Welcome to the demystifying medicine podcast measles virus
Edition.
We are lucky to have an expert here on the field.
Today to help us break down the Measles virus welcome.
Dr. Caitlin Mullarkey.
Thank you for taking the time to speak with us
today. Would you like to introduce yourself quickly for audience?
Sure.
Excellent.
Yes. I'm happy to be here.
Thank you for the invitation.
My name is Caitlin Mullarkey.
I am a faculty member and biochemistry and biomedical Sciences
at McMaster University.
I am a viral immunologist by training.
So I've spent a long time thinking about viruses and
the immune system and with a particular emphasis on
how to build better influenza virus vaccines.
Wonderful.
Thanks for joining us again.
Dr. Mullarkey and for agreeing to appear on our podcast.
If you don't mind,
we just going to jump right in and ask you
a few questions about the measles virus.
Sure,
what sort of the basic question to get our foundation
in order.
Can you give us a general overview of what measles is
is?
Sure measles virus,
is it belongs to a family of viruses that are
known as paramyxoviruses.
So,
these are viruses that have negative single-stranded RNA genome.
And measles virus in particular,
is an enveloped virus,
which means that in addition to the nucleic acids,
which is genome.
It's surrounded by a bit of protein in that bit
of protein is surrounded by a lipid and that's where
that this is what we mean by enveloped viruses.
Now,
with embedded within that lipid envelope are two surface proteins,
are known as hemagglutinin,
which is often abbreviated H,
and there's a fusion protein,
which is often abbreviated f,
and the hemagglutinin,
the fusion protein that are on the surface of the
virus are responsible for attachment and entry.
So,
this is how measles virus actually binds to host cell
receptors,
and gets into the cell in order to replicate.
Well,
thank you for that.
Just a little follow-up question.
So measles is kind of seen as a virus
of the past in many lights yet.
This is super important today.
Could you touch on what makes measles relevant today.
Measles
virus causes the infection,
which we commonly known as measles a little confusing there,
right? When we talked about the virus or the infection,
which is the manifestation of the virus once it
enters into the body.
So what's really important to put this whole conversation in
the context,
is really how contagious measles is?
measles is the most contagious virus,
that we know and when we talk about contagiousness,
There's a term that epidemiologist use and it's been batted
around with the SARS,
Covid-2 pandemic,
which is the basic reproduction number.
Which is often abbreviated as r-naught.
The basic reproduction number is the number of individuals that
will go on to be infected from one infected individual
by myself am infected and there aren't any interventions.
This assumes that there aren't any intervention.
So no vaccination,
no drugs,
no masking or social,
distancing,
measles will one
Infected individual with measles will go on to infect somewhere
between 12 to 18,
other individuals.
As there's a little bit of ranged.
Sometimes we estimate it and say
Basic reproduction number for measles is 15, and that's huge
right?
If you think about,
if one person goes on to infect 15 people in
those 15 people go on to the next fifty more
people.
You can see that the capacity to transmit by mean
it amplifies very,
very quickly.
and for comparison,
right?
We're all still living in a SARS,
Covid-2 pandemic.
Basic reproduction number for SARS cov-2 is between 2 and
3 or 8 is our best estimates,
right? So it's seven times more contagious than SARS.
covid-2 to which many of us already feel as is
quite ubiquitous and so measles.
We have a vaccine for measles that was introduced in
1963 before 1963.
Most individuals.
Before the age of 15 would have been infected with
measles.
So there were hundreds of millions of cases a year.
We seen a drastic decline since the introduction of the
of the vaccine in 1963 and
I'm sure we'll get onto the vaccine the
vaccine is very highly efficacious.
safe and efficacious.
So we currently,
there are,
there are less measles cases than there were decades ago,
but we still have millions of cases somewhere between.
I mean,
There's probably tens of millions of cases of measles globally
every year on those are enriched,
in developing countries.
And in Africa and Asia,
there are hundreds of thousands of deaths globally per year
from measles.
And I think what we've learned again,
to go back to living in a pandemic,
is that in the age of globalization,
with travel and trade viruses,
spread very quickly.
So,
even in in,
if there's a virus circulating in other places,
it threatens the whole global population.
Right?
And that leads nicely into my next question.
How does measles spread from person to person when
people think of measles the disease that we both think
of the stereotypical rash,
right?
Though. It causes a rash that has red flat spots and
then and then bumps that that come out of a
maculopapular erythematous rash
So you have
bumps but you have these red flat spots as well and its full body, and this is the classic
diagnostic feature of measles a full-body rash.
So you might think that contact with the rash or
contacts at the skin is how measles transmits?
It's not.
It's actually transmitted via respiratory droplets.
So we get measles is transmitted from coughing and sneezing
and breathing which releases small droplets
into the air and then individuals who come in contact with
those droplets or in close contact with nasal secretions or
throat
Secretions. That's how they are exposed to the virus.
So not unlike again,
what we've been hearing a lot about respiratory viruses with
with SARS Covid-2.
It just is transmitted in a similar way.
So you mentioned one of the characteristic symptoms was the rash
rash?
Could you expand on that symptoms as well as some
of the other symptoms typical of measles
So with measles,
okay.
So one interesting fact about measles is that it has
a relatively long incubation.
and what I mean by incubation period
Is the time between when you're exposed to the time
when you first develop symptoms,
so,
it's around 10 to 12 days of someone sneezing and
you're exposed.
You won't actually develop any symptoms that alert you to
the fact that you're ill or you're infected till 10
to 12 days later.
so some of the first symptoms for measles like
many other viruses fever runny nose cough,
and then a few days,
after the initial onset of symptoms often times,
we would you can observe in in the mucosa in
the inside of your mouth or what are known as
Koplik spots
These are areas where the virus is replicating and you
can see the small white spot on the inside of
an infected individuals mouth.
And then the rash appears the very classic rash appears
somewhere 3 to 5 days after the initial onset of
symptoms
I'm so the initial on that will will be the
generalized.
Fever,
cough,
runny nose,
and then these other more characteristic or even diagnostic features
of measles appear later.
And unfortunately,
you are contagious before you show the rash,
right?
So most you can transmit to other individuals before you
even know that you're infected with with measles,
which, again,
I think it demonstrates and how rapidly this particular
virus can spread because you don't feel ill enough to
stay home. You might be going out to the supermarket or
or a sporting event or the mall and transmits to
other individuals.
Wow,
that's so scary.
but it's so fascinating at the same time,
so you mentioned that they spread from
one spot and then eventually spread throughout the body.
And we're wondering what's the mechanism behind that has
a really interesting pathogenesis.
So I've already told you that is transmitted via respiratory
secretions. So it typically enters the body in the upper respiratory
tract and It actually infects immune
cells.
So often,
I mean it also affects the respiratory epithelium,
but that that happens later in the infection.
The first cells it's going to affect your immune cells
and immune cells traffic in your body through the lymphatic
system and then the lymphatic system crosses over into your
blood.
So essentially a virus is able to breach many inherent
layers of the fence that we have.
Anatomically.
to gain access into the blood and then once it's in
the blood, it can it can disseminate everywhere and until it happens
is once it gains access to the blood.
If it has access to things like your skin and
then when the virus gets access to the skin and
replicates in the skin,
that causes the rash.
It can also gain access to the brain.
encephalitis
is a severe adverse outcome from a measles virus,
infection that happens in probably about pre-vaccine it
would happen in about one in a thousand.
Individuals who are infected with measles
So once it gains access into your bloodstream and
it can actually also basically traffic
back to the respiratory epithelium,
which it it then infects through the bottom
of this is,
this is what is very counterintuitive about measles.
It's a receptor for entry into the virus is located
on what we called.
The basal lateral surface of respiratory epithelial cells,
which means it's not the side that faces out which
you would anticipate like the side that faces out into
the Lumen of the respiratory tract it faces the inside.
So it infects from the bottom and then is released through
the apical side or the outside and then that's how
someone transmits again.
So it's complex and unusual
in that way,
most viruses with infecting the complete opposite way they would
in the apical surface?
Thank you.
That was really in depth and.
Very interesting.
So you kind of talked a bit about the vaccine
already,
but I wanted to know obviously a bit more about
the vaccine and some pre-existing,
interventions as well as any existing intervention to stop measles
music. Once you are infected,
you think you could talk a bit about that
with the vaccine again,
we've had a vaccine since 1963.
It is highly highly efficacious.
So two shots of
The measles vaccine will protect 97% of individuals for
their entire lifetime.
Do it elicits lifelong protection in the vast?
That vast majority of individuals who receive it.
Obviously no vaccine is perfect.
No vaccine is a hundred percent,
but measles is really up there and terms of efficacious
as I think probably maybe the yellow fever vaccine has a
have a slightly higher efficacy,
right,
but we have a very good and safe vaccine.
I'm currently the measles vaccine is given in combination with
the mumps and rubella vaccine.
So it's given all together as one one shot.
That's known as the MMR which probably has some the name
recognition.
So we have a highly efficacious preventative
mechanism for measles if you were to become infected with
measles either because you're one of those 3% of individuals.
She didn't respond well to the vaccine or or had
suboptimal protection.
Or if you're unvaccinated and.
you didn't take up the vaccine,
there really aren't any interventions Beyond supportive care to treat
measles to things like hydration managing.
The fever,
with appropriate.
Usually NSAIDs drugs for fever management.
there aren't any license antivirals for measles.
So once you're infected really,
the only treatment is Supportive care.
Hey,
thank you.
So vaccinations are highly important to the measles
do, which
is global vaccine access.
So,
and again is,
were seeing in real time.
Even if certain areas have vaccine uptake nationally
there,
maybe may be pockets where there is lower,
vaccine uptake,
uptake. So there's communities that may be susceptible to outbreaks because
locally the vaccine uptake isn't high.
But again,
there's large regions of the world that don't have access
to the. or can't afford vaccines and so measles continues to be
a, a big problem in developing countries.
And in particular,
in light of the SARS COVID-2 pandemic dozen,
dozen dozens of countries have delayed vaccination campaigns for measles
So,
this is something that that has the potential really to
have a knock-on consequences in the upcoming years,
right?
Where we have affected the vaccine uptake rate,
so it's possible.
We could see a Resurgence of measles in higher numbers
then we seen previously.
I mean,
it will be interesting to see that because obviously,
what we have now,
we have social distancing and masking measures in place.
Those might not be in place forever,
and might not be observed in places.
So that might mitigate it to some extent.
But it is something that is of a global concern.
And measles is also,
what I'll point out individuals that are are most susceptible
to severe outcomes with measles are young and vaccinated
children. I'm so the measles vaccine isn't usually given until a
year, right?
So there for a year.
There is a large cohort of the global population that
aren't even eligible for vaccinations.
And then if if we talked about access to vaccine,
that number is compounded.
In.
So,
when we talked about the consequences of measles virus injection,
most severe in younger children where it can lead,
I told you that it infects immune cells,
right?
That's one of the target cells.
So as a consequence of measles infection,
you are transiently immunosuppressed,
and that leaves you vulnerable to secondary bacterial infection.
So for
period after measles virus infections,
you more susceptible to other other infections and is actually
a leading,
cause of death in developing countries.
Secondary bacterial infection.
So again measles the the
estimates for death,
right?
Morbidity,
and mortality. And we talked about those measurements for measles,
against pre-vaccine.
Probably one in a thousand infected individuals succumb to measles.
But that number can actually that number goes up to
almost 30%.
If you talk about populations where there is malnourishment.
So individuals,
and again in developing countries,
that might be undernourished.
If they're they become infected with measles,
are at a higher risk of Death at a higher
risk of death,
inherently from the first infection with measles and then subsequently
are also at higher risk for developing secondary bacterial infection.
and so it is,
there are long-term serious what we call sequelae of measles whichever
are basically outcomes.
Subsequent to infections or after infection.
So we think of measles as an innocent childhood disease,
but there are people still die from measles.
We can develop a secondary,
bacterial infections,
because of that immunosuppression and it's possible for again for the
virus to gain access into the brain and cause Encephalitis,
which is obviously very dangerous.
Thank you.
That was those really really,
really detailed I really appreciate that, that really helped, again thank you so much for joining us today
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