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 …
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 …
When 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.
Some fifteen years ago, suddenly and out of the blue, chickenpox
became a very serious disease and there were multiple TV and press
reports about children dying from chickenpox all over the country.
Economists weighed in and ominous warnings filled the air:
Chickenpox was not only killing kids and adults, it was a national
economic disaster that was eventually ultimately going to collapse
the United States economy because it kept mothers at home caring for
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 all, our children’s lives and our national economy
depended on it.
VARIVAX® was launched to the cheers of the Merck stockholders in
Within less than a year spent figuring
out reimbursement, it caught on in a grand way. With time, it became
apparent that two doses
were required to protect susceptible
children and adults and … in 2006, a second dose of VARIVAX® was
recommended. The children were not too happy; the stockholders were
jubilant and it is rumored that at Merck, people were heard humming:
“Double the shots! Double the Fun.” The vaccine is still
selling well at $83.77 per dose.
Pediatricians were first told that the vaccine, because it was
another attenuated live virus vaccine, had to be administered one
month after the MMR vaccine, between 12 and 15 months of age.
This was soon changed!
It 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 wait a month
. This was certainly peculiar but
then preventing chickenpox, most often a mild illness in children,
did not make much sense either!
Evidently forgetting the uproar about the MMR vaccine, some bright
people at Merck met with friends in Atlanta, and decided to
VARIVAX® with the MMR vaccine. The new vaccine MMRV was
licensed in 2005 and marketed under the name PROQUAD®. I thought the
name was as strange as the idea. [ii]
In early 2008, the FDA announced that the incidence of febrile
seizures had increased with the use of PROQUAD® at age 12-15 months
and that some reports of encephalitis following vaccination had been
The Agency then immediately
explained that this did not mean that the encephalitis was caused by
the 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
suspends or stops manufacturing the problem drug. On the other hand,
if someone has a serious reaction shortly after a vaccination, such
as an encephalopathy or encephalitis, it is almost always considered
. No matter the number of reports of
vaccine-related adverse events, the verdict is the same: They are
and nothing but unscientific observations
by nervous parents.
To deal with the increased risk of febrile seizures following the
first dose of PROQUAD® (MMRV), the CDC published a long and hard to
understand Morbidity and
Mortality Weekly Report (MMWR) [iv]
7, 2010 that included the following recommendations:
· The routinely recommended
ages for measles, mumps, rubella and varicella vaccination
continue to be age 12--15 months for the first dose and age 4--6
years for the second dose.
· For the first dose of measles, mumps, 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 both
vaccination options with the parents or caregivers. Unless the
parent or caregiver expresses a preference for MMRV vaccine, CDC
recommends that MMR vaccine and varicella vaccine should be
administered for the first dose in this age group.
· For the second dose of measles, 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 its equivalent component
vaccines (i.e., MMR vaccine and varicella vaccine).
Considerations should include provider assessment, patient
preference, and the potential for adverse events.
· A personal or family (i.e., sibling or parent) history
of seizures of any etiology is a precaution for MMRV
vaccination. Children with a personal or family history of
seizures of any etiology generally should be vaccinated with MMR
vaccine and varicella vaccine.
The 25 page current
PROQUAD® product insert
dated September 2010, that the doctors and their nurses are
supposed to read only includes the following recommendations:
FOR 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 needed, ProQuad may be used. This dose is usually
administered at 4 to 6 years of age. At least 1 month should
elapse between a dose of a measles-containing vaccine such as
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 varicella-containing vaccine and ProQuad.
The difference between the two sets of recommendations is at the
very least concerning.
After VARIVAX® was introduced, we all expected a decrease in the
number of cases of chickenpox among children and an increase in the
disease incidence among 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 certain surveillance sites. Unfortunately, that
brilliant result came with a price: The all important chickenpox
immunological boosting that had occurred since time immemorial
because of continued exposure to wild-type VZV was quickly
disappearing and with it all the protection it provided.
The Australians are well known for adopting new vaccination
initiatives rather 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
October 18, 2010, the Medical Journal of Australia, the official
journal of the Australian Medical Association published an article
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 consultations”.
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 3.4/1000 consultations
for the first half of 2010. The increase in shingles-related
consultations among patients older than 70 during the same period
was simply described as substantial.
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
about the recent sudden increase in the incidence of shingles.
Goldman, a quiet, soft-spoken and meticulous scientist remains
almost apologetic about his discovery; a flashback seems essential
to show its brilliance and importance.
Three Varicella Active Surveillance Projects (VASP) were created to
monitor trends of varicella (chickenpox) as VARIVAX® was launched.
Dr. Goldman worked in the California VASP, located in Antelope
Valley, an area of around 300,000 residents. The project easily
confirmed that the incidence of chickenpox (varicella) among
children was decreasing. Even though everyone knew that the absence
of natural disease was likely to compromise the immune boosting that
was essential to suppress shingles (herpes zoster) due to the
reactivation of varicella zoster virus, the declaration by Dr.
Goldman that cases of shingles were much more numerous than expected
was still met with denial. No one apparently wanted to concede that,
what was logically expected but shamefully overlooked by the vaccine
developers was indeed happening. Dr. Goldman begged the principal
investigators to address the problem; instead of thanking and
praising him, they fought him all the way, ignoring the evidence.
History was repeating itself! This was certainly not the first time
that people who had discovered important medical facts were
marginalized and persecuted.
It was only after the horse was way out of the barn, that
surveillance sites started monitoring shingles trends,
some five years
varicella vaccine had been introduced.
Even then, the pro-vaccine forces still remained in solid denial and
persistently downgraded the risk; after all, “their serious disease
called chickenpox that had killed people” had been wiped out. So
what if there was some “collateral damage”.
True to form, the CDC is still
not mentioning shingles as a complication of chickenpox vaccination.
On October 23, 2010, I reviewed the current Vaccine Information
Statement (VIS) for VARIVAX®, [vii]
official information pamphlet that a parent is supposed to read
before signing the permission slip allowing the administration of
The document, dated 3/13/2008 only stated that: “A person 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 States,
as a result of chickenpox."
It 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 complication. Nor
did it allude to the vastly
45,000 + chickenpox vaccine-associated
reactions so far reported to
The “11,000 hospitalizations” attributed to chickenpox are
impossible to confirm or deny. What is easier to do is to compare
them with other inflated CDC statistics such as influeza-associated
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
Because the vaccine is
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
statistics to include the approximately 100 children
plus adult deaths
. In any case, to help put
things in perspective, 82 individuals were killed by lightning
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
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
“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, compared with 3 of 7 (43%)
unvaccinated students. Vaccine effectiveness was 72% (95% confidence
What did Merck do?
Responding to the waves of Shingles nationwide and well immune (if
you forgive the pun) from litigation because of the National Vaccine
Injury Compensation Program, Merck did again what was best for
Merck: 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 Statement [xiii]
A single dose is recommended but those in the know quickly add that
“it is possible a second dose will be recommended in the future.”
If 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 country who paid millions for these achievements got NOTHING
for their money, except pain and grief.
According to the CDC October 6, 2010 vaccine price list,
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 and
with the increased risk of getting chickenpox as adults, when the
disease is usually much more serious.
What the varicella vaccination program did to the U.S. Economy was
no less unfortunate. Originally, one dose of varicella vaccine was
supposed to provide lifetime immunity and supposedly save an
estimated $70 million per year--primarily in societal costs
associated with a parent staying home from work to care for a child
with chickenpox. Instead, the present epidemic of shingles and
complications has caused a surcharge of several hundred million
dollars that no one anticipated. Added to that is the cost of the
now required second dose of VARIVAX®, also a non-anticipated
It has been proposed that around 25% of medical costs of VZV disease
are due to chickenpox and 75% are due to shingles. A relatively
small increase in shingles cases can therefore quickly offset any
cost-benefit previously expected from universal chickenpox
It is interesting that pediatricians, who were now administering
VARIVAX® because it was recommended and in places required,
had quite a bit to lose
There was a little secret we had known for sometime but did not
discuss too much, may be to ward off the evil eye: We pediatricians,
as a group, were less likely than others to get shingles as we
In 1998, Solomon, Kaporis et al [xv]
University of New York Health Science Center, Brooklyn confirmed
that fact statistically… at last. They conducted a study of
physicians and found that pediatricians, because they were
constantly exposed to Varicella-Zoster Virus, had distinctly lower
rates of shingles than psychiatrists who were rarely exposed to the
virus and the disease in their practice.
Obviously that is now changing and the thought is depressing!
Some prevalence reviews suggest that women may be more susceptible
to shingles than men.
Usually the first manifestation of the disease is pain that can be
severe and may represent early on a diagnostic challenge. Many
sufferers have been needlessly exposed to X-rays and even CT-scans
before the typical rash appeared 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 crops develop, the
previous lesions start blistering then become pustular and
ultimately crust over.
The skin eruption is painful and itchy and can involve any dermatome
and sometimes more than one. The rash, often in linear bands, very
rarely crosses the midline and is most commonly located on the side
of the torso, affecting a nerve root between the third thoracic and
the third lumbar roots.
Ophthalmic Zoster affects the distribution area of the ophthalmic
branch of the trigeminal nerve, a truly scary presentation. Other
sites such as the face are more rarely involved.
Postherpetic neuralgia is the most dreaded complication of the
disease. It is essentially an excruciating and almost unbearable
constant burning and tingling pain that follows the rash and may
last for weeks, months or longer.
In the debilitated elderly patients the blisters may be very deep
and may result in severe scarring. Around 5% of the affected elderly
develop muscle weakness.
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 complications. Success has also been achieved
recently with the use of intravenous vitamin C.[xvi]
Large scale studies are needed to confirm the findings. Oral vitamin
C has been used by some.[xvii]
Anticonvulsants have been used for the symptomatic treatment of
postherpetic neuralgia; Neurontin (Gabapentin) in particular appears
to have had more success than others. Antidepressants help
sometimes. Recently, Lyrica (Pregabalin) has been tried with good
results. All these medications require attentive medical
Over-the-counter painkillers are helpful in mild cases of neuralgia.
More often, physicians have to resort to opioids that carry a
distinct risk of addiction.
Application of anesthetic creams for local relief is another option
for those patients who are reluctant to take drugs.
Twenty-first century mainstream medical professionals insist that a
vaccine is needed for every acute illness. However, until and unless
we do studies comparing the vaccinated to the never-vaccinated, we
will never know what is really best for us and for our children.
Honest efforts to study both the long and short-term effects of each
vaccination are urgently needed otherwise we are fooling ourselves
and just whistling in the dark when we enumerate the alleged
benefits of a vaccination.
In years past, people felt that children were actually stronger and
healthier after they recovered from certain contagious diseases. At
least one California study seems to support that old belief.
Glioma is an aggressive malignant tumor of the nervous system.
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 varicella-zoster virus and three
other herpesviruses among 229 adults with the disease and 289
controls. They found that patients with glioma were less likely to
report a history of chickenpox than controls. Testing also revealed
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 tumors
or whatever else may be lurking, unexamined and/or ignored?
Prior to the introduction of the universal varicella vaccination
program in the United States, almost 95% of adults experienced
natural chickenpox, usually as school age children. These cases were
usually benign and resulted in long term immunity because of
constant boosting due to repeated exposures to other children and
adults with the disease.
This large reservoir of individuals having long term immunity has
been seriously compromised by the mass vaccination of children that
provides at best 70 to 90% immunity. The vaccine-acquired immunity
is of unknown duration and only causes the shifting of chickenpox to
the more vulnerable adults. To arrive to the bottom line, one needs
to now add the adverse effects of the required two doses of
chickenpox vaccine and the distinct potential for increased risk of
shingles for an estimated 30 to 50 years among adults.
One must also keep in mind that regardless of the number of
boosters, the acquired immunity from vaccination will never equal
the strong constantly-boosted natural immunity we all had in the
past, before the Universal Varicella Vaccination program was
Varicella vaccination was a mistake.
Mandating it as a universal vaccination program for every child was
an even bigger mistake.
Grant KA, Carville KS, Kelly HA.
Evidence of increasing frequency of herpes zoster management in
Australian general practice since the 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
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 Pt
Wittek AE. Immunologic evidence of
varicella-zoster virus. J Infect Dis. 1983 Aug;148(2):200-5.
reinfection with varicella-zoster
virus (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 suggests the
occurrence of subclinical reinfection.
immunity to varicella-zoster virus.
J Infect Dis
. 1992 Aug;166
virus (VZV) infection and immunization with live attenuated
varicella vaccine elicits T lymphocytes
that recognize VZV glycoproteins,
gpI-V, and the immediate early/tegument
protein, the product of gene 62 (IE62). Proliferation or
cytotoxicity assays, done under limiting
dilution conditions to estimate responder cell frequencies, indicate
no preferential recognition of VZV proteins by human T cells.
Analysis of the primary cytotoxic T
lymphocyte (CTL) response after vaccination demonstrates that both
gpI and IE62 are targets of the early
response. CD4(+)- and CD8(+)-mediated CTL
recognition of these viral proteins can be detected with natural and
vaccine-induced immunity. Responder cell frequencies for
protein-specific T cell proliferation and CTL function are generally
comparable 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 cellular immunity. Providing
exogenous reexposure by giving
varicella vaccine to individuals who
have preexisting natural immunity markedly increases the responder
cell frequencies of T cells that proliferate in response to VZV
antigen and the numbers of circulating CTL that recognize VZV
Y, Kawano S,
N. Incidence of herpes zoster in
pediatricians and history of reexposure
-zoster virus in patients
with herpes zoster. Kansenshogaku
) [Article in Japanese]
We found that pediatricians have enhanced
specific cellular immunity to varicella-zoster
virus (VZV) compared with the general population, which may be due
to reexposure to VZV from children with
chickenpox. There have been some reported that the
varicella vaccine enhance the specific
cellular immunity. To estimate the efficacy of
varicella vaccine for protection against herpes zoster in the
elderly, we investigated the incidence of herpes zoster in 500
pediatricians and family practitioners with their fifties and
sixties, and history of reexposure to
VZV in 61 patients with herpes zoster by questionnaires
retrospectively. Thirty four of 352 pediatricians had a past history
of herpes zoster. The incidence per 100,000 person-years of herpes
zoster was 65.2 in those in their fifties and 158.2 in those in
their sixties, which are 1/2 to 1/8 of other reports 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 age lived with their children less than 14 years of
age. Twenty-three (57.5%) of them lived without their
children and grandchildren. They are thought to be less chance to
reexpose to VZV through children. We may
think that the booster effect by reexposure
to VZV plays an important role to prevent herpes zoster. Therefore,
we can speculate that the varicella
vaccine may protect against herpes zoster in the elderly by the
enhanced specific cellular immunity due to the booster effect.
AA, LaRussa P, Steinberg S,
Mervish N, Lo SH, Meier P.
protective effect of immunologic boosting against zoster: an
analysis in leukemic children who were vaccinated against
chickenpox. J Infect Dis.
of varicella-immune persons to
varicella-zoster virus would protect
against or predispose to development of zoster was analyzed. The
rate of zoster in 511 leukemic recipients of
varicella vaccine who had 1 or > 1 dose of
varicella vaccine and in those who did
or did not have a household exposure to
varicella was determined. A Kaplan-Meier life-table analysis
revealed that the incidence of zoster was lower in those given > 1
dose of vaccine (P < .05). A Cox proportional hazards analysis
showed that both household exposure to
varicella and receipt of > 1 dose of vaccine were highly
protective (P < .01) against zoster. Thus, the risk of zoster is
decreased by reexposure to
varicella-zoster virus, either by
vaccination or by close exposure to varicella.
RW, Benjamin JA, Meissner HC. Universal vaccination against
Engl J Med, 1998 Mar 5;
To the Editor: Historically, chickenpox
has been largely a benign disease affecting predominantly preschool
and school-aged children. Times are changing: in Massachusetts,
children enrolled in day-care programs will soon be required to be
vaccinated against varicella (or have
evidence of having had the disease). Although it is generally held
that immunizing children is axiomatic for public health, vaccinating
all children against chickenpox is a bad idea. 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 in our communities. ... Yet policies of universal
vaccination of children [against chickenpox] will serve, over time,
to eradicate most, but not all, naturally occurring [chickenpox] and
its immeasurable booster effect.
MC, Hethcote HW.
Modeling the Effects of Varicella
Vaccination Programs on the Incidence of Chickenpox and Shingles.
Bulletin of Mathematical Biology 1999;61:1031-64)
Two possible dangers of an extensive
varicella vaccination program are more
varicella (chickenpox) cases in adults,
when the complications rates are higher, and an increase in cases of
zoster (shingles). Here an age-structured epidemiologic-demographic
model with vaccination is developed for
varicella and zoster. Parameters are estimated from
epidemiological data. This mathematical and computer simulation
model is used to evaluate the effects of
varicella vaccination programs. Although the age distribution
of varicella cases does shift in the
simulations, this does not seem to be a danger because many of the
adult cases 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 after initiation of a vaccination program,
because people who had varicella in
childhood age without boosting, but then it decreases. Thus the
simulations validate the second danger of more zoster cases.
PR. Evidence for frequent reactivation of the Oka
varicella vaccine strain in healthy
vaccinees. . Arch Virol
Serum antibody levels and infection
rates were followed for 4 years in 4,631 children immunized with the
recently licensed Oka strain varicella
vaccine. Anti-VZV titers declined over time in high-responder
subjects, but rose in vaccinees with low
titers. Among subjects with low anti-VZV titers, the frequency of
clinical sequelae and immunological
boosting significantly exceeded the 13%/yr rate of exposure to wild
type varicella. These findings indicate
that the Oka strain of VZV persisted in vivo, and reactivated as
serum antibody titers declined after vaccination. This mechanism may
improve vaccine-associated long-term immunity. Pre-licensure
clinical studies showed that mean serum anti-VZV levels among
vaccinees continued to increase with
time after vaccination. This was attributed to immunologic boosting
caused by exposure to wild-type VZV in the community.
SL, Wheeler JG, Hall AJ. Contacts with
varicella or with children and protection against herpes
zoster in adults: a case-control study.
Lancet. 2002 Aug 31;360(9334):678-82)
BACKGROUND: Whether exogenous exposure
to varicella-zoster-virus protects
individuals with latent varicella-zoster
virus infection against herpes zoster by boosting immunity is not
known. To test the hypothesis that contacts with children increase
exposure to varicella zoster virus and
protect latently infected adults against zoster, we did a
case-control study in south London, UK. ... INTERPRETATION:
Re-exposure to varicella-zoster virus
via contact with children seems to protect latently infected
individuals against zoster. Reduction of childhood
varicella by vaccination might lead to
increased incidence of adult zoster. Vaccination of the elderly (if
effective) should be considered in countries with childhood
Brisson M, Gay NJ, Edmunds WJ,
Andrews NJ. Exposure to varicella boosts
immunity to herpes-zoster: implications for mass vaccination against
2002 Jun 7;20(19-20):2500-7
We 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 highly protective against zoster (Incidence
ratio=0.75, 95% CI, 0.63-0.89). The data is used to
parameterise a mathematical model of
varicella zoster virus (VZV)
transmission that captures differences in exposure to
varicella in adults living with and
without children. Under the 'best-fit' model, exposure to
varicella is estimated to boost
cell-mediated immunity for an average of 20 years (95% CI,
7-41years). Mass varicella vaccination
is expected to cause a major epidemic of herpes-zoster, affecting
more than 50% of those aged 10- 44 years at the introduction of
M, Edmunds WJ.
vaccination in England and
Wales: cost-utility analysis. Arch
AIMS: 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 incidence
of varicella and zoster. Data from
national and sentinel surveillance systems were used to estimate age
specific physician consultation,
hospitalisation, and mortality rates. Unit costs, taken from
standard sources, were applied to the predicted health outcomes.
RESULTS: In England and Wales, the annual burden of VZV related
disease is substantial, with an estimated 651,000 cases of
varicella and 189,000 cases of zoster,
resulting in approximately 18,000 QALYs
lost. The model predicts that although the overall burden of
varicella will significantly be reduced
following mass infant vaccination, these benefits will be offset by
a significant rise in zoster morbidity. Under base case assumptions,
infant vaccination is estimated to produce an overall loss of 54,000
discounted QALYs over 80 years and to
result in a net cost from the health provider (NHS) and the societal
perspectives. 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 increase in overall morbidity.
Adolescent vaccination is the safest and most cost-effective
strategy, but has the least overall impact on
Thomas SL, Hall AJ. What does epidemiology tell us about
risk factors for herpes zoster? Lancet Infect
, 2004 Jan.; 4(1):26-33
Reactivation of latent
varicella zoster virus as herpes zoster
is thought to result from waning of specific cell-mediated immunity,
but little is known about its determinants in individuals with no
underlying immuno-suppression. We
systematically reviewed studies of zoster epidemiology in adults and
analysed data from a large morbidity
study to identify factors that might be modulated to reduce the risk
of zoster. Annual zoster incidence in population-based studies
varied from 3.6-14.2/10(3) in the oldest
individuals. Risk factors identified in analytical studies that
could explain this variation included age, sex, ethnicity, genetic
susceptibility, exogenous boosting of immunity from
varicella contacts, underlying
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 that could lead to
interventions to limit the incidence of zoster. Such research 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
the 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 disease.
Katherine Yih, Daniel R. Brooks, Susan
M. Lett, Aisha O.
Jumaan, Zi Zhang, Karen M.
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 and herpes
zoster. While varicella incidence would
be expected to decrease, mathematical models predict an initial
increase in herpes zoster incidence if re-exposure to
varicella protects against reactivation
of the varicella zoster virus. 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 Surveillance System.
RESULTS: Between 1998 and 2003, varicella
incidence declined from 16.5/1,000 to 3.5/1,000 (79%) overall with
>65% 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 (p<0.001). Annual age-specific rates were
somewhat unstable, but all increased, and the trend was 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
VZV 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 infection.
VK. Varicella Vaccine. Rev
and herpes zoster represent a significant public health problem.
Safe and highly effective varicella
vaccines against severe and moderate varicella
are currently available. Vaccine efficacy is lower and more variable
against mild disease and several risk factors have been associated
with mild breakthrough disease. Experts are currently discussing the
need for a second vaccine dose. Universal
varicella vaccination has been highly effective in reducing
morbidity and hospitalizations due to varicella,
a strategy that has proven to be cost effective in many regions when
the 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 but a continued evaluation is
needed in order to asses the effect of the changing epidemiology
associated with universal immunization.
, chickenpox vaccination and shingles.
Med J. 2006 May;82
“We know that exposure to chickenpox can
significantly prevent or delay shingles (by exogenous boosting of
immunity)… Having a child in the household reduced the risk of
shingles for about 20 years…”
Chaves SS, Gargiullo
P, Zhang JX,
L, Seward JF.
Loss of Vaccine-Induced Immunity to
Varicella Over Time NEJM 2007 Mar
Background: The introduction of
universal varicella vaccination in 1995
has substantially reduced varicella-related
morbidity and mortality in the United States. However, it remains
unclear whether vaccine-induced immunity wanes over time, a
condition that may result in increased susceptibility later in life,
when the risk of serious complications may be greater than in
examined 10 years (1995 to 2004) of active surveillance data from a
sentinel population of 350,000 subjects to determine whether the
severity and incidence of breakthrough
varicella (with an onset of rash >42 days after vaccination)
increased with the time since vaccination. We used multivariate
logistic regression to adjust for the year of disease onset
(calendar year) and the subject's age at both disease onset and
Results: A total of
11,356 subjects were reported to have varicella
during the surveillance period, of whom 1080 (9.5%) had breakthrough
disease. Children between the ages of 8 and 12 years who had been
vaccinated at least 5 years previously were significantly more
likely to have moderate or severe disease than were those who had
been vaccinated less than 5 years previously (risk ratio, 2.6; 95%
confidence interval [CI], 1.2 to 5.8). The annual rate of
breakthrough varicella significantly
increased with the time since vaccination, from 1.6 cases per 1000
person-years (95% CI, 1.2 to 2.0) within 1 year after vaccination to
9.0 per 1000 person-years (95% CI, 6.9 to 11.7) at 5 years and 58.2
per 1000 person-years (95% CI, 36.0 to 94.0) at 9 years.
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 of shingles: safety and efficacy of live
zoster vaccine. Ther
Clin Risk Manag.
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 pain and rash restricted to 1-3 dermatomes. More than 40% of
zoster patients over age 60 develop
postherpetic neuralgia (PHN), pain that persists for months
to years. The socioeconomic impact of primary
varicella infection has been lessened by introduction of VZV
vaccine for children. However, the effect of childhood vaccination
on the incidence of zoster is unknown. Virus reactivation correlates
with waning cell-mediated immunity (CMI) to VZV with normal aging.
Adults exposed to children with varicella
may have a boost in CMI to VZV. For at least several more decades,
the incidence of zoster may increase as the elderly population
grows. The anticipated increase in zoster burden of illness in
future decades was a major impetus for the Shingles Prevention
Study, a prospective, double-blind, placebo-controlled trial of
attenuated VZV 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 future role in disease
Yawn BP, Saddier P, Wollan PC, St Sauver JL,
Kurland MJ, Sy LS.
A Population-Based Study of the Incidence
and Complication Rates of Herpes Zoster Before
Zoster Vaccine Introduction. Mayo Clin
RESULTS: A total of 1669 adult residents
with a confirmed diagnosis of HZ were identified between January 1,
1996, and December 31, 2001. Most (92%) of these patients were
immunocompetent and 60% were women. When
adjusted to the US adult population, the incidence of HZ was 3.6 per
1000 person-years (95% confidence interval, 3.4-3.7), with a
temporal increase from 3.2 to 4.1 per 1000 person-years from 1996 to
H. Herpes zoster in Australia: evidence of increase in incidence in
adults attributable to varicella
Infect. 2010 Aug 23:1-8.
SUMMARY: Rates of herpes zoster (HZ)
hospitalizations, antiviral prescriptions, and New South Wales
emergency-department presentations for age groups <20, 20-39, 40-59
and 60 years were investigated. Trends were
analysed using 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 2% and 6% per
year in both antiviral prescriptions and emergency-department
presentations in all except the <20 years age group. When considered
together, the differential changes in rates observed by age group
provides preliminary evidence to indicate that HZ incidence is
increasing in adults aged >20 years. However, it is not possible to
attribute the increasing trends in HZ observed directly to the
programme, and continued monitoring and
analyses of data for a longer duration, both pre- and post-vaccine
introduction, is required.
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F. Edward Yazbak, MD, FAAP