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.

Impact of infection on risk of Parkinson's disease: a quantitative assessment of case-control and cohort studies.

Identifying modifiable risk factors for Parkinson's disease (PD) to help prevent this disease has attracted increasing interest in recent years for the limited effective drugs at present. Despite many studies indicated that infection acts as a risk factor for PD, there is no quantitative assessment of the impact of viral and bacterial infections on the risk of developing PD. The present study performed a meta-analysis on the basis of 38 datasets from 13 studies covering 287,773 PD cases and 7,102,901 controls to ascertain the association between PD and infection and the differences in the strength of the viral and bacterial infections. The overall meta-analytic results indicated that individuals with infection had a 20% increased risk of PD compared with controls (OR 1.20, 95%CI 1.07-1.32). The subgroup analysis according to the type of infection found that bacterial infection had a significant impact on increased risk of PD (OR 1.40, 95%CI 1.32-1.48). The present analysis indicated that infection could increase the risk of developing PD, and physician should be aware of the risk of developing PD in subjects with infection.

Increasing incidence associated with herpes zoster infection in British Columbia, Canada.

BACKGROUND: Recent studies have shown an increasing incidence of herpes zoster (HZ) infection, which may be related to the introduction of varicella vaccination programs in children. We examined the epidemiology and treatment costs of HZ and post-herpetic neuralgia (PHN) over time in British Columbia, Canada. METHODS: The cohort consisted of all cases with HZ infection from January 1, 1997 and December 31, 2012. Incident zoster was defined as a case (ICD-9 053 or ICD-10 B02) without a previous episode of HZ or PHN in the previous 12 months. We determined the incidence for HZ and PHN and the age-sex standardized rate for the overall population. We determined the association between the varicella vaccination program and increased HZ rates by evaluating the rate ratios in the publicly-funded varicella vaccine period compared to the non-publicly funded period in a regression model. We evaluated the hospitalization rates, treatment by GPs and their associated yearly costs for HZ and PHN. RESULTS: HZ incidence increased for the entire study period from 3.2 per 1000 population in 1997 to 4.5 in 2012. HZ rates were higher for females than males and all age groups had an increased incidence rate, except the 0-9 year olds, where the rate decreased. Crude and age-sex standardized incidence rates of PHN demonstrated very similar patterns to HZ incidence. Based on the regression model, rates of HZ were higher in the older individuals. No significant increase with HZ incidence was seen during the publically funded varicella vaccination program compared to the non-publicly funded period. From 1997 to 2012, the annual HZ-related costs associated with hospitalizations and GP visits were over $CDN4.9 million and $CDN537,286, respectively; treatment costs for hospitalizations have increased significantly over time. Majority of PHN-related cases are managed by GPs, with a steady increase over time in number of cases and associated annual costs. CONCLUSIONS: The incidence of zoster and PHN is increasing with time, particularly in the elderly population and the risk is greater in the over 65 year olds. Treatment costs for both HZ and PHN represent a significant burden on the Canadian healthcare system.

Healthcare Resource Utilisation Associated with Herpes Zoster in a Prospective Cohort of Older Australian Adults.

BACKGROUND: Herpes zoster (HZ) is a common condition that increases in incidence with older age but vaccines are available to prevent the disease. However, there are limited data estimating the health system burden attributable to herpes zoster by age. METHODS: In this study, we quantified excess healthcare resource usage associated with HZ during the acute/sub-acute period of disease (21days before to 90 days after onset) in 5952 cases and an equal number of controls matched on age, sex, and prior healthcare resource usage. Estimates were adjusted for potential confounders in multivariable regression models. Using population-based estimates of HZ incidence, we calculated the age-specific excess number of health service usage events attributable to HZ in the population. RESULTS: Per HZ case, there was an average of 0.06 (95% CI 0.04-0.08) excess hospitalisations, 1.61 (95% CI 1.51-1.69) excess general practitioner visits, 1.96 (95% CI 1.86-2.15) excess prescriptions filled and 0.11 (95% CI 0.09-0.13) excess emergency department visits. The average number of healthcare resource use events, and the estimated excess per 100,000 population increased with increasing age but were similar for men and women, except for higher rates of hospitalisation in men. The excess annual HZ associated burden of hospitalisations was highest in adults ≥80 years (N = 2244, 95%CI 1719-2767); GP visits was highest in those 60-69 years (N = 50567, 95%CI 39958-61105), prescriptions and ED visits were highest in 70-79 years (N = 50524, 95%CI 40634-60471 and N = 2891, 95%CI 2319-3449 respectively). CONCLUSIONS: This study provides important data to establish the healthcare utilisation associated with HZ against which detailed cost-effectiveness analyses of HZ immunisation in older adults can be conducted.

Varicella zoster virus transmission in youth during incarceration.

Purpose - Facility-based Varicella zoster virus (VZV) transmission is reported in a Canadian youth offender correctional centre (YOCC). Transmission occurred from an immunocompetent youth offender (YO) with localized Herpes zoster to another immunocompetent single dose vaccinated YO, resulting in Varicella zoster (VZ) breakthrough disease. The purpose of this paper is to identify infection prevention and control (IPAC) measures utilized in this setting. Design/methodology/approach - A retrospective chart and immunization record review was conducted for two VZV cases and 27 exposed YO contacts in order to obtain demographic, clinical and immunization data. Descriptive data analysis was performed. Findings - All VZV cases and exposed contacts were male with an average age of 14.2 and 15.6 years for cases and contacts, respectively. Both cases shared the same living unit in the YOCC. There were 28 identified YO contacts, of whom 70 percent were single dose vaccinated with univalent vaccine, followed by 22 percent with a previous history of Varicella disease. All cases and contacts were born in Canada. No foreign-born populations were involved with this event. Infection control measures included additional precaution management, enhanced surveillance and environmental cleaning. As such, no hospitalizations or post-exposure immunizations were required. Originality/value - This report highlights the role that VZ breakthrough disease could play in fueling an outbreak in a high-risk environment without rapid recognition and implementation of preventative measures. It also underscores the importance of IPAC presence and public health immunization programs within correctional centers to avoid infectious disease threats.

Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management.

IMPORTANCE: Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity. OBJECTIVE: To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management. DESIGN, SETTING, AND PARTICIPANTS: Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated. INTERVENTIONS: In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis). MAIN OUTCOMES AND MEASURES: Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting. RESULTS: Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation. CONCLUSIONS AND RELEVANCE: Rates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon. We recommend establishing the patient's VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.

Vaccination to prevent varicella: Goldman and King's response to Myers' interpretation of Varicella Active Surveillance Project data.

BACKGROUND: There is increasing evidence that herpes zoster (HZ) incidence rates among children and adults (aged <60 years) with a history of natural varicella are influenced primarily by the frequency of exogenous exposures, while asymptomatic endogenous reactivations help to cap the rate at approximately 550 cases/100,000 person-years when exogenous boosting becomes rare. The Antelope Valley Varicella Active Surveillance Project was funded by the Centers for Disease Control and Prevention in 1995 to monitor the effects of varicella vaccination in one of the three representative regions of the United States. The stability in the data collection and number of reporting sites under varicella surveillance from 1995-2002 and HZ surveillance during 2000-2001 and 2006-2007 contributed to the robustness of the discerned trends. DISCUSSION: Varicella vaccination may be useful for leukemic children; however, the target population in the United States is all children. Since the varicella vaccine inoculates its recipients with live, attenuated varicella-zoster virus (VZV), clinical varicella cases have dramatically declined. Declining exogenous exposures (boosts) from children shedding natural VZV have caused waning cell-mediated immunity. Thus, the protection provided by varicella vaccination is neither lifelong nor complete. Moreover, dramatic increases in the incidence of adult shingles cases have been observed since HZ was added to the surveillance in 2000. In 2013, this topic is still debated and remains controversial in the United States. SUMMARY: When the costs of the booster dose for varicella and the increased shingles recurrences are included, the universal varicella vaccination program is neither effective nor cost-effective.

Assessment of transcriptomal analysis of Varicella-Zoster-virus gene expression in patients with and without post-herpetic neuralgia.

Varicella-Zoster virus (VZV) is a human herpes virus that reactivates from a latent state in human trigeminal and dorsal root ganglia to cause herpes zoster (shingles) which is a painful vesicular dermatomal skin eruption. The major complication of herpes zoster is post-herpetic neuralgia (PHN) which is a serious condition occurring especially in individuals over 50 years. PHN is extremely painful, may be permanent, and is frequently very refractory to all treatment. The ability to identify those patients with herpes zoster who are likely to develop PHN would be highly beneficial as it would allow pre-emptive anti-viral therapy. We have assessed the potential of using long oligonucleotide VZV microarrays to determine whether MeWo cells infected with VZV isolates obtained from 13 patients with zoster who had subsequently developed PHN showed significant transcriptomal differences from MeWo cells infected with viruses isolated from ten zoster patients who had not developed PHN. We found that viral gene expression from sample to sample within a group (PHN patients or non-PHN patients) varied as much, or more, than the viral gene expression between those groups. Quantitative real-time polymerase chain reaction studies carried out on 11 open reading frames on four representative viral infected MeWo cell lines (two from each group) confirmed the transcriptomal heterogeneity between the two groups. Growth curve analyses of ten representative infected cell lines (five from each group) showed that PHN and non-PHN-associated viruses replicated equally efficiently. Taken together, these findings suggest that viral microarray-based transcriptomal measurements are unlikely to prove of clinical utility in predicting the incidence of PHN.

Varicella zoster vaccines.

In the past, the varicella zoster virus affected virtually the entire population and had substantial morbidity and mortality associated with both primary varicella and herpes zoster reactivation. Since the varicella vaccine was first approved in 1995, there has been a significant decline in incidence, morbidity, and mortality caused by primary varicella. Breakthrough disease with the one-dose vaccine schedule led to the recommendation in 2006 that children receive a two-dose vaccine series. Older adults have also benefited from the development of the zoster vaccine. In 2006, the Food and Drug Administration approved the zoster vaccine, a higher concentration of the same live attenuated virus used in the primary varicella vaccine, for persons 60 years of age or older. It has the potential to help millions of people avoid the pain associated with reactivation of the varicella zoster virus by reducing the incidence and severity of herpes zoster and postherpetic neuralgia.

Outbreak of varicella-zoster virus infection among Thai healthcare workers.

OBJECTIVE: To evaluate the correlation between self-report of a prior history of chickenpox and results of varicella-zoster virus (VZV) immunoglobulin (Ig) G serologic test results in an outbreak of VZV infection among Thai healthcare workers (HCWs) and to conduct a cost-benefit analysis of establishing routine VZV immunization as part of an occupational health program on the basis of the outbreak data. METHODS: All exposed patients received prophylaxis and the HCWs in our 3 intensive care units (ICUs) were prospectively evaluated. HCWs were assessed for disease history and serologic evidence of VZV IgG. A cost-benefit analysis was performed. RESULTS: After 140 HCWs and 18 ICU patients were exposed to VZV, 10 HCWs (7%) with active VZV infection were relieved from work until skin lesions were crusted. Acyclovir (ACV) was prescribed to all 10 HCWs with active disease, and all 18 exposed patients received prophylaxis with ACV. Of 140 HCWs, 100 consented to longitudinal follow-up. Twenty-three (100%) of the HCWs who reported a history of chickenpox also had serologic test results that were positive for VZV IgG, compared with 30 (39%) of 77 HCWs who reported no prior history of chickenpox, yet had test results that were positive for VZV IgG. Reported history of chickenpox had a sensitivity of 43%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 61% with respect to VZV infection immunity. The total cost estimate for this outbreak investigation was $23,087. CONCLUSIONS: An HCW's reported history of chickenpox was a reliable predictor of immunity; a report of no prior history of chickenpox was unreliable. Our cost-benefit analysis suggests that the costs of an occupational health program that included VZV surveillance and immunization for the next 323 HCWs would be approximately equal to the excess costs of $17,227 for the ACV therapy, HCW furloughs, and staff overtime associated with this outbreak.

Can varicella be eliminated by vaccination? Potential clinical and economic effects of universal childhood varicella immunisation in Germany.

Varicella is a potentially serious infection not only in immunocompromised individuals but also in otherwise healthy adults and children. Vaccination plays an important role in preventing the disease and its sequelae. A universal vaccination in childhood is expected to reduce substantially the number of uncomplicated cases of varicella and decrease the number of complicated cases requiring hospitalisation. To generate data as basis for decisions of the health authorities concerning prevention of varicella, epidemiological and health-economic data were collected in two studies. Using an age-structured decision analytic model the benefits, costs and cost effectiveness of a varicella immunisation program for a period of 30 years were assessed. It was shown that after the first year of life seroprevalence rates increased steadily and reached 62% among the 4- to 5-year olds and 94% among the 10- to 11-year olds, respectively; 90% of varicella patients were younger than 12 years. A severe course was assessed for 16.3% of the cases. Overall incidence of complications was estimated to be 5.7%. A routine varicella vaccination program targeting healthy children could prevent 82.7% of varicella cases and over 4,700 major complications per year provided the coverage level was 85%. Under these conditions the elimination of varicella is predicted to be achievable within 18 years. It is expected that a combined measles, mumps, rubella and varicella vaccine could provide the required coverage. Average yearly discounted net cost savings of universal childhood vaccination are 51 million Euro with a benefit-cost ratio of 4.12. Childhood vaccination with catch-up of adolescents provides additional clinical benefits. The break-even point indicating first net savings could be achieved already 3 years after the implementation of the vaccination program. In summary, routine childhood varicella vaccination appears to be a highly efficient strategy to significantly reduce the sizeable burden of varicella and would lead to net savings from both the societal but also the payer perspective.