This Podcast Will Kill You - Ep 4 The Poop Show

Episode Date: November 21, 2017

That's right.. this is the poop show! Today we talk cholera- the bacterial disease that makes you liquid-poop your pants (and then some). Travel back in time with us to when London was a sewage-filled cesspool until the Original John Snow stepped in to save the day and created the field of epidemiology. But is cholera a thing of the past? Not so much.  See omnystudio.com/listener for privacy information.

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This is a job for Indeed Sponsored Jobs. As we passed along the reeking banks of the sewer, the sun shone upon a narrow slip of the water. In the bright light, it appeared the color of strong green tea and positively looked as solid as black marble in the shadow. Indeed, it was more like watery mud than muddy water. And yet, we were assured that this was the only water the wretched inhabitants had to drink. As we gazed in horror at it, we saw drains and sewers emptying their filthy contents into it. We saw a whole tear of doorless privies in the open road, common to men and women. built over it. We saw a little child from one of the galleries opposite, lower a tin can with a rope

to fill a large bucket that stood beside her. As the little thing dangled her tin cup as gently as possible into the stream, a bucket of night soil was poured down from the next gallery. I want to say two things. Yes. One, I support the use of the words privy and night soil. Both. Nightsoil, by the way, is human feces used as compost. Poopie, poopy. Poopie. Poop. Also, that's disgusting. That's my second point. So I'm going to give you a little context to that.

Tell me. Tell me, please. That came from an article describing the ground zero of 1849's cholera outbreak in London. That was London? That was London. That's a city. And it was that just poop everywhere. There are a lot of cities that continue to be very poor sanitation just due to lack of funds for public health infrastructure.

Oh my God. Welcome to this podcast will kill you. Episode four. Today we're talking about cholera. I'm Erin. And I'm also Aaron. And before we get into the meat of this week's episode, we want to ask you, dear listeners, dearest darling listeners, to rate, review, and subscribe.

Because we love you. And we want to know how much you love us. Just kidding. But not really. Rating, reviewing, and subscribing is how other people. people are able to find our podcast. So wherever you listen to your podcast, please, please, please take a moment to just, you know, click five stars or whatever. Or, you know, anything you want, whatever's in your heart. And also, we are on all the social medias. We're on Twitter, Instagram,

Facebook. So, you know, if you want to keep up to date on little trivia about whatever infectious diseases, you know where to find us. See some grody photos. And also get our drink recipes. Oh, yeah, that's important. Yeah. Okay, Erin, I want to hear about cholera now. Tell me all about it. Let's talk about it. As it turns out, which I did not know before doing this research, cholera is really complicated. It's a complicated little bugger. Uh-oh. Yeah. So I'm going to hit on the real basics of the biology of this disease. And I want to encourage y'all to read more or, heck, if you research cholera and I get it wrong, give us a shout out. Let me know that we're so. incorrect about things. We are open to being corrected. Very open. Okay, so cholera. Cholera is a disease that's caused by a bacteria called vibrio cholera, which is a facultative pathogen. So that means that in

addition to causing disease in humans, it also can persist in the environment and reproduce in the environment. Usually in water, especially brackish water, so like at river mouths near the ocean and things like that is where it persists. Can you give me an example of an obligate pathogen? Smallpox. Okay, so smallpox, it can exist in the environment, but it can only persist if there is a human host for it to infect. Exactly. It can't reproduce without infecting a host, whereas cholera can actually reproduce in the environment. But there are also bacteria, maybe leprosy bacteria, which also can't reproduce without being in a host. It's also an obligate pathogen. Rocky Mountain spotted fever.

Yeah, definitely. Right. Cool. Okay, so generally cholera is transmitted fecaly orally, which means you have to ingest fecaly contaminated water or food, especially shellfish, which live in water, right? Really? Yeah, icky. Because a lot of shellfish are filter feeders, so they just filter all the poop out of the water and then you eat it.

Yum, you want to get some clams after this? So that's how you actually get infected. The infectious dose of cholera is actually really high, which means that you have to ingest a whole bunch of the cholera bacteria to actually get infected. And there are a bunch of different strains of the vibrio cholera bacteria, but only two of them actually cause the vast majority of the disease. And part of the reason that the infectious dose is so high for cholera is first because it has to survive the super acidic environment of your stomach because you ingest it, right? I think I actually read something about how people who take antio acids have higher chances of getting cholera. Yeah.

Did I preempt you? No, not at all. I wasn't going to talk about that, but I definitely saw that too. So if you lower the acidity in your stomach, it makes it easier for the cholera to get through that really harsh environment. Super cool. I've also heard something about that along the same lines with stomach cancer. Oh, really?

Question mark. Just because there's like various bacteria that can be associated with stomach cancer? No, well, potentially that, but also because acid will kill off the more like bad cells basically earlier. Oh, that's really interesting. And so if you don't have that pressure. Yeah. I don't know. I mean, this is all like me.

This is what scientists shouldn't do, which is just reading abstracts of things. You don't happen, though. Okay. And the other reason that there's a really high infectious dose is that after a cholera bacteria survives your stomach, it actually has to swim all the way through the rest of your GI tract and into. to your small intestine. So it has a little flagellum, which is a tail. So these bacteria actually look like spermies. Little sperms. I think that they make giant microbes of cholera. I think they do. That are really cute. Not probably as cute as Gerardia, because that's the cutest. It's so cute. It looks like a little Rastavarian. So once the little spermy bacteria get to your small intestine,

they attach themselves to your intestine wall and they begin producing, cholera toxin. And this is what actually makes you sick. So it's not the bacteria alone. It's the fact that the bacteria produces this toxin. And what's super crazy and cool about this toxin is that it is actually produced by a bacteria phage. A bacteriophage is pretty much a virus that infects bacteria. I don't know why we have to call bacteria viruses something different, but we do. They look really cool. They are really amazing. One time in college, We got like Hena paint, and we were all painting Hena and my roommate, Jocelyn, who's awesome, painted the most beautiful bacteriophage on her arm.

And I was like, that should be a, I want that. It's beautiful. Oh, that's great. Yeah. So anyways, this bacteriophage has basically inserted part of its genome into the cholera genome, and that is what's actually producing this toxin, which is super interesting to me. That's fascinating. Yeah.

And also, are you going to tell me how this toxin? works because I need to know. Yeah. So basically, this toxin essentially prevents your body from absorbing any water and forces you to push out all of the water in your body out of your intestine, which means you're basically pooping water. Oh my gosh. Yeah. I'll talk more about it in just a minute. Okay. So the incubation period, which we've talked about before as the period from when you get infected until when you show symptoms, for cholera is about one and a half days. Wow. That's very fast. They're super fast little swimmers, and they usually attach themselves to your small intestine within 12 to 72 hours of infection. So they're super quick. And another thing that's interesting is that there's

kind of a range of symptoms. So some people who get infected are almost entirely asymptomatic. Some people have a rather mild infection. And the ones that we'll talk about the most today have very, very severe infections. And the severity of the illness is likely based both on prior exposure. So if you got it when you were young, and then you get it again when you're older, you're a little better off. But also on infectious dose, since like I said previously, it actually takes quite a lot of bacteria to really get you infected. But in the severe cases, which let's face it, that's what we're here for, basically what happens is you just start pooping your guts out.

Oh, boy. So really, like, you just poop all of your water out. Adults that have severe infections can poop out, get this, more than a liter of fluid per hour. Oh my God. Are you serious? I'm totally serious. I have so many questions right now.

How long can you live by pooping out a liter of fluid an hour? I'm so glad you asked because I did some research. So we have four and a half to five liters of blood in our body, right? And that's the fluid that's the most available for you to get water out of. Oh my gosh. If you think about that. Whoa. Right.

And then we've got another 15 liters of fluid or maybe 10 liters of fluid that's surrounding all of our cells. That's the, we call it interstitial fluid in between ourselves, right? So that's 15 liters. But that's like all the fluid that you have available until you start sucking your actual cells dry. Whoa. Oh, my God.

Yeah. So is this where the disease got its character? characteristic symptom? It does. And what's that called? It's called rice water stool. Why is it called that? Because the poop that you're pooping out is literally all bacteria.

It's just like tons of bacteria and water and dead cells. And it looks like what murky, flaky? Yep. It looks like, so if you took a bag of rice and you soaked it and then you drained the rice out, that's what left. And what are we drinking right now, actually? Because we forgot to do quarantinis early. You're right. You're so right about that.

Tonight we're drinking ricewater stool. Can I provide a little correction? We're drinking a quarantini that we named ricewater stool. It actually is composed of cholera bacteria. No, just kidding. It's composed of rum chada. About one and a half ounces of rum chada. Chai.

Three ounces of chai concentrate or a really strong chai tea. And a half an ounce of whiskey. Yep. Feel free to add more whiskey. It'll just look more realistic. Because it will curdle. Yeah. But the most important part of this recipe is to gently warm it to body temperature.

It's actually pretty delicious. It's surprisingly good, you guys. I don't like warm. drinks that are like alcoholic, but this is, it's tasty. It's perfect for this time of year. It is. It's really good. Oh, happy Thanksgiving.

Happy Thanksgiving. Yeah. Rice water stool. Cheers. Cheers. Cheers. With our mugs. Yeah.

So severely ill patients will have poop that is literally a trillion individual bacteria per gram of poop. Whoa. Whoa. Whoa. Yeah. Whoa is right. I did that like a hundred times to make sure I was getting the number right. It's absolutely ridiculous. Which also makes sense why epidemics happen and are so easy to spread.

And the other reason is because, like I said, not everyone gets the severe illness. So people who have a mild illness are still pooping out about a million bacteria per gram of poop. And even patients who are completely asymptomatic can be shedding about 10 to 100,000. bacteria per gram of poop. That's really interesting. Yes. The biggest range, I mean, obviously there's a huge range in the number of bacteria per gram of poop, but also people who are severely ill are not just shedding while they're having massive diarrhea. They're shedding for up to one to two weeks after symptoms have alleviated. And people who have mild illness are shedding for less time. And people who are asymptomatic tend to shed for only about a day or two. Okay. So yeah, it's crazy. It's,

There are just tons and tons of this bacteria that are getting into the environment. And the other thing is that since this is a pathogen that can persist in the environment, the types of vibrio cholera bacteria that you're likely to find in the environment, meaning whether they are toxicogenic or non-toxicogenic, will largely depend on how many severely ill people you have in that environment. So it's this vicious cycle. Once you have people who are ill in a certain area, they're shedding so forking much virus.

I mean bacteria. Oh, shoot. That's embarrassing. How many times do you think I've said virus? I don't think you have. Okay. So once you have people who are ill in a specific area, they are shedding so forking much bacteria that if you don't have proper sanitation,

for example, if you're living in London in 1850 or many places today. Right. If you're, say, pooping in a river and then drinking from that river downstream, or even if you, you know, have like an outhouse or something, but that hole is near a well or upstream of a river, you're just spreading that infection like wildfire. What else do you want to know? So treatment for cholera? Well, the good news is that treatment for cholera, cholera is a very treatable disease.

So the World Health Organization basically calls for oral rehydration solution, which is just like salty, sugary water. Gatorade? Kind of, yeah, pretty much. They have like a proprietary blend, I'm sure. IV. IV for severe infections. Definitely need treatment up to like six liters in the first day.

Severe cases might need more than that. So it's quite a lot of liquid that you need. Generally, they don't recommend antibiotics except in super severe cases, primarily because A, antibiotics are wiping out all of the good bacteria in your gut, which can make it so that you're very susceptible to other potentially more serious diseases. Well, and cholera has kind of done that. Like if you have a severe infection of cholera, it pretty much has taken over your entire intestine anyway. Yeah. And the other thing is that because this is a bacteria that can persist in the environment, antibiotic resistance is a real concern.

And it's really kind of cool that it can be treated with just rehydration therapy. Right. Yeah. It's generally like a fairly short course of disease. The severe cases without treatment, fatality rate is about 50%. Wow. With treatment, it can be as low as 1%, which is amazing. What about a vaccine? So there is an oral cholera vaccine. There are actually three different types of OCVs. And WHO does have a stockpile of these in case of severe outbreaks and emergencies, which we'll probably talk more about when we talk about what's happening with cholera today.

Right. That's good that there's a vaccine. Yeah, it's great. Do you know anything about whether it provides long-term? As far as I know, it's not long-term, but it is short-term. And so that's why it's generally used in case of outbreaks. Yeah, so I mean, I feel like that's pretty much the biology of cholera. Am I right?

You better be. I hope I am. So can I tell you about the history then? Oh, I cannot forking weight. Okay. It's a good one. Good. I mean, they're all good.

Well, yeah. But this is a good one. It's a, I think as we are both epidemiologists, this is especially close to our heart. Am I right? Yeah. Because you can't really talk about the history of cholera without talking about the birth of epidemiology as a field. Yay. The struggle for germ theory to prevail over myasmatism, which is, okay, this word is

M-I-A-S-M-A-T-I-S-M. I'm not saying my asthma. Just FYI. It's not my asthma, yeah. And also the role that modern sanitation practices have played and continue to play in reducing disease burdens. Yeah, definitely. Huge.

But let's start a little more simply than that. Let's start with what we know about the oral. origins of the bacterium itself. Since cholera doesn't leave any physical mark on the body that would remain after death, you can't really detect it in skeletal remains the way that researchers have been able to with, like, leprosy and smallpox, as we've mentioned. I had never thought about that. Yeah. That is so interesting. It's really cool to look at how you can trace the physical evidence of certain bacteria, because this means that we have to rely more on ancient texts and writings, which may or may not refer to the same disease that we call cholera today.

Oh, that's so interesting. Yeah, it makes the history of cholera a little murky. Oh, just like ricewater's too? The first mention of cholera comes from the father of Western medicine himself. Hippocrates. In around 500 BC, he uses the word cholera to describe an intestinal illness that causes diarrhea. In fact, it's thought. that the word cholera itself comes from the Greek word for gutter, caledra.

What? Yeah. Yeah. That's so cool. So he may have chosen this word, cholera, to describe the way poop water gushes out of you if you have cholera. Oh, my God. Like the way water gushes out of a gutter.

Oh, wow. There are some other loose mentions of cholera prior to the 1800s. Your puns are killing me right now. But any that were written outside of India, we're probably just using the term cholera to refer to any diarrheal disease. Okay. It would be like saying, oh, man, I ate Taco Bell last night and I've had cholera all day today. Every time, dude. Every time.

So it wasn't until the early 1800s that the word cholera was directly linked to one disease caused by one organism, the cholera bacterium. Cool. Yeah. 1800s. 1800s. From Hippocrates to the 1800s. It was just in the Indian subcontinent. Interesting.

In fact, until 1817, cholera was confined entirely to India. Wow. When it would pop up occasionally and cause an epidemic, particularly during religious pilgrimages. Huh. Wonder why. Oh, I'm about to tell you. Because during these pilgrimages, there would usually be a lot of people in a very small place. And so a disease like cholera, which relies on high population density, can really take hold and tear through a population.

Just thousands of people shedding trillions of bacteria and then drinking poop water. Yeah, per gram. Isn't that crazy? That's a lot of poop. It explains why it spread so rapidly. Really, the world in 1817 was pretty perfect in terms of opportunities for cholera pandemics. I thought you were just going to leave it at perfect. I was like, pretty perfect. I mean, yeah. Women had the right to vote everywhere. Global population density was higher than it had ever been in 1817, and trade routes were really well-established. So basically bringing the furthest reaches of the world to the doorstep.

You could go anywhere much more rapidly than you ever had before or ever could before. But something happened in 1817 to tip the scales from cholera epidemic to cholera pandemic. Maybe one or two cholera victims hitched a ride on a ship or a caravan heading east. Who knows? And they continue to shed the cholera bacterium, even if they felt okay. Can you remind us the difference between an epidemic and pandemic for those people who maybe haven't listened to every one of our episodes? Basically, all the difference between epidemic and pandemic has to do with spatial scale. So epidemic is a lot smaller, regional outbreak.

And epidemiologists tend to define pandemic as because, being either countrywide or global, multiple countries. Yeah. In any case, cholera raged for the next seven years in India, China, the Philippines, Mediterranean countries, etc. All of which had probably, except for India, had never seen the disease before. Oh, man. So no immunity. No immunity.

People were dying all over the place. It was really bad. And this marked the start of the first of seven cholera pandemics that historians and epidemiologists describe. And they would happen one right after the other pretty much in all corners of the world. Yeah, I'm not sure how they defined like the edges. I was trying to find that too and I couldn't. So I mean, so we're currently in the seventh pandemic right now. Yeah. And that started a little bit later, which we'll get into more later in the episode. The rest of them were sort of almost separated by a year too. Right. How could you say? I wonder if it's just that if reports dropped below a certain level,

then they considered that epidemic or pandemic over, and then the next one started or whatever. I mean, that could be it. It's not like we're epidemiologists or anything. Uh-oh. What we are. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients, so there's no meal planning and no extra grocery trip. Their assemble and bake meals take about five minutes of hands-on prep.

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and 365-day returns, quince.com slash this podcast. During the third pandemic, in walks, one of the heroes of this story. Can you just keep going, I'll sing it. John Snow. No, this is not fantasy, disease ecology, crossover fan fiction. Oh, that'd be great, though. I mean, let's start it. This dude's name really was John Snow.

But this John Snow was an English physician living in London in 1854 when a cholera epidemic. broke out. Ooh. Allow me to set the stage for you, Aaron. Thanks. Okay, close your eyes. Closed. It's 1854.

Okay, I'm probably wearing like a large dress and a corset. Uh-huh. You probably smell really bad because bathing was not. Never showered. Yeah, never showered. You're living in London. Oh, I might. Mm-hmm.

Along with 2.5 million other people. Okay, let me give a little perspective. The population of London today is 8.7. Oh. Million. Okay. So just a few friends and I. Yeah.

But the city has never been bigger in terms of population density. And as a result, it's been unable to keep up with the rapid population waste output. Oh. Yeah. And there's no solution. Uh-oh. The vast majority of people were just tossing out their poop, their food scraps, and their dead pets or other animals into open cesspools that led to the sewer, which was often right next

to a water pump. A water pump for drinking water. I really appreciate that. Thanks. I was just trying to get in the mood. Also, horse poop was everywhere. Oh, God. Yeah.

The waste problem of London and other populous cities at the time was so enormous that there was an entire industry based on sorting through the stuff that got tossed out. Wow. Bone pickers. I was going to say pickers, so that's pretty close. Bone pickers, yeah. Night Soilmen. Oh, just shoveling through the poop.

They would collect the poop and then use it for fertilizer. Cool. Sewer hunters. These were actual names. I feel like I could be a sewer hunter. Yeah, you could be. I feel like that's a profession that I could do. Would you want to?

I don't know. Well, you can be. Just kidding. Yeah, so, and that was just to name a few. There were many more like in that same ilk. Wow. If you were to travel back in time to this London, the first thing you would notice was the putrid, pervasive smell of rot and filth. Oh, God.

And this London is the London that our hero, John Snow, experienced every day as he walked to patient's houses. Wow. Like the John Snow of HBO. This John Snow was also quiet and methodical, and he was also really curious. Did he have a great jawline? No. He didn't. Does the Johnstive HBO?

Yeah. Does he? Oh my God, yeah. I feel like he always has facial hair covering it. In the early episodes, he just had little wispies. He's got a good jawline. All right. Anyway, while the epidemic, the cholera epidemic was raging,

John Snow set out to do some detective work to see if he could track the pattern of spread, to see where the outbreak originated. And out he went, notebook and pen in hand, doing some, what do you call it? A cheerio, mate, can I get a sample of your poop there, love? Kind of like that. Kind of like that, but also shoe leather epidemiology, which is what, it's actually like a real term.

Yeah. It's what people say to do, when they do on the ground epidemiology. Yeah. And so when he went out to try to figure out what the cause of this outbreak was, what he was doing was interviewing people who had any sort of experience with cholera during that time. And what he was looking for was a common thread in all of their stories to see if he could find the cause of this horrible disease. And why was he so interested in this? Poop.

Poop everywhere. Because he loved poop. No. At the time, the prevailing thought was that all disease was spread by myasma. M-I-A-S-M-A, not my asthma. Which is, in other words, unpleasant atmosphere. This was what scientists, physicians thought at the time caused all disease. The wind blew in the wrong way today.

The air is so foul. I can't do a British accent. I should stop trying. Maybe. I don't know. I should really stop it. It's better than I could ever do. I was like really trying really hard to think of something to say there.

And I just, I'm going to. Yeah. We're losing all listeners in the UK. Sorry, loves. Oh, goodness. Yeah, so basically miasmatists were people who believed that miasma was what spread disease, and they thought that epidemics could be caused by the right weather conditions or proximity to the foul smell coming from the sewer. Myasma or miasmatism to disease biology is kind of like astrology to personality psychology.

It has a width of science. It piss a few people off. It has a whiff of science in its logic, but is mostly based in nonsense. Yeah. But the logic of myasmatism didn't quite make sense to snow, at least, who recognized that the rate of disease wasn't any higher in the people you'd expect it to be. Right. Like the people who spent so much time in the filth, such as bone pickers, nightsoil men,

etc. Which is interesting when you think about it just because they were probably getting so much poop water on their hand. that it could have been that they had higher rates of disease just from being exposed. But I guess when you have exposure just across all boards,

then it washes out. Well, or they could have been exposed in low enough dosages. That's very true. Yeah. That they would have had an increased resistance. Yeah, that's true.

Good point. Instead, though, the disease seemed to strike somewhat randomly. Entire families would be wiped out in some houses. Seriously, entire families. But others would be completely unscathed. to try to make sense of this, he mapped out the cases,

which is not the first time that maps had been used to study disease, but it was one of the most remarkable. I don't think I knew that. I thought that was like... I thought so, too. It was like the John Snow went his maps. It was like a big deal in all of our classes. It is a big deal because of some of the techniques he used.

Ah, yeah. But there were maps that had been used by the miasmatists at the time to show, oh, disease. Like up on this hill versus down in this valley and that kind of a thing. Right. Especially for malaria. Right. Right.

And so when he looked at the map, he saw a geographical component for sure with most of the cases appearing in a certain neighborhood. But it was the anomalies that struck out to him. A woman across town who died during the peak of the epidemic with no other cases around her. A brewery smack dab in the area with the highest prevalence. but without any cases at the brewery itself. Oh. Yeah. What was going on?

What was going on? Well, during his interviews, Snow gathered info on daily habits of those afflicted with cholera, including where they got their water. You see, in 1854, there was no indoor plumbing in London, and people got their water from public water pumps, some of which had a better reputation than others. The pump on Broad Street was considered to be one of the higher,

POMPS. I'm just feeling so excited, because this is such a fun story. And some people went out of their way to load up on the sweet, sweet, sweet tasting water from the Broad Street pump, unfortunately for them. Because that's where all the color I came from. In his interviews, Snow heard Broad Street mentioned over and over again. And sure enough, when he marked the side of the broad street pump on his case map, he was basically marking the epicenter of the outbreak. Yeah, with cases just spilling out from there.

Oh, it's so cool. All told, 700 people living within 250 yards of the Broad Street pump had died. 700 people? 700 people within 250 yards. Wow. And on Broad Street itself, the population had literally been decimated. 90 of its nearly 900 residents died. That's 10%.

Yeah, decimated. Dang. Wow. Yeah. And the anomalies he noticed. Well, the lone case far away from the pump, was a woman whose sons brought her Broad Street water every week as it was her favorite. Oh.

Yeah, isn't that? Poor old lady and her son's just trying to be nice. Yeah. I'll bring you the best water, Mama. That was better. That was better. I don't think Snow told them eventually, I mean, which is probably a kindness. Yeah, probably.

And the workers at the brewery. They never drank water during their shift, only beer. Oh, that's the moral of our story. Yeah. And so Snow took his findings to the Board of Governors, who actually, I was shocked about this, did something about it. They ordered that they handled the Broad Street pump be removed. Of course, by the time they actually removed it,

it was pretty much over the epidemic. Still, it was a victory for germ theory that marked the birth of epidemiology, which is, as we've mentioned before, the study of patterns of disease and populations. So you would think that by removing the handle of the pump, they were, you know, acknowledging that maybe John Snow was right about something. Yeah, I mean, he was the king in the north, after all.

I mean, yeah. North of London. Bend the knee. Bend the knee, people. To germ theory. Oh, that was good. It was terrible. That was on the fly.

I know it. Yeah, it was. And they probably agreed that, yeah, cholera was transmitted by drinking contaminated water. John Snow was almost pretty much unique in his assertion that that was how it was transmitted. But like Circy Lannister of Season 7 Game of Thrones, they remained firm in their denial. Oh, my God. Colora was transmitted by foul air slash white walkers weren't a real threat. Oh, my God.

I had to dig deep for that one. That was good. It wasn't until a couple of decades later that Snow would be vindicated, or until next season for the other John Snow. We anticipate. I just can't wait. Oh, it's like two years from now. Yeah, yeah, yeah. Sadly, Snow, the epidemiologist, would not live to witness his vindication.

Oh. Yeah. Does he die of cholera? No. Too bad. He died of a stroke at the age of 45. Oh, dear. When the causative agent of cholera was described in 18.

The germ theory had taken its rightful place on the iron throne of disease biology. We're never going to stop. Nope. And there were still, though, more than a few myasmatists lingering on. And one of them, pent and copper, drank an entire flask of cholera bacteria to prove that it wasn't the causative agent of the disease. Did he die? Unfortunately, no. No, he didn't get sick.

Probably, though, because he had cholera as a youth. Oh. And so it didn't matter really either way. He got like a mild or an asymptomatic infection probably. Right. So he might have killed somebody else by pooping into dirty water. His bacteria-filled poop. Yeah, that's a good point.

What was his name? Karkoff? Pent and Koffer. Koffer. Either way, though, germ theory had won. That guy is not, there's nothing that that guy could actually have done. Yeah. And Penton Koffer,

met his death in a very Game of Thrones way. Oh. Maybe. I don't know if it's that Game of Thrones. After realizing that his entire scientific career was based on a fallacy, because he spent so much energy promoting myasmitism, he killed himself. Oh, now I feel really bad. Yeah.

That's sad. Yeah, that's really sad. On a happier note, I don't know if you were going to mention this, but I would just like to point out for all the fans out there that you can visit the Broad Street Pump. Yes, you can. There is a little monument, too. John Snow there and I want to go so badly. If you've been there or if you live near there, can you like tweet us a picture because it's one of my favorite things? That would be incredible.

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Shop Lego Star Wars sets now on Lego.com or in Lego retail stores. Okay, back to cholera. Linking the spread of cholera to unclean water was a huge motivator for developing sewage systems. And in wealthier countries, the disease pretty much disappeared. Wow. Yeah, the 1854 epidemic in London marked one of the last real epidemics in that area. That's awesome. Yeah, because they were able to isolate the reason why it was being transmitted and stop that.

That's great news. Tea drinking? also may have helped. What? Boiled water. Oh. Isn't that crazy? That's really cool.

Yeah. Just like beer. Just like beer. Yeah. On a sad note, the problem of waste management does not belong in the past by any means. Definitely not. There are many economically poor countries today that are still struggling with waste disposal and sanitation practices where diseases such as cholera are still very prevalent.

Yeah. And in these places, it's kind of like a positive feedback loop. So these countries are unable to maintain or build adequate sanitation infrastructure because of the expense. And then cholera can take hold more easily, which then reduces people's ability to work, which then further destabilizes the economy. So cholera gets worse and so on and so on. Cycles. Cycles, cycles, cycles, cycles. So, Aaron, I'm guessing that you've got some stuff to tell me about where we stand with cholera today.

I sure do. So as you mentioned, we're basically currently in what is considered the seventh pandemic of cholera. So all the cholera in the world today can actually be traced back to a single origin that happened in 1961. And so my guess is that for most of our listeners, when they hear the word cholera today in 2017, they probably think Haiti. Yeah, I do. And it's likely because one of the most publicized outbreaks of cholera in recent history, happened in Haiti in 2010. And if you haven't heard of it, or even if you have, this outbreak happened pretty directly

as a result of UN peacekeepers who came to Haiti after the devastating earthquake that happened in January of 2010. And these peacekeepers had come from Nepal where an outbreak of cholera had been happening and they brought it with them. Oh, okay. I was wondering where they came from. Yeah, it was Nepal. They had cholera.

Okay. Yeah. So cholera has been endemic in Nepal for a very long time in the whole, yeah, that whole region. And so the UN still hasn't technically admitted that they were responsible. Really? Even after epidemiological research and molecular strain typing of the cholera bacteria has pretty conclusively shown that that is where this epidemic came from. They did issue an apology in December of last year about the way. way that they handled Haiti after the earthquake. That kind of sounds like, I'm sorry that you were hurt by what I said. Yeah, that's kind of how, like they didn't directly take the blame for it.

But anyways, that's probably a story for a different day. In the outbreak in Haiti, which to be clear, is not over. It's still going on. Colora is still a problem today. Over 9,000 people since 2010 have died. Wow. And over 700,000. people, which is about 7% of the population of Haiti, have been sickened. They're averaging, the stat that I saw is that to this day, they're averaging 37 people a month dying from cholera. Oh my God. And if you think of all of the hurricanes and everything that have been happening in the Caribbean at this time, like, because cholera is a disease that is very strongly associated with contaminated sources of drinking water and lack of sanitation, anytime that you see destabilization

of infrastructure, whether that's due to natural disasters or war, man-made conflicts, you see outbreaks of diseases such as cholera. Right. Today, or in 2015, rather, since that's the most recent stats that the WHO had on their website, 42 countries reported 172,000 cases of cholera that resulted in 1,304 deaths in 2015 in one year. Okay. But what's really astonishing to me, especially in doing this research, is that estimates of how many cases there actually are, 2.9 million. Interesting.

Yeah. So, and this has to do with asymptomatic cases or not seeking treatment? Probably both. So probably there are some asymptomatic cases, but a lot of it has to do with a lack of surveillance and a lack of reporting in a lot of areas. Right. You also, because this is a disease that can strike so rapidly, you can have people falling ill and dying in remote areas long before they have time to get to a hospital facility or anything like that. Estimates of the number of deaths that likely happen each year due to cholera are 95,000. Whoa.

Yeah. And this information is from a paper that used mathematical modeling and a bunch of disease data to make these estimates. So they estimate that it's actually happening, that cholera is likely endemic in about 60, over 60 countries, not just the 42 that actually report it. And the estimates range from 1.4 to 4 million cases per year. Wow. And between 21,000 to 143,000 deaths. Whoa. Yeah.

I mean, it's a really big range because there's not super great data from a lot of places. But still. But still. It's definitely a lot more than the 1,000 deaths that are actually reported. Yeah. So in addition to estimating the number of cases of cholera, this study also looked at what the most important risk factors were. My voice cracked. I noticed that.

Yeah. Unsurprisingly. Oh, thanks. Appreciate it. But unsurprisingly, the two most important risk factors, do you want to guess what they are, the two most important risk factors for cholera? For cholera? for cholera in a country? I think I'm going to try.

Okay. Sanitation. Definitely. Water infrastructure? Access to clean water? Exactly. The percentage of the population without sustainable access to improve sanitation and improved drinking water sources. And blood type?

And not blood type. But there are differences in susceptibility to cholera with different blood types, right? Weirdly, yeah, what blood type you are can actually affect the likelihood that you get infected with cholera and how severe the case is once you are infected. That's so weird. It's super weird. So people who are blood type O, like me, like me. Oh, I'm A-B.

You're so rare. I'm so common. So people who are type O are less likely to get infected with cholera, which sounds great. Uh-huh. But if they get infected, they actually are much. more likely to have severe symptoms. Okay. That's a bummer. It's a bummer, yeah.

So what's cool is that in some parts of the world, for example, in the Ganges River Delta, where cholera is endemic and has been for a very long time, you see a very, very low prevalence of people who are blood type O. Interesting. So one hypothesis is that this is at least in part because there is selection against this blood type because it's associated with higher risk of severe symptoms. I've always wondered about the geographical distribution of blood type. It's really interesting. We were just looking at maps of that. It's so weird that there's, I had no

idea there was such a range in distribution. It's huge. And so in Latin America, for example, there's a really high prevalence of blood type O. So all of like North and South America is like really high prevalence of blood type O. And so we see much more severe disease due to cholera. You have greater need for rehydration treatment and much greater rates of hospitalization. Wow. Yeah. It's really interesting. That is really fascinating. Yeah. So how worried do we need to be about cholera? It's a good question. It's a tricky one. It's a tricky one. I would say overall, the biggest thing that we can do to prevent and majorly reduce the burden of cholera is improve access to sanitation and water worldwide. And that's something that's very doable. It just honestly takes investment, you know, to make that happen.

People on the ground going out and trying to help create clean water sources. Exactly. The Gates Foundation is big in trying to do that. There are a lot of organizations that are doing that that I wish I had looked up the names of all of them. So maybe what we'll do is post on our Facebook page some of the organizations that are doing really great work on both sanitation and water improvement. The Carter Center, which last episode I kept saying was the Carter Foundation.

I was confusing with the Gates Foundation. It's pretty close. Actually the Carter Center. They also do a lot of work in terms of reducing the burden in neglected tropical diseases in countries. Yeah. So yeah, I say overall, cholera definitely is still prevalent in a lot of parts of the world. It's still something that's killing people every day. And it doesn't need to be, which is what's really sad about it, is that it is treatable and it's preventable.

Could it be eradicated? That's a really good question. It's an interesting question. I don't know, to be honest. Because it can persist in the environment, I think it would be really, really, really. hard. There are some interesting therapies out there that we don't have time to get into that could make a really big dent. Because in theory, if you could eliminate this bacteria phage from the cholera, then you're not going to be having symptomatic infections. So then it just becomes another

microbe in your gut. Okay. But because it does persist in the environment, it's a disease that would be very, very difficult to eradicate. I do think we could certainly reduce the disease burden and the mortality rate to basically zero. Right. Maybe that could happen in our lifetime. Who knows? Wouldn't that be wonderful? It would be really wonderful.

Is that it? What books did you read? Okay. This week. I've got a few. If you want a big overview of cholera itself, there's a book called Collara the biography by Christopher Hamlin. And if you want to learn more about the non-HBO John Snow, you should check out

the ghost map by Stephen Johnson. It's a pretty thrilling book, actually, about the race to try to find out what was the cause of cholera, the quite frankly shocking pushback from the miasmatists about germ theory. And also in the ghost map is where the quote from the beginning of this episode came from. A couple of other places that I looked for info was the power of plagues by Erwin Sherman and the Cambridge History of Human Disease by Kenneth Kippel. And a bonus is Love and the Time of Colora by Gabriel Garcia-Marquez, which is a great fiction book. And most of the information about the biology of cholera I got from this really interesting paper called

Cholera Transmission, The Host, Pathogen, and Bacterophage Dynamic by Nelson at all in Nature Reviews Microbiology. That was published in 2009. It's a really nice review paper, and there's a bunch of other ones out there as well. And most of the data about the mathematical modeling to estimate the actual burden of cholera worldwide comes from the article updated burden of cholera in endemic countries. And that was in the journal plus neglected tropical diseases. That was published in 2015 by Ali at all. So you can find that. Before we go, I thought of the most brilliant idea. Oh, tell it to me.

Kit Harrington, who plays Johnson. and HBO's Game of Thrones needs to play John Snow, the epidemiologist, in a biopic. That would be really funny. I'm serious. I mean, are you listening, Kit?

Are you listening? Screenwriters everywhere? Yeah, I mean, we gave you a plug last episode, you know, the smallpox movie. We're basically doing your jobs for you. Yep, yep. You're welcome. Welcome.

And speaking of more thanks and welcomes, thank you to Bloodmobile, who provided the music. for this and all of our episodes. Yep. Thanks. You're the best Bloodmobile. And also a big thank you to the band Cholera who let us use their song The Answer to Infection as the fade-out song at the end of this episode.

It's awesome. You guys should totally check them out. Just wait for it. It's so good. Once again, rate review and subscribe. Yep. We'll do it again. We'll tell you more. And thanks so much for listening. We hope you are having fun. we are. Wash your hands.

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