10. S1 Episode 10: Disseminated Gonorrhea Infections

Dr. Rupeena Purewal invites special guest Dr. David Alexander, PhD Microbiologist in Winnipeg, to discuss Disseminated Gonorrhea Infections.

Episode Transcript

(00:00):
Thanks for joining us again at the Canadian Breakpoint, a Canadian infectious diseases

(00:12):
podcast by Canadian infectious diseases physicians.
I'm Summer Stewart, here with Dr. Rupeena Purewal, pediatric infectious diseases specialist
from Saskatoon.
In this episode, we welcome Winnipeg microbiologist Dr. David Alexander to discuss disseminated
gonorrhea infections.
Dr. Purewal.

(00:33):
Welcome to another episode of our podcast the Canadian Breakpoint.
So today we have a very special guest with us, Dr. David Alexander, who's a PhD trained
microbiologist with a long standing interest in the epidemiology of infectious diseases.
For the past 15 years, he has worked in Canada's provincial public health laboratory system.

(00:54):
He's currently based in Winnipeg and is an assistant professor with the Department of
Medical Microbiology and Infectious Diseases at the University of Manitoba.
Dr. Alexander's research encompasses diverse topics, including novel diagnostics, genomics,
antibiotic resistant organisms, and the surveillance of bacterial pathogens that cause foodborne

(01:16):
illnesses and sexually transmitted infections.
So welcome, Dr. Alexander.
Thank you.
Thank you for the invitation and the introduction.
Perfect.
So today we're talking about a very important topic linked to sexually transmitted infections
on disseminated gonococcal infections.
And congratulations on your recent publication in the Journal of the American Sexually Transmitted

(01:41):
Diseases.
That's very exciting to see some of your work there.
And so I guess before we kind of start talking a little bit about the study and all of your
research results, why don't we give our audience a bit of a background on gonorrhea and disseminated
gonococcal infections, including presentations?

(02:02):
Of course.
So gonorrhea is a sexually transmitted infection.
It's caused by bacteria, nigeria gonorrhea, often just called the gonococcus.
And in most Western nations, gonorrhea is considered the second most common bacterial
sexually transmitted infection, second only to chlamydia.

(02:23):
Like most sexually transmitted infections that most commonly present either, well, in
your bits.
So you have uncomfortable urination, dysuria, bleeding.
There's lots of wonderful terms for your sexually transmitted infection.
Gonorrhea is sometimes called the drip because you just have this discharge that leaks out.

(02:45):
And yeah, I guess what one thinks of with sexually transmitted infections are infections
in the penis or urethra, vagina or cervix, that sort of thing.
However, the more work you do in the realm of especially gonorrhea, you realize that
it will affect a lot of other nuchal membranes.
So there's been increased recognition of proctitis from rectal infections, as well as pharyngitis

(03:09):
from throat infections.
And that's just really the bacteria will cause symptoms wherever it is introduced.
And due to the wonderful and varied ways that people interact with each other and have sex,
we see it in all sorts of different places.
What was new to me before we really started this study was what's called disseminated
gonococcal infection.

(03:30):
And that is infections that occur inside your body, so systemic presentations where you
have the bacteria in your blood or in your joints where they cause arthritis, joint pain.
And even there's sort of the worst case scenario is when it can spread and lodge in organs.
We've seen where we are in Manitoba, endocarditis, so heart infection, and even meningitis, brain

(03:57):
infection.
And that's unusual because even though gonorrhea has a cousin, nisteria meningitidis, that
causes, as the name suggests, meningitis or brain infection, it's really uncommon for
gonorrhea itself to do that.
So definitely, I mean, there's multiple different presentations, as you mentioned, and really

(04:18):
our focus today on disseminated gonococcal infections, because there hasn't been a lot
of research to, even my knowledge, or even in our clinical world, identification of such
cases like you mentioned, it's not as commonly spoken about.
And so I guess what really sparked your interest in this topic?
Well, working in the public health system in Canada, most provincial public health labs

(04:43):
basically do province-wide screening for a whole variety of sexually transmitted infections.
And that's really where I first encountered all of these diseases is as part of my routine
work, looking at the rates of infection.
And in the prairies, especially in Canada, the rates of infection are higher than in
the rest of Canada.

(05:04):
So yeah, so if you look at the history of sexually transmitted infections in Canada,
there's really like a before HIV and after HIV world.
And so it's remarkable to think that it's actually been now almost 40 years, like 1983,
when the first tests for HIV really became available.

(05:27):
And the AIDS epidemic was recognized, and there was this big push towards safer sex
and all these other things that you're of a certain age, you grew up with during the
80s and especially during the 90s.
And these campaigns were really, really effective.
And we saw plummeting rates of all sorts of diseases.
Of course, HIV was the primary one because at the time it was a death sentence.

(05:52):
And so you definitely didn't want to get HIV.
But the same precautions work against syphilis, which came close to elimination and really
dropped the rates of gonorrhea and chlamydia.
So if you look at data that's available from, for example, the Public Health Agency of Canada,
the rate of gonorrhea by about the year 2000 was maybe 25 cases per 100,000 people.

(06:18):
So quite, quite low.
By contrast, in Manitoba right now, we're about 10 times that, about 250 cases per 100,000.
And what's remarkable is that most of that increase has happened in the last, well, really
about since 2015, so the last five to 10 years is really when that rate has gone up.

(06:39):
And we're not really sure why.
We assume it has to do with changing behaviors and perhaps less concern because even for
HIV now there's very effective treatment, so it's no longer death sentence.
And certainly for things like gonorrhea, given uncomplicated case, currently we just use
two drugs and one dose of each of those drugs and you're pretty much cured.

(07:04):
So anyways, suffice to say when it comes to disseminated gonorrhea, if you look at historical
literature, they would argue that two to 3% of cases might present a disseminated infection,
so in your blood with arthritis.
It's been difficult to actually figure out that exact number, that portion.
But you know, if you're only seeing a thousand cases of gonorrhea a year and your DGI rate

(07:29):
is two or 3%, you don't see very many of these cases, even if you're a practicing clinician.
Whereas as soon as your rate of gonorrhea goes up, you expect to see more.
But what we've really been concerned about and what started some of the research we're
going to talk about has to do with the rate of the disseminated infection went up at a
much faster rate, about three times faster than the overall rate of gonococcal infection.

(07:55):
Okay.
And the one thing you can say about disseminated gonorrhea is if you look through the microbiology
literature, there's lots and lots of reports, lots of lots of case reports, and they always
say, oh, this is a rare presentation of gonorrhea.
But when you add up all these reports, it's actually not quite as uncommon as one would
think.

(08:15):
And so that's the other question that DogsR Research is, is the increase we're seeing
just due to increased awareness that these infections can occur.
Yeah.
Yeah.
So definitely having, you know, this on your radar as a clinician, I think you're more
inclined to kind of look for infections.

(08:40):
You're more inclined to send cultures.
And I think we'll talk a little bit about that in your study as well as to how much
is done, you know, diagnosed with PCR versus culture, which is sometimes a limitation when
we're dealing with sexually transmitted infections.
Yeah.
So I guess without further ado, because I'm excited to hear a little bit more about your

(09:01):
research, why don't we introduce your, you know, some of your research findings and talk
a little bit about your abstract in the paper.
Okay.
So I should start by saying this research project's been going on for a while and it's
gone through several stages.
So really our initial interest was because, you know, 15 years ago, disseminated gonorrhea

(09:26):
was very uncommon.
We would, the lab, even though it screens, you know, tens of thousands of people per
year and detects several thousand cases per year, disseminated gonococcal infections were
very, very rare.
We would see maybe two or three a year and some years there were none.
And then, as I mentioned, the rate of that started going up.

(09:48):
It was, you know, a dozen and then two dozen and three dozen a year.
So it really caught our attention.
And we were also getting contacted by physicians who were struggling to get a clear diagnosis
because this is a sexually transmitted infection, the approved normal commercial and health
Canada approved tests geared towards things like endocyclic swabs or urine samples, you

(10:13):
know, things you normally would associate with sexually transmitted infection.
But what was happening is these folks were showing up in the ER complaining about a sore
elbow or a sore knee.
And you know, you don't immediately think, oh, it must be a sexually transmitted infection
if it's in your elbow or knee.
So often in those cases, you would get a joint fluid draw.

(10:37):
So you could draw a culture to see if you can grow other organisms associated with those
sorts of infections here in floor like your strep and your staff and that sort of thing.
But Neisseria gonorrhea is actually a tricky organism to grow.
And unless you're using the right media, you're not going to catch it.

(10:57):
And even if you are using the right media, you may not catch it all the time.
And so we were being asked, are there better ways to diagnose it?
And initially, we really weren't sure our standard method for diagnosing gonorrhea uses
nucleic acid amplification.
So think of like a PCR type test where you're detecting the nucleic acid from the organism

(11:21):
itself and not you don't have to actually grow the bug.
Neisseria gonorrhea was introduced probably about 15 years ago and is universally used
now because it is so good.
And really, when it was first introduced, there was a bump in the rate of gonorrhea,
not because there was more gonorrhea around, but we were just so much better at detecting

(11:42):
it.
And even though it was initially designed for urine and the cervical and vaginal swabs,
the standard tests we used have been expanded to include rectal swabs and throat swabs.
And so we were thinking, well, if we're now finding this more commonly in joint fluid,
why don't we just test the joint fluid?

(12:02):
And so we did a study where we took about 170 samples collected over several months.
And after they've been fully worked up by our routine microbiology procedures, microscopes,
culture, and that sort of thing, we retested them using the nucleic acid amplification
test.
And we're quite surprised to see that even though we did grow a few samples by culture,

(12:29):
culture only detected about 40% of the samples that were positive by nucleic acid amplification.
Yeah, I mean, it wasn't a huge study, but we did test 170 samples of joint fluid.
And we really leave to find how well our tests performed on the joint fluid samples, even

(12:50):
though it wasn't a test necessarily designed for that.
And so yeah, if you want our actual numbers from there, five samples grew, or we grew
in Nigeria from five cultures, but there were actually 14 that were positive by nucleic
acid amplification.
And when we had an external lab retest some of those samples just to confirm our results,

(13:12):
they did confirm.
Basically this means that this is not an illusion.
There really is a lot more disseminated gonorrhea out there than we were expecting.
So that's really the first step is if you're going to look at infectious diseases, you
need to test that will detect them.
The next part we've moved into is really trying to understand is there something special about

(13:32):
the bacteria that cause these diseases relative to what's normally circulating in where you
are?
Because that's always the question when it comes to infectious diseases, is it something
about the bug or is it something about the host?
And of course, there's all these reasons why some people may be more susceptible to infection
than others.

(13:54):
And really when we started this work, I thought, well, we're probably just looking at a population
that is more susceptible or there's zone of access to healthcare or whatever reasons for
which you wouldn't necessarily get treated right away and the gonorrhea would have time
to spread.
And so to address that component of the question, we use genome sequencing.

(14:17):
I say that casually, but it's really taken a long time for genome sequencing technologies
to really come to where they are today.
I've been lucky enough to be involved with sequencing based approaches for a while now
and the power that they provide is really quite remarkable because unfortunately, we've

(14:41):
had so many cases lately and we've been able to isolate so many strains of gonorrhea.
We really were able to do a pretty decent sized project and sequence about a hundred
strains all from joints and blood sites.
So all associated with disseminated gonorrhea.
And so what we discovered when we sequenced them all and looked at them, they were more

(15:05):
similar than we expected.
Normally what happens with strains of any bacteria, if you take the time to what's called
type them and look at the differences between them, you see all sorts of different types.
I think people have sort of started to recognize this with COVID where every few months there
seems to be a new type of COVID, an alpha or a delta or different kinds of omicron.

(15:28):
And so there's this constant change in what the bacteria or the microbes look like.
And yet when we looked at our gonorrhea strains, we only found five different types, even though
we know that there are dozens, if not hundreds of different types of gonorrhea out there.
More than that, when we looked at these five types, they all shared something called the

(15:53):
poor B type, so poor B, it used to be called, I don't remember, protein one.
It's basically a marker that we use when typing.
And it's a really effective marker for typing because it has that perfect balance of it's
something that every gonorrhea strain has.
It's essential enough to the organism that it changes, that it's always going to be there,

(16:17):
but it also can change.
And it's the changes within between strains that we're actually looking at when we're
typing organisms.
But I don't want to get too technical, but the poor type we found is called poor 2206.
And it was found in all five of the different, I guess, flavors or strains of gonorrhea that
we were looking at.

(16:39):
And it was present in over 90% of the strains that we actually did sequence.
Now that's unusual because when we looked at a comparator group of strains in Canada
that don't cause disseminated infection, poor B is present in maybe 2% of those.
So even though it's only present in maybe 2% of what's out there in the world, it was

(17:02):
in over 90% of the strains associated with disseminated gonorrhea.
And that was a big surprise to me because I really thought it was probably a host associated
factor.
And then other sexually transmitted infections, it's individual behavior or susceptibilities
or things like that that predispose you to infections and then sometimes nasty infections.

(17:27):
And that's not the case with gonorrhea.
Yeah.
I was actually surprised to see that as well.
I mean, classically, what we learn in med school and also when we're training is to
when there are nyseria infections that are ongoing or persistent or recurrent nyseria

(17:47):
types of infections, then usually host factors like complement deficiencies or if they're
on certain immune suppressive drugs, those are the kind of areas that we focus on.
Then likely the patient might have this.
That's why they presented very severe with this.
But I think it's always two-sided and it's similar to how you mentioned with, we've seen

(18:10):
this with other infections, including COVID itself.
We've seen very severe presentations, milder presentations.
Sometimes it's host related, sometimes it's incidental.
And so, but I think looking at the molecular level, especially with gonorrhea here, identifying
a specific allele like this that is coming from 90% of your samples, I mean, definitely

(18:36):
has a correlation with that severity.
So that was a very interesting finding for myself as well.
So of course, when you have a finding like this, you go back to the literature to see
what else other people have seen.
And in retrospect, we shouldn't have been quite so surprised because this Orbi allele
has been associated with infections for a while.

(18:58):
And we live in an era of molecular diagnostics and genomics and all this exciting stuff where
sometimes we almost forget to look at the organism and just focused on the ACs and T's
and G's on our computer screen.
But if you actually go back to the bench or go back to sort of the classical microbiology
where folks are growing strains and really looking at them, it turns out that for decades

(19:24):
now it's been recognized that gonococcal isolates from disseminated infections actually are
quite different from the run-of-the-mill things you typically see with what's called uncomplicated
sexually transmitted infections.
And so we're continuing to look and try to correlate some of these old phenotypic findings

(19:45):
with what we can see in the genomics.
And we know some are quite well characterized.
For example, when you grow the disseminated strains on your agar plate that you see, and
normally they have what's called a transparent colony phenotype, they're sort of clear, they're
not sort of a solid dark opaque color.

(20:06):
And originally that phenotype was called opacity.
And so there's actually a protein called the OPA proteins that are now known to coat the
outside of gonorrhea and change how the organism interacts with your immune system.
Or B, which we've been focused on, is also something that's in the cell wall or the outer

(20:26):
membrane of the bacteria and interacts with the immune system.
And studies of Orbi have kind of revealed that it is actually able to interact with
the complement system, which is something you mentioned.
And so, I mean, briefly, I'm not an immunologist, but...
Neither am I, so okay.

(20:46):
But the complement system is part of your sort of innate immune system.
If it sees a foreign invader, it basically targets that invader to be cleaned up by other
components of the immune system.
So it sort of tags or targets you and says, get rid of this thing.
And what happens with gonorrhea, in part, do we think to the Orbi system, is that it

(21:10):
basically shuts that down.
It pulls this Jedi mind trick where it's like, oh, I'm not what you're looking for.
It basically down-regulates the complement system so it's no longer being targeted.
And the reason that's probably important is, you know, at the time the gonorrhea is doing
this, it's already in your blood.
It's already circulating through your system.
Right.

(21:30):
It can stop your immune system from taking it out.
It gets that much more time to persist in your blood and to spread to your organs, be
it your joints or your heart or wherever else it needs to go.
When you look at the disseminate gonorrhea literature, all sorts of sites can be acted
wherever the organisms land.

(21:51):
Most commonly in your guys' study, the isolates were blood and synovial fluid.
And was that specifically because that's where the isolates that were submitted or just with
correlation with the clinical presentations?
Yeah.
So in our case, we can only do the genome sequencing on organisms that we have actually

(22:13):
isolated in culture and grown in a lab.
And although we did have some cases with other, where the gonorrhea was in other sites, we
had a lot more trouble growing it out of that site.
So for example, we had some heart tissue that we knew was positive for gonorrhea using molecular
tests, but we weren't able to actually grow the gonorrhea from that site.

(22:34):
In at least one case, we had blood from that same individual and we could grow the gonorrhea
from the blood.
Yeah.
It's quite interesting.
You know, it's tricky.
Gonorrhea is a tricky pathogen for sure.
I prefer that.
So.
The only silver lining to a lot of these cases though, and again, this is something that
was noted in the older literature, but also confirmed in our study is that these bugs

(22:57):
are not particularly drug resistant.
They can still all be treated using common course of antibiotics.
The only catch is, as you might imagine, by the time, you know, gonorrhea is circulating
in your blood or other organs, treatment is a lot longer.
So it takes a week to four weeks to treat it rather than a single dose of a couple drugs.

(23:21):
And so that's one reason why it's great if you could do regular screening for gonorrhea.
And even if you're not thinking STI, if somebody is, you know, sexually active or is with new
partners or might've been exposed to do a screen for whatever STIs are out there.
Because that's the other trick about a lot of these organisms is infection is often asymptomatic.

(23:45):
And that's why we've changed our terms.
It's no longer sexually transmitted diseases, but sexually transmitted infections because
you can be having the disease actually present.
Yeah, exactly.
No, I think you mentioned a really good point there in terms of, you know, clinical presentations
because clinically a lot of times, you know, you're thinking about sexually transmitted

(24:08):
diseases in patients, but then all the testing doesn't get done or, you know, clinical picture
doesn't fit.
And then you lose them to contact or follow up and all of that combined, they can present
with like a disseminated infection.
So I think for clinicians out there, you know, having your work and, you know, some of these

(24:28):
findings being published, I think helps because people are then becoming more aware of a situation
that can present like disseminated gonorrhea.
And so really keeping in mind that that can be a presentation if somebody presents with
a joint infection, because typically that's not the first thing people think about when

(24:49):
they're thinking about STIs.
So our work still leaves a whole lot of unanswered questions.
We're still going through our genome data sets to figure out what other virulence factors
are probably present in these organisms.
And there's got to be some, but finding the right tests and methods to evaluate those
is tricky.
The other question too is that the strains we're seeing, they're not exclusive to disseminated

(25:12):
infections.
They're also out there circulating causing uncomplicated infections.
And so there's a whole other avenue of study that we're just trying to wrap our heads around
about, you know, maybe it's not exclusively something that's special that these disseminated
strains have.
It might be something that's absent from other strains that prevents them or limits them
from causing disseminated infection.

(25:33):
So there's a whole other set of questions out there.
And one other one we're wondering about is does the route of infection matter?
Is there something else going on there?
And again, this is purely speculation, but we're almost wondering if oropharyngeal exposure
or oral sex or something like that might predispose you to disseminated infections just because

(25:58):
folks often won't get tested for pharyngeal infections.
They may not be picked up.
And there's also some fascinating work being done on the natural history of infections
that suggests that throat infections will clear up on their own often within three or
four months.
They may be infected, never, never treated.

(26:19):
And yet over the time that you have this infection and maybe just like a little bit of a sore
throat, which has many, many causes, especially during winter respiratory season, it gives
a chance for the organism to get into your bloodstream.
But again, those studies are very, very difficult to set up and look at because of all the stigma

(26:40):
around studying sex and sexually transmitted infections and just the logistics of separating
people who may only engage in oral sex versus other forms.
Right.
That's fair.
Yeah.
So in terms of, I guess you answered a couple of these questions already, but why is Manitoba
or why was it speculated specifically Manitoba seeing these?

(27:02):
And I know you mentioned, you know, host factors.
We talked about specific areas that we normally see more sexually transmitted infections.
I think the Prairie province is to have higher incidences of that in Canada, as we've seen
with our syphilis rates as well, even here locally in Saskatchewan.

(27:22):
But is there another speculation as to, or in your literature search, because I definitely
didn't review the literature in Desemonee-Gonorrhea to see what Saskatchewan or Alberta was seeing,
is there mention of other provinces having an increase in Desemonee-Gonorrhea as well?
So it's hard to say specifically for Desemonee-Gonorrhea in Canada because it is a subject that's understudied

(27:48):
at this point.
But we do know that in the US there's been publications from several states who are seeing
similar trends.
And again, we're not sure at this point if it has something to do with the change in
the circulating strain or if it's just related to overall across the Western world, there's
an increase in sexually transmitted infections.

(28:11):
Again, I mean, it's been 40 years since the HIV scare and for the past 20 years, Canada's
been seeing an increase in sexually transmitted infections of all kinds.
So we might just have hit that critical threshold where everyone is seeing more of these or
at least recognizing more of these infections.
There's really not anything special about Manitoba except for the fact that, and this

(28:36):
is also true for Saskatchewan, because we are smaller provinces, we're able to do more
comprehensive surveillance for all infectious diseases.
We have laboratory capacity to do the testing.
And so, for example, the amount of gonorrhea and chlamydia testing we do in Manitoba works
out to be about one sample for every 10 people.

(28:57):
So if you're sampling, it's not exactly 10% of the population we're testing.
If you're looking at a significant proportion of the population every year for a given disease,
you're going to be able to find that and also have very, very good years of surveillance.
So what are, in the grand scheme, relatively subtle differences?
Plus, we've been interested to some extent in sexually transmitted diseases in Manitoba

(29:22):
for a while just because we are concerned about the growing rates of everything.
But again, this is not unique to us.
That's been across North America and especially also in Alberta.
They've been doing very good surveillance and reporting on increases in sexually transmitted
infections.
The other thing too is just the changing technology makes these studies more and more available.

(29:46):
And in Manitoba, we're lucky enough to have the Federal National Microbiology Lab.
And I should really say that none of the work we've done here would have been possible without
their gonococcal and streptococcus unit.
Irene Martin at the National Microbiology Lab has been working on this subject for, well,

(30:07):
a very long time and has also had a long-standing interest in the typing of gonorrhea for surveillance
purposes.
And so that was one of the early clues was that we were seeing the same molecular type
over and over and over again.
And really what the genomics has allowed us to do is take a much deeper dive into not

(30:27):
only the handful of targets that are used for routine typing of gonorrhea, but the entire
genome and the entire contingent of virulent factors and other things that are in a gonorrhea
genome.
And so we continue to work with her group to dig deeper into this.
The other thing we are also working with some of our clinical colleagues is to get a better

(30:50):
sense of who our patient population is.
There still might be something about the patients who are presenting with gonorrhea.
And a lot of that work is really just starting.
But we already know, anecdotally at least, that in a lot of cases, these folks did not
have gonorrhea.

(31:10):
They were not positive at the routine sites.
They didn't have positive urine.
They didn't have positive endocervical swabs.
So really the joint infection was their first presentation.
And that's why it's also good to raise awareness that if you're not a microbiologist or someone
who specializes in infectious diseases and somebody who's in their 20s, otherwise healthy,

(31:30):
doesn't really have risk factors for acute onset arthritis, think about doing a sexually
transmitted infection screen.
Or if you're going to draw some joint fluid for culture and routine testing, maybe say,
hey, could you query gonorrhea on the test?
There seems to be a lot more of it out there.

(31:51):
In some of the publications from the US, they are clearly seeing overlap with disseminated
gonorrhea and other kinds of sexually transmitted infections, especially syphilis or HIV that
may be associated with injection drug use or riskier habits or behaviors.
But again, in our disseminated gonorrhea population, we're not seeing that.

(32:11):
These are folks who don't seem to have other risk factors, which is also an indication
that there may be something about the strain.
They've just encountered a gonorrhea strain that is nastier than most, something that
can happen to anyone.
Yeah.
And I think you bring a good point about the presentation of especially what I've seen
from a joint that's infected with gonorrhea.

(32:34):
It looks very similar to other bacterial septic arthritis, where it's hot, swollen, tender
joints.
Sometimes it can be overlooked that are most common bacteria like staph and strep species
that would cause a septic arthritis being higher on the list.
But then looking at the population, I think is really important.

(32:57):
So I'm a pediatric infectious disease specialist.
So for me in my world, sometimes until I don't see adolescent patients, that's when we start
thinking more about STI screening and that type of thing.
And obviously one-off cases in younger populations.
But I think for some of our clinicians out there who are family physicians and practicing

(33:21):
adult medicine really should be keeping in mind that gonorrhea can have such a presentation
as well and sending off the right testing.
So in terms of, I guess, what's the future?
Can you predict the future for us, Dr. Alexander?
What are we going to see?
I will not even attempt to predict the future.

(33:44):
But I guess now that this is on our radar, it's something that we will continue to monitor
and continue to study.
We'd like to better understand the mechanics of how all this works now that we have some
targets from our genomic studies to go back to the lab bench and see if we can tease it
a part a bit more and understand the mechanisms that work behind this.

(34:04):
And as I mentioned, we're also very curious about taking a closer look at who gets disseminated
gonorrhea.
I mean, there are complement disorders in individuals that may predispose in these sorts
of infections.
And so that might be something that one might need to screen for if you present with disseminated
gonorrhea.

(34:24):
Well, maybe we should look at this because if you have an immune defect, there might
be other implications for your own health and well-being and precautions you might take
in the future.
Yeah.
And I think for some of our audience who are very clinical, that's like clinicians that
are seeing this, you did mention that resistance was not a factor seen in your guys' isolates.

(34:50):
Do we... so obviously anticipating that in the future, at this time right now, we're
seeing our conventional antibiotics, which usually the cephalosporins is our mainstay
of therapy still for gonococcal infections.
Exactly.
And so kind of going forward, is that something that you guys will keep kind of surveillance

(35:16):
on for future isolates in terms of like developing, if there is a chance for resistance development?
Yeah.
I think one thing that most Canadian provincial public health labs do is if they have an isolate,
they will do susceptibility testing.
And again, the Public Health Agency of Canada does annual reports to describe changing trends

(35:36):
in antibiotic resistance for gonorrhea as well as other organisms, because it's definitely
something we need to monitor.
And we know there are some nasty drug resistant strains out there.
Yeah.
And I think you did mention this in terms of diagnostics.
So at this time, so I mean, based off of your study, you guys were able to do PCR and molecular

(35:58):
methods from other sites, right?
Like synovial fluid and your other isolates.
So is that something that is available for North Americans or Canadians?
So there are...
So that's the other thing is there are no Health Canada approved diagnostic tests for
disseminated gonorrhea infections, but we have a lot of really good laboratorians in

(36:22):
Canada and they have the ability to validate these tests on their own and to offer them
where required.
Similarly, again, in part due to genomics and other advances in molecular techniques,
we're looking at ways to generate an antimicrobial susceptibility profile or at least identify

(36:45):
resistant genes even in the absence of having a clinical isolate to work with.
But a lot of that is still very...
It's a research and development stage and not wildly velo.
But it's something that a lot of microbiology groups are moving towards is to being able
to detect resistance without actually having an isolate.
So as long as you have a positive sample, you can do that extra work to type strains

(37:09):
for surveillance, to look at antimicrobial susceptibility, to help inform treatments
and really to provide the best care you can even in the absence of a...
Because now there's a lot of bugs out there that we still can't grow.
You can't culture syphilis, for example.
And even Brelia for Lyme disease, a lot of those diagnosis, you rarely, rarely isolate

(37:33):
the organism itself.
You have to go off of others.
That's fair.
Yeah.
One of the points that I got from this great conversation today about disseminating gonorrhea
is that obviously we should be aware that DGI, disseminated gonococcal infections are
on the rise, that we should, especially as clinicians, be identifying cases, probably

(37:58):
speaking with our local microbiologists and our laboratory staff members to kind of make
them aware that we're suspicious that this could be a case of that.
And if whether we could validate some of the molecular methods for certain samples and
then also attempt to grow in culture, I think that would be ideal.

(38:22):
But definitely, I think just keeping it on our radar that it doesn't have to present
only as a common site for sexually transmitted infections or symptoms don't have to be quite
classic.
That they can present with joint infections and other areas for sure.
And that we should be testing for it.

(38:44):
We should be looking for it.
And we should obviously, from a clinical standpoint, treatment varies too then, right?
Like we talked about duration is longer.
We are thinking about disseminated infections.
So is there any other points that you would like to highlight for our audience today in
terms of disseminated gonococcal infections?

(39:06):
Not really.
It's just great to have a chance to get the word out there.
And yeah, there are clear guidelines and recommendations for diagnosis and treatment of disseminated
infection.
Where possible, if you can work with your local infectious disease docs and provincial
public health labs to grow or investigate these cases, I think just documenting that
they're out there and that they're not as rare as one would think is a great first step.

(39:30):
Yeah, and it's exciting that we have such a great team out in Manitoba and with the
National Micro Lab as well to be able to identify some of these cases, do future research.
I think it's actually great to have such a center that can actually has the resources

(39:51):
and the ability to probably even, I mean, helps all the rest of us in Canada as well.
So we're quite grateful for that as well.
So thank you.
The thing I like about Manitoba is we're small but mighty.
Well said.
That's great.
Well, thank you so much, Dr. Alexander for coming on today's episode.
I think our audience is quite grateful.

(40:13):
I've had a lot of requests actually for this episode because there are adult physicians,
especially my adult colleagues that are seeing disseminated gonococcal infections.
So I think just to hear a little bit about what research is ongoing and things to look
for, I think definitely it's always refreshing to have somebody who's doing the actual work

(40:39):
in the labs to come and give us that insight.
So we're really appreciative.
Thanks for the chance.
All right.
Well, take care and thank you so much for coming on the episode.
Thank you, Dr. Purewall and thank you, Dr. Alexander for joining us.
This concludes our first season of the Canadian Breakpoint and thank you listeners for making

(40:59):
it a success.
We look forward to bringing you exciting new topics in 2023.
Have a topic suggestion?
Email us at thecanadianbreakpoint at gmail.com and follow us on Twitter at CABbreakpoint.
Have the happiest of holidays and see you in 2023 at the Canadian Breakpoint.