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REVIEW ARTICLEPEDIATRICS Volume 137 , number 3 , March 2016 :e 20153741
Global Varicella Vaccine Effectiveness: A Meta-analysisMona Marin, MD,a Melanie Marti, MD,b Anita Kambhampati, MPH,a Stanley M. Jeram, MD, MSc,b Jane F. Seward, MBBS, MPHa
abstractCONTEXT: Several varicella vaccines are available worldwide. Countries with a varicella
vaccination program use 1- or 2-dose schedules.
OBJECTIVE: We examined postlicensure estimates of varicella vaccine effectiveness (VE)
among healthy children.
DATA SOURCES: Systematic review and descriptive and meta-analysis of Medline, Embase,
Cochrane libraries, and CINAHL databases for reports published during 1995–2014.
STUDY SELECTION: Publications that reported original data on dose-specific varicella VE among
immunocompetent children.
DATA EXTRACTION: We used random effects meta-analysis models to obtain pooled one dose
VE estimates by disease severity (all varicella and moderate/severe varicella). Within
each severity category, we assessed pooled VE by vaccine and by study design. We used
descriptive statistics to summarize 1-dose VE against severe disease. For 2-dose VE, we
calculated pooled estimates against all varicella and by study design.
RESULTS: The pooled 1-dose VE was 81% (95% confidence interval [CI]: 78%–84%) against
all varicella and 98% (95% CI: 97%–99%) against moderate/severe varicella with no
significant association between VE and vaccine type or study design (P > .1). For 1 dose,
median VE for prevention of severe disease was 100% (mean = 99.4%). The pooled 2-dose
VE against all varicella was 92% (95% CI: 88%–95%), with similar estimates by study
design.
LIMITATIONS: VE was assessed primarily during outbreak investigations and using clinically
diagnosed varicella.
CONCLUSIONS: One dose of varicella vaccine was moderately effective in preventing all varicella
and highly effective in preventing moderate/severe varicella, with no differences by vaccine.
The second dose adds improved protection against all varicella.
aNational Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and bDepartment of Immunization, Vaccines and Biologicals,
World Health Organization, Geneva, Switzerland
Dr Marin conceptualized and designed the study, reviewed the articles and collected the data, supervised the analysis, interpreted the data, drafted the initial
manuscript, and revised the manuscript; Dr Marti conceptualized the study, reviewed part of the articles, interpreted the data, and reviewed and revised the
manuscript; Ms Kambhampati carried out the meta-analyses, interpreted the data, and reviewed the manuscript; Dr Jeram conducted an initial literature review,
reviewed part of the articles and collected the data, and reviewed the manuscript; Dr Seward conceptualized and designed the study, reviewed part of the articles,
critically reviewed the manuscript, and interpreted the data; and all authors approved the fi nal manuscript as submitted.
The fi ndings and conclusions in this report are those of the authors and do not necessarily represent the offi cial position of the Centers for Disease Control and
Prevention. For authors affi liated with the World Health Organization, the authors alone are responsible for the views expressed in this publication and they do not
necessarily represent the views, decisions or policies of the World Health Organization.
To cite: Marin M, Marti M, Kambhampati A, et al. Global Varicella Vaccine Effectiveness: A Meta-analysis. Pediatrics. 2016;137(3):e20153741
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MARIN et al
A varicella vaccine, based on the
attenuated live varicella zoster virus
(VZV) Oka strain, was developed by
Dr Takahashi in Japan in the mid-
1970s.1 Two decades later, the United
States became the first country
to implement a routine childhood
varicella vaccination program after
the vaccine was licensed in 1995.2
Varicella vaccines are now licensed
and available throughout the world;
however, they are recommended
for routine use only in a small
number of primarily industrialized
countries. Where coverage rates
are high, vaccination has resulted
in important declines in varicella-
related incidence, morbidity, and
mortality.3–12
Worldwide, there are several
formulations of varicella vaccines; all
contain live attenuated VZV, and all,
except the vaccine licensed in South
Korea, are based on the Oka strain
of VZV isolated in Japan. Currently,
varicella vaccines are licensed as
a monovalent or a combination
measles, mumps, rubella, varicella
vaccine (MMRV). Monovalent
vaccine is produced in the United
States (VARIVAX; Merck & Co., Inc),
Belgium (Varilrix; GlaxoSmithKline),
Japan (OKAVAX; Biken, distributed
by Sanofi Pasteur), China (4
manufacturers: Shanghai Institute
of Biologic Products, Changchun
Keygen Biological Products Co, Ltd,
Changchun BCHT Biotechnology Co
[Baike], Changchun Changsheng Life
Sciences Ltd), and Korea (Suduvax).
MMRV is produced in the United
States (ProQuad; Merck) and Belgium
(Priorix-Tetra; GlaxoSmithKline).
Vaccine safety and efficacy were
assessed in double-blind, placebo-
controlled, 1-dose studies for 3 of
the monovalent vaccines.13–15 MMRV
vaccines were licensed on the basis
of noninferior immunogenicity of
the antigenic components compared
with simultaneous administration
of MMR and varicella vaccines16,17;
an efficacy study for 2 doses of
MMRV vaccine was performed
after licensure.18 Efficacy studies
conducted used vaccines with
varying concentrations of the Oka
strain, making comparisons across
studies and inference of results
to licensed vaccine formulations
difficult; moreover, vaccine
performance may be different under
conditions of real-world use (vaccine
effectiveness [VE]). Therefore,
postlicensure evaluations of VE are
important to inform public health
programs and policies. We conducted
a systematic literature review and
descriptive and meta-analysis to
assess the effectiveness of varicella
vaccine among immunocompetent
children to prevent (1) varicella of
any severity (1 and 2 vaccine doses),
(2) combined moderate and severe
varicella (1 dose), and (3) severe
varicella (one dose).
METHODS
Identifi cation of Studies
The complete search strategy is
described in the Supplemental
Information (Supplemental Table
1). In brief, we searched for
reports published between 1995
(year the varicella vaccine was
first recommended for routine
vaccination) and December 15,
2014, in the following databases:
Medline, Embase, Cochrane
libraries, and CINAHL. We used
search terms including “varicella,”
“chickenpox,” “vaccine,” “vaccination,”
“effectiveness,” “effective,” and
“performance” to identify reports
that presented data on varicella
vaccine effectiveness. We did not
restrict our search by language.
Study Selection and Data Collection
Each article title and abstract was
reviewed by 2 authors, and relevant
publications were selected for
full-text review. The criteria for
assessment of eligibility for meta-
analysis included the following:
(1) original report on dose-specific
varicella VE and (2) the population
studied was immunocompetent
children. Clinical trials and studies
that reported VE for postexposure
prophylaxis were excluded. For each
study included in the analysis, we
abstracted information on study
setting, study design including
case definition and classification of
disease severity, vaccine studied,
number of vaccine doses, number of
study participants age ≥12 months,
and VE with confidence intervals.
Analysis
We used random effects meta-
analysis models to obtain pooled
1-dose VE estimates and 95%
confidence intervals (CIs) for
monovalent vaccines by disease
severity (against varicella of any
severity (all varicella) and against
combined moderate and severe
varicella). Within each of the 2
categories of disease severity we
assessed pooled VE by vaccine
and by study design. For studies in
countries where >1 varicella vaccine
is licensed, if publications did not
specify the vaccine studied, we
classified VE estimates as for “mixed/
multiple vaccines.” For 2-dose VE,
because most studies included
multiple vaccines, we calculated
pooled estimates and 95% CIs overall
against varicella of any severity and
stratified by study design.
To be included in the analysis, a
publication had to report VE and a
measure of its variance (CI) or the
raw numbers to allow us to calculate
CI. When CI or raw numbers were not
reported, we contacted the authors
to obtain 1 of them.19–22 For 1 study
that reported VE and CIs for 4 birth
cohorts and an overall VE without
CI, we pooled estimates from the
4 birth cohorts to calculate CI for
the overall VE.23 When publications
reported crude and adjusted VE,
we included the adjusted estimates.
VE was calculated as 1 – relative
risk (RR) or 1 – odds ratio (OR),
depending on the study design. To
calculate the pooled VE estimates, we
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PEDIATRICS Volume 137 , number 3 , March 2016
first obtained the RR / OR for each
study using the formula RR / OR =
(1 – VE) * 100. We then calculated
the pooled OR, and transformed the
pooled OR into a pooled VE estimate
([VE = 1 – OR] * 100). We assessed
residual heterogeneity by calculating
the I2 statistic. Publication bias was
assessed by using Egger’s regression
test. We conducted mixed-effects
meta-regression analyses by using
restricted maximum likelihood
estimation, among the studies that
reported VE on all varicella and
combined moderate and severe
varicella, to investigate potential
sources of heterogeneity and identify
any differences by vaccine or study
design. All analyses were conducted
by using the metafor package in
R.24,25
For the analysis of combined
moderate and severe varicella or
severe only we used the definitions
and classification from each study
and excluded studies that did not
provide these classifications. In
most studies, severity of disease was
defined by the number of skin lesions
and incidence of complications or
hospitalization as mild, <50 lesions;
moderate, 50 to 500 lesions; and
severe, ≥500 lesions or a serious
complication or hospitalization;
the combined moderate and severe
category includes cases in the last
2 categories. Several studies used
a different number of lesions to
define severe disease, or assessed
severity based on a disease-severity
score modified from the clinical
trials, a combination of criteria that
included number of days with fever,
number of lesions, number of days
the patient needed rest and presence
of complications, hospitalization
only, or parental assessment of
severity (Supplemental Information).
VE estimates against moderate
varicella only26,27 were included in
the analysis of VE against combined
moderate and severe varicella. One
study that also reported VE against
moderate disease alone provided
data in the publication that allowed
us to calculate VE against combined
moderate and severe varicella; we
used VE against combined moderate
and severe varicella for this study.20
We used descriptive statistics to
present the findings on 1-dose VE
against severe disease alone because
none of the publications reported
CIs for VE against severe disease,
mainly due to the absence of severe
cases among vaccinated patients.
Additionally, publications that
reported no cases of severe disease
were assigned a VE of 100% against
severe disease for our analysis.
One study reported VE against
varicella-related hospitalizations23;
this estimate was included in the
summary of findings for severe
disease.
RESULTS
We screened 872 nonduplicate
articles for eligibility and identified
105 potentially relevant studies
for further review. After excluding
63 studies, 42 original studies met
our inclusion criteria for meta-
analysis (Fig 1; references listed in
Supplemental Table 2 of the Online
Supplemental Information). These
studies originated from the United
States (23), China (4), Germany (3),
Israel (3), Italy (2), Spain (2), Taiwan
(2), Australia (1), Turkey (1), and
Uruguay (1).
One-Dose VE
Almost two-thirds of studies of
1-dose varicella VE (64%, 27
of 42) were conducted during
outbreak investigations and used
a retrospective cohort study
design; 2 additional studies used a
retrospective cohort study design
based on data from electronic
databases (Supplemental Table
2). Other methods used included
matched case-control study (24%,
10 of 42), prospective cohort
study (1), household contact study
(1), and time-series modeling
(1) (Supplemental Table 2). The
populations studied included
children in different settings such
as child-care centers, schools,
community clinical practices,
hospitals, outpatient setting, and
households. Ages of participants
varied, overall ranging from 12
months to 18 years, but VE was
predominantly calculated among
preschool and elementary school–
age children (Supplemental Table
2). Most studies used as an outcome
clinically diagnosed varicella with
details on illness obtained from
parents; 5 studies used laboratory
confirmed varicella as their outcome
(Supplemental Table 2).
The 42 publications reported for
1-dose monovalent vaccines 58
VE estimates for prevention of all
varicella (Fig 2), 34 estimates for
prevention of combined moderate
and severe varicella (including 2
studies that provided estimates for
moderate varicella alone; Fig 3), and
25 estimates for prevention of severe
varicella. Only 1 study reported
MMRV VE (1 and 2 doses).27
The pooled 1-dose VE for prevention
of all varicella was 81% (95% CI:
78%–84%, I2 = 88%; Fig 2). Most
postlicensure studies were reported
from the United States and as a result,
most VE estimates were for Varivax
(n = 26; Fig 2 and Supplemental
Table 2). Studies conducted in other
countries assessed Varilrix, Okavax,
and various other varicella vaccines.
When stratified by vaccine, pooled
1-dose estimates were as follow:
Varivax 82% (95% CI: 79%–85%,
I2 = 62%), Varilrix 77% (95% CI:
62%–85%, I2 = 92%), other vaccines
86% (95% CI: 78%–91%, I2 = 39%),
or mixed/multiple vaccines 81%
(95% CI: 76%–85%, I2 = 85%; Fig
2). The only VE reported for 1 dose
of MMRV/Priorix-Tetra was 55%
(95% CI: 8%–78%). Pooled VE
estimates were also similar by study
design: 81% (95% CI: 76%–84%, I2
= 92%) for cohort and 83% (95% CI:
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MARIN et al
79%–86%, I2 = 42%) for case-control
studies (Supplemental Fig 5).
The pooled 1-dose VE for prevention
of combined moderate and severe
varicella was 98% (95% CI: 97%–
99%, I2 = 85%; Fig 3). The estimates
by vaccine were similar to the overall
pooled VE: Varivax 98% (95% CI:
95%–99%, I2 = 86%), Varilrix 98%
(95% CI: 89%–100%, I2 = 79%),
mixed/multiple vaccines 99% (95%
CI: 95%–100%, I2 = 86%; Fig 3).
When stratified by study design the
pooled estimates were 98% (95%
CI: 97%–99%, I2 = 87%) for cohort
and 97% (95% CI: 93%–99%, I2
= 69%) for case-control studies
(Supplemental Fig 6).
In the meta-regression analyses,
no significant association was
found between VE and vaccine
type or study design (all Ps > .1;
Supplemental Table 3).
Of the 25 estimates for VE for
prevention of severe disease, for 24
VE was 100%; 1 study reported a VE
of 85% (for prevention of varicella-
related hospitalizations).23 The only
VE for 1 dose MMRV/Priorix-Tetra
for prevention of severe disease was
100%.
Two-Dose VE
There were 8 publications that
reported 9 estimates for 2-dose VE,
8 for monovalent varicella vaccines
and 1 for MMRV/Priorix-Tetra. The
pooled 2-dose VE for monovalent
vaccines was 92% (95% CI:
88%–95%, I2 = 57%) and by study
design: 91% (95% CI: 84%–95%, I2
= 74%) for cohort and 95% (95% CI:
90%–97%, I2 = 0%) for case-control
studies (Fig 4). The only VE reported
for 2 doses of MMRV/Priorix-Tetra
was 91% (95% CI: 65%–98%).
There was evidence of publication
bias as indicated by Egger’s
regression test in some subgroups
analyzed but not in others
(Supplemental Table 4).
DISCUSSION
This is the first study to
systematically assess the
effectiveness of varicella vaccines
currently available worldwide. In
our analyses that included children
in 42 studies, within the first decade
after vaccination, 1 dose of varicella
vaccine was moderately effective
at preventing all varicella (81%)
and highly effective at preventing
combined moderate and severe
varicella (98%). Noteworthy is the
consistency of the findings, with
similar pooled estimates whether
the analysis was stratified by
individual vaccines or study design.
Additionally, 2 doses of varicella
vaccine were highly effective at
preventing all varicella.
Most of the reported 1-dose VE
estimates for prevention of all
varicella were close to the pooled
estimate; however, 1 estimate
for MMRV was 55%, and 2
estimates were <50%, 1 each for
Varivax and Varilrix, 44% and
20%, respectively.27–29 These
estimates were all calculated
during outbreak investigations
4
FIGURE 1Study selection. *Articles excluded from the analysis originated from the United States (15), Australia (5), China (5), Germany (5), Japan (5), France (4), Spain (4), Brazil (3), Canada (2), Chile (2), Italy (2), Turkey (2), United Kingdom (2), and 1 each from Denmark, Finland, Hungary, Israel, Korea, Poland, and Thailand. **Articles included in the analysis originated from the United States (23), China (4), Germany (3), Israel (3), Italy (2), Spain (2), Taiwan (2), Australia (1), Turkey (1), and Uruguay (1).
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PEDIATRICS Volume 137 , number 3 , March 2016
that tend to underestimate the
performance of vaccines; outbreaks
that come to public health attention
may be exceptions in which the
vaccine failed and therefore may
represent the lower range of vaccine
effectiveness versus situations in
which the vaccine worked well and
prevented outbreaks and where no
investigations are done.30 Although
there are no definitive explanations
for the low effectiveness, in outbreak
investigations, there are confounders
not able to be controlled for, the
force of infection may be high in
some outbreaks or the degree of
exposure may be variable across
study participants; additionally, such
values could be identified by chance,
especially during investigations
conducted in settings where there
is epidemiologic evidence of vaccine
failure (outbreaks). This highlights
that more than a few estimates are
needed to accurately assess VE. A
previous meta-analysis that included
VE calculated during varicella
outbreaks from 14 publications
through 2004 reported a pooled
1-dose VE of 72.5%.31
Fewer studies assessed 2-dose
VE in children. Overall, 2 doses of
vaccine provided 10% or better
protection than 1 dose. However, 2
of the estimates, both from outbreak
investigations, were <90% and
that may have lowered the pooled
estimate to the lower 90s.32,33
The pooled VE estimates we report
for 1 dose are a compilation of VE
at different points of time since
vaccination, primarily within the
first decade. Considering the age
of participants in the studies and
vaccine recommendations in each
country, the median time since
vaccination is likely lower than 10
years. Within this time frame, some
studies described a higher risk
for vaccine failure with time since
vaccination (using a cutoff of 3, 4, or
5 years),22,26,28,34–36 but other studies
did not find this association27,37–41;
in all these studies, conducted during
outbreak investigations, the sample
sizes were usually insufficient to
assess the independent effect of time
since vaccination as a risk factor.
Four studies reported decline in VE
with time since vaccination; however,
the differences did not reach
statistical significance.42–45 Vazquez
et al used laboratory confirmed
cases and described a decline in VE
for Varivax between years 1 and 2
(from 97% to 86%) after vaccination
but not subsequently (up to 7 years
of follow-up, 84%)46; another study
in the United States reported a
significant decline in 1-dose VE from
94% within 5 years after vaccination
to 88% for 5 to 9 years and 82%
for ≥10 years after vaccination.47
Additionally, Bayer et al in their
meta-analysis of outbreak data,
concluded waning immunity based
on data from four studies which all
showed a decrease in VE by time
since vaccination (data available
for an average of 4 to 6 years since
5
FIGURE 2Random effects model of 1-dose varicella VE for prevention of all varicella, by vaccine.
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vaccination).31 When interpreting the
results of these studies, consideration
should be given to the fact that
they did not adjust for likelihood
of exposure or force of infection
which declined over time due to
changing varicella epidemiology with
the implementation of vaccination
programs. This results in differential
exposure by age group and can
confound interpretation of waning
effectiveness. One large study that
controlled for likelihood of exposure
and age examined 10 years of active
surveillance data (1995–2004) from
a sentinel population and reported
an increase in incidence of varicella
among vaccinated persons with time
since vaccination after the first dose
although the rate of breakthrough
varicella was still very low.48 Only
1 study examined 2-dose VE by
time since vaccination and found
no difference in VE through 5 years
since the second dose; there were too
few subjects to confidently examine
VE >5 years after the second dose.47
The VE findings are supported by
immunologic and epidemiologic
data. Immunogenicity studies from
the United States reported that
primary vaccine failure occurs in 9%
to 14% of children after 1 dose of
vaccine.49,50 A small study found that
24% of infants lacked VZV antibody
measured by fluorescent antibody
to membrane antigen a median of
4 months after vaccination.51 The
second dose of varicella vaccine
in children produced an improved
immunologic response as measured
by the proportion of subjects with
titers of ≥5 glycoprotein-based
enzyme-linked immunosorbent
assay, an approximate correlate of
protection, (99.6% vs 86% 6 weeks
after the second and first dose,
respectively) and higher geometric
mean titers.49 Countries that
introduced varicella vaccination have
experienced substantial reductions in
varicella incidence, severe morbidity
and mortality, and evidence of herd
protection beyond the age groups
targeted by vaccination. By the end
of the decade of the 1-dose program
in the United States, when vaccine
coverage had reached ∼90%,
varicella incidence had declined 90%
or more, hospitalization in children
decreased ≥95%, and deaths had
been nearly eliminated3,52,53; effects
of vaccination were documented
within 5 years of the program
in communities where vaccine
coverage among young children
had reached ∼80%.54 In Germany,
where a 1-dose national vaccination
program was implemented in 2004,
a decline of 55% in cases and 82%
in varicella complications was
observed from 2005 to 2009 using
data from physician-based sentinel
surveillance.7 In Canada, where the
1-dose varicella vaccination program
was recommended in 1999, declines
of 81% to 88% in the number of
hospitalized varicella cases were
reported between 2000 and 2008,
with impact of the vaccination
program being noted beginning 1 to
2 years after the start of the program;
6
FIGURE 3Random effects model of 1-dose varicella VE for prevention of combined moderate and severe varicella, by vaccine.
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PEDIATRICS Volume 137 , number 3 , March 2016
vaccination coverage ranged from
74% to 91% in 2007–2008.6 The
impact of a 1-dose vaccination
program on varicella and its severe
morbidity has also been described
from Taiwan, Uruguay, Australia, and
Italy.8,10–12 Protection against severe
disease among those vaccinated
appears to be maintained after 1
dose of vaccine. No increases in rate
of complications, hospitalizations
or deaths have been reported with
time since vaccination in countries
with a 1-dose program. The 1 study
mentioned earlier that used active
surveillance data reported that
among vaccinated persons, varicella
was twice as likely to be moderate/
severe in those who developed
disease >5 years after vaccination
compared with those who became ill
<5 years after vaccination; moderate/
severe varicella was defined as >50
skin lesions in this study.48
Despite considerable success
in controlling varicella and its
severe complications with the
1-dose varicella vaccine program
in the United States, cases and
varicella outbreaks (although less
in number, smaller in size, and of
shorter duration) continued to
occur in highly vaccinated school
students. This, coupled with the
evidence that 2 doses induce a
higher immune response and
higher effectiveness, resulted in
adoption of a routine 2-dose policy
for children in 2006.2,55 During the
first 5 years after introduction of the
2-dose program, reported varicella
incidence has declined further to
the lowest level since the start of
the vaccine program, with fewer
outbreaks and additional declines in
varicella-related hospitalizations.4,56
In Navarre region, Spain, where a
2-dose routine childhood program
was introduced from the beginning
and high coverage was achieved early
in the program, a decline of 98.5%
in incidence in children and 88%
in hospitalizations were achieved
within a period of only 5 years.9
Our study has several limitations. The
majority of studies assessed VE using
clinically diagnosed varicella cases
and the evaluations occurred during
outbreak investigations that tend
to underestimate the performance
of vaccines. We did not perform a
formal quality assessment of the
studies included; all were published
in peer-review publications however,
we excluded 2 due to methodologic
issues identified during the review.
When stratified by vaccine, there was
some evidence of heterogeneity in
the 1-dose estimates, suggested by
I2 >75%. This finding may be due to
variations in study design and size.
There was also some evidence of
publication bias in the estimates from
the publications that reported on
moderate-severe varicella, suggesting
that higher ORs could have come
from smaller studies, which could
lead to some overestimation of our
pooled estimates. Most studies are
from high-income countries with few
from middle-income and none from
low-income countries.
Available data support similar
performance of the various 1-dose
monovalent varicella vaccines in
preventing varicella. One-dose
varicella vaccine is moderately
effective (81%) for preventing all
varicella and highly effective (98%)
for preventing combined moderate
and severe varicella. The second
dose adds improved protection
against all varicella (92%). The
impact of varicella vaccination in
decreasing morbidity and mortality
due to varicella is well documented
during the first 2 decades of program
implementation. The duration of
protection after 1 dose is not fully
understood or studied, especially in
settings of low varicella incidence
however, live viral vaccines because
they actively replicate in the body
commonly provide durable immunity.
It is unknown what role waning
immunity after an initial response
and primary immunologic failure
rates play in the inability of 1 dose
of vaccine to provide complete
protection. The fact that varicella in
vaccinated persons is usually highly
modified suggests partial protection
or inadequate induction of a totally
protective immune response, not
primary vaccine failure. To date, there
is no evidence of increased severe
outcomes (death or hospitalization
rates) at population level with time
since 1 dose of vaccine. Assessment
of vaccine effectiveness in recipients
who are >10 to 20 years after
vaccinations with both 1 and 2 doses
is needed. One dose is sufficient
to reduce mortality and severe
morbidity from varicella but not to
prevent limited virus circulation and
outbreaks. To further reduce the
number of cases and outbreaks and
transmission 2 doses are needed.
Additionally, the widespread use of
7
FIGURE 4Random effects model of 2-dose varicella VE for prevention of all varicella, by study design.
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MARIN et al
varicella vaccine could reduce herpes
zoster incidence among the vaccinated
populations; several studies reported
a lower risk for herpes zoster among
varicella-vaccinated children57–61 and
a decline in herpes zoster incidence
among cohorts targeted for varicella
vaccination.59,62
ACKNOWLEDGMENTS
We thank Centers for Disease Control
and Prevention colleagues Chengbin
Wang, MD, PhD, for reviewing the
studies in Chinese; Joanna Taliano
for performing the literature search;
Ben Lopman, PhD, for meta-analysis
technical expertise; Daniel Feikin,
MD, for the suggestion to perform
meta-analysis; and Jessica Allen
for editorial assistance. We also
acknowledge the members of the
World Health Organization Strategic
Advisory Group of Experts Working
Group on varicella and herpes
zoster vaccines and Jon Abramson,
MD, Chair of the Working Group,
Wake Forest University School of
Medicine, Winston-Salem, NC, and
Philippe Duclos, DVM, PhD, World
Health Organization, Switzerland, for
their advice for analysis during the
leadership of the work group.
8
ABBREVIATIONS
CI: confidence interval
MMRV: combination measles,
mumps, rubella, varicella
vaccine
OR: odds ratio
RR: relative risk
VE: vaccine effectiveness
VZV: varicella zoster virus
Dr Jeram’s current affi liation is Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada
DOI: 10.1542/peds.2015-3741
Accepted for publication Nov 25, 2015
Address correspondence to Mona Marin, MD, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE; MS A-47, Atlanta, GA 30333. E-mail: mmarin@cdc.gov
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose.
FUNDING: Anita Kambhampati’s work was supported by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention
administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.
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DOI: 10.1542/peds.2015-3741 originally published online February 16, 2016; 2016;137;Pediatrics
SewardMona Marin, Melanie Marti, Anita Kambhampati, Stanley M. Jeram and Jane F.
Global Varicella Vaccine Effectiveness: A Meta-analysis
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. ISSN:60007. Copyright © 2016 by the American Academy of Pediatrics. All rights reserved. Print
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,has been published continuously since . Pediatrics is owned, published, and trademarked by the Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
by guest on May 12, 2018http://pediatrics.aappublications.org/Downloaded from
DOI: 10.1542/peds.2015-3741 originally published online February 16, 2016; 2016;137;Pediatrics
SewardMona Marin, Melanie Marti, Anita Kambhampati, Stanley M. Jeram and Jane F.
Global Varicella Vaccine Effectiveness: A Meta-analysis
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The online version of this article, along with updated information and services, is
. ISSN:60007. Copyright © 2016 by the American Academy of Pediatrics. All rights reserved. Print
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,has been published continuously since . Pediatrics is owned, published, and trademarked by the Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
by guest on May 12, 2018http://pediatrics.aappublications.org/Downloaded from