Speaker 1: I was called on to visit the Major about the
Speaker 1: middle of May. He was lying in bed and looked
Speaker 1: pale and emaciated. His eyes were sunk, his cheeks hollow,
Speaker 1: and his countenance dejected. He told me he was in
Speaker 1: violent pain which could not be palliated without taking two
Speaker 1: or three grams of opium every three or four hours.
Speaker 1: His bowels were obstinately costive, and he was obliged to
Speaker 1: take some purgative medicine every day. Food was loathsome to him,
Speaker 1: and he had profuse perspirations, for which he was taking
Speaker 1: wine and bark. I endeavored to restore his appetite by
Speaker 1: lessening the quantity of opium and substituting the tincture of
Speaker 1: hops as much as possible. His appetite was frequently coaxed
Speaker 1: by some delicacy, and the sweet oil was frequently alternated
Speaker 1: by magnesia and rhubarb. This treatment was regularly pursued until
Speaker 1: the last of June, and although he suffered much pain
Speaker 1: during that time, he was evidently much better and his
Speaker 1: appetite improved. The pain in his bowels was less frequent
Speaker 1: and not so violent. July fourth, I was sent for
Speaker 1: in great haste to visit him. When I entered his room,
Speaker 1: I was astonished at his altered appearance. His countenance was
Speaker 1: pale and fallen. He was sitting up in his bed,
Speaker 1: struggling for breath. His body was covered with cold and
Speaker 1: clammy sweats, and he had a most anxious and desponding look.
Speaker 1: I immediately gave him large quantities of ether and laudanum.
Speaker 1: These injections brought away from his bowels large quantities of
Speaker 1: dark and hardened feces. They were repeated every day during
Speaker 1: this month with the happiest effect. And it was astonishing
Speaker 1: what masses of these dark and indurated feces were evacuated
Speaker 1: during this time. September, he is much emaciated and exhausted
Speaker 1: by want of sleep. The pain and swelling have pervaded
Speaker 1: all his extremities. Opium can no longer lull his pain,
Speaker 1: and nothing but death now seems to offer him any
Speaker 1: hope of relief. Last entry, he is affected with arispolis
Speaker 1: and is gradually sinking into a state of insensibility. In
Speaker 1: this state he lingered until the thirteenth of September, when
Speaker 1: he expired without a struggle.
Speaker 2: Wow, Yeah, that is brutal. It's horrible.
Speaker 1: So that is an account of dysentery. And it is
Speaker 1: from a book titled Medical Sketches of the Campaigns of
Speaker 1: eighteen twelve, thirteen and fourteen by James Mann and it
Speaker 1: was published in eighteen sixteen. Hi, I'm Aaron Welsh.
Speaker 2: And I'm Aaron Allman Updyke.
Speaker 1: And this is this podcast will Kill You.
Speaker 3: And well, so today we're covering dysentery. We are, But
Speaker 3: that first handy count Aaron, when you read it, like,
Speaker 3: it doesn't really.
Speaker 2: Sound like dysentery.
Speaker 1: Here's my thoughts because I kind of agree, But I
Speaker 1: was like, you know what, Erin, you don't know anything
Speaker 1: about the biology, leave that to Erin. So so like,
Speaker 1: you know, just trust the physician from eighteen thirteen that
Speaker 1: you know that he knew what he was doing. Yeah,
Speaker 1: And the other thought I had is that, yeah, this
Speaker 1: could have been any sort of diarrheal pathogen. But I
Speaker 1: wonder if some of these symptoms were caused by the
Speaker 1: things he was taking, like opium and that lead was
Speaker 1: like a really popular treatment as well mercury.
Speaker 3: So yeah, I don't know absolutely, because it sounds like
Speaker 3: he was having a lot of issues losing weight in
Speaker 3: a lot of pain and then was given a ton
Speaker 3: of opium, which is gonna block you up really good.
Speaker 2: Yeah, so that's why.
Speaker 3: Then his bowels became compacted.
Speaker 1: Is that the word they used? I think what did
Speaker 1: they say? Did they say obstinate? No, yes, obstinately costive?
Speaker 2: Yeah, yeah, that'll do it.
Speaker 1: But in any case, it is horrific. And yeah, but
Speaker 1: also I think that, uh, let's see, the vagueness of
Speaker 1: this first hand account or like the hard to pin
Speaker 1: downness is kind of characteristic of the topic that we're
Speaker 1: covering today. Absolutely, yeah, because dysentery, why do we do
Speaker 1: this to ourselves? Again? Is not caused by one, not two,
Speaker 1: but by several pathogens and parasites. So it's gonna be
Speaker 1: an interesting ride.
Speaker 3: Yeah, as always, as always, as always, Yeah, and as
Speaker 3: always I believe that it's quarantiney time.
Speaker 1: It is. What are we drinking this week?
Speaker 2: We're drinking in flux.
Speaker 1: So flux was the one of the old timy names
Speaker 1: for this disease. I think it actually might still be
Speaker 1: called flux in some places flux or the bloody flux.
Speaker 1: And so you know, since the definition of dysentery has
Speaker 1: kind of been in flux, that's what we're going with.
Speaker 3: But Aaron what infos.
Speaker 1: Well, I thought it would be kind of a nice
Speaker 1: callback to the first hand account to include rhubarb. So
Speaker 1: we're gonna do a rhubarb syrup plus some gin, plus
Speaker 1: some sparkling water, strawberries and lime juice. Yum. And we
Speaker 1: will post the full recipe for this quarantine as well
Speaker 1: as the non alcoholic plus see burrita on our website
Speaker 1: This podcast will kill You dot com, as well as
Speaker 1: on all of our social media channels.
Speaker 3: And speaking of our website, this podcast will kill You
Speaker 3: dot Com. We just keep telling you guys to go there.
Speaker 3: Have you gone there yet? It's really great. We have
Speaker 3: a bookshop dot org link. We have a good Reads link,
Speaker 3: we have links to Bloodmobile, our music, we have links
Speaker 3: to our Patreon, to our merch to transcripts to all
Speaker 3: of the sources from all of our episodes.
Speaker 2: Wow.
Speaker 1: Yeah, it's a It's a gold mine.
Speaker 2: It really is. Yeah.
Speaker 1: Do we have any other business erin I do?
Speaker 2: I have a correction?
Speaker 3: I wanted to point out that somebody emailed us and
Speaker 3: I really appreciate this about One of our recent episodes
Speaker 3: was on Legionnaire's disease and erin. You and I talked
Speaker 3: a lot about atypical versus typical pneumonia.
Speaker 1: I recall that conversation.
Speaker 3: Yeah, and how like poor of a definition it is.
Speaker 3: It's still true. But a listener pointed out, and I
Speaker 3: think this is important, is that today the term atypical
Speaker 3: is mostly used to mean pneumonia that's caused by bacteria
Speaker 3: that don't gram stain very well, rather than previously atypical
Speaker 3: used to be like clinically a little different, or not
Speaker 3: responding to antibiotics, or maybe radiographic differences. But like we
Speaker 3: talked about in the episode, those are not good definitions
Speaker 3: to distinguish different types of pneumonia. So at least the
Speaker 3: way that we use it today is moderately better. Things
Speaker 3: that don't Grant stain well. But again, some things that
Speaker 3: are not considered atypical pneumonia's also don't Graham stain well.
Speaker 3: But that's besides the point. It's still an imprecise term,
Speaker 3: but it's at least a little bit better.
Speaker 1: Okay, So it's more about the pathogen now than it
Speaker 1: is about the symptoms or signs.
Speaker 3: Right, like the clinical picture, gotcha, Okay, that's something.
Speaker 2: Yeah, so thank you again. That's all I got. Should
Speaker 2: we dysenterry it up?
Speaker 1: I think so. She feels like a fast intro, but
Speaker 1: I'm here for it. Let's do it.
Speaker 3: We'll take a quick break and then we'll dive in.
Speaker 3: I'm going to go through this a little bit out
Speaker 3: of order from my usual because, like you said, Aaron,
Speaker 3: this isn't a very typical disease that we cover on
Speaker 3: this podcast.
Speaker 2: So first, what I'm going to do is cover kind.
Speaker 3: Of the symptoms of dysentery. We'll talk about like what
Speaker 3: does dysentery actually mean, and then I'll focus on a
Speaker 3: few of the specific causes, and then Aaron, you can
Speaker 3: ask me a million questions and I probably won't know
Speaker 3: the answers. Cool.
Speaker 1: I am very excited.
Speaker 2: Okay.
Speaker 3: So generally dysentery can be defined as bloody diarrhea.
Speaker 2: Is that cool? Can we all be cool with that definition?
Speaker 1: I mean, that's it, right?
Speaker 2: Like pretty much? Yeah, pretty much?
Speaker 3: Okay. Diarrhea we've talked about kind of a lot on
Speaker 3: this podcast, although not for a while. The the World
Speaker 3: Health Organization definition is three or more loose or liquid
Speaker 3: stools in a twenty four hour period. But even that
Speaker 3: definition is pretty loose. Huh.
Speaker 2: I swear the whole episode's not going to be like this.
Speaker 1: I think it absolutely is.
Speaker 3: Oh, but it is a loose definition because everybody is
Speaker 3: different in terms of their bowel movements, right, right, But
Speaker 3: everyone has had diarrhea at some point, so everyone knows
Speaker 3: what diarrhea feels like and what it means. So dysentery
Speaker 3: is diarrhea with blood, visible blood, and often sometimes mucus
Speaker 3: just for good measure.
Speaker 1: Okay, So question about the blood, Okay, is it bright
Speaker 1: red or is it black?
Speaker 3: Good question? It could be either color. So part of
Speaker 3: what you're asking gets at where is the blood coming
Speaker 3: from in your gi tract?
Speaker 1: Right?
Speaker 2: So, black blood.
Speaker 3: Usually means that the bleeding is coming from further up
Speaker 3: in the digestive tract. So if you have bleeding in
Speaker 3: your stomach, in your small intestine, those will usually be
Speaker 3: black by the time they make it all the way
Speaker 3: to your poop. If you have bleeding in most of
Speaker 3: your colon, then that bleeding is more likely to be
Speaker 3: bright red, although even if you bleed like a ton
Speaker 3: from higher up, it'll end up bright red. It just
Speaker 3: all depends on how long it transits.
Speaker 2: Okay, okay, okay, So.
Speaker 3: In the case of dysentery, it's probably going to be
Speaker 3: I would say, a mixture of two, but more on
Speaker 3: the red spectrum than the black spectrum. And that's because,
Speaker 3: as we'll see, it tends to be a colitis picture,
Speaker 3: and that means inflammation in the colon. So let's talk
Speaker 3: a little more about it. In order to have blood
Speaker 3: in your poop, it means that, in one way or another,
Speaker 3: your gut is very unhappy. Of course, in the case
Speaker 3: of dysentery, what it means is that you have some
Speaker 3: kind of severe inflammation going on, whether it's from a bacteria,
Speaker 3: a virus, a parasite, or even in some cases no
Speaker 3: pathogens whatsoever.
Speaker 2: So you can have a septic.
Speaker 3: Inflammatory bowel disease like Crohn's disease, or ul sort of colitis. Okay, okay,
Speaker 3: So these are autoimmune mediated conditions that cause massive inflammation
Speaker 3: of the colon that lead to bloody diarrhea aka dysentery.
Speaker 3: So any of these different things can cause dysentery. We're
Speaker 3: going to focus today really on just the pathogenic types
Speaker 3: of dysentery, and I'm going to focus even more specifically
Speaker 3: on two major causes of dysentery, but we'll get to
Speaker 3: that in a second. Let's focus on the symptoms, shall we.
Speaker 3: So you can imagine that if you have a very
Speaker 3: inflamed angry gut wall that is so inflamed that it's
Speaker 3: bleeding large enough amounts of blood that it's visible in
Speaker 3: your stools. Because if you just have a little blood
Speaker 3: you you won't notice it. You can imagine that this
Speaker 3: is a very painful process. So dysentery, like a lot
Speaker 3: of other diarrheas, are often accompanied by major abdominal cramping.
Speaker 3: And because today we're focusing on infectious dysentery, it's also
Speaker 3: common to have a fever, which of course causes total
Speaker 3: body pain. So with dysentery, you're often in terrible pain.
Speaker 3: You're pooping like crazy, you have this diarrhea, you have
Speaker 3: abdominal cramps. Often with this type of diarrhea, you have
Speaker 3: a lot of urgency, you know, that feeling like you
Speaker 3: have to go. It's like right this instant, and then
Speaker 3: it's going to be explosive and it's going to be painful.
Speaker 3: And with any type of diarrhea, one of the biggest
Speaker 3: issues is how much fluid you can lose your large intestines.
Speaker 3: One job, really like it's one job, is to absorb
Speaker 3: all of the water back from your stool so that
Speaker 3: we don't get dehydrated. And in massive diarrhea or in dysentery,
Speaker 3: that mechanism is destroyed, so you're just losing water through
Speaker 3: your behind. And so that's one of the major causes
Speaker 3: of death is just from dehydration.
Speaker 1: Okay, so you stated the definition of diarrhea as being
Speaker 1: three loose stools in a period of twenty four hours,
Speaker 1: but four dysentery? Is it three? Is it nine? Is
Speaker 1: it fifteen? Is it fifty?
Speaker 2: Yeah, so there's no number on it.
Speaker 3: It's just if those three loose stools have blood and
Speaker 3: or mucus in them, now you'd call that a dysentery
Speaker 3: rather like a regular old diarrhea.
Speaker 2: Okay, yeah, right, okay, yeah, great question.
Speaker 3: So, yeah, dehydration is one of the biggest concerns and complications,
Speaker 3: but of course it's this podcast, so there are more
Speaker 3: things that can go wrong. Of course, with dysentery and
Speaker 3: other types of diarrhea, like non bloody diarrhea, you also
Speaker 3: lose a ton of electrolytes. You're losing sodium. You're losing chloride,
Speaker 3: and so this can cause problems when your electrolytes then
Speaker 3: get out of whack, So you can end up with
Speaker 3: heart arrhythmias because of problems with your potassium. You can
Speaker 3: end up with neurologic problems because of the lack of sodium.
Speaker 3: And with dysentery, which is different than other forms of diarrhea, you're.
Speaker 2: Losing a lot of blood. So there's a risk of.
Speaker 3: Anemia, especially in the cases of more chronic dysentery, like
Speaker 3: a prolonged diarrhea.
Speaker 1: Right, like the guy on our first hand.
Speaker 3: Account exactly, And so that's how you get, like you
Speaker 3: heard in our first hand account, this kind of muscle wasting, malnutrition,
Speaker 3: and you're just sort of wasting away because you're not
Speaker 3: able to absorb anything.
Speaker 1: Right, how much blood are we talking?
Speaker 2: It's a good question.
Speaker 3: There's no like number or amount on it that would
Speaker 3: qualify something as dysentery versus not. It's really not a
Speaker 3: like strict definition, okay, yeah, And different sources would give
Speaker 3: you like slightly different definitions. I think even so the
Speaker 3: most general would be just to say bloody die diarrhea.
Speaker 3: And then, of course, because today we're going to focus
Speaker 3: on infectious causes of dysentery. There's always a risk of
Speaker 3: this infection spreading beyond the gut itself, so that even
Speaker 3: if it's not the dehydration or the malnutrition that ends
Speaker 3: up killing you, you could end up with a more
Speaker 3: widespread infection. So let's get into these specific bugs. There's
Speaker 3: a lot of different bugs that can cause bloody diarrhea,
Speaker 3: and like I mentioned, even non infectious things. It's possible
Speaker 3: that viruses can cause bloody diarrhea, but it's not super
Speaker 3: common because in general, viruses just cause regular diarrhea, not dysentery.
Speaker 3: It's possible that parasitic worms, like maybe even some we've
Speaker 3: already talked about, like hookworm or maybe tapeworms, These could
Speaker 3: potentially cause bloody diarrhea. But most commonly there's two things
Speaker 3: that cause bloody diarrhea. There's bacteria that cause bloody diarrhea,
Speaker 3: and there's an amoeba that causes dysentery.
Speaker 2: Mm hmm. We've already talked about one.
Speaker 3: Of these bacteria that are a very common cause of dysentery,
Speaker 3: and that is ecoli, right, right, So some forms of
Speaker 3: ecoli are massive causes worldwide of dysentery. There are lots
Speaker 3: of other bacteria, Salmonella we talked about typhoid already, which
Speaker 3: is a form of salmonilla that can definitely cause bloody diarrhea.
Speaker 3: Also Camplobacter, which is another bacteria. There's two that we're
Speaker 3: going to focus on today because they're the leading ladies.
Speaker 1: Well, and I think also like historically these two were
Speaker 1: the ones that caused classic dysentery. Typhoid had its own thing, right,
Speaker 1: had its own name, and so if you were to
Speaker 1: find a treatise on dysentery, it would probably be these
Speaker 1: guys would cause the vast majority, or these leading ladies
Speaker 1: would cause have caused the vast majority of them.
Speaker 2: I think so too.
Speaker 3: It's that's why we're focusing on them today. And that
Speaker 3: is Shigella uh huh and an amiba entamoba histolytica. These
Speaker 3: are the two major causes of bassillary and amobic dysentery.
Speaker 3: All right, I'm excited about this. So let's start with
Speaker 3: amoebic dysentery and then we'll talk about sigalosis or dysentery
Speaker 3: from shigella, and then we'll just like wrap up and
Speaker 3: you can ask me questions I don't know the answer to.
Speaker 2: Okay, okay, uh okay.
Speaker 3: I found this one seminar from the Lancet in two
Speaker 3: thousand and three, so it's a little bit old, but
Speaker 3: I just really liked this quote. I never read quotes.
Speaker 3: I'm going to read you a quote ready.
Speaker 1: Ooh yeah.
Speaker 3: Few pathogens are more aptly named than en amiba histolytica,
Speaker 3: the tissue licing amiba that causes amobic colitis and amobic
Speaker 3: liver abscess. Think of this protozoan parasite as a macrophage
Speaker 3: on steroids with pumped up phagastic, proteolytic and cytolytic capabilities,
Speaker 3: invading human colonic mucosa and occasionally penetrating through to the
Speaker 3: portal circulation, reaching the liver and causing fatal abscesses.
Speaker 1: WHOA, I dig the voice. If you wanted a career
Speaker 1: as a movie voiceover, I think you've got one.
Speaker 2: Thank you, thank you.
Speaker 1: But also I loved that. I love that quote because
Speaker 1: it really aptly describes and tomba histolytica. Plus it does
Speaker 1: the etymology so I don't have to do it. Yeah,
Speaker 1: it's it's.
Speaker 2: The whole thing. I really love it.
Speaker 3: Shout out doctor Samuel Stanley, excellent work. My biology is
Speaker 3: done right. Just kidding because a lot of those words,
Speaker 3: people are probably like, I'm sorry, let's talk about it more.
Speaker 2: Clearly, let's go over it. So this particular.
Speaker 3: Amiba and Tomba histolytica has a simpler life cycle than
Speaker 3: the last amba we talked about. Nagleia faleri. Amoeba exists
Speaker 3: in two forms in the environment as a cyst and
Speaker 3: this is the form that is infectious to humans when
Speaker 3: we ingest it. After we ingest it, it passes through
Speaker 3: our stomach, survives our stomach, acid, travels down our small intestine,
Speaker 3: reaches our terminal ilium or our colon.
Speaker 2: So those are the two places where.
Speaker 3: It exists and becomes a trophozoite like the amoeba shaped
Speaker 3: version of an amiba, and that's where it lives. It
Speaker 3: replicates by binary fission, so it just divides and it
Speaker 3: just lives kindly in our colon, munching on bacteria, which
Speaker 3: our guts are full of. We have plenty of bacteria
Speaker 3: for them to eat. And then it also eats our
Speaker 3: food and it's fine right until it's not. I was
Speaker 3: gonna say, I don't think so yeah, it's fine until
Speaker 3: it's not because it doesn't stop there. It's not satisfied
Speaker 3: with just eating our food remnants and our commensal bacteria. Instead,
Speaker 3: once it's in our gus, it attaches to the epithelium
Speaker 3: of our colon. It immobilizes those cells, and then it
Speaker 3: just kills them. It just lices them open and kills them,
Speaker 3: and then it invades its way, burrows its way through
Speaker 3: our mucosa and into the submucosa of our gutlaw, why.
Speaker 2: Does it do this? Aaron?
Speaker 3: I was just about to ask, I honestly want to
Speaker 3: know from what I read, it's not fully understood, like
Speaker 3: what exactly are the triggers that cause this adherence and invasion?
Speaker 3: Because the thing is only about ten to twenty percent
Speaker 3: of people who get infected with Antamyba hystolytica will end
Speaker 3: up having symptoms. A lot of people are infected and
Speaker 3: entirely asymptomatic. And you're not asymptomatic if it's invading your submucosa.
Speaker 1: Right, okay? And by infected, do you mean that like
Speaker 1: they're shedding.
Speaker 3: They're shedding cysts and you can find trophozoites in their
Speaker 3: poop as well, and that's how it has to complete
Speaker 3: its life cycle, right, it has to go back into
Speaker 3: its cyst form. You have to poop out those cysts
Speaker 3: so they can then travel to find another host via
Speaker 3: water or whatever. So it's a really interesting, like evolutionary question.
Speaker 3: What is the drive to seek out deeper spaces in
Speaker 3: our body and why do they have the capacity to
Speaker 3: do all of this damage to our tissues.
Speaker 1: It's really interesting because like, do people who are symptomatically
Speaker 1: infected shed more amibe than those who are just asymptomatically
Speaker 1: chronically infected.
Speaker 3: That's a good question. I'm not sure. I didn't see
Speaker 3: any papers specifically addressing that, but it's an interesting thought
Speaker 3: because if you have diarrhea, then yeah, you probably are
Speaker 3: shedding a lot more of whatever it is that you're shedding,
Speaker 3: But then if it kills you because of that, then
Speaker 3: you're going to stop shedding, whereas if you're infected chronically.
Speaker 3: So maybe it's a trade off between how long they're
Speaker 3: able to persist in someone before our immunes system shuts
Speaker 3: them down, versus causing massive infection but getting a lot
Speaker 3: out into the environment.
Speaker 1: Yeah, diseases trade offs.
Speaker 3: Yeah, but we can talk about sort of the ramifications
Speaker 3: of what happens when they do this burrowing, because spoiler alert,
Speaker 3: it's not good.
Speaker 2: It's horrible.
Speaker 3: Yeah, And if you thought the bloody diarrhea part was bad,
Speaker 3: it gets a lot worse. There's a vein in our
Speaker 3: bodies called the portal vein that drains blood from your
Speaker 3: small intestine and the right side of your colon are
Speaker 3: large intestine directly to the liver. So as the samiba,
Speaker 3: which we know is in the right side of your
Speaker 3: small intestine or large intestine, as it burrows its way
Speaker 3: through the mucosa and sepucosa, it can end up right
Speaker 3: in these blood vessels, hops straight on that portal vein
Speaker 3: highway and take the first exit to the liver. So
Speaker 3: the liver is the number one site of what we
Speaker 3: call extra intestinal outside of the intestine infection with ntomba histolytica,
Speaker 3: and it can be very severe because in the liver,
Speaker 3: what it does is it kills off chunks of our
Speaker 3: liver cells the same way that it kills off the
Speaker 3: epithelium of our intestine. But then our liver, in trying
Speaker 3: to protect itself, walls off these amoba, essentially forming an abscess.
Speaker 3: Within the liver, and so depending on how many amiba
Speaker 3: you have and how large these abscesses can get, this
Speaker 3: is a common cause of death in people with antomba
Speaker 3: histilitica who progress to liver abscess It can be very serious,
Speaker 3: and it's not limited to just the liver, right This
Speaker 3: amiba can theoretically travel anywhere in our body through any
Speaker 3: blood vessel that it makes it into, So it's not
Speaker 3: uncommon to find similar kinds of abscesses in the lungs
Speaker 3: or in exceedingly rare cases, in the brain. That's horrific,
Speaker 3: it is, but at least the brain is very very rare,
Speaker 3: like less than zero point one percent of people with
Speaker 3: liver abscesses have brain abscesses.
Speaker 2: And it's okay, almost.
Speaker 3: Never that you would get a brain absess without first
Speaker 3: having liver abscessed, since that's the number one site.
Speaker 1: So can you break down what those complications are like
Speaker 1: in terms of the proportion of people who are You know,
Speaker 1: if ten to twenty percent of people are symptomatic, what
Speaker 1: percentage of those would have like the liver manifestations and
Speaker 1: then the other abscesses develop and so on.
Speaker 3: It's actually more common than I realized, especially if someone
Speaker 3: has the diarrhea like is symptomatic with amoebic colitis. In
Speaker 3: those cases, one source that I found set up to
Speaker 3: seventy five percent of people that have the colitis will
Speaker 3: also then have liver abscesses.
Speaker 2: Wow.
Speaker 3: Yeah, so it's kind of like once this thing starts invading,
Speaker 3: it's really able to invade. Sure, So that's amoebic dysentery.
Speaker 1: I have a question before we move on to Okay,
Speaker 1: what is that shigella? So I really want to go
Speaker 1: back to that ten to twenty percent of people and so,
Speaker 1: like I assume there have been studies looking at the
Speaker 1: breakdown of people who are symptomatic versus asymptomatic. Are there
Speaker 1: any patterns?
Speaker 3: So yes, there there's a lot of things that are
Speaker 3: like risk factors for people who will then go on
Speaker 3: to have severe disease or this colitis. Some things are
Speaker 3: like if you're unfortunately, kids tend to have worse outcomes
Speaker 3: with all kinds of dysentery. Also, malnutrition is a huge one.
Speaker 3: But what's interesting is that amoebic dysentery specifically really tends
Speaker 3: to be associated with very poor living conditions and with impoverishment.
Speaker 3: So how much that's also associated with things like malnutrition
Speaker 3: or maybe like a very high amobic load because you're
Speaker 3: being repeatedly exposed. But kids tend to be have poor outcomes,
Speaker 3: and people who are otherwise malnourished or have other like
Speaker 3: pre existing conditions that would leave them immunosuppressed.
Speaker 1: Right, Okay, that makes sense, Yeah, that makes sense. Yeah. Yeah.
Speaker 1: I also wonder about the role of and this probably
Speaker 1: relates also to shigella, but the role of the gut
Speaker 1: microbiome in oh Aaron.
Speaker 2: We'll talk a little bit about that later because it's.
Speaker 3: Really interesting, Okay, wonderful, definitely, Uh, it's super interesting. But
Speaker 3: what's also interesting, especially in looking at the kind of
Speaker 3: overall worldwide prevalence of colonization with Antamba histalytica, is that
Speaker 3: not that long ago, and I don't have an exact
Speaker 3: date on it, but not that long.
Speaker 2: Ago, it was discovered that there's.
Speaker 3: Another amiba that looks identical to Antemyba histalytica.
Speaker 2: It's called Ntemyba.
Speaker 3: Die spar and that colonizes people but doesn't cause any disease.
Speaker 3: It doesn't cause dysentery. And so it's thought that some
Speaker 3: at least earlier prevalence studies that we're just looking for
Speaker 3: amiba in the stool, can't distinguish between these two different species,
Speaker 3: and so our estimates of overall like prevalence might be
Speaker 3: off in some cases.
Speaker 1: Yeah. Yeah, no, I have come across similar stuff. But
Speaker 1: I also wonder if you find an amiba in the
Speaker 1: stool of some in like the bloody stool of somebody,
Speaker 1: it's likely that the bloody stool is being caused by
Speaker 1: that and not coinfection with Well, that's the question, is
Speaker 1: is it because Antamoba histolytica exists both in the same
Speaker 1: areas where Antimoba dice bar does and under the same
Speaker 1: conditions that other.
Speaker 3: Forms of dysentery do. So then you have to ask
Speaker 3: the question of, like, you know, what does the clinical
Speaker 3: picture look like. So let's get into what bacillary dysentery
Speaker 3: looks like, and then we can kind of compare and
Speaker 3: contrast what these two diseases look like to see if
Speaker 3: you can tell if they're different. Yeah, because one thing
Speaker 3: I forgot to mention this is I guess the spoiler
Speaker 3: now is that amoebic dysentery, like the time course of
Speaker 3: disease can be really prolonged. I didn't get a great
Speaker 3: number on the exact incubation period, but the course of
Speaker 3: disease itself can be kind of insidious and last for
Speaker 3: a number of weeks. So it's not like a all
Speaker 3: of a sudden, you're having diarrhea and you're pooping your
Speaker 3: brains out like crazy and you have a high fever.
Speaker 2: It's not as much of that kind of a picture.
Speaker 3: So Shigella is a genus of bacteria in the family Enterobacteryca.
Speaker 3: There's a number of different species, at least four different species.
Speaker 3: Within those species, there are multiple serotypes, and these different
Speaker 3: species and serotypes cause a really wide range of disease,
Speaker 3: from a mild diarrhea without any blood to very severe
Speaker 3: dysentery with a substantial case fatality rate. Some species, like
Speaker 3: Shigella dysineria are known to cause massive epidemics, especially after
Speaker 3: times of upheaval or after natural disasters, whereas other species
Speaker 3: like Shigella flexneri tend to cause more endemic illness. And
Speaker 3: then there are a couple of other species that are
Speaker 3: just tend to be a little bit more mild but
Speaker 3: can still cause dysentery under the right conditions. Ah okay,
Speaker 3: So these are a gram negative rod shaped bacteria, hence
Speaker 3: the term bacillary, which I think we talked about in
Speaker 3: our Legionnaire's episode. They're transmitted either from fecal oral contact
Speaker 3: or any kind of person to person contact where poop
Speaker 3: is involved, from infected water, from food borne contamination, and
Speaker 3: in general these species are super infectious because Shigella survives
Speaker 3: the passage through our stomach very well. So as few
Speaker 3: as ten to one hundred individual bacteria can infect a person.
Speaker 1: It's wild how few it takes.
Speaker 2: Yeah, it's terrifying, truly.
Speaker 3: So it has pretty much the same transmission route we
Speaker 3: already talked about for a maybic dysentery. You get shigella
Speaker 3: in your mouth, it survives your stomach, It travels through
Speaker 3: your intestine, replicating the whole way that it goes until
Speaker 3: it gets to your colon or large intestine, and that
Speaker 3: is where shigella likes to make its home. Once it's there, unsurprisingly,
Speaker 3: it invades your epithelium, the lining of your gut, and
Speaker 3: in so doing, what it does is stimulate a massive
Speaker 3: inflammatory response from your body, and that inflammatory response just
Speaker 3: destroys the cells that line your gut wall, so that
Speaker 3: the bacterium can invade even further. So at this point
Speaker 3: you have hundreds, if not thousands, of bacteria burrowing into
Speaker 3: your gut wall, hence massive bloody, bloody, painful diarrhea.
Speaker 1: I have a question about the blood. Okay, why does
Speaker 1: this cause bloody diarrhea? Why does it cause bleeding whereas
Speaker 1: other diarrheas don't.
Speaker 2: Yeah, great question.
Speaker 3: It's specifically that invasion of the lining of your gut
Speaker 3: wall because in doing that, it's like think of it
Speaker 3: as your gut wall being like a wall, and this
Speaker 3: bacteria is just like poking holes into it. So the
Speaker 3: blood is just going to come leaking out because of that.
Speaker 1: Okay.
Speaker 3: Yeah, So other things that we've covered on this podcast
Speaker 3: that cause diarrhea, like for example, cholera, right, vibriocholare it
Speaker 3: just sort of hangs on to your epithelial cells like
Speaker 3: it holds on to them, but it doesn't invade them,
Speaker 3: it doesn't destroy them, it doesn't disrupt that lining. Whenever
Speaker 3: you get that disruption, that's when you get the blood.
Speaker 1: Okay.
Speaker 3: And so that's why also viruses don't tend to cause
Speaker 3: bloody diarrhea because they don't tend to invade through that
Speaker 3: gut wall.
Speaker 2: Hmm, okay, yeah.
Speaker 3: Some species of Shigella, especially the ones that cause more
Speaker 3: severe disease, also produce a variety of toxins, at least
Speaker 3: one of which we've talked about on this podcast. Because
Speaker 3: it's the exact same toxin that's produced by E. Coli
Speaker 3: seven H seven yep shigatoxin, and this is a cytotoxic toxin,
Speaker 3: so it kills.
Speaker 2: Cells great, right, really great.
Speaker 3: This particular toxin is especially dangerous, and what's interesting is
Speaker 3: that it seems to do this more often with E.
Speaker 3: Coli that produce shiga toxin than with Shigella that make
Speaker 3: this shiga toxin, but it's still possible with Shigella. Is
Speaker 3: that once this toxin gets into your blood stream, it
Speaker 3: can kill your red blood cells and lead to anemia,
Speaker 3: but then also destroy your platelets that since we know
Speaker 3: how important platelets are for clotting, it leads to excessive bleeding,
Speaker 3: and this also then leads to kidney failure because it
Speaker 3: causes damage to the vasculature of your kidneys. This is
Speaker 3: a syndrome called hemolytic uremic syndrome, and it's very bad
Speaker 3: and can be fatal.
Speaker 1: Does the production of this toxin in some way help
Speaker 1: the bacteria to replicate more or to spread more easily,
Speaker 1: Like is someone shedding more bacteria?
Speaker 2: It's a great question.
Speaker 3: It certainly tends to cause more severe disease, so in
Speaker 3: that maybe people are having more massive diarrhea and then
Speaker 3: are shedding more bacteria like we said before, But perhaps
Speaker 3: it also the cytolytic effects perhaps help it invade more
Speaker 3: deeply into the epithelium.
Speaker 2: I'm not sure, Okay.
Speaker 3: In general, the sort of clinical picture of shigella is
Speaker 3: more abrupt, and I think maybe a bit more like
Speaker 3: what we think of when you think of like a
Speaker 3: food borne diarrhea type thing, in that it tends to
Speaker 3: happen anywhere from one to four days, maybe rarely up
Speaker 3: to a week after infection, and often one of the
Speaker 3: first signs is a fever.
Speaker 1: It started with a fever.
Speaker 2: It started with a.
Speaker 3: Fever, and then headache, feeling crappy, and then boom, this
Speaker 3: diarrhea comes on and it's profuse. It's bloody, it's watery,
Speaker 3: it's mucasy. For people with mild symptoms, they'll probably recover
Speaker 3: within a few days. But people who progress to dysentery.
Speaker 3: Here's where you can have some numbers of poops erin
Speaker 3: Uh huh, they can pass more than twenty stools in
Speaker 3: a day.
Speaker 2: Wow. Yeah. Yeah.
Speaker 3: And while extra intestinal manifestations, so this bacteria fully leaving
Speaker 3: the intestine and causing illness elsewhere are rare and I
Speaker 3: don't have a number on it erin, so I don't
Speaker 3: know exactly how rare, but they are certainly possible, and
Speaker 3: in a case of Shagela, they can cause things like seizures,
Speaker 3: although this is mostly in kids and probably more related
Speaker 3: to fever or other metabolic derangements from like electrolyte imbalance,
Speaker 3: hemolytic uremic syndrome like I already mentioned, but in very
Speaker 3: severe cases, things like intestinal perforation or separation of the
Speaker 3: wall of your intestine, like the lining separates.
Speaker 2: Oh my god.
Speaker 3: Yeah, it's pretty severe.
Speaker 1: So for both of these amobic and Shigella dysenteries, if
Speaker 1: you survive either of those, what are some of the
Speaker 1: lasting effects? Like I would imagine that like lesions with
Speaker 1: amoebic dysentery are bad, and then like perforation would be
Speaker 1: really bad, Like are there lingering effects?
Speaker 2: Yeah, perforation is really bad.
Speaker 3: Like if you don't have surgery, you're just gonna die.
Speaker 3: Okay that Yeah, the lesions and ulcers themselves with treatment
Speaker 3: will heal most likely because your gut it actually turns
Speaker 3: over quite a lot, so it actually can really do
Speaker 3: a good job healing.
Speaker 2: Okay. But what's interesting, and I was going to.
Speaker 3: Talk about this like later in the episode, but we
Speaker 3: can talk about it now since you add microbiome.
Speaker 2: Yeah, microbiome.
Speaker 3: So there is increasing evidence that infection with I think
Speaker 3: most of the studies have looked at schagella specifically, but
Speaker 3: with diarrhea causing bacteria and especially dysentery causing bacteria and
Speaker 3: potentially ambe as well, can then put you at higher
Speaker 3: risk of having IBS. Oh, okay, veritable bowel syndrome. Yeah,
Speaker 3: and there's some pretty good evidence. I'll link to a
Speaker 3: paper that's kind of like a meta analysis of what
Speaker 3: we know so far, or like a review paper. It's
Speaker 3: really interesting because if you progress to dysentery that is
Speaker 3: pretty severe, your gut is very unhappy. You're destroying a
Speaker 3: lot of what was there, both in terms of the
Speaker 3: architecture of your gut and also the symbios that you
Speaker 3: had there. So it's not surprising that you could have
Speaker 3: potentially lasting effects. But these are treatable infections, so that's great.
Speaker 3: They're obviously different in terms of the antibiotics that you
Speaker 3: would use to treat them. But the most important thing
Speaker 3: for any kind of dysentery is oral rehydration therapy, and
Speaker 3: so that's to combat the massive amount of dehydration. So
Speaker 3: I that's that's dysentery.
Speaker 2: Aaron.
Speaker 1: Uh, it sounds horrible.
Speaker 3: Yeah, yeah, it doesn't sound great. So how Aaron, Like,
Speaker 3: I assume we've always gotten bloody diarrhea, but is like,
Speaker 3: when did we find out about it?
Speaker 1: Yeah? Yeah, it's a it's a tough question, and I
Speaker 1: will try to answer it right after this short break.
Speaker 1: The story of dysentery is it's an interesting one because
Speaker 1: it's not the story of one pathogen or one outbreak,
Speaker 1: or one epidemic or one discovery, right The main character
Speaker 1: changes constantly throughout the history of dysentery, and it can
Speaker 1: be difficult, I have to admit, to find one common
Speaker 1: thread sort of driving this story, especially I think because
Speaker 1: if you zoom in on like one time or place
Speaker 1: on one little snippet, one photo of that history, that
Speaker 1: common thread that you're looking at, what you've zoomed in
Speaker 1: on that branches off into a million other paths or
Speaker 1: stories that you could follow down, like, oh, I want
Speaker 1: to learn more about how the shigatoxin was discovered and
Speaker 1: the implications for that in terms of like sell tissue
Speaker 1: culture and the shigatoxin or shigella. You know, it's just
Speaker 1: like it's yeah, yeah, it's complicated, and you probably already
Speaker 1: gathered that from the fact that there are these many
Speaker 1: different species of microbes that can cause dysentery, right, And
Speaker 1: so what I want to do with this history section
Speaker 1: is to present a very broad picture of the history
Speaker 1: of dysentery, the flux, the runs, the trots, whatever name
Speaker 1: you want to use, and it has gathered its fair
Speaker 1: share over the years.
Speaker 3: Oh yeah, I bet where did.
Speaker 1: This come from? And how did we get to where
Speaker 1: we are today? And the answer to that question is, well,
Speaker 1: it's kind of the same as it has been for
Speaker 1: many of the other diseases that we've covered on this podcast.
Speaker 1: And if you're a repeat listener, you can probably make
Speaker 1: a pretty solid guess no pun intended. Oh, consider that
Speaker 1: these are pathogens or parasites transmitted through the fecal oral
Speaker 1: rout it makes sense that once humans started gathering in
Speaker 1: large groups and settling in one area for at least,
Speaker 1: you know, a growing season, that it became much more
Speaker 1: likely to come into contact with poop your own or
Speaker 1: someone in your community's poop, or like livestock poop. This
Speaker 1: is not new ground that I'm covering here, but in
Speaker 1: researching for this episode, I realized that I hadn't ever
Speaker 1: really stopped to consider, like what that transition from nomadic
Speaker 1: to sedentary lifestyle, what that looked like, and how sanitation
Speaker 1: or sanitation technology began to catch up, like it needed
Speaker 1: a period of time to catch up after humans started
Speaker 1: to settle in one place. Sanitation, especially latrines, you know,
Speaker 1: that serves such a hugely important purpose in our lives.
Speaker 1: It separates us from our urine and fecal waste, and
Speaker 1: it provides a place where that waste can decompose. And
Speaker 1: that's a process that also importantly helps to reduce the
Speaker 1: prevalence of pathogens. It's when sanitation breaks down or is
Speaker 1: suboptimal that we tend to see these outbreaks of intestinal
Speaker 1: pathogens and parasites, including those that can cause amobic and
Speaker 1: basilary dysentery. I think some of us maybe carry around
Speaker 1: this image of early human settlements as being just like
Speaker 1: absolutely filthy, with people and animals pooping everywhere and no
Speaker 1: clean water to be found, But in reality, nothing could
Speaker 1: be further from the truth. Latrines and sewers and drains
Speaker 1: and bathrooms and wells and aqueducts and cisterns and piping,
Speaker 1: these things have all existed for thousands and sometimes tens
Speaker 1: of thousands of years. The modern flushing toilet is dated
Speaker 1: to fifteen ninety SIVE, but older versions of a flush
Speaker 1: toilet have existed since at least the Neolithic, maybe to
Speaker 1: around three thousand BCE in the Indus Valley. Yeah, flushing toilet,
Speaker 1: uh huh, Like yeah, it's and elsewhere, like in ancient
Speaker 1: Mesopotamia or ancient Greece, there were pit toilets with variations
Speaker 1: in the size of the pit or the slope of
Speaker 1: the drain or the shape of the seat and so on,
Speaker 1: like they're the longest known horizontal drain from ancient Mesopotamia
Speaker 1: was two hundred meters long, Oh my goodness, and that
Speaker 1: was that was that the Moon God complex from around
Speaker 1: the first millennium BCE. So it's impressive, right.
Speaker 3: Yeah, that is impressive. Humans are more ingenious than I realized.
Speaker 1: I think it's sort of like necessity is the mother
Speaker 1: of invention. Yeah, yeah, yeah, I mean, you know, with
Speaker 1: things about ancient Rome, I think, you know, when I
Speaker 1: picture ancient Rome, maybe because the lead episode we did
Speaker 1: what seems like forever ago, but all the pipes and
Speaker 1: the baths and the drainage systems.
Speaker 2: Yeah.
Speaker 1: I read a fun little tidbit that there were apparently
Speaker 1: communal toilets in ancient Rome were very common, very popular,
Speaker 1: and they used to be used as like social gathering
Speaker 1: spots where you could catch up on gossip and plan
Speaker 1: your next get together.
Speaker 3: I mean that makes sense, Like bathrooms still are they
Speaker 3: are if you all go the bathroom together and you
Speaker 3: chit chat and have some time.
Speaker 1: Yeah, and no, I'm not going to spend the entire
Speaker 1: history section talking about the evolution of the toilet or
Speaker 1: sewage systems, although it would be kind of fun. Yeah,
Speaker 1: it could be a great episode. Yeah, But I did
Speaker 1: just want to emphasize that as soon as humans began
Speaker 1: settling in large permanent groups, they began to devise ways
Speaker 1: to manage waste over time and across you know, different
Speaker 1: geographic areas that visceral disgust that humans have for fecal waste.
Speaker 1: It found its way into culture in ancient Mesopotamia. For example,
Speaker 1: around the first millennium BCE, there was a demon who
Speaker 1: dwelled in latrines or bathrooms who was responsible for illness, injury,
Speaker 1: or bad luck. And there were also demons in ancient
Speaker 1: Mesopotamia associated with rubbish heaps. And then, of course, I'm
Speaker 1: sure you're familiar with the saying cleanliness is next to godliness.
Speaker 1: These cultural perceptions of waste. They led to the development
Speaker 1: of rules and regulations regarding where you could or could
Speaker 1: not dump your chamber pot, or your dead cow or goat.
Speaker 1: They influenced the frequency of bathing or hand washing, and
Speaker 1: the way that food was prepared. When miasma became this
Speaker 1: like leading theory as to the origins of disease, it
Speaker 1: wasn't far off from the truth. For several pathogens or parasites.
Speaker 1: The steps that you would take to avoid miasma, this
Speaker 1: bad contaminated air, those steps would in many cases be
Speaker 1: the same ones that you would take to avoid several
Speaker 1: intestinal diseases. For instance, in the fourteenth century CE, a
Speaker 1: Spanish physician wrote a book on army health, where in
Speaker 1: it he said that you should dig pits to use
Speaker 1: as latrines at the edge of army camp and to
Speaker 1: bury the dead bodies there, and also that you should
Speaker 1: dip a white cloth in a possible water source before
Speaker 1: you drink it to ensure that it remained unstained.
Speaker 2: M Yeah, I mean it's good advice.
Speaker 1: I mean it's good advice, and I think it's interesting
Speaker 1: to sort of see these practices that were developed before
Speaker 1: any knowledge of germ theory. Yeah. But of course this
Speaker 1: isn't to say that sanitation technology or these cultural practices
Speaker 1: or community rules or dipping a white cloth into water,
Speaker 1: these were always successful in preventing the spread of pathogens
Speaker 1: or parasites, especially those transmitted through fecal waste, because if
Speaker 1: they were one hundred percent successful, the world would look
Speaker 1: like a very different place, and this podcast might not exist,
Speaker 1: which is a great name I wrote down here, great
Speaker 1: name for Urban Legends or Conspiracy Theories podcast. But things
Speaker 1: like flooding rivers or stagnant streams, droughts, population growth leading
Speaker 1: to massive refuse piles, the proximity of cesspits to places
Speaker 1: where food was being prepared, the use of human feces
Speaker 1: as fertilizer, and the lack of knowledge of how diseases
Speaker 1: were truly transmitted. You know, all of these things led
Speaker 1: to the continued presence of many, many different pathogens and
Speaker 1: parasites that are transmitted fecal orally, and dysentery in its
Speaker 1: various forms was certainly one of those diseases, and not
Speaker 1: just occasionally transmitted, but frequently, like enough so that Hippocrates
Speaker 1: wrote about it, of course, gotta say Hippocrates, of.
Speaker 2: Course in our contract.
Speaker 1: It gets its name from ancient Greece. The word dysentery
Speaker 1: comes from the Greek ducenteria douce meaning bad and enta
Speaker 1: meaning bowels. And later, of course, it was known to
Speaker 1: many people as the flux or the bloody flux.
Speaker 2: Where does that come from? Exactly? Just because like your
Speaker 2: guts are.
Speaker 1: In flux, Like the flux just means flow.
Speaker 3: Yeah, okay, so it's just like bloody flow, yeah, sense okay.
Speaker 1: So we know that from writings, dysentery was present in
Speaker 1: many ancient Old World civilizations, But do we have physical
Speaker 1: proof or do we have any guests as to when
Speaker 1: it arose in humans or first started infecting humans kind of.
Speaker 1: I mean, yes, more to the first question than to
Speaker 1: the second. And so here I have to switch from
Speaker 1: talking about dysentery as a singular subject to one that
Speaker 1: is caused by different microbes. Okay, And like you, Aaron,
Speaker 1: I'm focusing on the two big ones, right, Antimyba histolytica,
Speaker 1: and I'm grouping them all into just shigella. I don't
Speaker 1: talk about the different species.
Speaker 3: Or yeah, that's fine. I didn't either, because that's.
Speaker 1: Yeah, well that's like one of the that's one of
Speaker 1: the multi branching pathways. I was talking about how different
Speaker 1: species have seemed to take over over time and they
Speaker 1: cycle in terms of their endemnicity and yeah, yeah, it's complicated.
Speaker 3: And they're like virulence and everything.
Speaker 2: It's oof, it's a mess.
Speaker 1: It's yeah. Oh, I did want to ask about the virulence.
Speaker 2: It's different?
Speaker 1: Is it from different different toxins? Is this weird to
Speaker 1: do this now?
Speaker 3: It might be weird, but yeah, I mean, yeah, toxins
Speaker 3: play a big role in it. But from what I read,
Speaker 3: at least, it's not like necessarily specific to toxin, Like
Speaker 3: that's one part of it, but it's not the whole story.
Speaker 2: Okay, gotcha, okay, all right, all right.
Speaker 1: Anyways, coming back, so, generally speaking, if we want to
Speaker 1: know the prevalence of things like intestinal pathogens and parasites
Speaker 1: in ancient human populations, we can't really use skeletal remains
Speaker 1: like the way we can for tuberculosis and syphilis for instance, right, Instead,
Speaker 1: we have to turn to coprolites. We love coprolites lovely,
Speaker 1: or soil samples taken from burial areas around where the
Speaker 1: intestines would have decomposed, so like the pelvic area, which
Speaker 1: is I hadn't thought of that before, very interesting, that's
Speaker 1: very interesting. Or we can analyze soil samples from archaeological
Speaker 1: remains of these latrines or cesspools. When it comes to dysentery, though,
Speaker 1: we're still pretty limited because dysentery is diarrhea. Yeah, and
Speaker 1: only well formed stools can be preserved as copper lights.
Speaker 2: Yeah yeah. Yeah.
Speaker 1: That being said, there is some paleoparasitological evidence of Antamoba
Speaker 1: histolytica infection in humans. The systs of Ehistilytica don't preserve
Speaker 1: particularly well, and only do so under very extreme conditions
Speaker 1: like extreme cold, extreme dryness, whatever, and so a microscopic
Speaker 1: examination of soil or preserved feces isn't often successful, and
Speaker 1: even if you do end up seeing, you know, an
Speaker 1: amiba or a cyst of an amoba under the scope,
Speaker 1: like you said, it might not be like you can't
Speaker 1: distinguish between Antamba histilytica and a nonpathogenic species, right, and
Speaker 1: so instead biomolecular tools like immunological tools you know and
Speaker 1: testing are used if possible, which is great because it
Speaker 1: can distinguish among species. But still there have been according
Speaker 1: to a book I read published in twenty fifteen, so
Speaker 1: those numbers might have changed, only five published articles describing
Speaker 1: the discovery of Antamoba histalytica and ancient samples using either
Speaker 1: macroscopy or immunological essays. Okay, The most ancient of these
Speaker 1: samples that tested positive for Ehstalytica antigens is from Switzerland
Speaker 1: around thirty four hundred BCE.
Speaker 2: Wow.
Speaker 1: Yeah. And there were a few samples that tested positive
Speaker 1: from Greece between five thousand and two thousand BCE, and
Speaker 1: there have been additional samples from various European sites in
Speaker 1: the Middle Ages that have also tested positive.
Speaker 2: Interesting.
Speaker 1: Yeah, the first reliable evidence for Antamoba histalytica in the
Speaker 1: New World is from the twelfth century CE. I couldn't
Speaker 1: find any estimates for the emergence of Antamoba histolytica or
Speaker 1: how long it's been associated with humans, but people do
Speaker 1: seem to think, and I think the paleoparasitological evidence points
Speaker 1: to this as well, is that it probably has an
Speaker 1: Old World origin and that it seems to be possible
Speaker 1: that it evolved with humans since there are antamba species
Speaker 1: that can infect great apes, and that also the possibility
Speaker 1: of being an asymptomatic carrier or being chronically infected asymptomatically,
Speaker 1: that would allow it to persist in a community even
Speaker 1: of smaller sizes, so you wouldn't necessarily need the crowd
Speaker 1: like crowd disease type thing.
Speaker 3: It's interesting if it's something that has been with us forever,
Speaker 3: has it always caused disease at a low level, or
Speaker 3: is that you know that, like at what point was
Speaker 3: it able? But if if there's similar ones that do
Speaker 3: cause disease and great apes, then maybe it is just
Speaker 3: like sort of has always caused disease, but just a
Speaker 3: little bit.
Speaker 2: Ah, that's interesting, arin Yeah.
Speaker 1: It's it's I wish that there was, and maybe I
Speaker 1: just like missed you had the wrong search terms or something,
Speaker 1: but I would love to read more about sort of
Speaker 1: the you know, early evolutionary history of Antamoba histiltica.
Speaker 2: Yeah.
Speaker 1: Yeah. And then, of course the other main cause of dysentery,
Speaker 1: these various Shigella species. Again I couldn't find an exact date,
Speaker 1: but their relationship with humans is also thought to be
Speaker 1: pretty darn old. So the various species of Shigella that
Speaker 1: cause dysentery all evolved from Ecoli or are still ecoal i,
Speaker 1: depending on who you ask.
Speaker 2: I remember we talked about that in our equal A episode.
Speaker 1: Uh huh uh huh, yep, yep. And so I actually
Speaker 1: went back to my notes for that episode and I
Speaker 1: was like, oh, okay, Ecoli has been with hu since
Speaker 1: humans were humans, Okay, And so I wrote here, Well,
Speaker 1: it stands to reason then that Shigella might also be
Speaker 1: fairly old.
Speaker 2: Yeah, pretty much. Yeah.
Speaker 1: But regardless of precisely when Antimoba histolytica or the dysentery
Speaker 1: causing Shagella species when they first started infecting humans, we
Speaker 1: can be absolutely sure that once humans began to form
Speaker 1: these large settlements, they weren't just building permanent homes for themselves,
Speaker 1: but also for the causative agents of dysentery. And under
Speaker 1: these conditions, dysentery absolutely flourished. It became a very familiar
Speaker 1: disease and also one that was very much dreaded. And
Speaker 1: part of that was something that you talked about who
Speaker 1: was most likely to be killed by the disease? Children? Yeah,
Speaker 1: and also armies. Not only did military campaigns and war
Speaker 1: create absolutely wonderful conditions for fecal oral pathogens or parasites
Speaker 1: to blossom. I mean remember the typhoid episode. Oh yeah,
Speaker 1: these military campaigns also played a direct role in increasing
Speaker 1: the geographic distribution of those microbes, including the ones that
Speaker 1: caused dysentery. Right, So you're like, oh, we're going to
Speaker 1: go on the Crusades and we're going to spread dysentery
Speaker 1: throughout everywhere we go.
Speaker 2: Yeah, just pooping it along with you, pooping it.
Speaker 1: Along with you. Dysentery ran through the Persian armies that
Speaker 1: invaded Greece in four ADBCE. In France in seventeen seventy nine,
Speaker 1: there was an epidemic of dysentery, likely bassilary, that was
Speaker 1: exacerbated by troop movements and led to the death of
Speaker 1: one hundred and seventy five thousand people, most of them children.
Speaker 1: Augh And in the US Civil War, the annual morbidity
Speaker 1: rate for dysentery for Union soldiers was eight hundred and
Speaker 1: seventy six per one thousand, so basically everyone got it
Speaker 1: and annual mortality rates were estimated at ten per one thousand.
Speaker 2: Wow.
Speaker 1: And these numbers were even higher in prisoner of war camps,
Speaker 1: such as the one where Union soldiers were held at Andersonville, Georgia,
Speaker 1: where sixteen thousand, seven hundred and seventy two cases of
Speaker 1: diarrhea and dysenteria were recorded and four thousand, five hundred
Speaker 1: and twenty nine soldiers died. Oh my gracious Benjamin Moseley,
Speaker 1: who was the former English surgeon General in Jamaica, he
Speaker 1: wrote in the early eighteen hundreds quote because you know
Speaker 1: I love quotes. Quote the dysentery or flux, being a
Speaker 1: disease so destructive to soldiers in camps and garrisons, and
Speaker 1: a constant attendant on all military operations, it is a
Speaker 1: medical inquiry of the utmost importance to investigate this disease
Speaker 1: with the utmost attention in hopes of finding some method
Speaker 1: to put a stop to its devastation. It is a
Speaker 1: subject in which the welfare of mankind is deeply interested,
Speaker 1: and often the glory and honor of a nation. If
Speaker 1: the cause of humanity were not alone a sufficient motive
Speaker 1: to induce to this research, we need but turn our
Speaker 1: eyes on the political field, where we should behold the
Speaker 1: best concerted measures, often defeated by its influence. So yeah,
Speaker 1: of course it devastated soldiers, and it was like, we
Speaker 1: need to get this taken care of and then off
Speaker 1: the battlefield entirely. It was also devastating. There's an impressive
Speaker 1: list of famous people killed by dysentery. The Byzantine Emperor
Speaker 1: Constantine the Fourth in six' eighty five, CE Louis the
Speaker 1: ninth of France in twelve seventy, King Henry the fifth
Speaker 1: of England in fourteen twenty two, Erasmus in fifteen thirty six,
Speaker 1: Sir Francis Drake in fifteen ninety six, Akbar, ruler of
Speaker 1: the Mughal Empire in sixteen oh five, Nathaniel Bacon six
Speaker 1: seen seventy six, and on and on and on, like
Speaker 1: I skipped a ton of people because I was like
Speaker 1: this is ridiculous, Like.
Speaker 3: Who didn't die of dysentery?
Speaker 1: Who didn't die of dysentery? I mean, and I'm sure
Speaker 1: that everyone remembers dysentery from the Oregon Trail.
Speaker 3: Yes, that's I remember it. You have died from dysentery.
Speaker 1: You have died from dysentery, yep, yep. And you know,
Speaker 1: dysentery was truly devastating. It was a plague, it was
Speaker 1: a pestilence, a scourge. Like there's no there's no word
Speaker 1: to hyperbolic, I guess to describe it. Yeah, yeah, And
Speaker 1: so of course people were looking into it for hundreds
Speaker 1: thousands of years. Even they were looking into it treatises
Speaker 1: upon texts, upon papyri, and quite honestly, it didn't do
Speaker 1: much good, at least until the late eighteen hundreds. For
Speaker 1: much of the human history of dysentery, there was no
Speaker 1: distinguishing between the amobic and basilary forms of the disease,
Speaker 1: and in many ways there didn't need to be. They
Speaker 1: were transmitted in the same way, the symptoms they caused
Speaker 1: were quite similar, and most importantly, there was no cure
Speaker 1: for either, right, but there were plenty of attempts. Yeah,
Speaker 1: bleeding naturally, right, but I know it gets worse.
Speaker 3: It's just so illogical in this case, like that's already
Speaker 3: part of your problem here.
Speaker 1: Oh, I know. It's like bleeding to reduce the inflammation
Speaker 1: in the intestine is like how it was prescribed.
Speaker 2: Oh my goodness, I know. Okay, give me.
Speaker 1: More ip acac or rhubarb for some vomiting to empty
Speaker 1: the stomach. Sure, yeah, hm, something like tartar to cleanse
Speaker 1: the bowels. What yeah, so you're basically empty and I
Speaker 1: these cures, as per usual, did more harm than good.
Speaker 1: Uh huh it is. I think it's interesting, Like it is,
Speaker 1: of course, really difficult to resist the temptation to be
Speaker 1: like what were you thinking? I know, these clearly are
Speaker 1: terrible things to do, but also I just find it
Speaker 1: fascinating because a lot of the way that treatments were
Speaker 1: designed were to keep the bodies like humors in balance,
Speaker 1: and so it's just like, but if you want to
Speaker 1: keep your electrolytes and your water imbalance, Like you're losing
Speaker 1: so much water, don't you think you might want to
Speaker 1: replace it?
Speaker 2: But did they know that?
Speaker 3: Now?
Speaker 2: I know they didn't know about electrolytes sarin.
Speaker 1: I know, I know, I know, I need to resist that.
Speaker 1: That's hard for this one in particular. I'm like, I
Speaker 1: just water and sugar and salt, okay, right, yeah. And
Speaker 1: it was only in the late eighteen hundreds that dysentery
Speaker 1: was recognized to be caused by different organisms. Antimba histolytica
Speaker 1: was first described in eighteen seventy five by Russian scientist
Speaker 1: Federal Lausch, who isolated the amiba from a patient and
Speaker 1: then confirmed its ability to cause disease by feeding amoba
Speaker 1: rich stools to a dog who developed similar lesions. Oh
Speaker 1: and there were plenty of also, I should mention of
Speaker 1: quote human volunteer experiments to confirm because it was heavily
Speaker 1: debated for a while whether it was the amiba itself
Speaker 1: causing disease or if the amiba was just something that
Speaker 1: sustained it. And this actually makes this debate makes sense
Speaker 1: in the context of the later discovery that there are
Speaker 1: indistinguishable species of entomba, one of which is pathogenic and
Speaker 1: the other is not. So that like there was a
Speaker 1: long debate being like, no, it's not the amiba that's
Speaker 1: causing disease, it's something else.
Speaker 2: Huh.
Speaker 1: Yeah, I don't know. Interesting, yeah, And this debate continued
Speaker 1: even after the Shigella basillis or I guess Shigella basilla
Speaker 1: were discovered in eighteen ninety eight by Japanese physician Kiyoshi Shiga,
Speaker 1: which was also the first time that it was demonstrated
Speaker 1: that dysentery could have multiple posative agents, and Shiga had
Speaker 1: culture of the Shigeala basillas from a patient with dysentery
Speaker 1: during a huge epidemic in Japan, the eighteen ninety seven outbreak,
Speaker 1: which had a mortality rate of twenty five percent and yeah,
Speaker 1: and ended up killing over twenty two thousand people, again
Speaker 1: the majority of them children. In fact, Shiga himself described
Speaker 1: dysentery as quote the most dreaded disease of children, and
Speaker 1: after Shiga published his findings, other researchers repeated his isolation
Speaker 1: and culture techniques and were able to confirm that this
Speaker 1: bacillus was responsible for dysentery, although later work, of course
Speaker 1: revealed that it wasn't this Bacillis, but rather these bacilli.
Speaker 1: As it turned out there were multiple species responsible for
Speaker 1: causing dysentery. I'm always struck by the period of time
Speaker 1: between the late eighteen hundreds and the early nineteen forties
Speaker 1: or so, when our knowledge of pathogenic microbes and parasites
Speaker 1: had greatly expanded, but we were still largely helpless against
Speaker 1: treating them. Yeah, the bacterial ones anyway, Like vaccines of course,
Speaker 1: were another story for many diseases. But yeah, like we
Speaker 1: were largely helpless against a lot of bacterial diseases. And
Speaker 1: so despite now having at least two causative agents in
Speaker 1: hand for dysentery, the disease still raged in the military,
Speaker 1: in prisons, in psychiatric institutions, killing so many people and
Speaker 1: so many children. We've talked recently about the horrific conditions
Speaker 1: of trench warfare and World War One in regards to
Speaker 1: trench fever, and dysentery was also an enormous contributor to
Speaker 1: morbidity and mortality during that war. The development of sulfonamides
Speaker 1: in time for the Second World War, or at least
Speaker 1: for the end of the Second World War, reduced the
Speaker 1: military mortality of dysentery enormously for that conflict, down to
Speaker 1: point oh seven percent.
Speaker 2: Wow.
Speaker 1: However, it was not the same situation in the concentration
Speaker 1: camps and prisoner of war camps of course during World
Speaker 1: War II, where dysentery raged unchecked and was absolutely horrific.
Speaker 1: But I have a bit of side trivia here. Before
Speaker 1: antibiotics were developed, dysentery caused by Shigella was one of
Speaker 1: the first diseases successfully treated by bacteria phages in nineteen nineteen.
Speaker 3: Oh my gosh, I saw that article, Aaron.
Speaker 1: Yeah, yeah, that's so interesting.
Speaker 2: It's fascinating.
Speaker 3: I was like, what this is like the early nineteen hundreds.
Speaker 1: I know, it's so cool. Shout out to Stephanie's Stratti,
Speaker 1: please check out our antibiotic resistance episode because it's really fascinating. Yeah. So, anyway,
Speaker 1: from the beginning of the twentieth century, the landscape of
Speaker 1: dysentery had greatly changed across the globe and is still
Speaker 1: changing today. An incredible amount of progress has been made
Speaker 1: on both Antimiba histolytica and the dysentery causing Shigella species
Speaker 1: in terms of rulence factors and plasmids and evolution and
Speaker 1: genetic diversity and all those other things, and dysentery has
Speaker 1: greatly dropped in prevalence in many places, especially with advancements
Speaker 1: in sanitation infrastructure, and the application of antibiotics, but it
Speaker 1: is still so extremely and frustratingly prevalent across the globe,
Speaker 1: causing devastating outbreaks such as the one in Guatemala in
Speaker 1: nineteen sixty nine, which led to an estimated ten thousand deaths,
Speaker 1: and over the next four years, it's estimated that there
Speaker 1: were five hundred thousand cases and twenty thousand deaths due
Speaker 1: to dysentery in Central America, and in the late nineteen
Speaker 1: seventies in Central Africa, an epidemic of dysentery began to
Speaker 1: spread and then to remain at high numbers. High incidents.
Speaker 1: In the early nineteen nineties, civil wars and mass genocide
Speaker 1: and the construction of refugee camps led to the sustained
Speaker 1: outbreak in Rwanda, with weekly dysentery attack rates in the
Speaker 1: camps estimated to be three point eight per one hundred people.
Speaker 1: And one of the most concerning things about the epidemics
Speaker 1: and the outs that have happened starting in the second
Speaker 1: half of the twentieth century is antibiotic resistance. Shigella were
Speaker 1: one of the first bacteria to show multi drug resistance
Speaker 1: starting in the nineteen fifties. The nineteen fifties.
Speaker 3: How many multiples of drugs do we even have?
Speaker 1: Then it's horrible And as far as I can tell,
Speaker 1: this trend towards antibiotic resistance. Maybe you'll tell me something different,
Speaker 1: but it hasn't seemed to turn around. It seems to
Speaker 1: be remaining fairly steady and on the rise.
Speaker 2: Yeah, I'm not going to tell you anything different, Okay.
Speaker 1: Dysenterry loves a disaster. It loves a disruption, whether it's
Speaker 1: a civil war or a busted sewer, an overflowing river,
Speaker 1: or a drought. It thrives on that disturbance. So much
Speaker 1: of the world does not even currently have access to
Speaker 1: clean water, leaving them extremely vulnerable too dysentery and other diseases.
Speaker 1: And I can't help. But now when I watch the
Speaker 1: news and I see all the horrific climate disasters that
Speaker 1: are happening, I can't help but think, Oh, dysentery is
Speaker 1: gonna love this. So, Aaron, I'm hoping you'll tell me
Speaker 1: some good news about dysentery.
Speaker 3: I let's just take a break.
Speaker 2: And then we'll just talk about it.
Speaker 3: So, like many of our episodes that get a little complicated,
Speaker 3: like we're dealing with a lot of different things.
Speaker 2: It's hard to put a.
Speaker 3: Number on how many people have bloody diarrhea, et cetera.
Speaker 3: So we're going to do the best that we can
Speaker 3: with numbers, I think we'll get an overall picture of
Speaker 3: how bad it still is. Okay, none of these estimates
Speaker 3: are super recent. Most of them come from like the
Speaker 3: early twenty tens or so.
Speaker 2: But overall, looking.
Speaker 3: Just first at shigella, it's estimated that there's between one
Speaker 3: hundred and sixty five and one hundred and eighty eight
Speaker 3: million cases of shigellosis, so that's shigella associated diarrhea or
Speaker 3: dysentery globally every year. It's estimated that includes over sixty
Speaker 3: million cases in kids underage five.
Speaker 2: Oh my gosh.
Speaker 3: And this twenty eighteen paper that I read also estimated
Speaker 3: that shigella infections are the second leading cause of death
Speaker 3: due to diarrhea after rotavirus, and cause over one hundred
Speaker 3: and sixty four thousand deaths annually. That includes over fifty
Speaker 3: four thousand deaths in kids under age five. That's just
Speaker 3: from shigella.
Speaker 1: Oh my gosh.
Speaker 3: Yeah, it's pretty horrific. Yeah, when we look at amobic
Speaker 3: dysentery we have, I think even harder numbers. I don't
Speaker 3: have numbers on the estimates of total infection worldwide, but
Speaker 3: I did find that it's estimated that fifty five thousand
Speaker 3: people a year die from Antimyba histolytica infection, and of
Speaker 3: course many of those are children. It's one of the
Speaker 3: top like fifteen causes of dysentery in developing countries for kids,
Speaker 3: especially with amoebic dysentery. There have been some studies that
Speaker 3: suggest that, like in endemic areas, up to forty percent
Speaker 3: or more of the population shows evidence of prior infection.
Speaker 3: So this is an amiba that's really widespread even when
Speaker 3: it's not causing disease.
Speaker 1: A quick question about that and about immunity, because I
Speaker 1: guess this will player role. Then if in any discussion
Speaker 1: of vaccines, Yeah, is there any immunity to either amobic
Speaker 1: or shigellosis.
Speaker 2: It's a good question.
Speaker 3: So off the bat, we don't have vaccines for either.
Speaker 3: There's good evidence that the potential to develop a vaccine
Speaker 3: exists for shigella. There's work being done, there's a lot
Speaker 3: of promise, there's been patents filed to develop vaccines for shigella,
Speaker 3: especially to try and like develop vaccines against both shigella
Speaker 3: and typhoid, like combining those both in one vaccine, because
Speaker 3: that would be really beneficial those are spread in similar ways,
Speaker 3: et cetera. But right now nothing exists like that. But
Speaker 3: animal model studies suggest that the type of immune response
Speaker 3: that we develop could be protective. The problem is that
Speaker 3: there's a lot of different species and there's a lot
Speaker 3: of different serotypes, so how much cross protection you would
Speaker 3: get from an immune response is unclear. With ntemyba histolytica,
Speaker 3: I could find even less information, so people mount an
Speaker 3: immune response, but again, because it can be kind of
Speaker 3: like an asymptomatic infection, it's not really clear like are
Speaker 3: you protected from reinfection, are you chronically infected, et cetera.
Speaker 3: So for that one, I think we're even further from
Speaker 3: the potential for a vaccine. It doesn't mean it's impossible,
Speaker 3: but we just have to hope.
Speaker 1: Yeah, jeez, gotcha.
Speaker 3: So if you look at these two causes alone of dysentery,
Speaker 3: we're talking about millions of cases and hundreds of thousands
Speaker 3: of deaths due to dysentery just from these two sources.
Speaker 3: And like I said before, there's other bacteria that can
Speaker 3: also cause the same illnesses essentially, So obviously the biggest
Speaker 3: deal when it comes to dysentery and diarrheal diseases in
Speaker 3: general is trying to prevent them, right, And like you mentioned, Aaron,
Speaker 3: getting better at prevention means access to clean water and
Speaker 3: sanitation so that people aren't coming into contact with human feces,
Speaker 3: and that's really the bottom line.
Speaker 2: The other bottom.
Speaker 3: Line, like I mentioned way towards the beginning, is addressing
Speaker 3: problems of nutrition, because malnutrition is a huge risk factor
Speaker 3: for severity of disease, especially for antamba histolytica, but also
Speaker 3: for other forms of diarrhea and dysentery and both of
Speaker 3: those things. Addressing malnutrition and addressing sanitation takes infrastructure, which
Speaker 3: takes money, right, So a lot of different organizations, the
Speaker 3: World Health Organization, UNICEF so many others, have a lot
Speaker 3: of lofty goals to eliminate deaths from diarrheal diseases by
Speaker 3: twenty twenty five.
Speaker 2: That's one of their goals.
Speaker 3: I don't actually know how well they're doing on that front. Again,
Speaker 3: it's hard to get some data on this, but if
Speaker 3: we just look at sanitation. Overall, the World Health Organization
Speaker 3: estimates that only forty five percent of the global population
Speaker 3: currently have a safely managed sanitation system, like one that
Speaker 3: is going to actually be effective at preventing intestinal pathogens
Speaker 3: from spreading.
Speaker 2: So that's not great.
Speaker 3: They also estimate the World Health Organization and this isn't
Speaker 3: specific to dysentery. So if we look a little more broadly,
Speaker 3: the World Health Organization estimates that eight hundred and twenty
Speaker 3: seven thousand people die as a result of inadequate water,
Speaker 3: sanitation and hygiene, and this altogether accounts for sixty percent
Speaker 3: of all diarrheal deaths.
Speaker 2: That's so wow.
Speaker 3: Yeah, so improving access to clean water sanitation can prevent
Speaker 3: literally hundreds of thousands of deaths, including nearly three hundred.
Speaker 2: Thousand children under the age of five, every year.
Speaker 1: Oh my gosh. Yeah.
Speaker 2: Yeah.
Speaker 3: So that's kind of where research needs to focus at
Speaker 3: this point, is like what are the best ways to
Speaker 3: sort of develop and implement those systems in ways that's
Speaker 3: actually going to be sustainable and make a difference.
Speaker 1: And permanent, like and not just like let's go in
Speaker 1: build a bunch of you know, sanitation infrastructure and then
Speaker 1: leave and then not provide any funds to maintain it exactly.
Speaker 1: That's such a problem, right, Yeah, yeah, yeah.
Speaker 3: So, I mean that's kind of the status of diarrhea,
Speaker 3: of sanitation of dysentery today. I kind of already mentioned
Speaker 3: some of the interesting research that's going on in terms
Speaker 3: of like how dysentery affects your overall microbiome and associations
Speaker 3: with the development of things like.
Speaker 2: Irritable bowel syndrome.
Speaker 3: So we kind of already jumped ahead and talked about that.
Speaker 3: And yeah, vaccines are something that's like people are doing
Speaker 3: research on it, but we're not super far along from
Speaker 3: what I read. That's dysentery, Aaron. It's not a super
Speaker 3: happy ending.
Speaker 1: It's not. I don't think we should have expected one.
Speaker 2: No, No, we never.
Speaker 1: Do, especially when it comes to diseases that predominantly affect
Speaker 1: developing countries.
Speaker 2: Definitely.
Speaker 1: Yeah, well, sources, let's do it. Okay, I want to
Speaker 1: shout out I have a bunch of articles, but I'm
Speaker 1: going to shout out one book and a couple of
Speaker 1: articles in particular. The book is titled Sanitation, Latrines and
Speaker 1: Intestinal Parasites in Past Populations, and the editor is Piers Mitchell,
Speaker 1: and then there was a great paper called a Brief
Speaker 1: History of Shigella by lampell at All from twenty seventeen,
Speaker 1: and then another paper by Haycock from two thousand and
Speaker 1: two called Exterminated by the Bloody Flux. Ooh, that's a
Speaker 1: good dab that was in the Journal for Maritime Research.
Speaker 2: Oh cool.
Speaker 3: I had a lot of papers for this one. That
Speaker 3: awesome quote that I read was from a two thousand
Speaker 3: and three paper titled Emibiasis in the Lancet. There was
Speaker 3: a number of other papers I really loved dysentery, including amibiasis.
Speaker 3: It was written in nineteen seventy three published in BMJ,
Speaker 3: but it was a really nice overview of both shigella
Speaker 3: and amybic dysentery. A few others on the biology, but
Speaker 3: if you'd like to read more about dysentery and irritable
Speaker 3: bowel disease, that paper is in the journal GUT, published
Speaker 3: in two thousand and four. We'll post all of these
Speaker 3: on our website, this podcast will Kill You dot Com
Speaker 3: under the episodes tab.
Speaker 1: We will a thank you to Bloodmobile for providing the
Speaker 1: music for this episode and all of our episodes.
Speaker 3: Thank you to exactly write network of whom we're very.
Speaker 1: Proud to be a part, And thank you to you listeners.
Speaker 1: Thanks for listening. You know this was a tough one,
Speaker 1: so we're very appreciative that you hung in there with us.
Speaker 3: Yeah, and a special shout out to our patrons. Thank
Speaker 3: you guys so much for supporting us.
Speaker 1: Yes, thank you. Okay, this feels very appropriate, So until
Speaker 1: next time, wash your hands
Speaker 2: You filthy animals.