**FTS-CDC-NIP**

**Moderator: Dale Babcock**

**January 17, 2008**

**11:00 am CT**

Coordinator: Welcome, and thank you for standing by. At this time, all
participants will be in a listen-only mode. To ask a question during the
question and answer session, you may press star, one on your touch-tone
phone. Today's conference is being recorded. If you have any objections,
you may disconnect at this time.

I will now turn the call over to Doctor (Andrew Kroger). You may begin.

(Andrew Kroger): Thank you very much. Good afternoon, and welcome to
Current Issues in Immunization, a CDC net conference. I'm Doctor Andrew
Kroger, a medical officer in the Education, Information, and Partnership
branch of the National Center for Immunization and Respiratory Diseases
and I will be the moderator for today's session.

> To participate in today's program, you need a telephone connection and
> a separate Internet connection.

The learning objectives for this session are, one, list a recent
immunization recommendation made by the Advisory Committee on
Immunization Practices, or ACIP and two, describe an emerging
immunization issue.

Today is January 17, 2008 and we have two parts for this net conference.
In part one, Doctor (Rafael Harpaz), a medical officer in the Viral
Diseases division will discuss zoster disease and zoster vaccine. In
part two, (Shannon Stokley), a lead epidemiologist in the Immunization
Service Division will talk about adolescent vaccine recommendations. A
question and answer session will follow.

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February 18, 2008.

CDC, our planners and our presenters wish to disclose that they have no
financial interests or other relationships with the manufacturers of
commercial products, suppliers of commercial services or commercial
supporters.

Presentations will not include any discussion of the unlabeled use of a
product or a product under investigational use, with the exception of
Doctor (Harpaz)' discussion of off-label use of zoster vaccine in
individuals who already have had a diagnosis of zoster. So now we will
begin with a presentation of zoster and zoster vaccine. Doctor (Harpaz)?

(Rafael Harpaz): Hi. Good afternoon and thank you very much, Doctor
(Kroger). Today, the title of my talk is "Herpes Zoster. It's now a
vaccine-preventable disease." So here's my outline. We're going to start
by talking about the clinical manifestations of herpes zoster, which I
designate in these slides as HZ.

I'll talk about the epidemiology of zoster, describe the pivotal zoster
vaccine study, go over provisional recommendations on zoster vaccine and
then finish up with some key remaining questions, activities and
challenges relating to zoster and zoster vaccine.

So let's start with Clinical Manifestations of Zoster. Zoster -- which
is also called shingles -- represents a reactivation of varicella zoster
virus (VZV), leading to a crop of blisters, shown here and it's in the
dermatomal pattern, which I'll describe in the next slide.

Following initial infection, which causes chicken pox, VZV establishes a
latent infection in dorsal root ganglia along the neuraxis. Years to
decades later, the VZV reactivates, though subclinical reactivation can
occur as well. The VZV variants reappear and spread to the skin via
peripheral nerves and this is shown in this cartoon over here, where it
shows infection leading to latency and then finally reactivation.

So moving on to the primary manifestations of zoster, it's a vesicular
rash in a dermatomal pattern. And a dermatome is an area of skin
supplied by sensory nerve fibers coming from one nerve root and this is
a dermatome map that shows the different dermatomes.

So continuing to talk about rash, it tends to be unilateral - one to
three adjacent dermatomes. There could be some scattered lesions
elsewhere. The most commonly affected dermatomes are thoracic, then
comes lumbar trigeminal or cervical dermatomes and finally, least common
are the sacral or other cranial dermatomes. New lesions can arise over
five to seven days. They start as erythematous macular papules, move to
vesicles and there could be some pustules as well. Finally, crusts form
over seven to 12 days and full resolution of the rash occurs in five to
25 days. Some of the occasional consequences of the rash can be
bacterial super-infections, scarring. Spread of VZV to susceptible
children, causing varicella. And zoster is maybe a fifth as contagious
as varicella. Other signs of zoster can be fever or regional adenopathy.

So let's look at some photographs of zoster. This shows a thoracic
distribution T1, T2. Another thoracic distribution T7, T8. This shows a
lumbar distribution L3, L4.

Here's some cranial distributions. This shows the mandibular division of
the trigeminal nerve and this shows the ophthalmic division of the
trigeminal nerve. When it goes out to the tip of the nose, that's called
Hutchinson's sign and that predicts involvement of the eye.

What about symptoms? Well, they could be headache, photophobia and
malaise but the key symptom is really pain. It could be excruciating
like renal colic or childbirth. It's been described as itching, burning,
stabbing or shock-like. It could be continuous or paroxysmal and it's
often associated with altered or painful sensitivity to touch. It can be
provoked by trivial stimuli like a breeze. It can cause exaggerated or
prolonged response to pain and it can cause unbearable itching.

The pain that occurs with zoster can precede the rash in 84% of cases.
It starts as an abnormal skin sensation with itching or tingling and it
can precede the rash by one to five days but sometimes even weeks. On
occasion, the rash never develops at all, in which case it's called
zoster sine herpete and that, as you can imagine, leads to diagnostic
dilemmas and workup for the pain including cardiac workups or gall
bladder disease workups. Once the rash appears, it's associated with
pain in about 90% of patients.

What are the complications of zoster? The most significant one is
post-herpetic neuralgia or PHN. This is the prolonged, sometimes
incapacitating pain that occurs after the rash resolves. Now prolonged
has been defined quite variably by different clinicians and researchers,
including any pain at all after rash resolution to one month of pain or
two months of pain on out to six months of pain but regardless, the pain
of PHN can persist for months or even years and some experience
recurrence. For the prevention of PHN, until the time that the vaccine
was available, we were using anti-virals including acyclovir,
famcyclovir, valacyclovir with or without steroids but this was not
fully effective. With regard to PHN treatment, different modalities were
used including opiates, tricyclic antidepressants, anticonvulsants like
Gabapentin, Capsaicin, intrathecal steroids, neurosurgical procedures
like nerve blocks and so forth but these too provided only partial,
inconsistent efficacy.

So what are the impacts of PHN on the quality of life? Well in formal
studies they have been found to be comparable to congestive heart
failure, diabetes and depression. In the physical domain, they cause
chronic fatigue, anorexia, weight loss, physical inactivity, insomnia.
In the psychological domain anxiety, difficulty concentrating,
depression, suicidal ideation. In the social domain, fewer social
gatherings. In the functional domain, interference with the activities
of daily living. And I still recall several years ago receiving a call
from a woman who was very concerned about her mom who had been 62 years
old and quite vigorous -- playing tennis weekly and very socially
involved. When she developed zoster, which was so severe -- the PHN was
so severe, that she was in excruciating pain, housebound, socially
isolated and attempted suicide on a number of occasions and this was
lasting for years. Now those types of cases are quite rare but they do
happen.

Another complication of zoster is herpes zoster opthalmicus, which is
involvement of the ophthalmic division of the trigeminal nerve --
there's that Hutchinson's sign again. This occurs in 15% of zoster
cases. Untreated, about 50 to 70% of those develop acute ocular
complications which in turn can lead to chronic ocular complications,
reduced vision or even blindness.

There are uncommon complications as well, including encephalitis,
myelitis, optic neuritis. Cranial and peripheral nerve palsies occur --
are not uncommon either. Hearing impairment can occur with vertigo, loss
of taste sensation, neurologic dysfunction involving the diaphragm,
bladder or colon. There could be osteonecrosis of alveolar or bone with
loss of teeth. In immunocompromised persons, the above complications
could be much more aggressive. They also experience dissemination, which
includes a generalized rash with or without visceral involvement such as
pneumonia, encephalitis, or hepatitis, in which case it could be
life-threatening. The complications are coincident with rash or can
occur weeks or months later. Mortality is rare in persons who are not
immunocompromised.

Let's move on to the epidemiology of zoster.

> There are about four cases per thousand population per year in the
> United States. That translates to about one million cases annually in
> the U.S. Age-adjusted rates appear to be increasing in several
> countries, including the U.S., Canada, Spain and the UK. The lifetime
> risk of developing zoster is about 32%. Repeated episodes of zoster do
> occur, though rates of second episodes are not really well-documented.

So what are the risk factors for zoster? Age is the most important one,
and we'll talk about that in the next slide and it influences the
incidence in the population. Immunosuppression is less common, but it's
influential due to the magnitude of the risk. So following bone marrow
transplants, patients with hematologic malignancies, those with HIV all
experience zoster rates that are many times higher than those in
age-matched persons.

So this shows data on the impact of age on the risk of zoster and these
were compiled by Doctor Edgar Hope Simpson who was a general
practitioner in the UK during the middle and latter part of the last
century. He was a keen observer and a theoretician that really advanced
our understanding of zoster.

So the Y-axis over here shows rates of zoster and the X-axis shows age
and this shows this patient population. There are 321 cases and you see
that there was a marked increase at the age of 50 but -- that there is
substantial number of cases at younger ages as well.

What about other risk factors for zoster in addition to age and
immunosuppression? Well, these other ones are unconfirmed or of lower
magnitude. So gender -- most studies show that the risk is greater in
age-matched females -- maybe 20% greater. Race. It appears to be less
common in Blacks and these are data from the United States as well as
the UK. Local trauma is interesting. The risk of zoster during the 30
days following trauma is increased 12-fold. Stress has been found in one
study, to be increased -- to increase the risks of zoster, though these
have not yet been confirmed. There are various illnesses which are
linked with zoster and that's even not counting the effect of
medication. So diabetes, Crohn's disease, rheumatoid arthritis are all
risk factors for zoster. There was a study that found an increase in
zoster risk in persons living near pesticide waste dumps. There are
genetic risk factors. Early exposure to varicella -- that is, infections
that occur in utero or in infancy seem to be a risk factor for pediatric
zoster and finally, there's varicella exposure. When people are exposed
to chicken pox, it seems to reduce the risk of zoster, perhaps by
increasing the immune response to VZV but these studies have not been
consistent. However, I want to emphasize that we still do not know why
some individuals who are immunocompetent develop zoster and others do
not.

Now we'll move on to the epidemiology of PHN in the United States. The
portion of people with zoster that develop PHN is about 10% if you
define PHN as 90 days of pain and 18% if you define it as 30 days of
pain. That translates to one to 200,000 cases of PHN a year.

What are risk factors for PHN among persons with zoster? Risk factors
include gender -- the risk may be greater amongst women with zoster.
Dermatome -- it might be increased with -- following ophthalmic zoster.
Interestingly, immunosuppression is not strongly associated with PHN. Of
those with zoster age is the key risk factor for developing PHN and
we'll look at that in the next slide.

Now this shows the data of Doctor Edgar Hope-Simpson again and in
addition to the zoster cases, I've shown the numbers that had progressed
to PHN. Once again, the incidence in on the Y-axis and the age on the
X-axis. You see that the rates really take off after the age of 60.
They're very, very few cases below the age of 60.

What about the burden of zoster in the United States? Well, I mentioned
there are about a million cases, annually. That translates to 12 to
19,000 hospitalizations with an average length of stay of five to seven
days, three -- about three outpatient visits per episodes of zoster and
that's over ten outpatient visits per episode of PHN. About 1/3 of
zoster episodes involve at least one visit to a specialist. Work loss
per episode of zoster is about three to seven days.

Now let's shift gears and talk about the Shingles Prevention Study.

> Let's first talk about what's the scientific basis for a vaccine for
> zoster? Well first of all, as noted, there's an increased incidence in
> the elderly and in immunosuppressed persons. What both of these have
> in common is decreases in VZV-specific cell-mediated immunity. In
> addition to that, studies done by Ann Arvin's group in Stanford show
> that inactivated VZV reduces the burden of zoster in immunosuppressed
> persons. In addition to that, (Myron Levin)'s group in Colorado showed
> that high doses of live attenuated VZV vaccine stimulates
> cell-mediated immunity in older adults. So the approach was to use a
> high-potency, attenuated VZV to ameliorate or prevent zoster in
> VZV-infected individuals.

So the study was a double-blind, placebo-controlled study in multiple
centers. The collaborators were the VA, the NIH and Merck. They enrolled
about 38,500 healthy men and women over 60 years of age who were
randomized to receive zoster vaccine versus placebo. The vaccine
consisted of an attenuated VZV with a titer about 14-fold higher than
that of varicella vaccine. The endpoints included incidence of zoster,
the burden of disease, which was an index including incidence times
intensity times duration of zoster and finally the incidence of PHN.
They used monthly phone calls to find cases in adverse events and median
follow up with about 3.1 years.

So these were the results in the New England Journal in June 2005. (Mike
Oxman) in San Diego was the study chairperson. (Myron Levin) in Colorado
was the principal investigator. Let's go to the results. So here are the
results in terms of vaccine efficacy. The Y-axis shows vaccine efficacy.
The white bars show zoster -- efficacy against zoster and the red bars
show efficacy against PHN. And you'll see that for all comers, the
vaccine was 51% effective at preventing zoster and about 67% at
preventing PHN.

The right side shows vaccine efficacy as a function of age. So it shows
60-64, 65-69 and so forth, out to over 80. You'll note that the efficacy
against zoster declines from about 70% down to about 18% and while some
people might say that that would mean that you wouldn't be that
interested in vaccinating older individuals, I would argue otherwise.
First of all, the vaccine retained fairly good efficacy all the way out
to 80 and above against PHN. For 80 and above it was about 40% but more
important than that, it's persons over 80 who experienced the greatest
burden of zoster and of PHN. In addition to that, they're the ones who
are least able to access medical care, least able to tolerate the kinds
of complicated medical regimens and interventions that I described
earlier and finally, the eldest -- the oldest of the old are the ones
that have the least social and physiologic reserve to be able to
tolerate zoster and PHN. So I would argue that it's particularly
important to try and vaccinate persons out to the oldest age groups.

Looking at the results a different way, we're looking at vaccine
efficacy for PHN of varying durations. So the left side shows different
durations of PHN -- 30 days, 60 days on out to six months. The right
side shows vaccine efficacy for these respective end points and you'll
see that vaccine becomes progressively more effective the more severe
the outcome is. So it's 73% effective at preventing zoster lasting 180
days.

What about adverse events? Well, the vaccine appears to be fairly safe.
There's no pattern suggesting a causal link to serious adverse events.
Vaccine rashes did not occur in the trial. There was an excess of mild
reactions in the vaccines, in particular local injection site reactions.
There were 48% in the vaccine recipients versus 17 in the placebo
recipients.

What about the durability of protection? This shows vaccine efficacy on
the Y-axis with 100%. This bar shows 0% and this bar shows 50%. On the
left side we have zoster. On the right side we have PHN. And the solid
bar shows the point estimates and it shows that -- and the dotted line
shows the 95% confidence limit but the solid line shows that the vaccine
efficacy declined from about 80% down to about 50% and it stayed stable
for the duration of the trial. PHN showed fairly similar results. The
efficacy started out at about 90%, declined over the course of the next
couple years but then stayed fairly stable at a little over 50% for the
duration of the study.

Let's shift now to provisional recommendations regarding the zoster
vaccine.

The vaccine was licensed in May of 2006. It's indicated for prevention
of zoster in persons over 60 years of age. Not indicated for the
treatment of zoster or PHN. Contraindications include a history of
anaphylaxis to vaccine components, immunodeficiency including leukemia,
lymphomas or other cancers affecting the marrow or lymphatic system,
AIDS or other clinical manifestations of HIV infection or individuals on
immunosuppressive therapy. Finally, pregnancy is a contraindication but
I would assume that would be pretty rare in persons over 60.

The ACIP issued provisional recommendations in October 2006. They called
for one dose of zoster vaccine for all adults over 60 years of age
whether or not they reported prior history of shingles, whether or not
they have other chronic conditions such as renal failure, diabetes or
heart disease and it's not necessary to check varicella history or
titer. The vaccine should be offered at the first clinical encounter and
include residents of chronic care facilities if appropriate. The vaccine
is not indicated for persons with acute zoster, that is to treat the
zoster or to prevent PHN and it's not indicated for patients with
ongoing PHN, that is to treat the PHN.

Vaccine must be kept at five degrees Fahrenheit or colder until
reconstitution. It can be administered with other vaccines at the same
time, simultaneously, whether live or inactivated. For inactivated
vaccines it could be administered non-simultaneously, for instance flu
vaccine, but the vaccine should not be administered within 28 days of
other live vaccines. Monitoring and reporting of adverse events is
emphasized by the ACIP. The vaccine is contraindicated for
immunosuppresed persons such as those on high-dose cortica steroids,
chemotherapy, biological response modifiers or AIDS. However, there is
neither a contraindication nor a recommendation for HIV persons without
-- for HIV-positive persons without AIDS.

It's important to target patients over 60 years of age who are
anticipating immunodeficiency due to initiation of immunosuppressive
treatments or progression of an underlying illness.

So now, we'll finish up with some key remaining questions, activities
and challenges.

> First, what is the duration of protection from zoster vaccine? I
> mentioned that the study averaged 3.1 years duration with the average
> follow up but follow up extended out to about five years and that's as
> far as we know in terms of the duration of protection. So we still do
> not know whether they'll be a need for booster shots or at what time.
> Might there be a role for zoster vaccine in immunosuppressed persons?
> After all, they are the ones who are at greatest risk of zoster and
> its severe complications. That can be broken down to two categories --
> persons with contraindications such as those on high-dose cortica
> steroids, chemotherapy, biological response modifiers and persons with
> AIDS and also on those people who are HIV-infected who have more
> intact immunity -- those that have CD4 counts greater than 200.
> Another question is, what about vaccinating persons under 60 years of
> age, especially if they anticipate becoming immunocompromised due to
> progression of illness or immunosuppressive treatment? Currently that
> is not the recommendation. Why do zoster rates appear to be increasing
> in many settings?

We're moving on to the key activities and challenges. Disease
surveillance is important in terms of monitoring the impact of zoster
vaccine. We do not plan on making zoster notifiable to health
departments.

The key impact of zoster is pain and the key burden that the vaccine is
trying to alleviate is intensity and duration of pain. How do we monitor
such end points? We do not have the capacity to distinguish wild-type
versus vaccine-strained zoster. That is to say, we don't have the
ability to discriminate vaccine failure from vaccine-adverse events.
Also, how do we track vaccine impact, given the changing baseline rates
of zoster in the absence of vaccines that I mentioned earlier? We do
plan to do ongoing state and national surveys and also to use
administrative data in order to address some of these issues. Another
challenge is assuring access and financing for those desiring vaccine.
Currently, the vaccine is financed for persons over 65 by Medicare Part
D and many will need to pay up front hundreds of dollars for the
vaccine. Another issue is that the vaccine must be stored frozen and
many adult providers are not used to or equipped to handle such
requirements.

> Another question is how to monitor vaccine coverage and disparities?
> We hope to be doing ongoing state and national surveys in order to
> monitor coverage and to use administrative data as well to supplement
> those data. And finally, how to monitor adverse events? This is the
> first live vaccine that is targeted to the older population. That
> older population is one that has a lot of medical events -- heart
> attacks or hip fractures or Alzheimer's disease \-- a lot of
> background noise but in addition they may be very frail, have
> co-morbidities and take multiple medications so unexpected adverse
> events can be plausible.

That concludes my talk and I thank you. And this shows a particularly
nasty case of shingles.

(Andrew Kroger): Thank you very much, Rafael. We'll do another
presentation before we do any questions. Now, Shannon Stokley will
describe Adolescent Vaccination Recommendations. Shannon?

(Shannon Stokley): Thank you, Doctor Kroger.

> Today my presentation will include a review of the vaccines
> recommended for adolescents and some recently published data on
> adolescent vaccination coverage levels. I'll also briefly discuss some
> strategies to improve vaccination coverage and also provide some
> education materials that are available for free.

Okay. Moving on, this slide presents The 2008 Recommended Immunization
Schedule for Persons Age 7-18 Years, and this was just recently
published. I want to bring to your attention, the column for 11-12 years
of age. This is the preferred age for administering adolescent vaccines
as it coincides with the preventive health care visit that's also
recommended for this age. And at this preventive visit, adolescents
should receive any vaccines and other clinical preventive services.

One can think about the vaccines recommended for adolescents in three
categories. Vaccines that are specifically recommended for all
adolescents -- and these would include the tetanus, diphtheria and
acellular pertussis vaccine, also known as Tdap. There's also the
tetravalent meningococcal conjugate vaccine, often called MCV4 and the
human papilloma virus vaccine or HPV. This vaccine is recommended for
females only. There are also vaccines that are recommended for teens
who've not been previously vaccinated. Basically these vaccines are for
catch up and this would include the Hepatitis-B series, the second dose
of the measles, mumps and rubella vaccine and a second dose of varicella
vaccine, mainly for teens who do not have a history of varicella disease
and also polio vaccine. And then finally, there are vaccines that are
recommended for special target groups, who may be at increased risk of
infection or complication and that would include influenza, pneumococcal
polysaccharide and Hepatitis-A.

But first, I want to talk about the Tdap vaccine. This vaccine was
licensed in 2005 and the ACIP recommendations for its use were published
in 2006. This vaccine is meant to replace the Td vaccine, which was
previously recommended for teens and it's licensed currently for a
single dose. It's recommended for all adolescents 11-18 years of age and
again, the preferred age is 11-12 years. Now some teens may have
previously been vaccinated with a Td vaccine and these teens should
still receive a dose of Tdap. However, a five-year interval is
recommended between Td and Tdap. In some situations, a shorter interval
is allowed, for example, in a pertussis outbreak or if the teen has
contact with infants.

Next, we have the meningococcal conjugate vaccine and this vaccine
replaces the meningococcal polysaccharide vaccine that was previously
available. The conjugate vaccine was licensed and recommended in 2005
and it's also administered as a single dose. In August of 2007, ACIP
simplified the recommendations for meningococcal conjugate vaccine. And
this vaccine is now recommended for all adolescents 11-18 years of age.
And again, the preferred age is 11-12 years. College freshmen living in
dorms and other populations that may be at increased risk are also
recommended to receive this vaccine.

The HPV vaccine was licensed in June 2006 and the ACIP recommendations
for its use were published in 2007. Currently, this vaccine is only
licensed for females. The quadrivalent HPV vaccine protects against four
types of HPV, two of the types that cause 70% of cervical cancers and
these would include Types 16 and 18 and the two types that cause 90% of
genital warts and that would be Types 6 and 11. The vaccine is
administered as a three-dose schedule with a timing of zero, two months,
and six months. And the HPV vaccine is recommended for females 11-12
years of age, although it can be given as early as nine years at the
provider's discretion. The vaccine should also be given to females 13-26
years of age if not previously vaccinated.

And finally, in June 2006, ACIP updated the recommendation for varicella
and included a second dose. Any unvaccinated child who's under 13 years
of age should receive two doses of the vaccine and the recommended
interval between doses is three months. Previously vaccinated teens who
may have received a dose when they were children should also receive a
second dose. If the child is less than 13 years of age, there is a
three-month interval recommended between doses. If the child is 13 years
or older, a one-month interval between doses is allowed.

Now, I would like to review some results from the National Immunization
Survey Teen Module, also known as NIS Teen. This survey was conducted in
2006 and it's the first national survey to produce provider-validated
coverage estimates for adolescents. The survey uses the National
Immunization Survey's sample frame methodology. It is a random-digit
dial telephone survey and included approximately 5000 parents of teens
13-17 years of age. Now the biggest strength of the survey is that the
immunization histories for the teens were verified with a medical
provider.

In this slide, are the estimated vaccination coverage levels for
adolescents 13-17 years of age. Coverage for MMR and the Hepatitis-B
series was above 80% and coverage for the varicella vaccine was assessed
for teens that did not have a reported history of disease. And coverage
for varicella was 66%. Coverage for one dose of Td or Tdap was 60% and
coverage for the meningococcal conjugate vaccine was 12%. Now this
survey was conducted soon after the licensure of HPV, so we did not
assess HPV coverage.

When we look at coverage for the Hepatitis-B vaccine by age, we see that
coverage decreases with increasing age. And this is somewhat expected,
since many of the older teens were born before the universal vaccination
recommendation for infants was approved by ACIP. And although we've had
successful catch up campaigns for adolescents and have had middle school
requirements enacted, there are still teens who have been missed. And so
it's important that healthcare providers continue to assess their
patients' vaccination status to make sure that they've received all the
vaccines, not just the new vaccines.

In an earlier slide, I showed coverage for receipt of Td or Tdap and
here I present coverage broken down by vaccine and by age. Coverage for
Td is highest among the older teens, which is also expected since these
teens were most likely vaccinated before the introduction of Tdap. And
Tdap coverage is highest among younger teens, indicating that providers
are implementing the recommendations. However overall coverage is low
and there's considerable work to be done to bring up the adolescent
coverage levels to the levels that we observe with infants. And one note
I want to make is that this survey will be repeated annually and we hope
to have the 2007 results available sometime mid-2008.

Next, I just want to briefly discuss some strategies to improve coverage
for adolescents. In 2000, a task force on community preventative
services reviewed the literature to identify evidence-based strategies
for improving vaccination coverage among children, adolescents and
adults. The committee strongly recommended the following strategies:
patient reminder recall, provider reminder recall, assessment and
feedback in standing orders. And the majority of the studies conducted
to evaluate these strategies were conducted with a childhood population
and very few studies have evaluated strategies for improving coverage in
adolescents although there are some underway. So although at this time
we may not have the studies to prove these strategies on adolescents, I
think it's reasonable to assume that many of these strategies would also
be effective if applied to this population. And I also want to remind
you about the Standards For Pediatric And Adolescent Vaccination, where
it's recommended that providers vaccinate at the earliest opportunity,
to access vaccination status at every opportunity and to administer all
indicated vaccines during the same visit and also to educate patients
about vaccine risks and benefits. And these standards are very important
because adolescents are known to make few visits to the doctor's office
and even fewer preventive health care visits. So it's important that we
take advantage of every opportunity and every encounter to make sure
that they're up to date with the recommended vaccines.

And next, I just want to talk briefly about the CDC Preteen Vaccination
Campaign, which was launched in August of 2007. And the purpose of this
campaign is to motivate parents to get their preteens vaccinated and
also to promote the 11 to 12 year-old preventive health care visit.

Materials are available for free at the Web site here on the screen
(www.cdc.gov/vaccines/preteen). Materials include posters and flyers.
They're in English and Spanish and include materials for general vaccine
recommendations and also HPV-specific materials.

And here's just an example of the one-page flyer about preteen vaccines,
again in English and Spanish.

> And here are some examples of the posters that are available for
> preteen checkups.
>
> And finally, materials for HPV vaccine.
>
> And again, these materials are free at the Website. And that concludes
> my talk. Doctor Kroger?

(Andrew Kroger): Thank you very much, Shannon, for that thorough
presentation. We would now like to invite our listeners to call in and
ask questions. To do that, please dial star one. Be sure to restrict
your questions to the contents discussed today and please tell us your
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utilizing a mute button when recording your name. Your name is required
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star, two. Once again, to ask a question, please press star, one.

(Andrew Kroger): While we are waiting for the first question, I would
like to provide some Continuing Education credit information. For CE
credit, please go to www.cdc.gov/tceonline. That is, T-C-E online. The
course number for our net conference is EC1268 and the verification code
is CR228F. And please remember that CE credit expires on February 18,
2008.

And so now, I guess we're ready to take the first question.

Question 1: Thank you. There have been several outbreaks of chicken pox
where the index case was a person with shingles. And I was wondering
whether those kinds of outbreaks you would expect to see from greater
use of zoster vaccine?

Answer 1: Thank you. That is a very good question. Well, there's only
been one study that actually looked at the contagiousness of zoster and
it's felt to be, as I mentioned earlier in the slides, only maybe 20% as
contagious as varicella. As the population immunity increases with the
use of the Varivax vaccine and other pediatric varicella vaccines, a
two-dose schedule, then the amount of susceptibility will decline. And
as the zoster vaccine is used, one would think that that would also lead
to a reduction in the amount of transmission from zoster. But, by the
same token, it's very plausible that the proportion of cases, as they
decline, that the proportion attributable to zoster may temporarily
increase.

Question 2: Thank you. The package insert of zoster vaccine says to
avoid contact with individuals that are susceptible to varicella after
vaccination with zoster vaccine. Have you heard of any problems with
that?

Answer 2: Thanks that's an important question, too. During the clinical
trials there were very, very few -- there were two generalized rashes,
occurring amongst thousands of vaccine recipients. And there was no
episodes of transmission at all from the vaccinees to others. So we
don't expect that to be very much of a problem, but of course we'll
continue to monitor for that. I would not tell somebody who'd received a
vaccine to avoid contact with an immunocompromised person unless they
happen to develop a rash, which like I said should be very, very
uncommon.

Question 3. Hello. I was wondering, since zoster vaccine is recommended
for persons who have previously had a history of shingles, is there a
period of time that we should wait between and outbreak of shingles and
vaccination?

Answer 3. That's an important question and it's a very thorny one. We do
know that there was a paper that was recently published that shows that
zoster can recur in individuals and it's even plausible that the rate
after having an episode of zoster may not be that different than in
individuals who never had zoster. And so there's no real good
evidence-based approach to say that before X amount of time, you should
not give the vaccine and afterwards you should.

It's a thorny question and we struggled with this. At this point, we do
not have any kind of threshold period of time but we will try to gather
data over time in the future and provide more guidance about that issue.
There's the other issue that a lot of individuals that come to their
providers reporting a history of zoster, many of them may be mistaken as
well. So we can't be 100% certain about the history as well. So for now,
the recommendation is that it's not necessary to ask about a history of
zoster and even when you're aware, specifically that an episode of
zoster occurred, we don't have any particular threshold and leave that
to your best medical/clinical judgment to do that.

Question 4: Thank you. If a new adolescent patient comes to the office,
and a parent says that the patient had chickenpox, but it was never
witnessed by a physician, how do you address that situation?

Answer 4: As the epidemiology of varicella has changed, the amount of
misclassified disease by parents is increasing and increasing. And at
this point in time, we are saying that a child with a history like that
should receive the vaccine --two doses of the vaccine. An alternative
approach could be to also check varicella titers in that individual.

Question 5: A new adolescent patient comes to the office, who had a
screaming reaction to DTP vaccine and has never received any subsequent
pertussis vaccine. What do you do with that patient?

Answer 5: Inconsolable crying for a period of three hours occurring
within a period of two days following a dose of either whole cell or the
acellular vaccine in infancy is considered a precaution for further
doses of DTaP -- further doses of the infant vaccine. However, these
conditions, while they were associated more strongly with the whole cell
pertussin's vaccine, they are thought to be precautions for the
pertussis-containing vaccines but they are thought to be conditions in
infancy. They are not considered conditions of adolescence and this type
of reaction occurring in the history of the patient when they're an
infant, is not considered a precaution. It is not considered a
contraindication. We would not expect to see reactions like this. We
haven't seen reactions like this in the trials. So the choice would be
to give the dose of Tdap to someone with that history.

Question 6: Okay. Our question concerns the meningococcal vaccination.
How long is that good for? I mean, how long are you protected from
meningitis once you receive that immunization?

Answer 6: Well because it's a conjugate vaccine, we are expecting it to
confer longer lasting immunity than what's seen with the polysaccharide
vaccine but because it's a new vaccine, we still need to monitor and
test to see the protection and the duration of immunity. So at this time
it's hard to give a specific answer but it is being monitored.

Question 7: How long was the meningococcal pure polysaccharide good for?

Answer 7: Roughly, about three to five years.

Question 8: I would like to know, did you say that Medicare Part B will
or will not pay for the zoster vaccine?

Answer 8: No. Zoster vaccine at this point is not covered by Medicare
Part B as in boy. Only the influenza pneumococcal and Hepatitis for
high-risk individuals are covered by Part B as in boy. So I believe that
if you are enrolled in Medicare Part D, you should be able to get zoster
vaccine reimbursed. The question is, the administrative issues and how
that happens -- whether you have to pay up front and get reimbursed --
it's a little -- it's a complicated process at this point and it depends
on a variety of factors. It also depends on this issue about the donut
hole that you may have heard about as well.

Question 9: Yes, hi. I have a question about not giving zoster vaccine
if on high-dose corticosteroids. What would be considered "high-dose"?
We've done, about 1500 vaccinations here and that's come up a couple of
times.

Answer 9: It's 20 milligrams per day equivalent for at least 14 days.

Question 10: I have a question. Before administering the zoster vaccine
should we ask the person's HIV status?

Answer 10: Another good question. It is not necessary to screen for HIV
status and there's a variety of reasons for that. First of all, the
prevalence of HIV in people 60 and above is not that great but we also
feel that a person who has profound immunosuppression -- as I mentioned
earlier, there's not a contraindication to HIV. There's only a
contraindication to AIDS, which is very, very different and it's
extremely unlikely that there'd be people who'd present for the first
time with AIDS at the age of 60 or above in order to get zoster vaccine.
And so it would be very difficult to encumber an entire program to cover
that very rare possibility.

Question 11: Yes, good afternoon. In a pertussis outbreak situation,
what is the recommended interval between and Td and Tdap?

Answer 11: Yeah. Well, the -- an interval between Td and Tdap can be as
less as two years but if you think it's warranted you probably could
give it sooner.The two-year interval comes from the data that we have
and the fact that it's two years and not less is just a function of the
fact that it wasn't studied. So there's no reason to expect there'd be
any problem with giving a dose of Tdap earlier than that. This all comes
out of the history of when providers used to incorrectly give tetanus
(toxoid) containing vaccine. They'd give smaller doses at two frequent
intervals. They'd try to half the dose and give them at frequent
intervals and it led to local reactions. And these were generally mild,
local reactions. Very rarely might there be a local reaction that was
painful and led to extensive erythema redness -- even that was a
self-limited thing. So that's where the issue with intervals comes in.
But when you're talking about giving Tdap in our pertussis vaccination
program, we know that we have been seeing outbreaks of pertussis in
adolescents. The key is to prevent pertussis infection, prevent the
acquisition and potential transmission of pertussis to siblings or
housemates that may be infants that could die from pertussis. So if
there is a pertussis outbreak going on, you know, we tend to say ASAP
for Tdap without respect to when that last Td dose was given because of
the concern and the benefit that you get from preventing pertussis.

Question 12: Just tagging on to a question that was answered earlier
about the DTaP in an infant who had a screaming reaction. What about a
child or a person who comes in saying that they had their first shots as
an infant and developed seizures after that and never received another
vaccine since then?

Answer 12: Yes. An issue when you're taking a history from someone that
had an adverse reaction in the past from the infant DTaP vaccine and
you're now deciding whether they can receive Tdap, you have to take a
history because you do need to tease out the contraindication for a
pertussis component. And that contraindication is encephalopathy that
occurs within seven days of a previous dose of pertussis-containing
vaccine. So if that was in fact what occurred, further doses of
pertussis-containing vaccines are contraindicated including Tdap in
adolescents.

However, there are a number of other conditions that were recognized,
such as the inconsolable crying, fevers of 105 or greater, seizures, as
well as the hypertonic, hyporesponsive episode. There were conditions
that were seen in infancy following a dose of pertussis-containing
vaccine and that was a precaution for further doses of the infant
vaccine. However, the evidence indicates, with the use of this new Tdap
vaccine, that conditions such as those are not considered precautions
nor contraindications. So it will require you to kind of get a good
history from the parent or the patient that - for whom you're going to
give Tdap vaccines.

Question 12 follow-up: And this patient never received any other
vaccines like her MMRs or anything else. So it most likely would have
been something to do with the DT or the DTaP.

Answer 12: It's a challenging situation because you're going to have to
talk to these parents and kind of figure out what's going on and why
they were resistant to receive other vaccines. Is it something that can
be worked on through education? Maybe talk about vaccines that have been
around a little bit longer. You just have to kind of talk to the
patient, provide adequate risk communication. There will be some cases
of course, where you can't do anything with a parent that's resistant
but you do have to try. And so that's pretty much what we would
recommend.

(Andrew Kroger): You're welcome. And since we are out of time, I am
going to move on to our closing information and I'll start with some
housekeeping. For Continuing Education credits, please go to
www.cdc.gov/tceonline or T-C-E online. The course number for the net
conference is EC1268 and the verification code is CR228S. I will repeat
that -- CR228S. Keep in mind that CE credit will expire on February 18,
2008.

Once you become familiar with the online system, you will find it easy
to use and a great way to keep track of CE credit earned from CDC
training programs. If you're having any difficulty or are new to the
system, you can get assistance by phoning 1-800-41-TRAIN, T-R-A-I-N or
another number, 404-639-1292. Both numbers during business hours from 8
am to 4:30 pm Eastern Time. To get help by way of email, you can contact
ce@cdc.gov.

If you were unable to ask your question today, or if you have other
questions related to this net conference or in general, you can contact
us at our email question and answer service at the address, nipinfo,
nipinfo@cdc.gov. If the question is related to the net conference,
please write the word "net conference" in the subject line and we do
definitely look forward to receiving feedback as well.

Another way that you can ask us a question is to call the CDC Hotline
and that's 1-800-CDCINFO, CDCINFO. This is a general hotline service
that handles immunization related questions in addition to other public
health-related questions. The hotline is staffed 24-hours a day, seven
days a week.

So I'd really like to thank everyone for joining us today, with special
thanks to our subject matter experts, (Raphael Harpaz) and (Shannon
Stokeley) and we thank you very much from Atlanta and have a great day.
Goodbye.

Coordinator: Thank you for participating in today's conference. You may
disconnect at this time.

END