October 2, 2024 • 33 mins
Dr. Rupeena Purewal welcomes Dr. Jason Kindrachuk whose research focuses on the circulation, transmission and pathogenesis of emerging viruses that pose the greatest threat to global human and animal health, to discuss Monkeypox.
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Episode Transcript
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Thanks for joining us at the Canadian Breakpoint, a Canadian infectious diseases podcast by
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Canadian infectious diseases physicians.
I'm Summer Stewart, back with Dr. Rupeena Purewal, pediatric infectious diseases physician
in Saskatoon.
For this episode, we welcome Dr. Jason Kindrachuk from University of Manitoba to discuss monkey
pox.
Dr. Purewal.
All right, welcome everyone to another episode of our podcast, the Canadian Breakpoint.
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Today we have a very special guest with us, Dr. Kindrachuk, who is an associate professor
and Canada research chair in emerging virus pathogenesis in the Department of Medical
Microbiology and Infectious Diseases and cross appointed in the Department of Internal Medicine
and Manitoba Centre for Proteomics and Systems Biology, the University of Manitoba.
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His work focuses on viruses that pose the greatest threat to global health, including Ebola virus,
orthophox viruses, coronaviruses and influenza viruses.
His research program centers on the circulation, transmission and pathogenesis of emerging
viruses.
Past and present findings from these investigations will help inform emerging virus therapeutic
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treatment strategies, outbreak prediction and preparedness efforts with impacts on both
human and animal health.
Dr. Kinderchuck leads multiple nationally funded emerging infectious disease research
investigations, including one health emerging zoonotic virus surveillance activities in
Canada and Africa.
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These include as a director for the International M-Pox Response Consortium, co-lead for pillar
two of the coronavirus variants rapid response network and ongoing investigations on the
long-term impacts of Ebola virus infection in disease survivors in West Africa.
Thank you so much, Dr. Kinderchuck for joining us today.
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Thank you for having me.
Perfect.
And so today we're going to talk about a very important topic and that's monkeypox for our
listeners out there.
So just so you're aware, there's pharmacists, physicians, nurses and many, many different
other healthcare professionals that tune into the podcast.
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And so I thought monkeypox was, you know, it's an episode I've been wanting to do for
a while.
And I think with, you know, the recent WHO global health emergency that was reported
just this past week, I think this is a pressing topic and all a lot of us are interested in
kind of hearing more about this.
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Absolutely.
All right.
So I think for, because we have so many different types of listeners, I think it would be really
important to kind of just start with a background and really what is this viral disease and
you know, what is monkeypox?
How does someone get this virus and what should we think about and when should we be thinking
about it?
Yeah, it's a great question, right?
And I think for this kind of have to go back a little bit to, you know, when monkeypox
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virus was first identified, it was actually first identified in 1958 actually at really
amongst captive non-human primates.
We didn't see any human infections diagnosed until 1970.
That was in democratic Republic of the Congo.
But if we think about this from a historic perspective, that's probably not that surprising
because there was this kind of other little thing going on in the world called smallpox
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that unfortunately had a very, very similar clinical presentation.
So following the eradication of smallpox and obviously the cessation of the global vaccination
program, what we've seen really from 1980 onwards, it's kind of steady increase in monkeypox
virus infections across endemic regions of Africa.
That's kind of been divided based on geography.
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Cameroon is the central point.
Cameroon is the only place where we find both clade one and clade two monkeypox virus co-circulating.
Anywhere west of Cameroon, we only find clade two monkeypox virus being endemic.
And to the east of there is clade one monkeypox virus.
Things get a little bit complicated when we start talking about how they differ from one
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another.
Historically, clade one monkeypox virus has been associated with more severe disease,
but we have to appreciate that that's also based on really kind of limited data for clade
two infections really up until the reemergence in Nigeria in 2017 and then the subsequent
movements out of Nigeria to the global north in 2022 and the obvious epidemic expansion.
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So historically, when we look at the disease, pre-2022, the disease looked really like a
composite of human smallpox.
Really the difference being the lymphadenopathy that's seen in monkeypox virus infections,
but you still saw the fully disseminated disease, really the face, arms, legs, hands, and feet
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being the areas where you saw the most lesions.
And the lesions tended to be all in the same stage of development.
So whether it was on the face or on the feet, everything seemed to be fairly symmetrical
in that regard.
Then 2022 hits and we start seeing atypical presentation.
So what we saw in 2022, virus moved out into Europe first and then moved globally across
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more than a hundred countries.
Those infections were associated with dense sexual networks.
That was something we hadn't really seen previously.
Then there was this high overrepresentation amongst men and those that identify as gay,
bisexual, or other men who have sex with men.
The presentation tended to actually look a lot like other sexually transmitted or bloodborne
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infections.
So a lot of lesions within the groin, some of the rectal lesions in men, isolated lesions
in other regions of the body, but not the fully disseminated disease that we typically
had seen historically and the lesions were not all in the same stage of development.
That has complicated the picture because now you can't just do a clinical diagnosis based
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on what the disease looks like.
So we still have virus moving through the global community.
Clay 2b, monkeypox virus, continues to circulate.
We've seen clusters in Canada since 2022 onwards.
But then we saw the tipping point in DRC starting in 2023 with this massive increase in infections.
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And that's led to where we are today with the public health emergency.
In terms of the signs and symptoms that people are seeing, is this widespread depending on
the age group?
Or younger children are seeing similar presentation as the adults?
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So far it really depends on the different clades.
We almost have to take clade 2 and separate pre-2022 and almost pre-2017 versus post Nigeria
reemergence and global reemergence.
Prior to 2017, very few cases of clade 2 had ever been reported.
We saw a small outbreak in the US in 2003.
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Some kids were infected.
That was all through zoonotic transmission.
We did see a couple of cases of severe disease there.
But predominantly we didn't see a lot of fatal infections.
2017, Nigeria, everything starts to skew a little bit older in terms of the average age
group where we're seeing the infections.
And then of course in 2022 onwards with the global outbreak, most infections in the 20
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to 40 age group in a game skewing towards men, very few infections in women and in kids.
In DRC, very, very different.
What we're seeing right now in really the last 20 months, even with this rapid increase
in cases, the demographics for severe disease and infections have not really changed.
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In DRC, vast majority of infections still are based off of zoonotic contacts, mostly
we think contact with rodents.
Those infections tend to skew towards children under the age of 15.
That tends to be the group that is in contact with those animals.
And we tend to see the highest mortality and morbidity amongst those age groups.
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Now we also shift a little bit because mid 2023 we picked up, and I say weeks, it includes
certainly at the forefront of this are Congolese colleagues and others from the US and Europe.
We picked up a cluster of cases that were related to sexual contact in Congolese province.
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An N of five, very small, still skewing towards an older age group.
But we saw men and women included in that.
Since that time point, really in Selkivu province, we've seen again this massive inflection of
cases in an area that historically had not seen much.
Those cases over highly overrepresented among sex workers and dense sexual networks, but
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even seemingly evenly spread between men and women so far.
We're not seeing much in terms of infections in kids, but that may change over time.
We've seen movement of that particular type of monkeypox virus.
What we've now termed clade 1B, more sustained human transmission.
That virus has moved in a North Kivu and we've seen cases in internal displacement camps
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and that's included in, at least in our case investigations, in a few children.
No severe disease so far, but we're still at the early stages.
It's complicated.
We're trying to follow the FD as closely as we can.
Definitely different routes of transmission and that's been evolving as well.
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Has it been different for hosts, like host dependent as well?
If somebody is immunocompromised, do they have more severe disease or they pick up the
virus quicker?
What we saw again in 2022 really opened our eyes a little bit to what monkeypox virus
infections could look like.
In 2022, there's a few global case series that looked at the risks for infection.
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There was an increased risk if somebody was HIV positive or a person living with HIV.
Same thing with other STIs.
We didn't know much at that point as to whether or not there was an increased risk for severity
of disease.
We've now seen with HIV that certainly people that have uncontrolled HIV can have a more
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severe course of M-pox than what we see in individuals who have control disease or otherwise
have a normal immune response.
But it's complicated.
In Congo, we don't know.
It certainly is top of mind for us.
There's not a lot of STI testing.
HIV rates tend to be quite low in Congo.
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That maybe has helped us a little bit, but we're hoping to deploy STI testing certainly
in the South Kivu and some of the surrounding areas over the next few months.
Then you talked a little bit about the common strains that are currently circulating.
What is the predominant strain right now that you're seeing?
Since it's Democratic Republic of the Congo, clade 1 monkeypox virus is the only type of
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monkeypox virus we've seen there before.
We've now subdivided that into clade 1A and clade 1B.
Clade 1A is the virus that's associated with zoonotic infections.
Those are still making up the vast majority of the cases we see in DRC at the moment.
Clade 1B we're seeing certainly in South Kivu starting to pick up in a few other areas now.
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That is associated with more sustained human-to-human transmission with no real zoonotic link.
We don't know a lot about clade 1B yet in terms of severity.
A number of factors we have to consider there, but we do know that it's certainly moving
between people far easier.
We think still through close contact and potentially with contaminated surfaces and shared materials
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or bedding and clothing, especially if somebody has a lesional disease.
We haven't seen much in terms of changes in terms of things like a big respiratory component
that's being included.
But zoonotic infections certainly far and away are still driving the current outbreak.
And then in terms of obviously, I think everybody is worried when they see a case like this.
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And so I guess we can divide it up into things because we can talk about prevention separately.
And then when you do see a case, what do you do in terms of therapeutic management?
So can you talk a little bit about how we can prevent and what kind of strategies are
out there right now?
Yeah, you know, the infection prevention control piece is something certainly I've been involved
in and many others have been involved in since 2022.
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One of the things that I think we appreciate very quickly is certainly that kind of risk
for broader airborne transmission.
We haven't seen any FD that's suggestive of that.
But historically, we've been able to gain a lot of knowledge, certainly from endemic
regions of Africa.
So really, the greatest risk for transmission we still see is that close extended contact,
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primarily through those that are providing care, whether they're health care workers
or family members, whether they're sharing a bed, whether they're sharing clothing or
bedding that is not being laundered.
And we've seen the potential for transmission through things like sponges or cleaning materials.
We've been working with a few groups, providing some guidance on looking at different disinfectants
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that are being used kind of in different areas of the world.
The kind of good news is the majority of what we would assume continues to be the case.
Bleach tends to work really well.
Most good, you know, kind of, you know, antiviral disinfectants work very well.
Soap and water work very well.
A big piece of this is trying to ensure that anybody that has lesional disease that thinks
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that they are in contact with or bedding or clothing are getting laundered and that the
people that are, you know, basically in contact with those things, either they're also monitoring
their symptoms and or also using personal protective equipment.
Okay.
Yeah.
So very similar to other viral diseases, encourage hand washing and inner basic hygiene and laundering.
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Absolutely.
And our concern, I think right now with DRC, I mean, there's a big focus on certainly the
sustained human to human transmission piece for good reason.
But there's also a big piece of this, which is, listen, we know where really kind of the
root of many of these infections are, and it's that zoonotic contact.
There's a big piece of this, which I think is still, you know, kind of embedded in this
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idea of community engagement and trying to understand where infection prevention control
practices can be implemented within communities that's done in a respectful and transparent
manner in a way that doesn't impede people's ability to still hunt or to still be able
to consume while game.
And then once you have somebody who has a condition like this, who's contracted the
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virus, they have symptoms and they have signs and you're considering, you know, thinking
about first, I guess we talk about diagnostics because if I'm an ER physician or a hospital
physician, oftentimes as an infectious disease specialist, we'll get phone calls to send
off.
So what I see a patient like this, what do I send off?
Yeah.
So the easiest thing really is still is lesional swabs.
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OP swabs tend to work fairly well as well.
There have been some studies that have looked at kind of longitudinal viremia in patients.
Those I think for the most part have suggested there's not a really strong viremic component,
at least in the majority of cases.
So I think we're still kind of focused on lesional swabs.
PCR by far and away is the method that still continues to be tried and true.
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There's been some changes though, because as we've seen kind of the emergence of clade
2b coming out as a subclade out of clade 2 and now clade 1b is a subclade of clade
1, we've also had to look at primers and whether or not those primers are still picking
up the virus that we assume that they're recognizing.
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So for clade 1b, one of the things that we have seen recently has been that the kind
of traditional primers that would be used normally for clade 1 infections, there's actually
a deletion in clade 1b and those primers could potentially give a false negative.
Colleagues in Europe have already reported primer sets that appear to recognize clade
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1b very, very well.
But we also know that kind of like the overall kind of orthpox virus kind of centric primers
work very, very well.
They just don't give you that clade distinction, right?
So PCR still works.
We do a lot of sequencing.
There's certainly something to be said about looking for antigens to try and identify people
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who have been previously exposed.
We have done quite a bit of serosurveillance in this realm.
The difficulty is pox viruses have very close antigenic similarities.
That's why we use vaccinia for eradicating smallpox and we use it now for the M pox vaccine.
That cross-reactivity somewhat precludes our ability to go in and say, okay, have you been
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exposed to monkey pox virus or cow pox virus or some other unknown human orth pox virus?
That being said, in many areas that are endemic, we have a pretty good idea of what's circulating.
And certainly if there's an outbreak situation, you can start to distinguish.
There's questions about if somebody has been vaccinated for smallpox, what does cross-reactivity
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look like?
But really if we use 1980 as that tipping point for people that were or weren't vaccinated,
you can start to surmise what's going on based on that.
That's fair.
And then most centers, do they have the PCR testing or is this sent to National Microlab
in Canada?
Well, it's a good question.
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So certainly for clade 2 right now, like Cepheid has there, the gene expert is certainly widely
being used for clade 2.
That I think continues to be the case.
For clade 1b, there's certainly been some questions about how we're going to be able
to test for this and really to try and distinguish clade 1b from clade 2b.
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Using orth pox virus centric primers, you're still able to pick it up and say, okay, yeah,
it's PCR positive.
It's monkey pox virus, but we don't know which clade.
For clade 1b, the issue that we have is this is a fairly recent development for the identification
in Congo.
So there's a lot of people that have been asking about access to nucleic acid to be
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able to validate tests within their own laboratories.
And that's not only in Canada, but certainly well beyond and in too many different places
across the globe.
That's going to be a big piece.
I think is that validation part likely, we're always a little bit behind with sharing materials
globally unfortunately.
I think right now, given the public health emergencies, that's going to be a big piece.
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But the confidence comes out of that the primer sets that have been reported so far that have
been in use through Congo and in other regions.
And then in terms of treatment, so are there antivirals out there or this is mainly supportive
management currently?
No, there's so for clade 2 infections, T-pox worked very, very well.
Ticaviromat, ST246, I kind of have gone through every iteration of the name at this point,
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worked very, very well.
And certainly in the US and Canada, that was kind of the antiviral that people were moving
towards to try and reduce the impact of these infections.
There's been an issue though that's come up in Congo, which is a very recent clinical
trial for Ticaviromat on the ground failed.
It didn't show any added benefit.
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The reality though is that it's unfortunate.
There's probably a number of reasons why that trial may have been limited in its potential
to be able to be successful.
But a big piece that came out of that was you reduce the overall mortality just with
providing good supportive care.
And I think to me, that's a really important piece of this, which is for countries that
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have been scrambling for T-pox, certainly in 2022, maybe looking to do that for 2024.
Blade 1B, we don't think it works, but if you provide good supportive care, you reduce
certainly the mortality.
I think the bigger kind of piece of all that though is saying in the areas where we see
endemic disease, one of the things that we can do to immediately reduce the impact is
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be able to provide extra assistance for being able to give supportive care on the ground.
So I think that's an important piece.
Vaccination still works well.
We have no reason to think the MDA, the very Nordic vaccine would not provide cross protection
against Blade 1.
It's still a vaccine based vaccine.
So I don't think we have any concerns that way.
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A big part is still trying to get vaccines to really the hotspots of the world where
we see circulation and that continues to be an issue.
And so, yeah, so I would say I've had a couple of questions from physicians and colleagues
and patients.
Is it worthwhile for them to get vaccinated or is it something only limited to if they're
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traveling to these endemic areas?
Even through travel, I don't know if there's a travel based vaccination program that's
available.
That may change because of the public health emergency.
My lab and myself have been vaccinated because we obviously work with samples as well as
with vaccine of virus and other pox viruses.
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I was vaccinated ages ago for ACAM2000 or with ACAM2000.
The public availability is still pretty limited, right?
Yeah.
We have lots of stocks and stockpiles of ACAM2000, but that was contraindicated for certainly
for very specific groups.
The JYNNEOS or MBA vaccine, we don't have nearly the stockpile that we did.
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So there's still basically the push to try and get that vaccine to those populations
where there is an increased risk for infection, close contacts of patients that have suspected
or confirmed cases.
That's still the focus, but as well kind of appreciating that we need to get vaccine into
certainly in the Congo and probably now into Burundi and surrounding areas very, very quickly.
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So I think if we start seeing influx in cases, whether clade two or clade one driven in Canada,
there's going to be a need to ensure that healthcare workers are vaccinated.
But there's the other piece too, which is good infection prevention control also is
very, very good at reducing those infections.
So we just have to kind of take it at face value.
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Right.
Okay.
And so kind of the idea being prevention right now.
Even if somebody does have the illness to be cautious, to not be around others, especially
those that are immune compromised, kind of similar to what we would say with any other
viral infections.
100%.
Right.
And we know the thing is we know that the routes transmission predominantly, right?
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You know, eucosal membranes are going to be key in ensuring that we don't have any open
wounds or abrasions.
Those kinds of things continue to be important.
And I think we go back to the idea of when people are vaccinating people, certainly old
school, like CAM 2000 or even way back in the flybacks, it was about those preventative
measures trying to remove the risk for exposure.
Right.
And so recently with WHO declaring this public health and global health emergency.
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And so how is situation evolving and appreciating that things are changing daily?
I'm sure.
Yeah.
I mean, the situation on the ground in Congo, you know, through certainly through the work
that we're doing, I don't think that the situation has necessarily changed.
We're looking at from 2023 and now around 30,000 suspected cases.
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We've seen movement of virus really to 25 to 26 provinces now with local transmission.
It continues to be widespread.
And we're not seeing any indication that things are starting to ramp down.
Right.
So that continues to be a big concern for us.
Probably as concerning of an issue though, is really the movement into Burundi and some
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of the surrounding regions.
Burundi in particular, because of the limited resources that are available in country from
a healthcare standpoint and just an overall standpoint, concerns about the increased circulation
that we're now seeing there.
You know, Uganda and Rwanda, we've seen cases.
Kenya, we've seen cases.
Those seem to be pretty controlled so far.
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That's assuming that people are feeling comfortable with self-reporting.
But I think for us that the focus right now is really what's going on in Congo, what's
going on in Burundi.
We've seen introduction or at least the kind of the indication of cases that have been
identified globally.
So we've seen a case in Sweden.
We've now seen a case in Thailand.
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That's not that surprising, right?
People are still traveling.
People are still living in a globalized community.
We're likely going to see those cases continue to be identified.
The bigger piece to me is going to be what happens afterwards?
Do you see any additional signs of community transmission or broader transmission within
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those local populations?
Or did you get good testing and contact tracing out and you don't see any local spread?
So that I think continues to be important for developments.
The other piece is we've seen, you know, really the kind of discussion about getting vaccines
on the ground in Congo go from being a few months down the road to now kind of like within
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the next couple of weeks there will be vaccine.
Don't know much about the deployment strategy yet, what that's going to look like, which
groups are going to be going to be kind of the focal groups for that first round.
But certainly we're there and others are there to help support where we can and certainly
to try to get some clinical information out as quick as possible where and when we can.
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Okay.
Seems like a very pressing situation, but you know, things, I think there's things are
in the works and hopefully, you know, we don't see more spread in circulating virus because
obviously we know what with the previous kind of virus activities we've seen over the last
few years, we know that things can change really quickly.
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So, and then, so in terms of Canada or other countries, what are they doing in terms of
like mitigating risks or surveillance for disease surveillance?
Yeah.
You know, I think one of the big pieces that, you know, that has maybe not gone as much
presses as it's needed to over the last bit is we have this pressing situation in Central
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Africa.
There's been a bigger question about, okay, well, what happens now if clade one moves
more broadly and especially clade one B.
The thing that I think we need to appreciate is, you know, two years out from 2022 to appreciate
that listen, our surveillance networks, our testing and tracing networks, the knowledge
base in our healthcare workers and as well, even within communities and community advocacy
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groups, all of that has increased to a much higher level than it was pre-2022.
So I think we're in a very good place for identifying cases.
We continue to see, you know, cases being identified in Ontario, a little bit of a surge,
you know, kind of coming through this summer.
Same thing with other regions of the world, not approaching anything what we saw in 2022,
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but it should be a reminder that like clay to virus didn't disappear.
It's still circulating globally.
It's still circulating here within Canada.
It's just at a very, very low level.
So I think we're doing very, very good in terms of our surveillance.
We now have to add the PCN about clay one B recognition, but we're in a place where
we should be able to identify those, those cases very, very quickly.
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That's really good to hear.
And so in terms of resources, cause I think that's also important for healthcare professionals
across the board, also sometimes just general public, you know, asking questions.
And so where can people find, I mean, like obviously CBC has always been a really good
resource, but are there other certain areas that we should be looking?
There, there are.
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I mean, I, you know, I don't want to, you've got to shine a spotlight on work that I've
done because I've sat on panels with far smarter people to myself to pronounce on this.
WHO a couple of years ago had a guideline development group for clinical management,
infection prevention control.
That's really available through, through WHO for M pox.
I think that's still largely applies to everything that we're seeing now.
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WHO just recently updated all their information on infection prevention control, their descriptions
of M pox, those resources are good.
And of course health Canada and public health agency of Canada continue to provide information
as well.
And of course there's, there are research groups that are doing work in this area.
You know, all of us have a lot of information as well, but I think going to those kind of
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big sources, European centers for disease control, U S T D C, WHO and, and health Canada
are major resources.
That's really helpful.
Cause I think a lot of people will be starting to see more questions come through and that's
kind of natural that happens clinically as well.
You know, we always think about what's happening with circulating and I think awareness is
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important.
And so that's why we're talking about this today, because I think most of us should have
some base knowledge on monkey pox and, and you've given us some really good information
today.
So in terms of kind of summarizing or some key points that you'd want the public or health
professionals to really take away from today's episode, what would you kind of summarize
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in terms of that?
Yeah, I think a big piece of this is right now that the global risk for, for clade one
introduction continues to be quite low.
I think also appreciating that, you know, things can change.
We know that that happened with clay too, but we're in a different place than we were
in, in 2022.
We have good surveillance networks.
We have good sharing of data and testing protocols.
I think that piece allowed us to be able to move forward.
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The kind of piece that I think is at the heart of this though, is we want to reduce the risk
globally.
We've got to reduce the risk locally, which still gets back to the need to not only get
things contained in, in DRC, but also to look at other endemic areas of Africa and say,
we need to get vaccination programs up.
We need to get surveillance programs sustained and as well go back to this piece about healthcare
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infrastructure and certainly the need to be able to harmonize data reporting globally
right now for M-POC.
So we all have a good impression of what we're looking for, but I think it's going to be
a key area.
Yeah.
And then just on a note that I actually forgot to ask was in terms of reporting.
So if physicians or anybody is seeing cases, are these then like, I mean, through the lab,
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we're definitely reporting to public health, like local public health authorities.
Is there something that a physician should be doing in terms of any surveillance network
that they should be entering their data into?
Not that I've seen so far, right?
And listen, that can just be my naivety for what, what's available in Canada.
In DRC, we've got, WHO has their centralized system for us to be able to report and upload
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data continually into.
So we've, we've been working on that and certainly most, most of those countries have good centralized
systems for entering in national data.
It can be a little bit slow at times, but we continue to do that on the ground as well.
And then of course, Africa CDC is obviously taking a much bigger role in this with trying
to ensure that there's good data reporting, data management, and as well sharing of information
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globally.
Okay.
That's great.
Definitely, I think everybody's on top of it and it's good to hear a little bit more,
you know, about Monkeypox and, and have a bit more background.
So I've learned a lot for sure.
And, and I always inform my listeners that this is an informational podcast and things
do evolve and, and over time, you know, even prevention or treatment options may change.
(32:37):
So currently this is the situation with Monkeypox and, and what we know about it right now.
So I'm sure our listeners will take a lot back from this episode and thank you Dr.
Kindertruck for being here today on our podcast and providing us with such great information.
It was an absolute pleasure.
Thank you.
Thanks.
(32:57):
Take care.
Thank you, Dr. Kindertruck for joining us today.
Have an episode suggestion?
Email the Canadian Breakpoint at gmail.com and be sure to follow us on X at CA Breakpoint
for updates.
See you again soon at the Canadian Breakpoint.
Thanks for joining us at the Canadian Breakpoint, a Canadian infectious diseases podcast by
(00:12):
Canadian infectious diseases physicians.
I'm Summer Stewart, back with Dr. Rupeena Purewal, pediatric infectious diseases physician
in Saskatoon.
For this episode, we welcome Dr. Jason Kindrachuk from University of Manitoba to discuss monkey
pox.
Dr. Purewal.
All right, welcome everyone to another episode of our podcast, the Canadian Breakpoint.
(00:34):
Today we have a very special guest with us, Dr. Kindrachuk, who is an associate professor
and Canada research chair in emerging virus pathogenesis in the Department of Medical
Microbiology and Infectious Diseases and cross appointed in the Department of Internal Medicine
and Manitoba Centre for Proteomics and Systems Biology, the University of Manitoba.
(00:56):
His work focuses on viruses that pose the greatest threat to global health, including Ebola virus,
orthophox viruses, coronaviruses and influenza viruses.
His research program centers on the circulation, transmission and pathogenesis of emerging
viruses.
Past and present findings from these investigations will help inform emerging virus therapeutic
(01:18):
treatment strategies, outbreak prediction and preparedness efforts with impacts on both
human and animal health.
Dr. Kinderchuck leads multiple nationally funded emerging infectious disease research
investigations, including one health emerging zoonotic virus surveillance activities in
Canada and Africa.
(01:38):
These include as a director for the International M-Pox Response Consortium, co-lead for pillar
two of the coronavirus variants rapid response network and ongoing investigations on the
long-term impacts of Ebola virus infection in disease survivors in West Africa.
Thank you so much, Dr. Kinderchuck for joining us today.
(02:00):
Thank you for having me.
Perfect.
And so today we're going to talk about a very important topic and that's monkeypox for our
listeners out there.
So just so you're aware, there's pharmacists, physicians, nurses and many, many different
other healthcare professionals that tune into the podcast.
(02:20):
And so I thought monkeypox was, you know, it's an episode I've been wanting to do for
a while.
And I think with, you know, the recent WHO global health emergency that was reported
just this past week, I think this is a pressing topic and all a lot of us are interested in
kind of hearing more about this.
(02:41):
Absolutely.
All right.
So I think for, because we have so many different types of listeners, I think it would be really
important to kind of just start with a background and really what is this viral disease and
you know, what is monkeypox?
How does someone get this virus and what should we think about and when should we be thinking
about it?
Yeah, it's a great question, right?
And I think for this kind of have to go back a little bit to, you know, when monkeypox
(03:05):
virus was first identified, it was actually first identified in 1958 actually at really
amongst captive non-human primates.
We didn't see any human infections diagnosed until 1970.
That was in democratic Republic of the Congo.
But if we think about this from a historic perspective, that's probably not that surprising
because there was this kind of other little thing going on in the world called smallpox
(03:27):
that unfortunately had a very, very similar clinical presentation.
So following the eradication of smallpox and obviously the cessation of the global vaccination
program, what we've seen really from 1980 onwards, it's kind of steady increase in monkeypox
virus infections across endemic regions of Africa.
That's kind of been divided based on geography.
(03:49):
Cameroon is the central point.
Cameroon is the only place where we find both clade one and clade two monkeypox virus co-circulating.
Anywhere west of Cameroon, we only find clade two monkeypox virus being endemic.
And to the east of there is clade one monkeypox virus.
Things get a little bit complicated when we start talking about how they differ from one
(04:13):
another.
Historically, clade one monkeypox virus has been associated with more severe disease,
but we have to appreciate that that's also based on really kind of limited data for clade
two infections really up until the reemergence in Nigeria in 2017 and then the subsequent
movements out of Nigeria to the global north in 2022 and the obvious epidemic expansion.
(04:37):
So historically, when we look at the disease, pre-2022, the disease looked really like a
composite of human smallpox.
Really the difference being the lymphadenopathy that's seen in monkeypox virus infections,
but you still saw the fully disseminated disease, really the face, arms, legs, hands, and feet
(04:58):
being the areas where you saw the most lesions.
And the lesions tended to be all in the same stage of development.
So whether it was on the face or on the feet, everything seemed to be fairly symmetrical
in that regard.
Then 2022 hits and we start seeing atypical presentation.
So what we saw in 2022, virus moved out into Europe first and then moved globally across
(05:24):
more than a hundred countries.
Those infections were associated with dense sexual networks.
That was something we hadn't really seen previously.
Then there was this high overrepresentation amongst men and those that identify as gay,
bisexual, or other men who have sex with men.
The presentation tended to actually look a lot like other sexually transmitted or bloodborne
(05:45):
infections.
So a lot of lesions within the groin, some of the rectal lesions in men, isolated lesions
in other regions of the body, but not the fully disseminated disease that we typically
had seen historically and the lesions were not all in the same stage of development.
That has complicated the picture because now you can't just do a clinical diagnosis based
(06:10):
on what the disease looks like.
So we still have virus moving through the global community.
Clay 2b, monkeypox virus, continues to circulate.
We've seen clusters in Canada since 2022 onwards.
But then we saw the tipping point in DRC starting in 2023 with this massive increase in infections.
(06:33):
And that's led to where we are today with the public health emergency.
In terms of the signs and symptoms that people are seeing, is this widespread depending on
the age group?
Or younger children are seeing similar presentation as the adults?
(06:54):
So far it really depends on the different clades.
We almost have to take clade 2 and separate pre-2022 and almost pre-2017 versus post Nigeria
reemergence and global reemergence.
Prior to 2017, very few cases of clade 2 had ever been reported.
We saw a small outbreak in the US in 2003.
(07:17):
Some kids were infected.
That was all through zoonotic transmission.
We did see a couple of cases of severe disease there.
But predominantly we didn't see a lot of fatal infections.
2017, Nigeria, everything starts to skew a little bit older in terms of the average age
group where we're seeing the infections.
And then of course in 2022 onwards with the global outbreak, most infections in the 20
(07:40):
to 40 age group in a game skewing towards men, very few infections in women and in kids.
In DRC, very, very different.
What we're seeing right now in really the last 20 months, even with this rapid increase
in cases, the demographics for severe disease and infections have not really changed.
(08:05):
In DRC, vast majority of infections still are based off of zoonotic contacts, mostly
we think contact with rodents.
Those infections tend to skew towards children under the age of 15.
That tends to be the group that is in contact with those animals.
And we tend to see the highest mortality and morbidity amongst those age groups.
(08:28):
Now we also shift a little bit because mid 2023 we picked up, and I say weeks, it includes
certainly at the forefront of this are Congolese colleagues and others from the US and Europe.
We picked up a cluster of cases that were related to sexual contact in Congolese province.
(08:48):
An N of five, very small, still skewing towards an older age group.
But we saw men and women included in that.
Since that time point, really in Selkivu province, we've seen again this massive inflection of
cases in an area that historically had not seen much.
Those cases over highly overrepresented among sex workers and dense sexual networks, but
(09:13):
even seemingly evenly spread between men and women so far.
We're not seeing much in terms of infections in kids, but that may change over time.
We've seen movement of that particular type of monkeypox virus.
What we've now termed clade 1B, more sustained human transmission.
That virus has moved in a North Kivu and we've seen cases in internal displacement camps
(09:36):
and that's included in, at least in our case investigations, in a few children.
No severe disease so far, but we're still at the early stages.
It's complicated.
We're trying to follow the FD as closely as we can.
Definitely different routes of transmission and that's been evolving as well.
(09:57):
Has it been different for hosts, like host dependent as well?
If somebody is immunocompromised, do they have more severe disease or they pick up the
virus quicker?
What we saw again in 2022 really opened our eyes a little bit to what monkeypox virus
infections could look like.
In 2022, there's a few global case series that looked at the risks for infection.
(10:21):
There was an increased risk if somebody was HIV positive or a person living with HIV.
Same thing with other STIs.
We didn't know much at that point as to whether or not there was an increased risk for severity
of disease.
We've now seen with HIV that certainly people that have uncontrolled HIV can have a more
(10:42):
severe course of M-pox than what we see in individuals who have control disease or otherwise
have a normal immune response.
But it's complicated.
In Congo, we don't know.
It certainly is top of mind for us.
There's not a lot of STI testing.
HIV rates tend to be quite low in Congo.
(11:05):
That maybe has helped us a little bit, but we're hoping to deploy STI testing certainly
in the South Kivu and some of the surrounding areas over the next few months.
Then you talked a little bit about the common strains that are currently circulating.
What is the predominant strain right now that you're seeing?
Since it's Democratic Republic of the Congo, clade 1 monkeypox virus is the only type of
(11:31):
monkeypox virus we've seen there before.
We've now subdivided that into clade 1A and clade 1B.
Clade 1A is the virus that's associated with zoonotic infections.
Those are still making up the vast majority of the cases we see in DRC at the moment.
Clade 1B we're seeing certainly in South Kivu starting to pick up in a few other areas now.
(11:54):
That is associated with more sustained human-to-human transmission with no real zoonotic link.
We don't know a lot about clade 1B yet in terms of severity.
A number of factors we have to consider there, but we do know that it's certainly moving
between people far easier.
We think still through close contact and potentially with contaminated surfaces and shared materials
(12:19):
or bedding and clothing, especially if somebody has a lesional disease.
We haven't seen much in terms of changes in terms of things like a big respiratory component
that's being included.
But zoonotic infections certainly far and away are still driving the current outbreak.
And then in terms of obviously, I think everybody is worried when they see a case like this.
(12:44):
And so I guess we can divide it up into things because we can talk about prevention separately.
And then when you do see a case, what do you do in terms of therapeutic management?
So can you talk a little bit about how we can prevent and what kind of strategies are
out there right now?
Yeah, you know, the infection prevention control piece is something certainly I've been involved
in and many others have been involved in since 2022.
(13:07):
One of the things that I think we appreciate very quickly is certainly that kind of risk
for broader airborne transmission.
We haven't seen any FD that's suggestive of that.
But historically, we've been able to gain a lot of knowledge, certainly from endemic
regions of Africa.
So really, the greatest risk for transmission we still see is that close extended contact,
(13:27):
primarily through those that are providing care, whether they're health care workers
or family members, whether they're sharing a bed, whether they're sharing clothing or
bedding that is not being laundered.
And we've seen the potential for transmission through things like sponges or cleaning materials.
We've been working with a few groups, providing some guidance on looking at different disinfectants
(13:53):
that are being used kind of in different areas of the world.
The kind of good news is the majority of what we would assume continues to be the case.
Bleach tends to work really well.
Most good, you know, kind of, you know, antiviral disinfectants work very well.
Soap and water work very well.
A big piece of this is trying to ensure that anybody that has lesional disease that thinks
(14:16):
that they are in contact with or bedding or clothing are getting laundered and that the
people that are, you know, basically in contact with those things, either they're also monitoring
their symptoms and or also using personal protective equipment.
Okay.
Yeah.
So very similar to other viral diseases, encourage hand washing and inner basic hygiene and laundering.
(14:39):
Absolutely.
And our concern, I think right now with DRC, I mean, there's a big focus on certainly the
sustained human to human transmission piece for good reason.
But there's also a big piece of this, which is, listen, we know where really kind of the
root of many of these infections are, and it's that zoonotic contact.
There's a big piece of this, which I think is still, you know, kind of embedded in this
(15:00):
idea of community engagement and trying to understand where infection prevention control
practices can be implemented within communities that's done in a respectful and transparent
manner in a way that doesn't impede people's ability to still hunt or to still be able
to consume while game.
And then once you have somebody who has a condition like this, who's contracted the
(15:26):
virus, they have symptoms and they have signs and you're considering, you know, thinking
about first, I guess we talk about diagnostics because if I'm an ER physician or a hospital
physician, oftentimes as an infectious disease specialist, we'll get phone calls to send
off.
So what I see a patient like this, what do I send off?
Yeah.
So the easiest thing really is still is lesional swabs.
(15:49):
OP swabs tend to work fairly well as well.
There have been some studies that have looked at kind of longitudinal viremia in patients.
Those I think for the most part have suggested there's not a really strong viremic component,
at least in the majority of cases.
So I think we're still kind of focused on lesional swabs.
PCR by far and away is the method that still continues to be tried and true.
(16:14):
There's been some changes though, because as we've seen kind of the emergence of clade
2b coming out as a subclade out of clade 2 and now clade 1b is a subclade of clade
1, we've also had to look at primers and whether or not those primers are still picking
up the virus that we assume that they're recognizing.
(16:34):
So for clade 1b, one of the things that we have seen recently has been that the kind
of traditional primers that would be used normally for clade 1 infections, there's actually
a deletion in clade 1b and those primers could potentially give a false negative.
Colleagues in Europe have already reported primer sets that appear to recognize clade
(16:57):
1b very, very well.
But we also know that kind of like the overall kind of orthpox virus kind of centric primers
work very, very well.
They just don't give you that clade distinction, right?
So PCR still works.
We do a lot of sequencing.
There's certainly something to be said about looking for antigens to try and identify people
(17:17):
who have been previously exposed.
We have done quite a bit of serosurveillance in this realm.
The difficulty is pox viruses have very close antigenic similarities.
That's why we use vaccinia for eradicating smallpox and we use it now for the M pox vaccine.
That cross-reactivity somewhat precludes our ability to go in and say, okay, have you been
(17:39):
exposed to monkey pox virus or cow pox virus or some other unknown human orth pox virus?
That being said, in many areas that are endemic, we have a pretty good idea of what's circulating.
And certainly if there's an outbreak situation, you can start to distinguish.
There's questions about if somebody has been vaccinated for smallpox, what does cross-reactivity
(17:59):
look like?
But really if we use 1980 as that tipping point for people that were or weren't vaccinated,
you can start to surmise what's going on based on that.
That's fair.
And then most centers, do they have the PCR testing or is this sent to National Microlab
in Canada?
Well, it's a good question.
(18:20):
So certainly for clade 2 right now, like Cepheid has there, the gene expert is certainly widely
being used for clade 2.
That I think continues to be the case.
For clade 1b, there's certainly been some questions about how we're going to be able
to test for this and really to try and distinguish clade 1b from clade 2b.
(18:42):
Using orth pox virus centric primers, you're still able to pick it up and say, okay, yeah,
it's PCR positive.
It's monkey pox virus, but we don't know which clade.
For clade 1b, the issue that we have is this is a fairly recent development for the identification
in Congo.
So there's a lot of people that have been asking about access to nucleic acid to be
(19:03):
able to validate tests within their own laboratories.
And that's not only in Canada, but certainly well beyond and in too many different places
across the globe.
That's going to be a big piece.
I think is that validation part likely, we're always a little bit behind with sharing materials
globally unfortunately.
I think right now, given the public health emergencies, that's going to be a big piece.
(19:26):
But the confidence comes out of that the primer sets that have been reported so far that have
been in use through Congo and in other regions.
And then in terms of treatment, so are there antivirals out there or this is mainly supportive
management currently?
No, there's so for clade 2 infections, T-pox worked very, very well.
Ticaviromat, ST246, I kind of have gone through every iteration of the name at this point,
(19:53):
worked very, very well.
And certainly in the US and Canada, that was kind of the antiviral that people were moving
towards to try and reduce the impact of these infections.
There's been an issue though that's come up in Congo, which is a very recent clinical
trial for Ticaviromat on the ground failed.
It didn't show any added benefit.
(20:14):
The reality though is that it's unfortunate.
There's probably a number of reasons why that trial may have been limited in its potential
to be able to be successful.
But a big piece that came out of that was you reduce the overall mortality just with
providing good supportive care.
And I think to me, that's a really important piece of this, which is for countries that
(20:39):
have been scrambling for T-pox, certainly in 2022, maybe looking to do that for 2024.
Blade 1B, we don't think it works, but if you provide good supportive care, you reduce
certainly the mortality.
I think the bigger kind of piece of all that though is saying in the areas where we see
endemic disease, one of the things that we can do to immediately reduce the impact is
(21:02):
be able to provide extra assistance for being able to give supportive care on the ground.
So I think that's an important piece.
Vaccination still works well.
We have no reason to think the MDA, the very Nordic vaccine would not provide cross protection
against Blade 1.
It's still a vaccine based vaccine.
So I don't think we have any concerns that way.
(21:24):
A big part is still trying to get vaccines to really the hotspots of the world where
we see circulation and that continues to be an issue.
And so, yeah, so I would say I've had a couple of questions from physicians and colleagues
and patients.
Is it worthwhile for them to get vaccinated or is it something only limited to if they're
(21:46):
traveling to these endemic areas?
Even through travel, I don't know if there's a travel based vaccination program that's
available.
That may change because of the public health emergency.
My lab and myself have been vaccinated because we obviously work with samples as well as
with vaccine of virus and other pox viruses.
(22:08):
I was vaccinated ages ago for ACAM2000 or with ACAM2000.
The public availability is still pretty limited, right?
Yeah.
We have lots of stocks and stockpiles of ACAM2000, but that was contraindicated for certainly
for very specific groups.
The JYNNEOS or MBA vaccine, we don't have nearly the stockpile that we did.
(22:30):
So there's still basically the push to try and get that vaccine to those populations
where there is an increased risk for infection, close contacts of patients that have suspected
or confirmed cases.
That's still the focus, but as well kind of appreciating that we need to get vaccine into
certainly in the Congo and probably now into Burundi and surrounding areas very, very quickly.
(22:52):
So I think if we start seeing influx in cases, whether clade two or clade one driven in Canada,
there's going to be a need to ensure that healthcare workers are vaccinated.
But there's the other piece too, which is good infection prevention control also is
very, very good at reducing those infections.
So we just have to kind of take it at face value.
(23:14):
Right.
Okay.
And so kind of the idea being prevention right now.
Even if somebody does have the illness to be cautious, to not be around others, especially
those that are immune compromised, kind of similar to what we would say with any other
viral infections.
100%.
Right.
And we know the thing is we know that the routes transmission predominantly, right?
(23:36):
You know, eucosal membranes are going to be key in ensuring that we don't have any open
wounds or abrasions.
Those kinds of things continue to be important.
And I think we go back to the idea of when people are vaccinating people, certainly old
school, like CAM 2000 or even way back in the flybacks, it was about those preventative
measures trying to remove the risk for exposure.
Right.
And so recently with WHO declaring this public health and global health emergency.
(24:01):
And so how is situation evolving and appreciating that things are changing daily?
I'm sure.
Yeah.
I mean, the situation on the ground in Congo, you know, through certainly through the work
that we're doing, I don't think that the situation has necessarily changed.
We're looking at from 2023 and now around 30,000 suspected cases.
(24:21):
We've seen movement of virus really to 25 to 26 provinces now with local transmission.
It continues to be widespread.
And we're not seeing any indication that things are starting to ramp down.
Right.
So that continues to be a big concern for us.
Probably as concerning of an issue though, is really the movement into Burundi and some
(24:43):
of the surrounding regions.
Burundi in particular, because of the limited resources that are available in country from
a healthcare standpoint and just an overall standpoint, concerns about the increased circulation
that we're now seeing there.
You know, Uganda and Rwanda, we've seen cases.
Kenya, we've seen cases.
Those seem to be pretty controlled so far.
(25:06):
That's assuming that people are feeling comfortable with self-reporting.
But I think for us that the focus right now is really what's going on in Congo, what's
going on in Burundi.
We've seen introduction or at least the kind of the indication of cases that have been
identified globally.
So we've seen a case in Sweden.
We've now seen a case in Thailand.
(25:27):
That's not that surprising, right?
People are still traveling.
People are still living in a globalized community.
We're likely going to see those cases continue to be identified.
The bigger piece to me is going to be what happens afterwards?
Do you see any additional signs of community transmission or broader transmission within
(25:50):
those local populations?
Or did you get good testing and contact tracing out and you don't see any local spread?
So that I think continues to be important for developments.
The other piece is we've seen, you know, really the kind of discussion about getting vaccines
on the ground in Congo go from being a few months down the road to now kind of like within
(26:11):
the next couple of weeks there will be vaccine.
Don't know much about the deployment strategy yet, what that's going to look like, which
groups are going to be going to be kind of the focal groups for that first round.
But certainly we're there and others are there to help support where we can and certainly
to try to get some clinical information out as quick as possible where and when we can.
(26:33):
Okay.
Seems like a very pressing situation, but you know, things, I think there's things are
in the works and hopefully, you know, we don't see more spread in circulating virus because
obviously we know what with the previous kind of virus activities we've seen over the last
few years, we know that things can change really quickly.
(26:53):
So, and then, so in terms of Canada or other countries, what are they doing in terms of
like mitigating risks or surveillance for disease surveillance?
Yeah.
You know, I think one of the big pieces that, you know, that has maybe not gone as much
presses as it's needed to over the last bit is we have this pressing situation in Central
(27:14):
Africa.
There's been a bigger question about, okay, well, what happens now if clade one moves
more broadly and especially clade one B.
The thing that I think we need to appreciate is, you know, two years out from 2022 to appreciate
that listen, our surveillance networks, our testing and tracing networks, the knowledge
base in our healthcare workers and as well, even within communities and community advocacy
(27:38):
groups, all of that has increased to a much higher level than it was pre-2022.
So I think we're in a very good place for identifying cases.
We continue to see, you know, cases being identified in Ontario, a little bit of a surge,
you know, kind of coming through this summer.
Same thing with other regions of the world, not approaching anything what we saw in 2022,
(27:59):
but it should be a reminder that like clay to virus didn't disappear.
It's still circulating globally.
It's still circulating here within Canada.
It's just at a very, very low level.
So I think we're doing very, very good in terms of our surveillance.
We now have to add the PCN about clay one B recognition, but we're in a place where
we should be able to identify those, those cases very, very quickly.
(28:22):
That's really good to hear.
And so in terms of resources, cause I think that's also important for healthcare professionals
across the board, also sometimes just general public, you know, asking questions.
And so where can people find, I mean, like obviously CBC has always been a really good
resource, but are there other certain areas that we should be looking?
There, there are.
(28:42):
I mean, I, you know, I don't want to, you've got to shine a spotlight on work that I've
done because I've sat on panels with far smarter people to myself to pronounce on this.
WHO a couple of years ago had a guideline development group for clinical management,
infection prevention control.
That's really available through, through WHO for M pox.
I think that's still largely applies to everything that we're seeing now.
(29:05):
WHO just recently updated all their information on infection prevention control, their descriptions
of M pox, those resources are good.
And of course health Canada and public health agency of Canada continue to provide information
as well.
And of course there's, there are research groups that are doing work in this area.
You know, all of us have a lot of information as well, but I think going to those kind of
(29:25):
big sources, European centers for disease control, U S T D C, WHO and, and health Canada
are major resources.
That's really helpful.
Cause I think a lot of people will be starting to see more questions come through and that's
kind of natural that happens clinically as well.
You know, we always think about what's happening with circulating and I think awareness is
(29:47):
important.
And so that's why we're talking about this today, because I think most of us should have
some base knowledge on monkey pox and, and you've given us some really good information
today.
So in terms of kind of summarizing or some key points that you'd want the public or health
professionals to really take away from today's episode, what would you kind of summarize
(30:11):
in terms of that?
Yeah, I think a big piece of this is right now that the global risk for, for clade one
introduction continues to be quite low.
I think also appreciating that, you know, things can change.
We know that that happened with clay too, but we're in a different place than we were
in, in 2022.
We have good surveillance networks.
We have good sharing of data and testing protocols.
I think that piece allowed us to be able to move forward.
(30:34):
The kind of piece that I think is at the heart of this though, is we want to reduce the risk
globally.
We've got to reduce the risk locally, which still gets back to the need to not only get
things contained in, in DRC, but also to look at other endemic areas of Africa and say,
we need to get vaccination programs up.
We need to get surveillance programs sustained and as well go back to this piece about healthcare
(30:57):
infrastructure and certainly the need to be able to harmonize data reporting globally
right now for M-POC.
So we all have a good impression of what we're looking for, but I think it's going to be
a key area.
Yeah.
And then just on a note that I actually forgot to ask was in terms of reporting.
So if physicians or anybody is seeing cases, are these then like, I mean, through the lab,
(31:22):
we're definitely reporting to public health, like local public health authorities.
Is there something that a physician should be doing in terms of any surveillance network
that they should be entering their data into?
Not that I've seen so far, right?
And listen, that can just be my naivety for what, what's available in Canada.
In DRC, we've got, WHO has their centralized system for us to be able to report and upload
(31:46):
data continually into.
So we've, we've been working on that and certainly most, most of those countries have good centralized
systems for entering in national data.
It can be a little bit slow at times, but we continue to do that on the ground as well.
And then of course, Africa CDC is obviously taking a much bigger role in this with trying
to ensure that there's good data reporting, data management, and as well sharing of information
(32:11):
globally.
Okay.
That's great.
Definitely, I think everybody's on top of it and it's good to hear a little bit more,
you know, about Monkeypox and, and have a bit more background.
So I've learned a lot for sure.
And, and I always inform my listeners that this is an informational podcast and things
do evolve and, and over time, you know, even prevention or treatment options may change.
(32:37):
So currently this is the situation with Monkeypox and, and what we know about it right now.
So I'm sure our listeners will take a lot back from this episode and thank you Dr.
Kindertruck for being here today on our podcast and providing us with such great information.
It was an absolute pleasure.
Thank you.
Thanks.
(32:57):
Take care.
Thank you, Dr. Kindertruck for joining us today.
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