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In this episode of Lab Medicine Rounds, Justin Kreuter, M.D., and Thomas Grys, Ph.D., Associate Professor of Laboratory Medicine and Pathology in the Mayo Clinic College of Medicine and Science and co-director of Microbiology at Mayo Clinic’s Arizona campus, discuss valley fever testing and the importance of clinical context.
A Mayo Clinic podcast for laboratory professionals, physicians, and students, hosted by Justin Kreuter, M.D., assistant professor of laboratory medicine and pathology at Mayo Clinic, featuring educational topics and insightful takeaways to apply in your practice.
(upbeat electronic music)
- This is Lab Medicine Rounds,
a curated podcast for physicians,
laboratory professionals, and students.
I'm your host, Justin
Kreuter, the Bow Tie Bandit,
a blood, a transfusion medicine
pathologist at Mayo Clinic.
As the weather turns
cold here in Minnesota,
we thought it'd be fun to travel south
and connect with some of our colleagues
from our other Mayo Clinic
campuses over the winter months.
And today we're rounding with Dr. Grys,
Associate Professor of
Laboratory Medicine and Pathology
at Mayo Clinic and
Co-Director of Microbiology
at Mayo Clinic, Arizona.
And we're gonna be talking
about valley fever testing
and the importance of clinical context.
Thank you for joining us today, Dr. Grys.
- [Thomas] Of course.
- I definitely wanna give you
a shout out and appreciate
the bow tie you've got
on for everybody today.
So for those of you that
are watching on YouTube,
you can see the wonderful design
that Dr. Grys has got
on his bow tie there.
- Yep, I've got a collection of bow ties
that are mostly microbial
or chemical structures,
things like that.
My wife finds them on Etsy.
So I don't always wear a bow tie,
but when I do it it's a nerdy one.
- I love it.
So let's kick into this podcast
and can you get us started
with why does clinical context matter
for what test clinicians order,
and to remind everybody,
we're talking about valley fever testing,
and so, can ya kinda launch in
with a little bit of the why here?
- Well, I'd like to back up
first and just remind ourselves
that you know, despite our best efforts,
not all of our lab tests are perfect.
There's always some level
of imprecision or inaccuracy
that we can expect.
And part of validating a
test is characterizing that
so that we can understand (clears throat)
what those weaknesses might be.
And part of what makes a test good or bad
is the likelihood that the
patient has that condition
or that analyte present
when we're doing the test.
Now some tests and like in chemistry,
if you don't have potassium in your blood
you're gonna be laying on the ground.
You can expect to find some,
so they're measuring how much of something
they expect to be there,
that's one type of question.
A fundamentally different question is,
is something there or not?
And that's a lot of what
we face in microbiology is,
is that thing really there or not,
and that's a different question
to set up your test for
and to set quality around
and then ultimately
should affect when that
test is being ordered.
(clears throat) So one of
the things I talk about
with the medical students
is pre-test probability
and the positive predictive value,
negative predictive value of the tests.
And the two good examples are
both respiratory diseases,
influenza, which varies by time of year
and things like valley fever,
which differs by geography.
So if you don't have the exposure
or if it's not the right season,
we can expect that result to be negative
because it's just not there, right?
So testing for influenza in
July generally is a bad idea
because it's not circulating.
We know it's not out there,
so any test that's positive
is likely a false positive
because the prevalence, and
we won't go through the math,
unless you're really want to.
But we'll just remind our
readers that the math exists,
that the positive and negative
predictive value is dependent
on the prevalence of that
disease in the population.
So during the summer months
in the Northern Hemisphere,
when influenza's not circulating,
the positive predictive value is very low,
even with a nucleic acid test.
And likewise, when flu is prevalent,
a negative predictive
value of a negative test
is quite high.
So if you get a negative test
when everyone around you has
flu, it's probably negative.
You probably have one of
the other many viruses.
Now in Arizona, 10 to 30% of
community-acquired pneumonia
is valley fever, 10 to 30%.
So that's pretty high.
We have the highest
prevalence of valley fever
in the world right here in this county.
A part of that has impacted
and however many million people
in the Phoenix area and
we're all breathing the air.
And valley fever is caused
by the fungal spores
of coccidioides immitis or posadasii.
So we think it only takes a
few Arthroconidia, the spores,
to cause disease, but to have disease,
you have to have exposure to the disease.
So if you've been born and raised
in another part of the country,
likely you don't have valley fever
'cause you haven't been here.
Now, there are anecdotes of sunbirds,
grandparents returning to
the Midwest or the East Coast
with dusty suitcases and the
grandkids playing in them
and being exposed or truckers
driving through the valley
and having their window
open and breathing the air
actually getting disease.
If you have lungs, you
can get valley fever.
So I mean, elephants,
chimpanzees in the zoo,
dolphins can get valley fever.
I mean, any mammal that
breathes is at risk.
So when I'm giving a talk in Arizona here,
I say, "Raise your hand,
"I've noticed you're all breathing.
"You're all at risk."
And it's true.
It's a bit of a stretch, but it is true.
It doesn't take much if you
breathe in the wrong bit of air
and you get some spores,
you could come down with the disease.
Now, most people,
probably two thirds don't,
there is some dramatic,
they get over it just fine.
But for those that do,
they have a lot of non-specific symptoms,
fever, cough, fatigue.
Fatigue can last for months.
Night sweats, various forms of rash.
We often say erythema nodosum,
but it can manifest in all sorts of ways.
So all these things mimic
influenza-like illnesses,
or right now, West Nile.
We're having the biggest year
on record here with West Nile,
almost a thousand cases
here and dozens of deaths.
So it's not specific, but it's common.
So we have to remember to test.
Now, if you were testing
someone with these symptoms
in North Carolina,
even Minnesota, likely
they have something else.
So a positive serology
is likely something else.
And in fact, you have your
own dimorphs up there,
dimorphic fungi.
So these are fungi that exist
as mycelia or hyphal forms
in soil in the environment
and in the lung.
A general, we call it a yeast form.
Sometimes historically
they call it parasitic form
'cause they didn't know it was fungus.
So it looks different,
so different morphology dimorphic.
We often characterize
Histoplasma and Blastomyces
as thermal dimorphs 'cause
you can take a plate
at 25 and move it to 37 and you get yeast.
If you do that with coccidioides,
you get warmer yeast,
sorry, warmer mycelia.
And it kind of makes
sense 'cause it's often
well above body temperature outside.
So it's not gonna automatically
turn to its yeast form
in the environment unless
there's other cues to do that.
So that's one of the
things on the research side
that we're interested in and others
in the field are working on
because if we can stop that transition,
maybe we can help prevent disease.
- You know, I really love
how you've started us off
with this example in showing about how
really considering
examples of time of year
or geography and reminding
us that a lot of the testing
in microbiology are kinda plus/minus
rather than a degree of measurement.
And I'm curious, so
that kind of plus/minus,
that might be a physician
might think about,
is this on my differential?
You brought up the idea of valley fever
consisting of about 10
to 30% of pneumonia,
I think you had said.
And so, if somebody is considering that
because the geography and
time and stuff makes sense,
what then determines which
kind of tests to order?
- Yeah, that's a great question
because despite being common,
it's actually not the
easiest thing to diagnose.
It's a dry cough, typically,
so oftentimes we don't
have sputum to work with.
If we have sputum, we can do culture.
It will grow readily,
even on bacterial media.
So if we start to see some gray fuzzies
on the bacterial side,
we have to move those to the fungal area.
We can do PCR,
which is about the same
sensitivity as culture.
But if we don't have
someone coughing up sputum,
then we're really reliant on serology,
and there's a number of serology tests,
all of which are quite mediocre.
And so, if you are
considering coccidioides,
you have to test for serology, not once,
but probably several
times because it can take,
you can get antibodies
within two weeks or so,
as we often think about,
but some patients won't
make them for two months,
three months until they have
a positive serologic response.
So that makes it really difficult.
Meanwhile, they're
getting multiple courses
of antibiotics sometimes,
and it's not that
everybody needs treatment.
Many healthy, normal people
will recover eventually.
And for a lotta these people,
giving them something like Fluconazole
won't shorten their course of disease.
So begs the question,
why do we need to know?
Well, if we cannot give them antibiotics,
which not only increases risk
of community resistance of microorganisms,
but also there are direct effects
from some of these antibiotics
that can be a bad outcome.
So for instance, 4-Quinolones
can give people tendonitis.
People have blown Achilles
heels and other things like that
after a course of antibiotics.
So these are not benign drugs.
So if we can withhold
the drugs they don't need
and stop doing additional testing,
save additional visits to the doctor,
then we can really have the
provider and the patient
allow them that conversation
of what to expect,
what are the warning signs?
And then it's just a matter
of dealing with the disease
over the next, often, few months.
So if you're negative,
sometimes we need to test again
in a couple of weeks and it's frustrating
'cause if your doctor doesn't
think of it right away,
you often go down the road
of assumed viral or bacterial pneumonia.
If they do think of it right
away, it can be negative.
So our ID team here has a CME course
in usually in January
that it's a ID update
for primary care physicians.
And they spend a chunk of time
talking about valley fever,
especially for those
in the local community
who may have trained elsewhere.
They need to know about
how this disease works.
And if you get an IgG positive,
that doesn't mean you're
immune and you had it passed.
It probably means you
had a recent infection
because unlike a lot of
infectious disease serology,
over time, that positive
serology will wane
if you have cleared the disease.
So if you have a persistent IgG,
it's likely that you still
have the fungus in your body,
in these granulomas and things,
which then can be cause for concern
if the patients gonna
undergo organ transplant
or cancer therapy or be
treated with a TNF inhibitor
or something like that.
Cocci can reactivate and
cause disease later in life,
regardless of the area of the country
they live in at that time.
So, you know, serology
is one of the oldest,
most mediocre and best tools
we still have, unfortunately.
- (laughs) I love that you describe it
as mediocre and best tools
'cause I think you took us
through those examples, right,
where it really requires
in one case you gave us
of where you're really going
to have a battery of this test,
repeat it over time as
opposed to a different test.
And in other contexts you might say,
that's not necessary or going overboard.
And I love the fact that you
brought in the CME course,
'cause then that highlights, you know?
I'm curious about how
that communication happens
between the lab and the clinician
or maybe how should that happen in order
to provide best care for the patient.
Keeping in mind here that we've got,
our audience is mixture of
laboratory professionals,
clinicians, and students.
- Right, so anytime we
validated a test in the lab,
part of that, like I mentioned earlier
is understanding its strong points
and weak points and communicating that,
when you go live at the test,
it's good to share those things
so that the providers know
when it's useful and not
useful to use that test.
And then, it's things like Grand Rounds
or CASE conferences where you
can just keep reminding people
that yeah, we can expect
the test with negative.
It had only been two weeks.
No one did anything wrong,
but then we do need to
remember to test again
if it's still in the differential.
So it's just a matter of
being persistent and engaged
in the practice because, I don't know,
hear something and it sticks.
Like we have to keep reminding
each other and our providers
across all the specialties,
they have a lot of their own details
within their specialty to keep up on.
So it's really our job to help them,
support them in their
endeavors and remind them
of when our lab tests
are good and not good.
And sometimes as a lab director,
our job is to remind
them of the situations
where our lab tests are not so helpful
because I tell the medical students too,
usually, the single best
source of information
is sitting in the exam room with you.
It's a matter of answer
asking the right questions.
We had a case of HLH, which
you can pronounce that
'cause I always mess it up.
Histiophacytic...
Lympho, yeah, HLH,
Google it, for pathology.
but it's the condition
that can be precipitated
by a number of infections.
And so, we had a patient
from a Pacific Northwest
who had gone to Mexico on vacation
and then showed up in our ED and had HLH.
And we're trying to figure
out what was happening.
A number of consultants
that had gone through
and interviewed the patient,
offered their recommendations.
Finally, I think it was
like the third team of ID,
fellow in an attending that came through.
Someone asked, "Well, what
did you do in Mexico?"
"Oh, I went spelunking."
(smacks legs) We're done.
It's histoplasma.
We don't even need to do any more testing.
Spelunking and a histoplasma
is such a tight correlation.
And then with his HLH diagnosis,
it's histoplasma until proven otherwise.
I mean, we're done.
One question, she'd been here, inpatient,
for like two weeks and it was free.
So I think, again,
sometimes we have to remind our providers,
it is not the lab test.
Sometimes, it often is,
but sometimes it's not the lab test
that answers the question.
We help rule things in or out,
but they still have to do their job.
We are not yet to AI where
you scan the drop of blood
and do imaging and you get your answer.
That can help you,
but you still have to
do the art of medicine.
And especially in infectious
disease and microbiology,
it's asking those questions
about exposure, history.
Do you live with a dog?
You know, we had a BMT, a
bone marrow transplant patient
who had salmonella
and serotype Arizonae,
which is highly associated with reptiles.
It turns out before she went
in for one of her treatments,
kissed her Gila monster pet.
Don't kiss reptiles if
you're immunocompromised.
So these sorts of exposures
and things are often,
they're not always as
textbook as you read,
but a lot of them are.
And so, it's just a matter
of doing that due diligence
of what are the exposures,
what are the symptoms?
And lab tests will help confirm
or exclude those differential diagnoses.
But it is our job to support
that art of medicine.
- Yeah, I'm really glad
that you highlighted
that I think for specialists
that have cultivated a relationship
with the microbiology lab in
this case, for example, right?
That connection is a
little bit more direct.
But what I hear in your answer too,
is that sometimes it's
the physician call it
picking up the phone and calling you
or the laboratory and also vice versa,
sometimes when we're getting tests
that maybe don't make sense
or that we're gonna pick up the phone
and call and have that conversation.
I'm curious, what do you
think kinda for the future?
You said a little bit,
maybe a hint of what your
answer here might be with AI,
but what do you think about for the future
of ordering laboratory tests?
- With the electronic health records,
I feel like we're halfway there.
Computers are here to
help us or so we thought.
It seems like sometimes
they make more work,
but when we offer a panel,
or even a selection of options,
it can facilitate bad
practice of bad utilization,
not thinking, but it can
also help us remember
not to forget something that is likely.
So to me, that's the balance,
and it can be difficult to
come up with these in a way
that's gonna work for most patients.
And I think each practice needs
to kinda come to their own balance point
of what's a good prompt and reminder,
and what's facilitating bad practice
because we have physicians who think
that all information is good,
and they just wanna keep ordering tests
to keep ruling in or out things.
But if the likelihood is low
and then you get a result
that you weren't expecting,
you paint yourself into a corner.
What are you gonna do with that result?
'Cause another whole
episode you should pursue
is discharged testing, right?
So there's a big push made a few years ago
with the Mayo to decrease the
amount of discharge testing
'cause a lotta people don't
ever look at those again.
They're meant to be like a safety catch
and just one last look,
but let's say one of those things
is out of range and you order
CBC and a bunch of things
where you're getting multiple
values for all those tests,
you might have 50 or 100 different
numbers come out of that.
And statistically speaking,
given that we're all
human, we're all different,
something's gonna be a
little bit out of range.
What's your plan?
Who's gonna document that?
Is it gonna be worth following up on?
I mean, if they're clinically well,
can we be good with that?
Because a lot of times ordering
more tests at that point
is only gonna create
problems and create costs.
So if we're not prepared to take action
and change therapy based on those results,
then let's think about
whether we really need
to order that test.
And so, the same is true here.
If it's plausible that
someone was in Arizona
10 years ago for a week,
and now they have pneumonia
and they're in Ohio,
yeah, they could have Coccidioides,
but if they were recently
cleaning out their farm,
it's probably a number of other things.
And you might end up testing for Cocci
as a third tier, last ditch effort,
if nothing else was positive,
but it should not be your first go-round
because if it's positive,
then you're gonna look at that.
Ah, it's probably not Coccidioides.
Well, you just wasted patient money
and our time doing that test.
But that's the hard part,
it's really zeroing in on,
what's first tier?
What should we leave
until we get the first
set of results back?
Because every physician
is looking at the patient,
saying, "Boy, I feel badly
they're in this state.
"I wanna help them."
And so, I'd like to give
them answers sooner.
Then we gotta balance
that with healthcare costs
and what's ultimately gonna be useful
or not useful in that situation.
- Wow, that's the hard part. (laughs)
Thank you so much, Dr. Grys, for this.
We've been rounding with Dr.
Grys on valley fever testing
and the importance of clinical context.
I think that you've
really given our listeners
a really nuanced perspective,
and I love that you're
hitting on the hard part
of clinical medicine.
And I love that we're kinda
tackling these issues here
and I think you've just pegged yourself
for a followup episode about
discharge labs. (laughs)
- [Thomas] Yeah.
(upbeat music)
- So to all of our listeners,
thank you for joining us today.
We invite you to share your thoughts
and suggestions via email.
Please direct any suggestions
to mcleducation@mayo.edu.
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Until our next rounds together,
we encourage you to continue
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through insightful conversations.
(upbeat music)