The Epidemiology of Herpes Zoster in Immunocompetent, Unvaccinated Adults ≥50 Years Old: Incidence, Complications, Hospitalization, Mortality, and Recurrence.

BACKGROUND: Data on the epidemiology of herpes zoster (HZ), particularly in the unvaccinated immunocompetent population, are needed to assess disease burden and the potential impact of vaccination. METHODS: The study at a large health care organization comprised: (1) incidence estimated from immunocompetent adults aged ≥50 years unvaccinated with zoster vaccine live who had incident HZ in 2011-2015; (2) proportion of HZ-related nonpain complications assessed by double abstraction of electronic health records (EHRs) of 600 incident patients 2011-2015; (3) HZ-related hospitalizations among HZ patients diagnosed in 2015; (4) HZ-related death determined from automated data and EHRs; and (5) recurrent HZ identified from a cohort initially diagnosed with HZ in 2007-2008 and followed through 2016. RESULTS: HZ incidence rate was 9.92/1000 person-years (95% confidence interval [CI], 9.82-10.01). Proportions of cutaneous, neurologic, and other complications were 6.40% (95% CI,1.73%-11.07%), 0.77% (95% CI, .00%-2.36%), and 1.01% (95% CI, .00%-2.93%), respectively. Only 0.86% of patients had an HZ-related hospitalization. The case-fatality rate was 0.04%. Recurrence rate was 10.96/1000 person-years (95% CI, 10.18-11.79) with 10-year recurrence risk of 10.26% (95% CI, 9.36%-11.23%). CONCLUSIONS: These recent HZ epidemiology data among an immunocompetent, unvaccinated population measure real-world disease burden.

Clinical spectrum and prognosis of neurological complications of reactivated varicella-zoster infection: the role of immunosuppression.

Immunosuppressed patients are at higher risk for developing herpes zoster (HZ), and neurological complications are frequent in them. However, the influence of immunosuppression (IS) on the severity and prognosis of neurological complications of varicella-zoster virus (VZV) reactivation is unknown. We studied retrospectively patients with neurological complications due to VZV reactivation who attended our hospital between 2004 and 2019. We aimed to assess the clinical spectrum, potential prognostic factors, and the influence of the immune status on the severity of neurological symptoms. A total of 98 patients were included (40% had IS). Fifty-five patients (56%) had cranial neuropathies which included Ramsay-Hunt syndrome (36 patients) and cranial multineuritis (23 patients). Twenty-one patients developed encephalitis (21%). Other diagnosis included radiculopathies, meningitis, vasculitis, or myelitis (15, 10, 6, and 4 patients, respectively). Mortality was low (3%). At follow-up, 24% of patients had persistent symptoms although these were usually mild. IS was associated with severity (defined as a modified Rankin scale greater than 2) (odds ratio, 4.23; 95% confidence interval, 1.74-10.27), but not with prognosis. Shorter latency between HZ and neurologic symptoms was the only factor associated with an unfavorable course (death or sequelae) (odds ratio, 0.82; 95% confidence interval, 0.71-0.95). In conclusion, the clinical spectrum of neurological complications in VZV reactivation is wide. Mortality was low and sequelae were mild. The presence of IS may play a role on the severity of neurological symptoms, and a shorter time between HZ and the onset of neurological symptoms appears to be a negative prognostic factor.

Severe Herpes Zoster Requiring Intravenous Antiviral Treatment in Allogeneic Hematopoietic Cell Transplantation Recipients on Standard Acyclovir Prophylaxis.

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out of 2163 patients who underwent allogeneic HCT, 22 (1.0%) developed severe HZ at a rate of 1 per 228 person-years, including dermatomal/multidermatomal disease (n = 5), disseminated skin disease (n = 5), HZ ophthalmicus (n = 4), meningitis/encephalitis (n = 4), pneumonia (n = 2), viremia (n = 1), and erythema multiforme (n = 1). Severe HZ infection occurred in a bimodal distribution during the early peri-HCT period and at 12 to 24 months post-HCT (median, 12.7 months). Twelve patients (54.5%) were compliant with ACV prophylaxis at the time of HZ diagnosis. Eleven patients (50%) died during the study period, only 2 of whom (9.1%) with active VZV infection. Mortality was higher in patients on immunosuppressive therapy (62.5% versus 16.7%; P = .045) and with concurrent graft-versus-host disease (75.0% versus 35.7%; P= .044). These data suggest that severe HZ remains an important consideration despite ACV prophylaxis.

Infectious causes and outcomes in patients presenting with cerebral spinal fluid pleocytosis.

To evaluate the infectious etiologies, clinical features, and outcomes of patients with CNS infections at a tertiary care center. Patients that present with a pleocytosis in the cerebral spinal fluid (CSF), defined as a CSF WBC count > 5 cells/mm3, from July 2015 to June 2016 at a tertiary care hospital were analyzed for this report. Data from patients with confirmed (n = 43) and presumed (n = 51) CNS infections were analyzed. CNS infection was the leading known cause of CSF pleocytosis (n = 43, 18% of all patients with a pleocytosis in the CSF), and HSV-2 was identified as the leading causative pathogen (n = 10) followed by varicella zoster virus (n = 5). Fifty-three percent of patients with a pleocytosis in the CSF did not receive a diagnosis. In the patients that did not receive a diagnosis, CNS infection was presumed to be the cause in 51 patients (21% of patients with CSF pleocytosis). The mean time to diagnosis for patients with confirmed CNS infection was 16 days, but time to diagnosis was highly variable depending on the causative pathogen. There was a significant overlap in CSF parameters and peripheral white blood cell counts in patients diagnosed with a viral, bacterial, or fungal infection. Neuroimaging changes were present in only 44% of CNS infections. The overall mortality was 7% for CNS infections, and 17% of patients with a CNS infection had a severe neurologic deficit at presentation while only 3% had a severe deficit at the last neurologic assessment. This study provides new insights into the infectious causes of disease in a cohort of patients with pleocytosis in the CSF. The study provides new insights into the time to diagnosis and outcomes in patients that present with pleocytosis in the CSF.

The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey.

Infections represent a major cause of morbidity and mortality in multiple myeloma and are linked to both therapy- and disease-related factors. Although it has been suggested that the rate of infections increased since the introduction of novel agents, controversies still exist. To better assess the risk factors associated with infections in the era of novel agents, we conducted a large retrospective analysis of 479 myeloma patients treated at Jena University Hospital over a period of 12 years. During their disease history, 65% of patients developed at least one infection, and 37% of therapies were associated with at least one infectious episode. The rate of infections was constant over the years, with no increase in infectious complications after the routine implementation of novel agents. Infections were mainly bacterial and strongly associated with high disease burden, relapsed disease, and treatment with high-dose chemotherapy. Varicella zoster virus (VZV) reactivations occurred late during treatment (median time between high-dose chemotherapy and VZV reactivation 6 months, range 0-44 months), and fewer patients developed a VZV reactivation after 2009 (p = 0.001). Infections are still one of the major causes of morbidity in myeloma patients, and prophylactic measures are urgently needed to reduce this potentially lethal complication.

Hospitalizations realted to herpes zoster infection in the Canary Islands, Spain (2005-2014).

BACKGROUND: Herpes zoster is an important problem of public health especially among the elderly in Spain. METHODS: A population-based retrospective epidemiological study to estimate the burden of herpes zoster requiring hospitalization in the Canary Islands, Spain was conducted by using data from the national surveillance system for hospital data, Conjunto Mínimo Básico de Datos. Records of all patients admitted to hospital with a diagnosis of herpes zoster in any position and cases of primary diagnosis (ICD-9-MC codes 053.0-053.9) during a 10-year period (2005-2014), were selected. RESULTS: A total of 1088 hospitalizations with a primary or secondary diagnosis of herpes zoster were identified during the study period. Annually there were 6.99 hospitalizations by herpes zoster per 100,000 population. It increases with age reaching a maximum in persons ≥85 years of age (43.98 admissions per 100,000). Average length of hospitalization was 16 days and 73 patients died, with a case-fatality rate of 4.03%. In 22% of the cases hospitalized, herpes zoster was the primary diagnosis. CONCLUSION: The hospitalization burden of herpes zoster in adults in the Canary Islands was still important during the last decade and justify the implementation of preventive measures, like vaccination in the elderly or other high risk groups to reduce the most severe cases of the disease.

Hospital-based herpes zoster diagnoses in Denmark: rate, patient characteristics, and all-cause mortality.

BACKGROUND: Herpes zoster (HZ) may result in severe complications requiring hospital treatment, particularly in patients with comorbidity. Nevertheless, data on HZ from nationwide population-based hospital registries are sparse. METHODS: We conducted a cohort study describing first-time hospital-based (inpatient, outpatient, and emergency room) HZ diagnoses in the Danish National Patient Registry, 1994-2012. We computed the diagnosis rate; prevalence of demographic characteristics, comorbidities, and complications; length of hospital stay; and standardized mortality ratios (SMRs) using the Danish population as reference. We classified comorbidity using the Charlson Comorbidity Index (CCI) scoring system and categorized patients in groups of no (score 0), moderate (score 1), severe (score 2), and very severe comorbidity (score ≥3). In addition, we computed the prevalence of certain conditions associated with immune dysregulation (stem cell or bone marrow transplantation, solid organ transplantation, HIV infection, primary immunodeficiency, any cancer, and autoimmune diseases). RESULTS: The diagnosis rate increased almost exponentially from 6 to 91.9 per 100,000 person-years between age 50 and ≥90 years. The age-standardized rate was stable throughout the study period. The median length of hospital stay was 4 days (interquartile range: 1-8 days) for inpatients with HZ as the main reason for admission. According to the CCI, 44.3 % of patients had no comorbidity, 17.3 % moderate comorbidity, 17.4 % severe comorbidity, and 21.0 % very severe comorbidity. Comorbidities involving immune dysregulation, such as malignant (21 %) and autoimmune diseases (17 %), were particularly prevalent. Thirty percent had neurological, ophthalmic, or other complications. HZ was associated with increased all-cause mortality overall (SMR 1.8, 95 % CI: 1.7-1.8), but not in analyses restricted to patients without comorbidity (SMR 1.0, 95 % CI: 0.9-1.0). CONCLUSIONS: This study provides estimates of the epidemiology of hospital-based (severe) HZ. The diagnosis rate increased substantially with age. Complications and comorbidities were prevalent, likely resulting in increased mortality.

Incidence and case-fatality of varicella-zoster virus infection among pediatric cancer patients in developing countries.

UNLABELLED: Limited evidence is available about varicella-zoster virus (VZV) infection among pediatric cancer patients in developing countries, which raises questions about the generalizability of VZV vaccine recommendations for pediatric cancer patients (derived from developed countries) to these settings. We assessed the incidence and case-fatality of VZV infection at three institutions in developing countries (Argentina, Mexico, and Nicaragua). Individuals eligible for our study were aged <20 years and actively receiving cancer-directed therapy. We estimated a summary incidence rate (IR) and case-fatality risk with corresponding 95 % confidence limits (CL) of VZV infection across sites using random-effects models. Our study population comprised 511 pediatric cancer patients, of whom 64 % were aged <10 years, 58 % were male, and 58 % were diagnosed with leukemia. We observed a total of 10 infections during 44,401 person-days of follow-up across the 3 sites (IR = 2.3, 95 % CL 1.2, 4.2). The summary case-fatality risk was 10 % (95 % CL 1.4, 47 %) based on one death. CONCLUSION: Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. VZV vaccine recommendations for pediatric cancer patients in developed countries may be generalizable to developing countries. WHAT IS KNOWN: • Current recommendations, based on evidence from pediatric cancer patients in developed countries, contraindicate varicella-zoster virus (VZV) vaccination until completion of cancer-directed therapy and recovery of immune function. • The generalizability of these VZV vaccine recommendations to pediatric cancer patients in developing countries is unknown because of limited information about the incidence and case-fatality of VZV in these settings. What is New: • Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. • VZV vaccine recommendations based on evidence from pediatric cancer patients in developed countries may be generalizable to pediatric cancer patients in developing countries.

Mortality in cancer patients previously diagnosed with herpes zoster in the hospital setting: a nationwide cohort study.

BACKGROUND: Herpes zoster (HZ) is associated with underlying immunodeficiency and may thereby predict mortality of subsequent cancer. METHODS: By using Danish nationwide medical databases, we identified all cancer patients with a prior hospital-based HZ diagnosis during 1982-2011 (n=2754) and a matched cancer cohort without prior HZ (n=26 243). We computed adjusted mortality rate ratios (aMRRs) associating prior HZ with mortality following cancer. RESULTS: Prior HZ was associated with decreased mortality within the year after cancer diagnosis (aMRR 0.87; 95% confidence interval (CI): 0.81-0.93), but not thereafter (aMRR 1.07; 95% CI: 0.99-1.15). However, prior HZ predicted increased mortality throughout the entire follow-up among patients aged <60 years (aMRR 1.39; 95% CI: 1.15-1.68) and those with disseminated HZ (aMRR 1.18; 95% CI: 1.01-1.37). The increased mortality rates were observed primarily for haematological and immune-related cancers. CONCLUSIONS: Overall, HZ was not a predictor of increased mortality following subsequent cancer.

Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection.

Adult patients with disseminated nontuberculous mycobacterial (dNTM) infections usually have severe immune system defects. Recently, several studies have shown that anti-IFN-γ autoantibodies may play an important role in the pathogenicity of dNTM infections. A considerable proportion of reported cases of anti-IFN-γ autoantibodies show either clinical or laboratory evidence of autoimmune disease. In the present study, we identified 19 formerly healthy adults who later developed dNTM infections, of whom 17 were further investigated immunologically. High-titer anti-IFN-γ autoantibodies capable of inhibiting IL-12 production in vitro were found in the plasma of all of these patients. In addition to dNTM infection, 35% and 71% of our patients also suffered from salmonellosis and herpes zoster, respectively. This observation suggests that IFN-γ may be crucial in controlling salmonella infection and reactivating latent varicella-zoster virus infection in humans. 2 HLA alleles, DRB1*16:02 DQB1*05:02 (odds ratio 8.68; 95% confidence interval, 3.47-21.90; P = 1.1 × 10(-6); Pc = 3.08 × 10(-5) and odds ratio 7.16; 95% confidence interval, 3.02-17.05; P = 1 × 10(-7); Pc = 1.4 × 10(-6), respectively), were found in 82% (14 of 17) of our patients. In conclusion, our data suggest that anti-IFN-γ autoantibodies may play a critical role in the pathogenesis of dNTM infections and reactivation of latent varicella-zoster virus infection and are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02.

A nationwide population-based cohort study to identify the correlation between heart failure and the subsequent risk of herpes zoster.

BACKGROUND: The association between heart failure (HF) and herpes zoster has rarely been studied. We investigated the hypothesis that HF may increase the risk of herpes zoster in Taiwan using a nationwide Taiwanese population-based claims database. METHOD: Our study cohort consisted of patients who received a diagnosis of HF in 2001 ~ 2009 (N = 4785). For a comparison cohort, three age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 14,355). All subjects were tracked for 1 year from the date of cohort entry to identify whether or not they had developed herpes zoster. Cox proportional-hazard regressions were performed to evaluate 1-year herpes zoster-free survival rates. RESULTS: The main finding of this study was that patients with HF seemed to be at an increased risk of developing herpes zoster. Of the total patients, 211 patients developed herpes zoster during the 1-year follow-up period, among whom 83 were HF patients and 128 were in the comparison cohort. The adjusted hazard ratio (AHR) of herpes zoster in patients with HF was higher (AHR: 2.07; 95% confidence interval (CI): 1.54 ~ 2.78; p < 0.001) than that of the controls during the 1-year follow-up. Our study also investigated whether HF is a gender-dependent risk factor for herpes zoster. We found that male patients with HF had an increased risk of developing herpes zoster (AHR: 2.30 95% CI: 1.51 ~ 3.50; p < 0.001). CONCLUSIONS: The findings of our population-based study suggest that patients with HF may have an increased risk of herpes zoster. These health associations should be taken into consideration, and further studies should focused on the cost-effectiveness of the herpes zoster vaccine should be designed for HF patients.

Herpes zoster-associated mortality in Europe: a systematic review.

BACKGROUND: Reactivation of latent varicella zoster virus, partly due to age-related immunosenescence and immunosuppressive conditions, results in herpes zoster (HZ) and its associated complications. The management of the most important complication, post-herpetic neuralgia (PHN), is challenging, particularly in the elderly, and is generally unsatisfactory. No previous reviews have reported the incidence of HZ-associated mortality. METHODS: We carried out a systematic literature review to identify studies and databases providing data for HZ-associated mortality in adults aged ≥ 50 years in Europe. RESULTS: We identified 12 studies: Belgium (1); France (1); Germany (1); the Netherlands (2); Portugal (1); Spain (4) and England/Wales (2) and 4 databases from Europe: France; Germany and England/Wales. The incidence was available from eight studies; it was highest in those aged ≥ 95 in France (19.48/100,000). In the European (WHO) database, the overall mortality ranged from 0 to > 0.07/100,000. The age- and gender-specific HZ mortality rates from the other databases showed that while in younger age groups the HZ mortality rate was higher in males, in older patients the rate was much higher in women. The case fatality rate was 2 and 61/100,000 in those 45-65 and ≥ 65 years, respectively. A similar increase with age was seen for the hospital fatality rate; 0.6% in those 45-65 years in the UK and 7.1% in those ≥ 80 in Spain. CONCLUSIONS: Although the data were sparse and heterogeneous, HZ-associated mortality clearly increases with age. In addition, the elderly who develop HZ often have underlying diseases and are at increased risk of functional decline and loss of independence. Mortality should be taken into account in health-economics models.

The risk of a subsequent cancer diagnosis after herpes zoster infection: primary care database study.

BACKGROUND: Herpes zoster and cancer are associated with immunosuppression. Zoster occurs more often in patients with an established cancer diagnosis. Current evidence suggests some risk of cancer after zoster but is inconclusive. We aimed to assess the risk of cancer following zoster and the impact of prior zoster on cancer survival. METHODS: A primary care database retrospective cohort study was undertaken. Subjects with zoster were matched to patients without zoster. Risk of cancer following zoster was assessed by generating hazard ratios using Cox regression. Time to cancer was generated from the index date of zoster diagnosis. RESULTS: In total, 2054 cancers were identified in 74,029 patients (13,428 zoster, 60,601 matches). The hazard ratio for cancer diagnosis after zoster was 2.42 (95% confidence interval 2.21, 2.66) and the median time to cancer diagnosis was 815 days. Hazard ratios varied between cancers, and were highest in younger patients. There were more cancers in patients with zoster than those without for all age groups and both genders. Prior immunosuppression was not associated with change in risk, and diagnosis of zoster before cancer did not affect survival. CONCLUSION: This study establishes an association between zoster and future diagnosis of cancer having implications for cancer case finding after zoster diagnosis.

Disease burden of herpes zoster in Sweden--predominance in the elderly and in women - a register based study.

BACKGROUND: The herpes zoster burden of disease in Sweden is not well investigated. There is no Swedish immunization program to prevent varicella zoster virus infections. A vaccine against herpes zoster and its complications is now available. The aim of this study was to estimate the herpes zoster burden of disease and to establish a pre-vaccination baseline of the minimum incidence of herpes zoster. METHODS: Data were collected from the Swedish National Health Data Registers including the Patient Register, the Pharmacy Register, and the Cause of Death Register. The herpes zoster burden of disease in Sweden was estimated by analyzing the overall, and age and gender differences in the antiviral prescriptions, hospitalizations and complications during 2006-2010 and mortality during 2006-2009. RESULTS: Annually, 270 per 100,000 persons received antiviral treatment for herpes zoster, and the prescription rate increased with age. It was approximately 50% higher in females than in males in the age 50+ population (rate ratio 1.39; 95% CI, 1.22 to 1.58). The overall hospitalization rate for herpes zoster was 6.9/100,000 with an approximately three-fold increase for patients over 80 years of age compared to the age 70-79 group. A gender difference in hospitalization rates was observed: 8.1/100,000 in females and 5.6/100,000 in males. Herpes zoster, with a registered complication, was found in about one third of the hospitalized patients and the most common complications involved the peripheral and central nervous systems. Death due to herpes zoster was a rare event. CONCLUSIONS: The results of this study demonstrate the significant burden of herpes zoster disease in the pre-zoster vaccination era. A strong correlation with age in the herpes zoster- related incidence, hospitalization, complications, and mortality rates was found. In addition, the study provides further evidence of the female predominance in herpes zoster disease.

Incidence and risk factors of herpes zoster among hiv-positive patients in the german competence network for HIV/AIDS (KompNet): a cohort study analysis.

BACKGROUND: HIV infection is a risk factor for the development of Herpes zoster (HZ) and its complications. Prior to antiretroviral therapy (ART), HZ incidence in HIV-infected individuals ranged from 2.9-5.1/100 person-years. There is limited evidence for the impact of ART on HZ occurrence among HIV-infected adults. We analysed the incidence of, and risk factors for, HZ in a large cohort of German HIV-positive patients. METHODS: The study population was taken from the German KompNet cohort, a nationwide multicenter HIV cohort study. The study population was defined by age (≥ 18 years), year of first positive HIV diagnosis, CD4 values ± 6 months from HIV diagnosis (t0), and month of HZ diagnosis. Incidences were estimated using a Poisson distribution, and uni- and multivariate Cox proportional Hazard ratio (HR) regression models were fitted to identify risk factors for developing an initial HZ episode. Independent variables were sex, age at HIV diagnosis, route of HIV transmission, ART status, CD4 count before HZ episode, immunosuppressive medication, and mode of data documentation (retrospective or prospective). RESULTS: HZ incidence in the overall study population was 1.2/100 person-years. In a subset of patients for that we were able to examine risk factors the following was observed: We examined 3,757 individuals whose mean age at t0 was 38 years. Of those individuals, 96% were diagnosed with HIV in 1996 or later, with a mean observation time of 5.8 years. HZ episodes (n = 362) were recorded in 326 patients (8.7%), resulting in annual HZ incidences of 1.7/100 person-years overall, and 1.6/100 person-years for initial HZ cases. The main risk factors associated with an initial HZ episode were: not partaking in ART compared with an ART regimen containing a non-nucleoside reverse-transcriptase inhibitor (HR 0.530, p < 0.001) or a protease inhibitor (HR 0.624, p = 0.004); and lower CD4 count by 100 cells/µl (HR 0.918, p=0.001). CONCLUSIONS: HZ incidence was 4-11-fold higher than in non HIV-infected individuals, but in our study HZ incidences were lower than in previous studies relating to HIV-positive patients. We showed that ART is an important protective factor for HZ episodes.

Herpes zoster-related deaths in the United States: validity of death certificates and mortality rates, 1979-2007.

BACKGROUND: Herpes zoster (HZ) vaccine was recommended in the United States to reduce HZ-associated morbidity. Vaccination may reduce HZ-associated mortality, but no strategy exists to monitor mortality trends. METHODS: We validated HZ coding on death certificates from California, using hospital records as the gold standard, and applied the results to national-level data to estimate HZ mortality. RESULTS: In the validation phase of the study, among 40 available hospital records listing HZ as the underlying cause of death, HZ was the underlying cause for 21 (52.5%) and a contributing cause for 5 (12.5%). Among the 21 hospital records listing HZ as the underlying cause of death, the median age of decedents was 84 years (range, 50-99); 60% had no contraindications for HZ vaccination. Of the 37 available records listing HZ as a contributing cause of death, HZ was a contributing cause for 2 (5.4%) and the underlying cause for 6 (16.2%). Nationally, in the 7 years preceding the HZ vaccination program, the average annual number of deaths in which HZ was reported as the underlying cause of death was 149; however, based on our validation study, we estimate the true number was 78 (range, 31-118). CONCLUSIONS: National death certificate data greatly overestimate deaths in which HZ is the underlying or contributing cause of death. The HZ vaccination program could prevent some HZ-related deaths, but the impact will be difficult to assess using national mortality data.

The health and economic burden of chickenpox and herpes zoster in Belgium.

Varicella-zoster virus causes chickenpox (CP) and after reactivation herpes zoster (HZ). Vaccines are available against both diseases warranting an assessment of the pre-vaccination burden of disease. We collected data from relevant Belgian databases and performed five surveys of CP and HZ patients. The rates at which a general practitioner is visited at least once for CP and HZ are 346 and 378/100 000 person-years, respectively. The average CP and HZ hospitalization rates are 5·3 and 14·2/100 000 person-years respectively. The direct medical cost for HZ is about twice as large as the direct medical cost for CP. The quality-adjusted life years lost for ambulatory CP patients consulting a physician is more than double that of those not consulting a physician (0·010 vs. 0·004). In conclusion, both diseases cause a substantial burden in Belgium.

Herpes zoster in Germany: quantifying the burden of disease.

BACKGROUND: Herpes zoster (HZ) is caused by a reactivation of the varicella-zoster-virus (VZV) and mainly affects individuals aged≥50 years. Vaccines have been licensed or are under development that can protect against HZ and its main complication postherpetic neuralgia (PHN). In Germany, the burden of disease caused by HZ is not well known. To support the decision making process related to a potential vaccination recommendation, we estimated annual HZ disease burden in people aged≥50 years in Germany by utilizing various data sources. METHODS: We assessed for 2007 and 2008 HZ-outpatient incidence (number of cases per 1,000 person-years, PY) by utilizing the Association of Statutory Health Insurance Physicians (ASHIP) database, which contains nationwide routine outpatient data. For the same time period annual number of HZ-inpatients and HZ-associated deaths were identified by using the Federal Health Monitoring System (FHM). PHN-incidence and loss of quality-adjusted life years (QALYs) caused by HZ were calculated by multiplying number of identified HZ-patients with upper and lower limit estimates for proportion of HZ-cases developing PHN and HZ-related QALY, respectively. RESULTS: For the study period we identified an annual average of 306,511 HZ-outpatients aged 50+, resulting in a HZ-incidence of 9.6/1,000 PY. A total 14,249 HZ-associated inpatients and 66 deaths were reported in both years on average. HZ-incidence increased by age from 6.21 in people 50-54 years to 13.19 per 1,000 PY in people aged≥90 years. Females were significantly more frequently affected than males in terms of outpatient HZ-incidence (11.12 vs. 7.8 per 1,000 PY), inpatient HZ-incidence (0.51 vs. 0.38 per 1,000 PY) and mortality (0.29 vs. 0.10 per 100,000 PY). PHN-incidence was estimated to range between 0.43 and 1.33 per 1,000 PY. Based on these figures, there were between 3,065 to 24,094 QALYs lost due to HZ in persons aged≥50 years in Germany per annum. CONCLUSION: Our study provides important baseline estimates for HZ-related disease burden in Germany. HZ poses a considerable burden on the health care system in Germany both in terms of outpatient and inpatient services. Follow-up assessments of HZ disease burden are needed to monitor the impact of VZV-vaccinations in Germany.

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

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

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