April 20, 2023 • 44 mins
Dr. Rupeena Purewal invites Dr. Marthe Charles, Medical Microbiologist and Infectious Diseases Specialist from Vancouver, BC to discuss new molecular diagnostics.
Link to some of the diagnostic tools discussed: bioMérieux | Pioneering Diagnostics (biomerieux.com)
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
Thanks for joining us again at the Canadian Breakpoint, a Canadian infectious diseases
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podcast by Canadian infectious diseases physicians.
I'm Summer Stewart, here again with Dr. Rupeena Purewal, pediatric infectious diseases physician
in Saskatoon.
In this episode, we welcome Dr. Marthe Charles, medical microbiologist and infectious diseases
specialist from Vancouver, British Columbia, to discuss new advances in molecular diagnostics.
(00:35):
Dr. Purewal.
Hi, welcome to another episode of our podcast, the Canadian Breakpoint.
Today we have a very special guest with us, Dr. Charles.
Dr. Charles has completed an MD, MSc degree from the University of Montreal in 2010.
Six years later, she finished her residency in medical microbiology and infectious diseases
(00:58):
at the University of Alberta.
Now she's the division head of the medical microbiology and infection prevention and
control and Vancouver Coastal Health for the last five years.
Her interest lies in more integrated diagnostics, increasing access and quality improvement.
She currently oversees urogenital infections and molecular diagnostics at Vancouver Coastal
(01:22):
Health.
From an IPAC perspective, she's involved in laboratory assessment of self-disinfecting
surfaces.
Welcome Dr. Charles.
It's a pleasure to have you on the podcast and I'm delighted to talk about some of these
molecular methods and products.
So obviously before we start, I would like to disclose that this is an informational
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podcast and we are no way endorsing a product.
So thank you for being here today.
Well, thank you so much for having me.
I'm really excited about this opportunity to be able to talk.
Great.
So why don't we get right into it?
Because I know a lot of our listeners are excited to hear about Biofire and different
panels.
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So I think to give an introduction to everybody, I would like to see if you can just talk a
little bit about some of the molecular based products that you're utilizing there in Vancouver
and really the main differences between them.
If you can touch on really from a lab perspective standpoint, it would be awesome.
Okay.
So I guess I'll probably start by saying that maybe I should disclose my concept of interest.
(02:33):
So yeah, I'm part of the Bureau of Speakers for CFI, but this presentation is representing
solely my own opinions and experience as a medical microbiologist at the Vancouver Coastal
Health.
So I think it's interesting really to have the perspective of the lab.
So as you mentioned, I'm a medical microbiologist, but I'm also an infectious disease specialist.
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And I'm trying to kind of bring those two hats when I'm thinking about technologies
that are being used in the lab.
Before I start, I think it's important for people that are listening in on this topic
that the molecular field has been for the longest time a really highly specialized area
in the laboratory.
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So if you look at a lot of our various public health laboratories or reference laboratories,
molecular diagnostic was normally a specific area in the laboratory while all of the people
that were working there were a lot of people that have graduated studies.
You know, you'll have like the masters, the PhDs and people that have a lot of training
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to be able to work in those facilities.
So looking back in terms of molecular diagnostic, I think it's important to kind of mention
like specific steps that are super important to be able to get to an answer at the end.
I think everybody has now vivid memories of getting tested for COVID, for example.
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So if we take a sample that was coming from your nasal pharyngeal area, well, that sample
doesn't just contain samples that are, I mean, material that is coming from viruses.
You'll have a melting pot of stuff, right?
So you'll have the human components, you'll have all of the bacteria that are part of
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our normal flora.
I think we talk a lot about that, what is part of the microbiome of the nose, and then
you'll have the viruses.
So the first step that any sample that comes in the lab for molecular diagnostic would
have to go through is what we call an extraction step.
So what we want to do is really making sure that whatever material that we're working
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with is the material coming, the genetic material coming from the virus.
So then what would happen is then once we know for sure that we have the genetic information
coming from the virus, what you want to be able is to amplify that signal and then to
be able to detect it.
So as I said previously, you had a specific area in the laboratory that would do that,
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and all of those steps that I was talking about of extraction, amplification, and detection
could have been done on various and different instruments.
So I think today what we'll mostly focus on, it's the ability of having all of those steps
within a black box and a super easy and fast way of detecting microorganism or pathogen.
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So I think the big players that we kind of hear about a lot would be like BioFire.
So that's the instrument and the company is BioMaria.
And then you have GeneXpert that people might have heard about.
GeneXpert is the instrument, but it's the company C-Feed.
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Other players that people might or might not have heard about would be things like Roche,
that's the big company, and the instrument that they have is Liat.
And then Kyagene is a little bit like of a later player in the multiplex diagnostic sphere
with the Kyastat.
So those are the instruments that we have right now.
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We call them black box because all of those steps that I've previously described are happening
without any intervention from the laborer or the technologist.
So they all happen without us being involved in the process.
Wow.
It's amazing that such a detailed process.
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And I'm sure from a lab perspective standpoint, that cuts down a lot of time for technicians
as well and turnaround time as well, I would imagine.
Oh, no, for sure.
Those type of instruments are a devil-edged sword in a sense because as a diagnostician,
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we want to be able to see what's happening and to be able to also troubleshoot.
But now it's completely out of our control really because all of the quality aspects
are taken into account by the instrument itself.
So it's quite fascinating that we were able to automate and miniaturize all of those parts
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in a way that it makes it way, way much easier and easily accessible, not only for the clinicians,
but also for the lab artisan.
And I know in the past, you've mentioned that like respiratory panels, for instance, would
be kind of the most commonly used, just like what we talked about with COVID.
And I think lots of people are kind of familiar with respiratory samples.
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So what other, like we'll definitely go into, I think, all the details of that because I
know you've done a lot of research in that area as well, because it is the most commonly
used panel.
But in terms of other panels, what's being offered right now?
Oh my God, there's so many.
So if we look at the BioMaria product with BioFire, and I think that's funny because
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a lot of the clinicians these days are phoning the lab and they're like, I want a BioFire.
And for me, my answer is always like, which one?
Yeah.
Which, what are we looking for here?
Yeah, which one?
Because I think people are not aware that there's a lot of different panels that are
available for BioMaria at this point.
So there's the pneumonia.
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So we're talking about lower respiratory pathogens, and they also have one for that are more upper
respiratory tract type of infection.
They also have GI panel.
They have a meningitis panel, the ME panel, they call it.
They have a blood culture ID.
So that's from positive blood culture.
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Then you can put it into that panel that goes onto the BioFire.
And I'm also interested to see that they also have what would be like for a joint infection,
but I didn't have the pleasure yet to be able to work with that one.
But it's just to show that please don't call your lab saying that you want a BioFire because
there's so many different panels that are available.
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So it's always more helpful to really be clear about what you're looking for.
If you're looking at GeneXpert, I'm not going to name all of the panels that they have because
they have more than five.
But things that you probably have heard is that they'll have like the COVID-2-AB-RSV
panel.
They have cartridges for all sorts of things like from C. diff, neuro, gyne, so STI testing
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on the GeneXpert, C. diff testing on the GeneXpert.
So they have a quite big array of cartridges that are available for testing.
And then in terms of the BioFire panels, so let's say the REST panel, what are we looking
at?
So obviously the type of specimen is going to depend on the type of panel and what we're
looking for.
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But what are some of the turnaround times that people are looking at?
And what does this really cost for the lab?
That's my big question.
Yeah.
Okay.
So we can talk about the differences between the various panels that are available, but
I think, I guess I'll just tell you the price.
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So depending where you are in Canada, I think the pricing might change depending on the
contract that you have with those companies.
But normally it's in the hundreds of dollars.
And the reason why we mentioned this, it's quite significant because for the longest
time in the molecular area, we use what we call lab-developed tests.
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The lab-developed tests are often super easy to establish in Canada in the sense that if
you have your set of primers and then you have your reagent for your real-time PCR,
so it's easy in terms of it wouldn't be really costly compared to hundreds of dollars for
a cartridge on a multiplex panel.
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So on the ABI, because that's the real-time PCR that we use here, often a lot of the tests
that we would do would be on the magnitude of less than 20 or $10 per patient.
Yeah.
So a huge difference.
So it's significant, right?
So the approach that we took here at my laboratory was to really try to have a laboratory stewardship
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in a sense to try to really make sure that the test that we're doing is providing the
answers that the clinician required to take the best care as possible for their patient
population.
Yeah.
And I think that's really important.
When we talk a lot about stewardship in the clinical world, but I think kind of taking
that into account and from a lab perspective standpoint is really creating that awareness.
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And sometimes when I'm a clinician, so when I'm wearing the clinician hat, you don't think
about these things.
You really are just trying to find the answer because the answer is going to help your patient
get better or the answer is going to help give us an answer to better treat the patient.
And we always think of it more from a stewardship standpoint in terms of antibiotic use.
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And I know that especially with the respiratory panel, you've done some work also in research
around this area.
So probably changing the gear a little bit because I know that we've talked a little
bit about the costs and some of the, I guess, advantages and disadvantages of this, but
really going into what clinicians, the reason that we are ordering these panels, what is
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some research that you, and do you want to talk a little bit about your research around
how you've seen these respiratory panels help us in the clinical world?
Yeah.
So here at our laboratory, I think the panel which we had the most experience with was
the respiratory panel, so the RP1 at the time.
So when I joined the lab, one of the research that I was able to participate in was about
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the utilization of biofire respiratory panel for the BMT, so the bone marrow transplantation
unit and the impact that the utilization of such equipment would have on infection control,
but also on antimicrobial stewardship.
So we know that that population has a tendency to present with high-grade temperature or
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fever, and it's always kind of the concern about, well, is it part of their evolution
of their disease or is it because of an infection?
And if it's an infection, is it due to viruses when you're in the respiratory viral viruses
season?
So what we were able to show, and for people that are curious and want to go and read about
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it, we have an article titled Biofire Film RA Decreases Infection Control Isolation Time
by Four Days in ICU, BMT and Respiratory Rewards.
So this was published by Dr. Wong and all, so I was one of the contributors to that study.
But I think the title will kind of say it.
We were able to show that the utilization of the biofire, despite the upfront cuts to
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the lab, had downside effect in the sense that we were able to reduce the isolation
time for those patients.
And we know that having patients in isolation is often problematic in terms of the quality
of the care that they're getting because often for the nursing staff, it's easier to keep
the care for a lot of people that you have to dawn and off precautions for.
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So that's just an example of how an equipment in the laboratory has a direct impact on the
care that patients are getting on the ward.
So I think that study was really good and it kind of helped us also build a business
case and show value for an instrument that would be used in the lab.
The only caveat that I would put there is that it made a difference as long as the laboratory
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was using this instrument as a stat instrument.
And we'll talk about it maybe a bit later about the impact of having those type of equipment
in the lab.
It's only true if I'm able to act on the sample right away.
So during that study design, what we had done is like all of those samples that were coming
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from ICU, BMT, and the respiratory wards had to be processed within one hour of receipt.
So then the fact that the instrument is so quick, you can really capitalize on that because
we were putting it on the instrument right away.
So I guess what I'm trying to say is if the wards collect the sample and doesn't send
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it to the lab, or if the lab received the sample and don't put it on the instrument
right away, then you lose the benefit of having an instrument that is really quick.
Definitely.
So those are some of the things.
And sometimes in the clinical world, as opposed to when we're doing some of the research,
we can sometimes find those discrepancies too.
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Because sometimes with clinical, there's like delay for collection, there's delay for multiple
reasons for the sample to get to the lab.
Probably also depends on the number of samples that are coming in.
And so hence why we always kind of talk about lab stewardship and really understanding,
are we sending the sample for the right reasons?
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And is this going to make the difference because we don't want to burden our lab colleagues
either.
Yeah, no, good point.
And I also like what you mentioned about, it's also knowing the specimen type that you're
sending.
Because sometimes if you don't have the conversation with your microbiologist in the lab, then
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you don't have that information.
But of all the instruments that we have in the lab, some can or cannot process certain
specimen type.
So what I'm trying to say here again is that if the only sample that you can collect on
one of your patients is a tracheal aspirate, well, it might not be compatible to be put
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on your biofiber and therefore you're not getting the result as fast as you were hoping
to get it.
Right?
So you have to change the methodology to process that sample.
But something else to keep in mind.
And that kind of brings me to the second paper that we've done in collaboration with the
BioFire, which was the utilization of bronchoscopy samples and try to put that on the BioFire
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and see that the performance was still fairly good, but not as good as we were hoping it
to be.
So right now for us, we're not yet putting BALs, for example, on the BioFire, but it's
a conversation that we would have with the clinicians in terms of how strong is their
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pre-test probability that they think that there's a viral infection going on.
And then knowing the performance on the test, we would decide if we would go that way or
not.
Right?
So just for our knowledge, for the listeners as well, the best sample right now would be
your nasopharyngeal sample.
Yeah.
So on the respiratory panel, on the BioFire, the best sample would remain to be the nasopharyngeal
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squad.
Okay.
And then also just because we have listeners that are clinicians, but we also have pharmacists
and we have nurses kind of from all across the world.
So just to kind of let them know what type of organisms and pathogens are we detecting
with like, for instance, the respiratory panel, just to name a few.
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Okay.
So the respiratory panel will have like your regular steps.
So you'll find the flu, A, B, RSV, you'll have the COVID.
In terms of the other viruses, it has the ability of detecting human metonymovirus,
rhino enteropara influenza as well.
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But it has also the ability of detecting other organisms depending which BioFire, if you're
on the pneumonia panel versus the RP2 panel.
I'm just going to provide the information for the RP2.
So the other organism that I was thinking about was, for example, certain bacteria,
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the bordetella paraparctis, the media pneumoniae and mycoplasma pneumoniae.
And then also all of the other human coronaviruses that were known prior to COVID were also part
of the RP2.
And then for the pneumonia panel, that would also include like strep pneumoniae homophilus,
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it'll be able to detect those as well.
Yep.
If we look specifically at the pneumoniae one, so yeah, so it's 33 target.
And that one would have like stuff more like streptococcus, biogenes, pneumoniae, even
some acinetobacter.
And the part that I think is also interesting about the pneumonia panel is the ability of
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detecting some antimicrobial resistance gene.
But again, this one is not a panel that we had the opportunity or luxury to be able to
use at my laboratory, but those would be some of the perceived like perks of having that
panel.
That would be fantastic.
Yeah.
But in its own way, right?
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So sometimes there could be pros and cons to technology as well.
And some of these molecular methods are super sensitive.
So I know in the past, you and I have had multiple discussions about biofire versus
gene expert.
And I know you want to talk a little bit about and tell the audience kind of the differences
between that, because even me as an infectious disease physician, I could tell you that I
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may not know all the differences, including kind of what the sensitivity specificities,
the CT values, we always talk about these numbers, but I love to hear it from a lab
expert.
Okay.
Well, I would say that, you know, when you look at the clinical performance or the laboratory
performance of the two assays, like it's a PCR assay.
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So their sensitivity specificity from a laboratory perspective would be above the 95%.
Right.
And I think they're pretty similar in that regards in terms of sensitivity of the assay.
To walk you through the differences between the two, what I would say is if we start with
CIFID, CIFID is a multiplex panel, but it's limited target.
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Okay.
So as I mentioned, they have a lot of different cartridges that you would have to build up
on.
But in terms of, if we just speak about respiratory panel, they have this combo of flu A, B, R,
S, V, and COVID.
So one of the advantage is that it would specifically answer your question because they have also
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a cartridge that is COVID only.
Okay.
So I feel like it's a bit closer to what a clinician with duty would think about like,
well, is this influenza?
Then you order a gene expert and you will get your answer.
It's pretty straightforward.
From a laboratory perspective, it's really, really easy to use.
As a matter of fact, it's one of the rare multiplex assays that is Health Canada approved
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to be used as a point of care assay.
And we've seen that during the pandemic as well.
It is quite fast.
So for the respiratory panel that I was telling you about, it can provide an answer within
35 to 40 minutes.
And then it used some end fluorescence in terms of detection.
But it also has the ability of providing you a CT value.
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And then overall, it might be a bit cheaper than the Biofire if we're just talking about
the respiratory panel in terms of the cost to the lab.
But if we look at the Biofire, this one, as I mentioned, is syndromic and it has more
than 20 targets if we're talking specifically about the respiratory panel.
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It's also easy to use, but there's no CT available on the Biofire.
Okay, so it's a real, completely real black box in the sense that you cannot see how strong
or low of a signal was detected by the instrument.
But it's quite sensitive.
I've mentioned the five panels that they have also, and it's just that it takes a little
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bit more time.
So it's just a bit over an hour to get the full panel result.
I also think that the Biofire kind of brings an ethical conundrum or conversation because
it's a syndromic approach.
So I think we've been accustomed to do an assessment of your patient, come up with your
diagnosis and then try to have the diagnostic support your hypothesis.
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But in this case, you might have been thinking about influenza, you're sending me the sample,
you're asking for a Biofire, but I'm testing for 22 other organisms that you have not requested.
So I feel like it's a good ethical conversation in terms of bioethics and what do you do with
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that?
And some people would say, well, you only have to report what the clinician has requested.
But what if it's positive for something that the clinician has not requested?
Can you really hide that information?
Yeah, and that's the thing with all of these reports, I think, is that you can tell us
more.
But for any of these respiratory panels, you usually get this line list of pathogens and
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then it'll just say positive or negative.
And then taking that into your clinical context, I think, can be actually quite challenging
because a lot of them have similar presentations.
So we're talking about the exact same patient, but you could have multiple viruses.
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And something that I deal with in my clinical world is obviously I'm a pediatrician, so
pediatric infectious disease, we're going to see a lot of respiratory illnesses.
And with PCR testing, although it's great, molecular methods give us a quicker result,
we also see those long lasting effects.
So six weeks prior infections are being detected as well.
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So you also have to, as a clinician, take into context, like, is this a previous infection
or is this really my acute illness?
And relying on that, and then let's say I take off antibiotics because I think this
is what's going on, is that harmful or problematic in that clinical case?
So I think it can be challenging, definitely from our perspective too, but I can't even
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imagine at least I have the clinical context.
And so from your standpoint, being on the lab side of things, and you do both sides,
so obviously right now I'm giving you the lab hat, but being on the lab side of things,
it's challenging because you don't get all of that information.
You're not fully involved from like day one with the case, you know, and so you get really
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what we place on the requisition.
Yeah, no, it's a good point.
Yeah, it's like anything, right?
The same way that when you see your patient, you come up with your differential and the
laboratory, we also come up with a differential based on the very limited information that
we get.
So if people could only remember one thing, I guess, from anything that I said today is
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get a good relationship with your laboratory and provide more information.
The same way that when you send a requisition form to diagnostic imaging, you would provide
with a little bit of a history.
It's the same thing for microbiology, right?
So a history can go a really long way in microbiology and helping us find what you're looking for.
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Because the reality is people think that the laboratory will find whatever is in your sample,
but that is not how the lab is made.
The lab is made to identify the common causes of issue for the syndrome that you're talking
about or the sample type that you're providing.
So if you're looking for a zebra, it's always better to get in touch with your medical microbiologist
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and let them know that you're looking for a zebra.
So I think that would be a big, big message.
The other thing that I'll always use as an example is it's always also important for
the clinician to understand the different technologies that we're using in the lab.
And we try to have this dialogue with our clinician in a sense that we provide comments
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with our reports so you know what we've tested your sample for.
And sometimes, I don't know, as a labartician, we feel like we're misunderstood or not fully
read.
So the best example would be, I think I've told you that story, but I kind of like that
story.
It kind of shows us how all those molecular assays are fantastic to look for the bread
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and butter stuff.
And also, I'll tell you about the strength of a story.
So I use that story with the resident a lot.
So the story goes as follow, and you can also Google it because it's a true story.
It's about a family that was presenting with rice water diarrhea.
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So for anyone who is ID trained or has interest in ID, if I tell you rice water diarrhea,
there's a diagnosis that comes in mind right away.
Exactly.
So I'm not giving the punch just right.
I'll keep it quiet over here too.
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So that sample was sent without a story to the laboratory, and then a molecular testing
was done, and it came back negative, no pathogen found.
So of course, we normally get involved when things are not fitting or it's not the result
that we're expecting.
So that's when the conversation happened.
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But we could have saved time and managed those patients differently if that conversation
happened earlier.
So what I was describing earlier on was a case of cholera in a family.
So it's just an example of you can have a molecular assay that detects cholera, but
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a cholera that is found all over the world, but not the one that you have locally.
Exactly.
Yeah.
And I think we've discussed that a lot during the pandemic, the whole conversation about
variant, but in the bacterial world, you also have different serotypes, for example.
So it's important for a labartician to also know the limitation of their technology.
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But from a physician seeing patient perspective, I think it's also always important to keep
the story in mind and bring the clinical diagnostic combined together and see if it makes sense.
And so in this case, you weren't able to pick up that specific strain on the serotype, and
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that's what the PCR was negative for?
That's why.
So the PCR was a multiplex.
It had the ability of detecting, you know, LTOR, so one of the cholera that we normally
see.
Yeah.
But then it seemed like we had a different one in BC, and the primers would not attach
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to the genetic information of the one that was local to us.
It's just another example of, you know, the history at the end of the day and the clinical
examination of your patient still makes a difference.
It's not because the PCR said it's negative that what you're saying is not infectious,
right?
Right.
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Yeah, and I actually deal with this, you know, often because people will come in and they
have respiratory symptoms, looks like a viral upper respiratory tract infection, and the
PCR respiratory panel comes back negative, and families will always ask, but I don't
understand.
We said they have a virus, but the thing to like, we always try to educate our families
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as well and also teams that we work with as, you know, being a consultant is that you don't
always get the answer for which virus it is.
You have to be looking for those specific viruses that are on there.
Now, if it's a different strain or it didn't pick up, it could be, I mean, there's multiple
reasons, right?
We talked about specimen type, we talked about, you know, the lab, like the technology itself,
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right?
And in the end, we also have to remember that it is obviously no longer, you know, it is
a machine-based test.
And so things can be, you know, not as streamlined as sometimes when it's done by hand, right?
And so because it's done quick, that's fine, but it's also machines can make mistakes.
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And so there could be lab errors, there could be specimen errors as well.
And so I always try to, but really important is that you don't have to detect all viruses
because I think it goes back to your cholera story is, you know, sometimes you don't pick
up the strain or this, the variant or the serotype.
So I think that's something that we should all remember as clinicians.
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In terms of, I know we talked a little bit about the advantages and disadvantages of,
I know specifically you've worked a lot with the BioFire respiratory panel.
Is there anything that comes to your mind that would be, that we didn't talk about today
that would be an advantage or disadvantage that you would want our listeners to remember?
Yeah.
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So, I mean, I think we covered a lot of the various aspects.
So if I have to summarize the disadvantages, I mean, we kind of talked about the fact that
the cost could have been a bit prohibitive.
I think there is some pressure on the laboratory to really be quick at handling those samples,
to put it on the instrument.
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So that's pressure on us if we want to be able to show the value of those faster and
around time.
But then related to that, you had mentioned the amount of samples that are coming in the
lab at the same time.
But the reality is a lot of those instruments like the, the GeneXpert or the LIAT or the
BioFire, they're limited in terms of how many samples can they run at the same time.
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So on average, they're all below 20 sample per hour compared to our routine in-house
PCR or real-time PCR.
Those can do hundreds of samples within three hours.
So I think that's something else to keep in mind in terms of the low throughput that those
instruments have.
(34:24):
And then I think lastly, it's really like all of the too many targets maybe that might
not be relevant to certain patient population that we're providing.
So that could be perceived as a disadvantage and an advantage.
And then in terms of advantages from a laboratory perspective, you know, I started off this
conversation by telling you, well, the people that work in molecular diagnostic have to
(34:48):
be like highly, highly trained.
To use those black boxes, you don't need to be highly trained.
Like often the manipulation of those cartridges are super easy.
So we can have that step being done by people that are not like the most trained people
in our laboratory.
And other advantages, I mean, I'm in Vancouver, you know, real estate is a real problem.
(35:12):
So a lot of those instruments have a really small footprint.
So I think it's an advantage and it can also be interfaced with your LIS.
So that makes it even faster for reporting.
So yeah, there's a lot of pros, a lot of pros and a little bit of cons.
Yeah.
I think that's a good, great summary of that.
(35:33):
So what is, what's the future then?
So what are we looking at?
Like, are we, are you validating, is your lab validating additional biophier panels
right now?
And what's kind of the new thing that's out there?
Yeah.
So good question.
I think there's a lot of conversation about what's going on in the world of molecular
diagnostics.
So, I mean, the multiplex panels are super interesting.
(35:57):
I told you about the pneumonia panel.
That's something that we will most likely want to be able to play with.
And then the sample type, the fact that it's putum and BL that's like major and makes sense.
So, but that would be probably in the future the same way with the, sorry, the joint fluid
samples.
(36:18):
Yeah.
So I think that's going to be super interesting because we know that joint fluid from a smear
when you do the ground smear, it's not super sensitive, but if we have the ability of having
a multiplex PCR or a multiplex black box that allows you to do early detection, it would
(36:38):
make a complete difference in terms of management of those or atopation.
Right.
So I think that's exciting.
Yeah, definitely.
In terms of timeline that are approaching a bit faster for us.
So we're interested in looking into the GI.
So we've done our validation for the GI panel and we're about to go live with that.
(36:58):
So that should be for, you know, this summer.
And then we're also looking into the meningitis panel.
Right.
So I think that also makes quite a big difference if we're able to detect early on any cases
of meningoencephalitis.
Yeah, exactly.
I think from a clinician standpoint, all of this sounds like great because there's a lot
(37:23):
of times when you, you know, it's challenging, especially like being in Saskatchewan, we
have a lot of remote communities and sometimes patients are very, very ill.
And so receive antibiotics prior to arriving at our center.
And so for me, the advantage of getting, for instance, like a PCR, at least if they've
(37:45):
had multiple courses of antibiotics prior to arriving, it can at least help me narrow
down even from an antibiotic standpoint.
Right.
And so, and also kind of figure out what is the most common pathogen.
Like we always kind of takes away that guessing game that sometimes makes clinicians a bit
uneasy, I would say, if that's the right term.
(38:11):
So you did talk a little bit about the BCID panel, which is that currently validated?
Like you guys are using that there?
So we had a chance to work with it and validated it.
But the thing, you know, it's always a balance.
The same way that when we see patients, you're always trying to figure out like how much
(38:36):
any type of management choices you take, how much would it impact your patients?
So it's the same in the laboratories.
So for us, because our volume of positive blood cultures were so high, so I'm at Vancouver
Coastal Health, so we provide service for more than 12 healthcare centers.
(38:59):
So we have a fair amount of blood cultures coming in.
And on average, we can have like anywhere between 15 to 20 positive blood culture a
day.
So trying to put that on the instrument in terms of volume will make it for us impossible
to also do respiratory.
(39:19):
So we had to make a choice.
So we had to decide like, what's more important for us?
Is it to get an answer quickly on the respiratory side?
Or do we think that the gain that we would do on the blood culture would make such a
big difference?
So because of the infection control components related to respiratory viruses, we decided
(39:43):
to go that route because we were fairly quick at identifying the organism on the blood
culture.
So the first thing that you have to keep in mind is that on the blood culture, it could
be anything and everything.
The BCID panel is limited to a set numbers, right?
(40:07):
So the moment it doesn't identify your organism, you just delayed by one hour if you weren't
already on top of it.
So we felt like with our workflow, it made more sense to dedicate the instrument on their
respiratory panel.
Yeah, and that's fair.
I think we're also practicing in an era where we have Malditov and other technologies.
(40:30):
And so previously when we just had biochemical tests, I think it was more challenging and
we wanted quicker identification.
But I think a lot of times with that MRSA select plates is a lot of technology that's
already come through that's making it easier for clinicians, especially those practicing
in an area where they are using this constantly.
(40:53):
But I think you're bringing up a super valid point in a sense of epidemiology and population
is super important in terms of those decisions that you take in the lab.
My conversation with you might have been different if 60, 70% of my people that had positive
blood cultures were Staph.
(41:13):
And then maybe 50% or 30% of them were MRSA.
So it would make such a big difference to be able to use BCID because it would have
a direct impact right away.
But that's not really my situation right now in terms of the patient population that we're
providing care for.
So yeah, it didn't make total sense at the time to go that route.
(41:37):
Yeah, fair.
And I think, yeah, that's one thing about ID, right?
It's infectious diseases, different everywhere.
You cross the border and it's like a provincial border and you're facing with different diseases,
different conditions, different demographics and the epidemiology is very different.
So I think it's important to always, I think one of the things that I've learned is that
(42:00):
there's a lot of technology out there and there's a lot of things that we'd want our
labs to be doing.
But I think having that conversation as clinicians with the labs, microbiologists and having
that close connection, that's I think really, really important because you can bring up
these types of topics and ideas and really understand it from, we obviously just want
(42:24):
the answer, but who's providing us the answer, that also depends, right?
We need to figure out what the rationale is behind having one panel versus the other using
gene expert over another respiratory panel, that type of thing.
So you bring up a very, very valid point.
That's why it's great having somebody who's in the field, in the lab and the clinical
(42:44):
world.
So is there anything you would want our listeners, I know you mentioned before a couple of key
points, is there anything else you have a burning desire to tell your listeners from
a lab perspective standpoint that something that they should do and follow and would be
helpful for our lab colleagues?
(43:07):
I mean, I'm going back to what I said earlier, I mean, having a history, really, really helpful.
So if you guys can provide more clinical information, we'll be better at supporting the team that
is seeing the patient, that's for sure.
And I think having conversation with your laboratory as well, trying to understand what
(43:28):
kind of technology are being used can also help you be better at the job that you're
doing.
So knowing the limitation of the instrumentation that you're using is also key.
Well, that's a very, very valid point.
And I think a lot of our listeners are going to enjoy this episode because we don't talk
a lot about diagnostic methods and what's new in the lab world.
(43:54):
So I'm excited to have you on our podcast today.
So thank you so much for taking the time and this great opportunity for us to learn a little
bit of, you know, the different technologies and molecular methods that a lot of us are
probably already using and don't even realize some of these details and points.
So really appreciative.
(44:14):
Oh my God, thank you so much.
It was a lot of fun.
So my pleasure.
Perfect.
Thank you so much.
Have a great day.
Thank you, Dr. Purwall, and a special thank you to Dr. Charles.
Thanks for joining us.
If you've got a topic suggestion, please email us at thecanadianbreakpoint at gmail.com or
(44:36):
get ahold of us on Twitter at CA Breakpoint.
See you again soon at the Canadian Breakpoint.
Thanks for joining us again at the Canadian Breakpoint, a Canadian infectious diseases
(00:13):
podcast by Canadian infectious diseases physicians.
I'm Summer Stewart, here again with Dr. Rupeena Purewal, pediatric infectious diseases physician
in Saskatoon.
In this episode, we welcome Dr. Marthe Charles, medical microbiologist and infectious diseases
specialist from Vancouver, British Columbia, to discuss new advances in molecular diagnostics.
(00:35):
Dr. Purewal.
Hi, welcome to another episode of our podcast, the Canadian Breakpoint.
Today we have a very special guest with us, Dr. Charles.
Dr. Charles has completed an MD, MSc degree from the University of Montreal in 2010.
Six years later, she finished her residency in medical microbiology and infectious diseases
(00:58):
at the University of Alberta.
Now she's the division head of the medical microbiology and infection prevention and
control and Vancouver Coastal Health for the last five years.
Her interest lies in more integrated diagnostics, increasing access and quality improvement.
She currently oversees urogenital infections and molecular diagnostics at Vancouver Coastal
(01:22):
Health.
From an IPAC perspective, she's involved in laboratory assessment of self-disinfecting
surfaces.
Welcome Dr. Charles.
It's a pleasure to have you on the podcast and I'm delighted to talk about some of these
molecular methods and products.
So obviously before we start, I would like to disclose that this is an informational
(01:47):
podcast and we are no way endorsing a product.
So thank you for being here today.
Well, thank you so much for having me.
I'm really excited about this opportunity to be able to talk.
Great.
So why don't we get right into it?
Because I know a lot of our listeners are excited to hear about Biofire and different
panels.
(02:07):
So I think to give an introduction to everybody, I would like to see if you can just talk a
little bit about some of the molecular based products that you're utilizing there in Vancouver
and really the main differences between them.
If you can touch on really from a lab perspective standpoint, it would be awesome.
Okay.
So I guess I'll probably start by saying that maybe I should disclose my concept of interest.
(02:33):
So yeah, I'm part of the Bureau of Speakers for CFI, but this presentation is representing
solely my own opinions and experience as a medical microbiologist at the Vancouver Coastal
Health.
So I think it's interesting really to have the perspective of the lab.
So as you mentioned, I'm a medical microbiologist, but I'm also an infectious disease specialist.
(03:00):
And I'm trying to kind of bring those two hats when I'm thinking about technologies
that are being used in the lab.
Before I start, I think it's important for people that are listening in on this topic
that the molecular field has been for the longest time a really highly specialized area
in the laboratory.
(03:21):
So if you look at a lot of our various public health laboratories or reference laboratories,
molecular diagnostic was normally a specific area in the laboratory while all of the people
that were working there were a lot of people that have graduated studies.
You know, you'll have like the masters, the PhDs and people that have a lot of training
(03:43):
to be able to work in those facilities.
So looking back in terms of molecular diagnostic, I think it's important to kind of mention
like specific steps that are super important to be able to get to an answer at the end.
I think everybody has now vivid memories of getting tested for COVID, for example.
(04:04):
So if we take a sample that was coming from your nasal pharyngeal area, well, that sample
doesn't just contain samples that are, I mean, material that is coming from viruses.
You'll have a melting pot of stuff, right?
So you'll have the human components, you'll have all of the bacteria that are part of
(04:25):
our normal flora.
I think we talk a lot about that, what is part of the microbiome of the nose, and then
you'll have the viruses.
So the first step that any sample that comes in the lab for molecular diagnostic would
have to go through is what we call an extraction step.
So what we want to do is really making sure that whatever material that we're working
(04:48):
with is the material coming, the genetic material coming from the virus.
So then what would happen is then once we know for sure that we have the genetic information
coming from the virus, what you want to be able is to amplify that signal and then to
be able to detect it.
So as I said previously, you had a specific area in the laboratory that would do that,
(05:13):
and all of those steps that I was talking about of extraction, amplification, and detection
could have been done on various and different instruments.
So I think today what we'll mostly focus on, it's the ability of having all of those steps
within a black box and a super easy and fast way of detecting microorganism or pathogen.
(05:39):
So I think the big players that we kind of hear about a lot would be like BioFire.
So that's the instrument and the company is BioMaria.
And then you have GeneXpert that people might have heard about.
GeneXpert is the instrument, but it's the company C-Feed.
(05:59):
Other players that people might or might not have heard about would be things like Roche,
that's the big company, and the instrument that they have is Liat.
And then Kyagene is a little bit like of a later player in the multiplex diagnostic sphere
with the Kyastat.
So those are the instruments that we have right now.
(06:20):
We call them black box because all of those steps that I've previously described are happening
without any intervention from the laborer or the technologist.
So they all happen without us being involved in the process.
Wow.
It's amazing that such a detailed process.
(06:41):
And I'm sure from a lab perspective standpoint, that cuts down a lot of time for technicians
as well and turnaround time as well, I would imagine.
Oh, no, for sure.
Those type of instruments are a devil-edged sword in a sense because as a diagnostician,
(07:02):
we want to be able to see what's happening and to be able to also troubleshoot.
But now it's completely out of our control really because all of the quality aspects
are taken into account by the instrument itself.
So it's quite fascinating that we were able to automate and miniaturize all of those parts
(07:25):
in a way that it makes it way, way much easier and easily accessible, not only for the clinicians,
but also for the lab artisan.
And I know in the past, you've mentioned that like respiratory panels, for instance, would
be kind of the most commonly used, just like what we talked about with COVID.
And I think lots of people are kind of familiar with respiratory samples.
(07:49):
So what other, like we'll definitely go into, I think, all the details of that because I
know you've done a lot of research in that area as well, because it is the most commonly
used panel.
But in terms of other panels, what's being offered right now?
Oh my God, there's so many.
So if we look at the BioMaria product with BioFire, and I think that's funny because
(08:13):
a lot of the clinicians these days are phoning the lab and they're like, I want a BioFire.
And for me, my answer is always like, which one?
Yeah.
Which, what are we looking for here?
Yeah, which one?
Because I think people are not aware that there's a lot of different panels that are
available for BioMaria at this point.
So there's the pneumonia.
(08:34):
So we're talking about lower respiratory pathogens, and they also have one for that are more upper
respiratory tract type of infection.
They also have GI panel.
They have a meningitis panel, the ME panel, they call it.
They have a blood culture ID.
So that's from positive blood culture.
(08:54):
Then you can put it into that panel that goes onto the BioFire.
And I'm also interested to see that they also have what would be like for a joint infection,
but I didn't have the pleasure yet to be able to work with that one.
But it's just to show that please don't call your lab saying that you want a BioFire because
there's so many different panels that are available.
(09:15):
So it's always more helpful to really be clear about what you're looking for.
If you're looking at GeneXpert, I'm not going to name all of the panels that they have because
they have more than five.
But things that you probably have heard is that they'll have like the COVID-2-AB-RSV
panel.
They have cartridges for all sorts of things like from C. diff, neuro, gyne, so STI testing
(09:40):
on the GeneXpert, C. diff testing on the GeneXpert.
So they have a quite big array of cartridges that are available for testing.
And then in terms of the BioFire panels, so let's say the REST panel, what are we looking
at?
So obviously the type of specimen is going to depend on the type of panel and what we're
looking for.
(10:01):
But what are some of the turnaround times that people are looking at?
And what does this really cost for the lab?
That's my big question.
Yeah.
Okay.
So we can talk about the differences between the various panels that are available, but
I think, I guess I'll just tell you the price.
(10:23):
So depending where you are in Canada, I think the pricing might change depending on the
contract that you have with those companies.
But normally it's in the hundreds of dollars.
And the reason why we mentioned this, it's quite significant because for the longest
time in the molecular area, we use what we call lab-developed tests.
(10:48):
The lab-developed tests are often super easy to establish in Canada in the sense that if
you have your set of primers and then you have your reagent for your real-time PCR,
so it's easy in terms of it wouldn't be really costly compared to hundreds of dollars for
a cartridge on a multiplex panel.
(11:11):
So on the ABI, because that's the real-time PCR that we use here, often a lot of the tests
that we would do would be on the magnitude of less than 20 or $10 per patient.
Yeah.
So a huge difference.
So it's significant, right?
So the approach that we took here at my laboratory was to really try to have a laboratory stewardship
(11:37):
in a sense to try to really make sure that the test that we're doing is providing the
answers that the clinician required to take the best care as possible for their patient
population.
Yeah.
And I think that's really important.
When we talk a lot about stewardship in the clinical world, but I think kind of taking
that into account and from a lab perspective standpoint is really creating that awareness.
(12:00):
And sometimes when I'm a clinician, so when I'm wearing the clinician hat, you don't think
about these things.
You really are just trying to find the answer because the answer is going to help your patient
get better or the answer is going to help give us an answer to better treat the patient.
And we always think of it more from a stewardship standpoint in terms of antibiotic use.
(12:25):
And I know that especially with the respiratory panel, you've done some work also in research
around this area.
So probably changing the gear a little bit because I know that we've talked a little
bit about the costs and some of the, I guess, advantages and disadvantages of this, but
really going into what clinicians, the reason that we are ordering these panels, what is
(12:50):
some research that you, and do you want to talk a little bit about your research around
how you've seen these respiratory panels help us in the clinical world?
Yeah.
So here at our laboratory, I think the panel which we had the most experience with was
the respiratory panel, so the RP1 at the time.
So when I joined the lab, one of the research that I was able to participate in was about
(13:16):
the utilization of biofire respiratory panel for the BMT, so the bone marrow transplantation
unit and the impact that the utilization of such equipment would have on infection control,
but also on antimicrobial stewardship.
So we know that that population has a tendency to present with high-grade temperature or
(13:39):
fever, and it's always kind of the concern about, well, is it part of their evolution
of their disease or is it because of an infection?
And if it's an infection, is it due to viruses when you're in the respiratory viral viruses
season?
So what we were able to show, and for people that are curious and want to go and read about
(14:03):
it, we have an article titled Biofire Film RA Decreases Infection Control Isolation Time
by Four Days in ICU, BMT and Respiratory Rewards.
So this was published by Dr. Wong and all, so I was one of the contributors to that study.
But I think the title will kind of say it.
We were able to show that the utilization of the biofire, despite the upfront cuts to
(14:27):
the lab, had downside effect in the sense that we were able to reduce the isolation
time for those patients.
And we know that having patients in isolation is often problematic in terms of the quality
of the care that they're getting because often for the nursing staff, it's easier to keep
the care for a lot of people that you have to dawn and off precautions for.
(14:50):
So that's just an example of how an equipment in the laboratory has a direct impact on the
care that patients are getting on the ward.
So I think that study was really good and it kind of helped us also build a business
case and show value for an instrument that would be used in the lab.
The only caveat that I would put there is that it made a difference as long as the laboratory
(15:15):
was using this instrument as a stat instrument.
And we'll talk about it maybe a bit later about the impact of having those type of equipment
in the lab.
It's only true if I'm able to act on the sample right away.
So during that study design, what we had done is like all of those samples that were coming
(15:36):
from ICU, BMT, and the respiratory wards had to be processed within one hour of receipt.
So then the fact that the instrument is so quick, you can really capitalize on that because
we were putting it on the instrument right away.
So I guess what I'm trying to say is if the wards collect the sample and doesn't send
(15:57):
it to the lab, or if the lab received the sample and don't put it on the instrument
right away, then you lose the benefit of having an instrument that is really quick.
Definitely.
So those are some of the things.
And sometimes in the clinical world, as opposed to when we're doing some of the research,
we can sometimes find those discrepancies too.
(16:19):
Because sometimes with clinical, there's like delay for collection, there's delay for multiple
reasons for the sample to get to the lab.
Probably also depends on the number of samples that are coming in.
And so hence why we always kind of talk about lab stewardship and really understanding,
are we sending the sample for the right reasons?
(16:42):
And is this going to make the difference because we don't want to burden our lab colleagues
either.
Yeah, no, good point.
And I also like what you mentioned about, it's also knowing the specimen type that you're
sending.
Because sometimes if you don't have the conversation with your microbiologist in the lab, then
(17:05):
you don't have that information.
But of all the instruments that we have in the lab, some can or cannot process certain
specimen type.
So what I'm trying to say here again is that if the only sample that you can collect on
one of your patients is a tracheal aspirate, well, it might not be compatible to be put
(17:28):
on your biofiber and therefore you're not getting the result as fast as you were hoping
to get it.
Right?
So you have to change the methodology to process that sample.
But something else to keep in mind.
And that kind of brings me to the second paper that we've done in collaboration with the
BioFire, which was the utilization of bronchoscopy samples and try to put that on the BioFire
(17:53):
and see that the performance was still fairly good, but not as good as we were hoping it
to be.
So right now for us, we're not yet putting BALs, for example, on the BioFire, but it's
a conversation that we would have with the clinicians in terms of how strong is their
(18:14):
pre-test probability that they think that there's a viral infection going on.
And then knowing the performance on the test, we would decide if we would go that way or
not.
Right?
So just for our knowledge, for the listeners as well, the best sample right now would be
your nasopharyngeal sample.
Yeah.
So on the respiratory panel, on the BioFire, the best sample would remain to be the nasopharyngeal
(18:41):
squad.
Okay.
And then also just because we have listeners that are clinicians, but we also have pharmacists
and we have nurses kind of from all across the world.
So just to kind of let them know what type of organisms and pathogens are we detecting
with like, for instance, the respiratory panel, just to name a few.
(19:02):
Okay.
So the respiratory panel will have like your regular steps.
So you'll find the flu, A, B, RSV, you'll have the COVID.
In terms of the other viruses, it has the ability of detecting human metonymovirus,
rhino enteropara influenza as well.
(19:23):
But it has also the ability of detecting other organisms depending which BioFire, if you're
on the pneumonia panel versus the RP2 panel.
I'm just going to provide the information for the RP2.
So the other organism that I was thinking about was, for example, certain bacteria,
(19:45):
the bordetella paraparctis, the media pneumoniae and mycoplasma pneumoniae.
And then also all of the other human coronaviruses that were known prior to COVID were also part
of the RP2.
And then for the pneumonia panel, that would also include like strep pneumoniae homophilus,
(20:06):
it'll be able to detect those as well.
Yep.
If we look specifically at the pneumoniae one, so yeah, so it's 33 target.
And that one would have like stuff more like streptococcus, biogenes, pneumoniae, even
some acinetobacter.
And the part that I think is also interesting about the pneumonia panel is the ability of
(20:31):
detecting some antimicrobial resistance gene.
But again, this one is not a panel that we had the opportunity or luxury to be able to
use at my laboratory, but those would be some of the perceived like perks of having that
panel.
That would be fantastic.
Yeah.
But in its own way, right?
(20:51):
So sometimes there could be pros and cons to technology as well.
And some of these molecular methods are super sensitive.
So I know in the past, you and I have had multiple discussions about biofire versus
gene expert.
And I know you want to talk a little bit about and tell the audience kind of the differences
between that, because even me as an infectious disease physician, I could tell you that I
(21:14):
may not know all the differences, including kind of what the sensitivity specificities,
the CT values, we always talk about these numbers, but I love to hear it from a lab
expert.
Okay.
Well, I would say that, you know, when you look at the clinical performance or the laboratory
performance of the two assays, like it's a PCR assay.
(21:36):
So their sensitivity specificity from a laboratory perspective would be above the 95%.
Right.
And I think they're pretty similar in that regards in terms of sensitivity of the assay.
To walk you through the differences between the two, what I would say is if we start with
CIFID, CIFID is a multiplex panel, but it's limited target.
(22:00):
Okay.
So as I mentioned, they have a lot of different cartridges that you would have to build up
on.
But in terms of, if we just speak about respiratory panel, they have this combo of flu A, B, R,
S, V, and COVID.
So one of the advantage is that it would specifically answer your question because they have also
(22:22):
a cartridge that is COVID only.
Okay.
So I feel like it's a bit closer to what a clinician with duty would think about like,
well, is this influenza?
Then you order a gene expert and you will get your answer.
It's pretty straightforward.
From a laboratory perspective, it's really, really easy to use.
As a matter of fact, it's one of the rare multiplex assays that is Health Canada approved
(22:45):
to be used as a point of care assay.
And we've seen that during the pandemic as well.
It is quite fast.
So for the respiratory panel that I was telling you about, it can provide an answer within
35 to 40 minutes.
And then it used some end fluorescence in terms of detection.
But it also has the ability of providing you a CT value.
(23:09):
And then overall, it might be a bit cheaper than the Biofire if we're just talking about
the respiratory panel in terms of the cost to the lab.
But if we look at the Biofire, this one, as I mentioned, is syndromic and it has more
than 20 targets if we're talking specifically about the respiratory panel.
(23:30):
It's also easy to use, but there's no CT available on the Biofire.
Okay, so it's a real, completely real black box in the sense that you cannot see how strong
or low of a signal was detected by the instrument.
But it's quite sensitive.
I've mentioned the five panels that they have also, and it's just that it takes a little
(23:53):
bit more time.
So it's just a bit over an hour to get the full panel result.
I also think that the Biofire kind of brings an ethical conundrum or conversation because
it's a syndromic approach.
So I think we've been accustomed to do an assessment of your patient, come up with your
diagnosis and then try to have the diagnostic support your hypothesis.
(24:19):
But in this case, you might have been thinking about influenza, you're sending me the sample,
you're asking for a Biofire, but I'm testing for 22 other organisms that you have not requested.
So I feel like it's a good ethical conversation in terms of bioethics and what do you do with
(24:41):
that?
And some people would say, well, you only have to report what the clinician has requested.
But what if it's positive for something that the clinician has not requested?
Can you really hide that information?
Yeah, and that's the thing with all of these reports, I think, is that you can tell us
more.
But for any of these respiratory panels, you usually get this line list of pathogens and
(25:06):
then it'll just say positive or negative.
And then taking that into your clinical context, I think, can be actually quite challenging
because a lot of them have similar presentations.
So we're talking about the exact same patient, but you could have multiple viruses.
(25:27):
And something that I deal with in my clinical world is obviously I'm a pediatrician, so
pediatric infectious disease, we're going to see a lot of respiratory illnesses.
And with PCR testing, although it's great, molecular methods give us a quicker result,
we also see those long lasting effects.
So six weeks prior infections are being detected as well.
(25:50):
So you also have to, as a clinician, take into context, like, is this a previous infection
or is this really my acute illness?
And relying on that, and then let's say I take off antibiotics because I think this
is what's going on, is that harmful or problematic in that clinical case?
So I think it can be challenging, definitely from our perspective too, but I can't even
(26:12):
imagine at least I have the clinical context.
And so from your standpoint, being on the lab side of things, and you do both sides,
so obviously right now I'm giving you the lab hat, but being on the lab side of things,
it's challenging because you don't get all of that information.
You're not fully involved from like day one with the case, you know, and so you get really
(26:35):
what we place on the requisition.
Yeah, no, it's a good point.
Yeah, it's like anything, right?
The same way that when you see your patient, you come up with your differential and the
laboratory, we also come up with a differential based on the very limited information that
we get.
So if people could only remember one thing, I guess, from anything that I said today is
(26:59):
get a good relationship with your laboratory and provide more information.
The same way that when you send a requisition form to diagnostic imaging, you would provide
with a little bit of a history.
It's the same thing for microbiology, right?
So a history can go a really long way in microbiology and helping us find what you're looking for.
(27:21):
Because the reality is people think that the laboratory will find whatever is in your sample,
but that is not how the lab is made.
The lab is made to identify the common causes of issue for the syndrome that you're talking
about or the sample type that you're providing.
So if you're looking for a zebra, it's always better to get in touch with your medical microbiologist
(27:46):
and let them know that you're looking for a zebra.
So I think that would be a big, big message.
The other thing that I'll always use as an example is it's always also important for
the clinician to understand the different technologies that we're using in the lab.
And we try to have this dialogue with our clinician in a sense that we provide comments
(28:10):
with our reports so you know what we've tested your sample for.
And sometimes, I don't know, as a labartician, we feel like we're misunderstood or not fully
read.
So the best example would be, I think I've told you that story, but I kind of like that
story.
It kind of shows us how all those molecular assays are fantastic to look for the bread
(28:33):
and butter stuff.
And also, I'll tell you about the strength of a story.
So I use that story with the resident a lot.
So the story goes as follow, and you can also Google it because it's a true story.
It's about a family that was presenting with rice water diarrhea.
(28:55):
So for anyone who is ID trained or has interest in ID, if I tell you rice water diarrhea,
there's a diagnosis that comes in mind right away.
Exactly.
So I'm not giving the punch just right.
I'll keep it quiet over here too.
(29:17):
So that sample was sent without a story to the laboratory, and then a molecular testing
was done, and it came back negative, no pathogen found.
So of course, we normally get involved when things are not fitting or it's not the result
that we're expecting.
So that's when the conversation happened.
(29:37):
But we could have saved time and managed those patients differently if that conversation
happened earlier.
So what I was describing earlier on was a case of cholera in a family.
So it's just an example of you can have a molecular assay that detects cholera, but
(29:57):
a cholera that is found all over the world, but not the one that you have locally.
Exactly.
Yeah.
And I think we've discussed that a lot during the pandemic, the whole conversation about
variant, but in the bacterial world, you also have different serotypes, for example.
So it's important for a labartician to also know the limitation of their technology.
(30:20):
But from a physician seeing patient perspective, I think it's also always important to keep
the story in mind and bring the clinical diagnostic combined together and see if it makes sense.
And so in this case, you weren't able to pick up that specific strain on the serotype, and
(30:44):
that's what the PCR was negative for?
That's why.
So the PCR was a multiplex.
It had the ability of detecting, you know, LTOR, so one of the cholera that we normally
see.
Yeah.
But then it seemed like we had a different one in BC, and the primers would not attach
(31:06):
to the genetic information of the one that was local to us.
It's just another example of, you know, the history at the end of the day and the clinical
examination of your patient still makes a difference.
It's not because the PCR said it's negative that what you're saying is not infectious,
right?
Right.
(31:26):
Yeah, and I actually deal with this, you know, often because people will come in and they
have respiratory symptoms, looks like a viral upper respiratory tract infection, and the
PCR respiratory panel comes back negative, and families will always ask, but I don't
understand.
We said they have a virus, but the thing to like, we always try to educate our families
(31:49):
as well and also teams that we work with as, you know, being a consultant is that you don't
always get the answer for which virus it is.
You have to be looking for those specific viruses that are on there.
Now, if it's a different strain or it didn't pick up, it could be, I mean, there's multiple
reasons, right?
We talked about specimen type, we talked about, you know, the lab, like the technology itself,
(32:15):
right?
And in the end, we also have to remember that it is obviously no longer, you know, it is
a machine-based test.
And so things can be, you know, not as streamlined as sometimes when it's done by hand, right?
And so because it's done quick, that's fine, but it's also machines can make mistakes.
(32:38):
And so there could be lab errors, there could be specimen errors as well.
And so I always try to, but really important is that you don't have to detect all viruses
because I think it goes back to your cholera story is, you know, sometimes you don't pick
up the strain or this, the variant or the serotype.
So I think that's something that we should all remember as clinicians.
(32:59):
In terms of, I know we talked a little bit about the advantages and disadvantages of,
I know specifically you've worked a lot with the BioFire respiratory panel.
Is there anything that comes to your mind that would be, that we didn't talk about today
that would be an advantage or disadvantage that you would want our listeners to remember?
Yeah.
(33:20):
So, I mean, I think we covered a lot of the various aspects.
So if I have to summarize the disadvantages, I mean, we kind of talked about the fact that
the cost could have been a bit prohibitive.
I think there is some pressure on the laboratory to really be quick at handling those samples,
to put it on the instrument.
(33:40):
So that's pressure on us if we want to be able to show the value of those faster and
around time.
But then related to that, you had mentioned the amount of samples that are coming in the
lab at the same time.
But the reality is a lot of those instruments like the, the GeneXpert or the LIAT or the
BioFire, they're limited in terms of how many samples can they run at the same time.
(34:04):
So on average, they're all below 20 sample per hour compared to our routine in-house
PCR or real-time PCR.
Those can do hundreds of samples within three hours.
So I think that's something else to keep in mind in terms of the low throughput that those
instruments have.
(34:24):
And then I think lastly, it's really like all of the too many targets maybe that might
not be relevant to certain patient population that we're providing.
So that could be perceived as a disadvantage and an advantage.
And then in terms of advantages from a laboratory perspective, you know, I started off this
conversation by telling you, well, the people that work in molecular diagnostic have to
(34:48):
be like highly, highly trained.
To use those black boxes, you don't need to be highly trained.
Like often the manipulation of those cartridges are super easy.
So we can have that step being done by people that are not like the most trained people
in our laboratory.
And other advantages, I mean, I'm in Vancouver, you know, real estate is a real problem.
(35:12):
So a lot of those instruments have a really small footprint.
So I think it's an advantage and it can also be interfaced with your LIS.
So that makes it even faster for reporting.
So yeah, there's a lot of pros, a lot of pros and a little bit of cons.
Yeah.
I think that's a good, great summary of that.
(35:33):
So what is, what's the future then?
So what are we looking at?
Like, are we, are you validating, is your lab validating additional biophier panels
right now?
And what's kind of the new thing that's out there?
Yeah.
So good question.
I think there's a lot of conversation about what's going on in the world of molecular
diagnostics.
So, I mean, the multiplex panels are super interesting.
(35:57):
I told you about the pneumonia panel.
That's something that we will most likely want to be able to play with.
And then the sample type, the fact that it's putum and BL that's like major and makes sense.
So, but that would be probably in the future the same way with the, sorry, the joint fluid
samples.
(36:18):
Yeah.
So I think that's going to be super interesting because we know that joint fluid from a smear
when you do the ground smear, it's not super sensitive, but if we have the ability of having
a multiplex PCR or a multiplex black box that allows you to do early detection, it would
(36:38):
make a complete difference in terms of management of those or atopation.
Right.
So I think that's exciting.
Yeah, definitely.
In terms of timeline that are approaching a bit faster for us.
So we're interested in looking into the GI.
So we've done our validation for the GI panel and we're about to go live with that.
(36:58):
So that should be for, you know, this summer.
And then we're also looking into the meningitis panel.
Right.
So I think that also makes quite a big difference if we're able to detect early on any cases
of meningoencephalitis.
Yeah, exactly.
I think from a clinician standpoint, all of this sounds like great because there's a lot
(37:23):
of times when you, you know, it's challenging, especially like being in Saskatchewan, we
have a lot of remote communities and sometimes patients are very, very ill.
And so receive antibiotics prior to arriving at our center.
And so for me, the advantage of getting, for instance, like a PCR, at least if they've
(37:45):
had multiple courses of antibiotics prior to arriving, it can at least help me narrow
down even from an antibiotic standpoint.
Right.
And so, and also kind of figure out what is the most common pathogen.
Like we always kind of takes away that guessing game that sometimes makes clinicians a bit
uneasy, I would say, if that's the right term.
(38:11):
So you did talk a little bit about the BCID panel, which is that currently validated?
Like you guys are using that there?
So we had a chance to work with it and validated it.
But the thing, you know, it's always a balance.
The same way that when we see patients, you're always trying to figure out like how much
(38:36):
any type of management choices you take, how much would it impact your patients?
So it's the same in the laboratories.
So for us, because our volume of positive blood cultures were so high, so I'm at Vancouver
Coastal Health, so we provide service for more than 12 healthcare centers.
(38:59):
So we have a fair amount of blood cultures coming in.
And on average, we can have like anywhere between 15 to 20 positive blood culture a
day.
So trying to put that on the instrument in terms of volume will make it for us impossible
to also do respiratory.
(39:19):
So we had to make a choice.
So we had to decide like, what's more important for us?
Is it to get an answer quickly on the respiratory side?
Or do we think that the gain that we would do on the blood culture would make such a
big difference?
So because of the infection control components related to respiratory viruses, we decided
(39:43):
to go that route because we were fairly quick at identifying the organism on the blood
culture.
So the first thing that you have to keep in mind is that on the blood culture, it could
be anything and everything.
The BCID panel is limited to a set numbers, right?
(40:07):
So the moment it doesn't identify your organism, you just delayed by one hour if you weren't
already on top of it.
So we felt like with our workflow, it made more sense to dedicate the instrument on their
respiratory panel.
Yeah, and that's fair.
I think we're also practicing in an era where we have Malditov and other technologies.
(40:30):
And so previously when we just had biochemical tests, I think it was more challenging and
we wanted quicker identification.
But I think a lot of times with that MRSA select plates is a lot of technology that's
already come through that's making it easier for clinicians, especially those practicing
in an area where they are using this constantly.
(40:53):
But I think you're bringing up a super valid point in a sense of epidemiology and population
is super important in terms of those decisions that you take in the lab.
My conversation with you might have been different if 60, 70% of my people that had positive
blood cultures were Staph.
(41:13):
And then maybe 50% or 30% of them were MRSA.
So it would make such a big difference to be able to use BCID because it would have
a direct impact right away.
But that's not really my situation right now in terms of the patient population that we're
providing care for.
So yeah, it didn't make total sense at the time to go that route.
(41:37):
Yeah, fair.
And I think, yeah, that's one thing about ID, right?
It's infectious diseases, different everywhere.
You cross the border and it's like a provincial border and you're facing with different diseases,
different conditions, different demographics and the epidemiology is very different.
So I think it's important to always, I think one of the things that I've learned is that
(42:00):
there's a lot of technology out there and there's a lot of things that we'd want our
labs to be doing.
But I think having that conversation as clinicians with the labs, microbiologists and having
that close connection, that's I think really, really important because you can bring up
these types of topics and ideas and really understand it from, we obviously just want
(42:24):
the answer, but who's providing us the answer, that also depends, right?
We need to figure out what the rationale is behind having one panel versus the other using
gene expert over another respiratory panel, that type of thing.
So you bring up a very, very valid point.
That's why it's great having somebody who's in the field, in the lab and the clinical
(42:44):
world.
So is there anything you would want our listeners, I know you mentioned before a couple of key
points, is there anything else you have a burning desire to tell your listeners from
a lab perspective standpoint that something that they should do and follow and would be
helpful for our lab colleagues?
(43:07):
I mean, I'm going back to what I said earlier, I mean, having a history, really, really helpful.
So if you guys can provide more clinical information, we'll be better at supporting the team that
is seeing the patient, that's for sure.
And I think having conversation with your laboratory as well, trying to understand what
(43:28):
kind of technology are being used can also help you be better at the job that you're
doing.
So knowing the limitation of the instrumentation that you're using is also key.
Well, that's a very, very valid point.
And I think a lot of our listeners are going to enjoy this episode because we don't talk
a lot about diagnostic methods and what's new in the lab world.
(43:54):
So I'm excited to have you on our podcast today.
So thank you so much for taking the time and this great opportunity for us to learn a little
bit of, you know, the different technologies and molecular methods that a lot of us are
probably already using and don't even realize some of these details and points.
So really appreciative.
(44:14):
Oh my God, thank you so much.
It was a lot of fun.
So my pleasure.
Perfect.
Thank you so much.
Have a great day.
Thank you, Dr. Purwall, and a special thank you to Dr. Charles.
Thanks for joining us.
If you've got a topic suggestion, please email us at thecanadianbreakpoint at gmail.com or
(44:36):
get ahold of us on Twitter at CA Breakpoint.
See you again soon at the Canadian Breakpoint.
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