J Clin Virol. 2010 May;48
Advances in the understanding
of the pathogenesis and epidemiology of herpes zoster.
Gershon AA, Gershon
MD, Breuer J, Levin MJ, Oaklander AL, Griffiths PD.
Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
The primary varicella
zoster virus (VZV) infection results in chickenpox (varicella), which is transmitted via the airborne route. VZV is highly
infectious, but in the USA the incidence of varicella has been reduced by 76-87% as
a result of the varicella vaccine. The virus establishes latency in the dorsal root ganglia during varicella and, when
reactivated, travels along the sensory nerve axons to cause shingles (herpes zoster [HZ]). There are over 1 million cases of HZ in the USA each year, with an estimated lifetime attack rate of 30%. The incidence
of HZ, which causes significant morbidity, increases with age and reaches approximately 10 cases per 1,000 patient-years by
age 80. Cell-mediated immunity (CMI) is known to decline with age as part of immunosenescence, and decreased CMI is associated
with reactivation of VZV. This article provides an overview of our emerging understanding of the epidemiology and pathogenesis
of varicella and HZ, in addition to exploring the current theories on latency and reactivation. Understanding the risk factors
for developing HZ and the complications associated with infection, particularly in older people, is important for prompt diagnosis
and management of HZ in primary care, and they are therefore also reviewed.
2010 Elsevier B.V. All
Neurology. 1995 Dec;45(12
Immunization to reduce
the frequency and severity of herpes zoster and its complications.
Medicine, University of California, San Diego, USA.
Herpes zoster (HZ) is
a localized disease that results from reactivation of an endogenous varicella-zoster virus (VZV) infection that has persisted
in latent form within sensory ganglia following an earlier attack of varicella. The incidence and the severity of HZ and its
complications increase with advancing age, and this is temporally associated with an age-related decline in cell-mediated
immunity (CMI) to VZV. Information on the cellular site and mechanism of VZV latency and on the events that follow reactivation
appears to explain many of the clinical features of HZ and to provide a pathophysiologic basis for the presumption that immunity to VZV plays a critical role in limiting the frequency and consequences of VZV
reactivation. The close temporal correlation between the decline in VZV-specific CMI and the increased frequency and severity
of HZ and its complications in older individuals suggests that HZ may actually develop because VZV-specific CMI falls below
some critical threshold. The development of a live attenuated varicella vaccine provides a means of stimulating VZV-specific
CMI and thus of determining its role in the pathogenesis of HZ. Levin and his colleagues have demonstrated that waning VZV-specific
CMI in elderly persons can be stimulated by varicella vaccine to levels typical of those observed in younger persons, in whom
the incidence and severity of HZ are much reduced. Thus the stage is set for a large placebo-controlled clinical trial that
will test directly the hypothesis that restoration of waning CMI to VZV will reduce the frequency and severity of HZ and its
complications in the elderly.
Drugs Aging. 2010 Feb
1;27(2):159-76. doi: 10.2165/10489140-000000000-00000.
Zoster vaccine (Zostavax):
a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults.
Sanford M, Keating GM.
SourceAdis, a Wolters
Kluwer Business, Auckland, New Zealand. firstname.lastname@example.org
Individuals who have
been infected with varicella zoster virus (VZV) are at risk for developing herpes zoster and this risk appears to be related
to a decline in VZV-specific cell-mediated immunity (CMI). Zostavax (zoster vaccine) is a one-dose, high-potency, live, attenuated
VZV vaccine that boosts VZV-specific CMI and this is its presumed mechanism of action. Zoster vaccine is registered in the
EU for use in adults aged >or=50 years for the prevention of herpes zoster and herpes zoster-related postherpetic neuralgia.
In the Shingles Prevention Study, a placebo-controlled trial in adults aged >or=60 years (n = 38 546), zoster vaccine led
to a sustained boost of VZV-specific CMI. Over a mean herpes zoster surveillance period of 3.1 years, zoster vaccine reduced
the herpes zoster-related burden of illness by 61%, reduced the incidence of herpes zoster by 51% and reduced the incidence
of postherpetic neuralgia by 67%. Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and
severity than placebo recipients who developed herpes zoster. Zoster vaccine had continuing efficacy in a Shingles Prevention
Study subpopulation followed for 7 years post-vaccination. Zoster vaccine was generally well tolerated in older adults. While
cost-effectiveness estimates in pharmacoeconomic analyses varied widely according to vaccine and herpes zoster parameter cost/benefit
estimates, an analysis from a UK perspective found a zoster vaccine immunization programme in adults aged 65 years to be cost
effective. In older adults, the zoster vaccine has the potential to significantly reduce the herpes zoster burden of illness
by decreasing the incidence of herpes zoster or reducing its severity.
Cochrane Database Syst
Rev. 2011 Mar 16;3:CD007795.
Vaccination for preventing
Chen N, Li Q, Zhang
Y, Zhou M, Zhou D, He L.
Neurology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, China, 610041.
BACKGROUND: Herpes zoster
virus vaccine was recommended for the prevention of herpes zoster and its sequelae by the Advisory Committee on Immunization
Practices (ACIP) in 2006. To date the efficacy and safety of vaccination for preventing the most common complication of zoster,
postherpetic neuralgia, has not been systematically reviewed.
OBJECTIVES: To assess
the efficacy and safety of vaccination in preventing postherpetic neuralgia.
SEARCH STRATEGY: We
searched MEDLINE (January 1966 to December 2010), EMBASE (January 1980 to January 2011), LILACS (January 1982 to December
2010), the Cochrane Neuromuscular Disease (NMD) Group Specialized Register (10 January 2010), the Cochrane Central Register
of Controlled Trials (CENTRAL) (10 January 2010 in the Cochrane Library, Issue 4, 2010) and the Chinese Biomedical Retrieval
System (January 1978 to December 2010). We also checked the references of published studies to identify additional trials.
We included all randomised controlled trials comparing varicella zoster virus vaccination with placebo, no vaccination or
another intervention, irrespective of publication status or language.
DATA COLLECTION AND
ANALYSIS: Two authors independently assessed trial quality, then extracted and analysed data from the trials which met the
inclusion criteria. We collected adverse effects information from the trials.
MAIN RESULTS: One trial,
which involved 38,546 subjects and compared vaccination with placebo, met our inclusion criteria. This included study was
of high quality. However, its participants were all aged 60 years or more and most of them were white, which may mean that
its findings are not applicable to all populations. The vaccine was effective in decreasing the incidence of herpes zoster,
but there was no evidence that it had efficacy in reducing the incidence of postherpetic neuralgia beyond its effect on the
incidence of herpes zoster. Adverse events at the injection site were more common among vaccine recipients than placebo recipients,
but they were mild and resolved in a few days. Serious adverse events were rare.
There is insufficient direct evidence from specialised trials to prove the efficacy of vaccine for preventing postherpetic
neuralgia beyond its effect on reducing herpes zoster, although vaccination may be efficacious and safe for preventing herpes
zoster and thus reduce the incidence of postherpetic neuralgia in adults aged 60 years or older.
Ann Intern Med. 2010
Safety of herpes zoster
vaccine in the shingles prevention study: a randomized trial.
Simberkoff MS, Arbeit
RD, Johnson GR, Oxman MN, Boardman KD, Williams HM, Levin MJ, Schmader KE, Gelb LD, Keay S, Neuzil K, Greenberg RN, Griffin
MR, Davis LE, Morrison VA, Annunziato PW; Shingles Prevention Study Group.
SourceNew York University
School of Medicine, New York, USA. Mike.SimberkoffMD@va.gov <Mike.SimberkoffMD@va.gov>
BACKGROUND: The herpes
zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However,
its safety has not been described in depth.
OBJECTIVE: To describe
local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults.
placebo-controlled trial with enrollment from November 1998 to September 2001 and follow-up through April 2004 (mean, 3.4
years). A Veterans Affairs Coordinating Center generated the permutated block randomization scheme, which was stratified by
site and age. Participants and follow-up study personnel were blinded to treatment assignments. (ClinicalTrials.gov registration
SETTING: 22 U.S. academic
PARTICIPANTS: 38 546
immunocompetent adults 60 years or older, including 6616 who participated in an adverse events substudy.
dose of herpes zoster vaccine or placebo.
adverse events and rashes in all participants and inoculation-site events in substudy participants during the first 42 days
after inoculation. Thereafter, vaccination-related serious adverse events and deaths were monitored in all participants, and
hospitalizations were monitored in substudy participants.
RESULTS: After inoculation,
255 (1.4%) vaccine recipients and 254 (1.4%) placebo recipients reported serious adverse events. Local inoculation-site side
effects were reported by 1604 (48%) vaccine recipients and 539 (16%) placebo recipients in the substudy. A total of 977 (56.6%)
of the vaccine recipients reporting local side effects were aged 60 to 69 years, and 627 (39.2%) were older than 70 years.
After inoculation, herpes zoster occurred in 7 vaccine recipients versus 24 placebo recipients. Long-term follow-up (mean,
3.39 years) showed that rates of hospitalization or death did not differ between vaccine and placebo recipients.
in the substudy were not randomly selected. Confirmation of reported serious adverse events with medical record data was not
CONCLUSION: Herpes zoster
vaccine is well tolerated in older, immunocompetent adults.
PRIMARY FUNDING SOURCE:
Cooperative Studies Program, Department of Veterans Affairs, Office of Research and Development; grants from Merck to the
Veterans Affairs Cooperative Studies Program; and the James R. and Jesse V. Scott Fund for Shingles Research.
Ann Intern Med. 2010
Aug 3;153(3):210-1; author reply 211-2.
Ann Intern Med. 2010
Ann Intern Med. 2010
Vaccine. 2010 Jun 7;28(25):4204-9.
Epub 2010 Apr 21.
and immunogenicity of zoster vaccine in subjects with a history of herpes zoster.
Mills R, Tyring SK,
Levin MJ, Parrino J, Li X, Coll KE, Stek JE, Schlienger K, Chan IS, Silber JL.
Research, Mount Pleasant, SC, United States.
BACKGROUND: Prior clinical
studies of zoster vaccine enrolled subjects without a history of herpes zoster (HZ), so there are limited data on safety and
immunogenicity in vaccinees with a prior history of HZ. This study was conducted to evaluate the safety and immunogenicity
of zoster vaccine recipients who had a prior episode of HZ.
METHODS: A total of
101 subjects > or = 50 years of age with a prior history of HZ were enrolled. They were stratified by number of years since
their HZ (5 to 9 years and > or = 10 years, in an approximate 2:1 ratio), and randomized 1:1 to one of two vaccination
groups. On day 1, Group I was administered zoster vaccine and Group II received placebo. At week 4, Group I received placebo
and Group II received zoster vaccine. Subjects were followed for adverse experiences (AEs), exposure to varicella or HZ, and
development of any varicella/varicella-like or HZ/HZ-like rashes, for 28 days after each injection. Blood samples were obtained
prior to study injection on day 1 and week 4, and at week 8. Serum was assessed for varicella-zoster virus (VZV) antibody
concentration by glycoprotein enzyme-linked immunosorbent assay.
RESULTS: No serious
AEs were reported within the 28-day safety follow-up period following any vaccination. Although a higher percentage of subjects
reported injection-site AEs after receiving zoster vaccine than did placebo recipients, the proportion of subjects reporting
systemic clinical AEs was similar in both groups. Zoster vaccine induced a VZV antibody response at 4 weeks post-vaccination.
The estimated geometric mean titer (GMT) ratio (vaccine/placebo) was 2.07 (95% CI: 1.48, 2.88). The geometric mean fold-rise
(GMFR) from prevaccination to week 4 post-vaccination was 2.1 in zoster vaccine recipients, versus 1.0 in placebo recipients.
CONCLUSIONS: In HZ history-positive
adults > or = 50 years of age, zoster vaccine: (1) was well tolerated; and (2) significantly boosted the level of VZV antibody
from baseline to 4 weeks post-vaccination as measured by GMT and GMFR. These data support the Advisory Committee on Immunization
Practices' recommendation for routine zoster vaccination for all immunocompetent persons >/=60 years of age irrespective
of HZ history.
Copyright 2010 Elsevier
Ltd. All rights reserved.
J Infect Dis. 2011 Feb
1;203(3):316-23. Epub 2010 Dec 21.
Varicella zoster disease
of the central nervous system: epidemiological, clinical, and laboratory features 10 years after the introduction of the varicella
Pahud BA, Glaser CA,
Dekker CL, Arvin AM, Schmid DS.
SourceDivision of Pediatric
Infectious Diseases, University of California, San Francisco, USA. email@example.com
BACKGROUND: Since the
introduction of live attenuated varicella zoster virus (VZV) vaccine in 1995 there has been a significant reduction in varicella
incidence and its associated complications, but the impact on VZV-associated central nervous system (CNS) disease has not
METHODS: In this descriptive
study we evaluated patients referred to the California Encephalitis Project from 1998 to 2009 with VZV PCR-positive cerebrospinal
fluid (CSF). Epidemiological, clinical, and laboratory data were collected using a standardized case form. Specimens were
genotyped using multi-single nucleotide polymorphism (SNP) analysis.
specimens were genotyped from patients 12-85 years of age (median, 46 years). Clinical presentations included meningitis (50%),
encephalitis (42%), and acute disseminated encephalomyelitis (ADEM) (8%). Only 11 patients (42%) had a concomitant herpes
zoster rash. Genotype analysis identified 20 European Group (Clade1, Clade 3) strains; 4 Asian (Clade 2) strains, and 2 Mosaic
Group (Clade 4, Clade VI) strains. One specimen was recognized as vaccine strain by identifying vaccine-associated SNPs.
CONCLUSIONS: VZV continues
to be associated with CNS disease, with meningitis being the most frequent clinical presentation. CNS VZV disease often presented
without accompanying zoster rash. Sequencing data revealed multiple genotypes, including 1 vaccine strain detected in the
CSF of a young patient with meningitis.