Thanks for meeting us again at the Canadian Breakpoint, a Canadian infectious disease
podcast by infectious disease physicians.
I'm Summer Stewart, back again with Rupeena Purewal, paediatric infectious disease specialist,
and for this episode, we welcome special guest Dr. Amita Singh, an infectious disease specialist
from Edmonton, Alberta for discussion regarding the rising cases of syphilis in Canada.
Dr. Purewal.
Welcome to another episode of our podcast, the Canadian Breakpoint.
Today we'll be discussing a very important topic, syphilis and the current situation
in many provinces in Canada.
As you may all be aware, syphilis is a reportable sexually transmitted infection that's caused
by the organism tropenia pallidum.
Living on the stage of syphilis in an individual, they are treated with a certain regimen and
the first line of treatment, especially in pregnancy and in pediatrics is penicillin.
Notably, if left untreated, syphilis has many complications and in all age groups.
The risk factors are very similar to other sexually transmitted infections, but the alarming
factor with syphilis is that we're seeing a steep increase in the number of cases in
many provinces in Canada since 2014.
Specifically, Alberta has shown us the greatest rise.
Here in Saskatchewan, we've had an exponential increase in the last few years and specifically
concerning that congenital syphilis has also increased and caused a rise in the number
of stillbirths, hydroxpitalis and other preventable complications in neonates.
So today we have a very special guest with us from Alberta who specializes in this area.
So please join me in welcoming Dr. Amita Singh.
Dr. Singh is an infectious diseases specialist and clinical professor with the University
of Alberta in Edmonton.
Her clinical practice and research areas of interest include bacterial sexually transmitted
infections, HIV, biomedical prevention and rapid diagnostic tests for syphilis and HIV.
So thank you, Dr. Singh.
We look forward to hearing from you about your thoughts on this topic.
Thank you for having me.
Perfect.
So why don't we start with just discussing the situation currently in Alberta in regards
to the syphilis outbreak.
Sure.
So you're probably aware that in 2019, our chief medical officer of health declared a
syphilis outbreak in Alberta after seeing syphilis rates in the province rising manyfold
and the highest rates seen since 1948.
And despite the COVID pandemic, that trend continued in 2020, even though I understand
that there has been decreased testing following the onset of the pandemic.
We had a record number of cases, 2,500 infectious syphilis cases in the province in 2020.
And sadly, 135 infants born with congenital syphilis with about 30 infants who died as
a result of congenital syphilis.
So very alarming to see that happen here in Alberta and of course, appearing to continue
into 2020.
Yeah, for sure.
Definitely seeing an increase there.
So why do you think this is an issue in the Prairie provinces specifically or in Alberta?
Or do you think it is limited to that?
We do seem to be seeing the highest rates of infectious syphilis in the Prairie provinces.
And if we look at the cases to try to understand why that is happening, it is very clear that
Indigenous persons, particularly those of First Nations ethnicity are disproportionately
affected.
And we know that Edmonton, for example, which has the highest number of cases in Alberta,
has the second highest urban population of First Nations and Métis persons.
And so that's definitely, unfortunately, the individuals who are being affected.
If we look at the breakdown of the cases, we see that about half of the cases are among
females and usually of childbearing age.
And many of those women are affected by multiple social determinants of health, including homelessness,
poverty, addictions and mental health problems.
So I think another thing that we have observed in the last few years in the Prairie provinces
is a significant rise in the use of methamphetamines.
And methamphetamines, as you know, are drugs that act as stimulants and they also increase
the sex drive and disinhibit behavior and makes it more likely for people to engage
in unprotected sexual behavior that puts them at risk for syphilis.
So we're actually in the process of taking a closer look at the link between stimulant
drug use and syphilis in our province.
But just anecdotally, I really feel that that is a very strong component of what is happening
or part of the explanation for what is happening with infectious syphilis.
And we have heard that many of the women are trading sex for drugs.
And this is the unfortunate consequence.
Yeah, it's a very difficult situation.
I mean, it's definitely multifactorial in terms of management wise.
And yes.
So currently with, I mean, we're here in Saskatchewan having, I think, from 2018, we've had a six
fold increase in our syphilis cases.
And it goes along with other sexually transmitted infections.
So we've seen a rise in our other sexually transmitted infections since kind of the methamphetamine
numbers have increased as well.
So in terms of provinces facing this obstacle, I know that you're currently involved in a
point of care study regarding syphilis testing.
So can you talk a little bit about kind of what brought you to kind of start this study
in Alberta specifically and kind of the design and the model and maybe some of the other
provinces can get some input from you in regards to that?
Yes, for sure.
So with the observation that many of our cases are street involved and have pretty significant
mistrust of the traditional health care system, when we first experienced a resurgence of
infectious syphilis in the mid 2000s, an outreach team was formed in Edmonton, which includes
nurses and community health representatives.
And all of those community health representatives or Aboriginal service workers, as they're
now called, are Indigenous and have some lived experience as well.
And that team, in my opinion, has been invaluable in going out literally onto the streets to
reach people and to offer testing and treatment right there and then.
Unfortunately, the COVID pandemic has put the brakes on that for now, but I'm really
hoping that we will be able to resume those activities very soon.
So the team is able to go out into the community and they're able to do blood draws and to
collect urine samples.
And if people meet certain criteria, so for example, if they're named as a sexual contact
to a known infectious case, or if they report symptoms suggestive of infectious syphilis,
the team are able to offer treatment right there and then.
So it may be in a community agency, for example, or in an inner city health clinic.
And on some occasions, it's even been done in the individual's home, or if they have
some sort of enclosed situation.
I remember several years ago going out with our outreach team and actually reaching people
who are living in tents in the River Valley here in Edmonton.
So it is possible and feasible to do this.
One of my wish lists for many years has been for us to have a mobile van that would make
this a lot easier.
For sure.
For a number of logistical reasons, we haven't been able to do that.
All that being said, we came to realize that although we could offer blood draws and urine
tests, it would then take up to a week for those test results to come back.
And then it would be very difficult to find those individuals, especially if they didn't
have a fixed address.
And so this is where I think point of care tests are invaluable.
Not only do we have the opportunity to test and treat right there and then, but we also
prevent ongoing complications if you are able to test and treat immediately and prevent
mother to child transmission, as well as prevent transmission to partners.
So this began the search, I guess, for a good syphilis test.
There are a number of syphilis tests on the global market.
A little over 10 years ago, we did try one test in the field, but unfortunately, that
test did not work very well for us because it took too long.
And by too long, I mean that it took about 20 to 25 minutes, but for truly field use,
that wasn't very practical.
And our field staff are not supportive of that because it was also a little bit cumbersome
to perform in the field.
And so we never moved ahead with that.
So fast forward now 10 to 15 years later, we're an even worse syphilis outbreak situation.
And so I once again had a look at the available tests on the global market and came across
two tests that could provide test results in under five minutes.
And so of course, that was very exciting.
Both happened to be made by Canadian companies, one in Vancouver, at BioLitical, and one in
Halifax, Medmyra.
And with the support from the companies, as well as the support from REACH, we were able
to obtain funding and to develop a study.
So we have implemented that study.
And our goal was to enroll about 1500 participants.
And we're currently just under halfway in terms of enrollment.
We had actually hoped to complete enrollment within six to seven months, but then the pandemic
hit.
And so continuing the study has been very slow.
But I am hoping that we will be able to complete the study by the end of the year.
The preliminary results suggest that both test kits perform very well in the field using
finger prick whole blood specimens.
And we have been able to offer point of care testing as well as treatment to all individuals.
And very interesting, we've picked up a number of new cases.
And we have been able to offer treatment to everyone immediately if they so wish.
And what has been interesting to me is that everyone that we've offered point of care
treatment to has accepted that.
So we explain the potential benefits of treatment, but also the small potential risks, which
include, of course, anaphylaxis and providing treatment that wasn't necessary.
And despite that, most people have gone ahead with treatment provided there and then.
The vast majority of our testing has been done by one of our part of notification nurses
who works at the Edmonton Remand Center.
And so that is another setting where we have had very high rates of loss to follow up after
standard serologic test results come back.
In fact, we've lost about 20 to 30% of people testing positive.
And so this has been fantastic for use in that setting.
Perfect.
So the primary outcome then of your study would be to compare the point of care test
to standard testing.
So do all these individuals then get serological testing done simultaneously?
That's correct.
So we are doing standard serologic testing simultaneously.
And we also inform patients upfront that there is a chance you could have a false positive
result and be treated unnecessarily, or you could have a false negative results because
we do expect that finger prick whole blood specimens will be less sensitive than a serum
specimen sent to the lab.
And so that they may either way, we ask people to follow up after the standard test results
are available.
But as I mentioned, not all of those individuals will necessarily return for follow up.
Yeah.
And I think that's probably one of the limitations that we have with syphilis is, I mean, there's
a number of factors like loss of follow up contact tracing.
So if something like this is in the picture where we have a point of care test, and you've
already treated, at least we've kind of eliminated some of the other risks of transmission then
to partners.
And if there is loss to follow up, then if they've received treatment, at least there's
that safety component that you've already given them the treatment.
So I think for some of our northern populations, even here in Saskatchewan, we're having a
lot of difficulty with access to care.
So I think if reaching out to them and doing the point of care, like you mentioned, or
even doing the mobile vans and mobile clinics is probably a good stepping stone for this,
for sure.
Yes.
And I think the trouble, one of the things that has been suggested may be a barrier to
testing though, the mobile van, as you know, if you say it's an STI.
Right.
Although we found that, you know, so if it could be offered together with other measures,
so for example, immunizations or I don't know, other kind of checks.
Maybe doing blood pressure or glucose or something like that, then perhaps it might be more acceptable.
So there are a number of things that would need to be taken into consideration there.
For sure.
Yeah.
And I know there was, you know, there's a huge stigma behind some of the other STIs
that we deal with such HIV.
So I'm sure with syphilis, we kind of have similar, similar kind of feelings and emotions
regarding the stigma behind it.
So yes, now that's very interesting because I've personally felt that it is so incredibly
important to do HIV testing because HIV testing not only affects how syphilis presents and
evolves if it remains untreated, but also how we follow up after treatment that I personally
think that HIV testing should be considered an essential component of syphilis testing.
And we've tried to present it that way when offering testing to patients.
You know, just say to them, you know, this is what we're testing you for, for STIs.
We're doing syphilis, HIV, gonorrhea and chlamydia in the hopes that eventually we will start
to normalize HIV testing in the same way and to hopefully reduce some of that stigma that
unfortunately, as you mentioned, continues to be in place.
Definitely.
That's a great thing.
Yes.
And so, you know, I didn't mention that we did choose to do a dual testing with syphilis
and HIV.
And so both of our test kits offer testing for both syphilis and HIV.
And I can tell you that that did create some concerns with our ethics board.
And with the communities as well.
But after I explained my rationale for doing this, and, you know, people do have the option
to opt out completely.
But in fact, we've not observed anyone opting out because we've had this combination of
tests.
Oh, that's fair.
Yeah.
And once they receive the point of care test, is it very similar to kind of the previous
HIV point of care tests that we've had in place where it gives you a positive or negative?
So it's almost identical.
One of the companies that makes the dual syphilis HIV test has the only Health Canada approved
HIV test in Canada.
And it is a fantastic test.
I was involved back in the mid 2000s when the test kit first rolled out in Canada and
helped to set up the point of care program for HIV in Alberta at that time.
And we were involved with the initial evaluations and it is an almost identical test kit, except
that it also includes the syphilis component.
And it is extremely user friendly, very fast.
In fact, most of the test results are under a minute.
And it is so user friendly that the company together with help from REACH has been able
to implement HIV self testing so that the individuals can obtain test kits from various
community organizations and perform the test on themselves.
So it is a fantastic kit and I'm really hopeful that it will work well for syphilis as well.
Wow, that's really good to hear.
In terms of sensitivity and specificity for the assays that we're currently testing in
your study, are there certain variables that the companies themselves have released or
is that something that you're also then kind of comparing and is that one of your outcomes
that you're measuring?
Yeah, so there is some preliminary data for both test kits and for the biological test
kit, the preliminary data suggests that the sensitivity is lower with infectious syphilis
cases where the RPR titer is less than or equal to one in eight dilutions.
But it seems to perform very well with high titer RPR cases.
So with that in mind, prior to rolling out the study, I had a look at all of the cases,
the infectious syphilis cases in the province and about 70% of the cases at diagnosis had
an RPR titer which was reactive at one in eight dilutions or higher.
So we anticipate that the vast majority of cases would be picked up on the point of care
test.
The MedMirror test has even less data, but the sensitivity does look pretty reasonable
from finger prick whole blood specimens.
But yes, that is the primary objective of this particular study, which we've coined
the acronym POSH for point of care tests for syphilis and HIV.
So for the POSH study, the primary objective is to look at the performance, primarily the
sensitivity, specificity and negative and positive predictive values as compared to
standard serologic tests.
Perfect.
All right.
Well, I think that's a great initiative because I think one of the biggest drawbacks with
syphilis testing is the turnaround time that we're having with the serological testing.
And a lot of centers that are dealing with outbreaks, I think, have the initiative to
kind of test and treat and then await results kind of similar to our other STIs such as
gonorrhea or chlamydia.
But again, for the patient as well and for the provider who's administering the therapy,
if we can have a point of care test that can weigh in on that decision, I think, and if
you're saying it's less than five minutes or even less than a minute, you can get those
results back.
I think that's definitely something that would be helpful for decision-making, clinical decision-making
as well.
Yes, absolutely.
Yeah.
So what obstacles?
I know COVID's been probably the biggest obstacle in all of...
Yes.
Basically in all of medicine.
In all time.
In all life.
Yeah, exactly.
So definitely none of us have gone through kind of something similar in our lives.
So I think it's definitely brought in a lot of obstacles for access to care, even in just
general day-to-day care, and definitely with our sexually transmitted infections.
But what other obstacles do you feel that we face right now to manage this syphilis
outbreak at this time?
Yes.
Well, maybe I'll discuss a little bit some of the obstacles with the point of care study.
Sure.
So yes, indeed, the pandemic was an issue and we won't go there.
But in terms of the actual test kits, I think that one of the challenges that we experienced
initially when training the staff is that people had the notion or preconceived notion
that these test kits, it's just like buying a pregnancy test over the counter and you
just dip it in the urine and away you go.
But unfortunately, there is a little bit more to it with these particular test kits.
And not in least part because the quality assurance of the test kits is absolutely critical.
So for example, to make sure that when the test kits are received from the company, we
have had each batch of test kits evaluated by our provincial lab.
And they will test sort of randomly test a few kits just to make sure that they're performing
as expected.
And only then do we have them distributed to the sites.
Now, the reason that this is important and we haven't experienced any problems in this
particular study, but another study that I'm involved with in Nunavut, there was an issue
when the test kits were shipped out in the wintertime and they did not perform as well.
And we were having some concerns about some of the results.
There were in fact, were a number of false positives.
And it turned out that the issue there was that the test kits had frozen in transport
and had stopped working as expected.
And so that's just kind of one very important piece.
But even after the, with our particular study, we experienced a bit of an issue after receiving
the test kits and distributing them because a small proportion of one of the company's
test kits had inadequate offer in one of the bottles that you mix the blood specimen into.
And so we actually had to return that batch of test kits and receive a new supply, but
that was only identified after the first few tests were done.
And we were able to identify that as an issue.
And then the third big problem that we experienced is that we were not aware that, so we spent
a lot of time focusing on the training about syphilis and the study protocols and how to
actually perform the test kits.
And when we did the training with the test kits, we mostly did that with stored sera
so that people could see what the positive test results look like and the negative test
results look like.
But we had not spent much time focusing on how to actually do and collect the finger
stick whole blood specimens.
So that was a bit of a learning curve for us.
And we actually had to go back and seek some additional training, not only for ourselves
as the investigators, but then to make sure that all of our study staff were retrained
in that finger stick whole blood collection process.
So those were just some learnings.
And I wish that we had known all this before we started, I guess, just to try to make it
a bit smoother with the rollout.
But I think now that we're up and running, we have a well-oiled machine.
Nice.
That's great to hear.
That's great.
So we've talked a little bit about the limitations and I think the strengths of your study is
something that we also want to touch on.
So how do you feel with the strengths of the study and how this information that we gather
from this POSH study, how it will help your list of lists outbreak in Alberta?
Yeah.
So in terms of the strengths of the study, we have managed to include a number of sites
in the Ebbinton zone, as well as in some of our northern communities.
So I think we have fairly good distribution in terms of use of the test kits or potential
for use of the test kits.
And then also, you know, different settings too, because one of the things we will also
be assessing is the test user experience with this.
And we'll be able to take a look at how the user experience in terms of the volume that
they've done affects their experience.
And so I think that that is one of the strengths of our study though, that we tried to identify
sites based on where the problem was happening.
And so that is continuing.
In terms of where we're hoping to go with this, I am really hoping that our study data
will be used by both companies, assuming that the data shows or confirms that both test
kits do have value for point of care testing for syphilis, that they will then apply for
Health Canada approval so that we no longer have to go through a research type of process
to use these test kits in Canada or to use it in an off-label capacity.
Because that does pose additional challenges, as you know, it would be nice if we could
simply buy the test kits, do all of the quality assurance and training, and away we go and
use them.
But the companies, neither of the companies has sufficient data on the performance of
the test kits currently to apply for Health Canada approval.
Right.
It's definitely going through an ethics approval approach for every centre is usually challenging.
So I agree if we have kind of...
It is challenging and I will be the first to say that I did try to persuade our ethics
board that having a four-page consent form was really not practical nor necessary.
But that is what we have.
We were able to make some progress though with the ethics board at the request of one
First Nations community to allow for verbal consent.
So allowing the testing provider to obtain consent from the person.
So that was a little bit of progress.
For sure.
I think there's...
Yeah.
We do provide everyone with a copy of the consent form should they wish to read it.
Perfect.
Yeah.
I think if there's anything that we can do to kind of limit the barriers to testing with
syphilis, I mean, that's always something that I think all provinces and all places
are having clinicians are having challenges with.
So definitely if you can have a streamlined process like you have in place, that would
be great.
So currently in our provinces in Saskatchewan, we've introduced kind of the point of care
testing as well, similar to, as you're aware of as part of the study as well.
And so if a province would like to be involved in the study, is that something that you guys
are currently still offering in terms of needing eligibility and where you guys are with enrollment?
Well, that's an excellent question.
So I did discuss this with our study team here, and unfortunately we don't have the
capacity to support all of the paperwork requirements.
So the Health Canada applications, as well as the ethics board requirements, particularly
if there are study modifications.
So what I have done instead, I guess, is that I've offered up all of our documents for people
to use.
And the fact that we have Health Canada approval will just make it easier for anyone else.
Wishing to do this to obtain Health Canada approval, as well as we're happy to provide
our ethics board approval, which could be used as well.
And the other thing that I have offered is my time, I guess, I'm happy to help to support
training in any way, if that would be helpful.
That's perfect.
Thank you so much, Dr. Singh.
So I guess kind of ending off on the topic of advice.
I mean, you're the expert and the specialist in this area.
Also being a clinician myself, I definitely kind of advocate always STI testing and including
syphilis because we know that we're seeing these numbers and we always advocate for testing
for all of the STIs and not picking and choosing because we know that they usually have a similar
risk factors.
So what advice can you give to let's say family doctors out there or any clinicians really
having first access in terms of testing and even if they don't have access right now to
the point of care test, how they should go about the syphilis outbreak or any kind of
expertise that you can give us because definitely the other provinces we're drowning in our
numbers as well.
And it's becoming quite an exponential increase here.
Yes, no, I mean, that's an excellent question.
Of course, it's always challenging because people have competing priorities.
But given what is happening with syphilis right now, particularly in the Prairie provinces,
I think it is really important that all providers have a heightened awareness.
Of course, as you've mentioned, you know, you do and I do, but that's not good enough.
I need everyone to be thinking about this possibility and to consider offering STI testing
as part of routine care.
And I am a strong advocate for normalizing this testing.
You know, most people are having sex, don't necessarily need to know the details.
You're offering it in the same way that you would offer testing for diabetes or hypertension.
Screening, I should say.
And you know, and if you're going to offer STI testing, do it as a package.
So definitely do HIV syphilis blood tests.
And for certainly for males and females, if you offer urine for gonorrhea and chlamydia,
that is a pretty good basic STI screen.
So you know, it's just thinking about it.
And then if people are presenting with weird symptoms that don't make sense, just about
absolutely every, any clinical manifestation you can ever think of or possibly conceive
of has been caused by syphilis as far as I can tell.
Think about syphilis and do a test.
So particularly patients presenting with changes in vision or neurological symptoms, including
acute psychosis.
We've seen a number of cases like that where there've been delays in diagnoses.
You know, if individuals presenting with stroke-like symptoms or trouble walking that you wouldn't
expect to have had a stroke, think about syphilis.
You know, and offer the testing.
No, that's great advice for sure.
Yeah, I think definitely the name for syphilis is the mimicker of all other diseases.
So I think it's done.
It stood by its name for sure.
Yeah, till today.
Yeah, no, definitely.
Well, that's really great.
Thank you so much for giving us some input regarding your point of care tests, the POSH
study, your expertise is invaluable.
Honestly, like in terms of what we're experiencing right now, even with congenital syphilis is
kind of what I'm seeing more of.
We're seeing two to three cases a week of presumed congenital syphilis.
And there's, you know, these are preventable complications that, you know, it's almost
as a clinician, it's always, always difficult when you know, something could have been prevented
and you're at the treatment phase.
So I think awareness for sure regarding syphilis testing, and if we can kind of limit the barriers
to testing with the point of care tests in place in the near future, I think we'll be
better on track to manage these syphilis outbreaks for sure.
Definitely.
And I guess last but not least is continuing to pay attention to the social determinants
of health because until we fix the roots or attempt to address the root problems that
is the syphilis is just the tip of the iceberg of so many things that are happening right
now that we need to address, particularly in our First Nations population and to work
with those populations to figure out how best we can support their needs.
Oh, definitely.
And thank you so much for all your help with this.
And I think clinicians like yourself and your expertise have definitely revolutionized a
lot of sexually transmitted infection diseases.
And there's been a lot of changes that have occurred in the last decade or more.
And so hopefully we'll see some new revolutionary changes with syphilis and its management.
Yes.
Thanks so much, Rapina.
Yeah.
Thanks a lot.
Nice chatting with you.
Yes, you too.
Thank you for joining us on another episode of our podcast, the Canadian Breakpoint.
Today we discussed an important issue regarding the ongoing syphilis outbreak in Canada.
I hope you enjoyed this episode.
I would like to thank Dr. Singh for taking the time to discuss the current situation
in Alberta and other provinces and for providing guidance and expertise with preventing and
managing syphilis.
Thank you to Dr. Purwall and Dr. Singh, as well as Verity Pharmaceuticals, their kind
sponsorship.
Follow us on Twitter at CABreakpoint and email us at thecanadianbreakpoint at gmail.com to
suggest infectious disease topics or discussions you'd like to hear.
We look forward to seeing you again at the Canadian Breakpoint.