Of all pediatric mandated vaccination programs, two seem to make even
less sense than others. The first is the universal hepatitis B
vaccination program, starting shortly after birth and intended to
decrease the risk and incidence of primary liver cancer. The
second is the universal pediatric chickenpox vaccination program, the
subject of this report.
My good friend Julienne has been suffering for over 3 months with
shingles, a viral illness related to an old chickenpox infection and
post-herpetic neuralgia, its most dreaded complication. The term
“suffering” hardly describes the excruciating pain she has been
experiencing. At times, she has even needed narcotic analgesics to
bring down the torture to the “Awful” level on the Richter scale of
pain. To make things worse, her left-handed eighty-year-old husband
fell and broke his left shoulder. In just three weeks, this very happy
and active couple was seriously sidelined and suffering … together.
When Julienne asked me when or where she could have “caught” shingles, I
told her as gently as possible that it was probably a gift from her
14-month-old granddaughter who had recently received her MMR and
chickenpox vaccines and who comes to visit on Sundays. Her first reaction was a long sad look as if I had stabbed her, a look every grandparent would have
easily recognized. Words were not needed, her face said it all: “What nonsense is that and how dare you blame my baby?” After she counted to ten, she asked defensively: “But shingles happen to old people, anyway…
right?” I agreed. This was definitely not the time to explain to her
the recent United States shingles epidemic.
As the visit went on, I could see the wheels turning as she was thinking
about what I had said, still bewildered. She knew I loved to tease but she
also knew that I would have never dared under the circumstances. I dropped the subject, she was hurting enough …
I saw my friends a couple of weeks later, they were still suffering, maybe a
little less but still considerably, at times.
Until the mid-nineties, everyone thought that chickenpox was a mild childhood illness that was catchy and made children itch for a few days. It rated somewhere between an inconvenience and a mild nuisance but it was a good excuse for mothers to stay home from work and “bond” for a while. The best part of the day for the poor itchy toddler was bath time when a tubful of tepid Aveeno seemed like heaven and where he
could splash and giggle and sing “If you’re happy, and you know it, clap your hands.”
For the longest time, mothers were delighted when their children developed chicken pox because they knew that the disease was so much more severe among adults. In fact, in spite of their doctors’ admonition, mothers sometimes chose to expose their toddlers to chickenpox in order “to be done with it.”
Pediatricians knew that the infection was caused by the varicella zoster
virus (VZV) and that children very rarely developed serious omplications,
unless they were immune-compromised.
It was also well-known that the elderly developed shingles, a late
complication caused by a reactivation of the chickenpox virus. It was postulated that particles of VZV migrated from the chickenpox blisters and moved to the nervous system where they laid dormant for years because of the repeated exposure to chickenpox in the community that boosted the
individual’s immunity. If an individual was compromised for any reason,
such as by lack of immune competence or stress, the VZV reactivated,
moved back through the nerve fibers and invaded the sensory cell bodies in the neighboring skin, eventually causing the typical rash of shingles. Because that last event took a little while, skin sensitivity and pain often preceded the skin eruptions.
fifteen years ago, suddenly and out of the blue, chickenpox became a
serious disease and there were multiple TV and press reports about
dying from chickenpox all over the country. Economists weighed in and
warnings filled the air: Chickenpox was not only killing kids and
was a national economic disaster that was eventually ultimately going
collapse the United States economy because it kept mothers at home
their children instead of at work.
Merck and the CDC joint efforts had succeeded in creating “a need”, a vaccine
for chickenpox was developed and the FDA quickly licensed it. After
children’s lives and our national economy depended on it.
was launched to the cheers of the Merck stockholders in 1995 [i]
Within less than a year spent figuring out reimbursement, it caught on
grand way. With time, it became apparent that two doses
protect susceptible children and adults and … in 2006, a second dose of
VARIVAX® was recommended. The children were not too happy; the
were jubilant and it is rumored that at Merck, people were heard
“Double the shots! Double the Fun.” The vaccine is still
selling well at $83.77 per dose.
were first told that the vaccine, because it was another attenuated
vaccine, had to be administered one month after the MMR vaccine,
between 12 and
15 months of age.
was soon changed!
was acceptable to give VARIVAX® and MMR on the same day at
different sites but
… if we did not give them on the same day
, then we had to
. This was certainly peculiar but then preventing
often a mild illness in children,
forgetting the uproar about the MMR vaccine, some bright people at
with friends in Atlanta, and decided to combine
with the MMR
vaccine. The new vaccine MMRV was licensed in 2005 and marketed under
PROQUAD®. I thought the name was as strange as the idea. [ii]
early 2008, the FDA announced that the incidence of febrile seizures
increased with the use of PROQUAD® at age 12-15 months and that
some reports of
encephalitis following vaccination had been filed. [iii]
explained that this did not mean that the encephalitis was caused by
vaccine, a standard argument with vaccine adverse events. If one takes
an arthritis or an anti-diabetic drug and gets a reaction,
the drug is immediately blamed, the lawyers take over and the company
or stops manufacturing the problem drug. On the other hand, if someone
serious reaction shortly after a vaccination, such as an encephalopathy
encephalitis, it is almost always considered a coincidence
reports of vaccine-related adverse
events, the verdict is the same: They are all anecdotal
To deal with the increased risk of febrile
seizures following the first dose of PROQUAD® (MMRV), the CDC
long and hard to understand Morbidity
on May 7, 2010 that included
mumps, rubella and varicella vaccination continue to
be age 12--15 months for the first dose and age 4--6 years for the
rubella, and varicella vaccines at age 12--47 months,
either measles, mumps, and rubella (MMR) vaccine and varicella
vaccine or MMRV vaccine may be used. Providers who are considering
administering MMRV vaccine should discuss the benefits and risks of
vaccination options with the parents or caregivers. Unless the parent
caregiver expresses a preference for MMRV vaccine, CDC recommends that
vaccine and varicella vaccine should be administered
for the first dose in this age group.
mumps, rubella, and varicella vaccines at
any age (15 months--12 years) and for the first dose at age ≥48 months,
use of MMRV vaccine generally is preferred over separate injections of
equivalent component vaccines (i.e., MMR vaccine and varicella
vaccine). Considerations should include provider assessment, patient
preference, and the potential for adverse events.
parent) history of seizures of any etiology is a precaution for MMRV
vaccination. Children with a personal or family history of seizures of
etiology generally should be vaccinated with MMR vaccine and varicella
25 page current
PROQUAD® product insert [v]
that the doctors and their nurses are supposed to read only includes
SUBCUTANEOUS ADMINISTRATION ONLY
Each 0.5-mL dose of ProQuad
is administered subcutaneously.
The first dose is usually administered at 12 to 15
months of age but may be given anytime through 12 years of age.
If a second dose of measles, mumps, rubella, and varicella vaccine is
may be used. This dose is usually administered at 4 to 6 years of age.
1 month should elapse between a dose of a measles-containing vaccine
M-M-R II (measles, mumps, and rubella virus vaccine live) and a dose of
ProQuad. At least 3 months should elapse between a dose of
vaccine and ProQuad.
difference between the two sets of recommendations is at the very least
VARIVAX® was introduced, we all expected a decrease in the number
of cases of
chickenpox among children and an increase in the disease incidence
adults, who were likely to be much sicker. That all happened!
As uptake of VARIVAX® increased, the incidence of chickenpox
decreased and by
2002, verified pediatric chicken pox cases had dropped by 85% in
surveillance sites. Unfortunately, that brilliant result came
price: The all important chickenpox immunological boosting that had
since time immemorial because of continued exposure to wild-type VZV
quickly disappearing and with it all the protection it provided.
Australians are well known for adopting new vaccination initiatives
promptly but for some reason they dragged their feet with the varicella
vaccine. The Australian health authorities
eventually surrendered, and the vaccine was licensed in 2000. On
2010, the Medical Journal of Australia,
the official journal of the Australian Medical Association published an
conceding that since the
introduction of the varicella vaccine in 2000
“…there has been a decrease in varicella
cases and a rise in HZ cases in Australian general practice
This was absolutely the first time that I had personally seen or heard
that very disturbing fact so
bluntly stated. The authors’ statistics were very sobering too: The
number of general practice consultations for shingles in Australia had
increased by 100% in 10 years from 1.7/1000 consultations in 2000 to
consultations for the first half of 2010. The increase in
consultations among patients older than 70 during the same period was
The fact that the incidence of shingles had increased after
the introduction of VARIVAX® has been known
for sometime. It was in fact in 2002
that my good friend Gary S. Goldman, Ph.D., had first warned
recent sudden increase in the incidence of shingles. Goldman, a quiet,
soft-spoken and meticulous scientist remains almost apologetic about
discovery; a flashback seems essential to show its brilliance and
Varicella Active Surveillance Projects
created to monitor trends of varicella
as VARIVAX® was launched. Dr. Goldman worked in the California
VASP, located in
Antelope Valley, an area of around 300,000 residents. The project
confirmed that the incidence of chickenpox (varicella)
children was decreasing. Even though everyone knew that the absence of
was likely to compromise the immune boosting that was essential to
shingles (herpes zoster) due to the reactivation of varicella
zoster virus, the declaration by Dr. Goldman that cases of shingles
more numerous than expected was
still met with
denial. No one apparently wanted to
that, what was logically expected but shamefully overlooked by the
developers was indeed happening. Dr. Goldman begged the principal
to address the problem; instead of thanking and praising him, they
all the way, ignoring the evidence.
was repeating itself! This was certainly not the first time that people
discovered important medical facts were marginalized and persecuted.
was only after the horse was way out of the barn, that surveillance
started monitoring shingles trends, some
after the varicella vaccine had been introduced.
then, the pro-vaccine forces still remained in solid denial and
downgraded the risk; after all, “their serious disease called
that had killed people” had been wiped out. So what if there was some
to form, the CDC is still
mentioning shingles as a
chickenpox vaccination. On October 23, 2010, I reviewed the current
Information Statement (VIS) for VARIVAX®, [vii]
that a parent is supposed to read before signing the permission slip
the administration of the vaccine.
document, dated 3/13/2008 only stated that: “A
who has had chickenpox can get a painful rash called shingles years
later”. It also still asserts that before the vaccine, about 11,000
people were hospitalized and about 100 died each year in the United
as a result of chickenpox."
did not say that the vaccine can double the
incidence of shingles among contacts and it certainly did not say how
frequently people all over the United States now suffered from the
Nor did it allude to the vastly under-represented
45,000 + chickenpox vaccine-associated reactions so far reported to VAERS
The “11,000 hospitalizations”
to chickenpox are impossible to confirm or deny. What is easier to do
compare them with other inflated CDC statistics such as
that averaged over
200,000 per year during the 1990s with individual seasons ranging from
a low of 157,911 in 1990-91 to a high of 430,960 in 1997-98.
According to information published by the CDC, varicella was the
underlying cause of death on average of
around 43 children aged less than 15 years, each year from 1990 to
1994, just before VARIVAX® was introduced. [ix]
Because the vaccine
primarily intended for children, wouldn’t it have been more honest for
the CDC to
just mention the number of pediatric
deaths in its Vaccine Information Statement instead of inflating the
to include the approximately 100 children plus
. In any
case, to help put things in perspective, 82 individuals were killed by
lightning strikes, [x]
on average, each year from 1980 through 1995 (range: 53-100).
Is VARIVAX® still very effective?
In the early years of administration of the vaccine, immunity of
vaccinated individuals was
still being boosted by other children with wild type varicella.
Because of that exogenous
boosting, the reports on varicella
vaccine efficacy were biased upwards, with levels above 90% sometimes
reported. When exogenous boosting became rare in most communities after
2000,varicella vaccine efficacy declined
in certain areas to under 60%.[xi]
According to a 2004 report by the CDC and the Oregon Department of
Human Services about a chickenpox outbreak
in a highly vaccinated pediatric population,[xii]
“Of 422 students,
218 (52%)had no prior chickenpox. Of these, 211 (97%)
had been vaccinated before the outbreak.
Twenty-one cases occurred in 9 of 16 classrooms. In these 9
classrooms, 18 of 152 (12%) vaccinated students developed chickenpox,
with 3 of 7 (43%) unvaccinated students. Vaccine effectiveness was 72%
(95% confidence interval: 3%–87%)."
did Merck do?
the waves of Shingles nationwide and
well immune (if you forgive the pun) from litigation because of the
Vaccine Injury Compensation Program, Merck did again what was best for
It invented ZOSTAVAX® to boost
the immune system of adults and help
suppress or postpone the
onset of shingles .That vaccine, essentially a much stronger
VARIVAX®, is effective in
preventing shingles in about 50% of those
individuals receiving it, according to the CDC’s Vaccine Information
single dose is recommended but those in the know
quickly add that “it is possible a second dose will be recommended in
future.” Why not?
one considers that VARIVAX®
doubled the incidence of shingles in the United States and
that ZOSTAVAX® can only prevent
50% of the
augmented cases, then the U.S. Government and the good people of this
who paid millions for these achievements got NOTHING for their money,
pain and grief.
to the CDC October 6, 2010 vaccine price list, [xiv]
a single dose
of ZOSTAVAX® costs doctors
$161.50 and costs
the CDC $116.70.
Merck’s chickenpox vaccine had truly become for shareholders the
gift that keeps on giving.
For the rest of us, it has just afflicted us with more shingles
the increased risk of getting chickenpox as adults, when the disease is
much more serious.
What the varicella
vaccination program did to the U.S.
Economy was no less unfortunate. Originally, one dose of varicella
supposed to provide lifetime immunity and supposedly save an estimated
million per year--primarily in societal costs associated with a parent
home from work to care for a child with chickenpox. Instead, the
epidemic of shingles and complications has caused a surcharge of
hundred million dollars that no one anticipated. Added to that is the
the now required second dose of VARIVAX®, also a
been proposed that around 25% of medical costs
of VZV disease are due to chickenpox and 75% are due to shingles.
relatively small increase in shingles cases can therefore quickly
cost-benefit previously expected from universal chickenpox
It is interesting that pediatricians, who were now administering
because it was recommended and in places required, had quite a bit
to lose …personally.
There was a little secret we had known for sometime but did not
too much, may be to ward off the evil eye: We pediatricians, as a
less likely than others to get shingles as we aged.
1998, Solomon, Kaporis et al [xv]
of New York Health
confirmed that fact statistically… at last. They conducted a study of
physicians and found that pediatricians, because they were constantly
to Varicella-Zoster Virus, had distinctly
of shingles than psychiatrists who were rarely exposed to the virus and
disease in their practice.
that is now changing and the thought is depressing!
Some prevalence reviews suggest that women may be more
shingles than men.
Usually the first manifestation of the disease is pain that can
and may represent early on a diagnostic challenge. Many sufferers have
needlessly exposed to X-rays and even CT-scans before the typical rash
and the diagnosis became evident.
The rash starts as a crop of contiguous red blind pimples in a
dermatome, the area of skin where sensations
from a single
nerve root in the spinal cord ultimately end. As new
develop, the previous lesions start blistering then become pustular
and ultimately crust over.
The skin eruption is painful
and can involve any dermatome and sometimes more than one. The rash,
linear bands, very rarely crosses the midline and is most commonly
the side of the torso, affecting a nerve root between the third
the third lumbar roots.
Ophthalmic Zoster affects the distribution area of the
branch of the trigeminal nerve, a truly scary presentation. Other
such as the face are more rarely involved.
Postherpetic neuralgia is the
dreaded complication of the disease. It is essentially an excruciating
almost unbearable constant burning and tingling pain that follows the
may last for weeks, months or longer.
In the debilitated elderly patients the blisters may be very deep and
result in severe scarring. Around 5% of the affected elderly develop
Early treatment of shingles – within 72 hours of the onset of the rash
– with antiviral drugs
such as Acyclovir can shorten viral replication and reduce
Success has also been achieved recently with the use of intravenous
studies are needed to confirm the findings. Oral vitamin C has been
Anticonvulsants have been used for the
symptomatic treatment of postherpetic
(Gabapentin) in particular appears to have
success than others. Antidepressants help sometimes. Recently, Lyrica
tried with good results. All these medications require attentive
helpful in mild cases of neuralgia. More often, physicians have to
to opioids that carry a distinct risk of
anesthetic creams for
local relief is another option for
those patients who are reluctant to take drugs.
insist that a vaccine is needed for every acute illness. However, until
unless we do studies comparing the vaccinated to the never-vaccinated,
never know what is really best for us and for our children.
study both the long and
short-term effects of each vaccination are urgently needed otherwise we
fooling ourselves and just whistling in the dark when we enumerate the
benefits of a vaccination.
In years past,
people felt that children were actually stronger and healthier after
recovered from certain contagious diseases. At least one California
study seems to support that old
Glioma is an aggressive
malignant tumor of the nervous system. Wrensch
et al conducted a large adult glioma study
in the San
Francisco Bay Area from 1997 to 2000 and
evaluated associations of immunoglobulin G antibodies to
virus and three other herpesviruses among
with the disease and 289 controls. They found that patients with glioma
were less likely to report a history of
than controls. Testing also revealed an inverse
with anti-varicella-zoster virus
immunoglobulin G, more so in glioblastoma multiforme cases, a
subclass. In the case
of chicken pox, could we have traded a nuisance of an illness for brain
or whatever else may be lurking, unexamined and/or ignored?
Prior to the introduction of the universal varicella vaccination
program in the United
almost 95% of adults experienced natural chickenpox, usually as school
children. These cases were usually benign and resulted in long term
because of constant boosting due to repeated exposures to other
adults with the disease.
large reservoir of individuals having long term
immunity has been seriously compromised by the mass vaccination of
that provides at best 70 to 90% immunity. The vaccine-acquired
is of unknown duration and only causes the shifting of chickenpox to
vulnerable adults. To arrive to the
line, one needs to now add the adverse effects of the required two
chickenpox vaccine and the distinct potential for increased risk of
for an estimated 30 to 50 years among adults.
must also keep in mind that regardless of the
number of boosters, the acquired immunity from vaccination will never
strong constantly-boosted natural immunity we all had in the past,
Universal Varicella Vaccination program
Varicella vaccination was a
Mandating it as a universal vaccination program for every
child was an even bigger mistake.
Grant KA, Carville KS, Kelly HA. Evidence of
frequency of herpes zoster management in Australian general practice
introduction of a varicella vaccine. Med J Aust. 2010 Oct 18;193(8):483
Goldman GS. Universal varicella
vaccination: Efficacy trends and effect on herpes-zoster. International
Journal of Toxicology, 2005 July-Aug.;24(4):205–13.]
Solomon BA, Kaporis AG, Glass AT, Simon
SI, Baldwin HE. Lasting immunity to varicella
in doctors study (L.I.V.I.D. study). J Am Acad Dermatol. 1998 May;38(5
CM, Wittek AE. Immunologic
evidence of reinfection with varicella-zoster
virus. J Infect Dis. 1983 Aug;148(2):200-5.
to reinfection with varicella-zoster
(VZV) was evaluated in immune adults who had household exposure to varicella. Sixty-four percent of 25 adults
exposed to varicella had a fourfold or
greater rise in IgG antibody to VZV or had
a high initial IgG antibody titer to VZV
that declined by fourfold. ...
The increase in immunity to VZV in many immune subjects exposed to VZV
the occurrence of subclinical reinfection.
Cell-mediated immunity to varicella-zoster
virus. J Infect Dis
. 1992 Aug;166
varicella-zoster virus (VZV) infection and
immunization with live attenuated varicella
elicits T lymphocytes that recognize VZV glycoproteins,
gpI-V, and the immediate early/tegument
product of gene 62 (IE62). Proliferation or cytotoxicity
assays, done under limiting dilution conditions to estimate responder
frequencies, indicate no preferential recognition of VZV proteins by
cells. Analysis of the primary cytotoxic T
(CTL) response after vaccination demonstrates that both gpI
and IE62 are targets of the early response. CD4(+)-
CD8(+)-mediated CTL recognition of these viral proteins can be detected
with natural and vaccine-induced immunity. Responder cell frequencies
protein-specific T cell proliferation and CTL function are generally
in subjects with natural and vaccine-acquired immunity to VZV.
Exogenous reexposure to VZV results in
enhanced T cell proliferation
and may be an important mechanism for maintaining virus-specific
immunity. Providing exogenous reexposure
by giving varicella vaccine to individuals
who have preexisting
natural immunity markedly increases the responder cell frequencies of T
that proliferate in response to VZV antigen and the numbers of
that recognize VZV proteins.
Y, Kawano S, Kataoka
Incidence of herpes zoster in pediatricians and history of reexposure
-zoster virus in patients with
zoster. Kansenshogaku Zasshi.
(8):908-12 ) [Article in
found that pediatricians have enhanced specific cellular immunity to varicella-zoster virus (VZV) compared with the
population, which may be due to reexposure
from children with chickenpox. There have been some reported that the varicella vaccine enhance the specific cellular
To estimate the efficacy of varicella
protection against herpes zoster in the elderly, we investigated the
of herpes zoster in 500 pediatricians and family practitioners with
fifties and sixties, and history of reexposure
in 61 patients with herpes zoster by questionnaires retrospectively.
four of 352 pediatricians had a past history of herpes zoster. The
per 100,000 person-years of herpes zoster was 65.2 in those in their
and 158.2 in those in their sixties, which are 1/2 to 1/8 of other
regarding the general population. Among 61 immunocompetent
patients with herpes zoster, only 4 patients (6.6%) had the chance for reexpose to VZV before their herpes zoster. Only 7 (17.5%) of the 40 patients older than 50 years of
with their children less than 14 years of age. Twenty-three
them lived without their children and grandchildren. They are thought
less chance to reexpose to VZV through
may think that the booster effect by reexposure
VZV plays an important role to prevent herpes zoster. Therefore, we can
speculate that the varicella vaccine may
against herpes zoster in the elderly by the enhanced specific cellular
due to the booster effect.
Gershon AA, LaRussa P, Steinberg
N, Lo SH, Meier P.
The protective effect of immunologic boosting
zoster: an analysis in leukemic children who were vaccinated against
chickenpox. J Infect Dis.
reexposure of varicella-immune
to varicella-zoster virus would protect
against or predispose to development of zoster was analyzed. The rate
in 511 leukemic recipients of varicella
had 1 or > 1 dose of varicella vaccine
those who did or did not have a household exposure to varicella
was determined. A Kaplan-Meier life-table analysis revealed that the
of zoster was lower in those given > 1 dose of vaccine (P < .05).
proportional hazards analysis showed that both household exposure to varicella and receipt of > 1 dose of vaccine
protective (P < .01) against zoster. Thus, the risk of zoster is
by reexposure to varicella-zoster
either by vaccination or by close exposure to varicella.
Spingarn RW, Benjamin JA, Meissner HC. Universal
against varicella N Engl J Med, 1998 Mar
5; 338(10):683) [Correspondence].
the Editor: Historically, chickenpox has been largely a benign disease
affecting predominantly preschool and school-aged children. Times are
children enrolled in day-care programs will soon be required to be
against varicella (or have evidence of
having had the
disease). Although it is generally held that immunizing children is
for public health, vaccinating all children against chickenpox is a bad
It is unknown whether long-term immunity to varicella
arises from an attack of the disease in childhood or from the virus's
repeatedly (and naturally) boosting immunity because it is maintained
communities. ... Yet policies of universal vaccination of children
chickenpox] will serve, over time, to eradicate most, but not all,
occurring [chickenpox] and its immeasurable booster effect.
MC, Hethcote HW. Modeling
the Effects of Varicella
Vaccination Programs on the Incidence of Chickenpox and Shingles.
of Mathematical Biology 1999;61:1031-64)
possible dangers of an extensive varicella
vaccination program are more varicella
cases in adults, when the complications rates are higher, and an
cases of zoster (shingles). Here an age-structured
model with vaccination is developed for varicella
zoster. Parameters are estimated from epidemiological data. This
and computer simulation model is used to evaluate the effects of varicella vaccination programs. Although the age
distribution of varicella cases does shift
simulations, this does not seem to be a danger because many of the
occur after vaccine-induced immunity wanes, so they are mild varicella cases with fewer complications. In the
simulations, zoster incidence increases in the first three decades
initiation of a vaccination program, because people who had varicella
in childhood age without boosting, but then it decreases. Thus the
validate the second danger of more zoster cases.
Krause PR. Evidence for frequent reactivation of the Oka
varicella vaccine strain in
healthy vaccinees. . Arch
Virol Suppl 2001;(17):7-15)
antibody levels and infection rates were followed for 4 years in 4,631
immunized with the recently licensed Oka
strain varicella vaccine. Anti-VZV titers
over time in high-responder subjects, but rose in vaccinees
with low titers. Among subjects with low anti-VZV titers, the frequency
clinical sequelae and immunological
exceeded the 13%/yr rate of exposure to wild type varicella.
findings indicate that the Oka strain of
VZV persisted in vivo, and reactivated as serum antibody titers
vaccination. This mechanism may improve vaccine-associated long-term
Pre-licensure clinical studies showed that mean serum anti-VZV levels
among vaccinees continued to increase with
vaccination. This was attributed to immunologic boosting caused by
wild-type VZV in the community.
Wheeler JG, Hall AJ. Contacts with varicella
children and protection against herpes zoster in adults: a case-control
study. Lancet. 2002 Aug 31;360(9334):678-82)
Whether exogenous exposure to varicella-zoster-virus
individuals with latent varicella-zoster
virus infection against herpes zoster by boosting immunity is not
test the hypothesis that contacts with children increase exposure to varicella zoster virus and protect latently
against zoster, we did a case-control study in south London, UK.
... INTERPRETATION: Re-exposure to varicella-zoster
via contact with children seems to protect latently infected
against zoster. Reduction of childhood varicella
vaccination might lead to increased incidence of adult zoster.
the elderly (if effective) should be considered in countries with
childhood varicella vaccination programmes.
Brisson M, Gay NJ, Edmunds WJ,
Andrews NJ. Exposure to varicella boosts
immunity to herpes-zoster: implications
for mass vaccination against chickenpox.
2002 Jun 7;20(19-20):2500-7
present data to confirm that exposure to varicella
boosts immunity to herpes-zoster. We show that exposure to varicella
is greater in adults living with children and that this exposure is
protective against zoster (Incidence ratio=0.75, 95% CI, 0.63-0.89).
is used to parameterise a mathematical
model of varicella zoster virus (VZV)
transmission that captures
differences in exposure to varicella in
with and without children. Under the 'best-fit' model, exposure to varicella is estimated to boost cell-mediated
an average of 20 years (95% CI, 7-41years). Mass varicella
vaccination is expected to cause a major epidemic of herpes-zoster,
more than 50% of those aged 10- 44 years at the introduction of
M, Edmunds WJ. Varicella
in England and Wales:
cost-utility analysis. Arch Dis
To assess the cost-effectiveness of varicella
vaccination, taking into account its impact on zoster. METHODS: An age
structured transmission dynamic model was used to predict the future
of varicella and zoster. Data from
sentinel surveillance systems were used to estimate age specific
consultation, hospitalisation, and
Unit costs, taken from standard sources, were applied to the predicted
outcomes. RESULTS: In England
the annual burden of VZV related disease is substantial, with an
651,000 cases of varicella and 189,000
zoster, resulting in approximately 18,000 QALYs
The model predicts that although the overall burden of varicella
will significantly be reduced following mass infant vaccination, these
will be offset by a significant rise in zoster morbidity. Under base
assumptions, infant vaccination is estimated to produce an overall loss
54,000 discounted QALYs over 80 years and
in a net cost from the health provider (NHS) and the societal
These results rest heavily on the impact of vaccination on
zoster….Conclusion: Routine infant varicella
vaccination is unlikely to be cost-effective and may produce an
overall morbidity. Adolescent vaccination is the safest and most
strategy, but has the least overall impact on varicella.
Thomas SL, Hall AJ. What does epidemiology tell us about
risk factors for herpes zoster? Lancet Infect Dis
of latent varicella zoster virus as herpes
thought to result from waning of specific cell-mediated immunity, but
known about its determinants in individuals with no underlying immuno-suppression. We systematically reviewed
zoster epidemiology in adults and analysed
a large morbidity study to identify factors that might be modulated to
the risk of zoster. Annual zoster incidence in population-based studies
from 3.6-14.2/10(3) in the oldest
factors identified in analytical studies that could explain this
included age, sex, ethnicity, genetic susceptibility, exogenous
immunity from varicella contacts,
cell-mediated immune disorders, mechanical trauma, psychological
stress, and immunotoxin exposure. Our
review highlights the lack of
information about risk factors for zoster. We suggest areas of research
could lead to interventions to limit the incidence of zoster. Such
might also help to identify risk factors for age-related immune decline.
Outbreak of varicella
among vaccinated children--Michigan, 2003.
MMWR Morb Mortal Wkly Rep. 2004 May 14;53(18):389-92.
Centers for Disease Control and Prevention (CDC).
On November 18, 2003, the Oakland County Health Division alerted
Michigan Department of Community Health (MDCH) to a varicella (chicken
pox) outbreak in a kindergarten-third grade elementary school. On
December 11, MDCH and Oakland County public health epidemiologists,
with the technical assistance of CDC, conducted a retrospective cohort
study to describe the outbreak, determine varicella vaccine
effectiveness (VE), and examine risk factors for breakthrough disease
(i.e., varicella occurring >42 days after vaccination). This report
summarizes the results of that study, which indicated that 1)
transmission of varicella was sustained at the school for nearly 1
month despite high vaccination coverage, 2) vaccinated patients had
substantially milder disease (<50 lesions), and 3) a period of >
or =4 years since vaccination was a risk factor for breakthrough
Daniel R. Brooks, Susan M. Lett, Aisha O. Jumaan, Zi Zhang,
Clements, Jane F. Seward. The incidence of varicella and herpes zoster
in Massachusetts as
measured by the Behavioral Risk Factor Surveillance System (BRFSS)
during a period of increasing varicella vaccine coverage, 1998-2003.
BMC Public Health. 2005 Jun 16;5(1):68
The authors sought to
monitor the impact of widespread varicella
vaccination on the epidemiology of varicella
herpes zoster. While varicella incidence
expected to decrease, mathematical models predict an initial increase
zoster incidence if re-exposure to varicella
against reactivation of the varicella
METHODS: In 1998-2003, as varicella
vaccine uptake increased,
incidence of varicella and herpes zoster
in Massachusetts was
monitored using the random-digit-dial Behavioral Risk Factor
System. RESULTS: Between 1998 and 2003, varicella
incidence declined from 16.5/1,000 to 3.5/1,000 (79%) overall with
decreases for all age groups except adults (27% decrease). Age-standardized
estimates of overall herpes zoster occurrence
increased from 2.77/1,000 to 5.25/1,000 (90%) in the period 1999-2003,
and the trend in both crude and adjusted rates was highly significant
age-specific rates were somewhat unstable, but all increased, and the
significant for the 25-44 year and 65+ year age groups. CONCLUSIONS: As
varicella vaccine coverage in children increased, the incidence of
varicella decreased and the occurrence of herpes zoster increased. If
the observed increase in herpes zoster incidence is real, widespread
vaccination of children is only one of several possible explanations.
Further studies are needed to understand secular trends in herpes
zoster before and after use of varicella vaccine in the United States
and other countries.
A. Editorial: varicella
and herpes zoster. Herpes: the
journal of the IHMF,
2005 Dec; 12(3):59
Boosting VZV immunity can protect against zoster: re-exposure to
via contact with children protects latently infected individuals.
Memory CD4 and CD8 cells that recognize VZV proteins are readily
detectable in younger adults, in whom zoster is relatively rare,
although the capacity of peripheral-blood T-cells in those who are
latently infected with VZV appears to diminish with age.... [Cellular
immunity] ... appears more likely to be a consequence of periodic
boosting on exposure to VZV or zoster... The decreasing incidence
of VZV following universal childhood
vaccination is of concern, because a reduced circulation of wild-type
VZV could lead to more cases of zoster in older people, whose immunity
is no longer being boosted by exposure to children with primary
Abarca VK. Varicella Vaccine. Rev
and herpes zoster represent a significant public
health problem. Safe and highly effective varicella
vaccines against severe and moderate varicella
currently available. Vaccine efficacy is lower and more variable
disease and several risk factors have been associated with mild
disease. Experts are currently discussing the need for a second vaccine
Universal varicella vaccination has been
effective in reducing morbidity and hospitalizations due to varicella,
a strategy that has proven to be cost effective in many regions when
societal-perspective is considered in the analysis. Recent data
suggests that varicella vaccination may be
associated with an increased
incidence of herpes zoster in the elderly. Immunity conferred by varicella vaccination seems to be long lasting
continued evaluation is needed in order to asses the effect of the
epidemiology associated with universal immunization.
vaccination and shingles. Postgrad
know that exposure to chickenpox can significantly prevent or delay
(by exogenous boosting of immunity)… Having a child in the household
reduced the risk of shingles for about 20 years…”
P, Zhang JX, Civen
of Vaccine-Induced Immunity to Varicella
Over Time NEJM
2007 Mar 15;356(11):1121-9)
The introduction of universal varicella
in 1995 has substantially reduced varicella-related
and mortality in the United States. However, it remains unclear whether
vaccine-induced immunity wanes over time, a condition that may result
increased susceptibility later in life, when the risk of serious
may be greater than in childhood.
Methods: We examined
10 years (1995 to 2004) of active
surveillance data from a sentinel population of 350,000 subjects to
whether the severity and incidence of breakthrough varicella
(with an onset of rash >42 days after vaccination) increased with
since vaccination. We used multivariate logistic regression to adjust
year of disease onset (calendar year) and the subject's age at both
onset and vaccination.
Results: A total of
11,356 subjects were reported to
have varicella during the surveillance
whom 1080 (9.5%) had breakthrough disease. Children between the ages of
12 years who had been vaccinated at least 5 years previously were
more likely to have moderate or severe disease than were those who had
vaccinated less than 5 years previously (risk ratio, 2.6; 95%
interval [CI], 1.2 to 5.8). The annual rate of breakthrough varicella
significantly increased with the time since vaccination, from 1.6 cases
1000 person-years (95% CI, 1.2 to 2.0) within 1 year after vaccination
per 1000 person-years (95% CI, 6.9 to 11.7) at 5 years and 58.2 per
person-years (95% CI, 36.0 to 94.0) at 9 years.
Conclusions A second dose of varicella
vaccine, now recommended for all children, could
improve protection from both primary vaccine failure and waning
Quan D, Cohrs RJ, Mahalingam R, Gilden DH. Prevention
shingles: safety and efficacy of live zoster vaccine. Ther Clin
Risk Manag. 2007 Aug;3(4):633-9
Primary infection with varicella
zoster virus (VZV) causes chickenpox (varicella)
after which virus becomes latent in cranial
nerve, dorsal root and autonomic ganglia along the entire neuraxis.
Virus may later reactivate, causing shingles (zoster), characterized by
and rash restricted to 1-3 dermatomes. More than 40% of zoster patients
age 60 develop postherpetic neuralgia
that persists for months to years. The socioeconomic impact of primary varicella infection has been lessened by
VZV vaccine for children. However, the effect of childhood vaccination
incidence of zoster is unknown. Virus reactivation correlates with
cell-mediated immunity (CMI) to VZV with normal aging. Adults exposed
children with varicella may have a boost
in CMI to
VZV. For at least several more decades, the incidence of zoster may
the elderly population grows. The anticipated increase in zoster burden
illness in future decades was a major impetus for the Shingles
Study, a prospective, double-blind, placebo-controlled trial of
vaccine to prevent zoster in older adults. This review discusses
clinical and virological aspects of zoster
and its complications,
current treatment options, and VZV vaccine development along with its
role in disease prevention.
Yawn BP, Saddier P, Wollan PC, St Sauver
JL, Kurland MJ, Sy LS.
A Population-Based Study of the
Complication Rates of Herpes Zoster Before
Vaccine Introduction. Mayo Clin Proc.
A total of 1669 adult residents with a confirmed diagnosis of HZ were
identified between January 1, 1996, and December 31, 2001. Most (92%)
patients were immunocompetent and 60% were
When adjusted to the US
adult population, the incidence of HZ was 3.6 per 1000 person-years
confidence interval, 3.4-3.7), with a temporal increase from 3.2 to 4.1
1000 person-years from 1996 to 2001.
H. Herpes zoster in Australia:
evidence of increase in
incidence in adults attributable to varicella
immunization? Epidemiol Infect.
2010 Aug 23:1-8.
Rates of herpes zoster (HZ) hospitalizations, antiviral prescriptions,
and New South Wales
emergency-department presentations for age groups <20, 20-39, 40-59
years were investigated. Trends were analysed
Poisson regression to determine if rates increased following funding of
varicella immunization in Australia in
November 2005. The
regression analysis revealed significantly increasing trends of between
6% per year in both antiviral prescriptions and emergency-department
in all except the <20 years age group. When considered together, the
differential changes in rates observed by age group provides
evidence to indicate that HZ incidence is increasing in adults aged
years. However, it is not possible to attribute the increasing trends
observed directly to the varicella
immunization programme, and continued
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F. Edward Yazbak, MD, FAAP