Vacunación frente al virus del herpes zóster / Vaccination against the herpes zoster virus

Objetivo: Revisar las últimas evidencias publicadas respecto a la vacuna utilizada en nuestro país frente al virus del herpes zóster, desglosadas por eficacia, eficiencia, efectividad y seguridad vacunal. Incluir las recomendaciones vacunales actuales. Diseño: Revisión secundaria. Revisión cualitativa descriptiva. Revisión con el término de búsqueda de «vacuna herpes zóster» y «vacuna recombinante adyuvada de subunidades HZ/su». Estudio observacional retrospectivo. Fuentes de datos: Embase, Medline y Google Scholar. Selección de estudios: Criterio de búsqueda con los términos «Shingrix vaccine» y «Adjuvanted Herpes Zoster Subunit Vaccine». Periodo de búsqueda 2013-2023. Se seleccionaron los estudios tipificados como ensayos clínicos o ensayos clínicos randomizados. Se evaluaron 21 estudios publicados. No hubo exclusiones. Resultados: Los estudios evaluados se mostraron coherentes y en todos ellos la eficacia en personas adultas tanto para prevenir la reactivación viral como para evitar complicaciones estuvo por encima del 80%. La efectividad vacunal con 2 dosis también se mostró estar por encima del 80%. Los estudios coste/efectividad fueron siempre favorables en personas adultas, pacientes inmunodeprimidos y personas con enfermedad crónica. La seguridad de la vacuna fue evaluada en los estudios pivotales y en los estudios poscomercialización realizados (aún escasos por el corto periodo de tiempo estudiado). El perfil de seguridad de la vacuna es muy alto, y en el caso de los efectos adversos graves su frecuencia fue similar a placebo. Conclusiones: Disponemos de una vacuna efectiva y segura frente al virus del herpes zóster, que nos permite proteger a los grupos de población más vulnerables frente al virus.(AU)

Objective: To review the latest published evidence on the vaccine used in our country against the herpes zoster virus, breaking down the results according to the efficacy, efficiency, effectiveness and safety of the vaccine. Include the current recommendations for vaccination. Design: Secondary review. Descriptive qualitative review. Review using the search term “herpes zoster vaccine” and “Adjuvanted recombinant Herpes Zoster subunit vaccine”. Retrospective observational study. Data sources: Embase, Medline and Google Scholar. Selection of studies Search criterion with the terms “Shingrix vaccine” and “Adjuvanted Herpes Zoster Subunit Vaccine”. Search period 2013-2023. Studies classified as clinical trials or randomized clinical trials were selected. 21 published studies were evaluated. There were no exclusions. Results: The evaluated studies were found to be coherent and in all of them efficacy in adult individuals in preventing viral reactivation and in preventing complications was higher than 80%. The effectiveness of the vaccine after two doses was also higher than 80%. Cost-effectiveness studies were always favourable in adults, immunodepressed patients and individuals with chronic pathology. The safety of the vaccine was evaluated in the pivotal studies and in the post-commercialization studies that were undertaken (although there were few of the latter due to the short period of time studied). The safety profile of the vaccine is very high and in the case of severe adverse effects, their frequency was similar to that of a placebo. Conclusions: We have a safe and effective vaccine against the herpes zoster virus that allows us to protect the most vulnerable population groups against this virus.(AU)

Clinical and economic impact of universal varicella vaccination in Norway: A modeling study.

BACKGROUND: Norway has not implemented universal varicella vaccination, despite the considerable clinical and economic burden of varicella disease. METHODS: An existing dynamic transmission model of varicella infection was calibrated to age-specific seroprevalence rates in Norway. Six two-dose vaccination strategies were considered, consisting of combinations of two formulations each of a monovalent varicella vaccine (Varivax® or Varilrix®) and a quadrivalent vaccine against measles-mumps-rubella-varicella (ProQuad® or PriorixTetra®), with the first dose given with a monovalent vaccine at age 15 months, and the second dose with either a monovalent or quadrivalent vaccine at either 18 months, 7 or 11 years. Costs were considered from the perspectives of both the health care system and society. Quality-adjusted life-years saved and incremental cost-effectiveness ratios relative to no vaccination were calculated. A one-way sensitivity analysis was conducted to assess the impact of vaccine efficacy, price, the costs of a lost workday and of inpatient and outpatient care, vaccination coverage, and discount rate. RESULTS: In the absence of varicella vaccination, the annual incidence of natural varicella is estimated to be 1,359 per 100,000 population, and the cumulative numbers of varicella outpatient cases, hospitalizations, and deaths over 50 years are projected to be 1.81 million, 10,161, and 61, respectively. Universal varicella vaccination is projected to reduce the natural varicella incidence rate to 48-59 per 100,000 population, depending on the vaccination strategy, and to reduce varicella outpatient cases, hospitalizations, and deaths by 75-85%, 67-79%, and 75-79%, respectively. All strategies were cost-saving, with the most cost-saving as two doses of Varivax® at 15 months and 7 years (payer perspective) and two doses of Varivax® at 15 months and 18 months (societal perspective). CONCLUSIONS: All modeled two-dose varicella vaccination strategies are projected to lead to substantial reductions in varicella disease and to be cost saving compared to no vaccination in Norway.

[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.

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.

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.

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.

Severe infections in systemic lupus erythematosus: disease pattern and predictors of infection-related mortality.

Infection is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). To describe the pattern of serious infections in patients with SLE and to identify the predictors of infection-related mortality among SLE patients with serious infections, we prospectively studied all SLE patients who were hospitalized with infections in Sarawak General Hospital during 2011-2015. Demographic data, clinical features, and outcomes were collected. Cox regression analysis was carried out to determine the independent predictors of infection-related mortality. There were a total of 125 patients with 187 episodes of serious infections. Our patients were of multiethnic origins with female predominance (89.6%). Their mean age was 33.4 ± 14.2 years. The patients had a mean disease duration of 66.8 ± 74.0 months. The most common site of infection was pulmonary (37.9%), followed by septicemia (22.5%). Gram-negative organisms (38.2%) were the predominant isolates within the cohort. There were 21 deaths (11.2%) during the study period. Independent predictors of infection-related mortality among our cohort of SLE patients were flare of SLE (HR 3.98, CI 1.30-12.21) and the presence of bacteremia (HR 2.54, CI 0.98-6.59). Hydroxychloroquine was protective of mortality from serious infections (HR 9.26, CI 3.40-25.64). Pneumonia and Gram-negative organisms were the predominant pattern of infection in our SLE cohort. The presence of flare of SLE and bacteremia were independent prognostic predictors of infection-related mortality, whereas hydroxychloroquine was protective of infection-related mortality among SLE patients with serious infections.

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.

Significant Associations of Neurological Complications of Herpes Zoster With Stroke in Rheumatoid Arthritis Patients.

BACKGROUND: Accumulating evidence suggests an increased risk of stroke after herpes zoster (HZ). This risk is elevated in immunocompromised patients. The incidence of HZ in Asia is higher than in Western countries. However, the epidemiology of HZ and HZ-related stroke among rheumatoid arthritis (RA) patients in Asia remains unclear. METHODS AND RESULTS: We conducted a retrospective cohort study using a population-based database to investigate the epidemiology of HZ in RA patients in Taiwan during the period of 2000-2011. A total of 27 609 newly diagnosed and eligible RA cases were identified, and 110 436 non-RA cases were matched for age and sex at a ratio of 4:1. HZ risk increased by 2.53-fold (P<0.0001) in RA patients compared with the general population. Exposure to corticosteroids (adjusted odds ratio=1.73, P<0.0001), adalimumab (adjusted odds ratio=1.61, P=0.002), and rituximab (adjusted odds ratio=2.06, P=0.008) was associated with an increased risk of HZ in RA patients. A significant association between the use of methotrexate or corticosteroids and HZ risk was dose-dependent (Ptrend<0.0001). Elevated risk of stroke was observed in RA patients with HZ (adjusted hazard ratio=1.27, P=0.047), particularly in those with neurological complications (adjusted hazard ratio=1.54, P=0.015). A 2.30-fold significantly increased risk of stroke within 90 days after HZ occurrence was observed in RA patients compared with those without HZ (P=0.02). Furthermore, death risk increased in RA patients with HZ (adjusted hazard ratio=1.18, P=0.026). CONCLUSIONS: The risk of HZ and HZ-related stroke has increased in RA patients. Monitoring the occurrence of HZ in RA patients and preventing HZ-related stroke or mortality during a specific immunosuppressive therapy are important.

Varicella zoster virus related deaths and hospitalizations before the introduction of universal vaccination with the tetraviral vaccine / Óbitos e internações relacionados ao vírus varicela-zoster antes da introdução da vacinação universal com a vacina tetravalente

Abstract Objective: To characterize varicella zoster virus-related deaths and hospitalizations in Brazil before universal vaccination with the tetravalent (measles, mumps, rubella, and varicella) vaccine, attempting to collect baseline data on varicella morbidity and mortality in order to evaluate the impact of the varicella vaccination program. Methods: Varicella-associated mortality data were evaluated between 1996 and 2011 and varicella zoster virus-associated hospitalizations between 1998 and 2013. Data were gathered from the Informatics Department of the Unified Health System, considering the International Classification of Diseases, 10th Revision, code B01. All age groups were assessed. Varicella-specific mortality rates were calculated and seasonality of varicella-zoster virus-associated hospitalizations was described. Results: There were 2334 varicella deaths between 1996 and 2011, 19.3% in infants aged less than 1 year and 36% in children from 1 to 4 years. In infants under 1 year, varicella mortality rates reached 3.2/100,000/year. In children aged 1–4 years, varicella mortality rates reach 1.64/100,000/year. Average annual mortality rates for varicella in Brazil are 0.88/100,000 in infants under 1 year and 0.40/100,000 in children aged 1–4 years. The total number of hospitalizations associated with varicella zoster virus was 62,246 from 2008 to 2013. Varicella-associated hospitalizations have a seasonal distribution in children, peaking in November. In the elderly, monthly averages of herpes zoster-associated hospitalizations present no significant seasonal variation. Conclusions: Varicella is associated, in the pre-vaccine period, to significant morbidity and mortality in Brazil. The universal vaccination program is expected to decrease the disease burden from varicella.

Resumo Objetivo: Caracterizar os óbitos e internações relacionados ao vírus varicela-zoster no Brasil antes da vacinação universal com a vacina tetravalente (sarampo, caxumba, rubéola e varicela), tentando coletar dados de referência sobre a morbidez e mortalidade por varicela, para avaliar o impacto do programa de vacinação contra a varicela. Métodos: Os dados de mortalidade associada à varicela foram avaliados entre 1996 e 2011 e as internações associadas ao vírus varicela-zoster, entre 1998 e 2013. Os dados foram coletados do Departamento de Informática do Sistema Unificado de Saúde, considerando a Classificação Internacional de Doenças, 10ª Revisão, código B01. Todas as faixas etárias foram avaliadas. Foram calculadas as taxas de mortalidade específicas por varicela e foi descrita a sazonalidade das internações associadas ao vírus varicela-zoster. Resultados: Houve 2.334 óbitos por varicela entre 1996 e 2011, 19,3% em neonatos com menos de 1 ano e 36% em crianças de 1 a 4 anos. Em neonatos com menos de 1 ano, as taxas de mortalidade por varicela atingiram 3,2/100.000/ano. Em crianças de 1–4 anos de idade, as taxas de mortalidade por varicela atingem 1,64/100.000/ano. As taxas de mortalidade anuais médias por varicela no Brasil são de 0,88/100.000 em neonatos com menos de 1 ano de idade e 0,40/100.000 em crianças de 1 a 4 anos de idade. O número total de internações associadas ao vírus varicela-zoster foi de 62.246 de 2008 a 2013. As internações relacionadas à varicela apresentaram distribuição sazonal em crianças, com pico em novembro. Em idosos, as médias mensais de internações associadas ao herpes zoster não apresentam variação sazonal significativa. Conclusões: A varicela está associada a morbidez e mortalidade significativas no período pré-vacinação no Brasil. O programa de vacinação universal deve diminuir a carga de doença da varicela.

The burden of hospitalisation for varicella and herpes zoster in England from 2004 to 2013.

OBJECTIVES: We aimed to determine the hospital burden of varicella-zoster virus infection (VZV) in England during 2004-2013 to support a future cost-effectiveness analysis of a childhood varicella vaccination programme. METHODS: We analysed the incidence, duration, outcome and costs of hospitalisations for VZV using the Hospital Episode Statistics (HES) database for the general and immunocompetent population. Mortality in HES was validated using data from the Office for National Statistics (ONS). RESULTS: The average annual incidences of admissions due to varicella and herpes zoster were 7.6 (7.3-7.9) and 8.8 (8.6-9.0) per 100,000, respectively. The immunocompetent population accounted for 93% and 82% of the admissions due to varicella and herpes zoster, respectively. The average yearly number of hospital days was 10,748 (10,227-11,234) for varicella and 41,780 (40,257-43,287) for herpes zoster. The average yearly hospital costs (£2013/14) were £6.8 million (6.4-7.2) for varicella and £13.0 million (12.8-13.4) for herpes zoster. The average annual numbers of deaths identified in HES due to varicella and herpes zoster were 18.5 (14.3-22.8) and 160 (147-172), respectively. Comparison with ONS mortality data indicated a high level of uncertainty. CONCLUSIONS: Most of the hospital burden due to VZV-virus in England occurs in the immunocompetent population and is potentially vaccine-preventable.

Varicella zoster virus-associated morbidity and mortality in Africa: a systematic review protocol.

INTRODUCTION: Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. METHODS AND ANALYSIS: Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. ETHICS AND DISSEMINATION: As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: CRD42015026144.

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.

Varicella zoster virus related deaths and hospitalizations before the introduction of universal vaccination with the tetraviral vaccine.

OBJECTIVE: To characterize varicella zoster virus-related deaths and hospitalizations in Brazil before universal vaccination with the tetravalent (measles, mumps, rubella, and varicella) vaccine, attempting to collect baseline data on varicella morbidity and mortality in order to evaluate the impact of the varicella vaccination program. METHODS: Varicella-associated mortality data were evaluated between 1996 and 2011 and varicella zoster virus-associated hospitalizations between 1998 and 2013. Data were gathered from the Informatics Department of the Unified Health System, considering the International Classification of Diseases, 10th Revision, code B01. All age groups were assessed. Varicella-specific mortality rates were calculated and seasonality of varicella-zoster virus-associated hospitalizations was described. RESULTS: There were 2334 varicella deaths between 1996 and 2011, 19.3% in infants aged less than 1 year and 36% in children from 1 to 4 years. In infants under 1 year, varicella mortality rates reached 3.2/100,000/year. In children aged 1-4 years, varicella mortality rates reach 1.64/100,000/year. Average annual mortality rates for varicella in Brazil are 0.88/100,000 in infants under 1 year and 0.40/100,000 in children aged 1-4 years. The total number of hospitalizations associated with varicella zoster virus was 62,246 from 2008 to 2013. Varicella-associated hospitalizations have a seasonal distribution in children, peaking in November. In the elderly, monthly averages of herpes zoster-associated hospitalizations present no significant seasonal variation. CONCLUSIONS: Varicella is associated, in the pre-vaccine period, to significant morbidity and mortality in Brazil. The universal vaccination program is expected to decrease the disease burden from varicella.

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.

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.