Emerging Tickborne Diseases

Emerging Tickborne Diseases

>>May I have your
attention please. Our network is down again, so
our webcast is not yet working. So if anybody’s listening
through some other mechanism, I hope IPTV might be recording. IPTV folks, if you
can be recording so we can broadcast our webcast
later, that would be helpful. We’re going to go ahead
and start timely anyway, and we’ll just resume
when we can. So, sorry about that. And I hope we get the
webcast going shortly.>>Good afternoon. And again, we are having
a little bit of difficulty with our webcast, but
we’re going to go ahead and get started with
the presentation. So, good afternoon, good
evening or good morning, depending from when and
where you are joining us. I’m Dr. Phoebe Thorpe, and it’s
my pleasure to welcome you here to the CDC Public Health
Grand Rounds for March, 2017, emerging tick-borne diseases. We have a very exciting
session, so let’s get started. But first, a few
housekeeping slides. We do offer continuing
education credits for public health Grand Rounds
for physicians, pharmacists, nurses, veterinarians,
health educators and others. Please see our website for
additional information. This is the disclosure
slide for this session. We are also available on all your favorite
social media websites. Please send your
comments and questions to the grand round’s email
box at [email protected] We also have a featured video
segment called Beyond the Data. This month’s segment features my
interview with Dr. Bobbi Pritt. It’ll be posted about a
week after the session. We have also partnered with
the CDC Public Health Library to feature scientific articles
related to tick-borne diseases. The full listing is available
at cdc.gov/scienceclips. Here is a preview of our upcoming Public
Health Grand Rounds sessions. Please join us live or on
the web at your convenience. In addition to our
outstanding featured speakers, I’d like to take a moment to acknowledge the
important contributions of the individuals listed here. Thank you. And now, for a few words from CDC’s acting
director, Dr. Schuchat.>>Thank you. Well thanks so much. It’s actually liberating knowing
that we’re not webcasting yet. Millions of Americans seek care for a tick bite each year
in the United States. And despite that, very
few of us are equipped to answer the questions
from friends and relatives that are in that category. Today you will be hearing
that the reported cases of tick-borne diseases
are increasing. That the range of ticks that
can carry diseases is expanding. That the number of
tick-borne diseases that we are aware
of is increasing. And that the laboratory
approaches to figure out what they are
is also increasing. If that list is making
you feel full, wait until you see the
pictures of the ticks who have been feeding
during this lecture. I believe it is the
most memorable part of the slides you’ll be seeing. We’re in for a treat, because
I think for the four speakers and the slides that
they’ve prepared, most of us will be better
equipped to handle that tick that you might find on
yourself or a loved one and to help the nation
be more prepared. Thanks.>>Thank you Dr. Schuchat. And now for our first
speaker, Dr. Eisen.>>Thank you for the
introduction, Phoebe. Good afternoon. I’m going to start with
some background information. All known tick-borne infectious
diseases are zoonosis. Ticks can maintain the
pathogens through transmissions to their offspring or acquire
infection through feeding on an infectious host. Importantly, humans
are incidental hosts that are infected through
the bite of infected ticks, but they do not serve
as a significant source for infecting other ticks or perpetuating the
pathogen’s lifecycle. Ticks are unique among
arthropods in the diversity of pathogens they transmit. Among the 18 tick-borne
disease agents described to-date in the United States,
14 are bacterial and are transmitted
by five tick genera. However, at least three unique
tick-borne viruses transmitted by three tick genera, and at least one tick-borne
protozoa have been shown to cause human disease. In the following slides
I’ll present data to show that the majority of
vector-borne diseases in the US are tick-borne. That in recent decades, the number of tick-borne
disease cases has increased. The geographic range over which
tick-borne disease cases have been reported has expanded. And a growing number of tick-borne disease
agents have been recognized to cause human disease. Among the nearly 50,000
cases of locally acquired, nationally notifiable
vector-borne diseases of humans reported annually
to the CDC from states and the District of Columbia, approximately 95% are
transmitted by ticks. Notably, Lyme disease
accounts for the majority of reported vector-borne
disease cases with over 30,000 cases
reported annually. Without denying the
significance of Lyme disease, the focus of this
Grand Rounds will be on other human pathogens
transmitted by ticks. Of the more than 84 tick species
described in the United States, roughly a dozen are frequent
human biters that are capable of transmitting human pathogens. Human-biting ticks are present across the contiguous United
States, however, for simplicity, here I’ll show the
generalized distribution of only three human-biting
ticks that are responsible for the majority of reported
tick-borne disease cases. Ixodes scapularis,
the blacklegged tick, is primarily a
woodland-associated tick that’s distributed across most of
the eastern United States, and it serves as a vector of the
agents that cause anaplasmosis, babesiosis, borrelia miyamotoi
disease, ehrlichiosis, Lyme disease and
Powassan encephalitis. Notably, an individual ixodes
scapularis can carry multiple disease agents, thus stressing
the importance of coinfections for diagnostics and prevention of ixodes scapularis-borne
diseases. The lone star tick,
amblyomma americanum, has a similar distribution
to ixodes scapularis but has a more southerly
distribution. It’s also primarily
woodland-associated and serves as a vector of the agents that
cause ehrlichiosis, tularemia and heartland virus disease. The American dog tick,
dermacentor variabilis, is among the most broadly
distributed human-biting ticks in the US. Found primarily in
grasslands, its range spans across the eastern US and
along the Pacific coast, primarily in California. It’s a vector of the agents that cause Rocky Mountain
spotted fever and tularemia. When looking at maps of nationally notifiable
tick-borne diseases shown by location of residents. There are obvious regional
differences that are explained, in part, by tick distributions. Notably, although ixodes
scapularis is present across the eastern US, reportable ixodes
scapularis-borne diseases, such as Lyme disease,
anaplasmosis, and babesiosis clustered in
the northeast, the mid-Atlantic and the upper Midwest where humans encounter
the tick more frequently than in other parts
of the tick’s range. In recent decades, the numbers of many notifiable
tick-borne diseases have suddenly increased. For example, the average number of reported Lyme disease
cases has roughly tripled from 1992 to 2015. Likewise, the number of
reported cases of anaplasmosis, ehrlichiosis and spotted
fever group, rickettsiosis, has suddenly increased
from 2000 to 2015. In addition to increasing
case counts, the geographic distribution of several tick-borne
diseases is expanding. To illustrate this point, the map on the left
shows the distribution of reported Lyme disease
cases in 2001 compared with 2015, shown on the right. Although less prevalent,
the geographic distributions of other ixodes scapularis-borne
diseases mirror the distribution of Lyme disease cases. Tick-borne organisms are
increasingly being recognized as human disease agents. This timeline shows when tick-borne pathogens
were recognized as causes of human disease. Over the first 60 years
of the last century, seven tick-borne
pathogens were recognized to cause human disease. Common colors on the timeline
represent a common tick genus that serves as the vector. In more recent decades, the rate of pathogen discovery
has accelerated, with 11 additional
pathogens described to cause human disease
since 1960. Notably, more than half of those
were discovered after 2000, and the majority were associated with blacklegged ticks,
ixodes scapularis. There are several explanations
for why tick-borne diseases and tick-borne disease
agents are increasingly being recognized and why case counts
are increasing in number and are being reported across
broader geographic extents. Improved diagnostics
and clinical recognition of tick-borne disease agents and tick-borne diseases
will be discussed in subsequent presentations. Here I’m going to
discuss the importance of expanding geographic
distributions of vectors and a lack of effective
prevention strategies. The accelerated discovery of ixodes scapularis-borne
pathogens may be attributable to an increased focus
on this vector after Lyme disease was
discovered in the early 1980s. In addition though,
the geographic range of this tick has
expanded considerably over the last two decades. From 1996 to 2015,
the number of counties in which ixodes scapularis
is considered to be established has
more than doubled. The expanding range of
ixodes scapularis also helps to explain the expanding
distribution of counties classified as high
incidents for Lyme disease. Over the last two decades, both have expanded following
similar spatial patterns. Another contributing factor to
the increase in reported numbers of tick-borne diseases is
increasing human contact with ticks that comes
with landscape changes. There are no human vaccines
currently on the market in the United States to
prevent tick-borne diseases. Although we have several
options for prevention, we lack a single effective,
widely accepted method for preventing tick-borne
diseases. Current prevention strategies
fall into three broad areas, personal protection, environmental modification
or tick suppression. Personal protection strategies
focus on avoiding tick habitat and use of repellants
specifically 20 to 30% DEET on exposed skin and wearing
permethrin-treated clothing. Daily tick checks and removal and to remove the ticks before
pathogen transmission occurs. To accomplish this, CDC
recommends bathing or showering as soon as possible after coming
indoors, checking yourself, your children, your pets and
your outdoor gear for ticks and removing them promptly
and tumble drying dry clothing on high heat to kill any ticks
that remain on the clothing. Other strategies aim to
modify the environment to make it less suitable
for ticks. Human contacts of
ticks may be reduced by using strategic
landscaping techniques. Tick abundance is reduced
through the use of acaricides and biological agents. Other strategies aimed to reduce
the abundance of important hosts for ticks in areas where humans
are likely encounter the ticks or to reduce the number of
ticks on hosts through the use of acaricide applied
to the host. Finally, developing technologies
focus on delivering vaccines or antibiotics to rodents to
reduce the infection rates in the host and ultimately
in the ticks. Each of the prevention
strategies I’ve described variant efficacy and
an acceptability. Despite the large number
of intervention strategies, we lack a single effective,
widely accepted method for preventing tick-borne
diseases. Looking to the future,
it’s likely that advances in molecular pathogen
detection and bioinformatics, coupled with a sustained
interest in tick-borne diseases
will lead to the discovery of more tick-borne diseases
and tick-borne disease agents. Reforestation, increasing
abundance of deer, which are important hosts
for many tick species, and changing climatic conditions
have led to the expansion of several vector species. Models suggests that some
tick species ranges are likely to continue to expand over
time, and this may lead to tick-borne disease
cases being reported from new locations. A single tick species or even
an individual tick can carry multiple disease
agents, therefore, coinfections will continue to
be important for diagnosing and preventing tick-borne
illnesses. Finally, there’s a need to
develop effective approaches to preventing tick-borne
diseases. But perhaps an even
bigger challenge is how to deliver effective prevention
strategies to large numbers of people and ultimately
reduce the trend of increasing tick-borne
diseases. It’s now my pleasure to
introduce Dr. Paddock. [ Applause ] Thanks Becky. In the next few minutes
I’ll be touching on a few things mentioned
previously in Dr. Eisen’s talk, using two rickettsial
diseases as examples. The beautiful place in the left
panel is the Bitterroot Valley, located in the far
western part of Montana. It’s not particularly large,
only about 120 miles long and ten miles across
at its widest point. But at the turn of the
20th century, a deadly and previously undescribed
disease emerged in this remote and sparsely populated valley. It was associated with a very
high fever and a petechial rash that covered most of the body. And it killed the majority of
persons who became infected, generally within the
first eight to ten days. Of the 343 cases identified in
western Montana between 1880 and 1909, 62% ended in death. This case fatality rate
rivals or exceeds some of the worst infectious
diseases. Investigators soon
learned that the disease, which was given the name
Rocky Mountain spotted fever, was transmitted by ticks and became the first
recognized tick-borne disease of humans in the United States. The severity of Rocky Mountain
spotted fever is linked to the tropism of the causative
agent, rickettsia rickettsii, to cells known as endothelium which line the small blood
vessels of every major organ and tissue of the body. This is represented by the
histologic image on the left which shows rickettsii
within the endothelial cells of a patient who died from
Rocky Mountain spotted fever. This disease progresses
rapidly to involve blood vessels in the skin, as shown by the
petechial rash in the center, as well as those in all of
the major organs of the body. The damaged blood vessels
caused by these bacteria result in extreme vascular
permeability, which can lead to death when it involves
the lungs and the brain. The panel on the right is a
histologic section from the lung of a patient with fatal
Rocky Mountain spotted fever that shows diffused
pulmonary edema caused by leaky alveolar capillaries. Fortunately, tetracycline class
antibiotics can cure the disease if administered in
a timely manner. Discovered in the mid-1940s, tetracycline drugs considerably
reduce the case fatality rates to contemporary estimates
of approximately 5 to 10%. Doxycycline is considered
the drug of choice for all tick-borne
rickettsioses, but to achieve the
most favorable outcome, it should be administered early
in the course of the illness to prevent irreversible
organ damage. Today, the majority cases of Rocky Mountain spotted fever
reported from a belt of states in the central and
southeastern US that extend from Oklahoma eastward to North
Carolina, the principle vector of Rocky Mountain spotted fever in this region is
dermacenter variabilis, also known as the
American dog tick. But I also want to draw
your attention to a region of eastern Arizona
which reports some of the highest incidents
rates in the country and where there are
no dermacenter ticks. Beginning in 2003,
epidemic levels of Rocky Mountain spotted
fever were recorded from several American Indian
communities in eastern Arizona where the incidents rates
approached 150 times the national average. CDC investigators, working
closely with tribal partners and the Indian Health
Service, soon determined that the brown dog tick,
rhipicephalus sanguineus, was responsible for
these outbreaks. Enormous populations of brown
dog ticks had proliferated among free-roaming dogs in
these communities. Because dogs serve
as an amplifying host for rickettsia rickettsii, and because rhipicephalus
sanguineus is an efficient vector, this created
a perfect storm for peridomestic transmission. This also represented a paradigm
shift, not only in the magnitude of case numbers, but
also the involvement of a tick vector not
previously considered relevant in the epidemiology of this
disease in the United States. Through a collaborative endeavor
involving multiple groups, a community-based
intervention was undertaken in a highly-impacted community. The yards of 550 homes were
treated with an acaricide spray, and tick collars impregnated with a long-lasting acaricide
were placed on over 1,000 dogs. These efforts resulted in
a marked reduction in on and off host tick numbers
and, most importantly, a 43% reduction in
the number of cases of Rocky Mountain spotted fever. So, for more than 100 years, Rocky Mountain spotted fever was
considered the only tick-borne rickettsiosis in
the United States. However, scientists were aware
of other tick-borne rickettsii, like the one reported in 1939
from the Gulf Coast tick, also known as amblyomma
maculatum. Sixty-five years
later, this rickettsia, known as rickettsia
parkeri, was isolated from an ill patient in Virginia. During the subsequent ten years, approximately 35
additional cases of rickettsia parkeri
rickettsiosis were identified across nine states in
the southeastern US. At first glance,
it’s not difficult to see how some patients with rickettsia parkeri
rickettsiosis might be mistaken as cases of Rocky
Mountain spotted fever. The distinction between
the rashes, particularly during
the early stages of the disease, can be subtle. Both are maculopapular,
but the rash caused by rickettsii parkeri is
generally more sparse, and often associated with small
vesicles or pustules as seen in the lower right-hand panel. Nonetheless, almost all patients with rickettsii parkeri
rickettsiosis have the distinctive lesion
known as an eschar, which is a scabbed necrotic area
of about a centimeter across, which represents the site where an infected tick
inoculated rickettsia parkeri to the skin. For reasons that
are still unclear, an inoculation eschar
occurs only very rarely with Rocky Mountain
spotted fever. So, as you can see, these diseases show
several clinical features, such as fever, headache
and rash. Where they differ is in
the frequency of an eschar, but most importantly,
in severity and outcome. To reiterate, Rocky
Mountain spotted fever is a life-threatening illness with contemporary case
fatality rates about 8%. Whereas rickettsia parkeri
rickettsiosis is a far milder disease with no known deaths. So how much spotted fever in
the United States is caused by the respected agents? We currently don’t have a
good answer to that question. But there is some
evidence to suggest that there is more rickettsia
parkeri rickettsiosis than we know. For example, we know
of multiple instances of individual clinicians
who are adept at recognizing this disease and
have identified up to five cases in just a few years
of searching. Another clue comes from the
relative rates of infection in the tick vectors with
each of these pathogens. Rickettsia rickettsii is rarely
found in dermacentor ticks in the eastern United States,
and current estimates suggest that fewer than 1 in 2,000 ticks
actually harbor this pathogen. In contrast, rickettsia
parkeri is commonly found in amblyomma maculatum
with one in about every two to four adult Gulf Coast ticks
infected with this agent. Finishing up, the
take-home points from this segment are
the etiologic spectrum of rickettsiosis in the US
has expanded during the last 15 years. Rocky Mountain spotted fever and rickettsia parkeri
rickettsiosis share many clinical features but differ
considerably in severity. And finally, and
perhaps most importantly, doxycycline is the
drug of choice for all tick-borne rickettsioses
and in all patients of all ages. Therapy needs to be
initiated immediately based on a presumptive diagnosis. Thank you, and at this
point, I’m going to turn over the podium to
Dr. Greg Ebel. [ Applause ]>>Thank you. Today, I want to provide
you with some information on tick-borne viruses. Most of us think of
tick-borne disease as fairly badly neglected
in the current environment. And tick-borne viruses are
neglected even among these neglected pathogens. This lack of attention
is somewhat strange, so I want to take a
minute to give you a sense of the wide diversity of viral
agents vectored by ticks. These agents belong to a wide
array of taxonomic groupings. They also have very
different strategies for storing genetic information
and packaging that information into infectious particles. Like other arboviruses,
outcomes of human infection with tick-borne viruses
are variable but may be quite
severe and often fatal. The other notable point that
I’d like to make here is that tick-borne viral diseases
are found all over the world, so tick-borne viruses
really a global problem. So why is it that ticks are
such great vectors of viruses? If we think about
the characteristics that impact the reproductive
rate of an arthropod-borne
pathogen, ticks have them all. They can be extremely abundant
in certain areas and tend to focus their feeding on a very
restricted set of host animals, often on a single host species. They also are extremely
long-lived, especially in comparison to
mosquitoes, with lifecycles of most taking several
years to complete. That means that they tend not to die before a virus
infects their salivary glands and is released into
their salivary secretions. There are also some other
biological factors that have to do with the way that their
saliva suppresses host immunity in order to permit the prolonged
feeding process ticks require, and with the way that they
digest their blood meals that are all critical in
making them outstanding arbovirus vectors. So in the next few slides I’m
going to review a few emerging and really interesting
tick-borne viral diseases that are of relevance
to us here in the US. And I’m going to
start with the one that in my mind is the
most problematic and about which we know the most and
has the greatest potential for emergence, and that’s
Powassan virus, also referred to as deer tick virus in
portions of the literature. Powassan virus is
maintained in nature in at least three fairly
distinct transmission cycles. The first has been
known since the 1950s and involves woodchucks
and a species of tick ixodes cookei
that’s generally confined to woodchuck burrows and
feeds almost exclusively on woodchucks. A second cycle involves
squirrels and a different species
of ticks, ixodes marxi. This cycle was also
noted shortly after Powassan virus
was discovered. More recently, it’s become
clear that a distinct genotype of Powassan can be maintained in a deer tick white-footed
mouse cycle alongside the agents of Lyme disease,
human babesiosis and human anaplasmosis. The extent to which
viruses spill over from one transmission cycle to another aren’t really well
understood at this point, but based on virus
genetic studies, it appears that at least the
deer tick-associated cycle is isolated from the others. Also notable is that most, if
not all, recent human cases of Powassan virus
infection appear to be linked to the deer tick-driven
transmission cycle. That is part of the reason that Powassan virus is
considered an emerging health threat in the US, and there is in fact some evidence
to support this. The first piece of evidence
is from wildlife studies. This shows that deer collected
in Connecticut from 1978 through 2010 had an
increasingly likelihood of carrying antibodies
directed against Powassan virus. The likely explanation
here is that more ticks in the environment equals
more tick bites to the deer which equals more transmission,
which also equals more risk because generally, human risk
is proportional to the intensity of enzootic transmission, which in this case is
clearly increasing. There’s also good clinical
evidence that the incidence rate of Powassan virus in human
beings is increasing. Although this could
partly be due to enhanced recognition
and detection. Given what’s known about
increasing enzootic transmission that I showed you about in the
previous slide, it seems prudent to consider the possibility that human infections are
indeed becoming more common. This table showing
clinical features of a case series collected from
2013 to 2015 demonstrates this. Also, please note that
the case fatality rate of approximately 25%
and the prevalence of severe long-term
sequelae among survivors, which was about 33%,
is consistent with what we thought we
knew about the severity of the infection dating
back to the earliest studies of Powassan virus in humans. Since 2006, 68 cases of
Powassan encephalitis have been recognized and reported. Because this disease
can initially look like other illnesses, it’s likely that only the
most severe hospitalized cases or deaths are the ones
that are being reported. Cases have occurred in the
northeast and upper Midwest, which of course, is consistent
with transmission by deer ticks. Severe Powassan virus
disease occurs due to neurological involvement. These images show that
this can occur via two distinct mechanisms. The first is due to inflammatory
changes within the perivascular and parenchymal portions of
the brain which are shown in panel A. The other mechanism by which Powassan
virus causes diseases, direct neuronal injury,
which is shown in panel E. In this particular case, nearly
all of the Purkinje cells, which among other things control
motor functions, were targeted by Powassan virus and were
nearly absent on this biopsy. So both direct infection
of neurons and inappropriate inflammation
due to infection contribute to pathogenesis in human
cases of Powassan virus. So we keep learning about
new tick-borne viruses. Well I want to take a
moment to discuss two that are cause for some concern. I’d like to stress that
very little is known about these viruses. The first is heartland virus, a
phlebovirus that was recognized in 2009 due to two cases
that occurred in Missouri. The virus is transmitted
by the lone star tick, amblyomma americanum, which
is currently expanding in its distribution. Wildlife studies suggest
widespread distribution of the virus in the southern
and southeastern United States. Another newly discovered virus
is bourbon virus, a thogotovirus that is known from a
single case report in 2015. Based on its biogenetic position
in in vitro replication studies, it seems highly likely that
this also is a tick-borne virus. The sole case resulted
in a fatal outcome. Again, though, the real
point is to highlight that we’re always finding new
pathogenic tick-borne viruses and that there is a wide
taxonomic array of agents that can potentially emerge. So these are things
that we really need to maintain vigilance about. I want to close by
taking a moment to talk about the state of the field. I mentioned that this is a
neglected area, but it’s not because we don’t
have interesting, relevant things to work on. It’s been clear that much of the
emergence of tick-borne diseases in our country is linked to the
reforestation of the eastern US, which has led to the broad
ecological changes we’ve seen in this region. So where are the knowledge
gaps and unmet needs that we should be
trying to fill? Well, first there’s
some lack of clarity in the field regarding
what’s required to facilitate virus perpetuation
in nature, and by extension, what factors impact when
and how these new tick-borne viruses emerge. What’s clear is that many
different transmission modalities exist, and that in
some cases, many may be required to allow the viruses to survive. A general problem in the field
is the disconnect that exists between theoretical,
experimental and field-oriented individuals. And this is currently
hindering progress. A second opportunity exists as
we’ve experienced an explosion and knowledge about tick
functional genomics that’s arisen due to fundamental
changes in the way that we collect and
analyze genetic information from arthropod vectors
and their pathogens. The work that’s been done
recently builds on years’ worth of work that’s characterized
the potent salivary secretions of ticks, work that’s continued to raise several
important questions on how tick saliva impacts
pathogen transmission. Those who work on functional
genomics will appreciate the large amounts of data
that can now be generated incredibly rapidly. I, however, would stress
analysis here, because it turns out that tick genomes are
incredibly large, almost as big as the human genome
and that much of the information they
obtain is duplicated in some way or another. The functions of many tick
genes are not well understood, as you can see from this figure of a paper describing
the transcriptome of the tick, hyalomma
marginatum. Forty-five percent
of the transcripts in this case are
classified as unknown. It’s also, of course,
become clear that many important
phenotypes are controlled, not only by the host
genome, but by the assemblage of other organisms that
inhabit ticks in all of us. Clearly, piecing this all
together is complicated, but new advances
in computational and experimental biology
are already allowing us to make some progress
in this area. So we’re at a very exciting
time in the history of the field of tick-borne virus
disease research. We have a broad expertise
in the ecology of ticks and their hosts, improvements
in in vitro and in vivo systems to study tick-borne
viruses, and new sequencing and computational tools to apply
to these important problems. But progress isn’t being made
as fast as we would like. There are both technical and
environmental reasons for this. Many tick-borne viruses, as I
mentioned, are highly pathogenic and require BSL-3, or even
BSL-4 containment for study. Here’s a picture of my
friend, Dennis, trying to work on tick-borne viruses at BSL-4. And as you can imagine
from the picture, that might present
a few problems. Also, the systems that we’re
talking about are complex, as they are for all
arthropod-borne disease. But the understanding
of ticks lags far behind that of mosquitoes. This is partly because of the
prolonged lifecycle of ticks. They live longer than the
grants many of us hope to obtain to use to study them. So the point is that
our system in the US for funding biomedical research in academia isn’t particularly
well-suited to work on ticks and the pathogens they carry. Finally, while tick-borne
viruses are clearly emerging, they tend to do so
much more slowly than do mosquito-borne
arboviral diseases which emerge in these explosive epidemics that we’ve seen repeatedly
in recent years. So there aren’t many
people left working on them. So thank you for your attention. I hope that I’ve convinced you that tick-borne viruses are
emerging health concerns, that we have interesting,
relevant and tractable questions, and
we have great opportunities to move the field forward. But that we do have
some difficult technical and environmental barriers
that are impeding our progress. So at this point, I’d
like to turn the podium over to Dr. Bobbi Pritt
from the Mayo Clinic. [ Applause ]>>Thank you, Greg,
for that introduction. So, so far in this program
we’ve discussed the clinical and epidemiologic features for
some select tick-borne diseases. I’m now going to shift
gears to talk about advances in laboratory detection methods for diagnosing tick-borne
diseases. So let’s first start with an
overview of the primary methods for diagnosis for
tick-borne diseases that we have available to us. And I’d like to actually start by emphasizing the clinical
evaluation of the patient that occurs by members
of the healthcare team. This is essential at this point that tick-borne diseases
be considered in the differential diagnosis. And this is not just so that
the crack laboratory test can be ordered but also that empirical
antimicrobial therapy can be begun if indicated. And as we heard from
Dr. Paddock, this is especially important
if rickettsiosis is expected or ehrlichiosis or anaplasmosis. Because some of these
infections can be rapidly fatal, and they need to
be treated quickly, often before the test
results are available. So, now let’s move on to
specifically laboratory methods. And these can be further
divided into indirect and direct laboratory methods. Indirect methods, as I’m
covering on this slide, don’t detect the organism itself but rather the host immune
response to infection. And typically, this
involves detection of IGM or IGG class antibodies in
serum or other specimen types. Now serology is the
method of choice for diagnosing many
tick-borne diseases. That’s especially true for
infection with rickettsia, ehrlichia and anaplasma species, and there are commercially
available options for these tests. Now tick-borne virus serology
is a little bit more challenging because there aren’t any
commercially available tests. Instead, these methods us
laboratory-developed tests, and these are available
primarily through the state public
health laboratories or the CDC. I also want to mention that serology is not the
primary diagnostic method for babesiosis. Instead, blood smear
should be used. Now one important,
very important, caveat about serology is
that the sensitivity varies by the time the specimen is
obtained during the course of illness. And I want to illustrate
that here on this chart. So this graph shows the
general patterns of IGM and IGG antibodies
following infection. And if we consider day one
to be the onset of infection, then you can see that IGM
antibodies start to rise in the first few days. They’re usually detectible
by seven days. And then Titer eventually
drop off after several months. Then, production of
IGG develops after IGM, and levels will continue to rise and then can remain
detectible for years. So as you can see
with this graph, there’s this first week lag where serology is an
insensitive method for detecting tick-borne
diseases. But by the second or third week, sensitivity increases
significantly. So, now in comparison
to indirect methods, let’s talk about direct methods. These detect the organism itself or some component
of the organism. So for example, microscopy
can be used to detect bacterial clusters
of anaplasma phagocytophilum, relapsing fever borrelia
spirochetes in peripheral bladder
CSF, or babesia parasites within red blood cells. Also nucleic acid
amplification tests are a method for directly detecting
the organism’s DNA or RNA. And then culture is
also a direct method. It’s not routinely used
today except for detection of francisella tularensis, the
causative agent of tularemia, but it is an important
research tool. So let’s go back to our graph
now to look at the utility of direct laboratory methods. In comparison to antibodies,
which the curves here show, DNA or RNA can almost
always be detected earlier on in the patient. This is just a generalization. You can see different curves
with different organisms. Now the onset of symptoms
is also quite important when you’re considering
molecular testing since this will still
influence when patients present with treatment or for
treatment by their physician. So for many tick-borne viruses,
as I’ve highlighted here in this yellow-orange
color, you can see the onset of symptoms occur, does
not significantly overlap with the period of time that
the patient has detectible DNA or RNA in their blood. So by the time the
patient presents to a healthcare provider
for evaluation, nucleic acid may no longer
be detectible in the body. So, in general, this explains
why nucleic acid amplification methods can be one of our
earliest detection methods for some organisms, yet can
also be an insensitive method for other organisms. They do happen to be
our most sensitive tool for detecting anaplasma
phagocytophilum, ehrlichius species and
babesius species, particularly in whole blood, because the DNA of these organisms
is present usually in high amounts during the stage
that patients are symptomatic. Now there are a variety of nucleic acid amplification
methods available. Unfortunately, none are
currently FDA cleared or approved for in vitro
diagnostic use at this time. Now let’s discuss
specifically one aspect of nucleic acid amplification
methods. That’s called real-time
polymerase chain reaction, or commonly known as PCR. By using one of several
different types of probes, DNA is detected as
it is amplified. And when designed well,
PCR allows for sensitive and specific detection. The greater amount of
nucleic acid that’s present in the specimen, the faster
it’s detected, and therefore, real-time PCR also
provides some measure for how much DNA is
present in the specimen. We can get even more information
out of the test reaction by incorporating a step called
melting temperature analysis. This can use either
nonspecific DNA-binding dyes or specific probes. This occurs after amplification, and melting curve
analysis can alert the user if there are any
mutations present. This could be a simple mutation, or it could represent an
entirely new organism. And I want to show
you an example of that on this next slide. In my laboratory at Mayo Clinic,
we have a real-time PCR test that targets grow
EL, that’s the gene that encodes the heat shock
operand of ehrlichia species. Now we designed the
primers to amplify a region of the gene that’s conserved
in all ehrlichia species, and then we differentiate the
two human pathogens ehrlichia ewingii and ehrlichia
chaffeensis, by melting temperature. And you can see the
melting peaks here. This is possible
because we chose probes that target the regions of DNA where there are two
base pair differences. So you get two distinct
discriminating peaks for each of the organisms. Now, what this was really
interesting for this assay, as we were using it
for several years, we then noticed this peak
right here in the middle. Now this peak indicated a
new organism that was clearly within outside of the range of ehrlichia ewingii
and chaffeensis. This prompted us to perform
some additional testing, and we recognized that this
is a new organism now called ehrlichia eauclairensis. So now, let’s just take a sec and talk a little bit more
beyond single plex PCR. Because this is talking about
just a single PCR reaction. Some of the things that
take us beyond that, one of them would be
multiplex molecular panels. This is when you use a
combination of primers and probes to detect
multiple bacterial, viral and parasitic
pathogens in a single test. We already have these four
respiratory pathogens, gastrointestinal pathogens, and now there are tick-borne
pathogens that are also panels that are under development. One aspect that takes
us a little bit beyond that even further would
be broad range sequencing. Unlike a multiplex panel where you only detect
what you’re looking for, broad range sequencing, you’re
targeting a specific gene. You amplify then and
then there’s subsequent sequence identification. We have common targets such as
16-S, the RRNA gene for bacteria and the internal transcribe
spacer region for fungi. Unfortunately, at this point, there is no equivalent
for viruses. So instead, we tend
to target groups of closely related viruses
such as flaviviruses. Now the last category
of emerging technology that I find particularly
exciting is metagenomics. And with this method,
amplification of all nucleic acids
that may be present in a specimen are amplified. That could be bacterial, fungal,
viral, parasitic and human. Because of the large amount of
nucleic acid that’s amplified, you then need to do extensive
pre and post processing steps to target the areas of interest and remove nonrelevant
nucleic acid. So, this is currently very
expensive and time consuming, but I think this is bound
to change in the future. So with that, I’d like to close with this last slide showing the
recently published guidelines for diagnosis and management of
tick-borne rickettsii diseases and thank you for
your attention. [ Applause ]>>Thank you, Bobbi. We’re going to open it
up for questions now. In the interest of time,
I’d just like to ask you to keep your questions succinct
and focused on the scope of the presentations
from this Grand Round. I’m going to start by asking
if there are any questions from online or remote
sites.>>We actually do have some
questions that came in, and again, our apologies for
future when this is recorded and posted on the
website by Friday. This is a technical difficulty
we haven’t experienced before, but we did receive a
couple of questions. One that I think is a good one. How do you remove a tick?>>Carefully.>>I can answer that. Well the best way to remove it
is using fine-tipped tweezers, or forceps if you have them. And you just grasp the tick as
close as possible to the skin and then just pull it out slowly
in a smooth, continuous motion. Try not to twist it or
squish it, because then that might possibly
inject some of the contents of the tick into the skin. And then you can dispose of it,
wash that bite site afterward.>>Okay, any questions from
the audience, we’ll take next.>>Nobody can access
this right now. So we’re still hoping.>>Okay, we’ll open it up then
to questions from the audience.>>I think you can hear me
right here in the front. In relation to behavior
change, campaigns related to this particular topic,
what are the two, three, four areas that you would
point to when we start looking at employing simple
modifications for folks to start practicing better
habits as relates to ticks?>>So you’re talking
specifically about prevention of tick-borne diseases? So there are a couple of
strategies, one includes trying to avoid tick habitat, which
is often easier said than done. And a lot of times the ticks
are in residential areas where you simply
can’t avoid them. When that’s not possible, we
recommend using a repellant, specifically containing 20 to
30% DEET that you can apply to exposed skin or clothing. Or using permethrin-treated
clothing. Those are probably the simplest
prevention steps you can take. But then it’s also recommended
that after coming indoors that you bathe and
do a tick check. And any tick that you
identify you remove promptly to prevent the likelihood of
the tick having the ability to transmit any of the
pathogens that it’s carrying. You can also tumble dry your
clothing at high heat to try to kill any ticks that
are still on your clothes. But most importantly, make sure
that you do the tick checks. Check yourself, your children,
your outdoor gear, your pets, so that you’re not
bringing those, the ticks into your
home for later exposure. Chris is going to
add something else.>>Yeah, I just want to follow
up on that because it relates to the previous question
in terms of tick removal. And as was mentioned previously,
that’s a very important process where you can reduce the
risk of transmission. Not all the ticks that
bite people are infected with a pathogen. But, enough of them are so
that getting that tick off you as quickly as possible reduces
the risk of transmission. And different pathogens take
different periods of time to transmit once the
tick is attached. But the quicker you can get that
tick off, the better you are. And the other thing is,
you need to be looking at your kids very,
very carefully. And ticks will go to places
that are hard to find. So you have to do a
very thorough tick check when you’ve been in
tick-infested areas. But that does minimize risk.>>Okay. Dr. Schuchat.>>One of you showed
that nice origin of the Rocky Mountain
spotted fever in Idaho. And in the maps it really
looks like, you know, the Rockies don’t
have it anymore. I was wondering if you could
clarify whether we are just seeing emergence of new vectors
on the eastern southern area, or has something changed
in the western states to make Rocky Mountain spotted
fever less frequent there.>>Well that’s a great question. And I think what’s really
important to realize is that tick-borne diseases,
like any zoonotic disease, they’re dynamic processes. These thing changes. There’s ebbs and flows in
terms of the distribution, the prevalence, you know,
the frequency of infection. The disease was first discovered in the Bitterroot Valley
of western Montana. But it existed in the
eastern United States. It just wasn’t diagnosed. It turned out that there was an
epidemic in this small valley, and it was so dramatic
that scientists from around the United
States came to that valley to investigate, much the way
scientists do now from CDC. So that’s where it
was discovered, and that’s why it got the name
Rocky Mountain spotted fever. It’s really a misnomer
because actually we now know that infection with rickettsia
rickettsii occurs all throughout the Americas. We know that it exists in Brazil
and Argentina and Columbia, as well as all the
states in the US. And actually, most of
the disease that we hear about now comes from
the eastern US where dermacentor
variabilis is the vector. What was very interesting is
the emergence of this disease in eastern Arizona associated
with the novel tick vector. And that, I don’t
have enough time to go into the details of that. But that was a very
intriguing process. And again, kind of
the whole concept that these diseases change over
time and new things emerge. We always have to be, you
know, prepared for new vectors, new pathogens and new
areas of emergence.>>So, over here. Thanks all. Just to follow up on Chris’
point, not a tough question, but what is your thoughts
on the next emerging virus or bacteria from ticks? Can you predict anything, what
are you expecting to happen?>>Sure. I think, you know,
there’s a couple of ways to answer the question. If by so, if we say, what
virus is going to emerge and give us the largest number
of cases in the shortest amount of time, something that
we know about already. I think in my mind, that’s pretty clearly
Powassan virus and its allies. And the reason for
that is that it is in exactly the same transmission
cycle that’s driven the emergence of Lyme
disease, human babesiosis, anaplasmosis and so forth. So, the question, I mean there’s
a lot of interesting questions around that why have we
not had a gigantic epidemic of Powassan virus encephalitis,
and so in a way, that’s almost as interesting of
a question as is that one really going to emerge. All of the kind of ecological
factors that could drive that sort of an epidemic
are there. Beyond that, are we likely to see more bourbon virus,
more heartland virus. I don’t know that I have a great
answer for that or the things that we don’t know about yet because we’re not doing a
particularly great job of going out and surveying
ticks for viruses. Some of that work is being done. But it makes it hard to kind of predict what’s
going to come next.>>So interesting, we’ve
recently seen two fatal cases of Powassan virus in our, which
is not common by any means. But that’s a good prediction.>>And.. I
think part of the answer to that question is the
availability of assays to actually pick it up. So if you don’t look for
it, you don’t find it. And I think one thing
that’s very apparent is that we haven’t discovered
all the tick-borne diseases that are yet to be discovered. As Bobbi mentioned,
more than half of them have been discovered
in the last couple decades. So, with the advancement of, you
know, technological diagnostics that Bobbi mentioned, I think
we’re going to find more. And then the other thing is, you’ve got to figure
there’s not just two or three viral diseases,
tick-borne viral diseases or two or three rickettsia diseases. It’s very likely that every one
of these ticks has its own suite of pathogens, whether
they’re viral or rickettsia or protozoal. And we found the
most serious ones, those declare themselves
usually pretty quickly like Rocky Mountain spotted
fever is very dramatic. So, it’s not surprise that
was sort of the first one. It’s the most lethal. But I think there are a lot of other probably more
subtle diseases out there that remain to be discovered.>>Do we have any more
questions from online? I don’t want to completely
neglect them.>>Yeah we do, but let’s
get other people in the room since we’re not webcasting.>>Okay.>>Thanks for the
great presentations. I noticed on some of your
incidents maps there’s a state-shaped hole of
lower incidents surrounded by areas of higher incidents. So could you just describe
surveillance systems for these types of diseases?>>So, most of the data,
or almost all of the data that we have for these
incidents maps are based on passive surveillance. And so, you have all
the limitations inherent in passive surveillance systems. So you may have some very
diligent people reporting from a particular county in
Florida or Oklahoma or Texas. And then people in other
counties in other states that, you know, aren’t
necessarily looking or considering tick-borne
diseases on their radar. So, I think that’s part of it. It’s hard, when you look at a
map like that, it’s hard to sort of say, this county has
it, this county doesn’t. Or this county has this high
incidence, this county doesn’t. I think it’s better to
look at it as a continuum. And also just a general pattern. And that’s why on
the incidents map for spotted fever rickettsiosis,
what I really wanted to emphasize is sort of the
overall pattern, which was sort of a band that extended from
Oklahoma to North Carolina. I didn’t want to say oh look
at this county in Tennessee. It’s got huge incidents, and
the county next to it doesn’t. The other thing is, these
are arthropod-borne diseases. Ticks don’t fly. The infections can be
very focal, you know, where you find a cluster of
cases in a particular area. And then, you know,
100 yards away, there aren’t any infected ticks. So, it’s tricky. I hope that answers
your question, Brian.>>It does, thanks.>>Thanks.>>Next question.>>It sounds like
prevention is a continuing and difficult challenge, trying
to get folks to repeat something that needs to happen regularly. Given the success apparently
that you had in the southwest with the experience with dog
tick collars, I’m struck. And I’m wondering if I’m
going to get a couple of those dog tick collars for
myself and use them to close up my trouser legs
next time I’m hiking. Is that a wearable
collar or bracelet or anklet strategy
something worth exploring.>>So I think the closest
you would come is repellant or permethrin-treated clothing. But you hit on one of
the toughest challenges.>>Oh I think I can get a dog
tick collar pretty easily. I’m sure Amazon will
ship them overnight.>>It would be fashionable. The one thing to note, Chris
had a notable success story with prevention of
tick-borne diseases. Rhipicephalus sanguineus
is a very different tick from the others that
we described. It’s a single host. So it can be very effective
to target domestic dogs. Whereas with your ixodes
scapularis-borne diseases, you tend to have the
immature life stages feeding on small mammals,
medium sized mammals, the adults feeding on deer. So you have multiple
hosts to keep track of, as well as those ticks
are often found very close to people’s homes and
in areas where they like to recreate
during the tick season. So repellant use,
permethrin-treated clothing and daily tick checks. Until the dog collar for people. Yep.>>So, on a number of the
slides, especially having to do with the ixodes range, the tick-borne disease range
was actually a much smaller than the ixodes range. So what is the ecologic
difference outside of the disease range where
the ticks still exist?>>Yeah, that’s a
great question. And there are several
differences. I think one of the key pieces
that separates your risk in the north and the south
is the behavior of the ticks. The southern ixodes ticks
are different enough from the norther ixodes ticks that at one point they
were two different species. And their host-seeking
behavior is really different. In the north the ticks more
actively ascend to vegetation and more aggressively
seek human hosts. Of course, humans are
still incidental hosts. But you’re more likely to
encounter a tick in the north than in the south strictly because of their
host-seeking behavior. Infection rates are
generally a little bit, are higher in the north
than the south, particularly for borrelia burgdorferi. The other pathogens
are quite low in prevalence across the board. But largely differences in
that host-seeking behavior.>>Hi, thanks for a
great presentation. You mentioned in
one of the slides that doxycycline is the
antibiotic of choice. But there are some
challenges associated with it. It’s not the first antibiotic
a doctor will usually prescribe for somebody with a
fever, for example. And it’s also a challenge
when it comes to pediatric population. So, I was just curious
if you had any insights into doxycycline use
in the United States and if there was anything
people should be doing if they know they’ve been
exposed to ticks when they go to their doctor to maybe push
them in that right direction.>>Yeah, that’s a
great question, Jenny. So, doctors are taught in
medical school very strongly that you don’t give
tetracyclines to kids under the age of eight
because it stains the enamel and causes hypoplasia
of the permanent teeth. Those studies were based on, or that dogma is
based on old studies. You know, essentially women who
were receiving tetracyclines in pregnancy for acne,
for multiple weeks and, what we know now is that
a single short course of doxycycline in kids
doesn’t cause cosmetic staining of teeth. So the real push now, and what
we’ve been trying to emphasize for the last two decades is that doxycycline is
the drug of choice. It’s really the only drug that
diminishes the fatality rates when administered in the
first five to six days. So we’ve been pushing
really hard to get physicians
to be aware of that. That you give that
drug regardless. It’s not going to cause
staining of the teeth if you give a five
to ten day course. I think that comes back to the,
you know, the very beginning in terms of how we prevent
and control these diseases. And you know, education and awareness are our most
powerful tools right now. You know, we are the CDC,
but I think the control part of this is going to be very
tough for years to come. Really the key to all these
tick-borne diseases is awareness and education of the clinicians
who are seeing patients, as well as the public
who are getting infected and presenting to
their clinicians.>>Thank you very much. And I’d like to take a
moment to thank the speakers for excellent presentations. Thank you. [ Applause ] Thank you very much for joining
us, and we’ll see you next month for CDC Public Health
Grand Rounds.

8 thoughts on “Emerging Tickborne Diseases

  1. I am sad to see a map indicating it is only on the east coast. And not even the full coast! There are plenty of cases in Canada as well. And on the west coast. I got Lyme disease in Napa Valley California in 1992. Also, see: Dr. Ernie Murakami in Hope, BC Canada.
    Hard to take the video seriously with such errors less than 7 minutes in.

  2. Does anyone know how many people suffer and suffer from Lyme in Brazil? We have given correct and up to date. Valter Moura

  3. I don't believe a word that comes out of the CDC …….they probably created this strain on plum island for our military to use as a bioweapon.
    Y'all " DO KNOW " that the US holds the patent for Ebola and AIDS….right ! Just to name a couple 😷

  4. My husband passed away from Babesia, a tick-borne disease that attacked his red blood cells and shut down his organs. He was young and healthy– please keep researching these parasites

  5. I suffer from AlphaGal, causing full blown anaphylaxis, as close to death as I have ever come and I have had a very adventurous life.
    I have found that health care providers in general, have a very limited knowledge and experience with this. I am interested in finding any published materials dealing with AlphaGal, any links or info would be appreciated. Thanks

  6. the CDC is probably releasing the diseased ticks as part of the depopulation agenda (see bill gates ted talk about reducing population w/Healthcare, Vaccines, technology)

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