New & Emerging Tickborne diseases: Agents, clinical features & surveillance

New & Emerging Tickborne diseases: Agents, clinical features & surveillance


Coordinator: Welcome and
thank you for standing by. At this time all participants
are in listen-only mode. This conference is being recorded and if you have any objections,
you may disconnect at this time. And I will turn the call over to
your host today, Dr. Joseph Breen. Sir, you may begin. Dr. Joseph Breen: Thank you. Good afternoon. My name is Joe Breen, I am a program
official at NIH in the National Institute of Allergy and Infectious Diseases. It’s my pleasure to be your moderator today
for our seminar here which is titled “Novel and emerging tick-borne diseases: agents, clinical features, and surveillance
information.” We’ve assembled a panel today of speakers
to talk about some of these agents and that panel is shown on the first slide. The way that we’re going to organize this is
each of the speakers is going to have to talk for about ten minutes on one of
these novel or emerging organisms and then we will take a few questions online. So we’ll have six ten-minute talks followed
by one to two online questions for each talk. And then to make sure that we
get all the presentations in, we’re going to move back to
the subsequent presentation. Any time we have for the balance since
we’re scheduled to go to 1:30PM Eastern, we’ll continue to take online questions. And in the case where we
can’t take all the questions or if there is a question following the session, the CDC has graciously provided an
e-mail address from the Division of Vector-Borne Diseases, [email protected] And I’ll repeat that again at
the end of the presentation. So my purpose here is to give you just a
little bit of context for our topic today, so I have just a few introductory slides and
then we’ll get right to the discussion of some of these novel and emerging tick-borne diseases. So tick-borne diseases, this is a list actually
that is on the NIH/NIAID website where I work as well as the CDC, the websites are
actually at the bottom of this slide. So tick-borne diseases, anaplasmosis,
babesiosis, ehrlichiosis, Lyme borreliosis, and rickettsioses, including
spotted fever rickettsia, Southern tick-associated rash illness, better
known as STARI, and tick-borne relapsing fever, as well as tick-borne viruses (Colorado tick
fever, and Powassan, which you’ll hear more about today), as well as tularemia. The ones with the stars are
actually all reportable to the CDC, so the others obviously are not, and
so in some cases we don’t know as much about them-for various reasons
they may not be reportable. But the reason I’m presenting you this list, is because actually these are all
important pathogens and certainly are within the research mission of
the NIH, as well as the CDC. So this slide actually comes
directly from the CDC. So tick-borne disease in the U.S.
from 2012-so these are reported cases, again total reported cases. For example, Lyme disease, which has the
highest number of reported cases, 30,000 cases. Some of the others that we’ll be hearing about
today are present on the slide all the way down to Powassan virus, which
was seven reported cases in 2012. And so it’s also important to know Anaplasma
or Ehrlichia are lumped together here, undetermined/other, 208 cases in 2012. So that’s informative, but really that’s just
one year, so I’m going to talk a little bit more about how things may have changed
over a much larger time span. The other important feature
is how do these occur across the U.S. in terms of tick-borne diseases? Another slide from data that’s presented from
the CDC showing some of the major suspects. Lyme disease, which has a foci in
the Northeast and upper Midwest, but is known to be expanding westward,
southward, and northward in some cases. Rocky Mountain spotted fever which is seen
here more, really in the tip of the South and the Midwest and actually all
the way up through the East coast. And anaplasmosis which has clear foci as
well in the upper Midwest and the East coast, and again you can imagine that these are
related to the vectors where they’re contained, but I’m not going to get into that so
much during this brief introduction. Ehrlichiosis, which is contained in a belt
here in orange, really again across much of Tennessee, east and west of Tennessee,
and in here in the Midwest as well, as well as up and down the East coast. And much more rarely seen, tularemia, with cases
still seen, and you can see plenty of blue dots. And I’ll remind you that this is again not
strictly speaking where the disease occurs, but where it is reported from the
residence of the person who is reporting. So in terms of a snapshot of disease from
2003 to 2012, this again is from the CDC, showing really ten years’ worth of surveillance
data for Lyme disease from 2003 reported cases for 21,000 has really steadily
increased to 30,000 cases in 2012. It’s also a definition change slightly
in terms of confirmed and probable cases which may account for some
of the differences in cases. Rocky Mountain spotted fever or the spotted
rickettsia group has increased fairly dramatically from 1,000 cases in
2003 to over 4,000 cases in 2012. And again Ehrlichia/Anaplasma
combination here has really increased from 700 to over 3,700 cases in 2012. And Babesia, which was really
not reported until 2010 is in the range of approximately 1,000 cases. And we’ll hear more about
Babesia later in this series. The purpose of this is really to indicate that
these are, that the cases are growing in each of these, and now we have some novel and
emerging tick-borne diseases that we need to consider as well moving forward. So I would like to then go right
to the subject matter talks here, so before I introduce Dr. DeVries, I’ll
just remind you again that what I’m going to do is turn it over to Dr. DeVries,
who will go through his presentation, then we’ll take a few questions online,
and then move on so that we can get through these interesting presentations
and get all of our content in and then come back to our questions at the end. So at this point I’m going
to pull down, Dr. DeVries, your presentation and turn it over to you. So this is Dr. Aaron DeVries from
the Minnesota Department of Health. Dr. DeVries, there you go. Dr. Aaron DeVries: Thank you. Thank you very much, Joe,
on behalf of David Neitzel, who’s head of our Vector-Borne Diseases unit
here at the Minnesota Department of Health, [I] really appreciate the opportunity be able
to talk a little bit about Powassan virus and share some of our experiences that we have
had here in Minnesota over the last few years. So as Joe mentioned, Powassan virus is a
tick-borne virus, and it was first described in 1958 in a case of fatal encephalitis that
occurred in Powassan, Ontario, in Canada. Subsequent work has shown that Powassan
virus is a tick-borne flavivirus, which is closely related to West Nile virus, and there’s at least two unique
strains of Powassan virus. There’s lineage 2 strain, sometimes
referred to as deer-tick virus, which is predominantly transmitted to humans
by the blacklegged tick or Ixodes scapularis. And lineage 1 are prototype virus which
is typically transmitted by Ixodes cookei, which is often referred to a ground hog tick,
which is commonly found close to burrows, where it feeds predominately
on medium-sized mammals and rarely quests for hosts more broadly. Now Powassan is just one of many known human
pathogens transmitted by the blacklegged tick, which is likely responsible for the majority of
Powassan disease that is observed in Minnesota. And I just showed you this list because some
of what I’ll be speaking to about the areas of risk is really based on surveillance for some of these other blacklegged
tick, tick-borne disease. In the U.S., Powassan disease has been
identified predominantly in the upper Midwest and the Northeast based on-really,
reports of neuroinvasive disease, which we’ll discuss in a little bit. This is probably just one of the larger
features, larger number of types of illnesses that may occur in the context
of Powassan disease. Now, typical blacklegged tick habitat is
characterized by a dense forest canopy, as imaged here, with thick
underbrush and a layer of rotting leaf litter on the forest floor. The ticks spend most of their time in
the litter, and they come up to quest for hosts near the ground level at times
when the environment is sufficiently humid. And humidity is very important
predictor of this. In Minnesota, there’s really four major
biomes, three of which are dominated by forest, and one is grassland, grassland
being in the western portion and southwestern portion of our state. And black-legged ticks are commonly found
in all of them, really with the exception of the prairie grassland
which is largely agricultural and typically too dry to support ticks. This is a map of our risk
areas of tick-borne disease, and as you can see it overlaps very
closely with these forested biomes. This is really based on our reported
Lyme disease and human Anaplasma over a period of time from 2007 through 2011. In recent years, as Joe mentioned, Minnesota has
experienced an expansion of the endemic areas of tick-borne diseases, especially in the
northern and northwestern portions of Minnesota. Powassan was first identified
in Minnesota in 2008, and through 2012 we’ve identified 21 cases. Now, based on our interviews with Powassan
cases, trying to understand a little bit more about where exactly they were exposed
in the month prior to their onset of illness-the areas here highlighted in red are
the counties in which Powassan cases appeared to have been exposed, and if
you overlay this with the areas of highest Lyme disease incidence, you
see that these areas overlap very closely. And this is really consistent with our thought
that the disease likely shares the same vector. Since 2009, we’ve identified Powassan
in Ixodes scapularis ticks by PCR in all of the five counties where ticks were
collected and tested over this time period. And depending on the year, and the location,
and the tick life stage, infection prevalence for Powassan virus ranged anywhere
from 0 to up to 15% of ticks. Now thinking about Powassan disease and its
manifestations, similar to West Nile virus, Powassan can cause central nervous
system disease, particularly encephalitis and meningitis, and this has been observed
in up to 10 to 15% of reported cases. I’m sorry, of 10 to 15% of the cases
reported have been noted to have died. And of those who do survive, long-term
sequela is actually quite common, being observed in about half
of those individuals. I think importantly though, the clinical
spectrum of Powassan virus is not fully known, and some infections may certainly
cause either just a febrile illness or may, in fact, be asymptomatic. Powassan has only rarely been
identified in all of North America with an estimated, around 60 cases. However, there is still very
likely substantial under-diagnosis, likely because the diagnostic
testing isn’t widely available. Diagnostic testing really has been
based on serology for the most part. Powassan IgM- and IgG-based on ELISA or
plaque reduction neutralization testing, as well as PCR of serum and CSF,
has really been the mainstays for the diagnosis of these individuals. Currently there are very
few laboratories in the U.S. that offer Powassan virus
testing on clinical specimens. We offer it here at the Minnesota
Department of Health. We are aware that the New York Department of
Health offers this, as well as the Division of Vector-Borne Disease at the CDC. Of our 21 cases that occurred between 2008 and
2012, our peak year was 2011, with 11 cases. Almost all of our reported cases have had
encephalitis or meningitis, including one death. We have had two who had a febrile
illness only, and really we feel that this is very likely biased due
to the nature of the surveillance and how these cases were reported. The median age has been 49
years, with a wide range. Almost all of our cases have had onset
between the months of May and August. The cases we’ve identified are likely biased, as
I mentioned, and really because we have a number of surveillance mechanisms-one
of them in particular focusing on unexplained critical illnesses and the
other related to unexplained encephalitis. Of individuals who have had neuroimaging, within
our experience, out of these eight individuals, seven of them have had an abnormal MRI, with
the majority having abnormal midbrain lesions, and again in our experience, most
frequently, within the thalamus. So despite the relatively low number
of reported human reported cases, Powassan virus has likely
increased in prevalence over time. This is data from a study of Powassan antibodies
among white tailed deer in Connecticut over the years from 1979 to 2009. And there was a consistent trend of
increasing prevalence of antibodies against Powassan virus that was observed. And this is very consistent with what we believe
is the same trend that’s likely occurring in Minnesota. Despite yearly variation in our case counts,
cases of tick-borne disease transmitted by black-legged ticks continue
to rise in Minnesota. The incidence of human Anaplasma
doubled from 2000 through 2006, during which time Minnesota ranked in the
top three states for disease incidence, and represented one-quarter of
reported U.S. human Anaplasma cases. Since 2000, cases of Lyme disease,
human Anaplasma, human ehrlichiosis, as well as Babesia in the state increased 170%, from 546 cases in 2000 to
over 1,400 cases in 2010. One important difference that impacts
public health recommendations related to Powassan disease prevention is that the
tick attachment time leading to transmission of Powassan is likely less time
than other tick-borne diseases. In this study looking at infection time in
mice, an attachment time of 15 minutes lead to 63% of the mice becoming infected. And you can compare that with Borrelia
burgdorferi, Babesia, and Anaplasma, where there’s approximately 24 hours or more that is typically
required for that transmission. So, in summary, be aware that Powassan
may be occurring in your state, and I think it’s important to think about
raising awareness among your medical community, as this is potentially an important disease, particularly if you have black-legged
tick disease activity within your state. I think one of the reasons why Minnesota has
been able to detect a number of these cases, is that we have a couple of
different programs, which I mentioned. One of them is a program for unexplained
critical illness and death reporting. This has actually been a
very important mechanism that we’ve heard about many
of these individuals. Powassan likely causes a wide
range of clinical manifestations, but clearly has a strong association with neuroinvasive disease,
particularly mid-brain lesions. And most Powassan disease, particularly in
Minnesota, is likely the result of transmission from the blacklegged tick, and disease frequency of blacklegged tick associated disease is
increasing in Minnesota, as it is elsewhere. So this likely will result in
increased Powassan frequency. I think it’s also important that the application
of tick repellent appears to be more important in the prevention of Powassan in comparison
to regular tick checks, because of the time of transmission is likely
as short as 15 minutes. And at this point I’d be happy to
answer, I guess, a couple of questions. Joseph Breen: Great, thank you Aaron. This is Joe again. We actually don’t have questions
that have come in electronically. I’ll remind attendees that they can ask
questions online, and we’ll go through them after each speaker, as we have time. And then at the end we should have some time
available to go through remaining questions. So we’ve had a lot of people join,
actually, in the past 10 minutes or so. So Aaron, there aren’t any questions
right now, maybe we’ll just have to table that until the end when more people have joined
and had a chance to ask questions online. Thank you very much. Aaron DeVries: Thank you. Joseph Breen: So I’d like to move now to
Dr. Roger Nasci from the CDC who’s going to talk about the heartland virus. Roger S. Nasci: I’m online Joe,
waiting for my slides to come up. OK, there we go, very good. Thank you very much. What I’m going to do in the next 10 minutes
is give you a very brief introduction to a newly discovered pathogenic virus in the
United States, that all indications suggest that it’s a tick-borne zoonosis,
hence its inclusion in this symposium. One thing I want to emphasize is that the
credit for all the work I’m presenting goes to a very large group of people that I’m listing
as the Heartland Virus Investigation Team, that came together quickly
to craft all this together. The team consists of four CDC
branches representing two divisions; the Heartland Regional Medical Center
in Missouri-that was the clinic that treated the first patients and
hence the source of this virus name, the Missouri Department of Health
of course; collaborators with USDA; and with Missouri Western States for
many of the field studies that were done; and of course the patients, residents, and land owners that permitted
access to do these investigations. What I want to cover in the next few minutes is
some background on the discovery of the virus, some information about phleboviruses, and then
some of the continuing activities that are going on related to the epidemiology,
the transmission ecology, and the virology of this
newly detected pathogen. The discovery and the identification
of the Heartland virus is described in a 2012 publication in the New England Journal
of Medicine, the front page is shown here. It’s an elegant and a really thorough
piece of work that I can’t do justice to in about 10 minutes, but I will try and give
you a sense of some of the events that led up to the discovery of the virus, and some
of the technologies that were applied. In June of 2009, two adult males, ages 57
and 67 years old, were seen at hospitals in the northwest Missouri region. Both patients were relatively healthy
prior to this onset of illness, although one reported a five-year
history of type 2 diabetes. Both presented with similar symptoms,
including fever, fatigue, anorexia and diarrhea, and their laboratory tests
demonstrated abnormalities that included leukopenia and thrombocytopenia. Epidemiological investigations showed that both
were residents of northwest Missouri and lived in relatively rural areas
located north of Kansas City. And if you look at the larger map, the
location of their residences shown by the pins, and the general region is
shown in the inset map. Both were farmers, who spent
considerable time working outdoors. Both reported multiple tick exposures prior to
their illness, and neither had recent travel, vaccinations, or other illnesses that
could be attributed to this onset. Both patients, because of their continuing
illness, were admitted to hospitals and received doxycycline
for suspected ehrlichiosis, given the symptoms that they presented. However, neither of the patients
responded to the antibiotic therapy, and their parameters worsened for both of
the patients during their hospitalization. Thrombocytopenia became more significant and moderately elevated liver transaminases
developed during the course of their illness. Laboratory testing was negative for potential
causes of the disease including ehrlichiosis, and they were discharged after
10 to 12 days of hospitalization. One recovered completely within a month, and
the second patient reported persistent fatigue and symptoms over the course of a year. The clinic where they were hospitalized
was participating in a CDC study with the Rickettsial Zoonoses Branch in
a longstanding study of ehrlichiosis. So as part of the study, acute blood samples
from both patients were taken to the CDC to culture for Ehrlichia chaffeensis. Both of them showed cytopathic
effects on culture in DH82 cells, the typical cells that are
used to culture Ehrlichia. However, the morulae that are characteristic
of Ehrlichia were not seen in those cells. But similar cytopathic effects were seen when
the samples were inoculated into Vero E6 cells. A subsequent investigation with the CDC’s
Pathology Branch using electron microscopy identified Bunyavirus-like
particles shown here in the black and white insert in the upper right. And then follow on with the biopsy samples in
immunohistochemical staining showed the presence of the virus in bone marrow biopsies
for one of the patients shown in the color insert in the lower right. Both of these images are in the
manuscript that I cited earlier. Now in 2011, next generation sequencing was
used in the Viral Special Pathogens Branch to further characterize the virus,
and it was identified as a member of the genus Phlebovirus,
within the family Bunyaviridae. However it was noted that the sequence
was distinct from the SFTS phlebovirus. Transition now to a little
bit about phleboviruses. The novel Phlebovirus belongs to the virus
family Bunyaviridae, and Bunyaviridae consists of five genera: Hantavirus, Nairovirus,
Orthobunyavirus, Phlebovirus, and Tospovirus. Previously, all of the known human pathogens in
the Bunyaviridae in the United States belonged to the genera Hantavirus and Orthobunyavirus. Sin Nombre virus, which is very well-known
now as a member of Hantavirus genus, and La Crosse virus, Jamestown Canyon virus,
several other California serogroup viruses, and Cache Valley virus are members
of the genus Orthobunyavirus. But the Phlebovirus genus
contains more than 40 viruses, and several of the better known
pathogenic examples are shown here and include Rift Valley fever,
transmitted by mosquitoes, sand fly fever, transmitted by sand flies, as the name implies, and severe fever with thrombocytopenia
syndrome [SFTS] virus, recently discovered in China, that is a tick-borne virus. Now there are other tick-associated
Phleboviruses in the U.S.– Lone Star virus, Sunday Canyon virus, Rio Grande
virus-are viruses that have been identified, but they are not known to be pathogens. The Heartland virus is shown to
cluster in a clade with the SFTS virus. And that’s demonstrated in this phylogenetic
analysis, that was done in the McMullen paper, the initial paper I’m still discussing, showing
that Heartland virus is most closely related to SFTS virus, though it’s not a particularly
close relationship, as shown by the degree of difference in the amino
acids of the nucleoprotein and the polymerase proteins in this phylogram. I’d like to shift now to some of the follow
on studies that have been put in place to obtain more information
about Heartland virus. One of the first things that we worked on was
developing and optimizing diagnostic tests that would be needed to conduct the various
studies that were needed to follow on. These included developing an IgG ELISA,
validation that we can do a neutralization test, a plaque reduction neutralization test in
Vero E6 cells to provide confirmation tests, and virus-specific RTPCR assays to
detect and identify Heartland virus RNA, which has proven useful in detecting
virus in acute human samples, and then in some of the other
investigations I’ll be mentioning shortly. An epidemiology study was initiated to look for
additional cases and to get a better description of the clinical disease presentation, and it’s
now in place in six hospitals in Missouri. So far approximately 60 patients meeting
the case definition have been recruited and tested for Heartland and ehrlichiosis. A few suspect Heartland cases have
been identified, and we’re continuing to work them up, and several
ehrlichiosis cases have been found as well. The diagnostic test protocol that’s
been approved by the IRBs is available to patients outside of those six hospitals,
but because it’s still experimental, enrollment in this study is required,
so if there’s interest in doing this, contact your state health department. We’ve been in communication with the
state health departments about this study, and there should be an awareness of how to
contact folks here to get through to them. Heartland antibody serosurvey using
blood donors is starting this fall in the northwest Missouri region
to provide some additional evidence about the prevalence of infection
in this community. A number of field and laboratory
studies have been put in place to describe the Heartland
virus transmission cycle. In one study, blood samples were obtained from a
large number of vertebrates, mammals and birds, in the vicinity of the initial patients. Antibody against Heartland virus was found in
horses, dogs, and raccoons, and we’re following up by examining additional species, and
expanding the geographic range of the samples, to get a better picture of where this
virus is located and being transmitted. In one of the studies, the groups
also collected a large number of ticks in the vicinity of the case residences. The most commonly collected species was
the Lone Star tick, Amblyomma americanum, so this appears to be one virus or
one pathogen that is not associated with deer ticks in the U.S., at least so far. And in this study, Heartland virus was
isolated from Lone Star tick nymphs. This graphic shows the geographic
range roughly of the Lone Star tick, so this is the reason why we’re looking
more broadly at the geographic distribution of Heartland virus in the environment. The results from that tick study were just
published in the Journal of the American Society of Tropical Medicine and Hygiene this month. The map shows the location of the collection
sites with the virus positive sites circled in red, and the phylogram on the
right shows that the viruses isolated from the ticks are very similar
to those isolated from the human cases two years previously. And it also shows the clustering of that
virus with other tick-borne phleboviruses. We’re continuing to examine other ticks,
mosquitoes, and sand flies as potential vectors in the field, and we’re working on
projects to describe the vector competence of Lone Star ticks in the laboratory. Finally, what I want to point out is that we’ve
developed a web page with general information about Heartland virus, and as
more studies become published and more information is gathered about the
clinical presentation, the disease burden, and the transmission dynamics, we’ll be updating
this page as we can relate more information. And I’ll stop there and see
if there are any questions. Thank you very much. Joseph Breen: Great, thank you Roger. We don’t have any questions
yet from this presentation. We actually had one that came in a little bit
after we turned it over, regarding Powassan. Aaron, are you on the line? Aaron DeVries: Yes, I am. Joseph Breen: Maybe we’ll take this question
now, since it’s from your presentation. “It looked as if the brain
lesions were asymmetrical. Is that common with Powassan
neuroinvasive disease?” Aaron DeVries: Again, these are very
small numbers, both in our experience, and in a few other published instances,
yes, they’re often asymmetric. The images that I showed you of the
three cases were all asymmetric. However, I think that there were at least
one or two of them that did have involvement in both sides, but they often had more
involvement on one side compared to the other. Joseph Breen: OK great. Another question just came
in, again about Powassan. “Is there data on the seroprevalence
of Powassan?” Aaron DeVries: There are data as I showed
regarding seroprevalence in animals. I am not particularly aware, and
maybe others on the call are aware, of data looking at human seroprevalence. To my knowledge, I am not aware of
broad data looking at large populations of humans looking for prevalence. Joseph Breen: I’m not either actually. I have been more familiar with-I mean
there have been a number of studies looking at adult ticks, but not human seroprevalence. Well thank you Aaron, and thank
you Roger for your presentations. So we may collect questions as this
happened for the first presentations, but at this point I think it’s best we move
on to Dr. Peter Krauss from the Yale School of Medicine, who is going to tell us
a little bit about Borrelia miyamotoi. OK Peter, there you go. Peter Krauss: Thank you. Good afternoon. I’d like to thank you, Joe and
Ben, for inviting me to speak about human Borrelia miyamotoi infections. This is a recently discovered Borrelia. I’m going to present some slides initially on
the history of the discovery of this organism and then proceed through
to talk about epidemiology, clinical manifestations,
diagnosis, and treatment. Borrelia miyamotoi is a relapsing
fever spirochete first discovered in 1995 in Ixodid hard-bodied ticks. The first report of human Borrelia
miyamotoi infection was published more than a decade later in 2011. Two types of relapsing fever have been
recognized in humans for a long time, louse-borne relapsing fever,
and tick-borne relapsing fever, transmitted by soft-bodied ticks. Louse-borne relapsing fever is caused by
a single species, Borrelia recurrentis. It’s transmitted by the human
body louse from human to human. It can cause epidemics and death in
areas with crowding and poor sanitation. During World War I and World War
II, there were millions of cases, and actually estimated millions of deaths,
as a result of louse-borne relapsing fever. It does have a world-wide distribution, but
currently is endemic only in Ethiopia and Sudan. Tick-borne relapsing fever that is
transmitted by soft-bodied ticks is caused by more than ten species of Borrelia. It is transmitted by Argasid or
soft-bodied ticks to rodents and humans. It has a world-wide distribution, and it’s
relatively uncommon in the United States, with about 500 cases reported between 1990
and 2011, primarily in the Western states. Borrelia miyamotoi was first discovered
in 1995 by Fukunaga and colleagues. They described a new relapsing fever Borrelia
in Ixodes persulcatus ticks in Japan. They named it Borrelia miyamotoi after Kenji
Miyamoto, who’s a world-famous entomologist. This discovery greatly expanded the
potential range of relapsing fever infection from regions enzootic for soft-bodied ticks and
lice to regions enzootic for hard-bodied ticks. The genome of Borrelia miyamotoi has
been sequenced, and it clearly belongs to the relapsing fever group of Borrelia,
rather than the Lyme disease group of Borrelia. These are slides showing the organism,
this is the work of Dr. Alexander Platonov, and these are isolates from blood in patients. You can see the blue dots
are actually white cells, and there’s a contrast picture in the center. The ticks that transmit tick-borne
relapsing fever are shown here. Soft ticks transmit the majority, but the hard
ticks now, with the discovery of miyamotoi, the hard ticks are now transmitting one species. In 2001, Scholten, Fish and others
described Borrelia miyamotoi in I. scapularis ticks in Connecticut. This was the first discovery
of the organism outside Japan. And then in 2009, Barbour and Fish
described B. miyamotoi in hard-bodied ticks in white-footed mice, in eleven
northeastern and northern Midwestern states, and concluded that B. miyamotoi
will likely be present in ticks wherever B. burgdorferi is found. And this prediction has been confirmed in
the northeastern and western United States, central Europe, central Russia, and in Japan. The first report of Borrelia miyamotoi
infections in humans was in 2011. These were 46 cases from central Russia
that were confirmed by PCR and antibody, and there were a few blood-smear
positive findings in several of the cases. In 2013, there have been four reports so far of human Borrelia miyamotoi
infection that have been published. The first, Gugliotta and colleagues described
meningoencephalitis due to Borrelia miyamotoi in an 80-year-old, immunocompromised
patient from New Jersey. And then in the same issue of the New England
Journal our group described seroprevalence and clinical manifestations of Borrelia
miyamotoi infections in residences of southern New England and New York. Chowdri and colleagues then described
two cases of Borrelia miyamotoi presented as human granulocytic anaplasmosis
from Massachusetts and New Jersey. And Hoveus recently described in the
Lancet, a meningoencephalitis case due to Borrelia miyamotoi in a 70-year-old,
immunocompromised patient from the Netherlands. The ecology of Borrelia miyamotoi
is summarized here. It’s transmitted by hard-bodied ticks
from mammalian reservoir hosts to humans. The average B. miyamotoi infection rate in I. scapularis ticks is found to be 1.9% in the
Barbour study with a range of 1.1 to 10.5%. And that compares with a rate of, in ticks of
Borrelia burgdorferi of 19%, with a range of 2.6 to 35% in the Northeast and northern Midwest. Interestingly, Borrelia miyamotoi is transmitted
both transovarially, as well as transstadially, which means that it can be
transmitted not just by nymph and adult ticks, but by larval ticks as well. And this of course lengthens
the transmission season. The geographic distribution
of human cases is shown here. Cases have been described in the United
States so far in Massachusetts, New Jersey, New York and Rhode Island,
in Europe in the Netherlands, and in Russia, and in central Russia. I’m going to talk a little bit
more in detail about this study that we did following the initial
discovery of miyamotoi in humans. We decided to try to determine whether
this infection was occurring in humans in the United States, and we decided to test
archived sera for antibodies to this agent. The methods we used, we made a
recombinant miyamotoi antigen GLPQ which is glycerol-phosphodiester
phosphodiesterase. This is an enzyme found in relapsing fever
Borrelia, but not in Lyme disease Borrelia. So we developed GLPQ antigen-based ELISA
and Western Blot for a two-tiered approach, as is similar to that used
for Lyme disease testing. We tested three different groups of subjects. Healthy adults that participated in
serosurveys we do – we do annual serosurveys, we’ve been doing that for the
past 20 years at study sites, primarily Block Island, Rhode Island. Patients come in, they get free antibody
testing for Borrelia and Babesia. We then save their sera, we have an archive
now of about 10,000 sera over the years. And so we tested a subgroup of
those sera for Borrelia miyamotoi. We also had a group of patients
with acute Lyme disease, and a third group who had summertime febrile
viral-like illness, but not Lyme disease. I’m sorry. So the results were that sera from
18 of 875 subjects, that is 2%, were Borrelia miyamotoi seropositive. 6 of 584, 1% of healthy adults in
southern New England, were positive. And 9 of 277, that is 3.2% of patients who
had Lyme disease, and 3 of 14 patients, that is 21% who had summertime
viral-like illness. We’ve subsequently done more testing of sera
and that 21%, we’ve tested many more patients with summertime viral like illness,
and that percentage is down to 3%. So that was just due to the small number
of cases that we got that high percentage. So we also demonstrated or found seroconversion,
that is a four-fold rise in antibody titer from acute to convalescent sera in 3 patients, 2
of whom were co-infected with Borrelia miyamotoi and Lyme disease, and one with Borrelia
miyamotoi disease alone, or infection alone, all three had a viral-like illness with fever. The clinical manifestations when one
looks at the 46 cases from Russia and then the subsequent cases that have
been described in the United States, and the one case in the Netherlands, all present with a viral-like illness,
they virtually all had fever. The most common findings are fatigue,
headache, muscle aches, chills and nausea. But one can also see sweats, nausea, vomiting,
and cough, sore throat and adenopathy. Now 10% of the Russian patients
had relapsing fever. 10%, that is 5 of the 46 Russian
cases, had relapsing fever. And these were patients who
experienced one or two bouts of fever before seeing their physician. And then when they did see their physician, they
were either on their second or third episode of febrile illness, and they
were diagnosed and treated. The other 90% of cases, the first few, were
seen by their physician, they were diagnosed to have this disease, and were treated as
we’ll talk about later with either Ceftriaxone or doxycycline, and their fevers resolved. So we think that it’s likely
that if patients are not treated, the majority would develop relapsing fever. Again, only 10% of the Russian
cases, and those again were people who did not seek a physician’s help
with their first bout of fever. There was also noted in the Russian cases
that 10% had either erythema migrans rash or an erythema migrans-like rash, that is a rash that didn’t quite make the 5 centimeter diameter
requirement, but there were erythema migrans or erythema migrans-like rash noted. It wasn’t entirely clear, although there
was an attempt to rule out the possibility of co-infection with Lyme
disease with antibody testing. It wasn’t clear whether these
patients might have had co-infection with a Lyme Borrelia agent garinii or afzelii that might have accounted for
the erythema migrans rash. So I think rash is a possible finding
with miyamotoi, and possibly not. It will require further research
to determine that. Neurologic complications, as we’ve
seen, have been described in 2 patients, meningoencephalitis, and these were
in older, immunocompromised patients. It remains to be seen whether this will
be observed in immunocompetent patients. What I’m going to do now
in the next two slides is to compare the diagnosis of
Lyme disease with miyamotoi. Both of course rely in part
on epidemiologic information, the patient needs to have either travelled
or resided in an area that’s endemic for these diseases, or that
should be part of the diagnosis. One looks for typical symptoms
in these patients. A physical exam is extremely important for
Lyme disease because most of the cases are made on the basis of the erythema migrans rash,
whereas with miyamotoi, most of the cases, or perhaps none, present with a
rash and the illness again is sort of a nonspecific viral-like febrile illness
that can be mistaken for many other infections, and so laboratory testing
becomes really important. The laboratory diagnosis is based on, for
miyamotoi, I apologize for that plus sign being to the right there, but basically
blood smear is a useful diagnostic tool for miyamotoi, not really for Lyme disease. And the number of spirochetes
in the blood is both high and sustained with relapsing fever Borrelia. That appears to be true for miyamotoi as well,
though at least initial data would suggest that the spirochetemia is not as intense as
some of the other relapsing fever Borrelia. Nonetheless, one can visualize
the organism on blood smear, and that should be part of
the diagnostic workup. The sensitivity and specificity of
that test is of course not known. We know that with tick-borne relapsing fever,
non-Borrelia miyamotoi relapsing fever, as many as 50% of patients may
be positive on blood smear. Polymerase Chain Reaction, PCR, is useful for
diagnosing both diseases, especially miyamotoi. Small rodent inoculation and culture, of
course, are really confined to research labs, but one can take a tenth of a CC of
blood and inject it into a SCID mouse, and if one then sees it in the
mouse, you’ve made the diagnosis. One can culture the Lyme disease
Borrelia-miyamotoi has been successfully cultured, that is the Japanese
isolates-but so far isolates from the United States have
not been successfully cultured. And antibody detection is useful
for diagnosis of both infections. This shows a slide of a thin blood smear
of a patient with Borrelia hermsii, and you see the red erythrocytes and then
numerous, abundant spirochetes on this slide. And this is a very intense
spirochetemia that one wouldn’t always see with hermsii, or certainly miyamotoi. But usually a lot fewer spirochetes
than this, but it does demonstrate that they can be visualized
on a peripheral blood smear. The treatment of Borrelia
miyamotoi is doxycycline, it’s the same as Lyme disease essentially,
doxycycline, 100mg every twelve hours, by mouth for 14 days, Ceftriaxone,
2g once a day, IV, for 14 days. And these were the antibiotics used in the
Russian cases, and were quite successful in clearing the infection
and resolving symptoms. Now in the Gugliotta case, they
started treatment with Ceftriaxone, and the patient had a Jarisch-Herxheimer
reaction and they switched to penicillin G, 24 million units, IV, once a day
for 30 days, and that was effective. So in conclusion, Borrelia miyamotoi
is a newly discovered infection, and its health burden remains to be determined. I did want to thank the many
co-investigators who’ve been involved with our work and there are many of them. And certainly our funding sources,
the National Institutes of Health, the Centers for Disease Control and Prevention,
and the Gordon and Llura Gund Foundation. Thanks very much. Joseph Breen: Great. Thank you very much Peter. There are a couple questions that came in. I think we’ll just take one now,
because we’re a little bit off time. “Have any studies described
transmission of infections with tick-attachment time
for Borrelia miyamotoi?” Peter Krauss: No. Actually, I should revise that. In the Russian studies, there
was information on that. Actually, in comparison with other
tick-transmitted agents -Basically, in those cases there was a history of
tick bites within the previous week, but really there was no data, really,
to determine how long the tick needed to be attached before transmission occurred. Joseph Breen: Okay thanks. Hopefully we’ll have time at the end to get
to a few more of the questions that came in. Thank you very much Peter. Peter Krauss: Thank you. Joseph Breen: So next I’d like to introduce
Dr. Jennifer McQuiston from the CDC, who’s going to talk about
Ehrlichia muris-like organisms. Jennifer McQuiston: Good afternoon. While we’re waiting for the
slides to be pulled up, I would just like to say
thank you for having me on. And like Dr. Nasci, I would just say that none of the data I’m presenting
here today is really my data. It’s really information that has been provided
by other people or through published literature, so we would just like to thank
them for their assistance in pulling this presentation together. So ehrlichiosis and anaplasmosis are both
reportable diseases in the United States, and you’ve already seen a map that
shows their relative distribution. But what I would like to point out here is
that for the United States during 2008 to 2012, these are the parts of the country
that really had the most cases reported for ehrlichiosis and anaplasmosis. For Ehrlichia, we are talking the southern
mid-western to east coast United States, and for anaplasmosis, it’s going to be
the northeast and the upper Midwest. This graph shows the number of reported cases
of ehrlichiosis and anaplasmosis during 2008 to 2012, and you can see that we have between
3,000 and 4,000 cases reported during 2011 and 2012, if you look at all
of these numbers combined. But relatively speaking, we have more reports of Anaplasma phagocytophilum
than we do ehrlichiosis cases. In 2009, we had an unusual
occurrence, in that a confirmed case of ehrlichiosis was actually found in
Wisconsin, which is in a part of the country which we have not frequently seen
confirmed ehrlichiosis in residents who have not travelled out of state. This particular patient had onset
in June, he was 51-years-old, and he presented with a fairly
typical tick-borne-like illness, with fever, headache, and myalgias. And he was suspected for tick-borne illness. Acute blood samples were sent
to Mayo Lab for PCR testing. He also experienced lymphopenia,
thrombocytopenia, and elevated liver enzymes which is quite a typical profile for
suspected tick-borne illness patients. Mayo used a multiplex PCR test,
which differentiates ehrlichiosis, particularly Ehrlichia ewingii
and Ehrlichia chaffeensis from Anaplasma phagocytophilum,
based on melting point curves. And what they found in this patient was a
completely unexpected melting point curve that seemed different than known Ehrlichia
and Anaplasma species at the time. And they sent a sample to CDC for
confirmation, and sequence analysis confirmed that there was a novel Ehrlichia
species causing this patient’s infection that was similar to Ehrlichia muris. In this talk, I will refer to
the agent as E. muris-like, as the species determinations have
not yet been made for this organism. This is a graph that shows Mayo’s multiplex
PCR assay and the melting point curves, and you can see that the EML agent falls
somewhere between Ehrlichia ewingii and Ehrlichia chaffeensis, in terms
of its melting peak [temperature]. After the index case was identified, a
little more attention began to be paid, and Mayo subsequently identified four
more cases of this EML agent infection in two more residents from Wisconsin and one
more resident from Minnesota during 2009. Like the index case, they all had fever,
fatigue, headache, and lymphopenia. If you combine them all together,
three of the four had thrombocytopenia, and one had elevated liver enzymes. Interestingly, two were prior
transplant recipients, and they were on immunosuppressive
therapy at the time of their infection. All patients reported exposure to ticks and
wooded areas and you can see a picture here of one of the case patient’s homes. It looks a lot like that picture
you saw in an earlier talk of typical Ixodes scapularis
habitat for the upper Midwest. In addition, out of the three patients
who had sera that were actually tested on commercial ehrlichiosis
and anaplasmosis assays, 3 out of 3 patients showed stronger
reactions to Ehrlichia chaffeensis than to Anaplasma phagocytophilum. Sequence analysis showed a 98%
sequence similarity to E. muris, and at the top of this picture you can kind of
see where this new Wisconsin species fell out. This phylogeny was based
on 16S ribosomal RNA genes and the GroEL heat-shock
protein, an operon gene. From 2009 to 2012 – I’m sorry
this is cut off at the top – but there have been 22 EML
cases diagnosed in Wisconsin. On this slide, the cases are mapped
by county of residence rather than exposure, with the exception of the stars. Those represent EML cases diagnosed
in out-of-state residences, and the stars are in the suspected county
of exposure for those particular patients. In addition, from 2009 to 2012,
the EML agent has been identified in 20 case patients from Minnesota. And you can see the distribution here really
closely follows the map that Aaron showed of Ixodes scapularis-borne
infections in Minnesota-sort of that wooded biosphere within Minnesota. This particular map shows cases based on county of possible tick exposure,
rather than county of residence. And from 2009 to now 2013, so this is adding a
year onto the data for the state-specific data that I just showed you, Mayo has collected
information on 63 cases of the EML agent. All of these are PCR positive. It includes 58 cases in Minnesota and Wisconsin
residents, and 5 travel acquired cases. Some of these cases represent the
ones that were reported in Minnesota and Wisconsin’s general summary,
but there are some additional cases in 2013 that represent new cases. 63% of these cases were male,
the mean was 60 years of age, and they ranged from 23 to 87 years old. 90% presented with fever, and a majority
had headache and thrombocytopenia, and lymphopenia was also reported in 57%. The majority of cases were not
hospitalized, about 23% were. All that received doxycycline treatments
were responsive to that antibiotic. Interestingly, Mayo has also done extensive
testing of specimens from other states, and among 11,000 specimens tested from
states other than Wisconsin and Minnesota, they’ve not found evidence of EML among any
of those except in travel acquired cases. I do want to just – again, I apologize this
slide got shifted when it was uploaded – but diagnostic testing is a bit of a
hot mess for the EML agent right now. In serology-based surveillance, it’s difficult
to interpret in Minnesota and Wisconsin. We know that EML cases cross react with
commercial Ehrlichia chaffeensis assays, and evidence says that they do not react
well on Anaplasma phagocytophilum assays, although I think most physicians in
Minnesota and Wisconsin currently rely more on anaplasmosis testing than
they do ehrlichiosis. But for those patients that are tested for
ehrlichiosis, and have positive titers, these may represent EML cases, even though
the only commercially available assay is to E. chaffeensis right now. Because of this difficulty right
now, PCR is the recommended way to diagnose EML infection
in Minnesota and Wisconsin. And if the serology is being used to diagnose
suspected tick-borne illness in these states, we recommend that providers request both
anaplasmosis and ehrlichiosis serology. And I’ll also say that IFA testing, using
the EML antigen is in early development, and I don’t anticipate that being
something that’s rolled out any time soon. Through initial published findings, DNA
from the EML agent has been detected in 3% of Ixodes scapularis nymphs and adult ticks
from Minnesota, and also in nymphal pools of ticks from Wisconsin during 2009. And of other ticks that have
been tested to date, EML agent has not been found
in any other tick species. In addition, a retrospective look at Ixodes
scapularis ticks collected from the 1990s in Wisconsin showed that 1%
contained DNA from the EML agent. And there’s also been a single
case report of E. muris infection, which is assumed to be the EML
organism, in a dog from Minnesota. From Sandor Karpathy and the CDC,
an environmental ecology group here, he’s provided some of the preliminary
data from some of the laboratory studies that they’re doing with the EML agent, and we can report that it is
highly pathogenic in C57/B6 mice. 90% mortality is observed
with 103 genomic copies and 40% mortality with 102 genomic copies. In addition, when you feed Ixodes
scapularis nymphs on EML-infected mice, those nymphs retain infection after molting
and can go on and transmit EML to naïve mice, suggesting that it is a competent vector. Tick transmission results in
60 to 70% mortality in mice, and it looks like that mortality occurs 10
to 13 days post-exposure, which is consistent with some of our understanding
for other Ehrlichial pathogens. There is also evidence that
co-feeding transmissions may occur, meaning that if you feed infected
ticks next to uninfected ticks, the infection can pass to those other ticks. And then preliminary data on DNA
samples that have been collected suggest that DNA is highly conserved among all samples
tested to date, but studies are ongoing. And these studies will help inform decisions
whether this represents a new species or not. And then finally, I’m happy
to answer any questions. This is my contact information, and as I
mentioned strong acknowledgment belongs to Bobbi Pritt at Mayo, who was the scientist
and researcher who found the first EML case and was the primary author on the New England
Journal paper reporting these first infections. Diep Johnson and Dave Neitzel from the
Wisconsin and Minnesota Departments of Health, and then CDC staff William Nicholson,
Marina Eremeeva, Sandor Karpathy, Cecilia Kato, and Scott Dahlgren. Thank you, I’m happy to take questions. Joseph Breen: Great. Thank you, Jennifer. There is a question, actually. I’ll read it for you. “Does the data on lab mice
suggest any morbidity or mortality in natural rodent populations
attributable to this bacterium?” Jennifer McQuiston: So by natural rodent
populations I’m presuming they mean Peromyscus species or am I misinterpreting the question? Joseph Breen: I guess we’ll
have to interpret it that way. Jennifer McQuiston: I think
right now our only experience is with these laboratory mice,
and it’s highly pathogenic. But I think in the wild rodent species
[that] we would likely expect to be serving as possible reservoirs, I don’t think that
we have any data yet to inform that answer. Joseph Breen: Great. Okay, thank you. Thank you for your presentation. That was the question. More may trickle in, so we may
come back, actually, to you. So at this point I’d like to move forward to our
next presentation, which Dr. Barbara Herwaldt, also from the CDC, who’s going
to tell us about Babesia microti. Barbara Herwaldt: Thank you very much. As my slides are being uploaded,
I wanted to thank the organizers for inviting me; this is a real privilege. And let’s see here. We can get to the first slide
– should I back it up, Joe? Joseph Breen: Why don’t you? Barbara Herwaldt: Okay. I’ll just give folks a heads up that, as
Jennifer mentioned with her presentation, some of [my slides] might have gotten
messed up when they got uploaded. Let’s see here. Not sure if I’m… We can get back to the beginning… Okay; there we go! Sorry about that, folks. I’m going to touch on principles
and perspectives. This is not going to be a
primer about babesiosis. I’m going to touch on multiple topics. In the United States, (again
this is an example of a slide in which the formatting got a bit messed up,
but I think we’ll be able to read through it), this is a potentially life-threatening zoonosis
caused by intraerythrocytic Babesia parasites. And the predominant etiologic
agent is Babesia microti. (I’ll be mentioning other agents later.) It’s transmitted by ticks, but also
is transmissible via transfusion, and occasionally via congenital routes. And tick-borne transmission
is seasonal and regional. Babesia microti tick-borne transmission
is occurring in evolving foci, and I want to underscore
“evolving”: it’s changing over time. In the Northeast, especially parts
of New England-New Jersey, New York, also Pennsylvania more recently,
and perhaps some other locales – and parts of the upper Midwest –
parts of Minnesota and Wisconsin. And a lot of us take some
of these areas for granted. But it’s been over the relatively recent past
that some of these states have been added to the map, so to speak, so again I want
to emphasize the dynamic nature of this. And, in fact, in our next slide, one of
the purposes is to emphasize that the risk for zoonotic transmission for Babesia
microti (and also other agents) is dynamic in time and place. And we have to keep in mind the various
factors: the parasites – and, by the way, I’m referring to it as Babesia microti
as if it’s one organism, one species, [whereas] there may be strain
differences that are relevant. But I’m going to oversimplify a
bit in this talk – and, of course, the tick vectors are important,
as are reservoir hosts. The first convincingly demonstrated
U.S. case of babesiosis– believe it or not– was documented
in California. It occurred in 1966. Of course, there may have been many other
cases in people before that in the U.S. But the first convincingly demonstrated
case was in the western U.S., and even now we’re not sure
what the species was. The first reported case in the Northeast
occurred in 1969 on Nantucket Island, and that case was caused by Babesia microti. And, by the way, whenever I mention
years, it’s the year of occurrence. In January 2011, babesiosis became nationally
notifiable, and most of the people participating in this symposium know the distinction
between being notifiable and being reportable. And babesiosis is reportable in
21 states (that is, as of 2012). And, in round numbers, CDC has been
notified of about a thousand cases per year since it became nationally notifiable
[including cases from the states in which babesiosis is a reportable disease]. This is including confirmed and probable cases. And the fact that in 2012 the number was
slightly lower [than in 2011] does not in any way, of course, mean
that babesiosis is going away. Not only is there underreporting,
but there can be real differences, as folks in this symposium know, from
year to year, in terms of tick populations and all the many different factors that
contribute to whether people become infected, let alone have their cases
diagnosed and reported. In terms of clinical aspects, again
focusing on principles and perspectives, the infection can range from
asymptomatic to severe. And both ends of the spectrum
are very important. I’ll mention a bit later why the
asymptomatic end of the spectrum is important. [As for] the severe end of the spectrum: I
don’t have time to go into detail today in terms of the complications; but,
again, as I already mentioned, this can be a life-threatening disease. But, regardless of how severe a case is,
the manifestations always are nonspecific. There are no pathognomonic
signs on physical examination. Nonspecific viral-like symptoms
are common, such as fever, and then on routine laboratory examinations,
hemolytic anemia, thrombocytopenia, etc. But people can be afebrile,
and some of the manifestations, such as hemolytic anemia,
sometimes are relatively subtle. But because the manifestations
always are nonspecific, diagnostic testing always is required. And the symptoms usually develop within several
weeks, sometimes months, of the exposure. And when I say sometimes months, that
can be because of delays in diagnosis. It also can be because of host factors. For example, someone might have asymptomatic
infection, and then have the spleen removed and become symptomatic at that point in time. Risk factors for severe babesiosis
include asplenia, advanced age, and the other age extreme,
prematurity, and various other causes of what I am loosely referring
to here as immune dysfunction, (again I’m oversimplifying matters). To emphasize the importance of the spleen, I just want to have this slide
to underscore it in your mind. It’s incredibly important
to have splenic function, and people who do not have a spleen
are at particularly high risk for (as I’ve said repeatedly) a
potentially life-threatening infection. I’m not going to talk about
treatment aspects right now. But I do want to underscore that
this is a treatable infection. But if it’s not caught soon enough, or if
there are complications-multi-organ system dysfunction, etc.- the person can die. Now, tick-borne transmission can
lead to transmission via transfusion. We’ve already talked about the fact that,
certainly there have been thousands of cases, even ignoring at the moment the fact that
babesiosis was not a notifiable disease until recently, it’s very clear
that there have been thousands. Probably nowhere near the numbers of cases
of Lyme disease, and I don’t have time to get into the many differences between
babesiosis and Lyme disease; there are similarities but also differences. But when we think of sort of the log scale for
[numbers of cases of] tick-borne transmission, we’ll have ~103 cases overall,
meaning thousands. [Regarding] transmission via transfusion,
more than 160 cases have been documented, and that’s over time; the first
documented case was in 1979. But transmission via transfusion, (which I
don’t have time to talk about in detail today), is of great concern in terms
of blood safety issues. But why can tick-borne transmission
lead to transmission via transfusion? Well, even persons who have
asymptomatic infection or whose symptoms resolve may have low-level,
subpatent parasitemia (meaning not demonstrable on blood-smear exam) for weeks to
months, even longer than a year. How long? We don’t know how long, and
we don’t know how often people who seem to be otherwise healthy have
persistent, relatively chronic infection. We don’t think it’s lifelong infection. But infection has been documented in some
people for, as I already said, more than a year, and maybe even more than two or three years. And, this subpatent parasitemia (low-level, not
demonstrable by blood smear exam) sets the stage for transmission via transfusion, and
protracted infection sets the stage for year-round transmission. So you can have a transfusion-associated
case even, for example, in winter months. And people can meet all the current criteria for donating blood despite
being infected and infective. To date, no Babesia donor
screening test has been licensed. But there are many investigators and many
agencies who are working on developing and evaluating donor screening tests. As some of you know, in some of your states
in fact, donor screening is being done under FDA-approved IND protocols. I want to briefly touch on principles
related to laboratory evidence of infections. First of all, thinking about people – not
blood donors – people who are symptomatic, who have acute cases of infection. In those people, Babesia parasites typically can
be detected on careful review of blood smears. And I underscore the word “careful,” and also
the need for someone experienced who’s looking at the blood smear, and sometimes more than
one blood smear may need to be examined. And so, if the diagnosis is being
considered, manual (or non-automated) review of blood smears should be requested explicitly. And, frankly, often the diagnosis is
serendipitous, even in people who are very sick, and even in people who have
high levels of parasitemia. Now, blood smear exam (parasitologic diagnosis): blood smear is a classic means
of parasitologic diagnosis. Of course, it’s important to
differentiate from malaria, and also to differentiate intraerythrocytic
structures from Howell-Jolly bodies that you might see in someone
who’s had the spleen removed, or also to differentiate
structures from artifact. So it’s not always easy to
examine a blood smear. Animal inoculations and other means of classic
parasitologic diagnosis are available just in reference laboratories,
for example, at the CDC. Some of you might not have realized that there is no culture technique
available for Babesia microti. There is [a culture technique] for some of the other Babesia species,
but not for Babesia microti. And I’m lumping molecular techniques
for now under parasitologic diagnosis. And when I speak of PCR, I’m just doing it in
very broad strokes; I’m not getting into any of the important differences
and the new advances with PCR. Serodiagnosis can provide supportive
evidence that someone has babesiosis, and there are various serologic techniques. (I’m not talking right now
about donor screening.) IFA (indirect fluorescent antibody testing) has
been the gold standard for diagnostic testing over time, and there are different
assays for different species. Immunoblot: there is a B.
microti immunoblot available, not through CDC, but through
a commercial source. And various agencies are working on
developing and evaluating EIA tests for donor screening as well
as diagnostic purposes. I want to underscore the general point of
considering the diagnosis of babesiosis, if indicated, particularly, but not only, in
people who have fever and/or hemolytic anemia and thrombocytopenia, but also to question the
diagnosis, if it doesn’t seem to make sense, or if things just don’t quite add up. But we’re here to help. And, of course, you folks
in state health departments and local health departments also often
have experts who are very experienced with the diagnosis of babesiosis. You’re also probably very familiar with DPDx, which is a telediagnostic
service that’s offered by CDC. And we’re very happy to help do various types
of testing for babesiosis and also to look at blood smears and to differentiate
Babesia from malaria. Now for diagnostics testing: again,
I want to underscore big picture. Diagnostic testing is very
different from donor screening. The point of this talk is not to
get into what donor screening tests or approaches should be used but, again,
just to underscore the differences. And that, again, if we think about
lab approaches, parasitologic or molecular techniques, of course, are to
detect the parasite or DNA; and that’s great, because that would determine if
someone has active infection. But, even PCR (again this is in broad
strokes) is not sufficiently sensitive to reliably detect low-level infection. A positive result from a good lab is
great; but, for example, in a blood donor, a negative PCR result would not exclude the
possibility of infection or infectivity. Serologic techniques– again in broad strokes–
highly sensitive, except early on in infection, but no techniques that, at least at the moment,
reliably distinguish active from past infection. I also want to touch briefly on the fact that
babesiosis can be caused by novel parasites that are not detectable by serologic
or molecular tests for Babesia microti. And since the 1990s – Joseph Breen: Barbara? Barbara, I’m sorry, I have to interject,
we’re going to run out of time here shortly, can you bring it to a [conclusion]…? Barbara Herwaldt: Yes. Joseph Breen: Okay, thank you. Barbara Herwaldt: Sporadic cases
have been caused by various agents, including Babesia duncani in several
western states, B. divergens-like agents in various regions (it’s not B. divergens sensu
stricto), and an unnamed agent in Tennessee. And we don’t know much about these organisms. B. duncani, for example, is morphologically
indistinguishable from B. microti, but not detectable by serologic or
molecular techniques [for B. microti]. And there have been less
than ten B. duncani cases that have been parasitologically confirmed. They’re very important cases. But it’s important to emphasize
that the threshold for considering an IFA result
positive has not been well-established, given that relatively few cases have
been parasitologically confirmed. And so much remains unknown about [B. duncani]. But be cautious
when interpreting lab results. And I just wanted to close with mentioning the
fact that, for transfusion-associated cases, most have been causes by B. microti; three,
in fact, have been caused by B. duncani. Most have been associated with
red cell components [and] several with whole blood-derived platelets. And, again, the incubation period
can range from weeks to months. And I already mentioned–
I’m closing with this– that because of the potential for
protracted infection, and also donor travel and interregional shipments
and distributions of blood, you can have transmission anytime, anywhere. But that’s not to imply equal risk. So thank you very much. Joseph Breen: Great, thank you Barbara. Appreciate that. So, there aren’t any questions, actually,
for this presentation, specifically, we do have a number of questions that
are collecting, but at this point I would like to our final speaker of the day,
and that is Anna Perea from the CDC, who’s going to tell us about
tick-borne disease prevention resources. Here you go. Anna Perea: Great. So I’m Anna Perea and I work in the
Bacterial Diseases Branch of the Division of Vector Borne Diseases, and today
I’d like to talk about the educational and communication materials that CDC has
made available for health care providers, public health practitioners,
and the general public. CDC felt that there was a need to
provide tick-borne disease resources to support health care providers,
including physicians, physician assistants, nurse
practitioners, and nurses. We began developing materials for these
groups based on surveys of provider practices, common questions that we received from
health departments and health care providers, and direct input that we began
receiving at conferences. These different types of
information have proved valuable in developing practical, educational materials. The most comprehensive tool we’ve
developed is the Tick-borne Diseases of the United States Reference Guide. It contains a wealth of general information
about the major tick-borne diseases you’d find in the U.S. Each disease section contains
information about incubation period, signs and symptoms, general lab findings, lab
confirmation, treatment, selected references, and key caveats about each disease. This is a really great tool, and
we think you’ll be pleased with it. The other thing that we’ve
tried to do is to leave space where local health departments can
put their own contact information. Currently, the manual is only available
for downloading or printing from the web, but we hope to have it available for order
online in time for the 2014 tick season. So please check back to the website frequently, and we will hopefully have
that available by spring. Another item we have developed
in response to questions about serology are Lyme disease
testing flow charts. The chart on the left describes
the step-by-step process involved in two-tiered testing for Lyme disease. The second chart describes the
effect of prior probability of false positives in non-endemic areas. These are to be used primarily by the clinician
to aid their own understanding of the concepts, but can also be used as a handout to
patients who need in-depth information. They’re available at the CDC website
for download at the URL shown here. CDC and Medscape currently collaborate to
develop expert commentary videos at no cost. To date, they’ve made over 200 videos together. Our branch has participated in this
program several times over the past year. The first video explains the proper use
of two-tiered testing of Lyme disease. The second video describes the appropriate,
limited use of PCR testing for Lyme disease. Most recently, we developed a video
describing the differences and similarities between Southern Tick-Associated Rash
Illness, or STARI, and Lyme disease. Other groups within our division
have produced videos on repellent use and Rocky Mountain spotted fever,
which have come out in previous years. Additionally, the Rickettsial Zoonoses
Branch recently just produced a video on tick-borne Rickettsial
infections among travelers to Africa. Overall, the amount of information
gained from these videos is more than worth the minute it takes to sign
up for a free, Medscape login account, so we encourage you to give this tool a try. Additionally, we’ve been
developing and refining Lyme disease and tick-borne disease webinars,
which are available for credit. The Clinician Outreach and
Communication Activity call, or COCA call, highlights the epidemiology and
clinical features of Lyme disease. Credits are available through
the end of the calendar year for physicians, nurses, and health educators. And most importantly, this particular
educational program is free. Next, for the mobile listeners out there,
we’ve got a podcast that talks about educating and talking to patients about tick bite
prevention, and I know this is kind of a weird conversation for health care
providers, so this might give them some tips for talking about prevention, and at two
minutes, it’s a short, sweet, little tool. Finally, I’d like to talk for a few minutes
about materials for the general public. We’ve developed a number of resources
for public health practitioners to distribute to the general public. These are found on the CDC Lyme disease site. Today I’ll focus on the items available in
the Lyme Disease Communications Toolkit. We do encourage you to explore the
website, as it’s constantly being upgraded with new frequently asked questions,
statistics, Lyme disease stories, and more. One quick note – If you’d like to
be notified of changes to the site, click the “Update” link circled in
blue above, and then you can sign up for GovDelivery services
for Lyme and other diseases. So that way you’ll be notified
when new things come out. One of our most comprehensive printed materials
is the newly updated Lyme disease brochure called “Lyme disease: What you need to know.” These can be viewed online, saved or printed
as a PDF, or ordered in bulk from the website. Next, we have a multitude of fact
sheets which provide similar information but are targeted to specific groups. All are available in Spanish and English,
and some are available in Portuguese. We’ve also got three items targeted to children. The first, bookmarks, have
been a spectacular hit. These can be ordered directly from the website. The other items are designed to be
printed and used by health teachers, camp counselors or others as needed. We’ve got a crossword puzzle, and as you
can see we also have a comic encouraging, especially young boys who
don’t like to shower, to do so. We’ve got the Lyme disease
communications trail sign. They’re available for order, or you can
print a PDF directly to post at a trail head. Many parks and rec departments
have ordered these. And finally, before we wrap up, I’d like
to highlight a service that CDC provides, which enables you or your partners
to directly mirror CDC’s web content. Each webpage from CDC.gov can be syndicated,
or made available to outside entities who’d like to share the latest
content with their readers. Most of the Lyme content is already available,
but if it’s not, it can be requested. And one benefit of using syndicated
content includes having accurate, up-to-date information that mirrors CDC content. Another benefit is that updates from CDC
automatically push to the syndicated site. So when we update our information,
yours is updated effortlessly. Again, you can do this with any disease
the CDC has web pages for, not just Lyme. So I’d like to thank you at this
point and if you have questions about the materials presented
here, you can contact CDC-Info or use the email that Joe had posted earlier. Thank you. Joe Breen: Great, thanks Anna. I’m going to put that slide
up with the email [addresses]. So we’re running out of time, so
there are a number of questions, and we’ll respond to those questions,
but it will have to be after this talk. And if you have follow-up questions that
weren’t addressed, you can also send them to the address here [email protected] I want to mention that this entire
presentation will be archived and available, but there will be a delay because
transcription needs to be performed and checked. So you can check the CDC website for
the Division of Vector Borne Diseases and it will also be available
at the NIAID website as soon as that transcription and
services are available. So thank you everybody for your
presentations and for your participation today. And we’ve reached the bottom of
the hour, so I believe I’ll need to close and thank everyone again. Coordinator: Thanks everybody for
participating in today’s conference. You may all disconnect at this time.


4 thoughts on “New & Emerging Tickborne diseases: Agents, clinical features & surveillance

  1. Hi just intrigued on the USA map how these tick borne diseases are on the right hand side of USA may it be that the salt off the California side and the charges coming off that ocean which form in the air kill these diseases seems kind of logical and that when the air blows on shore in the right hand side it is the opposite charged air which the ticks can survive it is fact that air has charges and not just like a magnet but chaotic spherical ac dc types

  2. As a teenager, I'm more aware than the normal and I don't know why not much people listen to this! I hope I get to work at the CDC as a public health program specialist. I enjoy the shared information from you guys,Thank You!

  3. These pathogens, including Babeosis should NEVER be transmitted via transfusion. The big problem is our blood supply is NOT tested for these pathogens. Shame, shame, shame. 12-28 days of treatment cures. BOLOGNA!!!!! I am a Lyme victim. Probably born with it, BUT NO DIAGNOSIS, until age 60. I responded very well to IV ABX until it treatment was jerked ABOUT 7 YEARS later. With treaMtent jerked, I have gone downhill since 2009. All this fancy testing, but NO LISTENING to victims. HOW STUPID AND CRUEL!!!!!!!!!!!!! Hope all of these presenters get Lyme and have to live with it for decades without treatment, or just 14-28 days of treatment. CRIMINALS!!!!!!!!!!

  4. Lyme Disease and tick borne diseases are very serious and I should know as I reside in Old Lyme Connecticut. Thank you for alerting us all about Borrelia miyamotoi, Powassan virus and Ehrlichia. Not many people know how serious these pathogens can be and are a life-long sometimes life threatening issue.

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