Project description:BackgroundHerpes 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.ObjectivesTo evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.Search methodsFor 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).Selection criteriaRandomised 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 analysisTwo review authors independently collected and analysed data using a data extraction form. They also performed 'Risk of bias' assessment.Main resultsWe 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.Authors' conclusionsHerpes 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.
Project description: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.
Project description:ObjectiveTo compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.DesignSystematic review with bayesian meta-analysis and network meta-analysis.Data sourcesMedline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.Eligibility criteria for study selectionExperimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.Results27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).ConclusionsUsing the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.Protocol registrationProspero CRD42017056389.
Project description:Importance:The live attenuated herpes zoster vaccine (ZVL) is recommended for immunocompetent adults 60 years or older, but the efficacy wanes with age and over time. A new adjuvanted herpes zoster subunit vaccine (HZ/su) has higher efficacy but might be more expensive. The choice of vaccines depends on their relative values. Objective:To assess the cost-effectiveness of HZ/su. Design, Setting, and Participants:Markov decision model with transition probabilities based on the US medical literature. Participants were immunocompetent adults 60 years or older. Data were derived from participant groups ranging in number from less than 100 to more than 30 000 depending on the variable assessed. The study dates were July 1 to 31, 2017. Exposures:No vaccination, ZVL (single dose), and HZ/su (2-dose series) vaccine administered at different ages. Main Outcomes and Measures:Total costs and quality-adjusted life-years (QALYs) were estimated. Results:Based on randomized clinical trial data, at a price of $280 per series ($140 per dose), HZ/su was more effective and less expensive than ZVL at all ages. The incremental cost-effectiveness ratios compared with no vaccination ranged from $20 038 to $30 084 per QALY, depending on vaccination age. The finding was insensitive to variations in most model inputs other than the vaccine price and certain combinations of low adherence rate with a second dose and low efficacy of a single dose of HZ/su. At the current ZVL price ($213 per dose), HZ/su had lower overall costs than ZVL up to a price of $350 per 2-dose series. In probabilistic sensitivity analysis, HZ/su had 73% probability of being cost-effective for 60-year-olds at $50 000 per QALY. Conclusions and Relevance:Under conservative assumptions, at a price of $280 per series ($140 per dose), HZ/su would cost less than ZVL and has a high probability of offering good value.
Project description:Herpes zoster (HZ) is the result of reactivation of latent varicella zoster virus (VZV) and occurs most frequently in older adults. Classically, HZ presents as a unilateral, selflimited, dermatomal rash. Postherpetic neuralgia (PHN) is a common sequela, presenting as severe pain that persists after the rash has resolved. In the elderly, PHN can be debilitating and requires a prompt diagnosis, treatment with antivirals, and adequate pain control. A longer-term pain management strategy is required if PHN occurs. A modestly effective vaccine exists and is recommended for older individuals.
Project description:Preserving good health in old age is of utmost importance to alleviate societal, economic and health care-related challenges caused by an aging society. The prevalence and severity of many infectious diseases is higher in older adults, and in addition to the acute disease, long-term sequelae, such as exacerbation of underlying chronic disease, onset of frailty or increased long-term care dependency, are frequent. Prevention of infections e.g. by vaccination is therefore an important measure to ensure healthy aging and preserve quality of life. Several vaccines are specifically recommended for older adults in many countries, and in the current SARS-CoV-2 pandemic older adults were among the first target groups for vaccination due to their high risk for severe disease. This review highlights clinical data on the influenza, Streptococcus pneumoniae and herpes zoster vaccines, summarizes recent developments to improve vaccine efficacy, such as the use of adjuvants or higher antigen dose for influenza, and gives an overview of SARS-CoV-2 vaccine development for older adults. Substantial research is ongoing to further improve vaccines, e.g. by developing universal influenza and pneumococcal vaccines to overcome the limitations of the current strain-specific vaccines, and to develop novel vaccines against pathogens, which cause considerable morbidity and mortality in older adults, but for which no vaccines are currently available. In addition, we need to improve uptake of the existing vaccines and increase awareness for life-long vaccination in order to provide optimal protection for the vulnerable older age group.
Project description: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.
Project description:The adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit herpes zoster vaccine (HZ/su) confers higher protection against HZ than the live attenuated zoster vaccine (ZV). To understand the immunologic basis for the different efficacies of the vaccines, we compared immune responses to the vaccines in adults 50 to 85 years old. gE-specific T cells were very low/undetectable before vaccination when analyzed by FluoroSpot and flow cytometry. Both ZV and HZ/su increased gE-specific responses, but at peak memory response (PMR) after vaccination (30 days after ZV or after the second dose of HZ/su), gE-specific CD4+ and CD8+ T cell responses were 10-fold or more higher in HZ/su compared with ZV recipients. Comparing the vaccines, T cell memory responses, including gE-IL-2+ and VZV-IL-2+ spot-forming cells (SFCs), were higher in HZ/su recipients and cytotoxic and effector responses were lower. At 1 year after vaccination, all gE-Th1 and VZV-IL-2+ SFCs remained higher in HZ/su compared with ZV recipients. Mediation analyses showed that IL-2+ PMR were necessary for the persistence of Th1 responses to either vaccine and VZV-IL-2+ PMR explained 73% of the total effect of HZ/su on persistence. This emphasizes the biological importance of the memory responses, which were clearly superior in HZ/su compared with ZV participants.
Project description:CDC recommends that U.S. adults ≥50 years receive the herpes zoster (HZ) vaccine; but few are vaccinated at the recommended age. Little is known about how social determinants of health (SDH) influence timely vaccination. This retrospective observational study included U.S. adults aged ≥50 years who were vaccinated against HZ between 2014 and 2016 from IBM MarketScan commercial claims and Medicare supplemental databases. The cohort was classified into three groups based on age of vaccination: earlier (50-59 years), timely (60-64 years), and later (65+ years). Select SDH data from publicly-available sources were linked and included in multinomial logistic regression assessing the impact of SDH on timely vaccination. The final cohort comprised 549,544 individuals, 49.5% of whom were vaccinated at the age of 60-64. Odds of later HZ vaccination increased with higher poverty (OR: 1.035, 95% CI: 1.031-1.038), more democratic voters (OR: 1.011, 95% CI: 1.010-1.012), and lack of Internet access (OR: 1.028, 95% CI: 1.024-1.032), but decreased with higher health literacy (OR: 0.971, 95% CI: 0.970-0.973). Conversely, higher health literacy and lower poverty were associated with higher odds of earlier vaccination. Being male, not receiving a seasonal influenza vaccine, and higher healthcare utilization were associated with later vaccination. Individuals on an EPO/PPO vs. HMO plan, or who resided in regions other than the Northeast were more likely to receive the vaccine earlier. This study demonstrates the influence of SDH on time of HZ vaccination, but further research is needed to fully understand the impact of SDH on vaccination.
Project description: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.