This Podcast Will Kill You - Ep 80 Dysentery loves a disaster

Episode Date: August 24, 2021

While many of us know how deadly dysentery can be from playing countless hours of The Oregon Trail, there’s only so much that the classic game covered regarding this multifaceted disease. For instance, did you know that it can be caused by multiple pathogenic microbes? Or that it is and always has been closely associated with warfare and armies? Or that it remains one of the leading causes of death globally for children under five? In this episode all about dysentery, we pick up where The Oregon Trail left off. Tune in to hear facts about ancient toilets and a list of famous people killed by the disease and to learn how dysentery isn’t just about diarrhea and how the “bloody flux” lives up to its (horrible) colorful name. See omnystudio.com/listener for privacy information.

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appetite, by lessening the quantity of opium, and substituting the tincture of hops as much as possible. His appetite was frequently coaxed by some delicacy, and the sweet oil was frequently alternated by magnesium and rhubarb. This treatment was regularly pursued until the last of June, and although he suffered much pain during that time, he was evidently much better, and his appetite improved. The pain in his bowels was less frequent and not so violent. July 4th. I was sent for in great haste to visit him. When I entered his room, I was astonished at his altered appearance. His countenance was pale and fallen. He was sitting up in his bed, struggling for breath. His body was covered with cold and clammy sweats, and he had a most anxious and desponding look.

I immediately gave him large quantities of ether and laudanum. These injections brought away from his bowels large quantities of dark and hardened feces. They were repeated every day during this month with the happiest effect, and it was astonishing what masses of these dark and indurated feces were evacuated during this time. September. He is much emaciated and exhausted by want of sleep. The pain and swelling have pervaded all his extremities. Opium can no longer lull his pain, and nothing but death now seems to offer him any hope of

relief. Last entry. He is affected with erasipolis and is gradually sinking into a state of insensibility. In this state, he lingered until the 13th of September when he expired without a struggle. Wow. Yeah, that is brutal. It's horrible. So that is an account of dysentery, and it is from a book, titled Medical Sketches of the Campaigns of 1812, 13, and 14 by James Mann, and it was published in 1816. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike.

And this is, this podcast will kill you. And, well, so today we're covering dysentery. We are. But that firsthand account, Aaron, when you read it, like, it doesn't really sound like dysentery? Here's my thoughts Because I kind of agree But I was like you know what Aaron You don't know anything about the biology

Leave that to Aaron So So like you know Just trust the physician from 1813 That you know that he knew what he was doing And the other thought I had Is that Yeah this could have been any sort of diarrheal pathogen

But I wonder if some of these symptoms Were caused by the things he was taking like opium and lead was like a really popular treatment as well, mercury. So I don't know. Absolutely. Because it sounds like he was having a lot of issues, losing weight, in a lot of pain, and then was given a ton of opium, which is going to block you up really good. Yeah. So that's why then his bowels became compacted. Is that the word they used? I think, what did they say? Did they say obstinate? No. Yes, obstinately cost of. Okay, yeah.

Yeah, that'll do it. Uh-huh. But in any case, it is horrific. And, yeah. But also, I think that the, let's see, the vagueness of this first-hand account or, like, the hard-to-pin-downness is kind of characteristic of the topic that we're covering today. Absolutely. Yeah. Yeah.

Because dysentery, why do we do this to ourselves? Again, is not caused by one, not two, but by several pathogens and parasites. So it's going to be an interesting ride. Yeah. As always. As always. As always. And as always, I believe that it's quarantini time. It is. What are we drinking this week? We're drinking in flux. So flux was one of the old-timey names for this disease. I think it actually might still be called flux in some places. Flux or the bloody flux.

And so, you know, since the definition of dysentery has kind of been in flux, that's what we're going with. So, Aaron, what's in flux? Well, I thought it would be kind of a nice call back to the first-hand account to include rhubarb. So we're going to do a rubarb syrup plus some gin, plus some sparkling water, strawberries, and lime juice. Yum. And we will post the full recipe for this quarantini as well as the non-alcoholic placebo-rita on our website. This podcast will kill you.com as well as on all of our social media channels. And speaking of our website, this podcast will kill you.com.

We just keep telling you guys to go there. Have you gone there yet? It's really great. We have a bookshop.org link. We have a Goodreads link. We have links to Bloodmobile, our music. We have links to our Patreon, to our merch, to transcripts, to all of the sources from all of our episodes. Wow. Yeah. It's a gold mine. It really is. Yeah. Do we have any other business, Erin? I do. I have a correction. I wanted to. point out that somebody emailed us, and I really appreciate this, about one of our recent episodes was on Legionnaires disease. And Aaron, you and I talked a lot about atypical versus typical pneumonia. I recall that conversation. Yeah, and how like poor of a definition it is. It's still true, but a listener pointed out, and I think this is important, is that today the term atypical is mostly used to mean pneumonia that's caused by bacteria that don't gram stain very well. Rather than previously, atypical used to be like clinically a little different or not responding

to antibiotics or maybe radiographic differences. But like we talked about in the episode, those are not good definitions to distinguish different types of pneumonia. So at least the way that we use it today is moderately better, things that don't graham stain well. But again, And some things that are not considered atypical pneumonia is also don't gram stain well, but that's besides the point. It's still an imprecise term, but it's at least a little bit better. Okay. So it's more about the pathogen now than it is about the symptoms or signs. Right, like the clinical picture.

Gotcha. Okay. Interesting. So that's something. Yeah. So thank you again. That's all I got. Should we dysentery it up?

I think so. This feels like a fast intro, but I'm here for it. Let's do it. We'll take a quick break and then we'll dive in. 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. There, assemble and bake meals take about five minutes of hands-on prep. Just spread the pre-chopped ingredients on a sheet pan, put it in the oven, and then

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typical disease that we cover on this podcast. So first what I'm going to do is cover kind of the symptoms of dysentery. We'll talk about like what does dysentery actually mean. And then I'll focus on a few of the specific causes. And then, Erin, you can ask me a million questions and I probably won't know the answers. Cool. I am very excited. Okay. So generally, dysentery can be defined as bloody diarrhea. Is that cool? Can we all be cool with that definition? I mean, that's it, right? Like, pretty much. Yeah, pretty much. Okay. Diarrhea, we've talked about kind of a lot on this podcast, although not for a while. The World Health Organization definition is three or more loose or liquid stools in a 24-hour period, but even that definition is pretty

loose. I swear the whole episode's not going to be like this. I think it absolutely is. Oh. But it is a loose definition because everybody is different in terms of their bowel movements, right? Right. But everyone has had diarrhea at some point. So everyone knows what diarrhea feels like and what it means. So dysentery is diarrhea with blood, visible blood, and often sometimes mucus, just for good measure.

Okay. So question about the blood. Okay. Is it bright red or is it black? Good question. It could be either color. So part of what you're asking gets at where is the blood coming from in your GI tract. Right. So black blood usually means that the bleeding is coming from further up in the digestive tract. So if you have bleeding in your stomach, in your small intestine, those will usually be black by the time they make it all the way to your poop. If you have bleeding in most of your colon, then that bleeding is more likely to be bright red. Although even if you bleed like a ton from higher up, it'll end up bright red. It just all depends on how long it transits. Okay. Okay. Okay. So in the case of dysentery, it's probably going to be, I would say a mixture of two, but more on the red spectrum than the black spectrum. And that's because, as we'll see,

it tends to be a colitis picture. And that means inflammation in the colon. So let's talk a more about it. In order to have blood in your poop, it means that in one way or another, your gut is very unhappy, of course. In the case of dysentery, what it means is that you have some kind of severe inflammation going on, whether it's from a bacteria, a virus, a parasite, or even in some cases, no pathogens whatsoever. So you can have aseptic inflammatory bowel disease, like Crohn's disease or ulcerative colitis. Okay. So these are autoimmune-mediated conditions that cause massive inflammation of the colon

that lead to bloody diarrhea, aka dysentery. So any of these different things can cause dysentery. We're going to focus today really on just the pathogenic types of dysentery, and I'm going to focus even more specifically on two major causes of dysentery. But we'll get to that in a second. Let's focus on the symptoms, shall we? So you can imagine that if you have a very inflamed angry gut wall that is so inflamed that it's bleeding large enough amounts of blood that it's visible in your stools, because if you just have a little blood, you won't notice it. You can imagine that this is a very painful process.

So dysentery, like a lot of other diaries, are often accompanied by major abdominal cramping. And because today we're focusing on infectious dysentery, it's also common to have a fever, which of course causes total body pain. So with dysentery, you're often in terrible pain. You're pooping like crazy. You have this diarrhea. You have abdominal cramps. Often with this type of diarrhea, you have a lot of urgency. You know that feeling?

Like when you have to go, it's like right this instant. And then it's going to be explosive and it's going to be painful. And with any type of diarrhea, one of the biggest issues is how much fluid you can lose. Your large intestine's one job, really, like it's one job, is to absorb all of the water back from your stool so that we don't get dehydrated. And in massive diarrhea or in dysentery, that mechanism is destroyed. So you're just losing water through your behind. And so that's one of the major causes of death is just from dehydration. Okay, so you state the definition of diarrhea as being three loose stools in a period of 24 hours.

But for a dysentery, is it three? Is it nine? Is it 15? Is it 50? Yeah, so there's no number on it. It's just if those three loose stools have blood and or mucus in them, now you'd call that a dysentery rather than just like a regular old diarrhea. Okay. Yeah.

Right. Okay. Yeah. Great question. So yeah, dehydration is one of the biggest concerns and complications. But of course, it's this podcast, so there are more things that can go wrong. Of course. With dysentery and other types of diarrhea, like non-bloody diarrhea, you also lose a ton of electrolytes.

You're losing sodium, you're losing chloride. And so this can cause problems when your electrolytes then get out of whack. So you can end up with heart arrhythmias because of problems with your potassium. You can end up with neurologic problems because of the lack of sodium. And with dysentery, which is different than other forms of diarrhea, you're losing a lot of blood. So there's a risk of anemia, especially in the cases of more chronic dysentery, like a prolonged diarrhea. Right, like the guy in our firsthand account. Exactly.

And so that's how you get, like you heard in our firsthand account, this kind of muscle wasting, malnutrition, and you're just sort of wasting away because you're not able to absorb anything. Right. How much blood are we talking? It's a good question. There's no like number or amount on it that would qualify something as dysentery versus not. It's really not a like strict definition. Okay. Yeah. And different sources would give you like slightly different definitions, I think even. So the most general would be just to say bloody diarrhea. And then, of course, because today we're going to focus on infectious causes of dysentery, there's always a risk of this infection spreading beyond the gut itself, so that even if it's not the dehydration or the malnutrition that ends up killing you, you could end up with a more widespread infection. So let's get into these specific bugs.

There's a lot of different bugs that can cause bloody diarrhea. And like I mentioned, even non-infectious things. It's possible that viruses can cause bloody diarrhea, but it's not super common because in general viruses just cause regular diarrhea, not dysentery. It's possible that parasitic worms, like maybe even some we've already talked about, like hookworm or maybe tapeworms, these could potentially cause bloody diarrhea. But most commonly, there's two things that cause bloody diarrhea. There's bacteria that cause bloody diarrhea, and there's an amoeba that causes dysentery. Mm-hmm. We've already talked about one of these bacteria that are a very common cause of dysentery,

and that is e-coli. Right. Right. So some forms of e-coli are massive causes worldwide of dysentery. There are lots of other bacteria, salmonella. We talked about typhoid already, which is a form of salmonella, that can definitely cause bloody diarrhea. Also, campllobacter, which is another bacteria. There's two that we're going to focus on today, because they're,

They're the leading ladies. Well, and I think also, like, historically, these two were the ones that caused classic dysentery. Typhoid had its own thing, right? It's its own thing. And so if you were to find a treatise on dysentery, it would probably be these guys would cause the vast majority, or these leading ladies would have caused the vast majority of them. I think so, too. So that's why we're focusing on them today.

And that is Shigella and an amoeba entamiba histolitica. These are the two major causes of basillary and amoebic dysentery. All right. I'm excited about this. So let's start with amoebic dysentery. And then we'll talk about Shigalosis or dysentery from Shigella. And then we'll just like wrap up and you can ask me questions. I don't know the answer too.

Okay. Okay. Okay. I found this one seminar from the Lancet in 2003, so it's a little bit old, but I just really liked this quote. I never read quotes. I'm going to read you a quote. Ready? Oh, yeah. Few pathogens are more aptly named than entomoeba histolitica, the tissue licing amoeba that causes amoebic colitis and amoebic liver abscess. Think of this protozoan parasite as a macrophage on steroids with punctualising amoeba. pumped up phagocytic, proteolytic, and cytolytic capabilities, invading human colonic mucosa, and occasionally penetrating through to the portal circulation, reaching the liver, and causing fatal abscesses. Whoa. I dig the voice.

If you wanted a career as a movie voiceover, I think you got one. Thank you, thank you. But also, I loved that, I loved that quote because it really aptly described. and to meba histolytica. Plus it does the etymology, so I don't have to do it. Yeah, it's the whole thing. I really love it. Shout out Dr. Samuel Stanley.

Excellent work. My biology is done, right? Just kidding. Because a lot of those words, people are probably like, I'm sorry. Let's talk about it more clearly. Let's go over it. So this particular amoeba entomiba histolytica has a simpler life cycle than the last amoeba we talked about, Naglera falari.

This amoeba exists in two forms, in the environment as a cyst, and this is the form that is infectious to humans when we ingest it. After we ingest it, it passes through our stomach, survives our stomach acid, travels down our small intestine, reaches our terminal ilium or our colon, so those are the two places where it exists and becomes a trophazoid, like the amoeba-shaped version of an amoeba. And that's where it lives. it replicates by binary fission so it just divides and it just lives kindly in our colon munching on bacteria which our guts are full of we have plenty of bacteria for them to eat and then it also eats our food and it's fine right until it's not i was going to say i don't think so yeah it's

fine until it's not um because it doesn't stop there it's not satisfied with just eating our food remnants and our commensal bacteria. Instead, once it's in our guts, it attaches to the epithelium of our colon. It immobilizes those cells. And then it just kills them. It just laces them open and kills them. And then it invades its way, burrows its way through our mucosa and into the submucosa of our gut wall.

Why does it do this, Aaron? I was just about to ask. I honestly want to know. From what I read, it's not fully understood. Like, what exactly are the triggers that cause this adherence and invasion? Because the thing is, only about 10 to 20% of people who get infected with entomoeba histolytica will end up having symptoms. A lot of people are infected and entirely asymptomatic. And you're not asymptomatic if it's invading your submucosa.

Right. Okay. And by infected, do you mean that, like, they're shedding? They're shedding cysts, and you can find trophazzoites in their poop as well. And that's how it has to complete its life cycle, right? It has to go back into its cyst form. You have to poop out those cysts so they can then travel to find another host via water or whatever. So it's a really interesting, like, evolutionary question. What is the drive to seek out deeper spaces in our body?

And why do they have the capacity to do all of this damage to our tissue? It's really interesting because, like, do people who are symptomatically infected shed more amoebae than those who are just asymptomatically chronically infected? That's a good question. I'm not sure. I didn't see any papers specifically addressing that, but it's an interesting thought because if you have diarrhea, then yeah, you probably are shedding a lot more of whatever it is that you're shedding. but then if it kills you because of that, then you're going to stop shedding. Whereas if you're infected chronically, so maybe it's a trade-off between how long they're able to persist in someone before our immune system shuts them down versus causing massive infection but getting a lot out into the environment. Yeah.

Diseases trade-offs. Yeah. But we can talk about sort of the ramifications of what happens when they do this burrowing because spoiler alerts is not good. It's horrible. Yeah. And if you thought the bloody diarrhea part was bad, it gets a lot worse. There's a vein in our body is called the portal vein that drains blood from your small intestine

and the right side of your colon or large intestine directly to the liver. So as this amoeba, which we know is in the right side of your small intestine or large intestine, as it burrows its way through the mucosa and subuncosa, it can end up right in these blood vessels, hop straight on that portal vein highway and take the first exit to the liver. So the liver is the number one site of what we call extra intestinal outside of the intestine infection with entomoeb histolytica. And it can be very severe because in the liver, what it does is it kills off chunks of our liver cells, the same way that it kills off the epithelium of our intestine. But then our liver in trying to protect itself walls off these amoeba, essentially

forming an abscess within the liver. And so depending on how many amoeba you have and how large these abscesses can get, this is a common cause of death in people with Entemoeb histolytica who progress to liver abscess. It can be very serious. And it's not limited to just the liver, right? this amoeba can theoretically travel anywhere in our body through any blood vessel that it makes it into. So it's not uncommon to find similar kinds of abscesses in the lungs or in exceedingly rare cases in the brain. That's horrific. It is. But at least the brain is very, very rare.

Like less than 0.1% of people with liver abscesses have brain abscesses. And it's almost never that you would get a brain abscess without. first having liver abscess since that's the number one site. So can you break down what those complications are like in terms of the proportion of people who are, you know, if 10 to 20 percent of people are symptomatic, what percentage of those would have like the liver manifestations and then the other abscesses develop and so on? It's actually more common than I realized, especially if someone has the diarrhea, like is symptomatic with amoebic colitis? In In those cases, one source that I found said up to 75% of people that have the colitis

will also then have liver abscesses. Wow. Yeah. So it's kind of like once this thing starts invading, it's really able to invade. Sure. So that's amoebic dysentery. I have a question before we move on to. Okay.

What is it? Shigella. So I really want to go back to that 10 to 20%. of people. And so like, I assume there have been studies looking at the breakdown of people who are symptomatic versus asymptomatic. Are there any patterns? So yes. There's a lot of things that are like risk factors for people who will then go on to have severe disease or this colitis. Some things are like if you're, unfortunately, kids tend to have worse outcomes with all kinds of dysentery. Also, malnutrition is a huge one. But what's interesting is that amoebic dysentery

specifically really tends to be associated with very poor living conditions and with impoverishment. So how much that's also associated with things like malnutrition or maybe like a very high amoebic load because you're being repeatedly exposed. But kids tend to be, have poor outcomes and people who are otherwise malnourished or have other like pre-existing conditions that would leave them immunosuppressed. Right. Okay. That makes sense.

Yeah. That makes sense. Yeah. Yeah. I also wonder about the role of, and this probably relates also to Shigella, but the role of the gut microbiome in. Oh, Erin. We'll talk a little bit about that later because it's really interesting.

Okay. Wonderful. Yeah, definitely. It's super interesting. But what's also interesting, especially in. looking at the kind of overall worldwide prevalence of colonization with Entomoeb histolytica is that not that long ago, and I don't have an exact date on it, but not that long ago, it was discovered that there's another amoeba that looks identical to Entomiba histolytica.

It's called Entomiba dyspar. And that colonizes people that doesn't cause any disease. It doesn't cause dysentery. And so it's thought that some, at least earlier prevalence, studies that we're just looking for amoeba in the stool can't distinguish between these two different species. And so our estimates of overall, like, prevalence might be off in some cases. Yeah. Yeah. No, I have come across similar stuff. But I also wonder if you find an amoeba in the stool of some, in like the bloody stool of somebody, it's likely that the bloody

stool is being caused by that and not co-infection with? Well, that's the question is, is it? Because Entimuba histolytica exists both in the same areas where Entimuba Dyspar does and under the same conditions that other forms of dysentery do. So then you have to ask the question of like, you know, what does the clinical picture look like? So let's get into what baccillary dysentery looks like. And then we can kind of compare and contrast what these two diseases look like to see

if you can tell if they're different. Yeah. Because one thing I forgot to mention, this is, I guess, a spoiler now, is that amoebic dysentery, like the time course of disease can be really prolonged. I didn't get a great number on the exact incubation period, but the course of disease itself can be kind of insidious and last for a number of weeks. So it's not like a, all of a sudden, you're having diarrhea and you're pooping your brains out like crazy and you have high fever. It's not as much of that kind of a picture. So Shigella is a genus of bacteria in the family enterobacteria. There's a number of different species, at least four different species. Within those species, there are multiple serotypes. And these different species and serotypes cause a really

wide range of disease from a mild diarrhea without any blood to very severe dysentery with a substantial case fatality rate. Some species like Shigella dysentery are known to cause massive epidemics, especially after times of upheaval or after natural disasters, whereas other species like Shigella Flexneri tend to cause more endemic illness. And then there are a couple of other species that are just tend to be a little bit more mild but can still cause dysentery under the right conditions. Okay. So these are a gram negative rod-shaped bacteria, hence the term basillary, which I think we talked about in our Legionnaires episode. They're transmitted either from fecal oral contact or any kind of person-to-person contact

where poop is involved, from infected water, from foodborne contamination. And in general, these species are super infectious because Shigella survives the passage through our stomach very well. So as few as 10 to 100 individual bacteria can infect a person. It's wild how few it takes. Yeah, it's terrifying, truly. So it has pretty much the same transmission route we already talked about for amoeic dysentery. You get chigella in your mouth. It survives your stomach. It travels through your intestine, replicating the whole way that it goes until it gets to your colon or large intestine. And that is where Shigella likes to make its home. Once it's there, unsurprisingly, it invades your epithelium, the lining of your gut, and in so doing, what it does is stimulate a massive inflammatory response

from your body. And that inflammatory response just destroys the cells that line your gut wall so that the bacterium can invade even further. So at this point you have hundreds, if not thousands of bacteria burrowing into your gut wall, hence massive, bloody, bloody, painful diarrhea. I have a question about the blood. Okay. Why does this cause bloody diarrhea? Why does it cause bleeding, whereas other diaries don't? Yeah, great question.

It's specifically that invasion of the lining of your gut wall. Because in doing that, it's like think of it as your gut wall being like, you're like a wall. And this bacteria is just like poking holes into it. So the blood is just going to come leaking out because of that. Okay. Yeah. So other things that we've covered on this podcast that cause diarrhea, like, for example, cholera,

vibrio cholera, it just sort of hangs on to your epithelial cells. Like it holds onto them, but it doesn't invade them. It doesn't destroy them. It doesn't disrupt that lining. Whenever you get that disruption, that's when you get the blood. Okay. And so that's why also viruses don't tend to cause bloody diarrhea because they don't tend to invade through that gut wall. Okay.

Yeah. Some species of Shigella, especially the ones that cause more severe disease, also produce a variety of toxins, at least one of which we've talked about on this podcast, because it's the exact same toxin that's produced by E. coli 0157H7. Mm-hmm. Yep. Shigatococin. And this is a cytotoxic toxin. So it kills cells. Great, right? Really great. This particular toxin is especially dangerous. And what's interesting is that it seems to do this more often with E. coli that produce shigotoxin than with shigella that make this shigotoxin. But it's still

possible with shigella. Is that once this toxin gets into your bloodstream, it can kill your red blood cells and lead to anemia, but then also destroy your platelets. That since we know how important platelets are for clotting, it leads to excessive bleeding. And this also then leads to kidney failure because it causes damage to the vasculature of your kidneys. This is a syndrome called hemolytic uremic syndrome, and it's very bad and can be fatal. Does the production of this toxin in some way help the bacteria to replicate more or to spread more easily? Like, is someone shedding more bacteria? It's a great question. It certainly tends to cause more severe disease. So in that, maybe people are having more massive diarrhea and then are shedding more

bacteria, like we said before. But perhaps it also, the cytolytic effects perhaps help it invade more deeply into the epithelium. I'm not sure. Okay. In general, the sort of clinical picture of Shigella is more abrupt. And I think maybe a bit more like what we think of when you think of like a foodborne diarrhea type thing. Okay. In that it tends to happen anywhere from one to four days, maybe rarely up to a week after infection. And often one of the first signs is a fever. It started with a fever.

It started with a fever. and then headache feeling crappy and then boom this diarrhea comes on and it's profuse it's bloody it's watery it's mucasy for people with mild symptoms they'll probably recover within a few days but people who progress to dysentery here's where you can have some numbers of poops Aaron they can pass more than 20 stools in a day Wow. Yeah. Yeah. And while extra intestinal manifestations, so this bacteria fully leaving the intestine and causing illness elsewhere, are rare, and I don't have a number on it, Aaron, so I don't know exactly how rare. But they are certainly possible. And in the case of Shigella, they can cause things like seizures, although this is mostly in kids and probably more related to fever or other metabolic derangements from like electrolyte imbalance. Hymolitic uremic syndrome, like I already mentioned. But in very severe cases, things like intestinal perforation or separation of the wall of your intestine, like the lining separates.

Oh, my God. Yeah. It's pretty severe. So for both of these amoebic and chigella dysentaries, if you survive either of those, what are some of the lasting effects? Like I would imagine that like lesions with amoebic dysentery are bad and then like perforation would be really bad. Like are there lingering effects? Yeah, perforation is really bad. Like if you don't have surgery, you're just going to die. Okay. Yeah. The lesions and ulcers themselves with treatment will heal most likely because your gut, it actually turns over quite a lot.

So it actually can really do a good job healing itself. Okay. But what's interesting, and And I was going to talk about this later in the episode, but we can talk about it now since you asked. Microbiome? Yeah. Microbiome. So there is increasing evidence that infection with, I think most of the studies have looked at Shigella specifically, but with diarrhea-causing bacteria and especially dysentery-causing bacteria and potentially amoebae as well, can then put you at higher risk of having IBS. Oh, okay. Heritable bowel syndrome.

Yeah, and there's some pretty good evidence. I'll link to a paper that's kind of like a meta-analysis of what we know so far or like a review paper. It's really interesting because if you progress to dysentery, that is pretty severe. Your gut is very unhappy. You're destroying a lot of what was there, both in terms of the architecture of your gut and also the symbionts that you had there. So it's not surprising that you could have potentially lasting effects. But these are both treatable infections. So that's great.

They're obviously different in terms of the antibiotics that you would use to treat them. But the most important thing for any kind of dysentery is oral rehydration therapy. And so that's to combat the massive amount of dehydration. So that's dysentery, Aaron. It sounds horrible. Yeah. Yeah. It doesn't sound great.

So, Aaron, like, I assume we. always gotten bloody diarrhea, but is like, when did we find out about it? Yeah, yeah. It's a, it's a tough question, and I will try to answer it right after this short break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and

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The story of dysentery is, it's an interesting one because it's not the story of one pathogen or one outbreak or one epidemic or one discovery, right? The main character changes constantly throughout the history of dysentery, and it can be difficult, I have to admit, to find one common thread sort of driving this story. Especially, I think, because, I think, Because if you zoom in on like one time or place, on one little snippet, one photo of that history, that common thread that you're looking at, what you've zoomed in on, that branches off into a million other paths or stories that you could follow down. Like, oh, I want to learn more about how the shigotoxin was discovered and the implications for

that in terms of like cell tissue culture and the shigotoxin or shigella. You know, it's just like it's, yeah. Yeah. It's complicated. And you probably already gathered that from the fact that there are these many different species of microbes that can cause dysentery. Right. And so what I want to do with this history section is to present a very broad picture of the history of dysentery, the flux, the runs, the trots, whatever name you want to use. And it has gathered its fair share over the years.

Oh, yeah, I bet. Where did this come from and how did we get to where we are today? And the answer to that question is, well, it's kind of the same as it has been for many of the other diseases that we've covered on this podcast. And if you're a repeat listener, you can probably make a pretty solid guess. No pun intended. Considering that these are pathogens or parasites transmitted through the fecal oral root, it makes sense that one, once humans started gathering in large groups and settling in one area for at least, you know, a growing season, that it became much more likely to come into contact with poop, your own

or someone in your community's poop or like livestock poop. This is not new ground that I'm covering here. But in researching for this episode, I realized that I hadn't ever really stopped to consider like what that transition from nomadic to sedentary lifestyle, what that looked like, and how sanitation or sanitation technology began to catch up. Like it needed a period of time to catch up after humans started to settle in one place. Sanitation, especially latrines, you know, that serves such a hugely important purpose in our lives. It separates us from our urine and faecal waste.

and it provides a place where that waste can decompose, and that's a process that also, you know, importantly, helps to reduce the prevalence of pathogens. It's when sanitation breaks down or is suboptimal that we tend to see these outbreaks of intestinal pathogens and parasites, including those that can cause amoebic and basillary dysentery. I think some of us maybe carry around this image of early human settlements as being just like absolutely filthy with people and animals pooping everywhere and no clean water to be found, but in reality nothing could be further from the truth. Latrines and sewers and drains and bathrooms and wells and aqueducts and cisterns and piping, these things have all existed for thousands

and sometimes tens of thousands of years. The modern flushing toilet is dated to 1596, but old versions of a flush toilet have existed since at least the Neolithic, maybe to around 3,000 BCE in the Indus Valley. Yeah. Flushing toilets? Uh-huh. Like, yeah. It's, and elsewhere, like in ancient Mesopotamia or ancient Greece, there were pit toilets with variations in the size of the pit or the slope of the drain or the shape of the seat and so on. Like, the longest known horizontal drain from ancient Mesopotamia was 200 meters long.

Oh, my goodness. And that was at the Moon God complex from around the first millennium BCE. So it's impressive, right? Yeah, that is impressive. Humans are more ingenious than I realized. I think it's sort of like necessity is the mother of invention. Yeah. Yeah.

Yeah, I mean, you know, think about ancient Rome. I think, you know, when I picture ancient Rome, maybe because the lead episode we did what seems like forever ago, but all the pipes and the baths and the drainage systems. I read a fun little tidbit that there were apparently communal toilets in ancient Rome were very common, very popular. And they used to be used as like social gathering spots where you could catch up on gossip and plan your next get together. I mean, that makes sense. Like bathrooms still are. They are. Like you all go the bathroom together and you chit-chat and have a fun time. Yeah. And no, I'm not going to spend the entire history section talking about the evolution of the toilet or sewage systems. Although it would be kind of fun. Yeah. Yeah.

It could be a great episode. Yeah. But I did just want to emphasize that as soon as humans began settling in large permanent groups, they began to devise ways to manage waste. Over time and across, you know, different geographic areas, that visceral disgust that humans have for fecal waste, it found its way into culture. In ancient Mesopotamia, for example, around the first millennium BCE, there was a demon who dwelt in latrines or bathrooms, who was responsible for illness, injury, or bad luck. And there were also demons in ancient Mesopotamia, associate. with rubbish heaps. And then, of course, I'm sure you're familiar with the saying cleanliness is next to godliness. These cultural perceptions of waste, they led to the

development of rules and regulations regarding where you could or could not dump your chamber pot or your dead cow or goat. They influenced the frequency of bathing or handwashing and the way that food was prepared. When myasma became this, like, leading theory as to the origins of disease, it wasn't far off from the truth for several pathogens or parasites. The steps that you would take to avoid myasma, this bad contaminated air, those steps would in many cases be the same ones that you would take to avoid several intestinal diseases. For instance, in the 14th century, CE, a Spanish physician wrote a book on Army health, where in it he said that you should dig pits to use as latrines at the edge of army camp

and to bury the dead bodies there and also that you should dip a white cloth in a possible water source before you drank it to ensure that it remained unstained. Yeah, I mean, it's good advice. I mean, it's good advice. And I think it's interesting to sort of see these practices that were developed before any knowledge of germ theory. Yeah. But of course, this isn't to say that sanitation technology or these cultural practices or community rules or dipping a white cloth into water, that these were always successful in preventing the spread of pathogens or parasites, especially those transmitted through fecal waste. Because if they were 100% successful, the world would look like a very different place and this podcast might not exist, which is a great name.

I wrote down here, great name for Urban Legends or Conspiracy Theory's podcast. But things like flooding rivers or stagnant streams, droughts, population growth leading to massive refuse piles, the proximity of cesspits to places where food was being prepared, the use of human feces as fertilizer, and the lack of knowledge of how diseases were truly transmitted, you know, all of these things led to the continued presence of many, many different pathogens and parasites that are transmitted fecal orally. And dysentery in its various forms was certainly one of those diseases. And not just occasionally transmitted, but frequently. Like enough so that Hippocrates wrote about it.

Of course, got to say Hippocrates. Of course. It's in our contract. Just going. It gets its name from ancient Greece. The word dysentery comes from the Greek du centeria, duce meaning bad, and entera meaning bowels. And later, of course, it was known to many people as the flux or the bloody flux. Where does that come from exactly?

Just because your guts are in flux. Flux just means flow. Yeah, okay. So it's just like, yeah. Bloody flow. Yeah, that makes sense. Okay. So we know that from writings, dysentery was present in many of the same.

many ancient old world civilizations, but do we have physical proof? Or do we have any guess as to when it arose in humans or first started infecting humans? Kind of, I mean, yes, more to the first question than to the second. And so here I have to switch from talking about dysentery as a singular subject to one that is caused by different microbes. Okay. And like you, Aaron, I'm focusing on the two big ones, right? Entimiba histolytica, and I'm grouping them all into just Shigella. I don't talk about the different species or, yeah. That's fine.

I didn't either because that's, yeah. Well, that's like one of the, that's one of the multi-branching pathways I was talking about. Exactly. How different species have seemed to take over over time and they cycle in terms of their endemicity. Yeah. Yeah. It's complicated. And their like virulence and everything.

It's, ooh, it's a mess. It's, yeah. Ooh, I did want to ask about the virulence. It's different. Is it from different toxins? Is this weird to do this now? It might be weird. Yeah, I mean, yeah, toxins play a big role in it.

But from what I read, at least, it's not, like, necessarily specific to toxin. Like, that's one part of it, but it's not the whole story. Okay, gotcha. Yeah. Okay. All right. All right. Anyways, back to it.

Going back to it. So generally speaking, if we want to know the prevalence of things like intestinal pathogens and parasites in ancient human populations, we can't really use skeletal remains, like the way we can for tuberculosis and syphilis, for instance. Right. Instead, we have to turn to coprolites. We love coprolites. Oh, lovely. Or soil samples taken from burial areas around where the intestines will.

of decomposed, so like the pelvic area, which is, I hadn't thought of that before, very interesting. That's very interesting. Or we can analyze soil samples from archaeological remains of these latrines or cesspools. When it comes to dysentery, though, we're still pretty limited because dysentery is diarrhea. Yeah. And only well-formed stools can be preserved as copperlights. Yeah. Yeah.

Yeah. That being said, there is some paleo-parasitological evidence of entomiba histolytica infection in humans. The cysts of e-histolytica don't preserve particularly well and only do so under very extreme conditions. So like extreme cold, extreme dryness, whatever. And so a microscopic examination of soil or preserved feces isn't often successful. and even if you do end up seeing, you know, an amoeba or a cyst of an amoeba under the scope, like you said, it might not be, like you can't distinguish between entomoebhystallitica and a non-pathogenic species. Right, right.

And so instead, biomolecular tools, like immunological tools, you know, antigen testing are used if possible, which is great because it can distinguish among species. But still, there have been, according to a book I read published in 2015, so those numbers might have changed, only five published articles describing the discovery of Entomiba histolytica in ancient samples using either macroscopy or immunological assays. Okay. The most ancient of these samples that tested positive for e-histolytica antigens is from Switzerland, around 3,400 BCE. Wow. Yeah. And there were a few samples that tested positive from Greece between 5,000 and 2000 BCE.

Hmm. And there have been additional samples from various European sites in the Middle Ages that have also tested positive. Interesting. Yeah. The first reliable evidence for Entimeba histolitica in the new world is from the 12th century, CE. I couldn't find any estimates for the emergence of Entomuba histolytica or how long it's been associated with humans. But people do seem to think, and I think the paleo-parasitological evidence points to this as well, that it probably has an old world origin, and that it seems to be possible that it evolved with humans,

since there are entomoeba species that can infect great apes, and that also the possibility of being an asymptomatic carrier or being chronically infected asymptomatically, that would allow it to persist in a community even of smaller sizes. So you wouldn't necessarily need the crowd, like crowd disease type thing. It's interesting if it's something that has been with us forever, has it always caused disease at a low level? or is that, you know, that like at what point was it able?

But if there's similar ones that do cause disease in great apes, then maybe it is just like sort of has always caused disease, but just a little bit. Ah, that's interesting, Aaron. Yeah, it's, it's, I wish that there was, and maybe I just like missed, you had the wrong search terms or something, but I would love to read more about sort of the, you know, early evolutionary history of Entima histolitica. Yeah, yeah. And then, of course, the other main cause of dysentery, these various chigella species, again, I couldn't find an exact date, but their relationship with humans is also thought to be pretty darn old. So the various species of chigella that caused dysentery all evolved from E. coli or are still E. coli, depending on who you ask. Yeah. I remember we talked about that in our E. coli episode. Uh-huh. Uh-huh.

Yep, yep. And so I actually went back to my notes for that episode, and I was like, oh, okay, E. coli has been with humans since humans were humans. Okay. And so I wrote here, well, it stands to reason then that Shigella might also be fairly old. Yeah, pretty logical. Yeah. But regardless of precisely when Entomiba histolytica or the dysentery causing Shigella species, when they first started infecting humans, we can be absolutely sure. that once humans began to form these large settlements, they weren't just building permanent homes for themselves, but also for the causative agents of dysentery. And under these conditions, dysentery absolutely flourished. It became a very familiar disease

and also one that was very much dreaded. And part of that was something that you talked about, who was most likely to be killed by the disease. children. Yeah. And also armies. Not only did military campaigns and war create absolutely wonderful conditions for fecal oral pathogens or parasites to blossom. I mean, remember the typhoid episode? Oh, yeah. These military campaigns also played a direct role in increasing the geographic distribution of those microbes, including the ones that cause dysentery, right? So you're like, oh, we're going to go. We're going to go on the crusades and we're going to spread dysentery throughout everywhere we go.

Yeah, just pooping it along with you. Pooping it along with you. Dysentery ran through the Persian armies that invaded Greece in 480 BCE. In France in 1779, there was an epidemic of dysentery likely basilari that was exacerbated by troop movements and led to the deaths of 175,000 people, most of them children. And in the U.S. Civil War, the annual morbidity rate for dysentery for Union soldiers was 876 per 1,000. So basically everyone got it. And annual mortality rates were estimated at 10 per 1,000.

Wow. And these numbers were even higher in prisoner of war camps, such as the one where Union soldiers were held at Andersonville, Georgia, where 16,000. and 772 cases of diarrhea and dysentery were recorded, and 4,529 soldiers died. Oh, my gracious. Benjamin Mosley, who was the former English Surgeon General in Jamaica, he wrote in the early 1800s, quote, because you know I love quotes. Quote, the dysentery or flux, being a disease so destructive to soldiers in camps and garrisons and a constant attendant on all military operations, it is a medical inquiry of the

utmost importance to investigate this disease with the utmost attention in hopes of finding some method to put a stop to its devastation. It is a subject in which the welfare of mankind is deeply interested, and often the glory and honor of a nation. If the cause of humanity were not alone a sufficient motive to induce to this research, we need but turn our eyes on the political field, where we should behold the best concerted measures often defeated by its influence. So, yeah, of course, it devastated soldiers, and it was like, we need to get this taken care of. And then off the battlefield entirely, it was also devastating. Right.

There's an impressive list of famous people killed by dysentery, the Byzantine Emperor Constantine the 4th in 685, C.E. Louis the 9th of France in. 1270, King Henry the 5th of England in 1422, Erasmus in 1536, Sir Francis Drake in 1596, Akbar, ruler of the Mughal Empire in 1605, Nathaniel Bacon in 1676, and on and on. Like I skipped a ton of people because I was like, this is ridiculous. Like, who didn't die of dysentery? Yeah, who didn't die of dysentery? I mean, and I'm sure that everyone remembers dysentery from the Oregon Trail.

Yes, I remember it very. You have died from dysentery. You have died from dysentery. Yep, yep. And, you know, dysentery was truly devastating. It was a plague. It was a pestilence, a scourge. Like there's no, there's no word too hyperbolic, I guess, to describe it. Yeah, yeah. And so, of course, people were looking into it. For hundreds, thousands of years, even, they were looking into it. treatises upon texts upon papyri and quite honestly it didn't do much good at least until the late 1800s for much of the human history of dysentery there was no distinguishing between the amoeic and bacillary forms of the disease and in many ways there didn't need to be they were transmitted in the same way the symptoms they caused were quite similar and most importantly there was no cure for either Right. But there were plenty of attempts. Yeah. Bleeding, naturally. Right. That, yeah. I know. It gets worse.

It's just so illogical in this case. Like, that's already part of your problem here. Oh, I know. It's like bleeding to reduce the inflammation in the intestine is like how it was prescribed. Oh, my goodness. I know. Okay. Give me more. Ipicac or rhubarb for some vomiting to empty the stomach. Sure, yeah. Mm-hmm. Something like tartar to cleanse the bowels. What?

Yeah, so you're basically empty. And these cures, as per usual, did more harm than good. Uh-huh. It is, I think it's interesting. Like, it is, of course, really difficult to resist the temptation to be like, what were you thinking? I know. These clearly are terrible things to do. But also, I just find it fascinating because a lot of you.

of the way that treatments were designed were to keep the bodies like humors in balance. And so it's just like, but if you want to keep your electrolytes and your water in balance, like you're losing so much water, don't you think you might want to replace it? But did they know that? No, I know. They didn't know about electrolytes, Aaron. I know, I know, I know. I need to resist that.

It's hard. For this one in particular, I'm like, Just water and sugar and salt. Okay. Right. Yeah. And it was only in the late 1800s that dysentery was recognized to be caused by different organisms. Entemoeba histolytica was first described in 1875 by Russian scientist Fedorlau, who isolated the amoeba from a patient and then confirmed its ability to cause disease by feeding amoeba-rich stools to a dog, who developed similar.

lesions. Oh, and there were plenty of also, I should mention, of, quote, human volunteer experiments to confirm because it was heavily debated for a while whether it was the amoeba itself causing disease or if the amoeba was just something that sustained it. And this actually makes, like this debate makes sense in the context of the later discovery that there are indistinguishable species of entomoeba, one of which is pathogenic and the other is not. Hmm.

So that, like, there was a long debate being like, no, it's not the amoeba that's causing disease. It's something else. Huh. Yeah. I don't know. Interesting. Yeah.

And this debate continued even after the Shigella bacillus, or I guess Shigella bacilli, were discovered in, 1898 by Japanese physician Kyoshi Shiga, which was also the first time that it was demonstrated that dysentery could have multiple causative agents. And Shiga had culture the Shigella bacillus from a patient with dysentery during a huge epidemic in Japan. The 1897 outbreak, which had a mortality rate of 25 percent. And, yeah, and ended up killing over 22,000 people again, the majority of them, children.

In fact, Shiga himself described dysentery as, quote, the most dreaded disease of children. And after Shiga published his findings, other researchers repeated his isolation and culture techniques and were able to confirm that this bacillus was responsible for dysentery. Although later work, of course, revealed that it wasn't this bacillus, but rather these bacilli, as it turned out there were multiple species responsible for causing dysentery.

I'm always struck by the period of time between the late 1800s and the early 1940s or so when our knowledge of pathogenic microbes and parasites had greatly expanded, but we were still largely helpless against treating them. Yeah. The bacterial ones anyway. Like vaccines, of course, were another story for many diseases. but yeah, like we were largely helpless against a lot of bacterial diseases. And so despite now having at least two causative agents in hand for dysentery,

the disease still raged in the military, in prisons, in psychiatric institutions, killing so many people and so many children. We've talked recently about the horrific conditions of trench warfare and World War I in regards to trench fever. And dysentery was also an enormous contributor to morbidity and mortality during that war. The development of sulfonamides in time for the Second World War, or at least for the end of the Second World War, it reduced the military mortality of dysentery enormously for that conflict down to 0.07%.

Wow. However, it was not the same situation in the concentration case. camps and prisoner of war camps, of course, during World War II, where dysentery raged, unchecked, and was absolutely horrific. But I have a bit of side trivia here. Before antibiotics were developed, dysentery caused by Shigella was one of the first diseases successfully treated by bacteriophages in 1919. Oh my gosh, I saw that article, Aaron. Yeah.

Isn't that so interesting? It's fascinating. I was like, what? This is from like the early 1900s? I know. It's so cool. Shout out to Stephanie Strathie. Please check out our antibiotic resistance episode because it's really fascinating. Yeah. So anyway, from the beginning of the 20th century, the landscape of dysentery had greatly changed across the globe and is still changing today. An incredible amount of progress has been made on both Entomiba histolytica and the dysentery causing Shigella species in terms of virulence factors and plasmids and evolution and genetic diversity and all those other things.

And dysentery has greatly dropped in prevalence in many places, especially with advancements in sanitation infrastructure and the application of antibiotics. But it is still so extremely and frustratingly prevalent across the globe, causing devastating outbreaks such as the one in Guatemala in 1969, which led to an estimated 10,000 deaths. And over the next four years, it's estimated that there were 500,000 cases and 20,000 deaths due to dysentery in Central America. And in the late 1970s in Central Africa, an epidemic of dysentery began to spread and then to remain at high numbers, high incidents.

In the early 1990s, civil wars and mass genocide and the construction of refugee camps led to the sustained outbreak in Rwanda with weekly dysentery attack rates in the camps estimated to be 3.8 per 100 people. Yeah. And one of the most concerning things about the epidemics and the outbreaks that have happened starting in the second half of the 20th century is antibiotic resistance. Shigella were one of the first bacteria to show multi-drug resistance starting in the 1950s. The 1950s? How many multiples of drugs do we even have then? That's awful. It's horrible. And as far as I can tell, this trend towards antibiotic resistance, maybe you'll tell me something different, but it hasn't seemed to turn around. It seems to be remaining fairly steady and on the rise. Yeah, I'm not going to tell you anything different.

Okay. Dysentery loves a disaster. It loves a disruption, whether it's a civil war or a busted sewer, an overflowing river or a drought. it thrives on that disturbance. So much of the world does not even currently have access to clean water, leaving them extremely vulnerable to dysentery and other diseases. And I can't help, but now when I watch the news and I see all the horrific climate disasters that are happening, I can't help but think, oh, dysentery is going to love this. So, Aaron, I'm hoping. I'm hoping. hoping you'll tell me some good news about dysentery. I, well, let's just take a break. Oh, great.

And then we'll just talk about it. So like many of our episodes that get a little complicated, like we're dealing with a lot of different things. It's hard to put a number out how many people have bloody diarrhea, et cetera. So we're going to do the best so we can with numbers. I think we'll get an overall picture of how bad it still is. Okay. None of these estimates are super recent. Most of them come from like the early 2010s or so. But overall, looking just first at Shigella, it's estimated that there's between 165 and 188 million cases of Shigalosis. So that's Shigella associated diarrhea or dysentery globally every year. It's estimated that includes over 60 million cases in kids under age five.

Oh, my gosh. And this 2018 paper that I read also estimated that Shigella infections are the second leading cause of death due to diarrhea after rhodovirus. And caused over 164,000 deaths annually. That includes over 54,000 deaths in kids under age five. just from Shigella. Oh my gosh. Yeah. It's pretty horrific.

Yeah. When we look at amoebic dysentery, we have, I think, even harder numbers. I don't have numbers on the estimates of total infection worldwide, but I did find that it's estimated that 55,000 people a year die from Entimuba histolytica infection. And, of course, many of those are children. It's one of the top like 15 causes of dysentery in developing countries for kids. And especially with amoebic dysentery, there have been some studies that suggest that like in endemic areas, up to 40% or more of the population shows evidence of prior infection. So this is an amoeba that's really widespread even when it's not causing disease.

A quick question about that and about immunity, because I guess this will play a role then if, you. in any discussion of vaccines. Is there any immunity to either amoebic or chigalosis? It's a good question. So off the bat, we don't have vaccines for either. There's good evidence that the potential to develop a vaccine exists for Shigella. There's work being done. There's a lot of promise.

There's been patents filed to develop vaccines for Shigella, especially to try and like develop vaccines against both Shigella and typhoid, like combining those both in one vaccine because that would be really beneficial. Those are spread in similar ways, et cetera. But right now, nothing exists like that. But animal model studies suggest that the type of immune response that we develop could be protective. The problem is that there's a lot of different species and there's a lot of different serotypes. So how much cross protection you would get from an immune response is unclear. With entomoebihistolytica, I could find even less information. So people mount an immune response, but again, because it can be kind of like an asymptomatic

infection, it's not really clear like, do you, are you protected from reinfection, are you chronically infected, et cetera. So for that one, I think we're even further from the potential for a vaccine. It doesn't mean it's impossible, but we just have to hope. Yeah. Yeah. Gotcha. So if you look at these two causes alone of dysentery, we're talking about millions of cases and hundreds of thousands of deaths due to dysentery just from these two sources. And like I said before, there's other bacteria that can also cause the same illnesses essentially. So obviously the biggest deal when it comes to dysentery and diarrheal diseases in general

is trying to prevent them. Right? And like you mentioned, Aaron, getting better at present. prevention means access to clean water and sanitation so that people aren't coming into contact with human feces. And that's really the bottom line. The other bottom line, like I mentioned, way towards the beginning, is addressing problems of nutrition because malnutrition is a huge risk factor for severity of disease, especially for entomoebihistolicica, but also for other forms of diarrhea and dysentery. And both of those things addressing malnutrition and addressing sanitation,

takes infrastructure, which takes money, right? So a lot of different organizations, the World Health Organization, UNICEF, so many others, have a lot of lofty goals to, like, eliminate deaths from diarrheal diseases by 2025. That's one of their goals. I don't actually know how well they're doing on that front. Again, it's hard to get some data on this. But if we just look at sanitation overall, the World Health Organization, estimates that only 45% of the global population currently have a safely managed sanitation system,

like one that is going to actually be effective at preventing intestinal pathogens from spreading. So that's not great. They also estimate the World Health Organization, and this isn't specific to dysentery. So if we look a little more broadly, the World Health Organization estimates that 827,000 people die as a result of inadequate water, sanitation, and hygiene. And this altogether accounts for 60% of all diarrheal deaths. That's... Wow.

Yeah. So improving access to clean water, sanitation can prevent literally hundreds of thousands of deaths, including nearly 300,000 children under the age of five every year. Oh, my gosh. Yeah. Yeah. So that's... kind of where research needs to focus at this point. It's like what are the best ways to sort of develop

and implement those systems in ways that's actually going to be sustainable and make a difference. Mm-hmm. And permanent. Like not just like let's go in, build a bunch of, you know, sanitation infrastructure and then leave and then not provide any funds to maintain it. Exactly. That's such a problem. Right. Yeah. Yeah. Yeah. So I mean, that's kind of the status of of diarrhea of sanitation of dysentery today. I kind of already mentioned some of the interesting research that's going on in terms of like how dysentery affects your overall microbiome and associations with the development of things like irritable bowel syndrome. So we kind of already jumped ahead and talked about that. And yeah, vaccines are something that's like people are

doing research on it, but we're not super far along from what I read. That's dysentery, Erin. It's not a super happy ending. It's not. I don't think we should have expected one. No, no, we never do. Especially when it comes to diseases that predominantly affect developing countries. Definitely. Yeah. Well, sources?

Let's do it. Okay. I want to shout out, I have a bunch of articles, but I'm going to shout out one book and a couple of articles in particular. The book is titled Sanitation Latrines and Intestinal Parasites in Past Populations, and the editor is Pierce Mitchell. And then there was a great paper called A Brief History of Shigella by Lampel et al from 2017. And then another paper by Haycock from 2002 called Exterminated by the Bloody Flux. Oh, that's a good title. Yeah, that was in the journal for maritime research. Oh, cool.

I had a lot of papers for this one. That awesome quote that I read was from a 2003 paper titled Emmibiasis in The Lancet. There was a number of other papers. I really loved dysentery, including amoebiasis. It was written in 1973, published in BMJ, but it was a really nice overview of both Shigella and amoebic dysentery. A few others on the biology, but if you'd like to read more about, dysentery and irritable bowel disease. That paper is in the journal Gut, published in 2004.

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