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CDC ZOHU Call March 2, 2022

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>> The webinar will begin soon. Please stand by. The webinar will begin soon. Please stand by. Good afternoon, everyone. I'm Laura Murell, and I work in
the National Center for Emerging and Zoonotic Infectious
Diseases at the Centers for Disease Control
and Prevention. On behalf of CDC's
One Health office, I'm pleased to welcome you to the monthly Zoonoses
& One Health Updates Call on March 2, 2022. Although the content of
this webinar is directed to veterinarians,
physicians, epidemiologists, and related public health
professionals in federal, state, and local positions,
the CDC has no control over who participates. Therefore, please exercise
discretion on sensitive content and material, as confidentiality
cannot be guaranteed. Today's webinar is
being recorded. If you have any objections,
you may disconnect now. Links to resources from each
presentation are available on our website at cdc.gov/onehealth/zohu/
2022/march.html. Today's presentations
will address one or more of the following
five objectives: describe two key points
from each presentation; describe how a multisectoral One
Health approach can be applied to the presentation topics;
identify an implication for animal and human health; identify a One Health approach
strategy for prevention, detection, or response
to public health threats; and identify two new
resources from CDC partners.

In compliance with continuing
education requirements, all presenters must disclose any
financial or other associations with the manufacturers
of commercial products, suppliers of commercial
services, or commercial supporters as well
as any use of unlabeled product or products under
investigational use. CDC, our planners,
presenters, and their spouses or partners wish to disclose
they have no financial interests or other relationships
with the manufacturers of commercial products, suppliers of commercial
services, or commercial supporters. The planning committee
reviewed content to ensure there is no bias. The presentations will
not include any discussion of the unlabeled use of
a product or a product under investigational use. CDC did not accept commercial
support for this activity. Instructions for receiving
free continuing education are available at cdc.gov/onehealth/zohu/
continuingeducation. The course access
code is ZOHUwebcast. To receive free CE for today's
webcast, complete the evaluate at cdc.gov/TCEOnline
by April 11, 2022. A captioned video of today's
webinar will be posted at cdc.gov/onehealth/zohu/
2022/march.html within 30 days.

To receive free CE for
the web-on-demand video of today's webinar,
complete the evaluation at cdc.gov/TCEOnline
by April 12, 2024. Before we begin today's
presentations, Dr. Casey Barton Behravesh, director of the One
Health office, will share some news
and updates. You may begin when you're ready. >> Thank you, Laura, and
greetings, everybody. Welcome to the March
ZOHU Call webinar. We really appreciate
you joining us today. Before our presentations begin,
I want to share a few updates, and as always, you can find
links to these resources in today's ZOHU Call
email newsletter. If you're not yet
subscribed, all you have to do is use the link at the top
of the main ZOHU Call webpage to access these resources. Our response to the COVID-19
pandemic continues to evolve. Please check CDC's website
for the latest guidance and resources, including
information about keeping people as well as animals
safe and healthy. Our next One Health Partners
COVID-19 webinar is scheduled for Tuesday, March 29th
at 2:00 Eastern Time. If you would like to join
this webinar to hear more about the One Health aspects
of COVID-19, just email us at onehealth@cdc.gov,
and we'll add you to the distribution list.

While there's no evidence that animals are playing
a significant role in spreading COVID-19 to people,
we do continue to see a variety of different animals reported with the virus that
causes COVID-19. In the United States, 356
animals have been reported, including companion animals
like cats, dogs, and ferrets; animals in zoos, sanctuaries,
or aquaria, including hyenas, large cats, a binturong,
a fishing cat, a kudamundi, otters,
and gorillas. There are production
animals like mink and also wildlife
like whitetail deer. Seventeen mink farms have
been affected by SARS-CoV-2 in the United States to date, and you can find the latest
animal case numbers available on the USDA APHIS website. And, of course, we have guidance
for pet owners, mink farmers, veterinarians, and many
others on CDC's website. You'll find links in
today's newsletter to several recent publications,
including risk factors for hospitalization among
adults aged over 65 years with non-typhoidal
salmonella infection linked to backyard poultry contact, and also highly pathogenic avian
influenza is an emerging disease threat to wild birds
in North America. We shared links to several
recent announcements, including that there's a
new population survey data on FoodNet Fast, and that CDC
reports a new US human infection with the variant influenza.

We've also shared links
to new web resources, including our brand-new Why is
One Health Important infographic and the Antibiotic
Resistance Investment Map. Some upcoming events of interest
include the National Invasive Species Awareness Week,
currently being observed through Friday, March 4th. And we're actually going to
hear a presentation related to this observance
today about feral swine, and there's another event
coming up April 4th through 7th in Atlanta, and that's
the Preparedness Summit: Reimaging Preparedness
in the Era of COVID-19. And finally, there are ongoing
outbreak investigations, including a salmonella outbreak
linked to pet bearded dragons, an E. coli outbreak
linked to packaged salads, and two listeria outbreaks
also linked to packaged salads. Please visit CDC's Healthy
Pets, Healthy People website for a selected list of ongoing and past US outbreaks
of zoonotic diseases. And we appreciate you sharing
the ZOHU Call website link with your colleagues from
human, animal, plant, and environmental health sectors
and other relevant partners and letting them know about the
live webinars, video recordings, and free continuing education.

Our next call is
scheduled for April 6, 2022, and please send presenter
and topic suggestions for future ZOHU presentations
as well as news from your organization that
you'd like for us to share with our newsletter
to zohucall@cdc.gov. Now I'll turn the call
back over to Laura. Thank you. >> Thank you. You can submit questions at any time using
Zoom's Q and A feature. Please include the topic
or presenter's name. The Q and A session will
follow the final presentation if time permits. You may also email questions
to today's presenters. We've included their email
addresses on this slide, on the ZOHU Call webpage
for today's webinar, and in today's email newsletter. Our first presentation, Three
US Human Rabies Deaths Linked to Bat Exposures in August
2021, is by Amber Kunkel. Please begin when you're ready. >> Thank you, Laura. So I'm an EIS officer in CDC's
Poxvirus and Rabies Branch, and I'll be talking today
about three human rabies deaths in the US this past year
that were all linked to bat exposures in August 2021.

Rabies is the deadliest
zoonotic disease in the world, with a nearly 100%
fatality rate. Exposure to rabies primarily
occurs through a bite when virus in the saliva is introduced
into a break in the skin. Rabies virus is neurotropic,
meaning it seeks out nerve cells for replication. The virus makes its way to the
brain, typically over the course of three weeks to three months,
but this timeframe can vary. The end goal of the virus
is entry into the brain, massive replication,
and excretion in the salivary glands. Reservoir species
typically shed virus for several days before they
look sick and can survive and shed for about
one more week.

Humans generally die within
a few weeks of symptom onset, and secretions are
assumed to be infectious up to two weeks prior
to symptoms. In humans, signs and symptoms
vary but typically begin with pain or paresthesia
near the site of the bite or non-specific symptoms like
fever, and they can progress to confusion, agitation,
delirium, hydrophobia, and/or hallucinations, almost
always leading to death. Rabies causes more
human deaths each year than any other zoonotic disease. It's estimated that about
59,000 people each year die from rabies. Most of these people
live in Africa or Asia and acquire rabies
from dog bites. Although post-exposure
prophylaxis, or PEP, is very effective at preventing
rabies, people may be unable to obtain PEP or not
even know to seek it out. In the US, the canine rabies
virus variant has been eliminated, but rabies persists
in certain wild animals, with occasional spillover to
domestic animals or humans. About 60,000 people each
year in the US receive PEP for a suspected rabies exposure,
preventing many possible deaths.

Modern-day post-exposure
prophylaxis in healthy individuals
involves four doses of rabies vaccine
given intramuscularly over a period of 14 days. It also includes an initial dose
of human rabies immune globulin as passive antibody coverage until the patient begins
responding to the vaccine. Thorough wound cleansing is also
important for reducing risk. This map shows the
distribution of rabies in terrestrial mammals
in the US. Rabies is enzootic to racoons,
skunks, foxes, and mongoose in the US within specific
geographic ranges. Other mammals can also
acquire and transmit rabies if they're exposed to the
saliva of a rabid animal, but these transmission
chains generally die off within a generation or two. And then there's rabies in bats. That rabies is found all
throughout the continental US and Alaska with the highest
detection of cases shown on this map and often
corresponding with population centers. In recent years,
since elimination of the canine rabies
virus variant from the US, human rabies deaths in the
US are most often caused by exposures to bats,
as you can see by the black bars
in this figure.

Since 1960, about 70% of
human rabies cases acquired in the US have come from bats. Most human rabies testing
in the US occurs at CDC. We are typically contacted by a
physician or a health department who believes a patient may
have rabies, and we will agree to test when the state health
department supports testing, the patient has a clinical
course consistent with rabies, and the patient has either a
concerning exposure history or other, more common causes of encephalitis have
already been ruled out.

Both antemortem and
postmortem testing is possible. After a positive test result, CDC supports the health
departments and clinicians by providing guidance on
the public health response, infection control,
and communications. The number of human rabies
deaths detected each year in the US is low, generally
between zero and three. In 2019 and 2020, there
were no cases detected. In 2021, five human rabies
deaths were detected in the US across five different states. One was attributed to a
dog bite in the Philippines and four to bat bites. Of these, three showed
particular similarities, and that all followed
exposures in August 2021, and none of the patients
received PEP.

The first of these three
deaths occurred in Illinois. In August, a man in his 80s
contacted his local health department to report
seeing a bat in his bedroom the night before. The man provided
inconsistent reports on whether he had direct
contact with the bat. The bat was submitted for rabies
testing and confirmed positive. However, the patient refused
to receive PEP, despite urging from the local health
department. This refusal was
apparently linked to a general vaccine
hesitancy related to an adverse vaccine reaction that the patient had experienced
several decades earlier. Approximately four weeks later, the patient saw his
primary care provider and reported a one-week history of neck pain and
arm paresthesia. He told his doctor about
his exposure to a bat with a positive rabies
result and was referred to the emergency department. The patient developed
fever, hypersalivation, and altered mental
status and died a few days after hospital admission. This is the first case
that we know of in the US where PEP was recommended
and refused, and it was apparently
due to vaccine hesitancy.

The second case was
confirmed from Texas. This case involved a
male school-age child who had touched a bat with his
bare hands outside his home in August. He reported to his parents
that he had been bitten, but the parents did not
observe any visible bite marks, and they did not realize that
bats could transmit rabies even if there is no visible bite. No medical advice was sought, and the child did not receive
post-exposure prophylaxis. The patient had a three-week
course of illness before death, including agitation, delirium,
hypersalivation, and seizures. The final case occurred
in Idaho. This case involved a man in
his 60s who had a bat collide with him and become tangled
in his clothing, both outside and inside his home, although
he did not notice a bite.

Because he did not realize the
potential risk of his exposure, he did not seek medical
advice or receive PEP. Six weeks later, he began
experiencing a three-week course of illness, including
arm and neck pain and ascending paralysis,
leading to his eventual death. Again, this case highlighted
that direct contact with a bat is a risk for rabies, even without a recognized
bite or scratch. Also, rabies was not suspected
for this patient until late in his course of illness, which shows how additional
rabies cases in the US may occur but never be detected. This slide shows a video
that the Idaho patient took of the bat after it became
tangled in his clothing.

Based on this video,
experts assessed that the bat species was big
brown bat, but sequencing of the viral strain showed a
rabies virus variant typically found in silver-haired bats. A public health investigation
was launched in each state to look for individuals
who may have been exposed to either the infected
bat or the human patient. The greatest number of community
contacts were identified in Texas, where 41 people
ultimately received PEP. The number of healthcare
contacts per patient were generally low, possibly
related to greater use of PPE during the COVID pandemic
than in the pre-pandemic era. If we compare to two cases
that occurred in 2017 and 2018, we can see a big drop in the
number of healthcare contacts who required PEP pre-pandemic,
about 70%, compared to one to 10 in our three fall of 2021 cases. Following these three cases,
we felt it was important to share bat rabies prevention
messaging with the public. CDC and the state health
departments took several steps to do so. First, each state released a
press release about the deaths that had occurred in
their jurisdiction. These were picked up by some
media outlets, as shown here. Case reports of each
individual case, as well as the other two rabies
deaths that occurred in the US in 2021, are also in progress.

We updated the CDC
webpage on bats and rabies to make it easier to
navigate and understand. This page includes
information on bats and rabies, what to do if you encounter a
bat, how to safely capture a bat for testing, and how to
keep bats out of your home. For example, here
are the instructions on safely capturing
a bat for testing. Capturing and testing
bats can prevent people from receiving unnecessary
PEP if the bat tests negative, but it's important
to do so safely to avoid any additional
bat contact.

When trapping a bat, people
should wear leather work gloves and place a container over
the bat to capture it, avoiding touching the bat
with their bare hands. Next, recognizing
that the occurrence of these three human rabies
deaths in such a short amount of time is rarely seen
in the US, we attempted to promote healthcare worker and
public knowledge about the risks of bat rabies by publishing
an MMWR Notes from the Field. This report described
these three cases and how to prevent rabies transmission
from bats to humans. Our key messages were
that direct contact with bats can be dangerous,
even if there is no visible bite or scratch, but the
transmission of rabies from bats to humans can be prevented. To prevent rabies
transmission from bats, people should first avoid
contact with bats; for example, by excluding bats from homes. Don't touch bats
with bare hands. Second, if contact does
occur, do not release the bat, and instead contact your
local health department about having the bat
tested for rabies.

Finally, if the bat cannot
be tested or tests positive, post-exposure prophylaxis
may be needed. Contact your doctor or local
health department to ask if you should receive PEP. Our communications team put out
a press release simultaneously with the MMWR and was successful at getting significant
media attention from nationwide news outlets,
including the AP, STAT News, and The New York Times. We hope that getting
these stories out there will remind
people that rabies from bats remains an
ever-present risk in the US, despite there being no
cases in 2019 and 2020. CDC also put out social
media messaging coinciding with the MMWR to
further spread the word. In conclusion, five human
rabies deaths occurred in 2021, an increase from recent years. Three of these were
linked to bat exposures that occurred in August of 2021.

Of these, one refused PEP, and two did not realize their
contacts posed a risk of rabies, so they did not seek PEP out. These deaths suggest a need
to educate the public on how to avoid getting
rabies from bats, which CDC approached
using an MMWR, news media, and social media. When it comes to rabies
in bats, knowledge is key to getting people started on
PEP and protected from rabies, so I'd encourage all of you
listening to share these stories with the people around
you as well. I'd like to acknowledge everyone
who worked on the investigation of these cases, as
well as the writeup and communications efforts. Thank you all for listening. That's the end of
my presentation. >> Thank you. Our next presentation,
Serosurveillance for Anthrax Exposure
in Texas Feral Swine: A Potential Biosurveillance
Tool for Mapping Risk, is by Rachel Maison
and Angela Bosco-Lauth. Please begin when you're ready. >> Great. Thanks, everyone,
for joining us today. I'm Angela Bosco-Laugh. I'm at Colorado State
University. And presenting this information
today is PhD candidate Rachel Maison, who's done a lot
of work in feral swine, particularly looking at serology
for use or- for serodiagnostics for potential pathogens.

So, Rachel, go ahead
and take it away. >> Thanks, Angela. So just to kind of jump
right in, for those of you who aren't aware or don't know, feral pigs are an incredibly
destructive invasive species in the United States. They were actually introduced
to the US back in the 1500s by Spanish settlers who were
colonizing the continent at the time and just kind of
released onto the landscape just to provide an easy source
of food for the people who were colonizing
the US at the time. But since then, their
populations have exploded to encompass most of the
Southeastern United States as well as some Western states,
and this is mostly because pigs as a species are very good at
adapting to most environments. They are omnivores with
a very generalist diet and have a very high
reproductive rate as well as can give rise to
very large litter sizes. And today, it's actually
estimated that feral swine cause around $1.5 billion worth of
damages annually, specifically to property and agricultural
crops.

This is because pigs like to
root and wallow in the soil and, in this way, can
more or less act like unwanted rototillers
on the landscape. They're also known to displace
native wildlife, either directly through predation or indirectly
through resource competition and sheer ecological
destruction, again, through their rooting
and wallowing behavior. And then lastly, and arguably
most important for this talk, feral pigs also can have
indirect and direct interactions with humans and domestic animals
and livestock species, which, in some cases, can
have implications for the transmission of
pathogens and disease.

So I'm sure many of you have
heard of anthrax disease, and so its introduction might
— it might not require too much of an introduction to you all, but there are a few things
worth highlighting about it and its causative agent,
Bacillus anthracis, just to give you all some
context to why we are interested in this pathogen specifically and how it might
relate to feral pigs. So it is caused by the
bacterium Bacillus anthracis, which is a soil-dwelling
bacterium. It is endospore forming and
can actually lie dormant for decades in the
soil profiles. There are reports
in the literature that have isolated spores
and have dated them to be over 100 years old, so it is
a very long-living pathogen.

But despite how long humans
have seemingly been dealing with this disease, based
on historical reports, we still don't have a good
handle on the true incidence of anthrax disease
in most regions, and the bacteria has
been isolated pretty much from every continent, so
it's just kind of assumed that you might be able
to isolate anthrax from most regions, but we
don't have a good handle on its distribution
on the landscape or its disease incidence. And then lastly, and most
importantly for this talk, it seems that anthrax doesn't
affect all species equally.

It causes high mortality
for herbivorous and ruminant species, but
for carnivores and omnivores, they seem to be more
resistant to infection and succumbing to disease. So falling into the
omnivorous species category, pigs have been documented
to be relatively resistant to developing anthrax after
exposure to the bacteria and do, in fact, require
higher infectious doses than do herbivores to develop
and succumb to full-on disease. But since we do know that Bacillus anthracis is
a soil-dwelling bacteria and that pigs do have this
propensity to root and wallow in the soil, we hypothesize
that, at least in contaminated
environments, that they may be a species
that are most likely exposed to this bacteria just through
their inherent behavior and relationship with the soil.

So, given this information, we
then asked, could swine exposed to Bacillus anthracis be used as indirect indicators
of anthrax risk? So I have two maps up here. The one on the left is estimated
feral swine distribution provided by the USDA across
the US today, and then the map on the right is the current
predicted environmental suitability for Bacillus
anthracis. Importantly to note, a lot
of studies have kind of tried to predict where anthrax is
occurring on the landscape to try to predict
future outbreaks, just taking past
outbreak data as well as environmental information
based on past isolations that have been made on the
ground and have used things like ecological niche
modeling to try to map out the most likely areas that
anthrax might be occurring. But a lot of this is
unfortunately unvalidated in the field right now, and so
what we're kind of proposing is, at least in the areas where
feral swine are present, might we be able to kind of start validating
these predictive models.

So we attempted to start
answering this question by looking to the field and
documenting the exposure of feral swine to anthrax,
specifically in Texas. The USDA actually
regularly removes pigs off of the landscape as part
of their invasive species and damage management
control program there and samples a subset
of those individuals by taking blood samples
from them for regular disease surveillance
for other pathogens. And so we kind of used archived
samples from USDA that are kind of out here regularly
sampling these pigs, and tried to evaluate
anthrax exposure across Texas. And then, secondarily, because
the agency also collects different demographic
information on all the pigs they
sample, we also wanted to see if any differences
in exposure existed by pig age-class and sex. So as I mentioned briefly, the samples we examined
were from Texas.

We actually consciously
chose Texas for our sampling as opposed to any other region
or state with feral pigs because Texas is a state that has pretty well-described
patterns of anthrax occurrence in domestic and wild ruminant
species, with the vast majority of those cases coming
from what's known as the anthrax triangle
region, which is highlighted in orange on the map below. Cases are alternatively very
rarely described outside of this triangle region,
despite being equally populated with domestic livestock, feral
pigs, and wild ruminants. So we have this really
interesting situation where we have documented cases
of anthrax in one region and not in another, and kind of
homogeneous populations of both ruminant species
that are highly susceptible to anthrax as well as
feral pigs who are not. So, for our purposes, we considered those seven
counties highlighted in orange as endemic for anthrax and kind of randomly selected seven
counties outside of that region and considered them non-endemic
for anthrax and went back into the USDA archives and
pulled half of our samples from each of those regions for
a total of 478 serum samples to then test for
anthrax exposure.

So in terms of our methods
for how we did this, we used an in-house
ELISA platform similar to the one diagrammed
here on this slide to look for antibodies against
anthrax bacteria, specifically the protective
antigen that's produced by wild-type Bacillus anthracis. A protective antigen is the
cell-surface binding protein used by wild-type anthrax
to enter into cells and then distribute anthrax
toxin into those somatic cells in what's currently
recognized as the bulk target of the humoral immune response
in most resistant species. And so that's why we chose that as our coating
antigen for our plates. And then, statistically,
we used logistic regression and fixed-effects models to
evaluate each of our covariates of interest and how they
might influence a pig's antibody status. And so this is a table
documenting the seroprevalence that we ended up
finding from our ELISA. And what we ended
up finding in terms of seroprevalence was
somewhat surprising, since most case reports of
anthrax seem to just come out of that anthrax triangle region
that we considered endemic.

And you can see that we actually
found similar levels of exposure between most of the covariates
that we were interested in. But looking at the values rather
crudely, we see that pigs coming from that endemic
triangle region do appear to exhibit higher apparent
seroprevalence than those in the non-endemic region. And then we also have
rather similar levels of exposure happening
in males and females, but with females
being more likely to be seropositive than males. So this is another figure
documenting the raw serology results by region, since that is
what we were most interested in.

And something I think that's
interesting to see here that you don't quite get
with the table that was on the previous slide is that,
while we do have similar numbers of pigs from each region
being considered seropositive by our assay, or above
that red cutoff line, we did have quite
a few individuals that also exhibited
absorbance readings above that, even from the positive
control of our assay up, on the upper right corner
of that figure there, and that these appear mostly
to be from individuals residing in that endemic triangle region.

So it's hard to say exactly what
this could be from with the data that we have here, but
we kind of hypothesize that this could potentially be
because the load effect here in that contaminated region
could just be higher than that from the non-endemic
region or, alternatively, from repeat exposure
events that result in higher antibody titers. And then regarding our
statistical models, it appeared that most variables
we considered were informative for predicting a pig's antibody
status, and the final model that was selected based
on AIC value included all of our covariates as well
as the coordinate location that was associated
with each pig sample. Interestingly, though, when
we examined each covariate individually and calculated
the confidence interval and respective odds ratio
for those covariates, only latitude was
statistically significant.

And area under the curve measure
suggested an overall poor model predictability, indicating that there might be some
unexplained variants in our model. So, to summarize, it does appear that feral swine throughout
Texas, both within and outside of that anthrax triangle endemic
region, have been exposed to anthrax-causing
bacteria indicated by their positive
antibody status. And despite similar
seroprevalence, both within and outside of that
anthrax triangle region, pigs within that
endemic region did appear to exhibit higher odds of being
seropositive than those outside. And additionally,
female pigs also appeared to exhibit higher
odds than males. And finally, despite our
statistical model being unable to distinguish between
endemic and non-endemic regions because of that unexplained
variance that we observed, it's important to remember these
that regions of endemicity, especially in Texas, are largely
anthropogenically defined.

And since we all
know that animals and microorganisms
don't often adhere to these nicely defined
political boundaries, it's not completely unsurprising that we might find exposure
occurrence outside of them. Also, given the fact that
Bacillus anthracis is known to reside in a variety
of environments and have been isolated
in areas outside of that anthrax triangle region
before, it's not unsurprising, again, that we might see
exposure occurring outside of that. And in fact, that map that
we showed in the beginning with those predictive models
did predict some environmental suitability outside of
that region as well. So, really quickly, before
we end our presentation here, I did want to kind of give
a bit of a sneak peek as far as next steps in terms
of anthrax research in relation to feral swine. This past year, we
actually just wrapped up an experimental infection
study looking to validate some of this field serology
where we took a group of naïve wild feral pigs and
exposed them to various levels of the vaccine strain
of Bacillus anthracis, and we did see that they had
a measured immune response after we collected
blood from them at several different time
points post-infection.

And looking at the
graph on the bottom, you can see that that
humoral immune response seems to correlate with
both the dosage that those pigs were exposed
to as well as the number of exposure events
that they experienced. So this project would not have
been possible without everyone in the Bowen/Bosco-Lauth lab. I want to thank Dr. Richard
Bowen and Dr.

Angela Bosco-Lauth for letting me be part of
this project and, of course, all of our collaborators at
USDA for providing our samples and the data, as well as helping
with our statistical analyses. And thank you all for listening. >> Thank you. Our final presentation, The Newly Approved Tick-Borne
Encephalitis Vaccine: Who Should Be Vaccinated,
is by Susan Hills. Please begin when you're ready. >> Thank you very much. So I am a medical epidemiologist
in the Arboviral Diseases Branch at CDC, and I have also been
leading the ACIP TBE vaccine workgroup for the
last 18 months or so as we developed recommendations
for use of the vaccine. And so I'm excited to
present that to you today. This is very new information. The recommendations were
approved by ACIP just last week, so I'm pleased to be able
to share this information. So today, I'm going to briefly
review TBE epidemiology, provide some information about the recently
approved TBE vaccine, and then discuss TBE
vaccine recommendations. And I'll begin with providing
just some basic information on TBE epidemiology.

The TBE virus is a
flavivirus, and it's related to Powassan virus,
which, of course, is a tick-borne flavivirus
found in the United States. There are three main subtypes of
TBE virus, including European, Siberian, and Far
Eastern subtypes. And TBE is focally endemic in a
geographic region that extends from the Western and
Northern parts of Europe right through to the Northern
and Eastern parts of Asia that you can see there
on the map on the right. TBE virus is primarily
transmitted to humans through the bite of infected
Ixodes species ticks, and that's mainly Ixodes
ricinus and Ixodes persulcatus. Transmission can
occur occasionally through other means, and
that includes ingestion of unpasteurized dairy products
through infected goats, sheep, or cattle, and then rarely
through some other means, including slaughtering
of viremic animals, blood transfusion, and organ
transplantation have been documented as modes of
transmission; breastfeeding, and also through exposure to
the virus in a laboratory.

So infections are
usually acquired in wooded or surrounding areas, and
there are certain recreational activities or also occupations
that can really result in an increased risk for
exposure to infected ticks. Some of the key recreational
activities that increase the likelihood
of exposure include hiking, camping, fishing,
and birdwatching. And then occupational
risk occurs to persons like our forestry workers,
farmers, military personnel, or also people doing
field work, for example, for research purposes and
exposed in that setting.

Humans must enter tick habitats
and come in contact with ticks to have a risk of TBE, and this
is important to keep in mind because this is different
from other arboviruses that are spread by mosquitos. Where the mosquitos will
actually search out humans, you know, ticks won't
actively search out humans. So we've been keeping that in
mind as we think about risk for exposure to TBE virus. Because ticks are more
active in the warmer months, the main risk period for
infection occurs from April through November, with
the majority of infections in those summer months,
July, August, and the months on either side, June
and September. Clinical presentations of
TBE can range from something like just a nonspecific
febrile illness through to neurologic
presentations, including meningitis,
encephalitis, or meningoencephalomyelitis.

The illness can have a
monophasic or a biphasic cause. With the biphasic illness,
the clinical cause consists of typically a first phase of
a non-specific febrile illness. This is followed by
remission of symptoms. That's normally for
four to seven days. And then the second,
more severe phase occurs, and that's when the
neurological illness occurs. The case fatality and sequelae
rates vary by TBE virus subtype, but case fatality rates
ranging from one to 20%, and sequelae rates
ranging from 10 up to about 50% have been reported
from different areas. In terms of risk
for poorer outcome, it's consistently been
shown that older persons are at higher risk for a poorer
outcome, and that's sort of incrementally
higher as age increases. In endemic areas, there are
about 5,000 to 10,000 cases of TBE that are reported
annually, although there may be
both underdiagnosis and underreporting of
cases from endemic areas. Among US persons
traveling to endemic areas, there have actually
been a very low number of TBE cases diagnosed.

So only 20 cases have been
diagnosed during the last 20 years, and they include 11
cases in US civilian travelers and nine cases among
military personnel. There, again, might have been
some underdiagnosis, but really, based on these cases that we're
aware of, there's been a median of only one case per year. So to just briefly describe one
fairly typical US traveler case, this was an adult male
in 2012, and he traveled to Finland to visit relatives. Soon after arrival, he
went on a camping trip, and he reported receiving
multiple tick and mosquito bites. Shortly after, he
developed fevers and myalgia, and those symptoms
subsequently resolved. He then returned to the
US, and about a week later, he again became sick, and
became very sick this time. He developed symptoms of
dizziness, confusion, headache, and photophobia, and he
was ultimately diagnosed with tick-borne encephalitis
with a biphasic presentation. He was hospitalized
for some time, but fortunately, he recovered.

So that's US cases among
travelers, and just to conclude, looking at cases of TBE
among other US persons and among other risk groups, I
just want to talk a little bit about TBE among laboratory
workers. So in laboratories, TBE virus
transmission has occurred through virus aerosolization, and that has occurred either
during laboratory procedures or handling of infected
animal waste. And transmission through
accidental percutaneous or mucosa exposures
is also possible. There have been more than 46
laboratory-acquired TBE virus infections reported globally. These were mainly prior to 1995
with only a few reported since, and among those, at least
four occurred among US laboratory workers.

All of them, however,
were before 1979, so none reported
for several decades. None reported for
several decades. Currently, there are
fewer than 10 laboratories in the United States that work
with TBE virus for diagnostic or research purposes, although
it's unclear if there's interest in use of work with TBE virus,
and there may be an increase in work with TBE virus now that there is a vaccine
available in the United States. In regards to TBE
diagnostic testing, there is no commercial assay
available in the United States for diagnosis of TBE, but
testing is available at the CDC.

So, to move on to
the TBE vaccine — So FDA approved the TBE vaccine,
which is called TICOVAC, and it's manufactured by Pfizer
last August, August 2021, and it was approved for individuals aged
one year or older. It's an inactivated vaccine, and there are two
dosing formulations, and that includes a 0.5
mil adult dose to persons who are 16 years and older,
and then a 0.25 mil dose for children and adolescents
aged one to 15 years. This slide shows the
vaccination schedule. So the primary vaccination
schedule includes three doses, and that's shown in yellow, and
one booster dose may be given, and that's shown
in the green color.

The schedule for adults
is there in the top row, and for children,
it's in the row below. For adults, the first two
doses are administered 14 days to three months apart, and the
only difference for children is that the first two doses are
one month to three months apart. For both adults and
children, the third dose of the primary series is
given five to 12 months later. Then a booster dose can be
given at least three years after the primary series if
ongoing exposure or re-exposure to TBE virus is expected. The TBE vaccine is newly
licensed in the United States, as I said, but it's actually
been available for more than 20 years internationally, and more than 75 million
doses have been administered. It's marketed in about
30 countries currently. These are countries
primarily in Europe.

And I don't have time
during today's call to present all the safety
and immunogenicity data, but it does have
a very good safety and immunogenicity profile. So just to summarize
all that information, so TBE is a focally
endemic disease that's found in parts of Europe and Asia. The virus is primarily
transmitted to people through tick bites as they
visit or work in forests or in the area on the edges
of forests in endemic regions. Clinical disease can be severe with potentially high
morbidity and mortality rates. Based on data from
the last 20 years, cases among US travelers
are very rare. Similarly, cases among
laboratory workers are rare, but they clearly are
at risk of infection when working with TBE virus. And a TBE vaccine has never
previously been licensed in the US, but one vaccine
has recently been approved and so is now available. Just based on that summary
and to sort of conclude here with recommendations,
I'm going to talk about the recommendations
for TBE vaccination that were approved by
the Advisory Committee on Immunization Practices
last week. As I said, they are
hot off the press, and they actually won't be final until the CDC director
approves them, so they are still
pending final approval, but they have received ACIP
approval last week, as I said.

They were developed by
a workgroup that met — we met about 30 times over 18
months to discuss epidemiology, to discuss the vaccine
data, vaccine immunogenicity and safety, and then draft
the vaccine recommendation. So quite a lot of
discussion and work went into preparing these
recommendations. The workgroup's discussion on
the risk-benefit assessment for use of the vaccine among
travelers ultimately focused on several key factors, and they
were that, as I've mentioned, the risk for TBE for
most US travelers to TBE-endemic areas
is very low.

Nonetheless, the disease has
potentially high morbidity and mortality, with older
persons at higher risk of severe outcomes, and
that there is a safe and effective vaccine, but
that there is a possibility, albeit a very low probability,
of severe adverse events, and that's just like
all vaccines. So the final recommendations for
persons who travel abroad were that TBE vaccine is recommended
for persons who are moving or traveling to a
TBE-endemic area and will have extensive
exposure to ticks based on the planned outdoor
activities and itinerary. In addition, TBE vaccine may be
considered for persons traveling or moving to a TBE-endemic
area who might engage in outdoor activities in areas
ticks are likely to be found.

The decision to vaccinate
should be based on an assessment of their planned activities
and itinerary, risk factors for a poorer medical outcome,
and personal perception and tolerance of risk. And then considerations
for vaccine use for the laboratory
workers included that there is a clear
risk for disease for workers handling TBE virus, that the disease has potentially
high morbidity and mortality, and that there is a safe
and effective vaccine, albeit with a very rare
likelihood of serious, adverse events, as I
said, like all vaccines.

Thank you. So the recommendation for
laboratory workers were that TBE vaccination
is recommended for laboratory workers
with a potential for exposure to TBE virus. So after the CDC director
approves the recommendations, they will be posted
on the CDC website, and the website will be updated with additional vaccination
resources to help healthcare providers who are considering
use of this vaccine. And an MMWR will
also be published, which will have detailed
disease and vaccine information. And finally, I want to
acknowledge the members of the ACIP TBE vaccine
workgroup. As I said, we worked over
a period of 18 months to develop the recommendations, and each of these
participants really put a lot of time and effort into that. So, thank you very much. Thank you very much
for your attention. >> Thank you.

Thanks to all of
today's speakers for your informative
presentations. Links to resources from each
presentation are available on our website at cdc.gov/onehealth/zohu/
2022/march.html. We do have time for
a few questions. Please use the Q and A feature
in Zoom to send your questions and include the presenter's
name or topic. We'll start off with
a question for Amber. "To your knowledge, have
there been any studies of public perceptions or
knowledge of rabies virus in the US or in other
countries?" >> Yep. I'm more aware of there
being different CAP studies in other countries, looking
at people's awareness of rabies and rabies vaccines. And I think, you
know, the barriers that we see are primarily
related to both awareness and access. If we look at human
rabies deaths in the US, we generally see similar
features to the two cases from this fall who
did not get PEP because they didn't realize
their risk, so I think lack of awareness is a major
problem in the US as well.

>> Thank you. Our next question is for Rachel. "Is there any evidence for
serologic cross-reactivity in your assay with
non-Anthracis bacillus species or other bacteria? And also, have you considered
testing feral swine outside of anthrax-endemic
regions to test if the assay may be reacting
with something else?" >> Sure. Yeah. That's a good question. So as far as I'm aware, and at least this is pretty well
documented in the literature, that protective antigen that
we were using for our assay as an antigen to coat our plates
is a very specific antigen for Bacillus anthracis, or generally anthrax-causing
bacteria.

I do know that there are
members of the B. cereus family and biovar anthracis
that do also produce that protective antigen,
but importantly, they've been demonstrated to
also cause anthrax-like disease. So I think, for our
purposes, you know, a measure of protective antigen
antibody is pretty indicative of exposure to anthrax-causing
bacteria. As far as cross-reactivity,
while we were kind of getting our assay up
and running, I did — so I mentioned that USA kind of
regularly collects serum samples from feral swine
throughout the United States. I actually did test a number
of samples, a couple hundred, I think, from Guam
to kind of confirm that there was no
cross-reactivity, because Guam, at least as far as
public reports go, has not experienced
any documents of anthrax in that region. So I did test Guam feral
swine samples from USDA, and all those were negative for
protective antigen antibody. >> Thank you. And then we have one
question for Susan. "You mentioned that TBE virus
is related to Powassan virus.

Do you know if the TBE vaccine
could potentially be effective for Powassan virus?" >> Yeah. Thank you
for that question. There is limited data
investigating that question, but the data that are
available do not suggest that the TBE vaccine
will protect against Powassan
virus infection. >> Thank you. Then we have time for
one last question. This one is for Rachel. "Given the results of your study
on feral swine, do you think that there is a risk of anthrax
transmission from feral swine to humans in regions of the
US; for instance, among hunters or those who may
have recreational or occupational exposure
to swine?" >> Yeah. I think
definitely, in some cases, there could be a documented risk of exposure specifically
to feral pigs.

Now, I'm not sure what kind of
exposure that would take just because feral pigs are a
relatively resistant species to developing disease. So I think it would
probably have to take a pretty high
exposure dose for them to successfully become infected
and then be able to pass it on through their carcass
or something like that. Now, I will say that we are
also interested in seeing if you might be able
to isolate spores that feral swine could
potentially be carrying, either on their fur or in
their nasal passages after kind of rooting around in
that contaminated soil. And so, hopefully,
more to come with that, but I think that that could
potentially be a risk, for sure.

>> Thank you. And that is all the time we
have for questions today. If you have other questions
for today's presenters, we've included their email
addresses on this slide, on the ZOHU Call webpage
for today's webinar, and in today's email newsletter. A video of today's
webinar will be posted within 30 days as well. Please join us for the next
ZOHU Call on April 6th. Thank you for your
participation. This ends today's webinar..

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