Population-based incidence of herpes zoster after introduction of a publicly funded varicella vaccination program

Background

Past varicella infection (chicken pox) may reactivate into herpes zoster (shingles). Varicella vaccination leads to a reduction in cases of varicella that may in turn increase herpes zoster rates due to reduction in the immune boosting effect of exposure to varicella zoster virus against varicella reactivation. We assessed the impact of childhood varicella vaccination in Ontario, Canada on zoster incidence and healthcare visits, and established baseline zoster rates prior to zoster vaccine introduction.

Methods

We used population-based, administrative databases to identify zoster incidence and healthcare use from April 1992 to March 2010.

Results

After routine varicella vaccination, zoster incidence rates decreased 29% for children aged 0-9 and changed minimally for other ages. Age-standardized rates of hospitalizations during the study period declined by 53%, while outpatient rates declined by 9%. The annual zoster incidence for those 60 or older was 740 per 100,000.

Conclusions

In the early post-varicella vaccination period, incidence rates of medically attended herpes zoster did not increase for the overall population and decreased moderately for children 9 years and younger, the age group targeted for varicella vaccination.     

Varicella susceptibility and incidence of herpes zoster among children and adolescents in a community under active surveillance

Licensure of varicella vaccine by the US Food and Drug Administration in March 1995 has given rise to concerns that include a potential shift in varicella incidence to susceptible adults and increase in herpes zoster (HZ) incidence. Baseline values prior to widespread vaccination were obtained through distribution of an adolescent survey to all 13 public middle (seventh and eighth grade) schools in the Antelope Valley, CA health district. Based on 4216 respondents aged 10-14 years, varicella susceptibility is 7.7% (95% CI, 6.9-8.5%) and true cumulative (1987-2000) HZ incidence rate is 133 per 100,000 person-years (95% CI, 95-182 per 100,000 person-years).     

Varicella and herpes zoster hospitalizations before and after implementation of one-dose varicella vaccination in Australia: an ecological study

Objective

To examine trends in varicella and herpes zoster (HZ) hospitalization following the availability and subsequent National Immunization Programme funding of one-dose varicella vaccination in Australia.

Methods

Varicella vaccination coverage for children born between 2001 and 2009 was obtained from the Australian Childhood Immunization Register. Principal or any coded varicella or HZ hospitalizations were retrieved from the national hospital morbidity database from 1998 to 2010. Trends in hospitalization rates in different age groups and indigenous status were assessed. Incidence rate ratios (IRR) were calculated between periods before and after implementation of immunization programme funding.

Findings

In the first year of the funded immunization programme, varicella vaccine coverage reached 75% in children aged 24 months and more than 80% in children aged 60 months. Compared with the pre-vaccine period, varicella hospitalization rates during the funded programme were significantly lower for age groups younger than 40 years; with the greatest reduction in children aged 18–59 months (IRR: 0.25; 95% confidence interval, CI: 0.22–0.29). Indigenous children had a higher varicella hospitalization rate compared with non-indigenous children before vaccine implementation (IRR: 1.9; 95% CI: 1.4–2.7), but afterwards reached equivalence (IRR: 1.1; 95% CI: 0.7–1.6). The age-standardized HZ hospitalization rate declined between the periods (IRR: 0.95; 95% CI: 0.92–0.97).

Conclusion

Rapid attainment of high coverage reduced varicella hospitalizations in the targeted age group, particularly for indigenous children, but also in non-targeted age groups, with no increase in HZ hospitalizations. This suggests high one-dose varicella vaccine coverage can have a substantial impact on severe disease.     

2006-2010年双塔区水痘流行病学分析

目的了解双塔区2006-2010年水痘疫情的流行特征,为水痘防制提供科学依据。方法对2006-2010年双塔区水痘疫情资料进行描述性流行病学分析。结果双塔区2006-2010年共报告水痘406例,无死亡病例,年平均发病率67.24/10万;常年均有发病,呈现4～6月、11～1月两个发病高峰,占发病总数的79.14%;5～14岁组病例占发病总数的82.67%;学生、幼托儿童、散居儿童占发病总数的95.78%。结论加强学校托幼机构水痘防控工作,提高重点人群水痘疫苗接种率。     

2006-2009年广元市水痘疫情分析

目的了解广元市2006-2009年水痘疫情的流行情况,为及时制定水痘预防控制措施提供科学依据。方法对2006-2009年水痘疫情报告资料进行描述性流行病学分析。结果 2006-2009年广元市共发生水痘3621例,在监测疾病及急性传染病监测排名中一直位居前列。发病以利州区、剑阁县、朝天区、苍溪县发病人数最多（74.78%）。全年各月均有发病,以4~6月及12月发病最多,占病例数的55%。病例中88.84%为10岁及以下儿童,学生居多（74.90%）,病例男女性别比为119.06∶100。发生暴发疫情13起,报告病例334例,波及人数9 619人,罹患率3.47%,暴发疫情均发生在学校,尤其是农村小学,患者无水痘疫苗接种史。结论水痘引起的公共卫生问题不容忽视,应采取推广水痘疫苗接种的有效等综合防控措施控制水痘疫情。     

2009-2018年珠海地区水痘流行与疫苗接种情况分析

目的 分析2009-2018年珠海市水痘流行趋势以及疫苗接种情况,为本地区调整和完善水痘防控措施提供科学依据。方法 对珠海市的水痘流行特征及疫苗接种情况采用描述流行病学的方法进行分析。结果 2009-2018年珠海市水痘报告发病率总体呈升高趋势(Z=67.794,P＜0.001);在时间分布上呈双峰分布的特点;男女发病率性别比为127.6[DK]∶100,在20~30岁之间出现性别比倒置的情况;发病年龄以≤15岁为主,近年来高年龄组发病构成比逐渐升高;近年水痘疫苗第一剂次接种率有所下降。结论 水痘疫苗接种率下降引起了近年来水痘发病率的升高,建议将水痘疫苗纳入计划免疫,加强接种,并保证疫苗的正常供应。     

Estimating the cost-effectiveness of vaccination against herpes zoster in England and Wales

A live-attenuated vaccine against herpes zoster (HZ) has been approved for use, on the basis of a large-scale clinical trial that suggests that the vaccine is safe and efficacious. This study uses a Markov cohort model to estimate whether routine vaccination of the elderly (60+) would be cost-effective, when compared with other uses of health care resources. Vaccine efficacy parameters are estimated by fitting a model to clinical trial data. Estimates of QALY losses due to acute HZ and post-herpetic neuralgia were derived by fitting models to data on the duration of pain by severity and the QoL detriment associated with different severity categories, as reported in a number of different studies. Other parameters (such as cost and incidence estimates) were based on the literature, or UK data sources. The results suggest that vaccination of 65 year olds is likely to be cost-effective (base-case ICER = £20,400 per QALY gained). If the vaccine does offer additional protection against either the severity of disease or the likelihood of developing PHN (as suggested by the clinical trial), then vaccination of all elderly age groups is highly likely to be deemed cost-effective. Vaccination at either 65 or 70 years (depending on assumptions of the vaccine action) is most cost-effective. Including a booster dose at a later age is unlikely to be cost-effective.     

Determinants of non-compliance with herpes zoster vaccination in the community-dwelling elderly

As part of a series of studies on vaccine acceptance, we assessed determinants of compliance of the community-dwelling elderly with herpes zoster (HZ) vaccination in an existing influenza vaccination program. General practitioners (GPs) sent out a questionnaire to 1778 patients aged > or =65 years, and offered them free HZ vaccination simultaneously with the yearly influenza vaccination. In all, 690 patients (39%) were vaccinated against HZ; 1349 patients (76%) accepted influenza vaccination. Determinants of non-compliance with HZ vaccination were perceived lack of recommendation by the GP, unwillingness to comply with the doctor's advice, perception of low risk of contracting HZ, perception of short pain duration of HZ, and the opinion that vaccinations weaken one's natural defenses. The same determinants were associated with non-compliance with both vaccinations, but objections in general towards vaccination, a high education and difficulties to visit GPs were also important. Uptake of HZ vaccination was rather low and more data on (cost-)effectiveness might encourage GPs to offer HZ vaccination to their patients.     

Incidence of herpes zoster, 1997-2002

We estimated age-specific herpes zoster (HZ) incidence rates in the Kaiser Permanente Northwest Health Plan (KPNW) during 1997-2002 and tested for secular trends and differences between residents of two states with different varicella vaccine coverage rates. The cumulative proportions of 2-year-olds vaccinated increased from 35% in 1997 to 85% in 2002 in Oregon, and from 25% in 1997 to 82% in 2002 in Washington. Age-specific HZ incidence rates in KPNW during 1997-2002 were compared with published rates in the Harvard Community Health Plan (HCHP) during 1990-1992. The overall HZ incidence rate in KPNW during 1997-2002 (369/100,000 person-years) was slightly higher than HCHP's 1990-1992 rate when adjusted for age differences. For children 6-14 years old, KPNW's rates (182 for females, 123 for males) were more than three times HCHP's rates (54 for females, 39 for males). This increase appears to be associated with increased exposure of children to oral corticosteroids. The percentage of KPNW children exposed to oral corticosteroids increased from 2.2% in 1991 to 3.6% in 2002. Oregon residents had slightly higher steroid exposure rates during 1997-2002 than Washington residents. There were significant increases in HZ incidence rates in Oregon and Washington during 1997-2002 among children aged 10-17 years, associated with increased exposure to oral steroids.     

Modelling a cost-effective vaccination strategy for the prevention of varicella and herpes zoster infection: A systematic review

BackgroundVaricella zoster virus (VZV) and its re-emergence as herpes zoster (HZ) is associated with significant morbidity and mortality. While studies show that VZV vaccination is effective in reducing VZV incidence, many decision makers have not added VZV to their vaccination schedule, largely due to uncertainty surrounding the effect of VZV vaccination on HZ incidence (exogenous boosting, EB), and the cost-effectiveness (CE) of vaccination.MethodsA systematic review was conducted to identify the current published evidence of CE of VZV vaccination strategies where both VZV and HZ incidence were modelled.ResultsSix studies (one published in 2003 and five between 2010 and 2019), were identified with all conducting cost-utility analysis using a dynamic transmission modelling approach and assuming EB. All predicted that mass infant VZV vaccination would rapidly reduce VZV incidence, but HZ incidence would increase. Compared with no-vaccination, the CE of VZV vaccination strategies ranged from higher costs and poorer outcomes (dominated), towards CE (incremental cost-effectiveness ratios of between $7,000 to $61,000 USD), or lower cost and better outcomes (dominant). However, without EB, HZ incidence immediately dropped below pre-vaccination levels making VZV vaccination quickly CE and/or dominant to a no vaccination strategy.ConclusionsCurrent models are sensitive to assumptions of EB suggesting that future studies consider an agent-based modelling approach to address the individual nature of variables that determine the infectiousness of VZV.     

广州市2006～2012年水痘流行病学特征分析

目的分析广州市2006-2012年水痘流行病学特征,为制订预防控制水痘策略提供参考。方法对广州市2006-2012年水痘发病资料进行描述性流行病学分析。结果广州市2006-2012年共报告水痘110 763例,年平均发病率为144.10/10万。冬春季高发,3-6月、12月-次年1月为高发月份;男性发病率高于女性;〈15岁儿童高发,发病率为556.90/10万;职业以学生为主。中小学和托幼机构是水痘突发公共卫生事件高发场所。结论广州市水痘发病率高,疾病负担严重。建议将水痘纳入国家法定丙类传染病管理。     

Epidemiology of notifiable diseases in Navarre, 2006

Epidemiological vigilance in Navarre (601,874 inhabitants) in 2006 included 34 diseases whose notification is compulsory and epidemic outbreaks. Notification is carried out on a weekly basis by the doctors from paediatrics, primary care and specialised care facing any suspicion of these processes, and is completed with microbiological diagnoses. In 2006 the incidence of influenza reached 16.8 cases per 1,000 inhabitants (Epidemic Index, EI: 0.46), showing a late seasonal peak (March) of low dimensions. The incidence of respiratory tuberculosis was 11.3 cases per 100,000 inhabitants, and that of non-respiratory tuberculosis was 2.3; both at similar levels to recent years. Seven cases of tuberculosis occurred in three aggregates amongst cohabitants, and another 7 in non-cohabiting persons resident in the same municipality. Six percent of the cases were coinfected with HIV, and 37% occurred in immigrants. The incidence of meningococcal disease rose to 19 cases (3.2 cases per 100,000 inhabitants; EI 1.46), all of them sporadic. Neisseria meningitidis serogroup B was isolated in 16 cases. There was one case of serogroup C, in a child who had received 3 doses of combined vaccine. In two cases (11%) death occurred. The incidence of legionnaire's disease rose to 28 cases per 100,000 inhabitants (EI:4.88), due to a community outbreak that affected 146 people. Excluding this outbreak, incidence was similar to previous years (3.3 per 100,000 inhabitants). In August an outbreak of parotitis began, and 911 cases had been counted until the end of 2006; and it has continued during 2007. Eleven cases of malaria were registered, all imported. Notifications of toxic food infections has continued to fall (IE:0.48).     

Cost-effectiveness of vaccination of the elderly against herpes zoster in The Netherlands

Background

Each year a substantial number of Dutch elderly suffers from herpes zoster (HZ), caused by the reactivation of the varicella zoster virus (VZV). A potential complication of HZ is postherpetic neuralgia (PHN) which results in a prolonged loss of quality of life. A large randomized clinical trial, labelled the Shingles Prevention study (SPS), demonstrated that a live attenuated VZV vaccine can reduce the incidence of HZ and PHN.

Objective

We aimed to estimate the incremental cost-effectiveness ratio (ICER) of vaccination of the elderly against HZ versus no such vaccination in The Netherlands.

Methods

A cohort model was developed to compare the costs and effects in a vaccinated and a non-vaccinated age- and gender-stratified cohort of immune-competent elderly. Vaccination age was varied from 60 to 75 years. Data from published literature such as the SPS were used for transition probabilities. The study was performed from the societal as well as the health care payer's perspective and results were expressed in euros per quality-adjusted life year (QALY) gained.

Results

In the base case, we estimated that vaccination of a cohort of 100,000 60-year-olds would prevent 4136 cases of HZ, 305 cases of PHN resulting in a QALY-gain of 209. From the societal perspective, a total of €1.9 million was saved and the ICER was €35,555 per QALY gained when a vaccine price of €87 was used. Vaccination of women resulted in a lower ICER than vaccination of men (€33,258 vs. €40,984 per QALY gained). The vaccination age with the most favourable ICER was 70 years (€29,664 per QALY gained). Parameters with a major impact on the ICER were the vaccine price and HZ incidence rates. In addition, the model was sensitive to utility of mild pain, vaccine efficacy at the moment of uptake and the duration of protection induced by the vaccine.

Conclusion

Vaccination against HZ might be cost-effective for ages ranging from 60 to 75 when a threshold of €50,000 per QALY gained would be used, at €20,000 per QALY this might not be the case. Additional information on the duration of vaccine-protection is needed to further optimize cost-effectiveness estimations.     

Epidemiology and costs of herpes zoster: background data to estimate the impact of vaccination

In 2004, we conducted a study in Piemonte (Italy), in order to describe incidence, treatment, hospitalizations and costs of herpes zoster (HZ), in population over 14 years of age. Twenty-four regional general practitioners, with 26,394 patients >14 years in charge (0.71% of the regional population), reported prospectively all diagnosed HZ cases. In addition, all regional hospital discharge records were reviewed. Forty-six HZ cases treated at home were reported, accounting for a total incidence of 1.74 cases/1000 population >14 years per year. HZ rate standardized by age on regional population 14 years older is 1.59/1000. The cost per observed home case was 136.06 euros. The incidence of hospital admissions was 0.12/1000 inhabitants. The mean cost of hospitalized cases was 4082.59 euros. These results contribute to depict the impact of HZ in the general population, and to provide background data for setting-up either mathematical models aimed to estimate the impact of vaccination on HZ, and the cost-benefit analyses of various preventive and therapeutic scenarios.     

Effectiveness of herpes zoster vaccination in an older United Kingdom population

BackgroundVaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71–79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed.MethodsIn a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013–31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN.ResultsAmong 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60–68%) against incident zoster and 81% (95%CI = 61–91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31–58%) versus 64% (95%CI = 60–68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65–74%) in the first year after vaccination to 45% (95%CI = 29–57%) by the third year.ConclusionThis first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK.     

带状疱疹的发生与脊柱损伤的关系探讨

目的探讨带状疱疹（Hz）的发生与脊柱损伤之间的关系。方法首先明确脊柱损伤的四项标准：即脊柱损伤史，与Hz相对应的脊柱部位的疼痛和压痛，相应的X线或cT检查诊断。然后将16例确诊为脊柱损伤的Hz病例与同期的56例Hz依其就诊时间和地点自然形成的6个组别进行检验。结果显示了脊柱损伤是Hz发生的重要原因之一。结合现代脊柱病学观点，一元化的解释了Hz的发病机制、临床体征，特别是呈单侧性的带状分布现象的原因。结论Hz的发生是脊柱损伤和类水痘病毒感染二者共同作用的结果，前者为先决条件，后者是继发感染的病原因素。     

The epidemiology of varicella and herpes zoster in The Netherlands: implications for varicella zoster virus vaccination

We studied the epidemiology of varicella (chickenpox) and herpes zoster (shingles) in The Netherlands to assess the desirability to implement routine varicella zoster virus vaccination in The Netherlands. Data on seroprevalence of varicella zoster virus in the general population (1995-1996), consultations of general practitioners for varicella (2000-2002) and herpes zoster (1998-2001) and hospital admissions due to varicella (1994-2001) and herpes zoster (1994-2001) in The Netherlands were analysed. The seropositivity increased sharply with age from 18.4% for both 0- and 1-year-olds, to 48.9%, 59.0%, 75.7% and 93.0% for 2-, 3-, 4- and 5-year-olds, respectively, and varied between 97.5% and 100% for older age groups. The average annual incidence of GP-consultations amounted to 253.5 and 325.0 per 100,000 for varicella and herpes zoster, respectively. The incidence of hospital admission due to varicella and herpes zoster was 1.3 (2.3 including side diagnosis) and 2.7 (5.8) per 100,000, respectively. Whilst for varicella, the incidence of GP-consultations and hospital admissions were highest in childhood, for herpes zoster, these were highest in elderly. Insight into epidemiology of varicella zoster is needed for the assessment of the desirability of introduction of routine varicella zoster vaccination.     

Modeling the impact of combined vaccination programs against varicella and herpes zoster in Norway

BackgroundAdoption of varicella immunization in Europe is limited due to a predicted increase in the incidence of herpes zoster (HZ) resulting from a removal of exogenous boosting by varicella vaccination. Most available assessments of immunization strategies only considered universal varicella vaccination (alone or in combination with HZ by the live vaccine). The development of a new subunit recombinant zoster vaccine may provide new perspectives of HZ control.MethodsWe used a mathematical model for VZV in Norway based on the progressive immunity formulation of exogenous boosting. We evaluated a complete range of alternative immunization options against varicella and HZ including both universal and targeted varicella vaccination, either alone or with zoster immunization, and zoster immunization alone. We considered all values of the boosting intensity consistent with the Norwegian HZ incidence and compared the performance of the currently available live vaccine vs. a new recombinant vaccine.ResultsUniversal varicella vaccination alone resulted in a marked increase in the incidence of HZ under all scenarios considered. Even under the most favorable hypotheses on the magnitude of the boosting intensity, this increase could be mitigated only by a parallel HZ immunization with a recombinant vaccine, assuming a long duration of protection. Targeted varicella immunization of adolescents resulted in a modest increase in the HZ incidence which could be counterbalanced by both the live and, especially, the recombinant vaccine.ConclusionsGiven current knowledge on HZ pathogenesis and exogenous boosting, targeted varicella vaccination of adolescents was the only strategy that was not predicted to impact the epidemiology of HZ, and therefore it may represent a suitable alternative to universal vaccination. These results are aimed to support vaccine policy decisions in Norway and other countries with a similar VZV epidemiology.