It is now my absolute honor, privilege, joy, and opportunity to introduce to all of you Dr. Elizabeth L. Maloney.
Dr. Maloney is a Minnesota family physician, policy consultant, and medical educator.
In 2021, she was appointed to the Federal Tick-Borne Disease Working Group, a federal advisory committee on tick-borne illnesses.
She served on several tick-borne disease working group subcommittees prior to her appointment from 2018 to 2020.
She has also provided testimony regarding tick-borne disease to several state legislative committees and Canada Health.
Since 2007, Dr. Maloney has been providing comprehensive, evidence-based, accredited continuing medical education courses.
Further, she has authored several peer-reviewed papers, including grade-based treatment guidelines on Lyme disease.
She also speaks to the general public on the need to consistently use effective tick-layer prevention strategies.
Dr. Maloney, thank you so much for being here.
Thank you. I want to thank the committee for inviting me to participate in this very wonderful event.
I have no relationship with commercial interests.
In my talk today, we'll highlight some of the nuances of the clinically available tests.
So these are the tests that you're ordering in your clinics.
So it's going to focus on serology because that's what's available right now.
Before I do that, though, I'm going to review some basic principles and concepts of laboratory medicine
because I want to make sure we're all on the same page as we move forward to talk about serology.
and so testing is not to be put in a vacuum it's part of the diagnostic process and the first part
of that process is obtaining a history and as you heard from Dr. Alcott there's a lot of questions
in history to be obtained if you're thinking that someone might have Lyme disease and with a good
history we can eliminate many potential diagnoses and as we work through our list and
then we move to clinical exam. An exam will eliminate even more, and so you're at that
phase where you are able to have a clinical impression. Now, clinical impressions and
final diagnoses are often the same, but in situations where there's still some uncertainty,
you can move to use testing to see if you can get to that final diagnosis.
I want to point out that we have surveyed, I'm not being personally, but there have been surveys of clinicians asking them to rank the relative value of history, exam, and testing, and they did it in that order.
And I think that's something to bear in mind when those three are not aligned.
So the goal of diagnostic testing is to help clarify a clinical situation.
situation. It's going to do that by providing additional information regarding potential
diagnoses. So diagnostic testing is diagnosis-directed. It is not a fishing expedition.
So in the case of Lyme disease, might diagnostic testing help when there's a tick bite or an EM
rash for someone with arthritis who's been exposed to ticks? But how about people in
endemic areas who have a new second degree or third degree AV block, someone who has cognitive
problems and peripheral nervous system findings. Or how about the people with PLD, persistent Lyme
disease? These are the people that have been treated and remain ill. So these would be similar
to Dr. Ock's would testing help would work out that way. When you're selecting a test,
is you want to look at various factors.
So the first is, how is the test performed?
Is it accurate?
Is it precise?
Is it available?
Is it going to be a lengthy procedure?
Is it a simple blood draw?
How costly is it for the patient?
And then how are you going to use the results?
Because that matters.
So you can describe a test by various characteristics,
and two of them are accuracy and precision.
So, accuracy gives results that are true.
So, a positive test means that the patient has the disease, and a negative test means
that they do not.
Precision is not interested in disease state.
They just want to know if the results are about the same when you repeat the test on
the same.
Now, the targets here are trying to demonstrate combinations of accuracy and precision.
So we would want all of our disease patients to be within the target, and we would
want the people who are disease-negative to be outside.
They should all cluster because that represents that they're good on repeat
testing, that they are all the same.
So in that first, you see that there's great precision.
The test results have clustered, but they're completely wrong.
And so you have a precise but inaccurate.
We flip it around in the middle, so now all the results are correct, but they're scattered, so they're very imprecise.
And it makes you wonder how long it's going to take to have one of those results fall outside of the area where it should be.
And then the last, of course, is the ideal test in terms of accuracy and precision.
But I think clinicians are very interested in two other characteristics, and this is sensitivity and specificity.
and they actually are the determinants of whether a test is accurate.
So a sensitive test is able to identify everyone who has the illness.
A specific test is available to identify those who don't,
and both are cutoff dependent,
and you can think of them as opposite ends of a teeter-totter,
and the fulcrum is the cutoff value.
So let me show you what I mean.
If we have a test where results can be anywhere from 0 to 100, and we set the cutoff at 50, it looks like it's favoring specificity over sensitivity.
But if I shift that fulcrum down to 30, I'm going to have more positive results.
So I'm going to raise sensitivity.
But unfortunately, some of those positives are false positives.
And so specificity goes down.
If I move that fulcrum in a different direction, I am going to get fewer positives.
So specificity is gonna go up
because there'll be fewer false positives,
but I'm going to increase false negatives
and so sensitivity goes down.
So it really does matter where that cutoff is.
Now, this two by two table shows us disease state
in columns, positive and then negative.
And in the rows, you're seeing test results.
And so the boxes are labeled
based on whether the test results actually agree
with the disease state.
And we can then plug that into equations
for sensitivity and specificity.
Sometimes people are interested in predictive value,
so you can have a positive predictive value
or a negative predictive value.
And this is an answer to the question,
how likely is this positive result,
something that I can hang my hat on?
And so people want to know positive result
Well, a positive predictive value is the proportion of people who have a positive test and actually have the disease.
And a negative predictive value
is the proportion of people
who have a negative test and don't have the
disease. And so that sounds
wonderful, but the trouble with predictive
values, if you look at that equation,
is you have to know the prevalence
of disease.
And unfortunately, that data is not
available to clinicians.
And prevalence really matters.
And here's an example. If we start with a test in an area of 1,000 patients and the prevalence is
only 10 percent, the table fills out like that. And you can see that the predictive
value of a positive test is not that great at 64 percent. But if the prevalence of the disease
increases to 30 percent, now you see a significant increase in the predictive value of
positive test. In many infections, we can have direct evidence of the organism in question.
So, direct tests identify the pathogen. Some examples are culture, microscopy,
PCR, and antigen capture, and we use those in other diseases. There's also indirect evidence
of infection. So, indirect tests actually are measuring the host response to the pathogen,
for not measuring the pathogen itself.
And so many of them are tests of immune activation,
but some of them look for byproducts of the infection.
In Lyme disease, it's hard to come by direct evidence.
Culture and microscopy are not offered,
and because it's too difficult,
culture in Borrelia is problematic.
You need special media with precise growing conditions,
conditions, and it's a long incubation time. So it's just impractical for labs to offer that.
A microscopy is a difficult, special stage, very few spirochetes in tissues, and so it's kind of
like searching for the needle in the haystack. And I think as Dr. Embers mentioned, you know,
it takes a lot of technical expertise, and I think at one point she said she went through 400 slides
to find Borrelia. So you can see why that's not awkward. Good news is you can get PCR.
So these are screenshots from LabCorp, Quest, and Mayo Laboratories. And PCR and positivity is great.
It's direct evidence of the current infection. You can have multiple specimens that you can try
to test with PCR so serum spinal fluid synovial fluid and even um tissue biopsies can be tested
like maybe if you're biopsied and rash um but there's low sensitivity and so you can see the
various values there um it's highest in synovial fluid but serology is is better than that so PCR
testing, when positive is great, when negative doesn't really tell you much. PCR tests, as far
as I know, have not been cleared by the FDA. So they're kind of in-house tests. So what are
clinicians left with? Well, we're left with serology. And that's the enzyme immunoassays,
the EIAs, or some of you know them as ELISAs, and then Western blots or immunoblots. And they're
measuring, there are indirect
tests and they are measuring
antibody levels to
and there
are many manufacturers
and dozens of tests on the market
and the antigens that are used
in the tests
these are all FDA
clear tests and that means
that when they were trying
to get on the
market, they had to demonstrate that they
were comparable to testing
that was already out there. They did
not have to demonstrate clinical validity. There are also something called lab-developed
tests. These are tests that are designed, manufactured, and used in the lab that created
them. So this is an even more simplified version of the antibody formation timeline in untreated
patients. And I really just want to show you that the IgM levels go up first, usually between
one to two weeks and then peak about four to six weeks and
then they decline as that IgG begins to rise and we have class
switching from IgM to IgG. IgG goes up and we think stays up
indefinitely in the ongoing. Now in 1994 the CDC conducted a
convened a meeting said you know what we gotta all get on
the same page about tests because prior to that different institutions were using different tests
they were interpreting Western blots differently and was causing confusion so a patient could be
Lyme be a Lyme patient at Yale and not be a Lyme patient at Stone and so they've got people
together and hashed out what's going to be the test procedures and how we're going to interpret
Western blots. And that makes sense, especially because, you know, the CDC is in the business
of epidemiology. You know, you have to understand a disease before you can prevent it
and treat it. And so they wanted to make sure that they were counting actual caseloads of
Lyme disease. And so they required a test that was specific. But inherent in their decisions
were some assumptions about the immune response, specifically that it would be the same regardless
of patient circumstances. And so that may or may not be true. So here's the two-tier testing
algorithm. So if you order a Lyme test on your patient, the patient sample will first be tested
with an EIA. And samples that are negative, we stop. But samples that aren't positive can either
be tested with immunoblots, which is the standard two-tier testing. Or there's a newer way to
approach, and that's to test with a second EIA, different than the first, and then that's either
read as a positive or negative. Now, what I liked in the old diagram that the CDC had was it popped
if you had a negative EIA, they had the word consider alternative diagnosis, as well you
should. But this, to my mind, is very different than saying it's not Lyme. In immunoblots, we have
some special rules on how to interpret them. So if someone's been ill for less than 30 days,
you do IgM and IgG, and if either one are positive, that's a positive case.
For people who have been ill for 30 days or more, the rule became you do the IgM and the IgG, but if the IgGs are not positive, it doesn't matter what the IgMs show.
So positive IgMs after 30 days without IgG positivity, those are false positives.
And so that's what became accepted.
Now, two-tier testing is sequential testing.
And it's really a neat idea. You're going to use a very sensitive test to capture a wide range of patients, and then you'll use a more specific second test to kind of narrow things down to throw out those false positives.
When you test in this sequence, what happens is that the sensitivity of the two-test sequence is always lower than the sensitivity
of the second test, and the specificity is always greater, and I'm going to demonstrate it here.
So another table, we've got 200 patients, and half of them have disease. These are the parameters
of the first test. Our little two-by-two grid fills out like this. There's 110 people who tested
positive. 20 of those are false positives, and unfortunately, we missed 10 people,
Well, we're only going to test the 110, and so if we use a test that is less sensitive
but more specific, we actually create another 18 false positives, and we have been able
to successfully winnow down 18 false negatives, and got the false positives down to one.
So in this sequence, testing was only 72% sensitive, but was 99% specific.
Here's a cartoon on how that first EIA is done.
This is with the original one with a whole cell sonicate.
You're breaking up that bacteria into its various antigens that get embedded in the
well of the test well.
And then patient specimens are added, and you can see those little Ys, if they can attach
to an antigen, those are antibodies, they'll be bonded.
And we wash that away so the free antibodies go away, and we add a second antibody.
Now, this is an anti-human antibody, so it's going to bind to the antibodies that remain in the test well.
And it's called TAG, and TAG means that it's got an enzyme on it that will react with the substrate and cause a color change.
And so, ultimately, you get a color change that can be read and then ultimately converted to an antibody concentration.
So, newer tests, newer EIAs are using synthetic or recombinant antigens.
So, in this case, we're using the C6.
So, it's the only antigen in the well.
You can put patient specimens in there, and there might be other antiviral antibodies, but they have nothing to attach to.
So they'll get washed away.
And then the rest of the procedure is similar to what I just showed.
Immunoblots are different.
So Western blots and Lyme blots are
different at how they look for antibodies.
Here, they're actually looking for a specific group of antibodies.
And this is a very detailed process.
And it begins by breaking up the Borrelia into different antigens
and separating them on a gel.
And so it's a very labor-intensive process, and there's potential bands.
There are dozens of them.
And so this becomes very cumbersome to evaluate and actually look at.
And so there are many performance issues that might add to imprecision of the Western blot, very tech-dependent.
It's hard to get those antigens to separate.
And then looking at the intensity of the bands, some of them, on this example, are very dark,
where others are very, very light.
And these tests take a long time to get, so you don't get your answer back the next day,
which is really what you'd like.
The newer immunoblots are line blots, and what they do is they use recombinant or purified
antigens, and they can put the exact same amount on each test.
So you have uniformity there, and they can put the antigens wherever they want.
They can often do it so that it mimics the alignment of a Western blot.
And the sample is added, and it's very similar to how the Western blots are performed.
The big advantage of the immunoblots, it's going to reduce the clutter that we saw in the whole cell sonicate Western blot.
So back at that 1994 conference, they told you how to do the two-tier sequence, and they also said how to interpret the immunoblots, and
they wanted it to be very specific. So they took criteria from a study by Engstrom, and here they're only interested in three potential bands.
You had to have two of the three. And then for the IgG immunoblots, they took
criteria from a study by Dressler. Now we're looking for potentially 10 different bands that
we can assess, and you need to have at least five. So some examples of positive IgM, you can see that
all three samples, one through three, meet the criteria, and that unfortunately four through six
do not. And indeterminate are the bands that they just couldn't break. It's hard to know sometimes
if something's really there or if it's just a very faint.
And so now when we switch to look at the results from an IgG,
we've got 10 bands to consider, and we want to have five.
And that's what you see in samples one through six.
Now, samples four through six are negative,
but my eye was caught by sample four
because those four bands are really lighting up.
The little blue pluses have to do with signal intensity.
So, the darker the band on the plot or immunoblot, the higher the intensity.
But intensity is not part of the interpretation criteria.
So, what do you choose?
Do you want to do standard two-tier testing or modified?
Well, modified two-tier testing is thought to be more sensitive in early Lyme disease, so that might be ideal then.
I, as a clinician, think you get a little bit more information from a standard two-tier testing, especially when the test is negative, because some tests, to my eye, are worth considering or giving a second look.
This is especially true if you've done your differential and you've tested for the other
items that you thought might be causing your patient's illness.
And if you haven't found anything, you might want to come back and say, well, am I being
too picky about this Western blot?
Because it turns out there are other Western blot schemes.
And so they differ on which bands to count, how many you need to have, and whether some
bands are more important than others.
Earlier I said that when they selected the two-test sequence and the Western blot
interpretation that there were some assumptions were made. And so it's my general nature to
question assumptions, so here we go. The first assumption was that the timing of the IgG
response was going to be the same across the board, and that's why you had that ignore IgMs
after one month. But as this quote from Dr. Branda points out, experience is a wonderful
teacher, and now we know that it can take up to two months for patients to develop an IgG response.
So, we know the timing of IgG is variable. Another assumption was that there's no impact
on the patient's immune status when they contracted Lyme disease. We know that immunosuppression
reduces antibody formation. So, if you have the misfortune of being on chemo for a B-cell cancer
and you happen to contract Lyme disease, you're not going to mount a response.
What I couldn't describe from the literature was the impact of corticosteroids. You know,
most of these trials are small, and so it's great that we have people like Dr. Aucott
really starting to accumulate patients because you would need a very large patient population
to then look at the subpopulation of people
who were on steroids when they got their Lyme disease.
So that work hasn't been done.
Another assumption is that the immune response
would be the same regardless of the clinical presentation.
And so I'm going to show you two tests that made me,
or two studies that made me question that.
So I looked at this paper from Bacon's group,
and they were looking at how the C6 performs.
And here you find that when it came to Lyme arthritis, it was 94% sensitive, great test.
But for late neurologic disease, it was only 73% sensitive.
And then Dressler's paper, which was the one where we got our 5 of 10 criteria, that
was a retrospective study.
So then in the same paper, they reported the results from a prospective study.
and they were using their own well-characterized patients. And what they did is they took the
arthritis and neuroborreliosis. And here in this table, they started with 25 with arthritis and 29
with neuroborreliosis. But it turns out that 24 were four of the 29 neuroborreliosis patients
or early. So I removed them and I redone the table. And now you can see that the sensitivity
for arthritis was still great, 96%, but there's a difference. Neuroborreliosis was only 84%
sensitive. Now, this is theoretical. Well, what if we took the findings from Bacon C6
and Dressler's IgG side and put them together? We would find that two-tier testing was 90%
sensitive for Lyme arthritis, but only 61% for late neuroborreliosis. Now, that's in theory,
but I think it's something that's worth pondering about, and I hope sometime we'll get to the point
where someone's researching to see if there is actually a difference based on clinical
presentation. Newer tests have much higher sensitivity, and if you read them, hey,
we're 100% sensitive for late Lyme disease. That always got me wondering, well, how'd you pull
that off. Dressler didn't do it. And so I think part of the issue is when they say late Lyme
disease, they've lumped the two groups together. And the specimens that you're testing against are
in a performance panel. And to be on a specimen labeled as late in a Performance Panel, you had
to meet the lab criteria of the CDC definition. So basically, newer tests are finding what had
already been found. And so what they didn't show us is does this bench sensitivity translate to
clinical sensitivity? Is it clinically valid? And I also looked at a lot of the papers that
were describing their results. And when you look at the panels that they were using,
they were primarily Lyme arthritis. In the CDC's repository that you could test against,
all of their patients were Lyme arthritis. So here again is that diagram of the antibody response
in the untreated. And we'd assume that in untreated people that IgG persists indefinitely.
But we don't know that for sure, because as soon as we find someone, we treat them.
You know, we can't ethically just say, oh, I'm going to follow you along and see what happens
So we can turn to animal studies, and Dr. Embers' study in 2012 was interesting in that she had 12 monkeys that were not treated.
They were infected, but not treated, and wouldn't you know, they all were C6 positive right at five to eight weeks as we would want, and that's what we would expect.
But then over the course of the next 80 to 90 weeks, in 7 of the 12, or 58%, the C6 reaction became undetectable.
So it raises the question of, do we have people out there who are untreated with a smoldering infection, but who we can't diagnose if we're reliant exclusively on serology?
Another assumption is that the results are precise doesn't matter what test you get
a positive is a positive and a negative is a negative well here we see that this
group of tests were being tested against the reference labs a reference test and the reference
test to decide determine whether a test was positive or negative happened to be the Marblot
But when these researchers used the Marblot against the same samples that the reference lab tested, they were only 85% sensitive for IgG and only 62% for the IgM.
So replication of results is difficult with Western blots.
And just to point out that they use the term relative sensitivity and relative specificity as kind of non-standard terminology,
but because they're doing their comparison against a reference value that may also have missed culture positive cases, this is appropriate terminology.
So here we have the same lab using the same samples, but different tests.
And you can see that there's quite a difference between the first and the next two in terms of sensitivity.
Now, the good news is that those line blots should improve precision because they're eliminating a lot of the technical errors that can occur when you're making a blot.
People often wonder, what about serology after someone's been treated?
especially the people who remain ill,
will it be of any value to test them again?
And the answer is no, it won't.
And that's because negative results
don't indicate that the person is clean.
We know that antibody values declined
over time after treatment.
And positive results don't mean that they're infected
because that duration of the antibody response
is highly variable and unpredictable.
And I know where I live in Minnesota, a lot of doctors think once you're positive, you'll always be positive on testing.
And that's not true. In most patients, the antibody response will eventually go away.
So what's the nuts and bolts of testing? What are you going to do in your clinic?
So if someone walks in with a tick bite, won't that be fun to take that out?
but should you test them? Well, it's too soon for that antibody, so don't make the mistake of
testing, because if you test and you happen to get a positive result, that's really evidence of
higher exposure, and I don't think it's coming from that particular bite. And similarly, in people
with post-treatment Lyme disease or persistent Lyme diseases, whatever term you're going to use,
We know that antibiotics can change the immune response, and so whatever you get is not going to be a reliable indicator.
So testing really won't help me, at least not serology.
Now, Lyme arthritis is interesting, and that's because more and more, it seems that people are showing up with arthritis without a preceding erythema migrans.
and they also there's not seasonality to Lyme arthritis it can occur within just a couple months
of being bitten by a tick or might emerge years later and so that makes it a trickier diagnosis
based on clinical grounds but you want to be able to separate out someone who has Lyme
arthritis versus someone who is a different bacteria causing their septic joint and so here
testing is quite valuable because it has high specificity and high sensitivity. So test away
if you're worried about Lyme arthritis. In these situations, Lyme disease testing can be useful
when it's positive because especially in an endemic state like Delaware, if someone comes in
with AV block who's had exposure or a facial nerve palsy or a smoldering type of meningitis,
or even those adults who get the summertime flu,
if they test positive, you can trust that that's a true positive.
Same with people who present with late neuroborreliosis.
Remember that in very early cases,
it might be that the modified two-tier testing would be more sensitive.
The trick here is if you get negative results,
don't throw away the idea that this could be Lyme
because you might find out once you work through your differential
that Lyme makes more sense than anything else.
Do not test if you see someone with an erythema migrans rash.
It's not the pathogen of Lyme,
but because we do know that STARI and other things
can cause a similar appearing rash.
But it is a hallmark lesion of early Lyme disease,
and you don't want to delay treatment and be confused by test results
because, as you see from Dr. Horn's study, she had only 29% of the people that had definitely
had an EM rash were two-tier positive. And so, use your clinical judgment, look at the clinical
evidence, and then make your diagnosis. One of the tricky ones are people who fail to do Lyme
prevention, and they've got Lyme not only once, but perhaps twice. And, so, you're trying to
discern if someone comes in with an EM rash with a history of Lyme disease. Is this a new case and
they've been reinfected or are they simply having a relapse of their disease? Because both can occur.
Testing here is tricky. If you want to look at the details, one of the references is to Dr.
Branda's 2021 paper. He does a nice section on
reinfection versus relapse. So this is when you're going to rely more on
clinical information. Did the patient have a new exposure history?
Did their EM rash, is it in the
a different location than their previous EM rash?
Do their symptoms, are they different in this
in illness than in their previous.
If the EM rash is at the same place,
then that speaks more likely to a relapse
because it would be, I hope, unusual for an EM
to be exactly in the same location on reinfection.
So to summarize, current testing,
serologic testing for Lyme disease is limited
because it's insensitive in certain situations.
However, the specificity is wonderful, and so someone in Delaware with a good clinical history suggestive of Lyme disease and two-tier testing that's positive certainly supports the diagnosis.
You always have to consider lab results in the context of an individual's risk factors, history, and exam findings.
and until we have good direct tests of infection you're going to have to use your clinical judgment
as you diagnose patients with Lyme disease. Thank you and I look forward to any questions.
I can talk. Okay.
So just a little bit of a I guess a technical question about the Western blot. I remember
one of your slides you had like the numbers for a patient had like 39 kilodaltons there was
a band or whatever so like i guess so you're my teacher if i see a band at 39 kilodaltons and that
band is there that's from Western blot that had a secondary antibody and stuck to a first
antibody that was created against the protein that's the rolling protein how is that negative
just in a generic like because i like it's the part you're saying about there's four bands but
how can there be a band and still be negative if that does that make sense i understand what
you're asking because you're you're saying hey this is an important band 39 and it's showing up
um why would i not just on the basis of that say that my patient has Lyme disease and it you know
some of these antibodies antigens cross-react with other uh infectious agents and so that's why
they don't hang their hat on a single band and that's they really want to be specific so that'S
they came up with the five or ten criteria but other um schemes for interpreting Western blots
do say you know you these two bands are important um and that they're sufficient for a diagnosis
but what was decided on at the 1994 conference was you had to have this type of band pattern
oh but that makes sense thank you i don't need it either sorry
if you've got five of those ten that are positive and you have the
Western blot that's also interpreted as positive is there any way that that could be a false positive
sure so the question is if you got a positive uh Western blot so uh the first two tests
first tier test was positive and now you have the positive uh Western blot um is there any way that
that could be a false positive well yes so you know if you do the numbers there's like a less
than one percent chance uh that that's a false positive uh but that means there's a 99 chance
that it didn't so especially in endemic states you do want to trust the positive results yes
I have a question about Lyme arthritis. How do you determine if the testing is negative
if the patient wasn't treated and they have arthritis syndrome but she's not in the toilet?
Oh darn. So the question was how do you
determine osteoarthritis from Lyme arthritis if the test is negative?
You know the testing was so good for Lyme
arthritis that I would not think that you're getting a false negative.
I think that you have to trust that test that they don't have Lyme arthritis.
It does get trickier as people age because we do develop osteoarthritis.
When I was practicing, I'm not practicing now, but when young people came in with their Lyme
arthritis, they were always positive.
And the other interesting thing about Lyme arthritis versus osteo, the joint can really blow up.
And yet they kind of hobble in.
Whereas if you have septic arthritis from another cause, they're not hobbling and they're coming in in a wheelchair.
And so there usually is clinical difference between osteoarthritis, Lyme arthritis, and then at the extreme end is septic arthritis.
All right.
Take the mic to the person in the short.
Thank you.
Something that I've read on false positives was having previous diagnoses of mononucleosis.
Is that something that you could maybe expand on just a little bit?
Well, sure.
So there are cross-reacting antibodies.
So if we think of bacteria, they can have similar antigens on their surface, or in this
case with mono or virus.
And so you can get cross-reacting antibodies, and so that is another reason why they didn't
hang their hat on a single antibody, but actually had to say, you know, you have to have more than
one. But what you're getting at is an interesting point. And so specificity is great if you're an
epidemiologist or a clinical researcher, because you need to make sure that you're not counting
or studying people who don't have your disease. But a clinician, you want to have sensitive tests
because you're trying to find anyone who might benefit from your therapeutic intervention.
And so there's kind of a dynamic tension between the two.
I'm also very cognizant that we don't want to give people a label of Lyme disease if they have something else.
When I speak to the public, I always say the goal is not to be diagnosed with Lyme
disease. It's to be diagnosed correctly. And so that's that's the basis.
but yes um obviously with a lot of research that you're referencing also is being referenced by a
lot of the other institutions that are teaching this thing um a lot stuff has happened since
about 20 but the CDC is basing a lot if there are results on 799 is there any way that they're
going to be updating things soon because it sounds like things have kind of gotten out of date and
And with presentations like this, when it endures you soon, it looks like there's a
lot of development in the Lyme world and in the CDC going to be hopefully updating things
a little soon because the five-band testing protocol limitation is a problem.
Do I need to repeat that?
It's basically, is the CDC gonna be kind of modernizing their criteria?
And I can't speak for the CDC, but I am gonna go to a round table that they're offering
next week on their vector borne disease policy.
You know, when I read these papers from the 90s and moving forward, it's always this promise
of the test, the good test is right around the corner.
And we're really needing testing to be direct testing, right?
And so I think that we have other people in the room that can speak to the future of testing.
Sadly, we're stuck right now with what we've got.
But there again, that first thing I said, how testing doesn't occur in a vacuum.
And so, yeah, sometimes you're going to move forward with treatment in someone who doesn't meet that two-tier standard.
But what I would suggest to you is someone who's done a lot of peer review in general, whenever you're
going off in a different direction, you just have to document your thinking quite well
and so that people can follow how you arrive at the decision to test or treat
when things aren't quite what they are told to do.
My question is, in human medicine, do you have a vaccine approved for Lyme disease in particular?
So the question is do we have a vaccine for Lyme disease?
Not at the moment, but I've got my fingers crossed that there's some vaccines in development.
I'm just curious, because in veterinary medicine, we have the Lyme vaccine for a long time already.
Right. I know that. And there used to be a human vaccine.
It was withdrawn from the market in 2002.
And depending on who you listen to, there's various reasons for it being withdrawn.
I think that we're careful about creating a vaccine.
We don't want to cause injuries in a vaccine, so there is one being tested now.
I think they might be in stage three clinical trials.
So I really want a vaccine because it's really hard to get people to practice prevention,
and so I think a vaccine is going to be very useful.
So hopefully it'll be soon.
All right.
Well, it looks like I'm done.
I want to thank you for your attention.
Have a lovely.