Herpes Zoster In Older Adults Research Articles

Herpes zoster in older adults: Impact on carbon footprint in the United States

ABSTRACT We provide estimates for (I) annual herpes zoster (HZ) cases, (II) carbon costs related to healthcare utilization, and (III) annual carbon emissions due to HZ among ≥50 years of age (YOA) United States (US) population. We estimated the annual number of HZ cases in the US based on available incidence data and demographic data of individuals ≥50 YOA. Both the healthcare resource utilization (HCRU) associated with HZ cases and the unit carbon dioxide equivalent (i.e. CO2e) costs associated with each type of HCRU in the US were estimated based on literature and studies available online. The carbon footprint associated with HZ annually among US adults ≥50 YOA was estimated by multiplying the unit carbon estimates by the HCRU. In the US population aged ≥50 YOA in 2020 (i.e. approximately 118 million), approximately 1.1 million cases of HZ occur annually assuming no vaccination. Based on 2 sources of HCRU the average kgCO2e per HZ patient ranged from 61.0 to 97.6 kgCO2e, with values by age group ranging from 40.9 kgCO2e in patients aged 50–59 to 195.9 kgCO2e in patients ≥80 YOA. The total annual HZ associated carbon ranged between 67,000 and 107,000 tons of CO2e in the US population aged ≥50 YOA. The impact of HZ on carbon footprint in the US results in considerable greenhouse gas (GHG)emissions. Assuming no vaccination, the burden of HZ is projected to rise over the coming years with the aging populations consequently worsening its impact on GHG emissions. (Figure 1)

Herpes Virus Infections in Kidney Transplant Patients (HINT) – a prospective observational cohort study

BackgroundKidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation.MethodsThe Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles.DiscussionThe study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk.Trial registrationClinicalTrials.gov (NCT05604911).

Use of disease-modifying antirheumatic drugs and the subsequent risk of herpes zoster in older adults.

To examine the association between DMARD use and subsequent risk of herpes zoster in a large, heterogeneous and prospective population-based cohort. Using data from a cohort of adults (45 and Up Study) recruited between 2006 and 2009 and linked to pharmaceutical, hospital and death data (2004-2015), the effect of DMARD use on zoster risk was analysed using Cox proportional hazards models, adjusting for sociodemographic characteristics, comorbidities and corticosteroid use. Among 254 065 eligible participants, over 1 826 311 person-years follow-up, there were 6295 new DMARD users and 17 024 incident herpes zoster events. Compared with non-users, the risk of zoster was higher in those who used biologic (b)DMARDs, either alone or in combination with conventional synthetic (cs)DMARDs than in those who only used csDMARDs (adjusted hazard ratio [aHR] 2.53 [95% CI: 2.03, 3.16]) for bDMARDs vs 1.48 [95% CI: 1.33, 1.66] for csDMARDs, P-heterogeneity < 0.001; reference: non-users). Among users of csDMARDs, compared with non-users, zoster risks were highest in those using exclusively cyclophosphamide (aHR 2.69 [95% CI: 1.89, 3.83]), more moderate in those using azathioprine (aHR 1.57 [95% CI: 1.07, 2.30]) and hydroxychloroquine (aHR 1.43 [95%CI: 1.11, 1.83]) and not elevated in users of methotrexate (aHR 1.24 [95% CI: 0.98, 1.57]), sulfasalazine (aHR 1.00 [95% CI: 0.71, 1.42]) and leflunomide (aHR 0.41 [95% CI: 0.06, 2.88]). The risk of zoster was high among bDMARD and cyclophosphamide users. Also, the risk was increased in those using hydroxychloroquine alone and in combination with methotrexate but not methotrexate alone. Preventative strategies such as zoster vaccination or antiviral therapies should be considered in these populations if not contraindicated.

Safety Profile of the Adjuvanted Recombinant Zoster Vaccine in Immunocompromised Populations: An Overview of Six Trials.

IntroductionThe adjuvanted recombinant zoster vaccine (RZV) has demonstrated high efficacy against herpes zoster in older adults and immunocompromised populations. We present comprehensive safety data from six clinical trials in immunocompromised populations (autologous hematopoietic stem cell transplant and renal transplant recipients, patients with hematologic malignancies, patients with solid tumors, and human immunodeficiency virus-infected adults) who are at an increased risk of herpes zoster.MethodsIn all trials, immunocompromised adults ≥ 18 years of age were administered RZV or placebo. Safety was evaluated in the total vaccinated cohort. Solicited adverse events (AEs) were collected for 7 days and unsolicited AEs for 30 days after each dose. Serious AEs, fatal serious AEs, and potential immune-mediated diseases were collected from dose 1 until 12 months post-last dose or study end. Data were pooled for solicited AEs; unsolicited AEs, (fatal) serious AEs, and potential immune-mediated diseases were analyzed for each individual trial. All AEs were analyzed for sub-strata of adults 18–49 years of age and ≥ 50 years of age.ResultsIn total, 1587 (RZV) and 1529 (placebo) adults were included in the pooled total vaccinated cohort. Solicited AEs were more common after RZV than placebo, were generally more common in the younger age stratum, and were mostly mild to moderate and resolved within 3 days (median duration). Unsolicited AEs and serious AEs were in line with underlying diseases and therapies. Across studies, the percentage of adults reporting one or more unsolicited AE was comparable between RZV and placebo, irrespective of age stratum. The percentage of adults reporting one or more serious AE, fatal serious AE, or potential immune-mediated diseases was generally similar for RZV and placebo, irrespective of age stratum. Overall, no safety concerns were identified.ConclusionsRecombinant zoster vaccine has a clinically acceptable safety profile. With the previously published vaccine efficacy and immunogenicity results, these data support a favorable benefit-risk profile of RZV vaccination in immunocompromised populations who are at an increased risk of herpes zoster.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01076-w.

Herpes zoster in older adults in Ontario, 2002–2016: Investigating incidence and exploring equity

Older adults are at increased risk of herpes zoster (HZ) and post-herpetic neuralgia (PHN) and HZ vaccines are available to help prevent infection. The objective of our study was to provide updated data on incidence of HZ and PHN related to clinical and demographic factors in older adults to inform immunization practices. We conducted a population-based, retrospective cohort study and included all cases of HZ seen in outpatient, emergency department, and hospital settings for adults aged 65 years and over between April 1, 2002 to August 31, 2016 in Ontario, Canada. We calculated the incidence of HZ and PHN, and estimated the proportion within each subgroup that developed PHN. We also assessed incidence by neighbourhood-level income quintile before and after the availability of vaccine for private purchase. The average annual incidence of HZ in any setting was 59.0 per 10,000 older adults, with higher incidence in outpatient as opposed to hospital settings. Incidence was higher in the oldest age groups, females, and those classified as immunocompromised or frail. Relative to the pre-vaccine era, the disparities in incidence of HZ by neighbourhood-level income increased, with higher rates of HZ and PHN seen in those residing in lower income quintiles. Additional prevention efforts should be targeted toward adults who are immunocompromised, frail, and those living in lower socioeconomic quintiles. Future work should assess the impact of the zoster vaccine program with a particular focus on equity in the publicly-funded era.

Archetype analysis of older adult immunization decision-making and implementation in 34 countries

The global population of adults over 65 years of age is growing rapidly and is expected to double by 2050. Countries will face substantial health, economic and social burden deriving from vaccine-preventable diseases (VPDs) such as influenza, pneumonia and herpes zoster in older adults. It will be essential that countries utilize several public health strategies, including immunization. Understanding the different approaches countries have taken on adult immunization could help provide future learnings and technical support for adult vaccines within life-course immunization strategies. In this study, we describe the priorities and approaches that underlie adult immunization decision-making and implementation processes in 32 high-and-middle-income countries and two territories (“34 countries”) who recommend adult vaccines in their national schedule. We conducted an archetype analysis based on a subset of two dozen indicators abstracted from a larger database. The analysis was based on a mixed-methods study, including results from 120 key informant interviews in six countries and a landscape review of secondary data from 34 countries. We found four distinct archetypes: disease prevention-focused; health security-focused; evolving adult focus; and, child-focused and cost-sensitive. The highest performing countries belonged to the disease prevention-focused and health security archetypes, although there was a range of performance within each archetype. Considering common barriers and facilitators of decision-making and implementation of adult vaccines within a primary archetype could help provide a framework for strategies to support countries with similar needs and approaches. It can also help in developing context-specific policies and guidance, including for countries prioritizing adult immunization programs in light of COVID-19. Further research may be beneficial to further refine archetypes and expand the understanding of what influences success within them. This can help advance policies and action that will improve vaccine access for older adults and build a stronger appreciation of the value of immunization amongst a variety of stakeholders.

Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis

The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients. We evaluated the safety and immunogenicity of this vaccine in adults with haematological malignancies receiving immunosuppressive cancer treatments. In this phase 3, randomised, observer-blind, placebo-controlled study, done at 77 centres worldwide, we randomly assigned (1:1) patients with haematological malignancies aged 18 years and older to receive two doses of the adjuvanted recombinant zoster vaccine or placebo 1-2 months apart during or after immunosuppressive cancer treatments, and stratified participants according to their underlying diseases. The co-primary objectives of the study were the evaluation of safety and reactogenicity of the adjuvanted recombinant zoster vaccine compared with placebo from the first vaccination up to 30 days after last vaccination in all participants; evaluation of the proportion of participants with a vaccine response in terms of anti-glycoprotein E humoral immune response to the adjuvanted recombinant zoster vaccine at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia; and evaluation of the anti-glycoprotein E humoral immune responses to the vaccine compared with placebo at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. We assessed immunogenicity in the per-protocol cohort for immunogenicity and safety in the total vaccinated cohort. The study is registered with ClinicalTrials.gov, number NCT01767467, and with the EU Clinical Trials Register, number 2012-003438-18. Between March 1, 2013, and Sept 10, 2015, we randomly assigned 286 participants to adjuvanted recombinant zoster vaccine and 283 to placebo. 283 in the vaccine group and 279 in the placebo group were vaccinated. At month 2, 119 (80·4%, 95% CI 73·1-86·5) of 148 participants had a humoral vaccine response to adjuvanted recombinant zoster vaccine, compared with one (0·8%, 0·0-4·2) of 130 participants in the placebo group, and the adjusted geometric mean anti-glycoprotein E antibody concentration was 23 132·9 mIU/mL (95% CI 16 642·8-32 153·9) in the vaccine group and 777·6 mIU/mL (702·8-860·3) in the placebo group (adjusted geometric mean ratio 29·75, 21·09-41·96; p<0·0001) in all patients, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. Humoral and cell-mediated immune responses persisted above baseline until month 13 in all strata and, as expected, vaccine was more reactogenic than placebo (within 7 days after vaccination pain was reported by 221 [79·5%] of 278 vaccine group participants and 45 [16·4%] of 274 placebo group participants; fatigue was reported by 162 [58·3%] of 278 vaccine group participants and 102 [37·2%] of 274 placebo group participants). Incidences of unsolicited or serious adverse events, potential immune-mediated diseases, disease-related events, and fatal serious adverse events were similar between the groups. The immunocompromised adult population with haematological malignancies is at high risk for herpes zoster. The adjuvanted recombinant zoster vaccine, which is currently licensed in certain countries for adults aged 50 years and older, is likely to benefit this population. GlaxoSmithKline Biologicals SA.

Understanding the immunology of Shingrix, a recombinant glycoprotein E adjuvanted herpes zoster vaccine.

Herpes zoster is common in older and immune suppressed persons due to diminished VZV-specific cellular immunity. A recombinant herpes zoster vaccine (RZV) consisting of a single VZV glycoprotein and an adjuvant system stimulates robust and persistent VZV-specific antibody and CD4+ T cell responses in these high-risk populations. VZV-specific immune responses induced by RZV, including the generation of polyfunctional T cells, are driven by the synergistic actions of the components of the vaccine adjuvant system. RZV provides unprecedented protection against herpes zoster in older adults regardless of age at vaccination and is efficacious in immune suppressed populations. Adjuvanted subunit antigens may represent a general strategy for vaccines in the elderly and other individuals typically considered immunologically resistant to vaccination.

Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4+ and CD8+ T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8+CD57+ senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4+CD69+CD57+PD1+ and CD8+CD69+CD57+PD1+ T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8+ effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4+ and CD8+ proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ.

Managing herpes zoster in older adults

Managing herpes zoster in older adults

Managing herpes zoster in older adults: Prescribing considerations.

NPs must be aware of special prescribing considerations for medication safety when managing the care of older adults with herpes zoster. Age-related physiologic changes of the body impact the pharmacokinetics and pharmacodynamics of antiviral and pain medications and can lead to potential adverse events.

Vaccines for preventing herpes zoster in older adults.

Herpes zoster, also known as 'shingles', is a neurocutaneous disease characterised by the reactivation of the latent varicella zoster virus (VZV), the virus that causes chickenpox when immunity to VZV declines. It is an extremely painful condition that can last many weeks or months and it can significantly compromise the quality of life of affected individuals. The natural process of aging is associated with a reduction in cellular immunity and this predisposes older people to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production avoiding viral reactivation. The Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus for clinical use among older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine has also been tested. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This new vaccine is not yet available for clinical use. To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. For this 2015 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE (1948 to the 3rd week of October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and LILACS (1982 to October 2015). Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). Two review authors independently collected and analysed data using a data extraction form. They also performed 'Risk of bias' assessment. We identified 13 studies involving 69,916 participants. The largest study included 38,546 participants. All studies were conducted in high-income countries and included only healthy Caucasian individuals ≥ 60 years of age without immunosuppressive comorbidities. Ten studies used live attenuated varicella zoster virus (VZV) vaccines. Three studies tested a new type of vaccine not yet available for clinical use. We judged five of the included studies to be at low risk of bias.The incidence of herpes zoster, at up to three years of follow-up, was lower in participants who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49; 95% confidence interval (CI) 0.43 to 0.56, risk difference (RD) 2%, number needed to treat to benefit (NNTB) 50; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of mild to moderate intensity adverse events. These date came from one large study that included 38,546 people aged 60 years or older.A study including 8122 participants compared the new vaccine (not yet available) to the placebo; the group that received the new vaccine had a lower incidence of herpes zoster at 3.2 years of follow-up: RR 0.04, 95% CI 0.02 to 0.10, RD 3%, NNTB 33; GRADE: moderate quality evidence. The vaccinated group had a higher incidence of adverse events but most them were of mild to moderate intensity.All studies received funding from the pharmaceutical industry. Herpes zoster vaccine is effective in preventing herpes zoster disease and this protection can last three years. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse events of mild to moderate intensity.There are studies of a new vaccine (with a VZV glycoproteic fraction plus adjuvant), which is currently not yet available for clinical use.

Herpes zoster in older adults and worsening of life quality

Herpes zoster in older adults and worsening of life quality

Risk of Stroke and Myocardial Infarction After Herpes Zoster in Older Adults in a US Community Population

ObjectiveTo assess the risk of stroke and myocardial infarction (MI) after herpes zoster in a US community population of older adults. Patients and MethodsWe performed a community cohort study (January 1, 1986, to October 1, 2011) comparing the risk of stroke and MI in 4862 adult residents of Olmsted County, Minnesota, 50 years and older with and without herpes zoster and 19,433 sex- and age-matched individuals with no history of herpes zoster. Odds ratios are presented for MI and stroke at 3, 6, 12, and 36 months after index herpes zoster plus hazard ratios for long-term risk (up to 28.6 years). ResultsIndividuals with herpes zoster had more risk or confounding factors for MI and stroke, suggesting that they had worse health status overall. When controlling for the multiple risk factors, those with herpes zoster were at increased risk for stroke at 3 months after herpes zoster compared with those without a history of herpes zoster (odds ratio, 1.53; 95% CI, 1.10-2.33; P=.04). The association between herpes zoster and MI at 3 months was not robust across analytic methods. Herpes zoster was not associated with an increased risk of stroke or MI at any point beyond 3 months. ConclusionsHerpes zoster was associated with only a short-term increased risk of stroke, which may be preventable with the prevention of herpes zoster.

Herpes Zoster in Older Adults: An Educational Approach

Patients presenting with herpes zoster often have misconceptions of the pathophysiology and treatment options. Educating patients is a prime action of the treatment plan and can enhance patient satisfaction with the care they receive from the nurse practitioner. Realistically, nurse practitioners work within limited time with each patient; thus, patient education often loses priority. This article offers information of the clinical management of herpes zoster and recommendations for practical educational approaches that can be timely managed to help patients understand herpes zoster.

Vaccines for preventing herpes zoster in older adults.

BACKGROUND: Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations. OBJECTIVE: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. METHODS Search methods: We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies. Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). Data collection and analysis: Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias. MAIN RESULTS: We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated zoster vaccine and one study compared zoster vaccine versus pneumococcal polysaccharide vaccine (pneumo 23). Confirmed cases of herpes zoster were less frequent in patients who received the vaccine than in those who received a placebo: risk ratio (RR) 0.49 (95% confidence interval (CI) 0.43 to 0.56), with a risk difference (RD) of 2%, and number needed to treat to benefit (NNTB) of 50. Analyses according to age groups indicated a greater benefit in participants aged 60 to 69 years, RR 0.36 (95% CI 0.30 to 0.45) and in participants aged 70 years and over, RR 0.63 (95% CI 0.53 to 0.75). Vaccine-related systemic adverse effects were more frequent in the vaccinated group (RR 1.29, 95% CI 1.05 to 1.57, number needed to treat to harm (NNTH) = 100). The pooled data risk ratio for adverse effects for participants with one or more inoculation site adverse effect was RR 4.51 (95% CI 2.35 to 8.68), and the NNTH was 2.8 (95% CI 2.3 to 3.4). Side effects were more frequent in younger (60 to 69 years) than in older (70 years and over) participants. AUTHORS' CONCLUSIONS: Herpes zoster vaccine is effective in preventing herpes zoster disease. Although vaccine benefits are larger in the younger age group (60 to 69 years), this is also the age group with more adverse events. In general, zoster vaccine is well tolerated; it produces few systemic adverse events and injection site adverse effects of mild to moderate intensity.

Zoster Vaccine Is Safe After Clinical Zoster

Although the herpes zoster vaccine is safe and effective in lowering incidence of herpes zoster in older adults, its nationwide uptake has been slower

Immunogenicity and safety of ZOSTAVAX® approaching expiry potency in individuals aged ≥50 years

Background: Age is a major risk factor for herpes zoster (HZ) and its potential long-term complication post-herpetic neuralgia (PHN). Due to the significant burden of HZ and PHN on patients’ quality of life, it is vital that effective and well-tolerated vaccines are available to prevent HZ in older adults. ZOSTAVAX® vaccine was developed to prevent HZ and PHN in individuals ≥50 years (y) of age, and its clinical efficacy and safety have been demonstrated.Aims and Methods: This phase 4, open-label, multicenter study was undertaken to assess the immunogenicity and safety of a single dose of ZOSTAVAX (refrigerator-stable formulation) given within 6 mo of its expiry date in individuals ≥50 y of age. The geometric mean fold rise (GMFR) from pre-vaccination to 4 weeks post-vaccination in varicella zoster virus (VZV) antibody titers was calculated. An acceptable antibody response was defined as a lower 95% confidence interval (CI) of GMFR >1.4. Solicited and unsolicited injection-site reactions and systemic adverse events were recorded.Results: The GMFR in VZV antibody titers was 3.1 (95% CI: 2.6, 3.8), satisfying the criterion for an acceptable VZV antibody response to ZOSTAVAX (minimum requirement: 1.4 GMFR). An acceptable rise in VZV antibody titers was observed in individuals of 50–59 y of age (GMFR 3.9; 95% CI: 2.9, 5.1) and in those ≥60 y of age (GMFR 2.5; 95% CI: 1.9, 3.2). ZOSTAVAX was well tolerated; no serious adverse events were reported.Conclusion: ZOSTAVAX elicits an acceptable immune response in immunocompetent individuals ≥50 y of age when stored as directed and administered during the 6 mo prior to expiration.

Hospitalizations to Treat Herpes Zoster in Older Adults: Causes and Validated Rates

The availability of a vaccine for the prevention of herpes zoster has increased interest in methods to measure zoster disease burden. Hospitalizations assigned a zoster diagnosis code have been used as indicators of severe zoster in prior studies. However, a zoster diagnosis code may not be a specific indicator of severe zoster illness, because the code may be assigned to a hospitalization for another cause in a person with coincident zoster. To assess the validity of a hospital diagnosis code of zoster as an indicator of hospitalizations that are attributable to zoster, we identified all hospitalizations with a zoster diagnosis code assigned in any position among members of a managed-care organization who were >or=50 years of age during 1992-2004. Of those, we selected a sample of 260 hospitalizations for chart review. Chart reviews were completed for 225 hospitalizations. Sixty-five (29%) were because of zoster or a complication of zoster treatment, and an additional 9 (4%) were because of postherpetic neuralgia or a complication of postherpetic neuralgia treatment. Although the overall age-adjusted rate of hospitalizations with a zoster diagnosis code was 42.5 hospitalizations per 100,000 population per year, the estimated rate of hospitalizations because of zoster, postherpetic neuralgia, or adverse effects of a medication used to treat zoster or postherpetic neuralgia was only 14.0 hospitalizations per 100,000 population per year. Rates of hospitalizations associated with a zoster diagnosis code will substantially overestimate the burden of hospitalizations attributable to zoster in older adults.

Vaccination to Prevent Herpes Zoster in Older Adults

Herpes zoster causes substantial morbidity, especially among older adults. Although the acute cutaneous manifestations can be painful and troublesome, the most important consequence of herpes zoster (shingles) is the chronic pain syndrome known as postherpetic neuralgia (PHN). Previous studies have suggested that declining varicella-zoster virus (VZV)-specific cell-mediated immune (CMI) responses account for the increased frequency of herpes zoster seen in older adults. This led to the idea that immunization designed to boost VZV-specific CMI responses might reduce the risk of herpes zoster. This hypothesis was tested in a large, randomized, placebo-controlled clinical trial called the Shingles Prevention Study (SPS). Compared with the placebo group, herpes zoster vaccine recipients had a 61.1% reduction in zoster "burden of illness" (an index incorporating incidence and severity of herpes zoster); a 66.5% reduction in the incidence of postherpetic neuralgia; and a 51.3% reduction in the incidence of herpes zoster. The incidence of serious adverse events was not different between the overall vaccine and placebo populations. The most frequently encountered adverse event among vaccine recipients was local reactogenicity, with self-limited and generally mild tenderness, warmth, or erythema occurring at the injection site in about one-half of vaccine recipients. The zoster vaccine was approved by the US Food and Drug Administration in 2006 and is indicated for prevention of herpes zoster in immunocompetent persons aged 60 years and older. The herpes zoster vaccine provides physicians with an effective means for reducing a patient's risk for developing shingles and its attendant complications. No significant safety concerns regarding the vaccine have been identified. Indications for use of the attenuated-virus vaccine in special subpopulations continue to evolve.