKGROUND: Infectious diseases are a major cause of illness and death among older adults. Vaccines can prevent infectious diseases, including against seasonal influenza, pneumococcal diseases, herpes zoster and COVID-19. However, the uptake of vaccination among older adults varies across settings and groups. Communication with healthcare workers can play an important role in older people's decisions to vaccinate. To support an informed decision about vaccination, healthcare workers should be able to identify the older person's knowledge gaps, needs and concerns. They should also be able to share and discuss information about the person's disease risk and disease severity; the vaccine's effectiveness and safety; and practical information about how the person can access vaccines. Therefore, healthcare workers need good communication skills and to actively keep up-to-date with the latest evidence. An understanding of their perceptions and experiences of this communication can help us train and support healthcare workers and design good communication strategies. OBJECTIVES: To explore healthcare workers' perceptions and experiences of communicating with older adults about vaccination. SEARCH METHODS: We searched MEDLINE, CINAHL and Scopus on 21 March 2020. We also searched Epistemonikos for related reviews, searched grey literature sources, and carried out reference checking and citation searching to identify additional studies. We searched for studies in any language. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored the perceptions and experiences of healthcare workers and other health system staff towards communication with adults over the age of 50 years or their informal caregivers about vaccination. DATA COLLECTION AND ANALYSIS: We extracted data using a data extraction form designed for this review. We assessed methodological limitations using a list of predefined criteria. We extracted and assessed data regarding study authors' motivations for carrying out their study. We used a thematic synthesis approach to analyse and synthesise the evidence. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each finding. We examined each review finding to identify factors that may influence intervention implementation and we developed implications for practice. MAIN RESULTS: We included 11 studies in our review. Most studies explored healthcare workers' views and experiences about vaccination of older adults more broadly but also mentioned communication issues specifically. All studies were from high-income countries. The studies focused on doctors, nurses, pharmacists and others working in hospitals, clinics, pharmacies and nursing homes. These healthcare workers discussed different types of vaccines, including influenza, pneumococcal and herpes zoster vaccines. The review was carried out before COVID-19 vaccines were available. We downgraded our confidence in several of the findings from high confidence to moderate, low or very low confidence. One reason for this was that some findings were based on only small amounts of data. Another reason was that the findings were based on studies from only a few countries, making us unsure about the relevance of these findings to other settings. Healthcare workers reported that older adults asked about vaccination to different extents, ranging from not asking about vaccines at all, to great demand for information (high confidence finding). When the topic of vaccination was discussed, healthcare workers described a lack of information, and presence of misinformation, fears and concerns about vaccines among older adults (moderate confidence). The ways in which healthcare workers discussed vaccines with older adults appeared to be linked to what they saw as the aim of vaccination communication. Healthcare workers differed among themselves in their perceptions of this aim and about their own roles and the roles of older adults in vaccine decisions. Some healthcare workers thought it was important to provide information but emphasised the right and responsibility of older adults to decide for themselves. Others used information to persuade and convince older adults to vaccinate in order to increase 'compliance' and 'improve' vaccination rates, and in some cases to gain financial benefits. Other healthcare workers tailored their approach to what they believed the older adult needed or wanted (moderate confidence). Healthcare workers believed that older adults' decisions could be influenced by several factors, including the nature of the healthcare worker-patient relationship, the healthcare worker's status, and the extent to which healthcare workers led by example (low confidence). Our review also identified factors that are likely to influence how communication between healthcare workers and older adults take place. These included issues tied to healthcare workers' views and experiences regarding the diseases in question and the vaccines; as well as their views and experiences of the organisational and practical implementation of vaccine services. AUTHORS' CONCLUSIONS: There is little research focusing specifically on healthcare workers' perceptions and experiences of communication with older adults about vaccination. The studies we identified suggest that healthcare workers differed among themselves in their perceptions about the aim of this communication and about the role of older adults in vaccine decisions. Based on these findings and the other findings in our review, we have developed a set of questions or prompts that may help health system planners or programme managers when planning or implementing strategies for vaccination communication between healthcare workers and older adults.

[Surveillance and epidemiology of Herpes Zoster in Spain.] / Vigilancia y epidemiología del herpes zóster en España.

OBJECTIVE: Herpes Zoster (HZ) results from reactivation of latent varicella-zoster virus infection and is associated with immunosuppression and ageing. HZ is of increasing importance in advanced societies. Vaccination appears as a powerful tool to reduce HZ as well as postherpetic neuralgia, the main zoster complication. This study aims to describe the temporal trend, the age and sex distribution of cases, hospitalisations and deaths by zoster occurred in Spain between 1998 and 2018. METHODS: The available information for zoster in Spain were used: cases from National Surveillance System (2014-2018), registries from Spanish hospitalisation database (1998-2018) and deaths from the Spanish mortality statistics (1999-2018). Incidence, hospitalization (HR) and mortality (MR) rates per year and period were calculated. Rates by age group and sex as well as percentage and cumulative percentage for cases and hospitalisations by age group, were also calculated. RESULTS: The global HZ incidence was 351.6/100,000 inhabitants and 625.5/100,000 among population aged 50 and over. The incidence increases with age, especially from the age of 50-54 years (41% increase over the 45-49 age group) and is always higher in women. The global HR was 6.75/100,000 and 15.7/100,000 in persons aged 50 and over; HR increases with age, especially from 60-64 years onwards (50% increase over 54-59 age group) and is always higher in men. The 68.8% of cases and 80.2% of hospitalisations for HZ occurred from the age of 50. CONCLUSIONS: In Spain HZ is a frequent and severe entity in adults and elderly people requiring public health interventions. The demographic changes and the introduction of vaccination require continued monitoring of HZ behaviour in terms of incidence and severity.

OBJETIVO: El herpes zóster (HZ) aparece debido a la reactivación de la infección latente por el virus de la varicela-zóster y está asociado a la inmunosupresión y al envejecimiento. El HZ es de creciente importancia en las sociedades avanzadas. La vacunación se vislumbra como una potente herramienta para reducir el zóster y su principal complicación: la neuralgia postherpética. El objetivo de este estudio fue describir la tendencia temporal y la distribución por grupos de edad y sexo de los casos, hospitalizaciones y muertes por HZ en España entre 1998 y 2018. METODOS: Se analizaron los casos de HZ notificados a la Red Nacional de Vigilancia Epidemiológica entre 2014-2018, las hospitalizaciones por HZ del registro RAE-CMBD entre 1998-2018 y las muertes por HZ de la Estadística de Mortalidad del INE entre 1999-2018. Se calcularon: tasas de incidencia, hospitalización (TH) y mortalidad (TM) anual y de periodo; tasas globales y por grupos de edad y sexo, así como porcentaje y porcentaje acumulado de casos y hospitalizaciones por grupos de edad. RESULTADOS: La incidencia global de HZ se estimó en 351,6 por cada 100.000 habitantes y en 625,5 por cada 100.000 habitantes en personas de 50 años o más. La incidencia se incrementó con la edad, sobre todo a partir de los 50-54 años (incremento del 41% respecto al grupo de 45-49 años) y fue siempre más alta en mujeres. La TH global por HZ fue 6,75 por cada 100.000 habitantes y 15,7 por cada 100.000 habitantes en personas de 50 años o más. La TH fue creciendo con la edad, sobre todo a partir de los 60-64 años (incremento del 50% respecto al grupo de 54-59 años) y resultó siempre más alta en hombres. El 68,8% de casos y el 80,2% de hospitalizaciones por HZ ocurrieron a partir de los 50 años. CONCLUSIONES: En España, el HZ es una entidad frecuente y grave en adultos y personas mayores, que requiere intervenciones en Salud Pública. Los cambios demográficos y la incorporación de la vacunación exigen seguir monitorizando estrechamente el comportamiento del HZ en términos de incidencia y gravedad.

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.

Herpes Zoster Vaccine Live and Risk of Stroke Among Medicare Beneficiaries: A Population-Based Cohort Study.

Background and Purpose: Herpes zoster (HZ) is associated with increased risk of stroke, and zoster vaccine live (ZVL, Zostavax) reduces the risk of HZ. No study has examined the association between ZVL (Zostavax) and risk of stroke. Present study examined association between receipt of ZVL (Zostavax) and risk of stroke among older US population. Methods: Our study included 1 603 406 US Medicare fee-for-service beneficiaries aged ≥66 years without a history of stroke and who received ZVL (Zostavax) during 2008 to 2014, and 1 603 406 propensity score-matched unvaccinated beneficiaries followed through to December 31, 2017. We used Cox proportional hazard models to examine association between ZVL (Zostavax) and composite fatal or nonfatal incident stroke outcomes. Results: During a median of 5.1 years follow-up (interquartile range, 3.9­6.7), we documented 64 635 stroke events, including 43 954 acute ischemic strokes and 6727 hemorrhagic strokes, among vaccinated beneficiaries during 8 755 331 person-years. The corresponding numbers among unvaccinated beneficiaries were 73 023, 50 476, and 7276, respectively, during 8 517 322 person-years. Incidence comparing vaccinated to unvaccinated beneficiaries were 7.38 versus 8.57 per 1000 person-years for all stroke, 5.00 versus 5.90 for acute ischemic stroke, and 0.76 versus 0.84 for hemorrhagic stroke (P<0.001 for all difference). Adjusted hazard ratios comparing vaccinated to unvaccinated beneficiaries were 0.84 (95% CI, 0.83­0.85), 0.83 (0.82­0.84), and 0.88 (0.85­0.91) for all stroke, acute ischemic stroke, and hemorrhagic stroke, respectively. The association between ZVL (Zostavax) and risk of stroke appeared to be stronger among younger beneficiaries, beneficiaries who did not take antihypertensive or statin medications and who had fewer comorbid conditions (P<0.05 for interaction) but largely consistent across sex, low-income status, and racial groups. Conclusions: Among Medicare fee-for-service beneficiaries, receipt of ZVL (Zostavax) was associated with lower incidence of stroke. Our findings may encourage people to get vaccinated against HZ to reduce HZ and HZ-associated stroke risk.

Effectiveness of the Recombinant Zoster Vaccine for Herpes Zoster Ophthalmicus in the United States.

PURPOSE: To examine the effectiveness of the recombinant zoster vaccine (RZV) for preventing herpes zoster ophthalmicus (HZO) in the general United States population. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Individuals enrolled in the OptumLabs Data Warehouse (OLDW; OptumLabs, Cambridge, MA) who were age eligible for herpes zoster (HZ) vaccination (≥50 years of age) from 2018 through 2019. The OLDW is a longitudinal, de-identified administrative claims and electronic health record database of patients in the United States with commercial insurance, Medicare Part D, or Medicare Advantage METHODS: Patients were required to have 365 days or more of continuous enrollment to be eligible. Those with a diagnosis code of HZ or an immunocompromising condition within 1 year before study inclusion were excluded. Vaccination with the RZV was ascertained by Current Procedural Terminology codes, and HZO was ascertained by International Classification of Diseases, Tenth Revision, codes. Cox proportional hazards regression models were used to estimate the hazard ratio of HZO associated with RZV, and inverse-probability weighting was used to control for confounding. Vaccine effectiveness was calculated from hazard ratios. MAIN OUTCOME MEASURES: Incidence of HZO in vaccinated versus unvaccinated person-times and vaccine effectiveness were assessed. RESULTS: From January 1, 2018, through December 31, 2019, a total of 4 842 579 individuals were included in this study. One hundred seventy-seven thousand two hundred eighty-nine (3.7%) received 2 valid doses of RZV. The incidence rate of HZO was 25.5 cases (95% confidence interval [CI], 17.4-35.8 cases) per 100 000 person-years in the vaccinated group compared with 76.7 cases (95% CI, 74.7-78.7 cases) in the unvaccinated group. The overall adjusted effectiveness of RZV against HZO was 89.1% (95% CI, 82.9%-93.0%). CONCLUSIONS: The effectiveness of RZV against HZO in individuals 50 years of age and older is high in a clinical setting. However, the low vaccination rate in this study highlights the public health need to increase HZV use. Ophthalmologists can play an important role in recommending vaccination to eligible patients.

Safety of live attenuated herpes zoster vaccine in Australian adults 70-79 years of age: an observational study using active surveillance.

OBJECTIVES: To assess the safety of live attenuated herpes zoster vaccine live (ZVL) through cumulative analysis of near real-time, participant-based active surveillance from Australia's AusVaxSafety system. DESIGN AND SETTING: ZVL was funded in Australia for adults aged 70 years from November 2016, with a time-limited catch up programme for those up to 79 years. This cohort study monitored safety in the first two programme years through active surveillance at 246 sentinel surveillance immunisation sites. PARTICIPANTS: Adults aged 70-79 years vaccinated with ZVL who responded to an opt-out survey sent via automated short message service (SMS) 3 days following vaccination (n=17 458) or contributed supplementary data through a separate, opt-in online survey at 16 and 24 days following vaccination (n=346). PRIMARY AND SECONDARY OUTCOME MEASURES: Rates of overall and prespecified adverse events following immunisation (AEFI) by sex, concomitant vaccination and underlying medical condition. Signal detection methods (fast initial response cumulative summation and Bayesian updating analyses) were applied to reports of medical attendance. RESULTS: The median age of participants was 72 years; 53% were female. The response rate following automated SMS was high (73% within 7 days of vaccination). Females were more likely than males to report any adverse event within 7 days of vaccination (RR 2.07, 95% CI 1.86 to 2.31); injection site reaction was the most commonly reported (2.3%, n=377). Concomitant vaccination was not associated with higher adverse event rates (RR 1.05, 95% CI 0.93 to 1.18). Rates of medical attendance were low (0.3%) with no safety signals identified. Supplementary opt-in survey data on later onset adverse events did not identify any difference in AEFI rates between those with and without underlying medical conditions. CONCLUSIONS: ZVL has a very good safety profile in the first week after vaccination in older adults. Active, participant-based surveillance in this primary care cohort is an effective method to monitor vaccine safety among older adults and will be used as a key component of COVID-19 vaccine safety surveillance in Australia.

Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients.

BACKGROUND: Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection. METHODS: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines. RESULTS: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes. CONCLUSIONS: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.

The Adjuvanted Recombinant Zoster Vaccine in Adults Aged ≥65 Years Previously Vaccinated With a Live-Attenuated Herpes Zoster Vaccine.

BACKGROUND: Efficacy of the live-attenuated herpes zoster (HZ) vaccine (ZVL) wanes substantially over time. We evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) in previous ZVL recipients. METHODS: Adults aged ≥65 years who were previously vaccinated with ZVL ≥5 years earlier (n = 215) were group-matched with ZVL-naive individuals (n = 215) and vaccinated with RZV. Glycoprotein E (gE)-specific humoral and cell-mediated immune responses and the correlation between them, polyfunctional gE-specific CD4 T-cell responses, safety, and confirmed HZ cases were assessed. RESULTS: Through 12 months after dose 2, anti-gE antibody concentrations, gE-specific CD4 T-cell frequencies, and activation marker profiles were similar between groups. Safety outcomes were also similar. No HZ episodes were confirmed. CONCLUSIONS: RZV induced strong humoral and polyfunctional cell-mediated immune responses that persisted above prevaccination levels through 1 year after dose 2 in adults aged ≥65 years irrespective of previous ZVL vaccination. The RZV safety profile was not affected. CLINICAL TRIALS REGISTRATION: NCT02581410.

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.