Skip to main content
Download PDF
  • Research article
  • Open access
  • Published:

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

BMC Infectious Diseases volume 16, Article number: 99 (2016) Cite this article

Abstract

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.

Peer Review reports

Background

Herpes zoster (HZ) is a neurocutaneous infection caused by reactivation of the varicella-zoster virus (human herpesvirus 3) from the sensory ganglia when cell-mediated immunity wanes below a critical level [1]. In a review of data from nine European countries, the overall incidence rate in the general population was approximately 100–400 per 100,000 person-years in adults aged 50 years or younger. Thereafter, it increased notably, reaching 1000 per 100,000 person-years after age 80 years [2]. The risk of HZ is increased in patients with cell-mediated immunodeficiency, including that caused by drugs (e.g., corticosteroids or chemotherapy), radiotherapy, viral infections (i.e., human immunodeficiency virus [HIV]), or malignancy.

HZ may have severe acute complications, such as meningo-encephalitis and cutaneous dissemination, in particular among individuals with the aforementioned predisposing conditions [3, 4]. These patients are more likely to be treated in the hospital or in hospital outpatient specialty clinics. When assessing the epidemiology of HZ, it is important also to consider these severe or potentially severe cases diagnosed in a hospital-based setting. Nevertheless, results from nationwide population-based hospital registries in Europe are sparse concerning the diagnosis rate and patient characteristics, including prevalence of complications and comorbidities. In particular, none of the previous population-based studies published data pertaining specifically to diagnoses from hospital outpatient specialty clinics. To address this paucity of data, we conducted a nationwide Danish cohort study describing HZ in a hospital-based setting, including diagnosis rate, patient demographics, severity, comorbidity burden, length of admission, and subsequent all-cause mortality.

Methods

The Danish National Health Service provides tax-funded universal health care to all residents (population 5.6 million), guaranteeing unfettered access to general practitioners and hospitals [5]. Utilization of health services is recorded in nationwide databases using the unique central personal register (CPR) number assigned to each Danish resident at birth or immigration [5]. The CPR number allowed for unambiguous individual-level linkage of the registries used in the current study.

The Danish National Patient Registry (DNPR) contains data on all admissions to Danish non-psychiatric departments since 1977 and visits to hospital-based outpatient clinics (i.e., ambulatory medical care) and emergency rooms since 1994 [6]. Each DNPR record contains the CPR number of the patient, dates of hospital admission and discharge or start and end of outpatient contact, information on procedures performed, and diagnoses. Each record includes a primary diagnosis, i.e., the condition considered the main reason for the hospital contact. Diagnoses are assigned by the discharging physician at the time of hospital discharge or at the end of an outpatient contact using the International Classification of Diseases, 8th revision (ICD-8) until the end of 1993 and 10th revision (ICD-10) thereafter [6]. Surgical procedures are coded by the surgeon according to a Danish classification system (1977 through 1995) and a Danish version of the Nordic Medico-Statistical Committee Classification of Surgical Procedures (from 1996 onwards). Since 2002, the DNPR has provided the basis for reimbursing both public and private hospitals. Reporting of all services provided in the private hospital sector became mandatory in 2003. General practitioners and private practice specialists do not report to the DNPR. Diagnosis codes and definitions used are provided in Additional file 1: Table S1.

We used the DNPR to identify all first-time inpatient, outpatient, and emergency room diagnoses of HZ. To ensure complete information on outpatient and emergency room diagnoses and to avoid potential problems associated with the transition between the ICD-8 and ICD-10 coding systems, we chose a study period from January 1, 1994 to December 31, 2012, when ICD-codes were used, exclusively. The date of discharge or end of outpatient contact was considered the diagnosis date. Based on patients’ first-ever HZ diagnosis recorded in the DNPR, we classified HZ diagnoses according to type of hospital-based contact (inpatient, outpatient clinic, or emergency room) and type of diagnosis (primary or secondary). We also identified individual ICD-10 codes for HZ. However, because of the clinical difficulty of distinguishing between HZ encephalitis and meningitis, we combined ICD-10 codes B02.0 and B02.1 in our analysis. Similarly, we grouped ICD-10 codes according to severity (complicated or uncomplicated) and extent (disseminated or localized), as shown in Additional file 1: Table S1. The difference between groups of complicated and disseminated HZ is attributed to codes for HZ ophthalmicus, which is regarded as a localized but complicated form.

To give an overview of reasons for healthcare contacts among patients with a secondary HZ diagnosis, we categorized the primary diagnosis according to a list of 203 morbidity groups based on the ICD-8 and ICD-10 World Health Organization morbidity tables. This code list has been published previously [7] and is outlined in detail in Additional file 1: Table S1. Additional codes outside this list comprised general and unspecific reasons for hospital contact. We grouped them into four categories (‘Symptoms, signs and abnormal clinical and laboratory findings not otherwise specified’, ‘Injury, poisoning and certain other consequences of external causes’, ‘Observation for or follow-up after treatment for cancer’, and ‘Contact with health services due to solid organ or bone marrow transplantation, and ‘Other factors influencing health status and contact with health services’). The HZ vaccine, which is approved by the European Medicines Agency for use in adults aged 50 years or older, did not become available in Denmark until September 2014, and hence not considered in the present study [8].

To quantify comorbidity, we obtained information on all primary, secondary, and additional diagnoses recorded in the DNPR before or on the same date as the HZ diagnosis. We classified comorbidity using the Charlson Comorbidity Index (CCI), a scoring system that assigns between one and six points to 19 groups of chronic diseases (Additional file 1: Table S1) according to their ability to predict death [9]. We obtained information on diagnoses in each disease group. Based on the total CCI score, we also categorized patients into levels of none (score 0), moderate (score 1), severe (score 2), and very severe (score 3 or more) comorbidity. We also obtained information on diagnosis history of conditions associated with immune dysregulation (i.e., stem cell or bone marrow transplantation, solid organ transplantation, HIV infection, primary immunodeficiency, any cancer, and autoimmune diseases) and thus potentially an increased HZ risk [1]. For the categories HIV infection, any cancer, and autoimmune diseases, there was an overlap with codes included in the CCI.

The Danish Civil Registration System (CRS) provides a record of changes in vital and migration status for the entire population since 1968 [5]. We used the CRS to follow HZ patients from diagnosis until the date of death, emigration, or December 31, 2012.

Statistical analysis

We computed the annual rate of hospital-based HZ diagnoses throughout the study period, with direct age standardization [10] to the 2000 Danish census. We characterized patients according to age, sex, comorbidities, calendar period of diagnosis (1994–1999, 2000–2005, and 2006–2012), and types of HZ diagnoses. For patients with an inpatient primary HZ diagnosis, we computed the median and total length of hospital stay.

We used the Kaplan-Meier estimator to compute absolute mortality risks. We computed standardized mortality ratios (SMRs) with 95 % confidence intervals (CIs) for HZ patients using indirect standardization [10], with the general Danish population as reference. The expected number of deaths was obtained by multiplying the number of person-years at risk in the HZ cohort with the rate of death in the general population according to 5-year age groups, sex, and calendar year. The SMR was computed as the ratio of the observed to the expected number of deaths. Corresponding 95 % CIs were computed assuming that the observed number of deaths followed a Poisson distribution. We performed analyses overall and in subgroups of demographic and patient characteristics.

Analyses were performed using STATA® (version 12.1, STATA, College Station, TX). The study was approved by the Danish Data Protection Agency (record number 1–16–02–1–08). Danish legislation does not require ethical review board approval or informed consent from subjects in registry-based studies.

Results

Hospital diagnosis rate

We identified 13,663 first-time hospital-based diagnoses of HZ in Denmark between 1994 and 2012, corresponding to a standardized HZ rate of 13.1 (95 % CI: 12.9–13.3) per 100,000 person-years (Table 1). The rate was stable throughout the study period, both overall (Fig. 1) and in subgroups defined by age and sex (Additional file 1: Figures S1 and S2).

Table 1 Diagnosis rates and median length of stay for hospital-based diagnoses of HZ, Denmark, 1994–2012
Full size table
Fig. 1
figure 1

Rates of first-time hospital-based diagnoses of herpes zoster, Denmark, 1994–2012, directly standardized to the age-distribution in the 2000 Danish Census

Full size image

The HZ rate varied markedly with age. The rate was 3–6 per 100,000 person-years for persons aged below 50 years after which it increased approximately twofold with each decade of age, reaching 91.1 per 100,000 person-years for those aged 90 years or older (Table 1). For all individuals aged 50 years or more (i.e., those potentially eligible for the HZ vaccine), the overall diagnosis rate was 30.1 per 100,000 person-years. The increase in rate with age was observed for all subtypes of HZ diagnoses, but was most pronounced for inpatient diagnoses (Fig. 2).

Fig. 2
figure 2

Age-specific rates of hospital-based diagnoses of herpes zoster according to diagnosis types, Denmark, 1994–2012

Full size image

The standardized diagnosis rate was slightly higher among women than men (13.6 vs. 12.5 per 100,000 person-years). This difference was primarily driven by a difference in rates for persons aged 50–89 years (Table 1).

Type of diagnosis, complications, and length of stay

Sixty percent of patients were diagnosed with HZ during a hospital admission, 25 % in an outpatient clinic, and 15 % in the emergency room (Table 2). The majority of diagnoses were primary (72 %). Reasons for hospital contact among patients with secondary HZ diagnoses are listed in Additional file 1: Table S2; the most frequent were the unspecific codes ‘other factors influencing health status and contact with health services’ (8.1 %) and ‘symptoms, signs, and abnormal clinical and laboratory findings’ (8.0 %), followed by ‘pneumonia’ (5.9 %), and ‘bronchitis, emphysema and other obstructive pulmonary diseases’ (4.8 %). In total, cancer was the primary diagnosis in 9.5 % of patients with a secondary HZ diagnosis.

Table 2 No. (%) of types of first-time hospital-based diagnoses of HZ, Denmark, 1994–2012
Full size table

Complicated HZ occurred among 30 % of patients, the most frequent being HZ ophthalmicus followed by nervous system involvement (Table 2). There was a slight increase in the incidence and proportion of patients with ‘HZ encephalitis’, ‘HZ meningitis’ and ‘HZ with other complication’ during the study period. Almost half of the outpatient HZ diagnoses were complicated (28 % were HZ ophthalmicus), compared with one-fourth of inpatient and emergency room diagnoses (Additional file 1: Table S3).

The median length of stay for inpatients with a primary HZ diagnosis was 4 days (interquartile range 1–8 days, mean 6.2 days), increasing with age (Table 1). On average, patients with primary inpatient HZ diagnoses had an annual total of 1634 inpatient days, of which 88 % were in patients aged 50 years or more. The longest stays were observed in patients with complicated HZ, especially HZ encephalitis (median 10 days, interquartile range 6–18 days, mean 15.5 days).

Comorbidity

A large proportion of persons with HZ had comorbidity. As measured by the CCI, 44 % had no comorbidity, 17 % had moderate comorbidity, 17 % had severe comorbidity, and 21 % had very severe comorbidity (Table 3). The most prevalent diagnoses were autoimmune diseases (17 %), chronic pulmonary disease (14 %), non-metastatic solid tumor (13 %), cerebrovascular disease (11 %), congestive heart failure (7.7 %), connective tissue disease (7.2 %), myocardial infarction (6.7 %), diabetes without end-organ damage (6.7 %), ulcer disease (6.2 %), and lymphoma (6.1 %). In total, 21 % had an active or previous cancer. Diseases possibly associated with immune dysregulation were recorded in 36 % of HZ patients. The prevalence of HIV infection was 1.5 %. Median age and comorbidity burden were highest in patients with inpatient and secondary HZ diagnoses (Additional file 1: Table S3).

Table 3 Characteristics of 13,663 patients with a first-time hospital-based diagnosis of HZ, Denmark, 1994–2012
Full size table

Mortality

The 30-day mortality for persons with HZ was 3 %, corresponding to 7 % (434/6059) of all deaths in the cohort in total. We observed higher mortality in patients with HZ compared with the general population (Table 4). The overall SMR was 1.8 (95 % CI: 1.7–1.8): 1.6 (95 % CI: 1.6–1.7) in women and 2.0 (95 % CI: 1.9–2.1) in men. The highest SMRs were found in young patients. However, after stratifying by comorbidity level, the SMR was not increased in patients without comorbidity (SMR 1.0; 95 % CI: 0.9–1.0). SMRs according to subtypes of HZ diagnoses are shown in Additional file 1: Table S4.

Table 4 SMRs among patients with a first-time hospital-based diagnosis of HZ, Denmark, 1994–2012
Full size table

Discussion

In this nationwide Danish study, the rate of hospital-based HZ diagnoses was stable at around 13 per 100,000 person-years over a study period of 19-years. The rate was 3–6 per 100,000 person-years for persons aged below 50 years, increasing by approximately twofold with each consecutive decade of age. Thirty percent of patients had complicated HZ and comorbidity was prevalent, particularly diseases involving immune dysregulation.

The age-specific hospitalization rates from the present study and previous European studies are shown in Additional file 1: Figure S3. While the overall and age-specific inpatient hospital diagnosis rates in Denmark accord with previous studies [11–24], however there is considerable variation across countries. This variation may result from differences in hospital admission practices or health-seeking behavior, as the overall incidence rate in the general population varies only slightly across Europe [2]. Nevertheless, the nearly exponential increase in the rate of hospital-based HZ diagnoses after age 50 years [11–18, 20–23] and the female predominance [12, 13, 16, 18, 19, 21] in our study are comparable with results from the previous studies. However, none of these studies presented data specifically on HZ diagnosed in hospital-based outpatient clinics, which accounted for one-fourth of patients in our study.

We observed a shorter length of hospital stay (mean 6.2 days) compared to previous studies (mean 7.5 to 11.2 days) [12, 13, 17–19, 22, 25, 26]. Our result was closest to that reported in a Swedish study [18], which also had a similar diagnosis rate and proportion of complicated infections. The shorter length of stay may be explained by hospitalization of milder cases of HZ in Denmark and Sweden, as the proportion of complicated infections (mainly ocular and neurological) was approximately twice as high in Southern Europe [12, 14, 19, 20, 25, 26]. Studies from Southern Europe also reported a higher prevalence of predisposing conditions, such as HIV [12, 14, 16, 20], organ transplantation [12, 16], diabetes [16], and ‘blood dyscrasias and some immune deficiencies’ [16] in HZ patients. Frequencies of malignancy [14, 16, 20] and connective tissue disease [16] were comparable to the results in our study. Finally, the length of stay for patients with neurological complications in our data accords with Italian and French data [19, 25, 26], further suggesting that differences in admission practices play a role. The slight temporal increase in the diagnosis rate of HZ encephalitis and meningitis in our study may result from increased use of polymerase chain reaction technology for detecting varicella-zoster virus in cerebrospinal fluid [27].

Chronic pulmonary disease, connective tissue disease, cancer, HIV, and solid organ transplantation were relatively more frequent in our study compared with other selected Danish patient populations [28–31]. This finding is consistent with the increased risk of HZ in patients with immune dysregulation due to either disease pathophysiology or treatment (e.g., with glucocorticoids) [1]. Apart from posing an additional burden to these patients, HZ could complicate their treatment, for instance by delaying chemotherapy for cancer. We lacked data on HZ treated in general practice and had no comparison cohort, which prevented us from examining whether HZ was associated with increased mortality in patients with certain comorbidities. Although we found increased mortality among patients with comorbidity, we obtained this result using standardization to the entire general population, including those without comorbidity. Thus, the increased SMRs may potentially reflect excess mortality from the comorbid condition rather than from an interaction between HZ and the comorbid condition. The difference in SMRs by age could also be explained by use of the general population as reference. A high prevalence of the exposure (HZ) in the general population would bias the SMR towards the null [32]. Because the prevalence of HZ increases with age, the risk of this bias also may increase with age, potentially explaining our finding of lower SMRs in the oldest age groups.

We used a comprehensive nationwide database to study hospital-based HZ diagnoses within a universal healthcare system, which limits selective inclusion of specific hospitals, insurance groups, or age groups. Nonetheless, our study has some limitations. Since 2002, reimbursements to public and private hospitals have been administered using the Diagnosis Related Group (DRG) system in the DNPR [6], which may have affected physicians’ choice of primary and secondary diagnosis codes. As well, the completeness and validity of HZ diagnoses in the DNPR is unknown. Still, other studies have found high diagnostic accuracy with positive predictive values ranging from 72 to 100 % [33–37]. Although there is a specific code for specifying consultation with post-herpetic neuralgia (ICD-10 G53.0), it is possible that some codes, particularly ‘other nervous system involvement’, were assigned alone to patients who had this chronic complication rather than acute HZ. However, we consider such misclassification of minor importance because these patients experienced recent varicella-zoster virus reactivation.

Our comorbidity assessment has some limitations. The positive predictive value for diagnoses included in the CCI are known to vary depending on the disease, department of origin, and reference standard [6]. Moreover, incompleteness is expected for conditions that are treated primarily in general practice, e.g., diabetes. Another concern is underestimation early in the study period due to left-censoring of outpatient and emergency room diagnoses before 1994. Similarly, changes in coding when new medical treatments are introduced may explain the lack of HZ patients with bone marrow transplantations early in the study period.

The majority of patients with HZ in Denmark are treated in general practices [38], which are not subject to systematic monitoring in national registries. Thus, analysis of temporal trends in our study may not reflect true changes in disease incidence in the population. Administrative factors (e.g., changing admission practices) are also important in determining whether patients receive a hospital-based diagnosis. As well, the lack of primary care data may have caused underestimation of the SMRs [32].

Conclusions

This nationwide Danish study provided pre-vaccination estimates of the epidemiology of hospital-based HZ. Because hospital-based treatment is likely linked to presence of complications or underlying diseases, our study likely comprises the most severe cases of HZ. Indeed, 30 % of patients had complicated HZ and diseases associated with increased risk of severe HZ (e.g., hematological cancer [3, 4]) were prevalent. These results stress the importance of considering hospital-based diagnoses in studies assessing the overall burden of HZ in the population.

Availability of data and materials

No additional data are available. According to the Danish Act on Processing of Personal Data, private and public institutions may obtain the health data used in the current study, after obtaining the necessary project-specific approvals.

Abbreviations

CI:

confidence interval

CPR:

central personal register

DNPR:

Danish National Patient Registry

ICD:

International Classification of Diseases

HIV:

human immunodeficiency virus

HZ:

herpes zoster

SMR:

standardized mortality ratio

References

  1. Wilson JF. Herpes zoster. Ann Intern Med. 2011;154(5):ITC31–15.

    Article  PubMed  Google Scholar 

  2. Pinchinat S, Cebrián-Cuenca AM, Bricout H, Johnson RW. Similar herpes zoster incidence across Europe: results from a systematic literature review. BMC Infect Dis. 2013;13:170.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Habel LA, Ray GT, Silverberg MJ, Horberg MA, Yawn BP, Castillo AL, et al. The epidemiology of herpes zoster in patients with newly diagnosed cancer. Cancer Epidemiol Biomarkers Prev. 2013;22(1):82–90.

    Article  PubMed  Google Scholar 

  4. Tran TN, Ray GT, Horberg MA, Yawn BP, Castillo AL, Saddier P, et al. Complications of herpes zoster in cancer patients. Scand J Infect Dis. 2014;46(7):528–32.

    Article  PubMed  Google Scholar 

  5. Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541–9.

    Article  PubMed  Google Scholar 

  6. Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449–90.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ording AG, Garne JP, Nyström PMW, Cronin-Fenton D, Tarp M, Sørensen HT, et al. Hospital recorded morbidity and breast cancer incidence: a nationwide population-based case–control study. PLoS One. 2012;7(10):e47329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rasmussen JG. Vaccine reaches Denmark with an 8-year delay. Dagens medicin [Internet]. [cited 2015 Feb 18]. Available from: Available from: http://www.dagensmedicin.dk/nyheder/vaccine-nar-til-danmark-med-otte-ar-forsinkelse/.

  9. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.

    Article  CAS  PubMed  Google Scholar 

  10. Curtin LR, Klein RJ. Direct standardization (age-adjusted death rates). Healthy People 2000 Stat Notes. 1995;6:1–10.

    PubMed  Google Scholar 

  11. Bilcke J, Ogunjimi B, Marais C, de Smet F, Callens M, Callaert K, et al. The health and economic burden of chickenpox and herpes zoster in Belgium. Epidemiol Infect. 2012;140(11):2096–109.

    Article  CAS  PubMed  Google Scholar 

  12. Mesquita M, Froes F. Hospital admissions for herpes zoster in Portugal between 2000 and 2010. Acta Med Port. 2013;26(5):531–6.

    PubMed  Google Scholar 

  13. de Melker H, Berbers G, Hahné S, Rümke H, van den Hof S, de Wit A, et al. The epidemiology of varicella and herpes zoster in The Netherlands: implications for varicella zoster virus vaccination. Vaccine. 2006;24(18):3946–52.

    Article  PubMed  Google Scholar 

  14. Gil A, Gil R, Alvaro A, San Martín M, González A. Burden of herpes zoster requiring hospitalization in Spain during a seven-year period (1998–2004). BMC Infect Dis. 2009;9:55.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Gil-Prieto R, Walter S, Gonzalez-Escalada A, Garcia-Garcia L, Marín-García P, Gil-de-Miguel A. Different vaccination strategies in Spain and its impact on severe varicella and zoster. Vaccine. 2014;32(2):277–83.

    Article  PubMed  Google Scholar 

  16. Gonzalez Chiappe S, Sarazin M, Turbelin C, Lasserre A, Pelat C, Bonmarin I, et al. Herpes zoster: Burden of disease in France. Vaccine. 2010;28(50):7933–8.

    Article  CAS  PubMed  Google Scholar 

  17. Brisson M, Edmunds WJ. Epidemiology of Varicella-Zoster virus in England and Wales. J Med Virol. 2003;70 Suppl 1:S9–14.

    Article  PubMed  Google Scholar 

  18. Studahl M, Petzold M, Cassel T. Disease burden of herpes zoster in Sweden--predominance in the elderly and in women - a register based study. BMC Infect Dis. 2013;13:586.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gabutti G, Serenelli C, Cavallaro A, Ragni P. Herpes zoster associated hospital admissions in Italy: review of the hospital discharge forms. Int J Environ Res Public Health. 2009;6(9):2344–53.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Di Legami V, Gianino MM, Ciofi degli Atti M, Massari M, Migliardi A, Tomba GS, et al. Epidemiology and costs of herpes zoster: background data to estimate the impact of vaccination. Vaccine. 2007;25(43):7598–604.

    Article  PubMed  Google Scholar 

  21. Ultsch B, Siedler A, Rieck T, Reinhold T, Krause G, Wichmann O. Herpes zoster in Germany: quantifying the burden of disease. BMC Infect Dis. 2011;11:173.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gialloreti LE, Merito M, Pezzotti P, Naldi L, Gatti A, Beillat M, et al. Epidemiology and economic burden of herpes zoster and post-herpetic neuralgia in Italy: a retrospective, population-based study. BMC Infect Dis. 2010;10:230.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Fairley CK, Miller E. Varicella-zoster virus epidemiology--a changing scene? J Infect Dis. 1996;174 Suppl 3:S314–9.

    Article  PubMed  Google Scholar 

  24. Siedler A, Dettmann M. Hospitalization with varicella and shingles before and after introduction of childhood varicella vaccination in Germany. Hum Vaccin Immunother. 2014;10(12):3594–600.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Blein C, Gavazzi G, Paccalin M, Baptiste C, Berrut G, Vainchtock A. Burden of herpes zoster: the direct and comorbidity costs of herpes zoster events in hospitalized patients over 50 years in France. BMC Infect Dis. 2015;15(1):350.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Levi M, Bellini I, Capecchi L, Pieri L, Bechini A, Boccalini S, et al. The burden of disease of Herpes Zoster in Tuscany. Hum Vaccin Immunother. 2015;11(1):185–91.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Linde A, Klapper PE, Monteyne P, Echevarria JM, Cinque P, Rozenberg F, et al. Specific diagnostic methods for herpesvirus infections of the central nervous system: a consensus review by the European Union Concerted Action on Virus Meningitis and Encephalitis. Clin Diagn Virol. 1997;8(2):83–104.

    Article  CAS  PubMed  Google Scholar 

  28. Schmidt M, Jacobsen JB, Lash TL, Bøtker HE, Sørensen HT. 25 year trends in first time hospitalisation for acute myocardial infarction, subsequent short and long term mortality, and the prognostic impact of sex and comorbidity: a Danish nationwide cohort study. BMJ. 2012;344:e356.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Schmidt M, Jacobsen JB, Johnsen SP, Bøtker HE, Sorensen HT. Eighteen-year trends in stroke mortality and the prognostic influence of comorbidity. Neurology. 2014;82(4):340–50.

    Article  PubMed  Google Scholar 

  30. Lash TL, Johansen MB, Christensen S, Baron JA, Rothman KJ, Hansen JG, et al. Hospitalization rates and survival associated with COPD: A Nationwide Danish Cohort Study. Lung. 2010;189(1):27–35.

    Article  PubMed  Google Scholar 

  31. Jensen AØ, Lamberg AL, Jacobsen JB, Olesen AB, Sørensen HT. Non-melanoma skin cancer and ten-year all-cause mortality: a population-based cohort study. Acta Derm Venereol. 2010;90(4):362–7.

    Article  PubMed  Google Scholar 

  32. Jones ME, Swerdlow AJ. Bias in the standardized mortality ratio when using general population rates to estimate expected number of deaths. Am J Epidemiol. 1998;148(10):1012–7.

    Article  CAS  PubMed  Google Scholar 

  33. Oxman MN, Levin M, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–84.

    Article  CAS  PubMed  Google Scholar 

  34. Rübben A, Baron JM, Grussendorf-Conen EI. Routine detection of herpes simplex virus and varicella zoster virus by polymerase chain reaction reveals that initial herpes zoster is frequently misdiagnosed as herpes simplex. Br J Dermatol. 1997;137(2):259–61.

    Article  PubMed  Google Scholar 

  35. Scott FT, Johnson RW, Leedham-Green M, Davies E, Edmunds WJ, Breuer J. The burden of Herpes Zoster: a prospective population based study. Vaccine. 2006;24(9):1308–14.

    Article  PubMed  Google Scholar 

  36. Weinmann S, Chun C, Schmid DS, Roberts M, Vandermeer M, Riedlinger K, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005–2009. J Infect Dis. 2013;208(11):1859–68.

    Article  PubMed  Google Scholar 

  37. Rimland D, Moanna A. Increasing incidence of herpes zoster among Veterans. Clin Infect Dis. 2010;50(7):1000–5.

    Article  PubMed  Google Scholar 

  38. Østergaard K, Damgaard M, Kristiansen TB, Madsen KG. Herpes zoster incidence in persons above 50 years of age (article in Danish). Ugeskr Laeger. 2009;171(26):2194–7.

    PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported by ‘Dagmar Marshalls Fond’, ‘Friedrich Wilhelm Frank og Hustru Angelina Franks Mindelegat’, ‘Kgl. Hofbuntmager Aage Bangs Fond’, Aarhus University, and the Program for Clinical Research Infrastructure established by the Lundbeck and the Novo Nordisk Foundations. None of the funding sources had a role in the design, conduct, analysis, or reporting of the study. The Department of Clinical Epidemiology, however, is involved in studies with funding from various companies as research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study.

Author information

Authors and Affiliations

  1. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200, Aarhus N, Denmark

    Sigrun A. J. Schmidt, Johnny Kahlert & Henrik T. Sørensen

  2. Research Unit and Section for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark

    Mogens Vestergaard

  3. Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark

    Henrik C. Schønheyder

  4. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Henrik C. Schønheyder

Authors
  1. Sigrun A. J. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Johnny Kahlert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mogens Vestergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henrik C. Schønheyder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henrik T. Sørensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sigrun A. J. Schmidt.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

SAJS conceived the study idea, carried out the analyses, reviewed the literature, and wrote the initial draft. JK performed initial data management. SAJS, JK, MV, HCS, and HTS participated in designing the study, critically revised the manuscript for intellectual content, and approved the final version.

Additional file

Additional file 1:

Supplementary figures and tables. (PDF 886 kb)

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schmidt, S.A.J., Kahlert, J., Vestergaard, M. et al. Hospital-based herpes zoster diagnoses in Denmark: rate, patient characteristics, and all-cause mortality. BMC Infect Dis 16, 99 (2016). https://0-doi-org.brum.beds.ac.uk/10.1186/s12879-016-1369-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://0-doi-org.brum.beds.ac.uk/10.1186/s12879-016-1369-6

Keywords

BMC Infectious Diseases

ISSN: 1471-2334

Contact us