E D I T O R I A L C O M M E N TA R Y
Varicella Zoster Virus Transmission in the Vaccine Era:
Unmasking the Role of Herpes Zoster
Karen C. Bloch and James G. Johnson
Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
(See the article by Viner et al, on pages 1336–41.)
Varicella (chickenpox) is a highly con-
tagious disease caused by varicella zoster
virus (VZV). After infection, the virus
remains dormant in sensory dorsal
root ganglia. Reactivation of latent
VZV is associated with cutaneous dis-
ease occurring in $1 dermatomes,
termed herpes zoster (HZ). Historically,
HZ has been considered significantly
less infectious than varicella and has not
been thought to play an important role
in person-to-person transmission. Since
the licensure of the varicella vaccine in
1995 and the more recent recommen-
dation that a second dose of vaccine be
given to children aged 4–6 years , the
epidemiology of pediatric varicella in-
fection has shifted dramatically .
Efforts to quantify the burden of
varicella in the community since vac-
cine licensure have been hindered by
the absence of mandatory case-based
reporting in most jurisdictions . The
article by Viner et al in this issue of
the journal  provides important new
insights into the epidemiology and
transmissibility of VZV in a highly im-
munized, healthy pediatric population.
The authors analyzed data obtained
through a combination of active and
passive surveillance for both varicella and
HZ in Philadelphia schools and day care
centers during 7 academic years. Cases
were linked to the Philadelphia De-
partment of Public Health immuniza-
tion registry for ascertainment of vaccine
status. Through this comprehensive
surveillance system, 2296 cases of VZV-
associated infection were identified, with
28% categorized as secondary varicella.
Much of what is known about VZV
transmission dynamics in the commu-
nity comes from outbreak investigations
at elementary schools or day care centers.
In these settings, varicella attack rates
among children who had previously re-
ceived a single dose of varicella vaccine
ranged from 12%–42% [5–7]. A recent
report found that prior receipt of a sec-
ond dose of vaccine did not appreciably
decrease the attack rate during a school
outbreak . In contrast, in an ele-
mentary school outbreak during which
the second dose of vaccine was given as
an intervention for outbreak control,
the attack rate was reduced from 43%
among children who had received only
a single vaccination to 5% among 2-dose
recipients . Large-scale, school-based
varicella outbreaks such as these serve
as important sentinel events but may not
be representative of the true burden and
infectivity of VZV in the community.
In the study by Viner et al, .80% of
epidemiologically linked transmissions
involved ,4 secondary cases and, in the
absence of a dedicated varicella surveil-
lance system, would be unrecognized and
Despite the continued documentation
of outbreaks among immunized school
children, the varicella vaccine epitomizes
a public health success story. In the
prevaccine era, varicella was an almost
universal disease of childhood. After the
widespread implementation of pediatric
vaccination in the United States, in-
cidences of VZV-related infection, hos-
pitalization, and death have all markedly
declined [10, 11]. In the present study,
.90% of children who developed sec-
ondary varicella had received $1 doses
of vaccine before the onset of infection,
representing vaccine failures. However,
even in these breakthrough cases, the
benefits of vaccination are evident. As
has been reported elsewhere [12, 13],
.70% of breakthrough varicella cases
had mild disease characterized by ,50
skin lesions. Vaccinated varicella cases
were associated with a significantly lower
proportion of secondary cases compared
withunvaccinated cases, presumably
related to lower virus burden and shorter
duration of viral shedding. Finally, there
was a significant decline in the inci-
dence of all VZV-related infections in
Philadelphia schools beginning in 2007,
Received 9 December 2011; accepted 12 December 2011;
electronically published 27 March 2012.
Correspondence: Karen C. Bloch, MD, MPH, Division of
Infectious Diseases, Vanderbilt University Medical Center,
A-2200, Medical Center North, Nashville, TN 37232
The Journal of Infectious Diseases
? The Author 2012. Published by Oxford University Press on
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rights reserved. For Permissions, please e-mail: journals.
d JID 2012:205 (1 May)
correlating with the recommendation
for a second dose of vaccine for school-
aged children. These ecological data are
supported by a case control study report-
ing that the odds of developing varicella
were decreased 95% among children after
receipt of a second dose of varicella
vaccine . Based on these results, it
is anticipated that with increasing 2-
dose coverage, the rates of varicella
among children will continue to de-
Paradoxically, although the number of
varicella cases has decreased since the
introduction of the varicella vaccine, the
incidence of HZ has been increasing
[15, 16]. One hypothesis to explain this
phenomenon is that reexposure to VZV
among individuals with latent wild-type
infection causes humoral boosting and
improved virologic control . As the
number of children with varicella declines,
waning immunity among previously in-
fected adults may allow viral reactivation
clinically manifested as HZ. Additionally,
HZ may occur in immunocompetent
children after immunization [18, 19].
How does this shifting balance be-
tween varicella and HZ affect the trans-
missibility of VZV infection? Historically,
localized HZ has been considered a lower
infectious risk than disseminated HZ or
primary varicella . However, in the
study by Viner et al, there was substantial
linkage between secondary varicella cases
and antecedent exposure to an individual
with HZ. Almost 10% of HZ cases were
compared with 15% of sporadic varicella
cases. Herpes zoster cases were as likely
as varicella cases to be associated with
clusters of .2 secondary cases, and the
severity of secondary varicella did not
differ after exposure to HZ or varicella.
Transmission of VZV occurs primarily
via inhalation of airborne droplet nuclei,
aerosolized either from the respiratory
tract or from vesicular skin lesions .
Virus aerosolization has been documented
with both HZ and primary varicella [22,
23], and reports of secondary varicella
after exposure to a source patient with
localized HZ have been described else-
where [24, 25]. Varicella zoster virus DNA
may persist in saliva and blood after HZ,
and exposure to these fluids may con-
stitute additional potential routes of
transmission [26, 27]. Varicella infection
is most common after close contact with
a source patient, with environmental
reservoirs unlikely to play a significant
role in transmission .
Prevention of varicella transmission in
both the community and the healthcare
setting depends on universal VZV vacci-
nation, as well as appropriate identifica-
tion and isolation of infected individuals
. Current guidelines recommend
standard precautions for hospitalized
patients with localized HZ, whereas
both airborne and contact isolation are
recommended for disseminated HZ
(including localized HZ in an immu-
nocompromised patient) or primary
varicella . In the community, pa-
tients with HZ are generally allowed to
return to group settings such as work or
school if the skin lesions can be covered
. The study by Viner et al calls the
approach to localized HZ into question.
Not only was the risk of secondary in-
fection with HZ comparable to that of
primary varicella, the risk was similar
regardless of the anatomic location of HZ.
This finding contradicts the assumption
that coverage of active skin lesions with
dressings or clothing reduces VZV aero-
solization and, if substantiated through
further investigation, may warrant a
change in current recommendations for
The study by Viner et al offers com-
pelling epidemiologic data regarding the
increasing importance of HZ in ongoing
transmission of VZV in school settings.
However, several features limit the in-
terpretation of these findings. Mis-
classification of unrelated skin eruptions
as HZ or varicella may have occurred,
based on the lack of virologic confir-
mation of VZV infection. Alternatively,
mild VZV infections may have been
overlooked or underreported. Because
contact tracing was limited to the school
environment, acquisition of VZV in-
fection through family or social networks
may have been unrecognized, potentially
leading to exposure misclassification.
Future studies would be strengthened
by molecular epidemiology to better
characterize infections as vaccine-type
or wild-type strains of VZV .
The landmark study by Viner et al
highlights the critical importance of
public health surveillance programs to
document the natural history of VZV
infections after implementation of vacci-
nation programs. Despite almost univer-
sal varicella vaccination, secondary cases
of varicella were reported in children
exposed to HZ at a frequency compara-
ble to that reported in children exposed
to sporadic varicella cases. As the absolute
number of varicella infections continues
to decline with universal implementation
of a 2-dose varicella vaccine schedule, it
is anticipated that HZ will play an in-
creasingly significant role in secondary
transmission. Recognition of the impor-
tance of HZ in perpetuating VZV in-
fections has significant implications for
public health practices in pediatric group
settings. Further studies focused on HZ
infectivity in both the community and
hospital are needed to accurately quantify
risk and guide prevention strategies.
by an Emerging Infections Program cooperative
agreement (GR1032692) with the Centers for
Disease Control and Prevention to K. C. B. J. G. J.
has received funding for research through the
Institute for Clinical and Translational Research.
J. G. J. received fellowship funding through the
Sanofi-Pasteur Fellowship in Healthcare Epide-
Potential conflicts of interest.
No reported conflicts.
All authors have submitted the ICMJE Form
for Disclosure of Potential Conflicts of Interest.
Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
This work was supported
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