Ep 158 Scarlet Fever: You’ve changed

A mere 150 years ago, uttering the words “scarlet fever” was enough to strike fear into the hearts of many, especially parents of young children. For a brief period of time, this disease, caused by an infection with the bacterium Streptococcus pyogenes, reigned as a leading cause of childhood death in many parts of the world. It left its mark on gravestones, in public health decrees, in literature like the Velveteen Rabbit, but then something changed. The disease became milder, no longer the deadly threat it once was. But it didn’t go away entirely or lose its bite completely. In this episode, we examine the biology of scarlet fever and trace how it can make you sick before exploring its strange and tragic history. How did such a deadly disease change almost overnight, before any effective treatment was developed? And what can that tell us about its potential to change back? Tune in to find out.

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Episode Transcript

Speaker 1 (00:00):
Weeks passed, and the little rabbit grew very old and shabby,
but the boy loved him just as much. He loved
him so hard that he loved all his whiskers off,
and the pink lining to his ears turned gray, and
his brown spots faded. He even began to lose his shape,
and he scarcely looked like a rabbit anymore, except to
the boy. To him, he was always beautiful, and that

(00:21):
was all that the little rabbit cared about. He didn't
mind how he looked to other people, because the nursery
magic had made him real, and when you are real,
shabbiness doesn't matter. And then one day the boy was ill.
His face grew very flushed, and he talked in his sleep,
and his little body was so hot that it burned
the rabbit when he held him close. Strange people came

(00:42):
and went in the nursery, and a light burned all night,
and through it all the little velveteen rabbit lay there,
hidden from sight under the bedclothes, and he never stirred,
for he was afraid that if they found him, someone
might take him away, and he knew that the boy
needed him. It was a long, weary time for the boy.
He was too ill to play, and the little rabbit
found it rather dull, with nothing to do all day long,

(01:05):
but he snuggled down patiently and looked forward to the
time when the boys should be well again, and they
would go out in the garden amongst the flowers and
the butterflies, and play splendid games and the raspberry thicket
like they used to, all sorts of delightful things. He planned,
And while the boy lay half asleep, he crept up
close to the pillow and whispered them in his ear.
And presently the fever turned and the boy got better.

(01:27):
He was able to sit up in bed and look
at picture books, while the little rabbit cuddled close at
his side. And one day they let him get up
and dress. It was a bright sunny morning and the
windows stood wide open. They had carried the boy out
onto the balcony, wrapped in a shawl, and the little
rabbit lay tangled up among the bedclothes, thinking the boy
was going to the seaside tomorrow. Everything was arranged, and

(01:49):
now it only remained to carry out the doctor's orders.
They talked about it all while the little rabbit lay
under the bedclothes with just his head peeping out and listened.
The room was to be disinfected, and all the books
and toys that the boy had played with in bed
must be burnt. Hurrah, thought the little rabbit. Tomorrow we
shall go to the seaside, For the boy had often

(02:10):
talked of the seaside, and he wanted very much to
see the big waves coming in, and the tiny crabs
and the sand castles. Just then Nana caught sight of him.
How about his old bunny, she asked that, said the doctor.
Why it's a mass of scarlet fever germs. Burn it
at once? What nonsense? Get him a new one. He
mustn't have that anymore. And so the little rabbit was

(02:31):
put into a sack with the old picture books and
a lot of rubbish, and carried out to the end
of the garden behind the fowl house. That was a
fine place to make a bonfire. Only the gardener was
too busy just then to attend to it. He had
the potatoes to dig and the green peas to gather.
But next morning he promised to come quite early and
burn the whole lot. That night, the boy slept in

(02:51):
a different bedroom, and he had a new bunny to
sleep with him. It was a splendid bunny, all white plush,
with real glass eyes, but the boy was too excited
to care very much about it, for tomorrow he was
going to the seaside, and that in itself was such
a wonderful thing that he could think of nothing else.
And while the boy was asleep dreaming of the seaside,
the little rabbit lay among the old picture books in

(03:13):
the corner behind the fowl house, and he felt very lonely.
The sack had been left untied, and so by wriggling
a bit, he was able to get his head through
the opening and look out. He was shivering a little,
for he had always been used to sleeping in a
proper bed, and by this time his coat had worn
so thin and threadbare from hugging that it was no
longer any protection to him. Nearby he could see the

(03:35):
thicket of raspberry canes growing tall and close, like a
tropical jungle in whose shadow he had played with the
boy on bygone mornings. He thought of those long sunlit
hours in the garden, how happy they were, and a
great sadness came over him. He seemed to see them
all pass before him, each more beautiful than the other,
the fairy huts in the flower bed, the quiet evenings

(03:57):
in the wood when he lay in the bracken, and
the little ants ran over his pause, the wonderful day
when he first knew that he was real. He thought
of the skin horse, so wise and gentle, and all
that he had told him. Of What use was it
to be loved and lose one's beauty and become real
if it all ended like this? And a tear, a

(04:17):
real tear, trickled down his little, shabby velvet nose and
fell to the ground. I'm crying.

Speaker 2 (05:10):
It's so sad. Oh a children's book, and it's like
so sad?

Speaker 1 (05:16):
I am you really?

Speaker 2 (05:18):
Are you really?

Speaker 1 (05:19):
You really are crying? Oh my god. It hit me,
a poor little thing. He just wanted to be real.
I need to take a break. That is so sad.
I can't get over this.

Speaker 2 (05:34):
I'm crying watching you cry. I have, you know, like
some people want it when you see other people want it.
I cry when I see people cry.

Speaker 1 (05:40):
Yeah.

Speaker 2 (05:42):
Oh my god, Oh Aaron, it's a happy ending.

Speaker 1 (05:45):
That is a happy ending. We just didn't want to
read too for like fifteen more minutes.

Speaker 2 (05:50):
A fairy comes and turns a Valentine rabbit into a
real rabbit. If anyone hasn't read that book since they
were a kid.

Speaker 1 (05:55):
Yeah, and then the little boy sees the rabbit playing
with the other rabbits and he's like like, oh, that
looks like my old velveteen rabbit.

Speaker 2 (06:02):
So he's so happy.

Speaker 1 (06:04):
Oh my god, I can't I have so many tears.
This is awful. Oh my god. Okay, well that is
from The Velveteen Rabbit by Marjorie Williams, and it's scarlet fever.
Scarlet plays a pretty predominant role as you can. As

(06:24):
you can tell, Hi, I'm Aaron Welsh.

Speaker 2 (06:27):
And I'm Aaron Allman Updike and.

Speaker 1 (06:29):
This is this podcast will kill you when.

Speaker 2 (06:31):
We're not going to cry for the entire episode, but
no promises.

Speaker 1 (06:35):
I don't know really, but.

Speaker 2 (06:39):
Today we're talking about scarlet fever. Yeah we are.

Speaker 1 (06:43):
This is such a classic TPWKY topic and story. It's
it's strange that we haven't done it before.

Speaker 2 (06:52):
I'm kind of excited about it, although it really just
made me ask so many questions about the bacterium that
causes scarlet fever that like, now I want to do
like six more episodisodes on strap biogenies. But we'll get there.

Speaker 1 (07:03):
Yeah, and is it just strap phyogenies. Yeah, yeah, Okay,
So this is what made me so confused because so
many papers and granted I didn't go into the biology,
but it would be like, oh, hemolytics, streptococcy, we'll.

Speaker 2 (07:16):
Get there, we'll get there. Okay. It's very obviously, it's
a lot. It's gonna be fun.

Speaker 1 (07:21):
Yeah, it's gonna be We're gonna learn so much. But
before we learn so much about strap piogenies and you know,
things like toxins, We've got a very special time.

Speaker 2 (07:34):
We've got a special time.

Speaker 1 (07:35):
Really, that book really threw me off my game. I'm
still like thinking about that.

Speaker 2 (07:41):
Great. Thanks, thanks, it's good. What are we drinking this week?

Speaker 1 (07:45):
Oh yeah, that's right, we are drinking. Let me see
if I can say it without stumbling through it. The
scarlatina rita.

Speaker 2 (07:54):
Yes, scarletina is an old Timy name for scarlet fever,
and it's basically a strawberry margarita. So it's a scarlet
tina rita.

Speaker 1 (08:04):
Yeah, strawberry because rash, strawberry rash is that what? Yeh?

Speaker 2 (08:08):
Strawberry tongue strawberry is one of the descriptions of what
your mouth ends up looking like. Delicious right, we'll post
the full recipe for that delicious sounding drink on our
website and also the non alcoholic version R plusy Berita
on our website. This podcast will kill You dot com
and on all of our social media channels.

Speaker 1 (08:28):
We certainly will. On our website This podcast will kill
You dot com you can find all sorts of things,
including transcripts for each and every one of our episodes.
You can find links to merch links to our bookshop
dot org, affiliate account, links to our Goodreads list, links
to music by Bloodmobile. You know, there's things like a
contact us form, there's a submit your first hand account form,

(08:51):
there's forms, there's links, and there's content. It out forms
links content, so you just start saying yes.

Speaker 2 (09:01):
Also, if you have not already, please be sure to
check your podcastcher make sure that you're subscribed to our feed.
And if you haven't left us a rating or of you,
we sure would love it if you did. Thanks so
much for listening. Thanks shall we content? You? Shall we?
Is that a can you verb?

Speaker 1 (09:21):
That I mean? I sure wekend we can do whatever
we want. This is our podcast. Oh, so let's take
a break and then get started.

Speaker 2 (09:32):
Let's do it. So here's the thing about scarlet fever.
It's a little bit weird, okay, And it's weird because

(09:57):
so scarlet fever is a disease that is by just
one single pathogen, but that pathogen causes a whole bunch
of other diseases as well. So the pathogen in question
here is the bacterium Streptococcus pyogenes. It's also called group

(10:17):
A strep. And we'll get there. So we'll get to
the pathogen in detail, but first I want to start with, like,
what is scarlet fever? So here's how it generally goes
because we only got a glimpse of it in the
velveteen rabbit. Most often a kid like the velateen rabbit's kid,
who's usually between three and ten years old, or sometimes

(10:39):
between five and fifteen. They'll get a sudden onset of
a fever. They'll get headache, malaise, they'll feel cruddy, kind
of nonspecific symptoms, and then they'll get the sore throat.
So the fancy term for this is a pharyngitis or
a tonsilitis you have a swollen, infected, super sore throat.

(11:00):
If you look in this kid's mouth, you'll see swollen tonsils.
They might even have some like kind of PUFs looking
stuff on their tonsils. They'll be red. You'll probably be
able to feel swollen lymph nodes just underneath their chin.
And then their tongue will start to look a little
bit almost furry, and that's because the taste buds, like

(11:21):
the papolla, the papillae, are like swollen and puffy. And
then usually on day two or sometimes three, the rash
will start to appear. And the rash is this really
kind of super super fine, really close together little bumps
with a flush of red on the background. So if

(11:43):
you run your hand over this rash, it almost feels
like sandpaper because it's these teeny tiny little bumps, Okay,
And it usually starts on either the neck or the trunk,
but then it spreads to like the whole trunk. It
can spread onto the arms or legs. It definitely spreads
up onto the face and on the face, this rash
is mostly on like the cheeks, and it doesn't go

(12:06):
right around the mouth, so you get this thing called
circumoral pallor where right around your mouth it's more pale
because you don't have a rash there.

Speaker 1 (12:13):
Yeah, does it itch or hurt? Good question.

Speaker 2 (12:18):
They don't really read like in everything you read, they
don't talk a lot about itching or pain. I think
that in part because everything else hurts so much. So
the rash is just kind of like there but not
necessarily like the most prominent feature in terms of the
symptoms that you're feeling.

Speaker 1 (12:33):
Okay, And why doesn't it go around your mouth?

Speaker 2 (12:36):
Oh my gosh, I have so many questions about this
rash though, I don't know. I don't know why, because
here's it gets even weirder than that. It also has
these extra in the skin folds, so like in the
armpits or the groin or even like your elbow pits.
That's a thing right here where your elbow bends. You
can the rash is like more pronounced, so it's like
a darker or like a brighter red, and it's more

(12:58):
pronounced than the rest of where the rash is. I
don't know why in these areas, these like flextial areas,
do we see more rash. I don't know. Often it
takes for the rash especially like almost a whole week
for it to disappear. And then once it goes away,
the skin, especially on the hands or the feet, or

(13:19):
even sometimes in the groin, you'll have peeling, like flaking
of your skin. And that is overall the most common
version of what we know of as scarlet fever. That
is usually how it goes. It is very often a
self limited disease. Just like in the velveteen rabbit. The
kid eventually gets better with or without antibiotics, and that's

(13:44):
usually how it goes. Sometimes it might go a little
differently and not start with that sore throat, but start
with a skin infection. But always it's starting with and
caused by this bacterium strip piogenies. The heck is Streptococcus pyogenies. Yeah,
so strap piogenies. It's also called group A strep. It's

(14:07):
a human specific bacterium. This bacterium it's a gram positive,
which just means we haven't done a bacterial disease. I
feel like in forever, I.

Speaker 1 (14:16):
Know, I feel like I haven't heard the phrase gram positive.

Speaker 2 (14:19):
I know it is, I know I felt weird writing it,
But what that just means is that if you look
at it on a typical microscope side where we stain it.
It looks purple, like a little cute little purple ball
because it's a cocksie. So it's these little round balls,
and they tend to form these little chains, like either
like double chains or like three four five little chains,

(14:41):
rather than clumping up the way Staph Aureus does. We
talked about staff Orius in our Mersa episode Pasture of grapes, yep.
And this bacterium streped piogenies is super super common. It's
a commensal in a lot of our throats and mucus membranes,
which means it's just living on us. It's living in us,
and it's a very common cause of a whole bunch

(15:04):
of diseases. Strep throat that's strip piogenies. Everyone knows strep
throat that's groupe strap impetigo. If you've heard of impatigo,
which is a skin infection where you get these kind
of like blisters that can crust over with this like
honey colored crust, that's group A strip strap biogenes. It

(15:27):
also can cause a deeper infection like a cellulitis or
an ariceplus, which is when the infection goes to all
the layers of your skin. It can also cause an
even deeper infection if it gets to the layer underneath
our skin called the fascia. And when it does this,
it's called necrotizing fasciitis, which is an extremely horrible, very

(15:52):
deadly infection that is a surgical emergency. It can even
then continue an infection down to the muscle and that's myocytis.
And strip pyogenes is also famous. Besides all these skin
infections and throat infections and scarlet fever, which we'll get to,
strip pogenies can also I'm calling it pull a covid.

(16:13):
I don't know if that's a thing, but strap poogenies
is one of the og post infectious complications culprits that
we know of. So, rheumatic fever is a post infectious
syndrome that happens after a streptococcle infection, usually after strep throat,
but it could be after a skin infection. And rheumatic

(16:35):
fever can lead to rheumatic heart disease, which is really
serious condition worldwide that kills hundreds of thousands of people
every year. And you also can get another post infectious
syndrome called post strep glomerulo nephritis, which is a fancy
word for your immune system attacking your kidneys as a
consequence of a STRAP infection. That one is usually after

(16:57):
a skin infection, but could be after a three infection.
And then there's another illness called pandas have you heard
of that? It's pediatric autoimmune neuropsychiatric disorders associated with strep
to cockle infections. It's like a long name. That's why
they acronymed it. And this is somewhat controversial because we
don't have as much data on it, but it's thought

(17:18):
to be another post infectious consequence after a group a
STRIP infection. So this is a pretty huge range of illnesses.

Speaker 1 (17:28):
And do these different manifestations of STRIP just have to
do with like individual characteristics, but like where the bacterium
enters the body, or like you know, why does something
turn it? Why is something ariscipulus rather than impetigo?

Speaker 2 (17:44):
Such a good question, It's that is a beautiful question.
There's a couple of different things that will help to
determine what kind of infection you're going to get, and
I don't think any of them are necessarily mutually exclusive. Okay,
one is going to be where are you getting this?
Are is someone coughing this bug into your mouth and
depositing it really close to your tonsils? Maybe then you're

(18:06):
more likely to get a tonsul or infection or a
strep throat. Are you getting strep underneath your skin because
you itch something and you scratch some bacteria into your skin,
Maybe now you're going to get impetita. But there's also
more to it than that, because this is it's one
species of bacteria, right, it's strip Piogenies, but it is

(18:27):
a huge amount of different stuff and different strains that
you can have. So I said that this is a
human specific bacteria. It's really really well adapted to live
on us and to live in us, and because of that,
it has a really huge range of adaptations that help

(18:48):
it to evade our immune system. So one of the
things that strip Piogenies has that makes it really hard
for us, like that basically allows for it to infect
us and to infect us over and over and over again,
like getting strep throat every single year when you're a kid.
For example, is it has an invisibility cloak that it wears.

(19:10):
That's how I'm imagining it. Okay, this invisibility cloak is
called M protein, and it's kind of like you know,
like influenza virus has h's and NS on its surface.
So Strepagenies has this M protein. It like coats the
surface of the bacteria and it makes it so that
our macrophages, the cells that usually run around and gobble

(19:33):
up bacteria, they can't see it. It literally makes it
almost invisible. So the only way that our body can
start to recognize a group BA strap is by making
antibodies that see that M protein, so they can put
little flags on it that like stick to the invisibility cloak.
Then our immune system can do its job.

Speaker 1 (19:51):
So why does that happen? So you said that often
scarlet fever cases are self limiting, and so why does
it happen then? But not like in our everyday lives
to this pathobion, like this thing that just like lives
and has the potential to hurt us all the time.

Speaker 2 (20:08):
Yeah, well it gets more than that, aaron, because it's
not just this invisibility cloak. Strep piogenies also brings with
it a whole bunch of different equipment that it can
use to help fight off our immune system. And this
equipment is a bunch of different kinds of virulence factors.

(20:29):
There are things like proteins, they're different enzymes that they
can make, different toxins that they can make, and all
of this different stuff essentially can go out and do
a lot of different things that help to either dampen
our immune response or somehow promote the survival of this bacterium.

(20:49):
And so not all strains of Strep. Piogenies is going
to have all of these different virulence factors because there's
a whole huge range of on that they can have.
So part of what is going to determine what type
of infection you get is what strain you get exposed to,
which proteins it has on its surface, which virulence factors

(21:09):
it happens to make, and then where you get exposed
to it as well, and then things like how much
did you get exposed to have you seen that strain before?
All of those kinds of things there are like a
huge range. Even just when we look at the m
proteins that invisibility cloak, there's over like two hundred different versions.
And then I read some papers that went into detail

(21:30):
on all of the different virulence factors, but they're like
there's too many. There's too many different types of these
virulence factors that they have. So then you asked, like
what makes it scarlet fever and.

Speaker 1 (21:45):
What makes your body eventually recognize strup piogenies?

Speaker 2 (21:50):
So eventually your body because we have a lot of
different ways, right, we have like our innate immune response,
our adaptive immune response, we have cellular immunity, and we
have what's called humoral immunity, which is like our antibodies.
So eventually our body finds a way to recognize it. Eventually,
that invisibility cloak is imperfect, and we'll be able to

(22:12):
find it, but it's not immediate, and it's going to
depend on what other virulence factors they have and how
that's interacting with our body. Okay, Scarlet fever, as it
turns out, is what happens when you get stuck with
a particular version of Strep. Piogenies that brings with it

(22:33):
one specific type of equipment, and that is called a superanigen.
So the strains of Strep. Piogenies that produce scarlet fever
make a group of toxins called streptococcal pyrogenic exo toxins,
and pyrogenic means it generates a fever, which is like
not specific, but basically this type of toxin, what it

(22:56):
does once STREP releases it in our bodies is it
actually activates our immune response. It activates a whole crap ton,
especially of our t cells, and it leads to what
we've called on this podcast before a cytokine storm. But
it basically is like our own immune system going into

(23:19):
absolute overdrive and then causing a whole bunch of damage
to our own cells. So the rash that you asked about,
Aaron like, why is it here? Why is it there?
I don't know why do we get it in specific places?
But what's interesting about the rash is that for a
long time we thought it was like, well, this bacteria
is going around and doing things and making you have

(23:41):
a rash, or this toxin is going around and that's
what's damaging cells and causing the rash. No, it turns
out that the rash is caused by what's called the
delayed hypersensitivity response, which is the same kind of thing
we see with poison ivy or poison oak. So it's
your body's immune response to the toxin that ends up

(24:05):
causing the rash. That also means that you won't get
scarlet fever the very first time you've ever been exposed
to structococus piogenies, even if it's the strain that makes
that right kind of toxin interesting. Okay, So you have
to have a previous exposure, you have to have the
right strain, and then you have to get infected at

(24:26):
really like the right time and in the right way. Okay.

Speaker 1 (24:42):
So two things have to happen for you to get
scarlet fever. The first is a previous exposure to strip piogenies,
and the second is exposure after that to the strip
piogenies with this super antigen exactly. Okay, question that's kind
of unrelated.

Speaker 2 (24:58):
Okay, give it to me.

Speaker 1 (24:59):
This is group A strap. Yeah, how many groups of
strap are there?

Speaker 2 (25:03):
I love it. I'm so glad you asked.

Speaker 1 (25:05):
And what makes a group A B whatever?

Speaker 2 (25:07):
There? So it's it's even more complicated than that. Erin
there is group A, B, CD, EFG, and H. All right,
so far, so far, those are all of a type
of strep that is called beta hemolytic or like hemolytic strap. Okay,
And that term hemolytic just means that when you plate

(25:29):
any of these ABC DFG on a certain type of
culture media they they grow in away blah blah blah.
There's an entirely different grouping of strap that's called alpha
hemolytic strap, which are not grouped as abc D blah
blah blah. Those are just like they're even separate from that,
and that is the ones that include like strep pneumonia,

(25:51):
which is a common cause of pneumonia, and there are
other ones within that grouping as well. But then within
strap of the groups like the hemolytics streps, Group A
strap is kind of synonymous with strip pyogenies, at least
in humans, because that's the main one that causes disease
in humans. Group B strep is another type of hemolytic

(26:13):
strap that, for example, we check for during pregnancy because
it lives in the vagina and it can infect newborns
and cosmeningitis. Okay, Group D strap you might have heard of,
because they've actually been renamed as enterococcus, so now they're
not even streped to caucus anymore. And then most of
the other ones don't cause as much disease in humans

(26:34):
and so we don't hear about them quite as much.
Is pupil fever group A strap, So pupil fever can
be group A or group B strap. I think historically
it was more group A strap, Okay, And certainly group
A strap is very virulent. Group B strep often can
cause infection in the newborn. Okay, And so that is

(26:54):
what we screen for and we treat if somebody is
colonized with group B strap.

Speaker 1 (26:59):
It's interesting to me, as someone who is not a
an evolutionary biologist or someone who studies speciation, why are
these groups or strains and not species do strep biogenies?
Are they able to acquire toxin genes, for instance, or

(27:19):
super antigen genes?

Speaker 2 (27:20):
Absolutely? Yeah, so a lot of the toxins and virulence
factors in general in strept biogenies. Some of them are
located on the chromosomes, but they can be turned on
or turned off by certain things, and some of them
are on like bacteria phasis so they can be more
easily moved around between strains. Okay, but yeah, there is
such a huge dreams. I wonder the same thing. Are

(27:43):
there actually a bunch of different species within this umbrella
called strut piogenies or are they all similar enough they
just move these virulence factors around that they're not really
different species. I don't know enough, and I didn't, in
all honesty look into the phylogenies enough to know that.

Speaker 1 (28:01):
But a standard strip throat infection like you get when
you're a kid multiple times, that's just strippagenies. There's no
super antigen involved necessarily.

Speaker 2 (28:10):
So that's a great question, Aaron. I mean, we'll talk
more about the epidymology later, but yes, scarlet fever has
drastically declined in incidents. It's not called scarlet fever unless
you have those other characteristic signs, especially that rash. So
if you have strip throat without any of that rash,

(28:31):
we would call it strip throat, we would not call
it scarlet fever.

Speaker 1 (28:34):
Why do children get it at higher rates than adults.

Speaker 2 (28:39):
It's a good question. We talked about this in our
tonsils episode a little bit too. I don't have a
good answer for it.

Speaker 1 (28:44):
I don't know.

Speaker 2 (28:45):
Is it just because of like especially with tonsils. Is
it something to do with the size of your tonsils
compared to the size of your throat, so you're just
more likely to get it. Is it something to do
with how much immunity you have, how many strains your
body has seen, and then by the time you get
to an adult, you have some antibodies to most of
the strains, so you're less likely to get it. Is

(29:06):
it a combination of all of that. I don't know.
It's a really interesting question. What's even more interesting, maybe
not even more, but also very interesting, is that kids
under age three almost never get strep infections.

Speaker 1 (29:19):
And that can't just be like maternal antibodies, like, no,
actually not, these are gone by six months. Yeah, exactly.

Speaker 2 (29:24):
So, Yeah, it's super interesting. I don't have an answer
to that. I've asked so many people, I've read so
many papers. I don't feel like I have a good
answer to that yet.

Speaker 1 (29:32):
My mom had scarlet fever in college.

Speaker 2 (29:34):
Really yeah, yeah, I mean adults can certainly still get it. Yeah,
we heard in our Tonsils episode.

Speaker 1 (29:42):
Yeah. So, I just have so many questions. I don't
know if I have answers to most of them. Okay,
you can get scarlet fever multiple times. Is that because
the super antigen itself is changing or is it the
bacterium like the antigens on that. I don't know.

Speaker 2 (30:00):
It's a good question. Yeah, it's a good question. I
don't I don't know. Uh, there are a couple different
versions of the exotoxins that are associated with scarlet fever,
but I think largely what allows the infection to establish
are the different types of M proteins. So I think
it's more that. But I don't know enough about the

(30:21):
like nitty gritty of this bacterium.

Speaker 1 (30:24):
To know are there Can I just keep going, yeah, please, Okay?
Are there some super antigen producing strete biogenies that are
more likely to cause epidemics or outbreaks than others?

Speaker 2 (30:39):
That's such a good question. Probably I have no idea. Okay,
I read an entire textbook. Why I didn't read every chapter,
but I read a lot of chapters of a textbook
that is only about strep biogenies, And as much as
we know so much detail about a bajillion of these
different virulence factors, because it's not just these superanergens, there's

(30:59):
so many other they're virulence factors. There's strepto license, there's
like so many. I don't know how many different strains
there are that can produce scarlet fever, which ones might
be more likely? What is it about certain strains that
make them more likely to cause an epidemic? Is it
something about the way that they're transmitted. Is it some
other virulence factors that are making them more likely to

(31:19):
establish an infection or do something else? There's there's I
have so many more questions.

Speaker 1 (31:26):
Well, and it's good because we're gonna like we're gonna
be covering. I'm sure more of this in other episodes
as we do, like you know, ariseplus or we do
necrotizing fasciitis or we do.

Speaker 2 (31:38):
Yeah, rheumatic fever needs its whole own one hundred episode.
I mean, there's there's so many things too write because
that's the whole can of forms that we can't even
get into. But like, what is it about people who
get infected versus the strains that they get infected with
that ends up having them have an immune response to
it thereafter that like damages their heart so severely.

Speaker 1 (32:00):
Know, we don't know is everyone in theory susceptible to
scarlet fever or able to get scarlet fever? You know
what I mean?

Speaker 2 (32:07):
Like, I know that there's a good question tests, but no, Yeah,
and it seems like not necessarily right or at least
we don't see every person who's exposed certainly getting scarlet fever.
Like even during an outbreak, even among household contacts. So
what is it? Is it because they've been exposed to
that same strain before? Is it? Like? What is it?
I don't know, I don't know.

Speaker 1 (32:28):
Okay?

Speaker 2 (32:28):
Is it host factors? Is it bacterial factors? Is it both?
It's probably both. If there's any good news about it,
it's that across the board, strup Piogenes is still very
treatable with antibiotics. It shows very little antibiotic resistance, especially
to penicillin and other penicillins like amoxicillin, which is what
we usually use to treat it. It does show antibiotic

(32:52):
resistance to some other types of antibiotics like macrolides and
things like that, So that's something to keep them in mind.
Because we use millions and millions of doses of antibiotics
for group based infections every year, so the threat of
antibiotic resistance certainly exists. But so far, despite how common
it is, and despite how many antibotics we use, penicillin

(33:14):
and other penicillins still work really well, which is great. Yeah,
also shocking that, like, yeah, you gotta love when like
good old penicillin is still our favorite things. Yeah.

Speaker 1 (33:26):
Not obsolete.

Speaker 2 (33:29):
So that is the biology of scarlet fever and a
little bit of piogenies in general.

Speaker 1 (33:36):
I'm fascinated because I feel like now what I'm about
to talk about is gonna generate some more questions.

Speaker 2 (33:44):
I can't wait. I'm really curious because I have really
big questions after looking at what the numbers are like
this now. So I really want to know about what
it was like historically. Can you tell me?

Speaker 1 (33:55):
I certainly will. Let's take a break and then I'll
get to it. Okay, before I get started, I should

(34:26):
mention that I will be discussing childhood mortality throughout the section,
and so if you prefer not to hear that, this
might be a good place to pause. The story of
scarlet fever. It really took me by surprise, Aaron. I
knew that it used to be more prevalent than today
and more feared, but I wasn't prepared for just how

(34:46):
different the scarlet fever of today is compared to the
scarlet fever of one hundred and fifty years ago. So
let's get into it. In Wellington, New Zealand, at the
Bolton Street Cemetery, there stands a gravestone that reads quote
sacred to the memory of William Stanton Wallace died May fifth,
eighteen sixty five, aged three years and seven months. John

(35:10):
Howard Wallace died May nineteenth, eighteen sixty five, aged ten
years and two months. George Frederick Wallace died May twentieth,
eighteen sixty five, aged seven years and seven months. Alice
Pennington Wallace died May twenty fourth, eighteen sixty five, aged
four years and eleven months. All died of scarlet fever.

Speaker 2 (35:32):
End quote.

Speaker 1 (35:34):
Five children in the same family all died of scarlet
fever within less than three weeks. It's unfathomable, like I can't,
I can't believe it, And yet as unfathomably sad as
this is, this gravestone is not unique. Throughout much of

(35:56):
the eighteen hundreds. Headstones like the one for the Wallace
children were created for families around the world who lost
to multiple children in quick succession to scarlet fever epidemics.
There are two family crypts in the Saint Peter's Anglican
Cemetery in Tasmania that are dedicated to the seven young
siblings that died within six weeks of each other in

(36:17):
eighteen fifty nine. All of scarlet fever.

Speaker 2 (36:20):
Oh my god, right, it's.

Speaker 1 (36:25):
I have no words for how.

Speaker 2 (36:28):
Awful.

Speaker 1 (36:30):
At that same cemetery is a plaque commemorating the nearly
seven thousand children under the age of ten who died
of scarlet fever in Tasmania in the ten year period
from eighteen fifty to eighteen sixty. Oh my god.

Speaker 2 (36:43):
Yep.

Speaker 1 (36:45):
Archibald Tate, who was the Archbishop of Canterbury in England
in the mid eighteen hundreds, had five of his daughters,
age two to ten, all die within five weeks of
each other from scarlet fever. One son and one daughter survived.

Speaker 2 (37:00):
Oh jeez.

Speaker 1 (37:01):
And these are just a handful of gravestones that represent
a larger tragedy, which is the deadly told that scarlet
fever took on children and on families in the eighteen hundreds.
Like if you search scarlet fever headstones gravestones, you will
find so many examples of these. From our vantage point
here in twenty twenty four, I think it's hard to imagine,

(37:25):
or at least easy to forget, how life was before antibiotics,
when every childhood illness held the thread of death, and
doctors were largely powerless. To treat or prevent infections. Stories
like that of scarlet fever remind us just how incredibly
fortunate we are today to live in a period where
modern medicine has drastically reduced the deadly impact of scarlet

(37:48):
fever along with many other childhood killers, with of course
the qualifier that that's if you have access to these medicines.
So let's trace the story of scarlet fever, starting with
its emergence as one of the most dreaded diseases in
the eighteen hundreds, which led to some of the earliest
preventative policies against a disease like sweeping preventive policies, and

(38:10):
ending with its decline over the twentieth century, thanks in
large part to diagnostic tests and antibiotics, but also thanks
to the bacteria themselves.

Speaker 2 (38:21):
Yeah, I'm really curious about that.

Speaker 1 (38:23):
Yeah. Whether or not scarlet fever was recognized or written
about in ancient times by people like Hippocrates or Avicenna,
it seems to be up for debate, but it's generally
accepted that this disease or the bacteria that cause it
have been with us for an incredibly long time. Like
you talked about Aaron stret Piogenes is just hanging out

(38:45):
in or on our bodies all of the time, and
we have some archaeological evidence of this. So I found
a paper from twenty fourteen by warrener at All that
described the microbial contents of dental calculus found from skeletons
from around nine hundred to twelve hundred CE, which is
really cool. I just love that, Like you can find

(39:05):
what is in your mouth.

Speaker 2 (39:08):
I love when you find dental pulp.

Speaker 1 (39:11):
This is dental calculus, not even pulp. It's like, yeah, yeah, yeah,
I mean that's like relatively recent as far as we
think about, like you know, ancient infections or whatever. But
I'm sure that this relationship is like very very very old.
And because this microbe is just kind of hanging out
with us, there doesn't necessarily have to be a minimum
population threshold for someone to develop scarlet fever like there

(39:36):
is with measles, for instance, because it's just it's there
and our body. It's just on our bodies. Despite the
fact that it presumably has had the ability to infect
us or give us scarlet fever for who knows how long.
The first agreed upon description of scarlet fever doesn't pop
up until fifteen fifty three, where in Gracia wrote about

(39:58):
scarlet fever quote unk quote rosalia as distinct from measles.
There are so many rashy illnesses of childhood with overlapping
symptoms that it's kind of amazing that anyone was able
to differentiate among any of them.

Speaker 2 (40:12):
I feel the same. And it's like it is written
as like this is so distinct from measles and other
like viral exanthems. Of course they didn't know a virus
from a bacterium, but like, yeah, and I think it's
in part because of like how specific I was saying
that rash is. It's like, yes, it is weird, right,
it's a weird rash.

Speaker 1 (40:29):
It's a very Yeah, it's distinctive that makes itself be known.
And remember how we talked about in parvovirus, how that
was fifth disease. Yeah, slap cheek, slap cheek. I think
this is second. I think this is like the second
of the rashy illnesses. Yeah, second disease. Okay, yeah, that's
what I thought. And even though scarlet fever is distinctive

(40:51):
with its sandpaper rashyness, people didn't always get it right,
especially when it came to diphtheria and scarlet fever. There
was a lot of either overlapping in terms of like misdiagnosis,
or that these outbreaks tend to happen at the same time,
same time, and same thing with like measles. There are
some interesting relationships about like measles epidemics preceding scarlet fever epidemics.

(41:14):
Like just looking at the periodicity of these different epidemics,
I think it's really interesting and reveals a lot about
population dynamics. Blah blah blah. Anyway, following in Gracia's report,
other descriptions of rosalia, or as it began to be
called in English vernacular, scarlet fever, appeared, including a sixteen

(41:35):
seventy six description by Thomas Sydonim where he refers to
it as scarletina, which is what it would be called
in scientific and medical circles for the next couple hundred years. Quote.
Scarlet fever may appear at any season. Nevertheless, it often
just breaks out towards the end of the summer when
it attacks whole families at once, and more especially the

(41:56):
infant part of them. The patients feel rigors and shivering
just as they do in other fevers. The symptoms, however,
are moderate. Afterwards, however, the whole skin becomes covered with
small red maculae thicker than those of measles, as well
as broader, redder, and less uniform. These last for two
or three days and then disappear. The cuticle peels off

(42:17):
and brandy scales remain lying on the surface like meal.
They appear and disappear two or three times.

Speaker 2 (42:23):
End quote.

Speaker 1 (42:26):
Interesting, Yeah, and people would have plenty of opportunity to
use the name scarletina or scarlet fever. By the early
to mid eighteen hundreds, the disease was widespread across the globe,
arriving in North America around seventeen thirty five, in South
America by around eighteen hundred or so, Australia eighteen forties,
And of course it had already been well established in Europe,

(42:47):
Africa and much of Asia for hundreds of years, if
not longer. And this I think is probably just referring
to the spread of that super antigen right or like
at least some sort of toxin related to that that
leads to scarlet fever. But the scarlet fever that the
world would experience in the mid nineteenth century barely resembled

(43:08):
the benign, mild infection that had in previous decades taken
a backseat to other infections like smallpox, measles, and plague.
An Irish physician wrote in eighteen forty three quote the
disease called scarlet fever assumed a very benign type in
Dublin soon after the year eighteen oh four, and continued
to be seldom attended with danger until the year eighteen

(43:29):
thirty one, when we began to perceive a notable alteration
in its character, and remarked that the usual undisguised and
inflammatory nature of the attack was replaced by a concealed
and insidious form of fever attended with great debility. We
now began occasionally to hear of cases which proved unexpectedly fatal,
and of families in which several children were carried off. Still,

(43:52):
it was not until the year eighteen thirty four that
the disease spread far and wide, assuming the form of
a destructive epidemic that contain agents seemed to act as
a more deadly poison on the individuals of some families
than upon those of others, and consequently, when one member
of a family had died, there was always much reason
to fear for the others when attacked end quote. Yeah.

(44:14):
In Great Britain, the case fatality rate went from virtually
non existent in the early eighteen hundreds to fifteen percent
by the eighteen thirties. By the middle of the century,
ten thousand people died each year in England and Wales
from scarlet fever.

Speaker 2 (44:30):
Wow. Right.

Speaker 1 (44:32):
In New York, the case fatality rate jumped ten times
what it had been in the early eighteen hundreds to
what it became in the eighteen thirties. Another doctor in
France noted how in the first two decades of the
eighteen hundreds he had never encountered a single death due
to scarlet fever, but then he observed the eighteen forty
two epidemic that caused such high rates of death that

(44:54):
he compared it to plague. Wow, isn't this strange.

Speaker 2 (44:59):
It's fast, I mean, it's terrible, it's terrifying, and like, biologically,
what the heck is.

Speaker 1 (45:07):
Going on exactly? And unfortunately these were not one offs.
These were not like one time, oh that was just
happened to be a really bad scarlet fever year. Fatal
scarlet fever would hold the world in its grip for
nearly fifty years. Wow. Yeah. Between eighteen forty and eighteen
eighty three, scarlet fever became the most common infectious disease

(45:29):
to cause death in most metropolitan areas.

Speaker 2 (45:32):
There's so much that I didn't know about this, Aaron.

Speaker 1 (45:34):
I know, some larger cities reported case fatality rates over
thirty percent.

Speaker 2 (45:41):
Thirty percent case fatality and like one hundred years before,
we did not see that, and we saw scarlet fever,
but it was not this deadly.

Speaker 1 (45:49):
Yeah.

Speaker 2 (45:50):
Wow.

Speaker 1 (45:51):
So I don't know what's going on, and I do
wonder how much of it is an interaction between scarlet
fever and other childhood illnesses, like some sort of like
dip theoria scarlet fever superinfection type thing. But it really
like scarlet fever is notorious. It was notorious. Outbreaks came
in waves, peaking every one or two years, and each

(46:14):
epidemic brought fear and dread. The disease was so contagious
and kids could get sick so rapidly and get really sick,
really quickly and unexpectedly, with multiple kids in the same
family dying, Unlike tuberculosis and other diseases that were common
at the time, Scarlet fever seemed to strike at random,
hitting all social classes equally. People did everything they could

(46:38):
to prevent it from spreading. I know there are a
lot of horrible, sad stories. I'm going to hit you
with one more. There was a story about a British
family who lost four of their five kids to scarlet fever,
and they left their house for weeks, having it like
deep cleaned and disinfected as much as they could, all
the clothes and linens cleaned, even furniture clean, and walls

(46:59):
re papered. Three months later, they came back only to
have their sole surviving child come down with fatal scarlet
fever a couple weeks after moving in. What yeah, and
who knows what happened in that case?

Speaker 2 (47:14):
Right, like, oh my goodness, Aaron, I know.

Speaker 1 (47:19):
Even knowing though that scarlet fever was incredibly contagious, which
was more or less generally accepted during this time, which
was pre germ theory, people could still say, oh, well,
that was contagious. Knowing that seemed to do little by
way of preventing spread of the disease, and doctors really
keenly felt their powerlessness to do anything about scarlet fever

(47:43):
or predict it. Spread from an eighteen thirty five article
by Charles Lee. Quote the laws by which it is
controlled are absolutely unknown to us, and probably will ever
remain so.

Speaker 2 (47:56):
End quote.

Speaker 1 (47:57):
Erasmus Darwin. So Charles Darwin's grandfather observed the wide range
and severity in the late seventeen hundreds. Quote the scarlet
fever exists with all degrees of virulence, from a flea
bite to the plague end quote, And sadly, one of
his sons, Charles Darwin's son Charles, died of scarlet fever
in eighteen fifty eight, which, for evolution nerds out there

(48:20):
is the same year that Alfred Russell Wallace sent Darwin
his observations on natural selection, which then prompted him to
be like, I need to release on the origin. Erasmus
also added that quote no one could do an act
more beneficial to society or glorious to himself than by
teaching humanity how to inoculate this fatal disease, scarlet fever,

(48:43):
and thus to deprive it of its malignity end quote. Essentially,
Darwin was suggesting that someone should make a vaccine for
scarlet fever, and for decades people tried, but to no avail,
at least on the vaccine front. And until there was
a vaccine and there still isn't spoilers, spoilers, any control
efforts aimed at scarlet fever would have to come in

(49:04):
the form of non pharmaceutical interventions or public health efforts, which,
speaking of this is I'm wearing one of my favorite shirts.

Speaker 2 (49:12):
Yeah, we just got these brand new shirts, yes, from
Iowa Immunizers. Thank you so much.

Speaker 1 (49:17):
It was a wonderful summit so much it was. I
loved it so much. I love public health, Aaron, and
my shirt says because I don't know if this is
going to make it into into our real but my
shirt says America needs public health.

Speaker 2 (49:29):
And mine says peace, love and vaccinations. We did not
really coordinate this either.

Speaker 1 (49:33):
We both just we both just love these shirts so much.

Speaker 2 (49:38):
I love the very soft You can check it out
Iowa Immunizes dot org and check out your local immunization
coalition because pretty much every state probably has one, and
if not, maybe you could start one. I don't know. Anyways,
moving on.

Speaker 1 (49:50):
Yeah, anyway, back to scarlet fever.

Speaker 2 (49:52):
Scarlet fever.

Speaker 1 (49:55):
In eighteen sixty nine, which was the year of an
extremely severe epidemic. John Simon, who the medical officer, said,
quote at the present time, with scientific knowledge limited as
it is, and with our very imperfect administrative resources, anyone
who was responsible for advising on the requirements of the
public health must feel extreme difficulty and indeed almost humiliation

(50:18):
in having to advise about Scarlatina end quote.

Speaker 2 (50:21):
Wow.

Speaker 1 (50:22):
He concluded that quote the isolation of infected individuals was
the only means of limiting the power of the disease
end quote. The proposed solution for London, which was later
adopted by other cities, was to isolate infected individuals at hospitals,
specifically the Metropolitan Asylum's Board Hospitals and the London Fever Hospital,

(50:44):
but only those from the poorest classes could be admitted
until the late eighteen eighties, and so it's not entirely
clear how effective these hospitals were as a public health
intervention in those earlier decades.

Speaker 2 (50:56):
Right, because they're only taking certain people.

Speaker 1 (50:59):
Yeah. Yeah. At the start of this policy, which was
around this eighteen seventies, seven percent of all fatal scarlet
fever cases occurred in these hospitals. But that number grew
to seventy five percent in eighteen ninety four, which shows
that more and more people were using these hospitals for
their intended purpose. But did this isolation policy actually do

(51:21):
anything in terms of scarlet fever epidemics. Maybe not. People
often didn't go to the hospital until they were super
sick and probably had already exposed others. Hospitals occasionally had
to turn away patients because they were too full. Wealthier
individuals would travel to the seaside to recuperate, bringing scarlet
fever with them, and some people could still be contagious

(51:42):
after their symptoms had ended, and so it was difficult
to know, like how long can you keep someone in
this hospital when we need the bedspace. But perhaps the
most telling thing was that places that didn't enact similar
policies saw the same downward trend in scarlet fever cases
scarlet fever severity as the nineteenth century drew to a close.

Speaker 2 (52:04):
This is so weird and interesting, Aaron, I.

Speaker 1 (52:07):
Know this downward trend wasn't necessarily in prevalence, but in mortality.
Scarlet fever suddenly became less deadly compared to the mid
eighteen hundreds, when case fatality rates approached thirty percent or
even the average of ten percent or so, just like
in those more severe years, scarlet fever killed two point

(52:30):
five percent of those who got sick. As the twentieth
century began, so it went from ten percent to two
and a half percent, Right, Why what changed the bacterium? Yeah,
we don't know for sure. It's got to be the
bacterium though, like it''t it's not right.

Speaker 2 (52:49):
The people didn't change.

Speaker 1 (52:50):
The people didn't change the preventative measures or sanitary reform.
That didn't really seem to change it.

Speaker 2 (52:56):
And it just pre antibiotics too.

Speaker 1 (52:58):
Yeah, yeah, it really just kind of seems like a
less virulent strep biogenies replaced the deadlier one. And there
is some suggestions of yeah, I know, like why why
was it more competitive? Like why was it more why
did it survive better? Why did it replace well?

Speaker 2 (53:16):
And why? But it was still a scarlet fever causing one,
like it was still scarlet fever exactly. So it's even
more weird.

Speaker 1 (53:23):
It's even weirder, and it does kind of beg the question,
could a deadlier strain come back today?

Speaker 2 (53:31):
Is it? My first question? Yeah, and maybe you'll tell
us this, don't expect me to answer it, Okay, But whatever.

Speaker 1 (53:38):
The reason for this decline, scarlet fever still remained in
the public consciousness and its impact was still very much felt.
Scarlet fever features in the literature of the day, like
the velveteen Rabbit, like Little Women, Beth ultimately dies from
scarlet fever spoilers or maybe rheumatic fever. I'm not sure.
Little House on the Prairie, although it may not have

(53:59):
actually been scarlet but meningitis like it even makes an
appearance in Frankenstein. Frankenstein's cousin dies from scarlet fever.

Speaker 2 (54:07):
I mean, I'll just say too, Scarlet fever can like
progress to more severe infections, including like a toxic shock
or a meningitis or so maybe.

Speaker 1 (54:15):
Yeah, it's I don't know, I don't know.

Speaker 2 (54:17):
I don't know. I've never read those.

Speaker 1 (54:19):
Yeah, I mean, I've ever read Little Women since high school,
I think, but I never read it. It's great. And
another way that scarlet fever kind of made this big
impact is something that I had never considered, which is
that those hospital quarantine policies for the infection helped to
normalize hospitals, which were still at the time and then

(54:44):
let's say mid eighteen hundreds, a relatively new concept, and
most people remained prejudiced against them up through the eighteen
eighties because they were like, no, that is for like
the super poor. No, I'm not going to go there.
That's where people get more sick, which was like sometimes true,
But that prejudice largely disappeared by the end of the
nineteenth century because so many people had to bring their

(55:06):
children or themselves to hospitals for treatment and isolation for
scarlet fever.

Speaker 2 (55:10):
Fever. Interesting, I know, I wonder if it too helped
with like I mean they're doing like isolation policies where
now like we have like this isolation policy for this
pathogen and this one for this pathogen.

Speaker 1 (55:21):
I normalize the quarantine sticker on the door type of
a thing.

Speaker 2 (55:24):
Right exactly.

Speaker 1 (55:25):
Yeah. And even though this disease was no longer as
deadly as it once was, it could still very much
kill and people dreaded its appearance in a home or
a school, and one of these appearances would ultimately lead
to three major developments in the understanding of scarlet fever.
The identification of its causative agent, the introduction of a

(55:46):
skin test to determine susceptibility to scarlet fever and the
development of effective treatment. In nineteen oh one, John D.
Rockefeller was visited at his New York mansion outside of
the city by his daughter Edith, her husband Harold, and
their two sons, John and Harold. While visiting, both of
Rockefeller's grandsons came down with scarlet fever and they were

(56:08):
immediately isolated in an upstairs room to prevent the disease
from spreading to other parts of the house. But how
do you keep the nurses and doctors from tracking the
disease throughout the mansion and exposing the rest of the household. Well,
if you're John D. Rockefeller, you build an enclosed staircase
on the outside of the mansion. And that's exactly what
he did. That went to the wing that had that.

Speaker 2 (56:31):
House choice just like in a day.

Speaker 1 (56:34):
I'm sorry, Like what I mean, I think probably pretty rapidly, okay, cool,
and he was like, get it done. Sadly though, one
of the boys, John died two weeks after getting sick,
and in his memory, his parents, Edith and Harold, established
the John R. McCormick Memorial Institute for Infectious Diseases in Chicago,

(56:54):
and it was there that doctor Gladys Dick and her husband,
doctor George Dick, performed the recent search that led to
the Dick test becoming a household name, which showed susceptibility
to scarlet fever. Gladys actually became interested in scarlet fever
after coming down with it in nineteen eleven while working
at a hospital shortly after finishing her med school training,

(57:16):
and a few years later she married George and they
teamed up to get to the bottom of scarlet fever,
and the rest, as they say, is history. In nineteen
twenty three, they determined that the disease was caused by
hemolytics streptococcus, and the following year they developed a test
for susceptibility to scarlet fever, the Dick test, and they
also produced anti toxin to help treat the disease. And

(57:39):
this was monumental work in a really short time span,
and they were nominated but were not awarded the Nobel
Prize in some year nineteen twenty eight maybe, but until
penicillin was introduced in the nineteen forties, their anti toxin
remained the frontline treatment for scarlet fever, really the only
effective treatment and for a while, scarlet fever went back

(58:01):
to being a typically mild, benign infection, and once penicillin
came on the scene, of course, it really kind of
just faded away. I mean, I know that a lot
of people have stories of scarlet fever, like my mom
had scarlet fever. I know this person has scarlet fever,
this person had rheumatic fever. But for the most part,
like it was, scarlet fever was not something you go

(58:22):
when you get antibiotics. But it hasn't always stayed that way.
In the last few decades, and I'm sure you're going
to talk more about this. We've seen a worrying resurgence
in scarlet fever and the types of streptococcus causing scarlet fever.
And so now, Aaron, I'm going to turn it over
to you to tell me whether we're seeing a repeat

(58:44):
of the mid eighteen hundreds and just how worried we
should be.

Speaker 2 (58:48):
I'll try my best right after this break. So when

(59:25):
we're talking about global numbers, I usually go to the
World Health Organization first to try and get a sense
of like where are we at, what's going on, what's
the global burden? The World Health organization doesn't have a
page that I could find that specific to scarlet fever.
What they focus on and what they're like working groups
are focused on is group based strep infections overall, mostly

(59:49):
because of rheumatic fever. And this is not a rheumatic
fever episode. It deserves its whole on episode. We will
do that someday, but rheumatic fever remains the main reason
that people are concerned about groupase strep infections overall. So
if we look at just like groupase strap because in theory,

(01:00:11):
if a group A strap picks up these arulin factors
that can these toxins that can cause scarlet fever, then
it could be causing scarlet fever. It's estimated that worldwide
there's over six hundred million cases of strep throat every year,
so streptococo pharyngitis, and over one hundred million cases of impetigo.

(01:00:33):
So that like more mild skin infection. Wow.

Speaker 1 (01:00:37):
The reason that.

Speaker 2 (01:00:38):
World Health Organization focuses so much on rheumatic fever is
that that is estimated to cause over almost half a
million new cases every year, which result in almost three
hundred thousand new cases of rheumatic heart disease and three
hundred thousand deaths every year from rheumatic fever and rheumatic
heart disease. But I don't have numbers like that for

(01:00:59):
scarlet fever. And it's in part because, like you talked
about Aaron, this is a disease that really started to
be on the decline in the early nineteen hundreds, even
before the rise of antibiotics, and since the rise of antibiotics,
we really have not seen a lot of it. I've

(01:01:20):
never seen a case of scarlet fever. Yet it doesn't
mean that it doesn't exist. It's just far less common
than the other forms of group A strap, which we
still see a ton of and we're able to treat
with antibiotics. But like you said, in the last couple
of decades, especially in the last ten years, there has
been an increasing number of outbreaks and cases in a

(01:01:43):
few countries, including in the UK, in China, in Hong Kong.
That's where I saw the most data for And we're
talking about places where there used to be maybe a
few hundred cases and now we're looking at thousands to
in some years, tens of thousands of cases. And the
numbers seem to still be increasing at least in the
data that I saw. Why is that?

Speaker 1 (01:02:08):
Why is that?

Speaker 2 (01:02:09):
We don't know? I mean, clearly, we know that scarlet
fever is caused by these particular strains of groupe strap,
But why are we seeing an increase in these strains?
We do not know the answer to that question. So far,
these strains have not seemed to be particularly virulent. That

(01:02:31):
doesn't mean that there haven't been deaths, but we're not
looking at eighteen hundreds numbers of deaths, which is good
because that's terrifying. It's also because we have antibiotics, so
even if we had a strain that was more virulent,
we at least have the ability to treat it as
long as people can get access to therapy. One of

(01:02:51):
the best things that we could do for the potential
rise in scarlet fever, as well as for rheumatic fever
and rheumatic heart disease, would be to develop act and
that is something that people have known for a long
time and have been trying to do for a very, very,
very long time. There's an entire working group called the
strep A Vaccine Global Consortium, and that is its main

(01:03:15):
focus is trying to develop a strip a vaccine, and
you kind of mentioned that people have been trying this
for a long time, like there are dozens and dozens
of different vaccines that have undergone various stages of clinical trials.
We do not have a vaccine, and there's a few
different things that make it really difficult to try and
develop a vaccine for Strep biogenies. One is that this
is a human pathogen, so we don't have a good

(01:03:37):
animal model. There's no natural animal reservoirs. It doesn't mean
we don't have animal models. We have like knockout mice
models and things like that, but they're just not perfect. Also,
we have about a gazillion of those m proteins that
we have to contend with, and those Historically that invisibility
cloak has been the main target for vaccines because that's
the surface protein, so if we could target it, then

(01:03:58):
we could prevent an infections. But people have really started
looking at other proteins, including trying to target these superan eigens,
so that we're really targeting the strains that are more
likely to cause severe disease, things like toxic shock, things
like scarlet fever. But here's one of the other big hurdles.
There is a worry that's not unsubstantiated based on previous

(01:04:21):
vaccine trials, that vaccines could actually trigger rheumatic fever and
rheumatic heart disease. And this is the most severe and
deadly forms that we have today.

Speaker 1 (01:04:31):
Is this after effect, and that's because people have likely
been exposed to it, and so it kind of creates
that secondary thing like that, why does that happen aarin
If we knew the answer to that, we would have
a yeah, exactly.

Speaker 2 (01:04:45):
If we knew exactly why some people get rheumatic fever
and other people don't, then we would have a lot
of answers to a lot of questions. But we don't.
We don't know. Not everyone who gets a strep throat
infection of any kind or an impetigo affection though it's
mostly from strep throat is going to develop rhumatic fever.
But some people do, and so we need to avoid
even that possibility when we develop a vaccine. So it's difficult.

(01:05:10):
We don't have a vaccine yet today, but there's a
lot of people who are really trying to do that research.

Speaker 1 (01:05:15):
I have a question that's kind of about the biology
of this pathogen it lives on our body, on our
bodies all the time.

Speaker 2 (01:05:24):
Not everyone's body necessarily, but yes, it's around. It lives
on a lot of them, lives on most of us
all the time.

Speaker 1 (01:05:33):
Does it play a role outside of being a pathotic
or what is its role outside of being a pathogen?
It's a good question.

Speaker 2 (01:05:41):
I don't know.

Speaker 1 (01:05:42):
I don't know that.

Speaker 2 (01:05:44):
I didn't see anything in anything that I read about
it being like a beneficial bacterium that's hanging out with us.
We mostly think of it as something that is like
a commensal at best, so it's just living on us,
not doing anything bad until it does something bad. But
what's interesting is that it's not often considered like an

(01:06:04):
opportunistic pathogen, where it's like, ooh, just if I get
the option, I could maybe get you sick. It really
is like it is a pathogen that also can exist
without making us sick. Is the way that it's usually
described in everything that I read about it. Okay, For example,
if somebody does get rheumatic fever, one of the main
things to do to treat that, even though it's not

(01:06:29):
caused by the bacterium directly, is to use really high
doses of penicillin antibiotics to eradicate carriage so that people
don't get reinfected with strep biogenies.

Speaker 1 (01:06:43):
Okay, interesting, and where does it live? It lives in
our mouths, right, It can.

Speaker 2 (01:06:47):
Live in our mouths or mucus membranes. Some people are
colonized in the back of their throat. It also can
be like a skin infection, so it can potentially live
on your skin, although I don't know how often it's
really just like hanging out on our skin the way
that staff does, because for example, this is maybe going
too deep. But like you know, if you go into
the hospital and they have to take blood and they're

(01:07:08):
looking for an infection in your blood, sometimes we can
accidentally grow certain types of staff bacteria, and if it's
only in like one bottle, they'll be like, well, that's
probably just because it's on your skin and we contaminated it.
But that's not true for streptococcus. If you find streptococcus
in the blood stream, that's an infection or you have
to treat it like it's an infection. So I don't

(01:07:28):
think it tends to hang out on our skin as
much as in our mucous membranes. Okay, Yeah, that's I mean,
that's what we've got for scarlet fever. There's so much
more to strut piogenies, And honestly, I am still so
curious about this rise of scarlet fever. It hasn't yet
been worldwide. I don't know what's going to continue to happen.

(01:07:50):
Is it going to continue to spread?

Speaker 1 (01:07:51):
Is it not? Why?

Speaker 2 (01:07:53):
Why? Why? We have so many questions.

Speaker 1 (01:07:56):
We have a lot more tools at our disposal, public
health tools, you know, therapeutic tools, preventive tools, et cetera.
But the fact that it was so deadly, right, more
deadly than I had ever ever expected it to be,
and then it just stopped being deadly.

Speaker 2 (01:08:14):
Right, Yeah, the evolutionary biology of this pathogen has got
to be super interesting.

Speaker 1 (01:08:19):
Yeah, Like how and how can we stop that from
happening again?

Speaker 2 (01:08:24):
Yeah? Why did it happen in the first place?

Speaker 1 (01:08:27):
So many questions that if you would like to try
to find the answers to in the papers that we found,
We've got some papers for you.

Speaker 2 (01:08:35):
We do.

Speaker 1 (01:08:37):
I have a bunch I'm going to shout out to
in particular. One is by Swedland and Danta from two
thousand and three called Scarlet fever epidemics of the nineteenth century,
a case of evolved pathogenic virulence question mark. And another
is a chapter from a book by Anne Hardy called
The Epidemic Streets, and this particular chapter was about scarlet

(01:08:57):
fever and all of these different hospital policies and I
thought it was really fascinating.

Speaker 2 (01:09:02):
I have a couple of papers and a textbook for
this one. The textbook was actually really great and I
enjoyed it, and there's a lot of great chapters in there.
It was called Streptococcus Piogenies Basic Biology to Clinical Manifestations,
and I read a number of different chapters from that,
so that textbook is available online. I also really loved
a paper from twenty twelve called Streptococcus Piogenies and re

(01:09:25):
Emergence of Scarlet Fever as a Public health problem, and
there's a number of other papers. We will post the
list of our sources from this episode and every single
one of our episodes on our website this podcast with
Killy dot Com under the episode stab.

Speaker 1 (01:09:38):
Thank you to Bloodmobile for providing the music for this
episode and all of our episodes.

Speaker 2 (01:09:43):
Thank you to Tom Bryfogel and Leona Scolacci for the
audio mixing.

Speaker 1 (01:09:46):
Thank you to everyone at Exactly Right, and thank.

Speaker 2 (01:09:49):
You to you listeners. We hope you enjoyed this episode.
Thanks for listening to it. Do you have more questions
I do? Do you have answers to our questions? Are
you in evolutionary biologists to study strip piogenies? Can you
email us?

Speaker 1 (01:10:00):
What is your favorite piece of scarlet fever literature? Is
it The Velveteen Rabbit? Or is it Little Women? Or
is it Frankenstein? Let us know? And a big thank you,
of course, also to our wonderful, generous, lovely, fantastic patrons.
We appreciate your support so very much. It means the
world to.

Speaker 2 (01:10:16):
Us, it really does.

Speaker 1 (01:10:17):
Thank you well. Until next time, wash your hands, you
filthy animals