The Chickenpox Vaccine
F. Edward Yazbak MD
Shingles, the clinical picture
Thoughts and Reflections
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 …
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
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 1995
[i] 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 combine 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.
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 filed. [iii] 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 a coincidence. No matter the number of
reports of vaccine-related adverse events, the verdict is the same: They are all
anecdotal 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] on May 7, 2010 that included the following
· 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 [v] 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
Arvin AM, Koropchak CM, Wittek AE. Immunologic evidence of reinfection with
varicella-zoster virus. J Infect Dis. 1983 Aug;148(2):200-5.
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”. [vi]
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 after the 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
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] the official
information pamphlet that a parent is supposed to read before signing the
permission slip allowing the administration of the vaccine.
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
under-represented 45,000 + chickenpox vaccine-associated reactions so far
reported to VAERS.
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 hospitalizations [viii]
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 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 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, compared with 3 of 7 (43%)
unvaccinated students. Vaccine effectiveness was 72% (95% confidence interval:
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] published 10/6/2009.
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.” Why not?
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, [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
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
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 expenditure.
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 vaccination.
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 aged.
In 1998, Solomon, Kaporis et al [xv], State 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!
Shingles, the clinical picture
Some prevalence reviews suggest that women may be more susceptible to shingles
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.
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.
Thoughts and Reflections
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.
Weinberg 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 an
inverse association 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 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 launched.
Varicella vaccination was a mistake.
Mandating it as a universal vaccination program for every child was an even
http://www.vaccinationnews.com/node/19913 (Accessed 10/24/10)
[vi] 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
http://www.cdc.gov/flu/about/qa/hospital.htm (Accessed 10/25/10)
http://www.cdc.gov/mmwr/preview/mmwrhtml/00052600.htm (Accessed 10/25/10)
[xi] Goldman GS. Universal varicella vaccination: Efficacy
trends and effect on herpes-zoster. International Journal of Toxicology, 2005
[xv] 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 1):763-5).
www.jpands.org/vol11no1/orient.pdf Accessed 10/23/10
http://www.orthomolecular.org/resources/omns/v01n05.shtml Accessed 10/23/10
Resistance to 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.
Arvin AM. Cell-mediated immunity to varicella-zoster virus. J Infect Dis.
1992 Aug;166 Suppl
Natural varicella-zoster 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 proteins.
Terada K, Hiraga Y, Kawano S, Kataoka N. Incidence of herpes zoster in
pediatricians and history of reexposure to varicella-zoster virus in patients
with herpes zoster. Kansenshogaku Zasshi. 1995 Aug;69(8):908-12 )
[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.
Gershon AA, LaRussa P, Steinberg S, Mervish N, Lo SH, Meier P. The protective
effect of immunologic boosting against zoster: an analysis in leukemic children
who were vaccinated against chickenpox. J Infect Dis. 1996
Whether reexposure 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.
Spingarn RW, Benjamin JA, Meissner HC. Universal vaccination against varicella
N Engl J Med, 1998 Mar 5; 338(10):683) [Correspondence].
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
Schuette 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.
Krause PR. Evidence for frequent reactivation of the Oka varicella vaccine
strain in healthy vaccinees. . Arch Virol Suppl 2001;(17):7-15)
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
Thomas 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 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.
Vaccine. 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
Brisson M, Edmunds WJ. Varicella vaccination in England and Wales:
cost-utility analysis. Arch Dis Child. 2003 Oct;88(10):862-9
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 varicella.
Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for
herpes zoster? Lancet Infect Dis, 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.
W. 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,
BMC Public Health. 2005 Jun 16;5(1):68
BACKGROUND: 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
Volpi A. Editorial: varicella immunization 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
Abarca VK. Varicella Vaccine. Rev Chilena Infectol. 2006
Varicella 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.
Welsby PD.Chickenpox, chickenpox vaccination and shingles. Postgrad Med J. 2006
“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, Civen R, Guris D, Mascola 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 childhood.
Methods: We 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 vaccination.
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.
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 of 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 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
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 Proc. 2007
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 2001.
Jardine A, Conaty SJ, Vally H. Herpes zoster in Australia: evidence of
increase in incidence in adults attributable to varicella immunization?
Epidemiol 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 varicella immunization
programme, and continued monitoring and analyses of data for a longer duration,
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assistance was very much appreciated.
F. Edward Yazbak, MD, FAAP
January 13, 2011