Ep 150 Norovirus: Tip of the poop iceberg

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When I was nine months pregnant, I woke up one morning and felt really off.

I was nauseous and could only eat peanut butter toast.

Being nine nine months pregnant, I figured it had something to do with that, so I just continued on to work where I was in a rheumatology clinic during my pediatrics residency.

After about a half hour in clinic, I felt like I might vomit, so I apologized to the team and I went home.

Luckily, I made it home before the vomiting started.

Once it started, it was pretty continuous, and I could not keep down even sips of water.

I started having abdominal cramping as well, which started to be more worrisome, especially since I was nine months pregnant.

I reached out to friends and family who thought it could be signs of labor so we went into labor and delivery floor to get checked out.

There they determined I was not in labor.

They did some labs which looked good and then sent me home with nausea meds.

At home

I started having fevers and full body aches.

I could barely move from bed and my husband kept waking me up to drink sips of electrolyte solution.

With the nausea meds the night was pretty okay, but the next day the diarrhea started which was horrible and unforgiving.

That wrapped up quickly, however, and the whole thing was over in about 36 hours.

Two days later, I was scheduled for induction.

And even then, when I went in, I was still dehydrated and the nurses were finding it hard to get an IV.

So they had to poke me a few times.

We started the induction and my husband started feeling a little nauseous.

And then he also started vomiting.

He gets a nervous stomach, so at first we didn't really think too much about it.

But within a few hours, he had profuse vomiting, fevers, and diarrhea at at the same time.

He looked bad enough that the labor and delivery nurses insisted he go to the emergency department, and we decided to stop the induction, and I went home.

As my husband was evaluated in the emergency department and eventually admitted for fluids, I was at home waiting to hear how he was doing and my water broke.

So I went back in and delivered a healthy baby girl the following morning.

We had some really phenomenal L ⁇ D nurses who helped coordinate my husband coming up to see the baby from the emergency department.

And our first family photo was of all of us in hospital attire and all of us in diapers.

We found out from my husband's testing that we both had norovirus, which was, I probably picked up at work somewhere, but it could have truly been anywhere.

I was really scared that our baby would get it, knowing it was so much worse for little ones that had no reserve.

But she remained healthy and we all went home in a couple of days.

It was a really humbling experience for all of us, and I will never underestimate norovirus.

You know,

yeah, yeah,

it's not great

understatement

understatement, yeah.

That

I thank you for reliving that for us.

I know that it was a horrible experience.

So we appreciate it.

Thank you.

Hi, I'm Erin Welsh.

And I'm Erin Allman Updike.

And this is this podcast will kill you.

And today we're talking about none other than norovirus.

You know, Erin, I was getting ready.

for like for tonight, like, you know, brushing my hair or whatever.

And I was like, have I ever had norovirus?

And for some reason, this, that in that moment, after spending a week reading about norovirus and writing about it, that was the first I actually wondered if I had personally experienced it.

And I think yes is the answer.

Yes.

I feel like I can remember times when you almost certainly had norovirus.

Are you thinking of the one when I was in Finland and I had to get off the bus in the winter and barf everywhere?

That one was very bad.

I remember that.

That was really bad.

I feel like there were several other times too when you had really bad GI things.

And I was like, yeah, it's probably norovirus.

Oh my gosh.

I can very distinctly remember the most recent, the most memorable time that I almost certainly had norovirus.

Don't know what else it would have been.

I mean, I guess there's many other things it could have been, but it was when.

My older son was in daycare when he was a baby and all the other kids at daycare had had some barfing thing.

And then both Brett and I got it and my kid did not.

And I was like, What is this?

I don't get it.

We'll talk about it.

Wait, though, okay, yeah.

Oh, okay.

Um, yeah, I have so many questions already.

We can't do this.

That would be the earliest yet for

on record for us.

Uh, yeah,

we'll get there.

I can't wait first.

But first,

it's quarantining time.

Quarantin time,

Erin, what are we drinking this week?

We're drinking the cruise.

shs.

I mean, I think that for most of us, when you hear norovirus, your first thought is, oh, that thing that happens on cruise ships.

For me, it's the opposite.

Like when I hear cruise ships, the first thing I think of is norovirus.

Oh, it's norovirus.

Well, in any case, I don't know if we can dispel that, but we will dispel the fact or the notion that cruise ships are somehow the only place that you can get norovirus.

Oh, yeah.

It's far far from the truth.

I've never been on a cruise and I have gotten norovirus.

So N of one counts.

But we decided to make this delicious, not delicious sounding quarantini a martini because martinis pair really well with another great source of norovirus, which is oysters.

None of this sounds appealing in all honesty, but no, I know.

We're going to make people like never eat food again or have fun again.

It's going to be a great episode.

Yeah, it's going to be awesome.

I mean, there's really nothing you can do.

Yeah.

No, we'll post the full recipe for that quarantine-y and our non-alcoholic placey burrito on our website, thispodcastwillKillyou.com and all of our social media channels.

We certainly will.

On our website, thispodcastwillKillyou.com, it is a treasure trove of things, of links that you can click,

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And then you can find non-link things like our sources for all of our episodes and other stuff.

Check it out.

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Well then.

Any other business?

Rate, review, subscribe, merch.

Check it out.

You got a cool merch.

Yeah.

Should we just get into the biology of norovirus?

Let's do it.

Let's take a quick break and then get nauseous together.

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Norovirus is an RNA virus.

It's in the family Calisseviridae, which I don't think that we've ever covered any viruses in that family before, except

Erin?

RHDV.

RHDV.

Yeah, rabbit hemorrhagic disease virus.

Yes.

It's like that came out fast.

We talked a little bit about that in our myximatosis episode, but then Erin, you interviewed an expert on rabbit hemorrhagic disease virus.

So

Robin, she's amazing.

Check out that episode.

Yes.

It's such a fascinating story, too.

But anyway.

So these are RNA viruses.

They're small.

They're round.

They are a family of viruses that infect a pretty wide range of mostly vertebrate hosts.

And the one that we're talking about today, norovirus, there are a bunch of different genotypes and it's a few of them, mostly one, two, and four, that are the ones that cause the most human disease.

And norovirus is a human enteric virus, which means it's infecting and causing us to get sick in our guts, our GI tract.

Oh, yeah.

And like many of our GI tract infecting friends on this podcast, be they viral, bacterial, or otherwise, norovirus is spread through fecal oral contact, which means poop gets in your mouth.

Yep.

But good stuff.

Great stuff.

Norovirus gets a lot more creative than that because norovirus has been shown to be spread through aerosolized vomit.

You know, Erin, when I learned about that, I was just in awe

of both the fact that norovirus can do that, but also that we're not all constantly sick with norovirus.

It's disgusting.

It gets so much more disgusting, Erin.

Excellent.

Just keep it, just keep piling it on.

I'm ready.

Literally.

Aerosolized vomit, that's a way that it can spread.

It also is a frequent offender in contaminated food.

And with norovirus, food is often contaminated either at the point of production, think about things like spinach recalls, etc., from like when it was packaged, as well as the point of preparation.

So that kale salad that you ordered and someone didn't wash their hands that well.

We also see water contamination, not just drinking water, but also oceans, rivers, you name it, and in general, contaminated environments.

And here's where it starts to get even worse.

Okay.

It starts to get

it.

It's just beginning, Erin.

Norovirus is an incredibly infectious virus.

It often takes less than 100 viral particles to produce an infection, which is not a lot of virus.

And when people get norovirus, when they're infected with norovirus, they're pooping it out.

It's shed in their feces and people can shed it for an incredibly long time, even if they never show any symptoms of it.

Do you have a question, Erin?

Yes.

Yes, Erin, I do.

I have multiple questions.

So number one,

how long can people shed?

Number two, asymptomatic.

Tell me more about that.

Oh my gosh.

I'm so excited.

Except it was not the exact two questions that I thought you were going to ask.

Oh,

what did you think of that?

I'm going to ask you.

I have two questions from you right here, and I have those two answers.

Okay, okay.

Let me see what else I could ask.

You said that

they shed?

I said they shed a lot of virus in their poop.

How much virus do they shed in their poop?

So glad you asked, Aaron.

Okay, let me answer these one at a time.

How long can people shed norovirus?

At a minimum, we're talking seven to ten days, but many studies suggest four to eight weeks, Erin.

Excellent news.

Really great news.

How much virus per poop?

Literally, so glad you asked, because if you hadn't, I was going to tell you, anyways.

This is mind-blowing, Erin.

People shed anywhere from a hundred thousand

to 1 billion viral particles per gram of poop.

No!

That is not possible.

Per gram.

Do you want to know how much a gram of poop is?

Because the amount of time that I spent looking this up is not insignificant.

A gram of feces

is about a quarter teaspoon.

We are talking at a minimum, 100,000 to a million, up to a billion.

Some papers say even potentially more, but I couldn't do that math

per quarter teaspoon of poop.

And as we'll see, norovirus often gives you diarrhea.

So it's not like a small amount that you're pooping.

No, it's easily in the cups to liters range of things, right?

Yes, easily.

Okay, like a pinch, a pinch of poop contains

billion, potentially.

Yep.

How are we not all infected all the time?

I ask you again.

And then once people poop it out, this virus can also survive in the environment for how long, you might ask?

Another great question.

Two weeks on surfaces and up to two months in water.

And yes, I have not two months, but two citations to back all of these ridiculous numbers up because they're ridiculous.

Yeah.

Okay, so it really was like the tip of the poop iceberg.

Yes.

When you said things are going to get worse,

I didn't fully appreciate that.

Yep, you're welcome.

Excellent.

And Erin, to continue answering your questions, asymptomatic carriers.

Yes, asymptomatic individuals can.

harbor this virus and continue the cycle of infection even without ever suffering its consequences.

And I knew that you would ask, how often is this asymptomatic and what's the deal here?

I don't have an exact answer as to how often people are asymptomatic.

But in various studies that have been done during outbreaks, just where they would check, for example, like random kids poop in daycare centers and things like that, the range was anywhere from like 11 to 40 percent of people that they examined in these various studies who didn't have diarrhea would end up testing positive for norovirus, depending on the setting that they were studying.

People, so potentially a pretty high amount of people can harbor norovirus and not necessarily have symptoms from it.

And I'll get into a little bit more detail as to why that might be.

Yeah, blood types, etc.

I'm curious.

Kind of, kind of.

Okay, yeah, because I was trying to read about it and then I was like, ooh, don't spoil yourself, but also, wait, what?

And then I couldn't understand it.

And then I was like, just leave it to Erin to tell you later.

But,

okay, in these studies, these are, are these like high-risk environments or during outbreaks?

Or is it just straight up, we're going to go to an elementary school, which I guess could maybe could be considered a high risk environment?

Right, right.

Depends on your definition.

It was a variety.

So there was a bunch of different studies that were cited in a bunch of different review papers.

And some of them were like.

during outbreaks where they tested people who maybe were associated but didn't have symptoms.

And so you might think that they were more likely to be exposed.

But then other studies where they, yeah, just checked random kids poop in daycare centers to be like, how many of these kids are pooping on norovirus?

And so that's why there's such a big range.

Okay.

Yeah.

And like, I mean, how many of these kids maybe like had norovirus like three weeks ago?

And then so they're still pooping it.

I don't have those numbers.

But in any case, you definitely can have asymptomatic carriers.

Yeah.

If you're going to be symptomatic from norovirus, the incubation period is usually quite short.

It can be as short as 12 hours.

More often, it's between 24 and 48 hours.

And there is only one good thing, if there is any good thing about this virus.

The silver lining.

Let's hear it.

Yeah.

It's that it's almost always self-limited.

And so the symptoms are usually pretty short, about 48 to 72 hours, like two to three days.

Just three days of literally barfing water that you're trying to to ingest.

I know.

It's not, I didn't say it was good news.

I just said

the closest that we come.

Oh my gosh.

Yeah.

Well, anyways, I think that we got a really great description of symptoms in our firsthand account.

So thank you again so much for being willing to share your story with us.

But I will go in once again to a little bit of detail for us on what the symptoms of norovirus look like.

Paint a picture, if you will.

Oh, please, yes.

For any of us who have, Erin, myself, listeners, ever woken up, or just like you're going about your day feeling normal, and then suddenly in the middle of what you thought was going to be a normal day,

you just start feeling a little bit like trash, like kind of all over.

You just start feeling like unwell in your body.

And then you start to feel a little bit nauseous.

And then shortly thereafter, you start just, just vomiting, just really truly vomiting your brains out.

And then after that, you have body aches and maybe a bit of a fever, some chills.

You think you can drink some water, you vomit again.

And the next time that you vomit, you poop all over yourself on the bathroom floor and then feel so horrible that you cry about it and you're still fevering.

And this cycle repeats itself a few more times throughout the night.

And you wake up the next day.

It's still kind of going, though maybe you know when it's going to be diarrhea and when it's going to be vomit.

The age-old question.

You never quite know.

Then you survive on sips of Gatorade.

You wake up the next day feeling a little bit improved and you think, is it it over?

You nibble on some crackers and you think at least you'll survive today,

you probably had norovirus.

Yep.

So that's usually how it goes.

It's usually vomiting predominant at the forefront, often with fever, headaches, body aches.

and usually moving into diarrhea, which usually comes after the vomiting.

But these symptoms are all a little bit nonspecific, and none of them are like an absolute clincher.

That's just kind of the most common scenario.

And like I said, most of the time this lasts for just a few days and then you get better on your own.

If it happens in the setting of an outbreak or a little mini outbreak where it just spreads through your household, then you also notice or might notice this really short incubation period where you get sick and then a day and a half later, later, your husband gets sick and then a day and a half later, your friend who came over gets sick, etc.

So that is the most common way that we see both outbreaks happen and individual cases.

But that does not mean that norovirus can't be more severe because it absolutely can.

So especially in people with comorbidities, be they just age.

So kids who are very, very young under the age of five are more likely to get very ill because of the diarrhea and vomiting that they have with norovirus.

And same thing with our elders, those who are over 75, 80, even over 65, if they have other comorbidities.

And more and more in recent years, we are also seeing that people with various immune deficiencies have the potential to have a more severe infection.

And that didn't always used to be the case, which is interesting.

And we're not quite sure whether it's changes in the genotype of the virus or what exactly is the reason for that.

But in these populations, then norovirus can cause a severe enough infection that people need to go to the hospital for IV fluids or supportive care, and people can end up dying.

We will talk in the current event section about how many people die, but it's hundreds of thousands of people a year who die from norovirus infection.

In the tiniest of babies, so teeny tiny newborn babies, norovirus can also cause something called necrotizing enterocolitis, which sounds bad because it is bad.

And this means essentially that the bowels, the guts die.

And this can be very, very severe for these babies.

That's awful.

Yeah.

So that's the main story when it comes to norovirus.

But usually, in this podcast, in these episodes, I like to try and dive into more detail on like how do these viruses like make us sick

but here's where things get interesting as if this wasn't interesting enough already uh

right here is where things are interesting everyone at the moment how many

timestamp

with norovirus we don't have an animal model for norovirus

So we don't have a lot of data on like, how is it entering our cell?

Which cells is it entering?

Why does it cause so much vomiting?

Why does it then cause diarrhea?

Like we don't really have a lot of that level of detail on the pathophysiology of this virus, which I wasn't expecting in all honesty.

But here's what we do have, Erin, and it gets at your question of asymptomatic carriers.

Yeah.

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I don't know if this is when this data first started, but I was reading this paper that cited a really, really old study that has since been verified.

And now we have some data as to why they found these results.

There was this old study that showed they took a group of people and they challenged them with poop, norovirus, a bunch of poop.

Yeah.

Like 12 of them.

And half of them got sick and half of them didn't.

And then they re-challenged those same people with more poop.

And when they re-challenged them, The ones who got sick the first time got sick again.

And the ones who didn't get sick the first time didn't get sick the second time either.

So the researchers were like, what?

That's weird.

Why?

And why is this like a repeatable finding?

You might think like, oh, well, maybe just someone wasn't exposed to as much or whatever.

It turns out that this who gets sick and who doesn't might have and likely has something to do with a combination, of course, of the many different strains of this RNA virus, because there's a lot of different strains, but also our genetics, and specifically some of the sugars that attach to our red blood cells.

It's so weird.

It's so weird.

It's weird.

It's not our blood type specifically.

So, Erin, you mentioned blood type.

We have an ABO blood typing system, which more accurately should be called an ABOH system, but everyone ignores the H.

And I'm not going to get into a lot of detail on the blood typing system because it doesn't actually matter that much for norovirus.

But

these sugars, they're called antigens.

These antigens that are attached to our blood cells also get secreted into our saliva and other mucous membranes.

including other antigens as well, like Lewis antigen.

There's a few others that people secrete.

However, some people

don't secrete these antigens into their saliva.

And these people are called non-secreters.

And non-secreters happen to be somewhat protected from norovirus.

Why?

Why?

Great question.

So these histoblood group antigens, these are HBGAs, and it's the A and the B and the H, et cetera, these are the receptors that the virus binds to on our cells.

And so the thought is that because non-secreters just don't have as much of this in the environment for the virus to bind to in your mouth or in your gut or wherever you're getting exposed to this virus, then that is why they are at least relatively protected because they just,

it's not there for the virus to bind to.

Mm-hmm.

That makes sense.

Okay.

Yeah.

It's not that satisfying of an answer, but it's interesting.

I mean, it makes sense.

It's like, it's logical.

But also, I just want to know, like, why, what else is this involved in?

Right.

Yeah.

Do you mean just like the blood types and stuff?

I feel like when people realized that blood typing was a thing.

Right.

Or that we had these, you know, different blood types, that it was going to answer everything.

Right.

Or at least that's my perception about it.

But then it turns out it doesn't really seem to have all that much effect size in terms of differences.

Yeah.

So it's interesting that like, and again, I know this is not blood types, but it's, you know, on the fringe of that.

Right.

It's, it's related to your blood type.

And if what is very interesting to me is that it's not necessarily that like someone with this blood type is a necessarily a non-secreter, right?

Like those two things don't go hand in hand.

And at the same time, at least some of the data that I saw suggested that maybe some people with you, Erin, blood type AB, might be relatively protected.

So here I am calling you a norovirus queen when it's me.

Yeah,

I

have had norovirus.

So well, I mean, there's who knows, maybe it was adenovirus.

There's a lot of others.

In any case, though, that's what we know about the like nitty-gritty of norovirus.

When it comes to diagnosis, a lot of times, like we did for ourselves during this episode, Erin, we can clinically diagnose norovirus,

especially during outbreaks.

There's a really interesting set of criteria that you can use to diagnose norovirus during outbreaks, even without having molecular tools.

And it holds up even like many years after people came up with this criteria.

They went back and looked at outbreaks that they had like PCR data and they were like, wow, these criteria actually do a pretty good job.

It's essentially that like.

almost everyone's vomiting, like more than half of people are vomiting.

The incubation period is 24 to 48 hours.

The total duration of illness is between 12 and 60 hours, and not total, but like the mean duration of illness.

And that in the people that you were able to get samples from, you didn't find any bacterial pathogen, obviously.

Right, right, right.

Yeah.

But so those are like the outbreak criteria that people can use.

And the bummer is we still don't have any specific treatment for norovirus.

And so when people do get very ill from norovirus, all we really have is supportive care.

And we still still don't have any vaccine, but there's a lot of work being done.

So

prevention is really the key to norovirus.

I mean,

hand sanitizer doesn't work.

No, but washing your hands does.

Yeah.

But it's still our tagline.

One of the, yeah, one of the outbreaks that I read about was on the Pacific Crest Trail in 2022, I think.

And I think that last year is when the CDC was like, oh, we connected the dots.

It was norovirus.

But basically on the trail, people were getting, who were doing a through hike were getting super sick after staying in like this cabin or whatever.

And I feel like I saw someone at TikTok on TikTok who probably had gotten that.

Anyways, sorry.

Oh, like from like on the PCT.

Yeah.

Yeah.

Yeah.

And like it completely makes sense to me, even though I never would have thought of it before.

When you're hiking and camping, especially if you're like doing backpacking, like you can't, you don't get to thoroughly wash under running water 20 seconds, 25 seconds, whatever it is.

It's just,

yep.

And so there was-I mean, unless you are lucky enough to have a stream where you can, but then you're washing in stream water.

So then you're washing in stream water.

And yeah, then what a horrible place to

also have non-stop vomiting and diarrhea, just like potentially backcountry trail.

Yeah.

Yeah.

Yeah.

So, Aaron, can you tell me where did this virus come from?

How is it here with us?

What, what, all about it?

Let's let's do that.

Let's let's get into it right after this break.

The first part of our story begins in 1929 with a report written by John Zahorski, a pediatrician in St.

Louis.

In this report, titled Hyperemesis or Hyamis or the Winter Vomiting Disease.

The Winter Vomiting Disease.

The Winter Vomiting Disease.

In this report, Zahorski describes how he's observed and treated epidemics of gastrointestinal illness over the past 30 years, over his entire career, and they all tended to happen in the winter months.

And this report seemingly struck a nerve with other pediatricians who were like, yeah, mass outbreaks of vomiting in the winter, a lot of kids.

Yep, that sounds familiar.

Been there, done that.

And they also had been wondering, like, what on earth could this be caused by?

Is it one disease or not?

The most popular working theory at the time was that it was milk.

Milk?

Milk.

Like cows' milk.

Like cow's milk.

Yeah.

Like, and specifically that milk, having been delivered on the doorstep, would freeze in the winter months.

And then it would pop, the liquid would expand and freezing, and it would pop off the bottle top, exposing the milk to some sort of contamination.

How interesting.

Because then it would only happen in places that get cold enough to freeze.

It's not happening here.

Yeah.

Okay.

You know, it's not happening in the future because of global warming.

So,

but the milk hypothesis was not right.

Zahorski, in a later report describing a multi-thousand strong outbreak in St.

Louis in 1940, he agreed that milk, yeah, it's probably likely to blame and that it was probably something to do with an overabundance of bacteria despite pasteurization in the winter months.

It was, this was a hunch, like there was no evidence to back this up.

And his idea, this idea of his was not borne out in subsequent outbreaks where investigators could find no single food item or exposure linking everyone together.

And that particular characteristic of these outbreaks is sort of the randomness of it, or the not so much randomness, but just like, how did everyone get sick?

And the timeline of things that called into question whether or not this was a distinct clinical entity or just coincidence.

So I came across a paper from 1943 titled, Is There an Epidemic Vomiting Disease of Winter?

Question mark?

Like, just like, does that, is that even a thing?

Does it exist?

And I think their conclusion was like, maybe?

Interesting.

More research.

Yep.

And then there was another paper that I read that detailed an outbreak in Charleston, South Carolina in 1941 and 1942.

And at the end of it, the author of this paper writes, quote, this account adds very little to the knowledge of the vomiting disease.

And quote.

We did all of this work and we know nothing more than we did before.

Honestly, like I can empathize a lot with that feeling.

I can, but I also cannot imagine a paper today getting that does not overstate.

Like,

and then this has the potential to greatly influence our knowledge of X, Y, and Z.

Oh, that's really funny.

But I loved it.

But yeah, and then the paper does go on to say that hopefully, though, this will get people more interested in winter vomiting disease.

And it did.

There continued to be sporadic reports about winter vomiting from all over the globe, trying to make sense of an acute gastroenteritis that seemed to strike members of a family at random, where there seemed to be no central point of contamination, and where no one had found consistently an infectious agent responsible for the infection.

But for the most part, epidemic winter vomiting was kind of like a background player on the foodborne illness outbreak scene for decades.

And it just didn't draw nearly as much attention or resources as bacterial contaminants like salmonella or E.

coli, which were much more easily detectable, which also made them the biggest targets for food safety measures.

Okay.

And this lack of appreciation continued even after the causative agent of winter vomiting disease or acute infectious non-bacterial gastroenteritis, which is also such a mouthful.

I mean, let's go back to winter vomiting disease.

I guess norovirus is fine, but

so the causative agent of this was discovered in 1972, and still people didn't really care that much about it at the time.

Ah, interesting.

And so, when it was discovered, it was given the name the Norwalk agent.

Later, it was called Norovirus, but at the time, the Norwalk agent.

Do you want to know how it got the name Norwalk

Agent?

Okay.

In October of 1968, at an elementary school in Norwalk, Ohio, it was right around Halloween time, 50%,

116 of 232 of the students and teachers at this elementary school came down with acute gastrointestinal illness.

50%.

50%, like all like within a day or like what?

The burn.

Death was within 48 hours, but I think it was like not over a very long period of time.

Right.

It was not a slow burn.

It was,

yeah.

Flush flood, I guess.

Just imagine the smells.

Yeah.

Oh, my God.

I mean, and elementary school.

No one can hold that.

There's not enough sawdust to cover the vial.

Oh, the elementary sawdust.

Yeah, yeah, yeah.

I can still picture it and smell it.

Exactly.

Oh, yeah.

And then, but of course, because it's norovirus, the illness didn't stop there.

It spread to other family members and then friends and other contacts in the community.

And so public health investigators were like, oh, God, what is happening?

We let's test everything we can.

We're testing water, we're testing food, we're testing poop for bacterial agents.

And they also surveyed the students and the teachers for any sort of commonality.

And they came up empty.

to the researchers this strongly suggested a viral origin but

how do you prove that back then

not filtering something something yeah right

no not not that

well my answer here was two words human volunteers oh yes

there was a

surprising to me number of papers that talked about all of the human volunteer studies that they did with norovirus where they were like, and then these 12 people, we fed them poop, and then we fed them poop again, and then again.

And I was like, who are these people?

Who are these people?

How can you be saying this so casually?

Like

fecal, like oral administration of stool filtrates is what is the technical words?

Yeah, that's just poop in mouth, dude.

Poop in mouth.

Horrible.

Okay, and so in this specific instance, they took poop, like actual poop or rectal swabs from people in the Norwalk and other outbreaks.

And they added some special ingredients like veal infusion broth, bovine serum albumin.

And then they shook it all up and then filtered so that at the end result was this nice little cocktail of filtered poop.

The filtrate, the liquid that came through was then treated with antibiotics and then, yeah, fed to the volunteers, which in this study was a mix of, you asked who are these people, a mix of male prisoners.

So a mix of men

volunteers.

Uh-huh.

And then they also said, so we had, I think, I don't remember the exact phrasing, but it was like these 50 male prisoners and then, quote, normal volunteers.

Oh, dear.

Oh, actually.

Yeah.

Informed consent was obtained.

They clarified that.

But

pretty much everyone who was fed samples from Norwalk got sick within 48 hours.

A few remained asymptomatic.

Interesting.

And one person in the study vomited approximately 20 times within a 24-hour period and needed like fluid administration.

Uh-huh.

Yeah.

Just 20 times.

I just.

20.

Yeah.

And I'm not sure if it was this paper or a different paper because this, like we talked about, this fecal or this administration of fecal whatever was done multiple times.

But in one of those studies, the researchers wanted to test for immunity.

And so they tested the volunteers again.

They exposed them again to more poopy samples.

Yep.

I mean, can you imagine like vomiting 20 times in an hour and then getting better?

And then a few, I don't know how long it was afterwards being like, so do you want to, do you want to go through that again?

Do that.

We don't know the likelihood.

Yeah.

But yeah.

But fortunately, there was enough immunity that the person or the people who were tested again a second time didn't get sick.

Okay.

At least in that instance.

With the help of these volunteers, researchers were able to demonstrate that, yes, winter vomiting disease was a viral infection.

And it also helped to lay out some of the infection characteristics like incubation period, like how many times you can hope to vomit or poop your pants in a 24-hour period, stuff like that.

Right.

And because these samples were from Norwalk are the ones that got people the most consistently ill, hence Norwalk agent or Norwalk virus.

Yep.

A few years later, researchers Kapikian and colleagues visualized the virus for the first time.

And that was fantastic news because it meant that if you suspected an outbreak of Norwalk virus or Norovirus, you didn't have to spin down poop and then get a bunch of volunteers to feed it to them to prove that you had a virus on your hands or this virus on your hands.

You could just like look for it in the samples.

Right.

Actually find the virus.

The virus.

Unsurprisingly, being able to test for norwalk-like viruses or noroviruses as they were soon to be called led to the virus being detected in more and more outbreaks of acute gastroenteritis.

But it still remained a really underappreciated cause of AGE, acute gastroenteritis, because I don't want to keep saying that, until the late 1990s, perhaps because of the long-standing belief that viruses were rarely responsible for AGE and that most cases were down to E.

coli or salmonella, but also because norovirus infections tended to be self-limiting.

And so not everyone sought treatment for them.

And so that a lot of cases went underreported or undetected.

Right.

You don't appreciate the full scale or scope of it.

Exactly.

Yeah.

Yeah.

Yeah.

And there could be entire outbreaks that you just completely miss too, right?

But this also meant that the food safety measures targeted primarily foodborne bacteria and weren't necessarily effective against norovirus, which is a different beast entirely.

Things like, I think, chlorination or refrigeration, some of these things, I mean, like we talked about hand sanitizer, norovirus is like, okay, nobody, like, I'm not bothered at all.

So,

and we can kind of see this in action.

So, between 1993 and 1997, more than than 2,500 foodborne outbreaks were reported to the CDC in the U.S.

And 68% were labeled as unknown etiology.

Like, great question, we don't know.

And less than 1% were attributed to noroviruses.

That just means that they didn't look for norovirus in 68% and they would have found noro or another virus in most of those.

Yeah.

Yeah.

And then, though, the advent of reverse transcription PCR in the 1990s made detection of noroviruses even easier.

You didn't even have to look under a scope.

And they began to draw more and more of the spotlight.

And so today, they're estimated to cause about 50% of all foodborne acute gastroenteritis cases in the U.S., which is a lot.

The numbers are wild, Aaron.

They are truly.

And to borrow from the title of a 2005 paper, are noroviruses noroviruses emerging?

Probably.

They're making up a bigger piece of the foodborne illness pie, partly because of better detection, partly because of food safety measures leading to a drop in bacterial foodborne outbreaks, and partly because our behaviors are changing around the globe.

Global travel, the cruise ship industry, which I know makes up only part of the norovirus story and also probably is we have such that link because the reporting is mandated, whereas I think it's not like at home.

with norovovirus.

Yeah, no, like especially not like single out, like single cases are not like norovirus is not a reportable illness, right?

But if there's an outbreak on a cruise ship, that's definitely reportable.

And so, I think it just sort of like underlines the link between norovirus and cruise ships, is that it's just like, yeah, important to identify

what it is.

Yeah.

But then there's also things like irrigating crops with sewage-contaminated water, the globalization of food distribution, contamination of fresh and seawater leading to higher accumulation by shellfish.

And as norovirus continues to grow, as we enable it to grow and spread, it's also evolving.

We've already seen genetic changes in globally circulating strains, which may impact transmission efficiency.

Norovirus isn't going anywhere anytime soon, unless there's a vaccine on the brink of introduction and you're about to tell me about that, Erin.

Maybe fingers crossed.

No, it's not going anywhere anytime soon.

Cool, great, awesome.

Well,

until there is a vaccine or something that we can do, our best bet is in controlling the virus, preventing exposure, cleaning contaminated surfaces.

And that takes a better understanding of what exactly it is doing and how it is being spread.

Let's talk about vomit.

Okay.

Yeah.

Okay.

If you have emetophobia, I think that's how you say it.

It's extreme fear of vomiting.

Now might be the time to fast forward if you have made it this far somehow.

Because I felt so nauseous in writing this and reading about this.

Like I had to, I had to stop several times and be like, I got to take a breather.

This is making me feel actually ill.

As a physiological response, vomiting or emesis is an ancient one, like deep time ancient.

So,

so many animals vomit.

Reptiles, fish, amphibians, birds, primates, so many mammals.

It's incredibly widespread in the animal kingdom, with some surprising exceptions, like rodents and lagomorphs, which either never evolved the response in the first place or lost it somewhere along their evolutionary journey.

And this, you talked about how we don't have a good animal model for norovirus.

It might be in part because, like, this has been a challenge because rodents, like, our go-to is labs, rats, lab mice, they don't vomit.

So, that's been a challenge overall in understanding the physiological mechanisms of vomiting and how that pathway is formed, and how different stimuli affect different things, and so on.

The neural responses and linking, is nausea different from vomiting?

Are they on the same pathway or different pathways?

All of this stuff, which is really fascinating, has been difficult to do.

Also, horses don't vomit.

What?

Yeah.

And probably more animals that I missed, but those are the ones that I came up with.

I don't think I've ever wondered if animals vomit because I've always just assumed.

I bought my niece a book called Does It Fart?

Yeah.

when she was younger, like that someone wrote that's a hilarious book examining who farts in the animal kingdom because not all animals fart.

But I just assumed that all animals vomit.

We need a sequel.

Yeah, we do.

I feel like my Google skills are pretty good.

I'm pretty good at searching for things.

I found it difficult to find

a review on vomit.

Well then.

That's another book idea for you, Aaron.

There we go.

I don't know if I could make it through.

It's like,

does it seem to get a little too nauseous?

It might, yeah.

How interesting.

Yeah.

But it's also, it's surprising that it's not more widespread, right?

Because vomiting is a super helpful defensive response.

Like, let's say we eat something poisonous, something that bypasses our other defensive barriers like taste and smell.

Our vomiting response can protect us from being harmed by those ingested toxins.

Morning sickness, which is like nausea and vomiting in the early months of pregnancy, that's thought to be beneficial because it helps to avoid certain foods that might contain more pathogens.

Nausea and vomiting evolved in a very different setting than most of us find ourselves today.

Compared to the past, we're not doing too bad when it comes to foodborne illness and safe food practices, but we still have these super sensitive responses that may at times feel very unwelcome.

Like seasickness or motion sickness, reactions to certain medications or anesthesia.

There are occasions where that vomit pathway is activated where it might not be protecting us from foodborne toxins, but it still happens because evolutionarily it was so beneficial.

And of course, too much of a good thing can be a bad thing, like vomiting that goes on for long periods or happens too frequently during pregnancy, that can be harmful to both the pregnant person and the fetus.

So, like, seems to be beneficial up to a point.

Motion sickness still seems to be a bit of a mystery in terms of why that response would evolve.

Like, does it provide any evolutionary advantage?

Unclear.

We're going to maybe do an episode about it.

And of course, if I think it's on our list, Aaron.

I feel anxious.

And of course, if you're barfing a lot after a bout of food poisoning or a GI infection, you're at risk of dehydration and just like full body system collapse.

And sometimes this vomit response can be co-opted by our little pathogen friends so that they can get to know everyone in your close circle or on your cruise ship.

Researchers have for a long time recognized how important vomiting is in the transmission of norovirus, but it was only relatively recently that they were able to directly measure just how important.

And they did it using vomiting Larry.

Vomiting Larry.

I need to know so much more.

It's a capital V, capital L.

Of course it is.

Yes, proper noun.

So let me introduce you to Vomiting Larry.

So Vomiting Larry was created by the UK's Health and Safety Laboratory.

Picture a CPR mannequin.

You know, like from the one episode of The Office or Erin, you've, you know, seen them, I'm sure, all over the place, but you know that that's the reference.

Yep.

That's what comes to my head.

You can call him Airway Larry.

That's actually his real brand name.

Airway Larry is great for teaching things like intubation, ventilation, CPR, et cetera, because he has teeth, he has a tongue, he has a larynx, he has trachea, vocal cords, cords, just the full shebang of, you know, upper torso gear.

Yeah.

And what you want to do is now remove Airway Larry's head from the plastic organs he came with, like lungs and stomach.

And then you want to attach Larry to a pressurized set of tubes, basically like a mannequin head, mouth fully agape, sitting on top of a long, clear plastic tube.

which you can fill with fluid to then be forcefully ejected through vomiting Larry's mouth.

Okay.

It's incredible

to see.

There's videos, I assume, we can find of course there are videos.

Okay.

And so what researchers did is that they filled Larry's tube with his stomach, his food pathway with fluorescent fluid and let her rip.

And when they flip on the black light UV bulbs, they can see just how far his projectile vomit made it.

And so you can do this with differing differing amounts of vomit.

You can do this with like different force.

You can do this with different, I would assume, consistency of consistencies or like different trajectories like towards the toilet versus

make it.

Versus just pure projectile like came on suddenly.

Yeah.

Like my kid all over the couch.

Excellent.

Yep.

Exactly.

Oh, you'll be.

Yep.

Oh my God.

You signed up.

Okay.

So, but they did this with one liter of barf, of fluorescent barf,

which is a lot.

That's a lot.

It's like kind of a worst case scenario.

Yeah.

But in norovirus, sometimes it maybe feels worst case.

So

one liter, most of the one liter that was ejected through Larry's mouth hung around in an area of around 1.2 by 1.6 meters.

So like four by five feet.

Still a lot.

But there were splashes that made it over three meters in front of Larry, over nine feet, like splashes, and seven feet to the sides.

Gross.

Absolutely horrific, but probably not surprising to anyone that has experienced or witnessed projectile vomiting before.

But what that means is that you have a tremendously huge area that you need to disinfect, an estimated 84 square feet or 7.8 meters squared.

Yeah.

I watched a YouTube video of vomiting Larry and another vomiting machine, which is like a mini one.

It's very cute.

I don't know if this one has a name, but it's created at North Carolina State University.

And in one of the vomiting Larry videos, a researcher let Larry spew his fluorescent liquid all over the

arena and then cleaned it up the best that they could under normal lighting.

Oh, love this.

Uh-huh.

And then when they were like, okay, all done.

This looks clean.

I think I got it all up.

Flip on the black light and there's like still spatters

everywhere.

And so I know that vomit doesn't contain quite as much norovirus particles as poop.

The poop.

But still, it's there.

And if it's going to live on that surface for a while,

it is

rough.

But even

more

was that this researcher looked down at themselves and was like, oh, it's on my gloves.

Okay.

It's on my cuffs.

It's on my face.

Because you can imagine if you're cleaning up and let's say that your hair falls into your face, you just,

yeah.

And it's not like this person wasn't trying.

Like they really were trying to clean up every bit possible.

It's just that vomit really goes.

everywhere and norovirus is so so dang infectious

and then, of course, you mentioned the aerosolized particles.

So, part of how we know more about this is creatures like vomiting Larry and the NC state one.

One study detected per cubic meter of air between 14 and 2,400 genomes of human norovirus in healthcare facilities experiencing an outbreak.

Like actual transmissible amounts in the air, just there.

Erin,

I am like both in awe and still terrified of norovirus.

And I would really love for you to tell me that there's some good news on the horizon for this bug.

Okay.

I do have to mention that I have a list of vomit trivia that I didn't know how to squeeze into the rest of the narrative.

So if you would like to hear any of those, I can share them with you or we can just chat later.

I think I'd like to at least hear some of this vomit trivia because what?

Okay, it's just a few.

number one you know the so-called like vomitorium the vomitoria from ancient rome where people would allegedly go to vomit after eating a bunch of you know really rich food gorge themselves and then bulimia yeah yeah that's not apparently there's no actual unsurprisingly like yeah evidence for this vomitoria is a real term that used to be used but it was what the entrances and exits of like theaters or public arenas were called because people would just like spew forth to get good seats or when they're all leaving in a rush.

Oh, that's really funny.

Isn't that great?

Oh, that's good trivia.

These are all over the place.

I love it.

In 1992, George H.W.

Bush barfed on the Japanese prime minister during a visit.

There was a new slang word created,

basically meaning to pull a bush.

So like if you vomited, it was you're pulling a bush.

Oh, that's really funny.

I liked that one.

According to the Guinness World Records, the oldest vomit is 160 million years old and is from an ichthyosaur.

Petrified vomit.

Petrified vomit, yeah.

Fun.

Did you know that there is a...

a diterpenoid substance, like a secondary metabolite produced by certain types of corals in subtropical waters.

And this compound, scientists named it pucolide.

Do you know what pucolide does?

It induces vomiting in fish that consume it.

And so it's a great defensive mechanism for these corals because fish will come up, eat a small amount of it, and then just vomit a lot, which I really like.

Yeah.

You really like that, Erin.

I do like that.

And speaking of vomit as a defense mechanism, I guess, vultures are well known for their defensive vomiting.

This is a quote that I pulled from a paper an older.

Sorry, I did not know this about vultures.

Thank you.

I think I've just been deep in the vomit literature, so it feels like familiar knowledge.

Like, as everyone knows.

As everyone knows, of course.

Those old vultures and their vomit.

Okay, this is a quote that I pulled.

When wounded or entrapped, the turkey vulture has two means of defense.

It ejects at the enemy the putrid contents of its gullet.

And if this is not enough, the bird can play possum, apparently dying.

Doesn't actually die.

It just pretends to die.

Right, right, right.

I know what playing possum means.

That I do know.

I've just been deep in the possum literature, so I wasn't sure.

Oh, wow.

What is this fun?

One last one.

Give it to me.

Okay.

This one makes me nauseous.

This is when I was like really feeling sick.

It's so fascinating, though.

It turns out that our perception of odors can be greatly influenced by verbal cues.

So what do I mean by that?

There was a study from 2001 where researchers exposed participants to various smells that aren't super specific.

You know what I mean?

Like they can be found in multiple different things or sources.

Okay.

And on the first exposure, they said, okay, the source was one thing.

And on the the second exposure, they exposed the participants to the same exact scent, but they said it came from a different source.

Okay.

Then they asked whether the participants believed that the two scents were the same or different.

Okay.

One of these scents was a one-to-one combination of isovaleric and butyric acids.

On the first exposure of IB acid, and this is the compounds, participants were told that they were smelling Parmesan cheese.

On the second exposure, they were told that they were smelling vomit.

83% of them thought that they were smelling two different things.

Oh, wow.

Which as a Parmesan cheese eater, I find really disturbing.

But like also how amazing that your perception of smell or like your response to it can be so influenced by words.

That is really interesting.

Yeah.

There were some other ones like patchouli.

They said this is either a musty basement or incense.

Well, I mean, that's that's just six and one half dozen of the other to me.

So

oh, that's really funny.

Oh my gosh.

But yeah, those are those are all of my vomit trivia that I gathered.

I really loved it.

I really hope that we have a trivia night sometime soon so that I can really pull those out.

The culture one.

Golden.

Well,

I can move us a little bit forward from vomit, if you like.

Please do.

I'm ready to leave this behind.

We'll take a quick break and then I'll tell us what's up with norovirus in the world today.

Norovirus is a very big deal worldwide.

And even though most of the time, as we talked about, it is self-limited, it is also the today

leading cause of epidemic gastroenteritis worldwide across every single age group.

What this means, and you mentioned this a little bit, Erin, is 50% of outbreaks are estimated, at least 50% of outbreaks are estimated to be caused by gastroenteritis, which means anytime that there's like a cluster of people who get sick from a single source, 50% of the time that's noro.

And 90%

of non-bacterial gastroenteritis outbreaks.

So anything that's not bacterial gastroenteritis, it is norovirus.

I want to know what the other 10% is.

Other viruses, most likely, and then sometimes toxins.

Okay, okay.

Yeah.

And it causes countless.

I don't have an exact number of the number of outbreaks, but so many outbreaks.

every year in hospitals, in schools, in military facilities, at fancy resorts, and on cruise ships, literally everywhere.

But norovirus is not just limited to outbreaks.

Norovirus is a cause of regular old gastroenteritis as well.

And it's estimated that overall, norovirus causes close to 20% of all cases of acute gastroenteritis worldwide.

Like every time that someone gets sick and starts vomiting and having diarrhea, 20% of the time, it's probably norovirus.

So what does that number look like?

At least 685 million cases every year.

So we're talking over half a billion cases every year.

Okay.

And while this is most of the time self-limited, we know that this infection can also cause more serious illness.

So it's estimated that norovirus results in 200,000 deaths worldwide, 50,000 of which are in children under age five every year.

And these deaths are primarily in low and middle income countries that don't have access to as much supportive care.

If you want data from just the U.S., it's estimated that norovirus causes 21 million cases every year of acute gastroenteritis just in this country.

And that's about 60% of all cases where we know what the cause was, like where we're able to identify the cause.

This results in 71,000 hospitalizations and over 400,000 ER visits.

Wow.

Like this is not minor because all of that also has an economic burden.

And globally, the total economic burden of norovirus is estimated at $60 billion

every year due to both healthcare costs and economic losses.

I have a question.

about

i'm sorry vomiting again but like at what point what are the signs to be like, now you should go to urgent care, ER, whatever?

Yeah, that's a really good question.

Certainly, if you're not peeing, if you go the day and you're vomiting and you haven't peed all day, that's not normal.

Okay.

So if you have like a reduction in, or if you're looking at your kid's diaper, for example, and they have like one or two wet diapers in a day, that's not normal.

So that's very worrisome.

So we think about urine output.

But also just if you are every time that you try and take a sip of water, you're barfing it back up, then you're not retaining any of that liquid.

So then that's a reason that you would want to seek care.

Or similarly, if every time you take a sip of water, you're just pooping your brains out because it could go either direction, especially with norovirus.

Those are the main.

It's not like an exact number because it's also going to be different for every person, depending on how hydrated were you before you got sick.

How tiny are you?

How young are you?

How old are you?

Yeah.

Okay.

So what do we do about it?

I have a little niche

fun fact.

Since we're doing fun facts in this episode,

trivia.

One of the things I found that is so interesting and cool about Norovirus when it comes to the current research is that there exists a thing called Noronet.

And this is a data sharing network that is this international, quite informal network of people that you can like join.

You can like submit your information to try and join Noronet.

I don't know what the vetting process is like, but it exists.

And it's been around since the mid-90s.

And it's just this international network of people who study norovirus and share all of the detes that they find about it.

So it's mostly genomic data from all over the world.

There's like 25 countries that are represented on every single continent.

And this data sharing network has led to some really important like advancements in knowledge with regards to things like the changes in genotype that we're seeing, with some genotypes being more prevalent now than they were before, or maybe is the virus becoming more virulent, like things like that.

And all of this is really important for the biggest area of research in norovirus, then

vaccine development.

There's a lot of interest in the development of a vaccine.

But we don't have one yet.

That's the short answer.

And what I think is, there's a few things that make it really hard.

One is that, and you kind of mentioned this, Erin, like we do have data that people can develop immunity to norovirus, but what we don't really know is how long this lasts.

We also don't know like how robust that immunity is when we're talking about so many different genotypes and an RNA virus that does mutate fairly rapidly.

And because most people don't get that sick from norovirus,

from an economic perspective, it's hard to maybe think of the incentives for vaccine developers, which is a huge downside when you have capitalism, et cetera.

But what I found really interesting is that there was a cost analysis that they did this like simulation model that said that even if a vaccine were only about 50% effective, so that's like our best flu shot, for example, and only lasted for about 12 months.

So think you'd have to get a norovirus vaccine every year like you do the flu shot, and you'd only have about partial protection.

It was estimated that even a vaccine that met those criteria would save $1,000 to $2,000 in healthcare costs per case averted of norovirus.

And again, there's 685 million cases.

So if you could have adequate vaccine uptake, you could have some pretty significant cost savings.

But how do you get good vaccine uptake?

How many people get their flu shots, COVID shots, etc.

But that being said, there are a lot of people who are working on vaccines.

And the World Health Organization has a great website actually that you can see a list of a whole bunch of different vaccines of various types.

So using different like vaccine platforms, a lot of which are in phase two or three clinical trials as of this recording in 2024 so that's pretty exciting stuff yeah

someday someday

we could maybe prevent norovirus with more than just washing your hands and bleaching the world but until then wash your hands and bleach the world yeah you filthy animals that's not the end of the episode though because we got to tell you about our sources

Okay, I will go.

I have got, Erin, I have so many sources for this.

If you want to to read about Vomiting Larry, I've got a couple papers.

One is from Mackison Booth in 2014 titled Vomiting Larry, a simulated vomiting system for assessing environmental contamination.

And then, in terms of sort of some of the history of norovirus or like the future of norovirus, there's a paper by Widowson from 2005, Are Noroviruses Emerging?

And then if you want to read some of the early work on norovirus, there's a paper from 1942 by Waring titled titled The Vomiting Disease.

And there's a whole lot more that I'll post.

I did the opposite, Erin.

I found a couple really great review papers.

So my list is surprisingly short for this episode.

But there was a great review paper from 2015 simply titled Norovirus from Clinical Microbiology Reviews, and another one from Nature Reviews Microbiology from 2016 called Human Norovirus Transmission and Evolution in a Changing World.

And there were a few other ones looking at the epidemiology of norovirus.

You can find the list of our sources from this episode and every single one of our episodes on our website, thispodcastwillkillYou.com under the episodes tab.

Thank you again so much to the provider of our first-hand account for sharing your awful norovirus story.

Thank you and sorry.

Yeah, thank you.

Thank you also to Bloodmobile for providing the music for this episode and all of our episodes.

Thank you to Tom Breifogel and Liana Squolachi for our fantastic audio mixing.

And thank you to Exactly Right Network.

And thank you to you, listeners.

I really hope that this was enlightening and not just nauseating.

And thank you, as always, to our incredible patrons.

Thank you so much for your support.

It really means the world to us.

It does.

Well, we've said it before, but we really, really mean it this time.

Wash your hands.

You filthy animals.

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