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A systematic literature review of herpes zoster incidence worldwide

Authors:
  • GSK Vaccines, Wavre, Belgum
  • Pallas health research and consultancy

Abstract and Figures

We conducted a systematic review to characterize the incidence rate of herpes zoster (HZ) in the general population, specifically in individuals ≥50 years of age. A total of 69 publications were included in the review. We found a cumulative incidence of HZ ranging from 2.9-19.5 cases per 1,000 population and an incidence rate of HZ ranging from 5.23-10.9 cases per 1,000 person-years. The cumulative incidence (3.22-11.2 versus 2.44-8.0 cases per 1,000 population) and incidence rates (6.05-12.8 versus 4.30-8.5 cases per 1,000 person-years) were higher in females than males. Studies revealed a trend of increasing incidence of HZ with increasing age and over time. Variations in incidence estimates can be attributed to the various study designs, case ascertainments, age distributions of the population and year of the study. HZ is associated with a substantial disease burden and is expected to increase due to population aging.
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A systematic literature review of herpes zoster
incidence worldwide
Désirée van Oorschot, Hilde Vroling, Eveline Bunge, John Diaz-Decaro,
Desmond Curran & Barbara Yawn
To cite this article: Désirée van Oorschot, Hilde Vroling, Eveline Bunge, John Diaz-Decaro,
Desmond Curran & Barbara Yawn (2021): A systematic literature review of herpes zoster incidence
worldwide, Human Vaccines & Immunotherapeutics, DOI: 10.1080/21645515.2020.1847582
To link to this article: https://doi.org/10.1080/21645515.2020.1847582
© 2021 GlaxoSmithKline Biologicals SA.
Published with license by Taylor & Francis
Group, LLC.
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Published online: 02 Mar 2021.
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RESEARCH PAPER
A systematic literature review of herpes zoster incidence worldwide
Désirée van Oorschot
a
, Hilde Vroling
b
, Eveline Bunge
b
, John Diaz-Decaro
c
, Desmond Curran
a
,
and Barbara Yawn
d
a
Health Economics, GSK, Wavre, Belgium;
b
Pallas Health Research and Consultancy, Rotterdam, The Netherlands;
c
Vaccine, GSK, Rockville, MD, USA;
d
Department of Family and Community Health, University of Minnesota, Minneapolis, MN, USA
ABSTRACT
We conducted a systematic review to characterize the incidence rate of herpes zoster (HZ) in the general
population, specically in individuals ≥50 years of age. A total of 69 publications were included in the
review. We found a cumulative incidence of HZ ranging from 2.9–19.5 cases per 1,000 population and an
incidence rate of HZ ranging from 5.23–10.9 cases per 1,000 person-years. The cumulative incidence
(3.22–11.2 versus 2.44–8.0 cases per 1,000 population) and incidence rates (6.05–12.8 versus 4.30–8.5
cases per 1,000 person-years) were higher in females than males. Studies revealed a trend of increasing
incidence of HZ with increasing age and over time. Variations in incidence estimates can be attributed to
the various study designs, case ascertainments, age distributions of the population and year of the study.
HZ is associated with a substantial disease burden and is expected to increase due to population aging.
ARTICLE HISTORY
Received 28 May 2020
Revised 9 October 2020
Accepted 2 November 2020
KEYWORDS
Incidence; herpes zoster;
shingles; adults; vaccination;
epidemiology; review
Introduction
Primary infection with the varicella zoster virus (VZV) often
leads to acute varicella or chickenpox, typically in childhood.
After recovery from chickenpox, the virus remains dormant in
the dorsal root ganglia.
1
Age-related decline in immunity or an
immunosuppressed condition may lead to the reactivation of
VZV causing herpes zoster (HZ), also called shingles. HZ is
distinguished by a painful or pruritic, commonly unilateral,
blistering rash. Although pain may persist for much longer, the
average duration of the HZ rash ranges from 7 to 10 days, with
the skin healing completely within approximately 2 to
4 weeks.
2
The pain associated with HZ has been described as aching,
burning, stabbing, or shock-like. Individuals with HZ may also
experience altered sensitivity to touch, pain provoked by trivial
stimuli, and unbearable itching.
3
The median duration of pain
is approximately 32.5 days (the mean duration is 45 days).
3
Postherpetic neuralgia (PHN) is frequently defined as pain
persisting for at least 3 months after rash onset, and occurs in
5% to 30% of patients.
4
Pain associated with PHN can disrupt
all aspects of daily life and patients with PHN may experience
depression, reduced quality of life, and social withdrawal.
2
Other complications associated with HZ include stroke or
other cardiovascular events, neurological sequelae, palsy and
gastrointestinal ailments.
5
Severe cases of the above complica-
tions often require hospitalization.
5
The lifetime risk of HZ disease without vaccination ranges
between 20% and 30%.
6,7
Gender, ethnicity, family history, and
comorbidities such as systemic lupus erythematosus, asthma,
diabetes mellitus and chronic obstructive pulmonary disease
are risk factors for HZ.
8
An increase in age leads to higher
incidence and severity of HZ disease, especially after the age of
50 years, due to age-related decline in immunity.
9
Considering
the significance of age as a risk factor, the increasing life
expectancy in the general population may considerably
increase HZ annual cases and disease burden.
10
It is becoming
crucial for healthcare professionals and health policy-makers to
be informed of the latest evidence on the disease burden of HZ.
Findings from a previous review conducted in 2014 provides
a comprehensive overview of HZ as a significant global health
burden.
4
To our knowledge, there are no reviews summarizing
the evidence from more recently conducted epidemiology and
burden of disease studies.
The objective of this review is to provide an up-to-date
evidence base on the incidence of HZ. Specifically, this review
aims to summarize the incidence rates of HZ in the general
population with a focus on individuals ≥50 years of age (YOA).
In addition, when available in the literature, the incidence of
HZ by risk factors such as gender, age, ethnicity and immuno-
competence is described. Trends of HZ incidence stratified by
different geographical regions and over time are also presented.
Methods
We performed a systematic review of the literature according to
guidelines specified in the Cochrane Handbook for Systematic
Reviews of Interventions
11
and Preferred Reporting Items for
Systematic Literature Reviews and Meta-Analyses (PRISMA)
12,13
to obtain relevant information using a reproducible, robust and
transparent methodology.
CONTACT Désirée van Oorschot desiree.x.van-oorschot@gsk.com GSK, 20 Avenue Fleming 1300, Wavre, Belgium.
Previous congress activities: Data reported in this manuscript have been presented as a poster at ISPOR-EU – 02–06 November 2019 (Copenhagen, Denmark) and at
the Shingrix Specialty Advisory Board.
Supplemental data for this article can be accessed on the publisher’s website.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
https://doi.org/10.1080/21645515.2020.1847582
© 2021 GlaxoSmithKline Biologicals SA. Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Search sources and strategy
We searched the following online databases: PubMed, Embase,
and the Virtual Health Library (VHL) including the Latin
American & Caribbean Health Sciences Literature (Lilacs)
database. The search strategy was developed using both
indexed terms and terms described in the title or abstract.
Search terms for the different databases were combined using
Boolean operators. Details of the search strategy are provided
in Supplementary Table 1. All searches were restricted by
publication date from 1 January 2002 onwards and were con-
ducted on 7 December 2018.
Article selection and quality control
Publications identified from the searches were screened in
three phases using the inclusion and exclusion criteria pro-
vided in Supplementary Table 2.
In the first phase, publications were screened based on the titles
and abstracts. All titles and abstracts were screened in duplicate by
two independent researchers (HV, EB). The results were com-
pared, and deviations were discussed. In the second phase, the first
10% of eligible full-text publications were checked for relevancy in
duplicate by two independent researchers (HV, EB). The results
were compared and discussed early in the process to minimize the
differences between both researchers with regards to the full-text
publications screened in duplicate.
The process of selection of publications was registered in an
EndNote library by one of the researchers. The full-text selec-
tion was documented per article with reason of exclusion in an
Excel file to ensure that a clear overview of all selection steps
across all phases was maintained, and reproducibility of the
results was assured.
Data extraction, quality assessment and descriptive
analyses
After the eligible publications were identified for this review, one
researcher (HV) extracted the relevant data from these publica-
tions into an Excel database. A reviewer (EB) quality checked the
extracted data. Data extraction parameters were established
a priori and included publication details, country, study charac-
teristics (design, time period, setting), population characteristics
(inclusion and exclusion criteria, sample size, age groups, gender,
ethnicity, underlying immunocompromising conditions), metho-
dology (case detection, case definition, type of patients and inci-
dence denominator), incidence of HZ (per person and per
person-years separately) by gender, age, ethnicity, year and case
definition and information to assess the quality of the study.
There are several well-known and validated checklists avail-
able to assess the quality of publications with “classical” study
designs (e.g., cohort, case-control, randomized controlled trial,
etc.). However, there are no formal validated checklists which
focus on incidence studies that are typically designed as sur-
veillance studies. We defined three questions in order to assess
the quality of the included HZ incidence studies
(Supplementary Table 3).
In this paper, we provide a descriptive overview of the inci-
dence of HZ in the general population ≥50 YOA. Incidence
(number of HZ cases per 1,000 population hereafter referred to
as cumulative incidence or as number of HZ cases per 1,000 per-
son-years hereafter referred to as incidence rate) is presented for
the overall population and for the general population stratified
by gender, age, ethnicity, study year and case definition. Where
incidence was expressed as a cumulative, we transformed the
data from a percentage (i.e., per population) to an incidence rate
assuming an exponential distribution (i.e., s(t) = 1-exp(-ƴt)
where ƴ is the incidence rate and t is time, assumed to be equal
to 1.
14
This transformation facilitated the presentation of trends
in HZ incidence.
Results
Included studies
A total of 4,848 publications were identified from the data-
bases. After the removal of duplicates, titles and abstracts of
2,375 publications were screened for eligibility based on the
pre-specified inclusion and exclusion criteria (Supplementary
Table 2). After excluding 2,225 publications based on title and
abstract screening, 150 full-text publications were assessed for
full-text eligibility using the same criteria. A total of 69 pub-
lications were included in the review Figure 1.
Study characteristics
The characteristics of the 69 individual studies are provided in
Table 1. The majority of studies were conducted in the United
States of America (USA; n = 14),
6,15–27
followed by Canada
(n = 6),
28–33
the United Kingdom (UK; n = 6),
34–39
Germany
(n = 5),
40–44
Japan (n = 5),
45–49
the Netherlands (n = 5),
36,50–53
Spain (n=5),
54–58
Taiwan (n = 4),
59–62
Australia (n = 3),
63–65
China (n = 3),
66–68
Italy (n = 3),
69–71
France (n = 2),
72,73
New
Zealand(n = 2),
74,75
Sweden (n = 2),
76,77
Denmark (n = 1),
78
Israel (n = 1),
79
Norway (n = 1),
80
Poland (n = 1),
81
and South
Korea (n = 1).
82
One study presented data for both the
Netherlands and the UK separately;
36
this study is captured
within the individual countries Figure 2; Table 1.
Figure 2A provides the distribution of the 69 included studies
by study design. Most studies (n = 51) were passive surveillance
studies, with either a retrospective (n = 50) Table 1 or prospec-
tive (n = 1)
63
design. Furthermore, 15 active surveillance studies
(10 prospective [Table 1] and 5 retrospective
15,26,66–68
), and 3
unmatched retrospective cohort studies
21,24,34
were found.
Figure 2B provides the distribution of the 69 included
studies by the method used for HZ case identification. Fifty-
two studies used the International Classification of Diseases
(ICD) codes or equivalent codes to define HZ cases (Table 1),
while 9 studies also used antiviral drug prescriptions (Table 1),
10 studies used a clinical diagnosis based on symptoms (Table
1), 5 studies used a self-report of HZ (Table 1), and one study
used a natural language processing software algorithm
(Table 1).
Figure 2C provides the distribution of the studies by the
type of incidence data reported. More studies (n = 42; Table 1)
expressed the HZ incidence as cumulative incidence than as
incidence rate (n = 27; Table 1). While 6 studies gave only one
overall HZ incidence (Table 1), 58 studies stratified the
2D. VAN OORSCHOT ET AL.
Table 1. Characteristics of included studies (N = 69).
Author, year Country Study design Study period Setting
Age
(years) Case definition Patient type
Type of incidence
data reported Stratifications
Liu, 2015
63
Australia Prospective passive
surveillance
study
1 January 2006–31 December 2009 The 45 and Up Study in New
South Wales
≥45 Drug prescription
or ICD codes
(inpatients only)
Inpatients and
outpatients
Incidence rate Age
MacIntyre, 2015
64
Australia Retrospective
passive
surveillance
study
1 July 2006–31 March 2013 6,302 GPs captured in the
Bettering the Evaluation of
Care and Health database,
and the (Repatriation)
Pharmaceutical Benefits
Scheme database
≥50 ICPC codes or drug
prescription
Outpatients Cumulative
incidence
Age, case definition
(GP visits or antiviral
prescriptions)
Stein, 2009
65
Australia Retrospective
passive
surveillance
study
1 April 2000–30 September 2006 6,460 GPs captured in the
Bettering the Evaluation of
Care and Health database,
and the (Repatriation)
Pharmaceutical Benefits
Scheme database
≥50 ICPC codes or drug
prescription
Outpatients Cumulative
incidence
Age, case definition
(GP visits or antiviral
prescriptions)
McDonald, 2017
30
Canada Retrospective
passive
surveillance
study
1 November 2009–31 October 2015 Alberta Health Care Insurance
Plan Registry, an Albertan
health insurance
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, gender
Marra, 2016
29
Canada Retrospective
passive
surveillance
study
1 January 1997–31 December 2012 Population-DataBC® Medical
Services Plan and Discharge
Abstract Database, linked to
the outpatient prescription
database PharmaNet;
British Columbia
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age, year
Russel, 2014
31
Canada Retrospective
passive
surveillance
study
1 January 1994–31 December 2010 Alberta’s universal, publicly
funded health-care
insurance system databases
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age, year
Tanuseputro, 2011
33
Canada Retrospective
passive
surveillance
study
1 April 1992–31 March 2010 Canadian Institute of Health
Information Discharge
Abstract Database (Ontario)
and Ontario Health
Insurance Plan
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age, year
Russel, 2007
32
Canada Retrospective
passive
surveillance
study
1 January 1990–31 December 2002 Hospital Morbidity Inpatient
database and the Alberta
Health Care Insurance Plan
Registry; Alberta Province
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age, gender, year
Edgar, 2007
28
Canada Retrospective
passive
surveillance
study
1 January 1994–31 December 2003 British Columbia Ministry of
Health Medical Services
Plan database (physician
billing data)
≥65 ICD codes Outpatients Cumulative
incidence
-
Lu, 2018
67
China Retrospective
active
surveillance
study
December 2012 – March 2013 52 communities/villages in
three districts of Beijing
(Xicheng, Changping and
Miyun)
≥50 Self-report Outpatients Cumulative
incidence
Age, gender
Li, 2016
66
China Retrospective
active
surveillance
study
May 2013 – May 2014 One rural township each in
Jiangsu, Jiangxi,
Heilongjiang and Hebei and
one community from
Shanghai
≥50 Self-report Inpatients and
outpatients
Cumulative
incidence
Age, gender, year
(Continued)
HUMAN VACCINES & IMMUNOTHERAPEUTICS 3
Table 1. (Continued).
Author, year Country Study design Study period Setting
Age
(years) Case definition Patient type
Type of incidence
data reported Stratifications
Zhu, 2015
68
China Retrospective
active
surveillance
study
28 October 2013 – NR 34 of the 126 counties/
districts in Guangdong
Province, selected using
random sampling
≥50 Self-report Outpatients Cumulative
incidence
Year
Schmidt, 2017
78
Denmark Retrospective
passive
surveillance
study
1 January 1997–31 December 2013 Danish National Prescription
Registry and Danish
National Patient Registry
≥50 Drug prescription
ICD codes
(inpatients only)
Inpatients and
outpatients
Cumulative
incidence
Age, gender
Amirthalingam,
2018
34
England Retrospective
unmatched
cohort study
1 October 2005–30 September 2016 164 Royal College of General
Practitioners – Research
and Surveillance Centre
practices across England
60–89 READ codes Outpatients Incidence rate Age, gender, year
Jain, 2018
38
England Retrospective
passive
surveillance
study
1 September 2003–31 August 2013 385 Clinical Practice Research
Datalink practices across
England
≥65 CPRD codes ICD
codes
(inpatients only)
Inpatients and
outpatients
Incidence rate Age, ethnicity, gender
Mick, 2010
73
France Prospective active
surveillance
study
1 January 2005–31 December 2005 225 GPs, 36 dermatologists, 15
neurologists and 5
physicians in pain clinics
from a random sample of
these physician types
≥50 Clinical Outpatients Cumulative
incidence
Age, gender
Gonzalez Chiappe,
2010
72
France Retrospective
passive
surveillance
study
1 January 2000–31 December 2008 ~1200 GPs reporting to the
French general
practitioners’ Sentinelles
electronic surveillance
network
≥45 Clinical Outpatients Cumulative
incidence
Age
Schmidt-Ott, 2018
42
Germany Prospective active
surveillance
study
November 2010 – December 2014 GPs, dermatologists and
ophthalmologists in 3
German regions (Fulda,
Leverkusen and Marl)
≥50 Clinical Outpatients Incidence rate Age, gender
Hillebrand, 2015
40
Germany Retrospective
passive
surveillance
study
1 January 2005–31 December 2009 German
Pharmacoepidemiological
Research Database,
a national database
≥50 ICD codes Inpatients and
outpatients
Incidence rate Year
Ultsch, 2013
43
Germany Retrospective
passive
surveillance
study
1 January 2005–31 December 2008 German Statutory Health
Insurance System
Allgemeine
Ortskrankenkasse and
Regional Association of SHI-
Accredited Physicians (KV)
in Hessen
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age
Ultsch, 2011
44
Germany Retrospective
passive
surveillance
study
1 January 2007–31 December 2008 Association of Statutory
Health Insurance Physicians
database
≥50 ICD codes Outpatients Cumulative
incidence
Age, gender, year
Schiffner-Rohe,
2010
41
Germany Retrospective
passive
surveillance
study
1 January 2003–31 December 2004 An insurance database
(Allgemeine
Ortskrankenkasse Hessen/
KV Hessen)
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age, gender,
population (general
population and IC
only)
(Continued)
4D. VAN OORSCHOT ET AL.
Table 1. (Continued).
Author, year Country Study design Study period Setting
Age
(years) Case definition Patient type
Type of incidence
data reported Stratifications
Alicino, 2017
69
Italy Retrospective
passive
surveillance
study
1 January 2013–31 December 2015 56 GPs in Liguria, Puglia,
Toscana and Veneto
≥50 ICD codes or drug
prescription
Outpatients Incidence rate Age, gender
Gialloreti, 2010
71
Italy Retrospective
passive
surveillance
study
1 January 2003–31 December 2005 342 GPs reporting in the
Health Search Database of
the Società Italiana Medici
Generici, from Northern,
Central and Southern Italy
≥50 ICD codes Outpatients Cumulative
incidence
Age, population
(general population
and IC only)
Di Legami, 2007
70
Italy Prospective active
surveillance
study
1 January 2004–31 December 2004 All 24 GPs working in Torino
and Cuorgnè, Piemonte
≥45 Clinical Outpatients Cumulative
incidence
Age
Weitzman, 2013
79
Israel Retrospective
passive
surveillance
study
1 January 2006–30 September 2010 Maccabi Healthcare Services
database
≥45 ICD codes Inpatients and
outpatients
Incidence rate Age
Toyama, 2018
49
Japan Prospective active
surveillance
study
1 January 1997–31 December 2017 33 dermatology clinics and
dermatology departments
of 10 flagship general
hospitals associated with
the Miyazaki Dermatologist
Society, in Miyazaki
Prefecture
≥60 Clinical Outpatients Cumulative
incidence
Year
Imafuku, 2018
45
Japan Retrospective
passive
surveillance
study
1 January 2005–31 December 2014 Japan Medical Data Center-
Claims Database, a national
health insurance database
50–74 ICD codes and drug
prescription
Inpatients and
outpatients
Incidence rate Age, gender
Shiraki, 2017
46
Japan Prospective active
surveillance
study
1 June 2009–30 November 2015 36 dermatology clinics and
dermatology departments
of 7 flagship general
hospitals belonging to the
Miyazaki Dermatologist
Society, Miyazaki Prefecture
70–79 Clinical Outpatients Cumulative
incidence
Gender
Takao, 2015
47
Japan Prospective active
surveillance
study
1 December 2008–30 November 2012 Shozu County, Kagawa
Prefecture, Japan
≥50 Clinical Inpatients and
outpatients
Incidence rate Age, gender
Toyama, 2009
48
Japan Prospective active
surveillance
study
1 January 1997–31 December 2006 39 dermatology clinics and
dermatology departments
of 7 flagship general
hospitals associated with
the Miyazaki Dermatologist
Society, in Miyazaki
Prefecture
≥50 Clinical Outpatients Cumulative
incidence
Age, gender
Pierik, 2012
53
NL Retrospective
passive
surveillance
study
1 January 2004–31 December 2008 ZorgGroep Almere, a database
of 22 GPs in Almere
≥60 ICPC codes Outpatients Cumulative
incidence
Age
Opstelten, 2006
52
NL Prospective active
surveillance
study
1 January – 31 December 2001 Second Dutch National Survey
of General Practice; 186 GPs
in 90 practices nationwide
≥45 ICPC codes Outpatients Cumulative
incidence
Age, gender (no both
genders data)
(Continued)
HUMAN VACCINES & IMMUNOTHERAPEUTICS 5
Table 1. (Continued).
Author, year Country Study design Study period Setting
Age
(years) Case definition Patient type
Type of incidence
data reported Stratifications
Opstelten, 2005
51
NL Prospective active
surveillance
study
1 January – 31 December 2001 Second Dutch National Survey
of General Practice; 186 GPs
in 90 practices nationwide
≥65 ICPC codes Outpatients Cumulative
incidence
-
Opstelten, 2002
50
NL Retrospective
passive
surveillance
study
1 August 1994–31 July 1999 Huisartsen Netwerk Utrecht,
a general practice research
database in the province of
Utrecht; 22 GPs in 6
locations
≥45 ICPC codes Outpatients Incidence rate Age
Rimseliene, 2016
80
Norway Retrospective
passive
surveillance
study
2008–2012 Norwegian Health Economics
Administration database
≥70 ICPC codes Outpatients Cumulative
incidence
-
Turner, 2018
75
New Zealand Retrospective passive surveillance
study
1 January 2005–31 December 2015 39 consenting general
practices from two primary
health organizations in
lower North Island
≥50 natural language
processing
software
algorithm
Outpatients Incidence rate Age, year
Reid, 2014
74
New Zealand Retrospective passive surveillance
study
1 January 2009–31 December 2013 A large group practice in
Lower Hutt
≥51 Coding (NR) or
drug
prescription
Outpatients Cumulative
incidence
Age, gender
Albrecht, 2015
81
Poland Retrospective
passive
surveillance
study
2013 Świętokrzyskie Province
Division of the National
Health Fund
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
-
Kim, 2014
82
South
Korea
Retrospective
passive
surveillance
study
1 January 2011–31 December 2011 National Health Insurance
Service database
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age
Muñoz-Quiles, 2017
58
Spain Retrospective
passive
surveillance
study
1 January 2009–31 December 2014 SIA (not defined) database
and Hospitalization
Minimum Data Set,
Valencian Region
≥50 ICD codes Inpatients and
outpatients
Incidence rate -
Esteban-Vasallo,
2014
55
Spain Retrospective
passive
surveillance
study
1 January 2005–31 December 2012 Madrid regional public health
system
≥45 ICPC codes Outpatients Cumulative
incidence
Age, gender, year
Morant-Talamante,
2013
57
Spain Retrospective
passive
surveillance
study
1 January 2007–20 December 2010 Abucasis electronic medical
database and the Hospital
Data Surveillance System, in
the Valencian community
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, gender, year
Cebrian-Cuenca,
2010
54
Spain Prospective active
surveillance
study
1 December 2006–30 November 2007 24 GP offices of the public
healthcare system of the
Autonomous Community of
Valencia
≥50 Clinical Outpatients Cumulative
incidence
Age
Garcia-Cenoz, 2008
56
Spain Retrospective
passive
surveillance
study
1 January 2005–31 December 2006 “La base de datos de la
historia clinica
informatizada de atencion
primaria”, Navarra
≥50 ICPC codes Outpatients Cumulative
incidence
Age
(Continued)
6D. VAN OORSCHOT ET AL.
Table 1. (Continued).
Author, year Country Study design Study period Setting
Age
(years) Case definition Patient type
Type of incidence
data reported Stratifications
Sundström, 2015
77
Sweden Retrospective
passive
surveillance
study
January 2008 – December 2010 Västra Götaland County ≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, gender, year
Nilsson, 2015
76
Sweden Retrospective
passive
surveillance
study
1 January – 31 December 2011 Swedish National Pharmacy
Register
≥50 Drug prescription Inpatients and
outpatients
Cumulative
incidence
Age
Lu, 2018
62
Taiwan Retrospective
passive
surveillance
study
1 January 2004–31 December 2008 NHIRD, a national health
insurance database
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age, year
Chao, 2011
59
Taiwan Retrospective
passive
surveillance
study
1 January 2000–31 December 2008 National Health Insurance
Research Database
≥50 ICD codes Outpatients Cumulative
incidence
Age, year
Lin, 2010
62
Taiwan Retrospective
passive
surveillance
study
1 January 2000–31 December 2005 National Health Insurance
Research Database
≥50 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age
Jih, 2009
60
Taiwan Retrospective
passive
surveillance
study
1 January 2000–31 December 2006 National Health Insurance
Research Database
>80 ICD codes Inpatients and
outpatients
Incidence rate -
Walker, 2018
39
UK Retrospective
passive
surveillance
study
1 September 2013–31 August 2016 Clinical Practice Research
Datalink practices across
the UK (number of practices
NR)
68–79 READ codes
ICD codes
(inpatients only)
Inpatients and
outpatients
Incidence rate Gender
Gauthier, 2009
37
UK Retrospective
passive
surveillance
study
1 January 2000–31 March 2006 603 General Practice Research
Datalink practices, the UK
≥50 GPRD codes Outpatients Incidence rate Age, gender
Fleming, 2004
36
UK and
NL
Retrospective
passive
surveillance
study
1 January 1994–31 December 2001 Weekly Returns Service of the
Royal College of General
Practitioners in England and
Wales and Dutch Sentinel
practice network (number
of GPs NR)
≥45 Clinical Outpatients Cumulative
incidence
Age, gender (no “both
genders” data)
Brisson, 2003
35
UK Retrospective
passive
surveillance
study
1 January 1991–31 December 2000 69 Royal College of General
Practitioners practices
across England and Wales
and participating GPs in the
National Survey of
Morbidity in General
Practice database
≥45 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age
Harpaz, 2018
27
USA Retrospective
passive
surveillance
study
1 January 1998–31 December 2016 Two Medstat MarketScan
databases: Commercial
Claims and Encounters, and
Medicare Supplemental and
Coordination of Benefits
≥45 ICD codes Outpatients Cumulative
incidence
Age, year
(Continued)
HUMAN VACCINES & IMMUNOTHERAPEUTICS 7
Table 1. (Continued).
Author, year Country Study design Study period Setting
Age
(years) Case definition Patient type
Type of incidence
data reported Stratifications
Kawai, 2016
19
USA Retrospective
passive
surveillance
study
1 January 1980–31 December 2007 Rochester Epidemiology
Project, conducted in
Olmsted County, Minnesota
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, year
Johnson, 2015
18
USA Retrospective
passive
surveillance
study
1 January 2011–31 December 2011 Two Medstat MarketScan
databases: Commercial
Claims and Encounters, and
Medicare Supplemental and
Coordination of Benefits
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, gender
Chen, 2014
16
USA Retrospective
passive
surveillance
study
1 January 2005–31 December 2009 Commercially insured,
Medicare and Medicaid
administrative medical and
pharmacy claims databases
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age
Krishnarajah, 2014
20
USA Retrospective
passive
surveillance
study
1 January 2006–31 December 2010 MarketScan Medicaid
database
50–64 ICD codes Inpatients and
outpatients
Cumulative
incidence
Age, gender, year
Suaya, 2014
24
USA Unmatched
retrospective
cohort study
1 January 2005–31 December 2009 Three MarketScan databases:
Commercial, Medicare and
Medicaid databases
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, population
(general population
and IC only)
Hales, 2013
17
USA Retrospective
passive
surveillance
study
1 January 1992–31 December 2010 Medicare, a national health
insurance program
>65 ICD codes Inpatients and
outpatients
Incidence rate Age, ethnicity,
gender, year
Langan, 2013
21
USA Unmatched
retrospective
cohort study
1 January 2007–31 December 2009 Medicare, a national health
insurance program
≥65 ICD codes and/or
drug
prescription
Inpatients and
outpatients
Incidence rate Age, ethnicity, gender,
population (general
population and IC
only), case
definition (with or
without antiviral
prescriptions)
Leung, 2011
22
USA Retrospective
passive
surveillance
study
1 January 1993–31 December 2006 Two Medstat MarketScan
databases: Commercial
Claims and Encounters, and
Medicare Supplemental and
Coordination of Benefits
≥45 ICD codes Outpatients Cumulative
incidence
Age, gender, year
Chaves, 2007
15
USA Retrospective
active
surveillance
study
2 February 2004–27 May 2004 National Adult Immunization
Survey
≥65 Self-report Outpatients Cumulative
incidence
Age, ethnicity, gender
Yawn, 2007
25
USA Retrospective
passive
surveillance
study
1 January 1996–31 December 2001 Rochester Epidemiology
Project, conducted in
Olmsted County, Minnesota
≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, gender
Insinga, 2005
7
USA Retrospective
passive
surveillance
study
1 July 2000–30 June 2001 Medstat MarketScan database ≥50 ICD codes Inpatients and
outpatients
Incidence rate Age, gender,
population (general
population and IC
only)
Mullooly, 2005
23
USA Retrospective
passive
surveillance
study
1 January 1997–31 December 2002 Kaiser Permanente North-
West California
≥45 ICD codes
x estimated % of
probable HZ
Inpatients and
outpatients
Incidence rate Age, gender, year
(Continued)
8D. VAN OORSCHOT ET AL.
Table 1. (Continued).
Author, year Country Study design Study period Setting
Age
(years) Case definition Patient type
Type of incidence
data reported Stratifications
Yih, 2005
26
USA Retrospective
active
surveillance
study
1 January 1999–31 December 2003 Behavioral Risk Factor
Surveillance System survey,
Massachusetts
≥45 Self-report Inpatients and
outpatients
Cumulative
incidence
Age, year
Cumulative incidence: Number of new HZ cases per 1,000 population
Incidence rate: Number of new HZ cases per 1,000 person-years
GP, general practitioner/practice; GPRD, general practice research database; HZ, herpes zoster; IC, immunocompetent; ICD, International Classication of Diseases; ICPC, International Classication of Primary Care;
NL, The Netherlands; NR, not reported; QAT, quality assessment tool; UK, United Kingdom; USA, United States of America.
HUMAN VACCINES & IMMUNOTHERAPEUTICS 9
incidence by age (Table 1), 33 studies by gender (Table 1), 23
studies by study year (Table 1), and 4 studies by
ethnicity.
15,17,21,38
In 5 studies, the HZ incidence was reported
for the overall general population as well as the immunocom-
petent population only.
6,21,24,41,71
Lastly, 3 studies reported the
HZ incidence for two different case definitions of HZ.
21,64,65
Thirty-six of the included studies were nationwide studies
or claimed to be representative of the national population,
while the remaining studies were conducted in one or several
country regions. Study periods varied, with the oldest data
reported for the period 1980–1989
19
and the most recent data
for the year 2017.
49
The number of studies including outpati-
ents only (n = 32) was similar to the number of studies includ-
ing both inpatients and outpatients (n = 37) (Table 1). The HZ
incidence was reported for a study population ≥50 YOA in 42
studies (Table 1). In 12, 2 and 6 studies, the study population
was ≥45 YOA (Table 1), ≥60 YOA
49,53
and ≥65 YOA (Table 1),
respectively. In the remaining studies, the HZ incidence was
described for a study population of ≥70 YOA,
80
>80 YOA,
60
60–89 YOA,
34
50–74 YOA,
45
50–64 YOA,
20
70–79 YOA,
46
or
68–79 YOA.
39
Overview of the incidence of HZ
Overall incidence of HZ in the general population
The overall HZ incidence in the general population ≥50 YOA
was reported in 30 of 42 studies (Figure 3). When comparing
the geographical regions, the cumulative incidence ranges were
5.49–8.67 per 1,000 population for North America, 5.77–
9.85 per 1,000 population for Europe and 2.9–19.5 per 1,000
population in the Asia-Pacific region. Incidence rates were
6.6–9.03 per 1,000 person-years for North America, 5.23–
10.9 per 1,000 person-years for Europe and 10.9 per 1,000 per-
son-years in the Asia-Pacific region.
Trends in cumulative incidence, over time
Figure 4A shows the cumulative incidence of HZ which is seen
to be increasing over time. It should be noted that these studies
do not all cover the same age groups, hence a wide difference in
incidence estimates is observed. Most studies report the
observed increase of HZ incidence over time. One study by
Yih et al. specifically presented the relationship between var-
icella vaccination introduction and HZ incidence increase over
time.
26
Incidence of HZ in the general population, by gender
The HZ incidence in the general population ≥50 YOA stratified
by gender was reported in 14 studies. All 14 studies reported
a higher incidence of HZ in females compared to males. In
females, the cumulative incidence in the general population
≥50 YOA ranged from 3.22 cases per 1,000 population in 2010
in China
66
to 11.2 cases per 1,000 population in 2004 in
Germany.
41
In males, the corresponding incidence ranged
from 2.44 per 1,000 persons to 8.0 per 1,000 persons in the
same studies.
41,66
The incidence rate in females ranged from
6.05 cases per 1,000 person-years in the period 2006–2012 in
Figure 1. PRISMA diagram. *The authors were contacted to retrieve the underlying data (numerators and denominators) of these figures.**Systematic reviews/meta-
analyses were checked for possibly missed relevant original articles.HZ, herpes zoster; N, number; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-
Analyses
10 D. VAN OORSCHOT ET AL.
the UK
37
to 12.8 cases per 1,000 person-years in the period
2008–2012 in Japan.
47
In males, the corresponding incidence
ranged from 4.30 cases per 1,000 person-years to 8.5 cases per
1,000 person-years in the same studies.
37,47
Twenty-eight studies reported a higher incidence of HZ in
females than for in males in age groups besides the ≥50 years
group. However, Chaves et al. reported a higher HZ incidence
in males in the ≥65 years group, but corresponding confidence
intervals were wide and overlapped.
15
In two studies a higher
incidence in males was found in the highest age groups
only.
23,74
Incidence of HZ in the general population, by age
Almost all studies (n = 58) reported the HZ incidence for
different age groups (Supplementary Table 4). In 35 studies,
the incidence increased with increasing age. However, in 14
studies a drop in incidence was reported for the highest age
groups, i.e., ≥70 YOA,
67,82
≥75 YOA,
56
≥80 YOA,
42,47,48,57,61,71
or ≥85 YOA.
37,62,69,75,79
In 8 studies, both scenarios (i.e.
increasing incidence with increasing age and a decline in
incidence for the highest age group) were reported during
different time periods.
17,23,31–33,55,59,64
Moreover, in one study
the incidence of HZ decreased in individuals of 60–69 YOA
compared to those of 50–59 YOA, after which it increased in
individuals ≥70 YOA.
54
Except for one Japanese study that did
not report the incidence for persons ≥75 YOA
45
and one
Chinese study,
66
all Asian studies reported a drop in incidence
for the highest age groups.
47,48,59,61,62,67,82
Furthermore, 2
Italian studies,
69,71
2 Spanish studies,
56,57
one UK study
37
and
one study from New Zealand
75
reported a decline in the inci-
dence for the highest age groups. From the other European
countries, Australia, Canada and the USA, no studies were
found that solely reported a declining incidence in the highest
age groups.
Trends in cumulative incidence, by age
The cumulative incidence for all geographical regions by age is
provided in Figure 4B (data for all individual studies is pro-
vided in Supplementary Figure 1). Most studies depict a steady
increasing trend in HZ incidence with age. Four studies
Figure 2. Distribution of publications (N = 69) by (A) Study design, (B) Case identification method, (C) Incidence data stratification.
The total number of studies add up to 77 studies as 8 studies utilized more than one method to detect HZ (see Table 1). HZ, herpes zoster; ICD, International
Classification of Diseases
HUMAN VACCINES & IMMUNOTHERAPEUTICS 11
covering North America,
15
Europe
70
and two studies from the
Asia-Pacific region
68,82
report incidence estimates that deviate
from the overall trend.
15,68,70,82
Incidence of HZ in immunocompetent persons
Nine studies reported the HZ incidence in immunocompetent
persons only.
6,21,24,37,39,41,58,71,73
In seven studies, the HZ incidence
for those ≥50 YOA was reported, with a range of 6.31–9.5 cases per
1,000 persons
41,71,73
and a range of 5.23–7.2 cases per 1,000 per-
son-years.
6,24,37,58
In five studies, the HZ incidence was separately
reported for the overall general population and the
immunocompetent population only.
6,21,24,41,71
In all five studies,
estimates of incidence in the overall general population were
numerically higher compared to the immunocompetent
population.
Incidence of HZ in the general population, by ethnicity
In 4 studies, the HZ incidence was reported by
ethnicity.
15,17,21,38
In 3 studies, the highest incidence was
reported in Caucasians, while in the fourth study, persons
with an American Indian/Alaskan native ethnicity were
found to have the highest HZ incidence.
17
The lowest HZ
Figure 3. Overall HZ incidence in the general population ≥50 years by country (A) Cumulative incidence (B) Incidence rate. *Number of new HZ cases per 1,000
population † Number of new HZ cases per 1,000 person-years
HZ, herpes zoster
12 D. VAN OORSCHOT ET AL.
incidence was generally found among persons reported as
black, except in the study of Chaves et al. where those with
either Hispanic or other ethnicity had the lowest HZ
incidence.
15
Incidence of HZ in the general population, by study year
In 23 studies the HZ incidence was reported for different years,
and in 17 of these studies the HZ incidence increased during
the years. In addition, Amirthalingam et al. also reported such
an increase until the introduction of the zoster vaccine in the
UK.
34
Harpaz et al. also found an increase in HZ incidence over
time, but specifically reported a decline in the rate of increase
among older adults from 2006 through 2016; reasons for this
trajectory over time for older adults could not be confirmed as
a consequence of the impact of HZ vaccination introduction.
27
In the remaining five studies, no clear increasing trend over the
years was reported.
20,32,33,57,68
Incidence of hz in the general population, by case definition
In 3 studies, the HZ incidence was compared for different case
definitions of HZ. Langan et al. reported the HZ incidence
based on ICD codes only and based on these ICD codes in
combination with the use of antivirals within 7 days before or
after the diagnostic code for HZ.
21
Among those individuals
≥65 YOA, the incidence was much lower when using the latter
definition (9.9 per 1,000 person-years) compared to ICD codes
only (15.0 per 1,000 person-years). The lower incidence using
the latter definition remained when the data were stratified for
different age, gender and ethnicity groups. Two Australian
studies compared the HZ incidence based on general practi-
tioner (GP) visits with incidence estimates based on antiviral
prescriptions. In both studies, no clear difference was found
between both case definitions.
64,65
Quality assessment of the included studies
The methodological quality of each publication was assessed
using the quality assessment tool provided in Supplementary
Table 3. The majority of studies had a valid case definition for
the diagnosis of HZ and the denominator to calculate incidence
was properly defined. However, the majority of studies did not
capture individuals that were representative of the target popu-
lation (Supplementary Table 5).
Discussion
This review provides an overview of the worldwide incidence of
HZ in the general population with data from 69 studies. It also
provides important contemporary insights on the incidence of HZ
by gender, age, immunocompetent status, ethnicity, study year
and case definition since the last published systematic review on
this topic by Kawai et al.
4
in 2014. It should be noted that this
review found little to no evidence for the regions of Eastern
Europe, Middle East, South America or Africa. HZ may be
a low health priority in many of these countries; however, the
proportion of older adults is projected to double over the next
several decades,
14
and the numbers of HZ cases may increase
worldwide. The evidence base from Kawai et al.
4
together with
this review provides a comprehensive overview of how an appro-
priate study methodology leads to consistent methods being used
for worldwide incidence studies to help deliver reliable estimates
of disease burden. These updated data could also be utilized in the
Figure 4. Cumulative HZ incidence (number of new HZ cases per 1,000 population) by (A) Time, (B) Age (region).
Source: Table 1
Figure 2A: Studies with at least 2 years of data are depicted
*Incidence rate (number of HZ cases per 1,000 person-years) converted to cumulative incidence (number of HZ cases per 1,000 population)
HZ, herpes zoster
Note: While 42 publications reported cumulative incidence, only 30 of these presented an overall incidence for those ≥50 years and are depicted here.
HUMAN VACCINES & IMMUNOTHERAPEUTICS 13
Figure 4. (Continued).
14 D. VAN OORSCHOT ET AL.
context of healthcare policy surrounding the implementation of
effective preventive measures such as vaccination against HZ.
Overall, the cumulative incidence of HZ ranged from 2.9 to
19.5 cases per 1,000 population and from 5.23 to 10.9 cases per
1,000 person-years in the general population ≥50 YOA. Among
geographical regions, the highest and lowest incidence rates
were both reported in the Asia-Pacific countries, although
incidence estimates overlap, and the lowest incidence came
from the same region. In the general population ≥50 YOA,
the cumulative incidence (3.22–11.2 versus 2.44–8.0 cases per
1,000 population) and incidence rates (6.05–12.8 versus
4.30–8.5 cases per 1,000 person-years) were higher in females
than in males. The incidence of HZ was higher in Caucasians
compared to persons of Black ethnicity, but this was examined
in only a few studies and could be attributed to under-
reporting. Only a few studies reported incidence data based
on these stratifications. Across regions, a trend of steadily
increasing HZ incidence over time is observed.
Variations in incidence estimates summarized in this review
could be related to several factors and warrant discussion in the
interpretation of the overall review findings. Methodological
variations related to geographical spread, sample size, diagnos-
tic methodology, time period and age of the study population
were observed among studies. This made comparisons between
studies difficult while simultaneously affecting generalizability.
Specifically, studies varied in terms of study setting (ranging
from a single region to national surveillance), and sample size
(ranging from 2,135 to 31,943,930 individuals) with informa-
tion on sample size lacking in 32 studies. In some studies,
antiviral prescriptions were used to define HZ. Individuals
with a mild case of HZ may not receive formal treatment but
may choose to obtain over-the-counter treatment; it is also
expected that treatment uptake differs by age which could
have led to differential case ascertainment. These factors
could have led to an underestimation of the overall HZ inci-
dence. To the contrary, the overall HZ incidence may have
been overestimated if only antivirals were used to confirm HZ
diagnosis, attributable to the fact that antivirals are also pre-
scribed for other diseases. Additionally, the study period also
differed between publications, with the oldest data reporting
for the period 1980–1989 and the most recent data for the year
2017. As HZ incidence tends to increase over the years and
differs by age, the study period and the age of the study
population should be kept in mind when comparing studies.
Most studies revealed a trend of increasing incidence of HZ
with increasing age. A few deviations were seen on this trend in
different regions, where the highest age groups (i.e. >80 YOA)
reported a drop in incidence. Reasons for this observation
could be that older adults have pain and rash due to other
conditions and, as such, HZ may be under-diagnosed, or the
fact that many subjects in insurance databases represent
a healthier cohort of individuals.
45
In addition, GP visits for
individuals who are institutionalized or in nursing homes are
not always captured in traditional databases. In this review, half
of the studies included outpatient-only settings, which lends
bias toward the representation of subjects with milder disease
(i.e. hospitalization not required). It is well documented that
the risk of hospitalization increases with age,
9
thereby conse-
quently under-representing the incidence in older adults.
Other studies can be considered as outliers when looking at
the overall trend with age, as they report either lower or higher
incidences. The deviations could generally be explained by the
type of study design, choice of population, case definition and
healthcare-seeking behavior of individuals in a specific setting.
Some of these studies used different case definitions, for exam-
ple; self-reporting using a random digit dialing survey;
15
use of
clinical confirmation only via GP clinics;
70
and self-reporting
via surveying individuals door to door
68
and a national data-
base study that captures mild cases with an over-representation
of females
82
).
The results of the quality assessment of the included studies
revealed that a majority of the 69 studies had a valid case
definition for the diagnosis of HZ and the denominator to
calculate incidence was generally properly defined. However,
most studies did not capture individuals that were representa-
tive of the national population. These methodological aspects
are seldom reported in the individual studies yet useful in
contextualizing and interpreting data from epidemiological
studies. In this review, it was often unclear from the individual
studies whether these regional studies were representative of
the overall national population due to several reasons. First, 36
of the included studies were nationwide studies or claimed to
be representative of the national population, while the remain-
ing studies were conducted in one or several regions. Second,
in all studies, baseline characteristics of the older adults were
generally lacking, as the focus of most of the studies was on the
total population instead of older adults. Third, most of the
included studies in this review were passive surveillance studies
that utilized a retrospective design which could have issues
surrounding quality of data or incomplete datasets.
Information coming from these databases is often dependent
on the quality of the information reported by the physicians,
with the possibility of mis-coding or under-diagnosis. Fourth,
few of these studies reported using a validated algorithm to
detect HZ while many of the studies noted misclassification of
HZ as a potential limitation. Many of the active surveillance
studies failed to provide the proportion of eligible patients that
were finally enrolled, making it difficult to state whether the
results were generalizable to the overall population. In some of
these studies a HZ case was defined by self-reporting, the
accuracy of which was never verified, as self-report of HZ is
subject to recall bias. Additionally, misclassification of HZ
disease due to other rashes (e.g., herpes simplex) or other
rashes classified as HZ based on ICD codes may also have
occurred. Thus, misclassification of HZ could inadvertently
lead to an underestimation or overestimation of HZ cases in
the overall population.
Review limitations
Several limitations of this review are worth noting in the
interpretation of the overall findings. The search strategy
was not designed to find publications on the epidemiology
or disease burden of HZ in general. Therefore, some publica-
tions that did not specify incidence in the title or abstract or
to which an incidence medical subject heading term was not
assigned, may not have been captured in this review.
However, by screening all systematic reviews and meta-
HUMAN VACCINES & IMMUNOTHERAPEUTICS 15
analyses for potentially relevant publications, we feel that this
limitation has largely been overcome. A time limit was
applied to the searches to identify publications beginning
from 1 January 2002. This was considered appropriate by
the authors for the update of the evidence base on incidence
as a previous review by Kawai et al. summarizes the incidence
data from studies that covers time periods from as early as
1945 until 2012.
4
Another limitation of this review is the use
of an invalidated checklist to perform a quality check of the
included studies. However, the quality check performed in
this review is simplistic but sheds light on important gaps in
the study methods and results reported in the individual
studies. Performing such quality checks could drive improve-
ment and harmonization of reporting standards for these
types of publications in the future.
Conclusion
Over the last few decades, the incidence of HZ has increased
with increasing age due to the aging of the population world-
wide, and this trend is visible independent of geographic
location.
10
Independently of geographic location, the world’s
population is aging: the number of older persons is rising,
and older age groups constitute a growing share of the popu-
lation in nearly every country, with implications foreseen for
the healthcare sector among others. The aim of many health-
care systems around the world is to focus on promoting
healthy aging to prevent diseases and chronic conditions. In
this context, the occurrence of HZ, and its associated com-
plications, is expected to place an additional burden, espe-
cially in older patients who already have health problems to
cope with in their everyday life. Effective vaccines to prevent
HZ are available and are known to have a substantial positive
impact on improving the quality of life and on decreasing the
burden of complications associated with HZ in older
individuals.
Plain language summary
What is the context?
Herpes Zoster (HZ) occurs due to the reactivation of the varicella
zoster virus and is common among adults ≥50 years of age (YOA) as
cell-mediated immunity declines due to aging.
Age is a significant risk-factor related to HZ and an increase in life
expectancy of the general population may considerably increase the
number of HZ cases.
In the context of the world’s aging population, the occurrence of HZ is
expected to place an additional burden on patients ≥50 YOA who
might already have other health problems to cope with in their every-
day life.
What is new?
This systematic review of 69 full-text publications demonstrates that
the worldwide incidence of HZ is high among individuals ≥50 YOA
with little variation in the different regions of the world.
When comparing the geographical regions, the highest incidences
were mostly reported in the Asia-Pacific countries.
Our results suggest that the incidence of HZ is higher in females than
in males.
The majority of studies also reported a higher incidence of HZ with
increasing age.
Incidence rates did not seem to differ when different case definitions
were used.
By ethnicity, incidence rates were the highest among Caucasians and
the lowest among Black, Hispanic or other ethnicities.
Studies which reported HZ incidence by year mostly showed an
increase in incidence over time.
What is the impact?
This review provides a comprehensive overview of HZ disease burden,
that could be considered during the planning and implementation of
preventive measures such as vaccination against HZ.
Health care systems around the world are increasingly focusing on
promoting healthy aging to prevent diseases and chronic conditions.
In this context, the prevention of HZ among the ≥50 YOA population
could bring about a reduction in the risks to their health and improve
their quality of life.
Acknowledgments
The authors would like to thank Business & Decision Life Sciences plat-
form for editorial assistance and manuscript coordination, on behalf of
GSK. Maxime Bessières coordinated manuscript development and editor-
ial support. Amrita Ostawal (Arete Communication UG) provided writing
support for this literature review.
Contributorship
All authors were involved in the design of the study. EB, DC, DVO, and
HV collected or generated the data. All authors analyzed and/or inter-
preted the data and participated to the development of this manuscript
and in its critical review with important intellectual contributions. All
authors had full access to the data and gave approval of the final manu-
script before submission. All authors agreed to be accountable for all
aspects of the work in ensuring that questions related to the accuracy or
integrity of any part of the work are appropriately investigated and
resolved. The work described was carried out in accordance with ICMJE
recommendations for conduct, reporting, editing and publications pub-
lishing of scholarly work in medical journals. The corresponding author
had the final responsibility to submit for publication.
Conicts of interest
DVO, DC and JDD are employed by the GSK group of companies. DC
and DVO hold shares in the GSK group of companies. BY reports personal
fees from the GSK group of companies during the conduct of the study
and personal fees from the GSK group of companies outside the submitted
work. HV and EB report grants from the GSK group of companies during
the conduct of the study and grants from the GSK group of companies and
Sanofi Pasteur outside the submitted work.
Disclosures
Trademark
Shingrix is a trademark owned by or licensed to the GSK group of
companies.
Zostavax is a trademark owned by or licensed to Merck Sharp &
Dohme Corp.
Funding
GlaxoSmithKline Biologicals SA funded this study (GSK study identifier:
HO-18-19810) and was involved in all stages of study conduct, including
analysis of the data. GlaxoSmithKline Biologicals SA also paid all costs
associated with the development and publication of this manuscript
16 D. VAN OORSCHOT ET AL.
ORCID
Désirée van Oorschot http://orcid.org/0000-0002-0382-0333
Eveline Bunge http://orcid.org/0000-0001-7988-909X
John Diaz-Decaro http://orcid.org/0000-0001-6487-2113
Desmond Curran http://orcid.org/0000-0002-7423-0111
Barbara Yawn http://orcid.org/0000-0001-7278-5810
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HUMAN VACCINES & IMMUNOTHERAPEUTICS 19
... The incidence of HZ reactivation is strongly linked to the immune status of the individual. Variables such as advanced age, immunosuppression, metabolic and neoplastic disorders are among the most common risk factors [3,[6][7][8]. Reactivation in immunocompromised patients is usually associated with a more extensive local rash than in heathy individuals and is often accompanied by viremia and a decline in VZV-specific cell-mediated immunity [8]. Visceral involvement in high-risk patients increases the morbidity and mortality associated with VZV requiring prompt diagnosis and treatment of cutaneous VZV infection to reduce the risk of dissemination. ...
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Diagnosis of atypical generalized forms of herpes zoster can be a challenge and may lead to a delay in treatment. Herpes zoster can present with atypical clinical manifestations, some with higher risk of complications that are potentially life-threatening. We describe a patient that presented with several ulcerated papules and plaques in a non-dermatomal distribution in whom disseminated cutaneous herpes zoster was proven by molecular amplification testing. Patients with disseminated herpes zoster should be treated initially with intravenous antiviral therapy, followed by oral acyclovir, valacyclovir, or famciclovir in most adults, with close follow-up. Earlier treatment may reduce the risk of developing complications and progression of visceral involvement. This case adds to the evolving literature related to herpes zoster, especially regarding patients with immunosuppressed status.
... [13] The mean duration of the rash ranges from 7 to 10 days and is a self-limiting disease. [14] HZ is caused by the reactivation of VZV, which tends to remain in a latent state in the dorsal root ganglia of cutaneous nerve endings following a primary episode of chickenpox. [15] Reactivation happens when the immunological mechanisms that suppress VZV replication fail to contain the virus. ...
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Previous evidence has linked the relationship between newly onset skin disorder and SARS-CoV-2 infection. Cutaneous manifestations have been reported after exposure to COVID-19 vaccines that are linked to body immune responses. There is limited information about skin disorder that occurs after the COVID-19 vaccination. We report a case of varicella-zoster virus reactivation following inactivated COVID-19 vaccination in a young female patient.
... Herpes zoster (HZ), or shingles, a painful dermatomal vesicular rash, is caused by the reactivation of a latent varicella-zoster virus (VZV) infection and is increasingly common as adults age, affecting almost one in three people in the United States (USA) during their lifetime [1][2][3][4]. A significant subgroup of people with shingles experience complications, including long-lasting neuropathic pain (postherpetic neuralgia (PHN)), eye complications (herpes zoster ophthalmicus), or recurrences [2,5,6]. ...
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Herpes zoster (HZ) is common in older adults with conditions such as chronic obstructive pulmonary disease (COPD). Effective prevention is available through vaccination, but HZ vaccine uptake remains incomplete. Using an online survey of people with self-reported COPD, ShiPPS assessed HZ risk awareness, HZ vaccine use and barriers, and the impact of an HZ educational video on vaccine intent. USA members of the COPD Foundation’s Patient-Powered Research Network aged >50 years were surveyed in fall 2020. The responses were analyzed using descriptive and comparative statistics. Of the 735 respondents (59.6% female, mean age 68.5 years), 192 (26.1%) reported previous HZ, of whom 49 (25.5%) reported increased COPD symptoms during HZ episodes. Most participants (94.0%) knew of HZ vaccines, but only 33.1% reported receiving the Advisory Committee on Immunization Practices-preferred recombinant HZ vaccination. The recall of receiving HZ vaccine recommendations differed by the site attended: 68.8% primary care, 26.6% pulmonology offices. Most (74.7%) were unaware that COPD increases HZ risk. Among unvaccinated participants, interest in getting the HZ vaccine increased from 32.0% to 73.5% after watching the video. These results highlight the need for people with COPD to receive further HZ education, such as the five-minute video, and HZ vaccine recommendations from healthcare professionals.
... The results of a systematic review that characterized the incidence rate of HZ in the general population showed that the cumulative incidence of HZ was higher in women than in men worldwide [23]. It was clearly demonstrated that female sex was an independent risk factor for HZ, and women with HZ more frequently had PHN [24]. ...
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Introduction: Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments. Studies have shown that pulsed radiofrequency (PRF) can alleviate ZAP and reduce the incidence of postherpetic neuralgia (PHN). This study aimed to explore the clinical characteristics associated with PRF responsiveness, develop a model for identifying risk factors of inadequate PRF management, and help clinicians make better decisions. Methods: Patients who underwent PRF for ZAP between January 2017 and October 2020 in our hospital were included in this study. Patients were evaluated using the numerical rating scale (NRS), Insomnia Severity Index, Patient Health Questionnaire-9, and 36-Item Short Form Health Survey (SF-36) before and 3 months after the procedure. Patient demographic data and blood test results were also collected. We defined the effectiveness of PRF for ZAP as relief of > 50% in NRS scores compared to pre-PRF. Least absolute shrinkage and selection operator (LASSO) regression analyses were subsequently performed to identify factors related to the therapeutic effect of PRF in patients with ZAP. The performance of the prediction model was assessed by the area under the receiver operating characteristic curve (AUC). Results: The effectiveness of PRF in patients with ZAP was 69.6% (total 313 patients) after 3 months. LASSO regression analysis extracted the seven most powerful features in the developed prediction model: sex, stage of herpes zoster (HZ), pregabalin dose, bodily pain indicators of SF-36, lymphocyte count, and low-density lipoprotein cholesterol (LDLC) and complement C4 in peripheral blood. Model = 1.586 + 0.148 × lymphocyte + (-0.001) × bodily pain indicators of SF-36 + (-0.001) × pregabalin dose + 0.028 × LDLC + 0.001 × C4 + (-0.508) × sex + (-0.128) × stage of HZ. We generated the ROC curve for the prediction model, and the final AUC was 0.701. The sensitivity, specificity, and overall accuracy of the model were 90%, 33%, and 73%, respectively. Conclusions: Seven factors were significantly associated with poor PRF outcome: male sex, advanced stage of HZ, higher pregabalin dose, higher bodily pain indicators of SF-36, and lower lymphocyte count, LDLC, and complement C4 in the peripheral blood. PRF should be applied to patients with ZAP as early as possible to achieve satisfactory outcomes.
... per 1000 persons per year in elderly patients (i.e., >65 years) [12]. According to a systematic review of studies from 2002-2018, the cumulative incidence has been estimated between 2.9-19.5 cases per 1000 population with female predominance [13]. ...
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The Varicella-zoster virus (VZV) or human herpes virus 3 is a neurotropic human alpha herpes virus responsible for chickenpox/varicella and shingles/herpes zoster (HZ). This review will focus on HZ. Since HZ is secondary to varicella, its incidence increases with age. In children and youngsters, HZ is rare and associated to metabolic and neoplastic disorders. In adults, advanced age, distress, other infections (such as AIDS or COVID-19), and immunosuppression are the most common risk factors. HZ reactivation has recently been observed after COVID-19 vaccination. The disease shows different clinical stages of variable clinical manifestations. Some of the manifestations bear a higher risk of complications. Among the possible complications, postherpetic neuralgia, a chronic pain disease, is one of the most frequent. HZ vasculitis is associated with morbidity and mortality. Renal and gastrointestinal complications have been reported. The cornerstone of treatment is early intervention with acyclovir or brivudine. Second-line treatments are available. Pain management is essential. For (secondary) prophylaxis, currently two HZV vaccines are available for healthy older adults, a live attenuated VZV vaccine and a recombinant adjuvanted VZV glyco-protein E subunit vaccine. The latter allows vaccination also in severely immunosuppressed patients. This review focuses on manifestations of HZ and its management. Although several articles have been published on HZ, the literature continues to evolve, especially in regard to patients with comorbidities and immunocompromised patients. VZV reactivation has also emerged as an important point of discussion during the COVID-19 pandemic, especially after vaccination. The objective of this review is to discuss current updates related to clinical presentations, complications, and management of HZ.
... 6,7 The rash lasts about 7-10 days on average, and it is a self-limiting illness. 8 Although it is usually a mild infection, it can lead to disseminated cutaneous eruptions, encephalomyelitis, and pneumonia in immunocompromised people. 7 Our patient had no history of hypertension, diabetes, or any chronic illness. ...
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COVID‐19 has been linked to a number of cutaneous symptoms in COVID‐19 patients. Although herpes zoster (HZ) was the first sign of COVID‐19 infection in several patients, cases of HZ after COVID‐19 vaccination are rare. Here, we report a case of 51‐year‐old male patient with herpes zoster after Sinopharm (Vero cell) vaccination.
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Background: Herpes zoster (HZ) infection is seen in 2.9-19.5 per 1000 people worldwide. The perioperative risk of myocardial infarction (MI) following HZ reactivation is unknown. Case Presentation: We present the case of a middle-aged female without prior history of coronary artery disease (CAD) who underwent a paraesophageal hernia repair following two episodes of shingles. The preoperative assessment indicated a “below average” risk (0.1-0.4%) of major adverse cardiac events (MACE). However, the patient experienced an intraoperative MI. Conclusions: The case raises awareness that HZ reactivation may be a potential risk factor for perioperative MI. Further research is needed to establish the associated risk along with determining the appropriate perioperative management for patients with HZ reactivation.
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Postherpetic neuralgia (PHN) is a common, painful, and long-term complication of herpes zoster (HZ). PHN increases the demand for healthcare services and, previous studies showed that patients who received antiviral agents were less likely to develop PHN. The objective of this study was to compare the efficacy of prodrugs and acyclovir in treating PHN among patients with HZ. The search included the PubMed, Medline, Embase, and Cochrane Center of Register of Controlled Trails databases through February 2022. Clinical trials and randomized controlled trials (RCTs) involving antiviral agent intervention for HZ patients diagnosed with PHN were eligible for inclusion. A meta-analysis was conducted to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs) with a fix-effect model. Five RCTs with 1147 HZ patients met our eligibility criteria. Our meta-analysis found that there was a significantly lower risk of PHN for members of the prodrugs group (famciclovir and valaciclovir) compared with those who received acyclovir (RR = 0.86, 95%, CI: 0.75 to 0.98, p = 0.03). The review of studies indicated that the efficacy of prodrugs was better than acyclovir for reliving PHN.
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Purpose: Herpes zoster ophthalmicus (HZO) is a sight-threatening condition that is defined as HZ involving the ophthalmic division of the trigeminal nerve. Cases of bilateral HZO in recent literature question the notion of HZO being a strictly unilateral disease. Its pathogenesis is a topic of debate and current literature on VZV dissemination lacks insight into the underlying immunology. This review focuses on novel research in immunology of HZO and aims to formulate hypotheses of spread of lesions through the CNS. Methods: A literature search was conducted on Entrez PubMed using the search terms "bilateral" and "herpes zoster ophthalmicus". Articles on ("Immunology" or "immune cells") and "herpes zoster ophthalmicus" were also searched for. Articles published from January 1942 to April 2020 that were in English language were included. Results: Our findings revealed that hypothesised mechanisms of dissemination causing bilateral ocular disease include transmission from nerves to vessel walls, the synergistic action of the immune and nervous systems through the action of substance P and the von Szily reaction. Conclusions: These mechanisms may be investigated using newer models of animal experimentation. It is imperative to define the molecular mechanisms behind VZV transmission to improve methods of identification, treatment, and prevention of HZO.
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Introduction: Many studies have been conducted worldwide to estimate herpes zoster (HZ) incidence rates. We synthesized studies of HZ incidence rates in the general population using meta-analysis models. Methods: A random effects meta-analysis was conducted to estimate HZ incidence from a published worldwide systematic literature review (SLR) including only individuals aged 50 years and older. Meta-regression was used to explore whether variability in incidence rates could be explained by a combination of study-specific characteristics including age, gender, continent and year of study data. The impact of adding additional covariates-case detection method (general practitioner surveillance, healthcare database, sentinel network, etc.), case definition (medical record-based, self-reported), study design (retrospective passive surveillance, retrospective active surveillance, etc.), incidence type (cumulative incidence/1000 persons or incidence rate/1000 person-years), patient type (outpatients or in- and out-patients) and latitude to the base model-was also assessed. Results: Sixty-one records from 59 studies were included in the analysis: 25, 20, 11 and 5 from Europe, North America, Asia and Oceania, respectively. There was variation in study methodology and outcomes. Heterogeneity of incidence rates was greatest among studies conducted in Asia. Meta-analysis showed that incidence increased with age, was lower in males compared to females, tended to be lower in Europe and North America compared to Asia and Oceania and increased with year of study data. The data-driven meta-regression model included continent, year of study data, gender, age and an age × gender interaction term. The difference in incidence between males and females was greater in younger ages (e.g., 50-59) compared to older age groups (e.g., 80+). None of the additional covariates contributed significantly to the model. Conclusion: Incidence rates were shown to vary by age, gender, continent and year of study data.
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Background Herpes zoster (HZ), also known as shingles, is a painful and commonly occurring condition in the United States. In spite of a universally recommended vaccine for use in immunocompetent adults aged 60 years and older, HZ continues to impact the American public, and a better understanding of its current incidence is needed. The objective of the current study is to estimate the overall and age- and gender-specific incidence rates (IRs) of HZ among an immunocompetent US population in 2011 following availability of a vaccine. Methods Claims data from the Truven Health MarketScan® Research databases between 01/01/2011 and 12/31/2011 were extracted. Immunocompetent adult patients, enrolled as of January 1, 2011 were analyzed. The denominator was defined as eligible subjects who were immunocompetent, had no evidence of zoster vaccination, and no diagnosis of HZ (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 053.xx) in the 90 days prior to January 1, 2011. Subjects contributed person-days to the denominator until the occurrence of one of the following events: end of continuous enrollment in the database, a claim for zoster vaccination, diagnosis of HZ or end of the observation period (December 31, 2011). The numerator was defined as enrollees within the denominator file exhibiting evidence of HZ. Annual IRs were calculated for the entire population in the database as well as by gender and age group; standardized IRs were also produced using the 2010 US Census data. Results The overall annual IR of HZ across all ages was 4.47 per 1000 person-years (95 % confidence interval [CI]: 4.44–4.50) which monotonically increased with age from 0.86 (95 % CI: 0.84–0.88) for those aged ≤19 to 12.78 (95 % CI: 12.49–13.07) for patients ≥80 years. The IR was 8.46 (95 % CI: 8.39–8.52) among adults ≥50 years and 10.46 (95 % CI: 10.35–10.56) among those aged ≥60 years. Women compared to men had higher HZ incidence (5.25, 95 % CI: 5.21–5.29 vs. 3.66, 95 % CI: 3.62–3.69) and this was seen across all age groups. When adjusted for age and gender using 2010 US Census data, the annual IR was 4.63 per 1000 person-years (95 % CI: 4.61–4.66). Conclusions Despite the availability of a vaccine, HZ remains common among immunocompetent adults in the US with incidence rates of HZ observed to increase with age and be higher in women than men.
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Introduction The aim of this study is to describe the disease burden and costs of herpes zoster (HZ) in the general adult Japanese population or patients with immunocompromised (IC) conditions or chronic disorders. Methods A retrospective cohort study of individuals aged 18–74 years was conducted using January 2005 to December 2014 records from the Japan Medical Data Center claims database. Twenty-eight IC conditions and chronic disorders were defined by diagnosis codes and/or procedures/treatments. HZ and its related complications were identified. Incidence rates (IR), frequency of HZ-related complications, healthcare resource utilization (HRU), and direct medical costs were estimated. HRU and costs were estimated on a subcohort of HZ cases occurring April 2012–January 2014. Results The overall IR of HZ in the total cohort of 2,778,476 adults was 4.92/1000 person-years (PY) [95% confidence interval (CI): 4.86–4.98] and increased with age. The IR in the IC cohort (51,818 subjects) was 8.87/1000 PY (95% CI: 8.29–9.48), ranging from 5.55/1000 PY (95% CI: 4.26–7.09) in psoriasis to 151.68/1000 PY (95% CI: 111.45–201.71) in hematopoietic stem cell transplant recipients; most IRs were in the range 6–10/1000 PY. The IRs in individuals with chronic disorders were also relatively high, in the range 5.40–12.90/1000 PY. The frequency of postherpetic neuralgia was 4.01% (95% CI: 3.72–4.33) in the total cohort and 11.73% (95% CI: 9.01–14.93) in the IC cohort. The mean [standard deviation (SD)] number of outpatient visits was 3.4 (4.9) and 5.0 (5.7), respectively, and the proportion of HZ patients hospitalized was 2.20% and 6.70%, respectively. The mean (SD) direct medical cost per HZ episode was ¥34,664 (¥54,433) and ¥55,201 (¥92,642) in the total and IC cohort, respectively. Conclusions The elevated burden of HZ in Japanese individuals harboring IC conditions and chronic disorders documented in our study underlines the need for prevention of HZ in people with these conditions. Funding GlaxoSmithKline Biologicals SA.
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Background: Effects of universal varicella vaccination on the herpes zoster (HZ) incidence have not been elucidated. Universal varicella vaccination was introduced in Japan in October 2014. Objective: We investigated the effects of universal varicella vaccination on HZ epidemiology. Methods: Patients with HZ have been monitored by the Miyazaki Dermatologist Society since 1997, and the effects of universal vaccination on the HZ incidences have been analyzed to determine which generation is most affected. Results: The number of HZ patients increased 1.54 times, and the gradual increase in the HZ incidence was observed in not only patients >60 years, but also other generations during the period from 1997 to 2017. The number of varicella patients was gradually reduced from 2010 to 2017 before introduction of universal varicella vaccination, and the HZ incidence in yearly change significantly increased from 2014 to 2016 in the total population associated with the significant decrease in varicella incidence. The HZ incidence significantly increased for individuals aged 20 to 49 years from 2014 to 2015 and most for individuals age 20-29 years (odds ratio [OR], 1.270; 95% confidence interval [CI], 1.071-1.505, P < 0.001). We identified the child-rearing generation of age 20 to 49 years (OR, 1.270; 95% CI, 1.071-1.505, P < 0.001) as the generation most influenced by universal varicella vaccination, when the HZ incidence increased gradually by approximately 2% per year. Conclusions: Universal vaccination increased the HZ incidence in the child-rearing generation among the generations, possibly by reduced chance of boosting their immunity by exposure to varicella.
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Objective To investigate the incidence of primary care presentations for herpes zoster (zoster) in a representative New Zealand population and to evaluate the utilisation of primary healthcare services following zoster diagnosis. Design A cross-sectional retrospective cohort study used a natural language processing software inference algorithm to identify general practice consultations for zoster by interrogating 22 million electronic medical record (EMR) transactions routinely recorded from January 2005 to December 2015. Data linking enabled analysis of the demographics of each case. The frequency of doctor visits was assessed prior to and after the first consultation diagnosing zoster to determine health service utilisation. Setting General practice, using EMRs from two primary health organisations located in the lower North Island, New Zealand. Participants Thirty-nine general practices consented interrogation of their EMRs to access deidentified records for all enrolled patients. Out-of-hours and practice nurse consultations were excluded. Main outcome measures The incidence of first and repeated zoster-related visits to the doctor across all age groups and associated patient demographics. To determine whether zoster affects workload in general practice. Results Overall, for 6 189 019 doctor consultations, the incidence of zoster was 48.6 per 10 000 patient-years (95% CI 47.6 to 49.6). Incidence increased from the age of 50 years to a peak rate of 128 per 10 000 in the age group of 80–90 years and was significantly higher in females than males (p<0.001). Over this 11-year period, incidence increased gradually, notably in those aged 80–85 years. Only 19% of patients had one or more follow-up zoster consultations within 12 months of a zoster index consultation. The frequency of consultations, for any reason, did not change between periods before and after the diagnosis. Conclusions Zoster consultations in general practice are rare, and the burden of these cases on overall general practice caseload is low.
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Background: The objectives of this study were to characterize the burden of herpes zoster, as well as the longitudinal and incremental changes of healthcare service utilization among individuals with herpes zoster and postherpetic neuralgia (PHN) compared to those without. Methods: Using the National Health Insurance Research Database (NHIRD), we established a herpes zoster cohort of people diagnosed with herpes zoster between 2004 and 2008 as study cases. Another subset of the NHIRD, which was randomly selected from all elderly beneficiaries between 2004 and 2008 served as a non-herpes-zoster elderly control pool. Each case was then assigned one matched control according to age, gender, index date and propensity score. PHN cases were defined as those with persisting pain for more than 90 days after the onset of herpes zoster. Results: Between 2004 and 2008, about 0.6 million patients were newly diagnosed with herpes zoster. The incidence increased with age, and most cases were identified during the summer period. Herpes zoster cases were found to have higher consumption of all types of healthcare services in the first year after the index date. Such increases were particularly obvious for patients with PHN, who showed incremental increases on average of 16.3 outpatient visits, 0.4 emergency room visits and 0.24 inpatient admissions per year. Conclusions: The incidence of herpes zoster increased with age and changed according to the seasons. Patients with herpes zoster were associated with higher healthcare utilization and this increase in healthcare utilization was most obvious for herpes zoster patients with PHN.
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Background: Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. Methods: In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. Results: Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. Conclusion: This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK.
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Background: Zoster vaccination was introduced in England in 2013, where tackling health inequalities is a statutory requirement. However, specific population groups with higher zoster burden remain largely unidentified. Objective: To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England. Methods: This population-based cohort study utilised anonymised UK primary care data linked to hospitalisation and deprivation data. Individuals aged ≥65 years without prior zoster history (N=862,470) were followed from 01/09/2003-31/08/2013. Poisson regression was used to obtain adjusted rate ratios (ARR) for the association of socio-demographic factors (ethnicity, immigration status, individuals' area-level deprivation, care home residence, living arrangements) with first zoster episode. Possible mediation by co-morbidities and immunosuppressive medications was also assessed. Results: There were 37,014 first zoster episodes, with incidence of 8.79 (95% confidence interval (CI):8.70-8.88) per 1,000 person-years at risk. In multivariable analyses, factors associated with higher zoster rates included care home residence (10% higher versus those not in care homes), being female (16% higher versus males), non-immigrants (~30% higher than immigrants) and White ethnicity (for example, twice the rate compared to those of Black ethnicity). Zoster incidence decreased slightly with increasing deprivation (ARR most versus least deprived=0.96 (95%CI:0.92-0.99) and among those living alone (ARR 0.96 (95%CI:0.94-0.98). Mediating variables made little difference to the ARR of social factors but were themselves associated with increased zoster burden (ARR varied from 1.11-3.84). Conclusions: The burden of zoster was higher in specific socio-demographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination. This article is protected by copyright. All rights reserved.
Article
Historic herpes zoster incidence trends in US adults have been hard to interpret. Using administrative databases, we extended previous descriptions of these trends through 2016. We observed an age-specific transition, with ongoing increases among younger adults but deceleration in older adults. The patterns are not readily explained.
Article
Little data are available on the overall incidence and characteristics of herpes zoster (HZ) in China, thus a community-based retrospective survey was conducted during December 2012 to March 2013 to collect HZ incident data over the past year in selected districts of Beijing, China. A total of 237 incident HZ cases were identified from 118,220 residents and majority of HZ patients (219/237, 92.4%) sought healthcare. Annual HZ incident rates were 1.90/1000 after adjusted and higher among females (2.4/1000) than males (1.7/1000). HZ rates increased with age and with a sharply rise among those aged ≥50 years particular for female. 217 cases were available for interview with 193 (88.9%) primary, 24 (11.1%) recurrent and 10 (4.6%) postherpetic neuralgia (PHN) cases respectively. No difference was shown between the primary and recurrent HZ cases in sex (P = 0.42), age (P = 0.72), times of healthcare seeking (P = 0.45), number of dermatome (P = 0.72), pain degree (P = 0.54), and hospitalization (P = 1.0). According to the survey, it can be speculated that disease burden of HZ is serious and caused at least 2.77 million cases annually in China. The recurrent HZ cases has similar characteristics to primary HZ cases. High proportion of healthcare seeking reminds that HIS records would be a feasible source for HZ surveillance to evaluate the trends and changes in China.
Article
Objectives: Herpes zoster (HZ) mainly affects elderly people and immunocompromised individuals. HZ is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain. This study aimed to estimate the HZ incidence in individuals aged ≥50 years in Germany, the proportion of PHN and the economic burden. Methods: From 2010 to 2014, HZ patients were recruited when consulting physicians in physician networks covering about 157,000 persons aged ≥50 years. PHN was defined as "worst pain" rated ≥3 on the zoster brief pain inventory persisting or appearing over 90 days after rash onset. Costs were calculated based on medical resource utilization and lost working time. Results: HZ incidence was estimated as 6.7/1000 person-years, increasing with age to 9.4/1000 in ≥80 year-olds. Among 513 HZ patients enrolled, the proportion of PHN was 11.9%, rising with age to 14.3% in HZ patients ≥80 years. Estimated total cost per HZ patient was €156 from the healthcare system perspective and €311 from the societal perspective. Conclusions: The study confirmed previous findings that HZ causes a substantial clinical and economic burden in older German adults. It also confirmed the age-related increasing risk of HZ and PHN.