Ep 158 Scarlet Fever: You’ve changed

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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 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, 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 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 was too ill to play, and the little rabbit found it rather dull with nothing to do all day long.

But he snuggled down patiently and looked forward to the time when the boy should be well again, and they would go out in the garden amongst the flowers and the butterflies and play splendid games in 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.

He was able to sit up in bed 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 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 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 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 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 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 his coat had worn so thin and threadbare from hugging that it was no longer any protection to him.

Nearby he could see the 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 and the flower bed, the quiet evenings in the wood when he lay in the bracken and the little ants ran over his paws, 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 real tear, trickled down his little shabby velvet nose and fell to the ground.

I'm crying.

It's so sad.

Oh my God.

It's a children's book, and it's like so sad.

You really are.

You really are crying.

Oh, my God.

It hit me.

Oh, the 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.

I'm crying watching you cry.

I have, you know, like some people vomit when they see other people vomit.

I cry when I see people cry.

Yeah.

Oh my God.

Oh, Erin.

It's a happy ending.

It is a happy end.

Happy ending.

We just didn't want to read to you for like 15 more minutes.

A fairy comes and turns a Velveteen rabbit into a real rabbit, if anyone hasn't read that book since they were a kid.

Yeah.

And then the little boy sees the rabbit playing with the other rabbits and he's like, oh, that looks like my old Velveteen rabbit.

So he's so happy.

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 fever.

Plays a pretty.

predominant role as you can as you can tell.

Hi, I'm Erin Welsh.

And I'm Erin Alman Updike.

And this is this podcast will kill you.

And we're not going to cry for the entire episode, but

no promises.

I don't know.

Really?

But today we're talking about scarlet fever.

Yeah, we are.

This is such a classic TPWKY topic and story.

It's it's

strange that we haven't done it before.

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 episodes on strep pyogenes but we'll get there yeah and is it just strep pyogenes yeah aaron 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 hemolytic streptococci

we'll get there we'll get there okay it's very honestly it's a lot it's gonna be fun yeah it's gonna be we're gonna learn a lot so much

so much we are but before we learn so much about strep pyogenes and, you know, things like toxins, we've got a very special time.

We've got a special time.

I really, that book really threw me off my game.

I'm still like thinking about that poor dog.

You're doing great.

You're doing great.

Thanks.

Thanks.

It's good.

What are we drinking this week?

Oh, yeah, that's right.

We are drinking.

Let me see if I can say it without stumbling through it.

The Scarletina Rita.

Scarletina Rita.

Yes.

Scarletina is an old timey name for scarlet fever.

And it's basically a strawberry margarita.

So it's a scarletina rita.

Yeah.

Strawberry because rash, strawberry rash?

Is that what the teacher is?

Yeah, strawberry tongue.

Strawberry tongue is one of the like 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, our placebarita, on our website, this podcastwillkillyou.com and on all of our social media channels.

We certainly will.

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Thanks, thank you.

Shall we content you?

Shall we?

Is that a can you verb that?

I mean, I, sure.

Let's, we can.

We can do whatever we want.

This is our podcast.

So let's take a break and then get started.

Let's do it.

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So here's the thing about scarlet fever.

It's a little bit weird.

Okay.

And it's weird because, so scarlet fever is a disease that is caused 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 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 is how it generally goes, because we only got a glimpse of it in the velveteen rabbit most often a kid like the velveteen rabbit's kid who's usually between three and 10 years old or sometimes between five and 15 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 tonsillitis.

You have a swollen, infected, super sore throat.

If you look in this kid's mouth, you'll see swollen tonsils.

They might even have some like kind of pus-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 the papilla, 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 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 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.

Yeah.

Does it itch or hurt?

Good question.

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.

Okay.

And why doesn't it go around your mouth?

Oh my gosh.

I have so many questions about this rash.

So I don't know.

I don't know why.

Cause 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 pronounced than in the rest of where the rash is.

I don't know why in these areas, these like flexural 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 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 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, strep pyogenes.

So what the heck is streptococcus pyogenes?

Yeah.

So strep pyogenes, it's also called group A strep.

It's 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 know.

I feel like I haven't heard the phrase gram-positive

in ages.

I know.

I felt weird writing it.

But what that just means is that if you look at it on a typical microscope slide where we stain it, it looks purple like a little cute little purple ball because it's a cocci 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 rather than clumping up the way staph aureus does we talked about staph aureus in our merci episode cluster of grapes yep and this bacterium strep pyogenes is super, super common.

It's a commensal in a lot of our throats and mucous 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 of diseases.

Strep throat, that's strep pyogenes.

Everyone knows strep throat, that's group A strep.

Impotigo, if you've heard of impetigo, 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 strep, strep pyogenes.

It also can cause a deeper infection like a cellulitis or an erysipelis

which is when the infection goes to like 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 deadly infection that is a surgical emergency.

It can even then continue an infection down to the muscle and that's called myositis.

And strep pyogenes is also famous, besides all these skin infections and throat infections and scarlet fever, which we'll get to, strep pyogenes can also, I'm calling it pula COVID.

I don't know if that's a thing, but strep pyogenes 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 streptococcal infection, usually after strep throat, but it could be after a skin infection.

And rheumatic 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 glomerulonephritis, which is a fancy word for your immune system attacking your kidneys as a consequence of a strep infection.

That one is usually after a skin infection, but could be after a throat infection.

And then there's another illness called PANDAS.

Have you heard of that?

It's pediatric, autoimmune, neuropsychiatric disorders associated with strep to coccal 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 to be another post-infectious consequence after a group A strep infection.

So this is a pretty huge range of illnesses.

And do these different manifestations of SREP 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 erysipalis rather than impotigo?

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 you getting this?

Is someone coughing this bug into your mouth and depositing it really close to your tonsils?

Maybe then you're more likely to get a tonsiller infection or a strep throat.

Are you getting strep underneath your skin because you itched something and you scratched some bacteria into your skin?

Maybe now you're going to get impatigo.

But there's also more to it than that

because this is, it's one species of bacteria, right?

It's strep pyogenes, but it is a huge amount of different stuff and different strains that you can have.

So I said that this is a human-specific bacterium.

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 it to evade our immune system.

So one of the things that strep pyogenes 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.

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 N's on its surface.

So Streppyogenes 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 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 A strep 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.

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?

Yeah, well, it gets more than that, Erin, because it's not just this invisibility cloak.

Strep pyogenes 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.

There are things like proteins.

There are 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.

And so not all.

strains of strep pyogenes is going to have all of these different virulence factors because there's a whole huge range of them that they can have.

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 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 200 different versions.

And then I read some papers that went into detail 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 what makes your body eventually recognize strep pyogenes?

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 find it, but it's not immediate.

And it's going to depend on what other variance 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 pyogenes that brings with it one specific type of equipment, and that is called a superantigen.

So, the strains of strep pyogenes that produce scarlet fever make a group of toxins called streptococcal pyrogenic exotoxins, and pyrogenic means it generates a fever, which is like not specific.

But basically, this type of toxin,

what it 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 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 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 causing the rash.

That also means that you won't get scarlet fever the very first time you've ever been exposed to Streptococcus pyogenes, 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 really like the right time and in the right way.

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Okay, so two things have to happen for you to get get scarlet fever.

The first is a previous exposure to strep pyogenes, and the second is exposure after that to strep pyogenes with this super antigen.

Exactly.

Okay,

question that's kind of unrelated.

Okay, give it to me.

This is group A strep.

Yeah.

How many groups of strep are there?

I love it.

I'm so glad you asked.

And what makes it group A, B, whatever?

So

it's even more complicated than that, Erin.

There is group A, B, C, D, E, F, G, and H.

All right.

So far.

So far, those are all of a type of strep that is called beta hemolytic or like hemolytic strep.

Okay.

And that term hemolytic just means that when you plate any of these A, B, C, D, E, F, G on a certain type of culture media, they grow in a way, blah, blah, blah.

There's an entirely different grouping of strep that's called alpha hemolytic strep, which are not grouped as A, B, C, D, blah, blah, blah.

Those are just like, they're even separate from that.

And that is the ones that include like strep pneumonia, which is a common cause of pneumonia.

And there are other ones within that grouping as well.

But then within strep of the groups, like the hemolytic streps, group A strep is kind of synonymous with strep pyogenes, at least in humans, because that's the main one that causes disease in humans.

Group B strep is another type of hemolytic strep that, for example, we check for during pregnancy because it lives in the vagina and it can infect newborns and cause meningitis.

Okay.

Group D strep, you might have heard of because they've actually been renamed as Enterococcus.

So now they're not even streptococcus anymore.

Okay.

And then most of the other ones don't cause as much disease in humans.

And so we don't hear about them quite as much.

Is pupereal fever group A strep?

So pupereal fever can be group A or group B strep.

I think historically it was more group A strep.

Okay.

And certainly group A strep is very virulent.

Group B strep often can cause infection in the newborn.

Okay.

And so that is what we screen for and we treat if somebody is colonized with group B strep.

It's interesting to me, as someone who is not an evolutionary biologist or someone who studies speciation,

why are these groups or strains and not species, do strep pyogenes, are they able to acquire toxin genes, for instance, or superantigen genes?

Absolutely, yeah.

So a lot of the toxins and virulence factors in general in strep pyogenes, 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 bacteriophages, so they can be more easily moved around between strains.

Okay.

But yeah, there is such a huge range.

I wonder the same thing.

Are there actually a bunch of different species within this umbrella called strep pyogenes?

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 this.

But a standard strep throat infection, like you get when you're a kid multiple times, that's just strep pyogenes.

There's no superantigen involved necessarily.

So that's a great question, Erin.

I mean, we'll talk talk more about the epidemiology later, but yeah, scarlet fever has drastically declined in incidence.

It's not called scarlet fever unless you have those other characteristic signs, especially that rash.

So if you have strep throat without any of that rash, we would call it strep throat.

We would not call it scarlet fever.

Why do children get it at higher rates than adults?

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.

I don't, I don't know.

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 it a combination of all of that?

I don't, 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.

And that can't just be like maternal antibodies.

Like, no, absolutely not.

Those are gone by six months.

Yeah, exactly.

So, yeah, it's super interesting.

I don't, 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.

My mom had scarlet fever in college.

Really?

Yeah.

Yeah.

I mean, adults can certainly still get it.

Yeah.

We heard Nar Tonsil's episode.

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.

I don't know.

It's a good question.

Yeah, it's a good question.

I don't,

I don't know.

There are a couple different like versions of the exotoxins that are associated with scarlet fever.

But I think largely what like 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 like nitty-gritty of this bacterium to know.

Are there, can I just keep going?

Yeah, please.

Okay.

Are there some superantigen producing strep pyogenes that are more likely to cause epidemics or outbreaks than others?

That's such a good question.

Probably.

I have no idea.

Okay.

I read an entire textbook.

Well, I didn't read every chapter, but I read a lot of chapters of a textbook that is only about strep pyogenes.

And as much as we know so much detail about a bajillion of these different variance factors, because it's not just these superantigens, there's so many other variance factors.

There's streptolysin.

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 is it something about the way that they're transmitted is it some other virulence factors that are making them more likely to establish an infection or do something else

there's there's i have so many more questions

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 erysibalis or we do necrotizing fasciitis or we do yeah rheumatic fever needs its whole own

episode i mean there's there's so many things too right Because that's a whole can of worms 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?

Right.

I don't know.

We don't know.

Is everyone in theory susceptible to scarlet fever?

or able to get scarlet fever.

You know what I mean?

Like, I know that there is a good question.

No, yeah.

And it seems like not necessarily.

Right.

Or at least we don't 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.

Okay.

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, strep pyogenes 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 resistance to some other types of antibiotics like macrolides and things like that.

So that's something to keep 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 antibiotics we use, penicillin and other penicillins still work really well, which is great.

Yeah.

Also shocking that like it just is, yeah.

You got to love when like good old penicillin is still our favorite drug for things.

Yeah.

Not obsolete.

So that is the biology of scarlet fever and a little bit of strep pyogenes in general.

I'm fascinated because I feel like now what I'm about to talk about is going to generate some more questions.

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?

Yeah, I certainly will.

Let's take a break and then I'll get to it.

Okay.

Before I get started, I should mention that I will be discussing childhood mortality throughout this 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, Erin.

Like, I knew that it used to be more prevalent than today and more feared, but I wasn't prepared for just how different the scarlet fever of today is compared to the scarlet fever of 150 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 5th, 1865, aged three years and seven months.

John Howard Wallace died May 19th, 1865, aged 10 10 years and two months.

George Frederick Wallace died May 20th, 1865, aged seven years and seven months.

Alice Pennington Wallace died May 24th, 1865, aged four years and 11 months.

All died of scarlet fever, end quote.

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 the 1800s, headstones like the one for the Wallace children were created for families around the world who lost multiple children in quick succession to scarlet fever epidemics.

There are two family crypts in the St.

Peter's Anglican Cemetery in Tasmania that are dedicated to the seven young siblings that died within six weeks of each other in 1859, all of scarlet fever.

Oh my God.

Right?

It's,

I have no words for how

awful.

At that same cemetery is a plaque commemorating the nearly 7,000 children under the age of 10 who died of scarlet fever in Tasmania in the 10-year period from 1850 to 1860.

Oh my God.

Yep.

Archibald Tate, who was the Archbishop of Canterbury in England in the mid-1800s, had five of his daughters, aged two to 10, all die within five weeks of each other from scarlet fever.

One son and one daughter survived.

Oh, geez.

And these are just a handful of gravestones that represent a larger tragedy, which is the deadly toll that scarlet fever took on children and on families in the 1800s.

Like if you search scarlet fever headstones, gravestones, you will find so many examples of these.

From our vantage point here in 2024, I think it's hard to imagine, or at least easy to forget, how life was before antibiotics, when every childhood illness held the threat 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 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 1800s, which led to some of the earliest preventative policies against a disease, like sweeping preventative policies, and ending with its decline over the 20th century, thanks in large part to diagnostic tests and antibiotics, but also thanks to the bacteria themselves.

Yeah, I'm really curious about that.

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, Erin, strep pyogenes is just hanging out in or on our bodies all of the time and we have some archaeological evidence of this so i found a paper from 2014 by warriner et al that described the microbial contents of dental calculus found from skeletons from around 900 to 1200 ce which is really cool i just love that like what you can find what is in your mouth i love when you find dental pulp in mulch

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 is with measles, for instance, because it's just, it's there in 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 1553,

where Ingracia wrote about scarlet fever, quote unquote, rosalia, as distinct from measles.

There are so many rashi illnesses of childhood with overlapping symptoms that it's kind of amazing that anyone was able to differentiate among any of them.

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.

It's a, it's a very, yeah, it's distinctive.

Yeah.

It 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 with its sandpaper rashiness, 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.

At the same time.

Okay.

And same thing with like measles.

There are some interesting relationships about like measles epidemics preceding scarlet fever epidemics.

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 Ingracia's report, other descriptions of Rosalia, or as it began to be called in English vernacular, scarlet fever, appeared, including a 1676 description by Thomas Sidenham, 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 oftenest breaks out towards the end of the summer when it attacks whole families at once and more especially the 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 and branny scales remain lying on the surface like meal.

They appear and disappear two or three times.

End quote.

Interesting.

Yeah.

And people would have plenty of opportunity to use the name scarletina or scarlet fever.

By the early to mid-1800s, the disease was widespread across the globe, arriving in North America around 1735, in South America by around 1800 or so, Australia 1840s, and of course, it had already been well established in Europe, 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-19th century barely resembled 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 1843: quote: The disease called scarlet fever assumed a very benign type in Dublin soon after the year 1804 and continued to be seldom attended with danger until the year 1831, 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, it was not until the year 1834 that the disease spread far and wide, assuming the form of a destructive epidemic.

The contagion 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.

In Great Britain, the the case fatality rate went from virtually non-existent in the early 1800s to 15% by the 1830s.

Wow.

By the middle of the century, 10,000 people died each year in England and Wales from scarlet fever.

Wow.

Right?

Yeah.

In New York, the case fatality rate jumped 10 times what it had been in the early 1800s to what it became in the 1830s.

Another doctor in France noted how in the first two decades of the 1800s, he had never encountered a single death due to scarlet fever.

But then he observed the 1842 epidemic that caused such high rates of death that he compared it to plague.

Wow.

Isn't this strange?

It's fast.

I mean, it's terrible.

It's terrifying.

And like biologically, what the heck is 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 50 years.

Wow.

Yeah.

Between 1840 and 1883, scarlet fever became the most common infectious disease to cause death in most metropolitan areas.

There's so much that I didn't know about this, Erin.

I know.

Some larger cities reported case fatality rates over 30%.

30% case fatality.

And like 100 years before, we did not see that.

And we saw scarlet fever, but it was not this deadly.

Yeah.

Wow.

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 diphtheria, scarlet fever, super infection type thing.

But I.

It really, like scarlet fever is notorious.

It was notorious.

Yeah.

Outbreaks came in waves, peaking every one or two years, and each 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 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 cleaned and walls repapered.

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, right?

Like, right.

Oh my goodness, Erin.

I know.

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 or predict its spread.

From an 1835 article by Charles Lee, quote, the laws by which it is controlled are absolutely unknown to us and probably will ever remain so, end quote.

Erasmus Darwin, so Charles Darwin's grandfather, observed the wide range in severity in the late 1700s, 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, Charles, died of scarlet fever in 1858, which for evolution nerds out there 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, and thus to deprive it of 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 the form of non-pharmaceutical interventions or public health efforts.

Which, speaking of, this is, I'm wearing one of my favorite shirts.

Yeah, we just got these brand new shirts.

Yes.

From iowa immunizes thank you so much 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 reel but my shirt says america needs public health and mine says peace love and vaccinations we did not really coordinate this either we both just

we both just love these shirts so much

also the very soft you could check it out iowaimmunizes.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 yeah anyway back to scarlet fever scarlet fever

um

in 1869 which was the year of an extremely severe epidemic john simon who was a medical officer said quote at the present time with scientific knowledge limited as it is and with our very imperfect administrative resources anyone who is responsible for advising on the requirements of the public health must feel extreme difficulty and indeed almost humiliation in having to advise about Scarletina.

End quote.

Wow.

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 Asylums Board hospitals and the London Fever Hospital.

But only those from the poorest classes could be admitted until the late 1880s.

And so it's not entirely clear how effective these hospitals were as a public health intervention in those earlier decades.

Right, because they're only taking certain people.

Yeah, yeah.

At the start of this policy, which was around the 1870s, 7% of all fatal scarlet fever cases occurred in these hospitals.

But that number grew to 75% in 1894, which shows that more and more people were using these hospitals for their intended purpose.

But did this isolation policy actually do 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 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?

Yeah.

But perhaps the most telling thing was that places that didn't enact similar policies saw the same downward trend in scarlet fever cases and scarlet fever severity as the 19th century drew to a close.

This is so weird and interesting, Erin.

I know.

This downward trend wasn't necessarily in prevalence, but in mortality.

Scarlet fever suddenly became less deadly.

Compared to the mid-1800s when case fatality rates approached 30%, or even the average of 10% or so, just like in those more severe years, scarlet fever killed 2.5% of those who got sick as the 20th century began.

So it went from 10% to 2.5%.

Right.

Why?

What changed?

The bacterium.

Yeah,

we don't know for sure.

It's got to be the bacterium, though.

Like, there's not, it's can't, it's not.

The people didn't change.

The people didn't change.

The preventative measures or sanitary reform, that didn't really seem to change it.

And it just had pre-antibiotics, too.

Yeah, yeah.

It really just kind of seems like a less virulent strep biogenes replaced the deadlier one.

And there is some suggestions of that.

Yeah, I know.

Like, why?

Why?

Why was it more competitive?

Like, why was it more, why did it survive better?

Why did it replace?

Well, and why, but it was still a scarlet fever causing one.

Like, it was still scarlet fever.

Exactly.

So it's even more weird.

It's even weirder.

And it does kind of beg the question, could a deadlier strain come back today?

This is my first question.

Yeah.

And maybe you'll tell us this.

Don't expect me to answer it.

Okay.

But whatever 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 actually been scarlet fever, but meningitis, like it even makes an appearance in Frankenstein.

Frankenstein's cousin dies from scarlet fever.

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.

It's, I don't know.

I don't know.

I don't know.

I've never read those.

Yeah.

I mean, I haven't 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.

a 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 in the, let's say, mid-1800s, a relatively new concept.

And most people remained prejudiced against them up through the 1880s 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 19th century because so many people had to bring their children or themselves to hospitals for treatment and isolation for scarlet fever.

Scarlet 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.

Like, normalize the quarantine sticker on the door type of a thing.

Right, exactly.

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 skin test to determine susceptibility to scarlet fever, and the development of effective treatment.

In 1901, 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 immediately isolated in an upstairs room to prevent the disease from spreading to other parts of the house.

But how do you 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 housed voice.

Just like, in a day?

I'm sorry.

Like, what?

I mean, I think probably pretty rapidly.

Okay, cool.

I think 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.

And it was there that Dr.

Gladys Dick and her husband, Dr.

George Dick, performed the research 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 1911 while working at a hospital shortly after finishing her med school training.

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 1923, they determined that the disease was caused by hemolytic streptococcus.

And the following year, they developed a test for susceptibility to scarlet fever, the Dick test, and they also produced antitoxin to help treat the disease.

And this was monumental work in a really short time span.

And they were nominated, but were not awarded awarded the Nobel Prize in some year, 1928, maybe.

But until penicillin was introduced in the 1940s, their antitoxin remained the frontline treatment for scarlet fever, really the only effective treatment.

And for a while, scarlet fever went back 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 had scarlet fever.

This person had rheumatic fever.

But for the most part, like it was scarlet fever was not something you go and 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, Erin, I'm going to turn it over to you to tell me whether we're seeing a repeat of the mid-1800s and just how worried we should be.

I'll try my best right after this break.

So, when 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's specific to scarlet fever.

What they focus on and what their like working groups are focused on is group A strep infections overall, mostly because of rheumatic fever.

And this is not a rheumatic fever episode.

It deserves its whole own episode.

We will do that someday.

But rheumatic fever remains the main reason

that people are concerned about group A strep infections overall.

So if we look at just like group A strep, because in theory, if a group A strep picks up these virulence 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 600 million cases of strep throat every year, so streptococcal pharyngitis, and over 100 million cases of impotigo, so that like more mild skin infection.

Wow.

The reason that 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 300,000 new cases of rheumatic heart disease and 300,000 deaths every year from rheumatic fever and rheumatic heart disease.

But I don't have numbers like that for scarlet fever.

And it's in part because, like you talked about, Erin, this is a disease that really started to be on the decline in the early 1900s, even before the rise of antibiotics.

and since the rise of antibiotics,

we really have not seen a lot of it.

I've 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 strep, 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 10 years, there has been an increasing number of outbreaks and cases in a 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?

Why is that?

We don't know.

I mean, clearly we know that scarlet fever is caused by these particular strains of group A strep, 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 doesn't mean that there haven't been deaths, but we're not looking at 1800s 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 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 a vaccine.

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 focus is trying to develop a STREP 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 pyogenes.

One is that this is a human pathogen, so we don't have a good 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 we could like prevent infections.

But people have really started looking at other proteins, including trying to target these superantigens 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 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: this after-effect.

And that's because people have likely been exposed to it.

And so it kind of creates that secondary thing.

Like, why does that, why does that happen?

Aaron.

If we knew the answer to that, we would have a

yeah, exactly.

If we 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 impotycho affection, though it's mostly from strep throat, is going to develop rheumatic fever.

But some people do.

And so we need to avoid even that possibility when we develop a vaccine.

So it's difficult.

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

I have a question that's kind of about the biology of this pathogen.

Yeah.

It lives on our body, on our bodies all the time.

Not everyone's body necessarily, but yes, it's around.

It lives on a lot of us.

It lives on most of us.

Most of us, all the time.

Yeah.

Does it play a role outside of being a pathogen, or what is its role outside of being a pathogen?

It's a good question.

I don't know.

I don't know that we, 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 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 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 pyogenes.

Okay, interesting.

And where does it live?

It lives in our mouths, right?

It can live in our mouths, our mucous 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 staph 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 looking for an infection in your blood, sometimes we can accidentally grow certain types of staph 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 bloodstream, that's an infection or you have to treat it like it's an infection.

So I don't 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 strept pyogenes.

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.

Is it going to continue to spread?

Is it not?

Why?

Why?

Why?

I don't know.

I'm so nice questions.

We have a lot more tools at our disposal, public health tools, you know, therapeutic tools, preventative tools, et cetera.

But the fact that it was so deadly,

more deadly than I had ever, ever expected it to be.

And then it just stopped being deadly.

Right.

Yeah.

The evolutionary biology of this pathogen has got to be super interesting.

Yeah.

Like how?

And how can we stop that from happening again?

Yeah.

Why did it happen in the first place?

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.

We do.

I have a bunch.

I'm going to shout out two in particular.

One is by Swedland and Danta from 2003 called Scarlet Fever Epidemics of the 19th Century, a Case of Evolved Pathogenic Virulence, question mark.

And another is a chapter from a book by Ann Hardy called The Epidemic Streets.

And this particular chapter was about scarlet fever and all of these different hospital policies.

And I thought it was really fascinating.

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 Biogenes, 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 2012 called Streptococcus Piogenes and Reemergence 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 podcastwillkilly.com under the episodes tab.

Thank you to Blood Mobile for providing the music for this episode and all of our episodes.

Thank you to Tom Breifogel and Liana Scolacci for the audio mixing.

Thank you to everyone at Exactly Right.

And thank 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 an evolutionary biologist who studies stretch piogenes?

Can you email us?

What is your favorite piece of scarlet fever literature?

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Or is it Frankenstein?

Let us know.

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