Soon after my attention had been directed to the liver and its associated structures, I found in the blood of the portal vein a number of long white helmets, which, with the naked eye I considered to be nematodes, but soon recognized as something new. A look into the microscope revealed a splendid dystomum with a flat body and a spiral tail at least ten times as long as the body. I have not yet reported the new stages of my
portal vein worm. It did not, as I had expected, develop into an old wives tail, but into something more wonderful, a treematode with divided sex. I performed an autopsy on a boy who died of meningitis. Upon opening the urinary bladder, we found lentil to pea size soft, spongy excrescences. When I cut through the largest of the excrescences, a white thread adhered to the knife. Examining it more closely, I
recognized our dystomum hematobium. I searched the depth of the incision and pulled out several more the areas of the bladder mucosa, where the earliest stages of the tumors appeared were covered with viscous, clear mucus containing large numbers of dystomum hematobium eggs singly or in clumps. When I showed Doctor Lautner the dystomum hematobium found in the bladder, he remarked that he too had seen the eggs while studying the pathologic changes of the bladder, but had not been
able to explain them. He and doctor Greisinger encouraged me to examine the pathologic changes of the bladder, which were so similar to those found in dysenteric degenerations of the intestine. Further investigations in this country, which I shall continue zealously, as well as those being carried out in Europe, investigations to which I invite my colleagues, will have to decide whether Dystomum hematobium stands in the same relation to dysentery
as a Kears scabii does to the itch. All right, then, So that was from excerpts from letters from Theodore Billar's to his supervisor von Siebold while conducting research in Egypt, and this was essentially the discovery of Schista's soma hematopium.
The subject of today's.
Episode one of the subjects just a semiasis in jen Hi.
I'm erin Welsh and I'm erin Oman Updyke and this.
Is this podcast will kill you. Yeah, welcome to just a Semiasis.
Just a semiasis my first true love of disease.
I like the qualifier there, not just well. Yeah, I'm excited too. I mean, we love a good multi host parasite. Yeah, fascinating the ecologies there. It typically has some long history.
You know, I can't wait.
To hear the history because I know nothing about it.
Oh man, this I'm I'm very excited about this. This is like a full rich history. I didn't have to like color in the edges with some other.
External historic et cetera.
Hey, now, no, that was great, not true. Okay, so what are we drinking this week?
We're drinking just a fluke.
Because also shist ames are known as flukes.
Flukes. Yeah, it's a type of platform.
Yeah, and in justin luke is pomegranate juice, vodka, club soda, mint, simple syrup, maybe a little bit of lime juice, and then you garnish with some pomegranate seeds if we can find them from the store.
And as always, will post the full recipe for this quarantini as well as our non alcoholic plusy burrita on our social media and our website, so you can check it out there.
Yeah.
Now let's dive into schisto.
After this quick break. So shst a semiasis also called bill harcia. Yeah, because of as you mentioned from our first hand account, the person who discovered.
It, Theodore bill Ars.
Can we call him Teddy? Do you think you went by Teddy?
I have no way of knowing. There probably is Google actually.
But Teddy bill Ars. That's a cute name.
I like it. I like the name Teddy.
So shst a semiasis aka bill harcia. It's caused by a worm. We haven't done a ton of worms, so this is exciting. It's a flatworm, and specifically one that's called a fluke. That's like the type of worm that it is.
Why is it called a fluke?
You know?
That's a good question that I don't know. Okay, I feel like that's a history question.
Oh dang it, how dare you?
So? There are a number of different species of shist as ome that infect humans. The three most common are Schistosoma Mansoni japonicum and Hematobium. There are a few other species as well that are less common, and they all have the same basic life cycle and overriding general pathways by which they travel through the human body and cause disease, but they do cause slightly different diseases, especially between Schistosoma, Mansoni Japonicum and Hematobium.
It's kind of like the special one.
So what we're gonna do is talk about the general life cycle and pathway first as a group, like all the shistosomes, and then we'll talk about the symptoms. We'll talk specifically about the differences between them.
Does that sound good?
Sounds great? Also, I just looked up fluke etomology, Oh tell me, and apparently it means it's like the old English word flock means flatfish, and so the worms were called that because they resembled.
Flat flat fish little flounders. I can see that. Cool.
Thanks Aaron, answering your own question. All right, So, like we mentioned briefly, one of the reasons that Aaron and I get excited about a parasite like this is that it has a very complex life cycle and transmission cycle.
So it goes a little something like this.
I'm I'm simplifying this a little bit, but this is the general overview.
Okay.
So we'll start with the eggs, because you have to start somewhere in a cycle. So the eggs are present in the environment, and they hatch in fresh water.
Okay.
And out of these eggs hatch these little mirrorciitia is what they're called, but we'll call them baby shisto.
Okay, okay.
So baby shisto have all these little still around their edges which act like swimmers so that they can swim through their environment. Aaron I wrote, they swim their way into a crab.
Why did I write crab? What that is incorrect? That is incorrect is one percent incorrect. I can't believe I wrote crab. How funny.
So with these little swimmers, they swim their way through fresh water into a snail.
Okay.
And it depends on what species of schistosome what species of snail they go into, but they all make their way into snails, and inside these snails, the baby shistos begin to multiply asexually.
When you say, so, that's really interesting, it is, that's really wild. I started to talk as you were finishing that sentence. Also, how do they get into the snail. Do they penetrate the snails?
Yep, little fleshy body parts.
Yeah, okay, but they so they replicate a sexually, which is wild considering in the first hand account we learn.
That will get there.
Okay, don't you worry.
These are just these are baby shistos. Okay, baby through life stage by live stage. So the baby shistos swam their way into a snail. They begin to replicate asexually, so multiply and multiply, and then they change into what are called sir Carrie a mm hmm.
And these are.
Kind of like a kid shisto. Okay, kiddo shistos. They look kind of like sperms. Okay okay, not quite like a sperm, but sperm esque. They have like a head and a tail that they use for swimming. So these kiddo shistos, spermy looking things, swim burrow their way back out of the snail and are released again into fresh water, and then they use that to swim around through fresh water.
How over how many days or how long do they replicate in the stale?
I knew you were gonna ask that question, so let me tell you. The eggs they can live in the environment for up to seven days, and then once the baby shistos make it into the snail, it takes four to six weeks before they start shedding the kiddo shistos.
The cir carrier. It's a long time, it is.
And now these cir carrier can live in the environment for up to seventy two hours, so they're swimming around time.
That's a short time.
They're swimming around in fresh water. And now here you come, as a human mammal walking around for a nice walk through these fresh water ponds or whatever. You're obviously barefoot because you wouldn't want to get your shoes wet. And these little kiddo shistos see you, swim right up and burrow their way through your.
Skin and into your foot. Okay, okay, all right, okay.
So now these little spermy circaria have wormed their way into your body, okay, and then they're going to change yet again. That spermy tail is going to fall off and they are going to start to swim in your body a mammal body and make their way into your bloodstream. So now you can think of them kind of as teenagers. These are called schistosomula at this point. Okay, so they're
like the sperm without the tail, just the little head part. Okay, Okay, So inside of you, they make their way, as many parasites do, into your bloodstream, either directly through your little capillaries or through your lymphatic system.
First.
Then they're going to travel. This is where it gets really fun. It's already fun because how complicated is this. They travel through your venous system, and remember your veins are what carried the deoxygenated blood back to your heart, right, so they're going to travel through your veins to the
right side of your heart. The right side of your heart is going to pump these teenage schistos out into your lungs, where they can then cross the capillaries and travel to the arterials, which go back to the left side of your heart, and then your heart can pump them out yet again to the rest of your body. And where they go from there is actually they make their way from your heart.
To your liver.
Okay, this is a very complicated route. Okay, they've entered your foot, they travel through your bloodstream, make their way to your lungs in order to get to your heart. In order to get to your liver.
Okay, So it's kind of like it almost follows the root of the hookworm up until the liver part.
Yeah, exactly, yes, or no, it's before the liver part to the lungs.
Yeah, to the lungs.
So yeah, hookworms also make it to your lungs, but then they make you cough and then you swallow them to get into your intestine.
So these guys go a different way. In your lungs.
They stay in your blood stream, so they're basically just riding your blood flow all the way to your liver.
The that's their target destination for now, Okay. Then in your liver, and this is all all the different species of schistosoma do this, okay, Okay, They make their way to your liver, and then they're going to in your Like your liver has so much blood flow, lots of veins, lots of arteries all in there, and so in your liver, they're gonna leave the arterial system yet again and make make their way back into the veins in your liver, and that is where they're going to mature into full
fledged adult sistosomes. And like you mentioned in the first hand, account, they now have male and female shistos Okay. I don't know whether you could identify them previously, but at this point as adults, there are male schistosomes and female schistosomes. And then just like on Love Island, UK.
Yes, they're going to coupull up okay and sleep in the same bed together. Just kidding.
What happens is the female schistosome literally wedges into a canal in the male sistosome called a gaynacophoral canal, and then as a pair, they traveled together to their final destination.
Okay.
For Schistosoma Mansoni and Japanicum, this final destination is the venus plexus around your intestines, the mesenteric veins. For schistosoma hematobium, it's the venus plexus around your bladder.
Huh.
Okay, I don't know why. Okay, I can see on your face you're about to ask me that I was. Yeah.
It's a very interesting question as to why these like most species of shistosoma tend to go to the veins around your intestines, but hematobium goes to your bladder.
It's a really interesting question that I don't know the answer to.
But that is where they go, and then they live their lives as adult schistosomes where the female just lays eggs and eggs and eggs and eggs, so many eggs. And then what has to happen for them to complete their life cycle is these eggs have to make their way out of your body. So the way that they do that if they're in the veins around your intestine is those eggs will burrow through those veins into your
intestine and you poop them out. If they're in your bladder, they have to borrow their way all the way through your bladder, which is a really thick organ like it has a thick wall, cool into your bladder and then you pee them out.
Okay, okay, is there ever any recoupling?
Recoupling Aaron I practiced for like ten minutes last night how to say couple up, and I think I still did a terrible job of it.
Do you mean you watched ten episodes of violence?
I literally sat with Brett saying the words couple up, like for ten solid minutes, trying to get a good accent.
Anyways, time well spent.
Mm hmm. So that's the life cycle of schistosama.
Cool.
Cool.
They can live in your body, these adult worms.
You haven't asked me, but let me tell you, for three to ten.
Years in your That's impressive.
Just layand eggs, laying eggs, lant eggs.
Okay, that also makes it very difficult to get rid of environmental.
Do you want to know what the theoretical reproductive potential of one schistosome pair is? Six hundred billion sistosomes? Oh, because not only are the adults living in you shedding for years, but one single Mirricidium that infects a snail can shed thousands of circaria every day for months. They live in the snail for months.
That is incredible.
I know whoa yep, Yeah, it's incredible, and it does it makes control of this very very difficult. Okay, so let's talk about the path of physiology of how this this We know how it moves through your body, but how does it actually cause symptoms? How does it actually make you sick? What's really important to keep in mind about shi just a semiasis is that the symptoms that we see from this disease are not from the worms themselves.
They're from the eggs, and they're also not even necessarily from the eggs doing what eggs are supposed to do, which is leave your body through your poop or pee. But the symptoms are caused by what happens when the eggs don't leave your body.
Really, yes, the fact that the.
Eggs have to cross through, so they have to leave your veins. Right, they're living in the veins around your intestines or around your bladder. They have to penetrate through your vein walls and either into your bowels or your bladder. So you can imagine that this causes inflammation.
Right.
They have to make holes in your veins and your bowel or bladder wall to make their way into the lumen of these organs. So in the case of the bowels in your intestines, what can happen is they can leave essentially little holes behind, so you can get micro tears,
micro perforations, you can get intestinal bleeding. Anytime you damage the wall of the intestine, you can mess up its absorptive capacity, so you can have malabsorption, which means diarrhea and also potentially malnutrition because of this, because you have bleeding from these little ulcerations, you can end up with anemia, especially in children. Who are already prone to anemia. Yeah, okay,
so that's in the intestine. In the bladder, what can happen really commonly is that the bladder wall is very thick, so and this can happen in the bowels as well, but especially in the bladder because of how thick it is, the eggs don't always penetrate all the way through, so they can get stuck in the wall of the bladder. And what happens when the eggs get stuck in the wall of your tissue, essentially, is it causes a massive inflammatory response in your body, and your body tries to
wall off this egg. Like your body recognizes this egg doesn't belong here, I'm going to wall it off, and it forms what's called a granuloma, which is basically inflammatory cells and tissue and debris walling off this egg. It's the same thing that we saw in tuberculosis. It happens in your lungs. Yeah, so that happens as well in shs a semiasis, and in the bladder wall. This can
cause chronic inflammation. So one of the hallmark symptoms is bleeding in your p so huematuria, and that's from actual penetration through but also from this chronic inflammation that happens in the wall of your bladder. And then the other thing that can happen is that if you think about which direction blood flow in your veins, blood is flowing away from most of your organs in your veins, right, So the blood in the veins around your intestines is
not flowing into the intestine. It's flowing away from the intestine. But the eggs are trying to get into the intestine, so they're swimming against the current.
They don't all make it, so.
Some of them get swept up backwards, and where they go is the liver because that's where those veins drain to. Oh, the liver, that's where they came from, right, yeah, So then they can get lodged in the liver and also the spleen because a lot of blood flow drains into the spleen as well. So then you have the same thing happening that happened in the wall of the bladder, these granulomas forming this intense inflammation in the liver and
the spleen. So this can cause hippatosplenomegaly, so that means enlargement of the liver and the spleen.
Wait, we just talked about this and I said it was a great word.
Yeah you did.
Which episode?
Oh, let's see in is it hepsy? No, because hepsy doesn't cause spleen? Dangae dangay. It was okay, yeah, dangay.
Cool.
Yeah, so fun So connections yep. So it can cause hepatosplinamagally. It can also cause what we did talk about with hepatitis C, which is fibrosis of the liver. Especially now, anytime that you have veins being clogged, like we talked about in the hepsy episode, you can have portal hypertension, so the veins are being clogged, so the pressure is
building up on the back end. So you can see all the same symptoms that you see with other chronic liver disease, like acide's fluid being filled up in your belly. You can get esophageal varices, so Varico's veins in your esophagus, which can cause massive bleeding if they rupture.
Oh my gosh, yeah.
Yeah, isn't that Isn't that fascinating?
It is. So that's kind of like the pathophysiology of how and why it causes the disease that it causes. It's not the worms themselves, it's the eggs getting lodged in places and then our bodies mounting a massive immune response to try and wall these eggs off.
Okay, fascinating.
Okay, So then let's talk about the actual symptoms. We've kind of touched on them, but we'll go through the stages of infection. Okay, okay, so super acutely, like hours after you get infected, especially the first time you ever get infected. You're right, there is symptoms that happen right away from the circarria themselves, and that is an itch uh huh, where those little spurmes penetrate your body. Okay, This is sometimes called swimmers itch.
It's also really funny to me that you're calling them little spurmes because of something that I'll talk about in the history section.
Oh really yeah yeah, So yeah, you can get a rash. It's sometimes called swimmer's itch because again this is from freshwater ponds and things like that. That is where they live, and it'll be blistery, it'll be itchy, but it's generally self limited and it kind of goes away over time. Right then there is an acute disease that can happen in a number of weeks, usually like two to ten
weeks after infection. It tends to only really happen with Schistosoma japonicum infection, but it also can happen in travelers who get infected with Sistosoma mansoni and hematobium, But it doesn't tend to happen in people who live in areas where this disease is endemic with the other two species, if that makes.
Sense, Uh huh okay.
And so this acute disease essentially is your body mounting a hypersensitivity reaction to all the worms swimming through your bloodstream and making their way that long travel down to the veins of your intestine or your bladder. It's your body seeing those worms swimming and mounting a response to it. So again, it is the worms, but it's also not
the worms. It's your body reacting to the worms. And so the symptoms that you see are the same kind of general inflammatory symptoms that we see with a lot of diseases, fever, fatigue, maybe muscle pains, things like that. If you were to test someone's blood at this time, what you would see is something called eosinophilia, which is I think another fun word, fun words. So that means an elevation in the number of eosinophils, which is a specific type of white blood cell that we have that
we use to fight off parasitic infections. So it's your body going, hey, I know that there is a parasite, a worm here in my body, and I'm trying to fight it off, which I think is so cool.
It's very cool because it just shows how important parasites have been to us throughout our evolution.
We have a whole line of blood cells that are specifically four parasites.
Oh, it's so cool. It's very cool.
And then the other thing that you'd see if you took like a chest X ray of someone with this acute shisto reaction, you would see patchiness on chest X ray and that's likely because of you know, the worms have made their way through your lungs and that causes some inflammation in your lungs as well.
Okay, okay, but this is just two to ten weeks.
This is just two to ten weeks. This is also called Katayama fever. Uh huh, pronouncing that right, But that's that's what it's called and yeah, that's sort of the acute it doesn't it in endemic areas where schistosoma, mansoni and hematopium are the primary causes this, This isn't a disease you tend to see very often, right, which is very interesting. So the majority of problems associated with just asmiasis are in fact the chronic infection of course from the eggs.
And so we've kind of.
Already talked about what those symptoms are, but will kind of just go through system by system to talk about what you actually see symptom wise. So in your intestine, when you have these eggs burrowing their way through into your intestine wall, you're going to have symptoms associated with intestinal pain, abdominal pain. I mentioned, you can get micro
ulcerations in your intestinal wall, which can cause bleeding. So you can get diarrhea, either bloody or non bloody diarrhea in kids especially, this can lead to malnutrition if you think about the intestinal wall being damaged, not being able to absorb all the nutrients.
That you need.
On top of that having diarrhea, you can have malabsorption problems. And then yeah, exactly, you can also get anemia, especially in children. So that's the intestinal symptoms. When those eggs make their way up into your liver, you can have all that those hepatic symptoms that we mentioned already, so ascide's portal hypertension, liver fibrosis, all of that kind of stuff in your urinary tract. Bloody urine hmaturia is kind of the hallmark sign of shostosimiasis, especially in children.
Okay, especially in children.
Yeah, there's really no like, there's there's no other well in endemic areas. If there is a kid with bloody urine, it's.
Just a samiasis especially Okay.
What's very interesting is that in adults, chronic infection with shistosoma heemotobia that affects the urinary tract is associated with an increased risk of bladder.
Cancer because of the inflammation.
It's thought, yeah, it's thought that it's because of the inflammation. At least one thing I read said it's also possible that just the the action of these eggs, like constantly going through your walls, can make your bladder more susceptible to other carcinogens like poaking and things like that. So it's not entirely clear whether it's like but overall. Yeah, it's inflammation, right, yeah, right, yeah, And now here's the other really important thing about shys asmachematobium. So it's living
in the veins around your bladder. Your bladder is in your pelvis, which means that this can also affect other organs in your pelvis, and so this can cause it causes what's called genito urinary just a semiasis, So it can affect it can affect the prostate, the seminal vesicles, so you can see things like hematospermia, so bloody semen. It can also result in very substantial cervical lesions. So the cervix is the bottom part of your uterus, top
part of your vagina. This can cause very substantial cervical lesions, vaginal lesions. And what's really important is that this type of genito urinary just a semiasis is associated with an increased risk of HIV infection and transmission. Yes, yeah, because of these lesions you have like open wounds, you have increased inflammatory cells, and so it's easier for HIV to be transmitted. So that's really important.
I had no idea about these other manifestations of disease until I was reading a review paper about the history of it, and then it has you know, I got scrolled to page ten and it was just like picture after picture of eurogenitor. Wow, of eurogenital just a semiasis, and.
Yeah, yeah, it's terrible, it's horrible.
It's horrible.
Now, because this is something that's in your blo blood, it can technically also cause disease anywhere that your blood goes, which is to say the rest of your whole body as well. So these eggs can also end up traveling all the way back to your lungs, which can cause the same kind of granulumitus changes that we saw in everywhere else in the liver, in the bladder, et cetera. So that can end up causing what's called pulmonary hypertension. So think of the increased pressure in your portal veins
of your liver. The same thing can happen in your lungs. If you have an increase in pressure in your lungs, that causes a backup of pressure onto the right side of your heart, which can cause right sided heart.
Failure, which is called core pullman Al.
Okay, so does worm burden my favorite phrase, relate to these symptoms or the increase of you know, risks for bladder cancer and HIV.
Absolutely it does because we are talking about eggs.
So the more as you.
Have in your body, the more symptoms that you're going to have, and the more inflammation that you're going to have. So the more warm pairs that you have, the more eggs are going to be releasing.
Absolutely.
What is the average worm burden in endemic areas?
That's such a good question. I don't know. I'm going to look it up. Okay, that's a really important question. It's high. I know that.
But the other place that this can also affect is your nervous system.
I was wondering, does it go into your brain?
Yeah, it can cross your blood brain barrier potentially, these eggs because they have enzymes that let them like break down barriers. Right, That's how it makes its way into your bowels. So it can break its way into your central nervous system and cause neuros. Just a semiasis which can cause seizures other neurodegenerative type symptoms. Yeah, it's gnarly. That's just a semiosis.
Wow, that's a very complicated story.
Super super complicated.
And a lot of bad manifestations.
Yeah, it's a really nice disease. Yeah, what the heck, Aaron, what the heck?
Where did this thing come from? How did it get here? And why did it take us for forty five minutes to talk about?
Oh? Good god, Well, let's dive into the very long history of shisto right after this break awesome. After hearing about the biology, I'm even more excited to talk about the history because the history has all the fun things. It's got mummies, imperialism, a little bit of climate change, phylogenies, it's got everything.
That's everything you could ask for in an episode of TPWKY.
Right. Okay, so you asked how did we get here? But I want to change that question a little bit by asking and hopefully answering, how did we get from there to hear? But first, what is there? Basically, where did shistisomes come from? And how did some of them become parasites of humans? So you mentioned that shistisms are a super diverse group. There is about one hundred species, and the majority of those actually infect birds and don't
have anything to do with mammals. But of the ones that infect mammals, which is around twenty three species, seven of those infect humans regularly. With the three that you mentioned being the biggest causes of disease, Okay, but the rest of them infect like tons of species of mammals like rodents, ungulates, et cetera. And some of the ones that infect humans vary in their specificity to humans. So, for instance, just to so much japonicum, is that how
you've been saying it, I I don't know. Just to so much Japonicum, which has an Asian origin, can infect a wide range of mammals, which suggests that maybe only recently on an evolutionary timescale, started infecting humans. But others, which may have originated in Africa, that's sort of an asterisk. We don't really know. I'll talk about it. They seem much more human specific and are even associated with human
behavior that may enhance the possibility of transmission. So like peak infectivity coincides with the time of day and the time of year that bathing is most frequent in endemic areas. Answering the question where did shistisomes come from was a little bit more difficult than I expected, because it turns out it doesn't seem entirely clear. Did they originate in Asia or in Africa? Don't really know, we can definitely rule out the America's, Australia, Antarctica. I'm glad you know,
because there isn't any fossil evidence of schistosomes. Researchers have relied on a few other tools to try to trace the origins of the mammal infecting schistosomes. So you know, you can do the genomic approach where you compare different genomes of different species to estimate when they diverged or
split from one another. And also you could use the evolutionary history of snail hosts or mammal hosts to estimate a timeline and geography of their history, which is really cool, and so for a long time people most people seem to believe that an African origin of the parasites was the most likely, but recent research puts the origin in what is now northern India, and then they suggest that from there sistosomes first spread east to central and Eastern
Asia and then later spread west to Africa, where they more recently diversified into the more human specific species just A. Soma mansoni and shsto Soma humatobium. That divergence occurred as much as four million years ago. Or as recently as three hundred thousand years ago, but again it's not entirely clear.
We don't know.
Yeah, but what's cool about this evolutionary history of sistosome's is that the evolution of a couple of species seems to coincide pretty well with human evolution when early humans or the ancestors of modern humans started spreading out all across the savannah essentially, so regardless of where shistosmes as a group originated exactly, there was probably a longer association between humans and some of the parasites in Africa, which
led to the specialization of Shistosoma humanatobium and Shistosoma mansoni in Africa, and that's where they tend to be the most. That's where you find the highest burdens typically.
So I was pronouncing that one wrong too, huh which one? Mansoni?
I don't know. I just said, Manson.
What did you say, Manson?
I manson? I I honestly, I mean your guess is as good as mine.
People must hate me, I think.
No, people must hate our pronunciations. Yeah, Mansona Mansoni, I don't know.
I like Mansoni sounds more better.
But this is just how I was reading it in my head. So yeah, I don't know, are you ready to talk? Ancient Egypt always erin, I live for it. For hundreds of thousands of years, humans and schistosomes coexisted, I guess, in relative peace, or as much relative peace as there could be. But that changed when humans began to settle in large communities and practice agriculture and domesticate animals for livestock. What's one of the things that is
crucial for humans their livestock and their crops water? Ah huh, Yes, exactly. And so when humans settled, they pretty much always chose a place where they could reliably get fresh water. Makes sense, Yeah, And as the Sahara Desert got drier and drier, humans in North Africa began to seek more hospitable lands, and the Nile Valley was a pretty ideal place to form
large sedentary communities. And so around eight thousand years ago when we see these earliest settlements, and just a few thousand years after that, these communities had developed extensive irrigation systems and canals to provide water for crops, which is pretty amazing the technology that they developed that was handed to them by ancient aliens just kidding. Probably according to the History Channel, a lot of people had extensive contact
with water, probably every day. They used it for swimming, for bathing, sailing, fishing, and some trades like brickmaking that required a water source. And what else needs water, of course, snails and schistosomes, and so these activities, combined with the lack of sanitation, perfectly set the stage for the proliferation of snails and of course the schistosomes themselves, and we see physical evidence for this in mummies from.
The time mummies mummies.
The earliest known case of schistosomiasis actually appears in a mummy from modern day in northern Syria dating back to around four thousand BCE. Wow, which is incredible. But schistosome infections in ancient Egyptian mummies follow not that far behind, and so the first retrospective diagnosis of a disease in human remains thousands of years old happened around nineteen ten, and it was a case of shistasimiasis in a three thousand year old Egyptian mummy.
In nineteen ten. In nineteen two sit. Wow.
Yeah, So that's that's when paleo epidemiology got its start essentially.
Wow.
And so paleo epidemiological studies of mummies from the area on the border of Sudan and Egypt shows a sixty five percent prevalence of Schistoh.
Right, everyone had it.
Every everyone had it. Wow, I mean, hearing about the biology, I'm like, well, how is that not one hundred percent?
Yeah, it's true. We can talk about it.
Actually, ooh, this is a fun episode, okay. Is the finding of fossilized snails that are the host species in these areas and beyond, like into Mesopotamia and Palestine also suggests that the disease was there as well. What about any physical evidence in Eastern Asia? Yeah, so shistosome eggs of Shistosoma japonicum were found in a preserved corpse in China dating to twenty one hundred BCE. So again, very old,
long time ago. And so we have Yeah, we've got this this physical evidence of schistosomes infecting humans going back thousands and thousands of years. So what's in the written record. Yeah, let's start with ancient Egypt. Okay, So I have to because I say ancient Egypt, I have to mention the Yeah, so in the ebslavirus, there's a description of a disease that I actually mentioned in the hookworm episode called like AAA disease like the letter A three times. I don't know.
Ah uh huh.
And so Egyptologists for a long time had thought this was likely referring to schistosomiasis, since it seemed to have something to do with blood and urine, and it's said to avoid polluted water to prevent infection.
That's so amazing.
Well this this interpretation has been disputed more recently. Okay, okay, moving on, okay, So Herodotus observed that Egypt is the land where men men straight, which people have taken to mean hematuria, which is caused by schistosoma hematobium. Penile sheaths, so like protective sheaths for penises.
Like a condom kind of essentially. Okay.
These appear in early writings and illustrations in ancient Egypt, and people have suggested that they were used as a preventative against schisto since it was thought that the disease could enter the body through the penis. That's too bad, yeah, but this interpretation has also been called called into question. Anyway, and finally, The last bit of evidence that has been called into question is that circumcision, which is apparently of Egyptian origin. I didn't know that.
I didn't know that either.
Yeah, that circumcision was advocated as a way to prevent infection, possibly of schistosimiasis.
That's really interesting though.
Yeah. So there's a relief like a picture from an Egyptian tomb from like twenty four hundred BCE that shows someone performing circumcisions with the caption I will do you good. But that also has been challenged. Okay, Okay, So basically in ancient Egypt, there are a lot of possible references to shista simiasis, but nothing that's absolutely accepted across the board. Okay, except for the fact that it's in mummies like that we know for sure, so you.
Know it was there, But writing wise, we don't know what.
They're talking about exactly. Okay, Now on to the Bible. Oh, does Jericho ring a bell?
Like for sure a song about it? Yeah?
Huh, exactly.
Yeah.
So Jericho was an old walled city, like one of the oldest in the world, eleven thousand years old maybe.
Wow.
In one passage of the Bible, Joshua was ordered to kill everyone in the city and then destroy the city itself. It ended with him cursing the city with low fertility, which was thought to be caused by infected well water. And so a lot of people have said that this legend or belief for this story could refer to the fact that shistosomi humantobium may obstruct fallopian tubes.
YEP and seminal tubes as well.
Yeah.
Yeah, And so the city was abandoned after its destruction and then and there's actually archaeological evidence to support its abandonment. The curse on the town was removed when Elisha went forth onto the spring of the waters and cast the salt in there. There shall not be from thence any more death and barren land. And so they're saying, oh, if you throw the salt in there, you'll kill all the snails, and then she will. But also, I feel like, if you salt.
Your drinking water, it's not it's not gonna be good for you.
It'll be good. Yeah, all right, I promise. I'm almost done with the ancient section. So we got to move on to ancient China though, So you mentioned Katayama disease and symptoms resembling this can be found in old Chinese medicine writings dating back to around four hundred BCE. So
that's all I got for that. But basically, all of these little bits of evidence here and there suggest that schistosomiasis was widespread and probably pretty dang prevalent across much of the tropical and subtropical Old World.
Makes sense.
The New World seems to have been shisto free until the slave trade began in the sixteenth century, when Schistosoma mansoni was brought over, and so that species was able to establish where indigenous snail hosts could maintain the parasite's life cycle, so like Brazil surname Venezuela and some Caribbean islands. All right, So now we're caught up on the origins of schistosome's and the evidence for human infection and antiquity.
But when did people discover the parasite like that first hand account, Well, there are descriptions of a disease resembling some of the manifestations of schistosomiasis in Italy in the sixteenth century, but no one really took much note of that, and it wasn't really until Napoleon's army invaded Egypt in seventeen ninety eight that a French physician with the army noted how men in Egypt menstruate and how many of the French troops also had blood in their urine and
pain in their bladder. And then about fifty years later, researchers on two separate continents began to take a closer look at this disease. In Japan, in eighteen forty seven, a researcher named doctor yoshinow Fuji described what he assumed was a new disease. So quote, during the past two or three years, farmers have had small eruptions on their legs when they entered the water to cultivate the rice field. The eruptions are unendurably painful and itchy. Cows and horses
also show the same symptoms. Most of the residents suffer from this disease.
So that's sounds like shisto.
Sounds like shisto, the acute shisto at least, right. And so one of the counties that was heavily affected by this disease was Katayama, which is what gave the disease its name. In Japan, to indicate a new and with schistosomes. It would be decades though, before the parasite causing this
Katayama disease was discovered in Japan. In eighteen fifty one, a guy named Theodore bill Ar's teddy Bet, was working as an assistant professor at a hospital in Cairo when he observed this trematode in the portal vein of a young guy. And so this is what was in the first hand account. But he thought that this might have something to do with both the bloody urine and also dysentery,
both of which were common throughout Egypt. And this is what actually got the attention of a lot of people, his descriptions and his suggestion of a link between those
diseases and the parasite itself. This is like in eighteen fifty one, Yeah, eighteen fifties, and people started trying to figure out the transmission cycle of this parasite, but were thwarted, partly because Billar's didn't realize that the morphological differences he was seeing in the worms were because they were different species, and partly because another leading researcher was adamant that there was no intermediate host for the parasite.
Why would you be so adamant about that?
Part of it was like, I think hookworm and other worms that showed Yeah, I know, but he was very I had a lot of conviction, which is a dangerous thing in science when you close your mind off. During the sixty years following Billar's discovery, many researchers tried to pick apart the puzzle of this parasite, including its transmission cycle, how it entered the body, and the question of how
many species were actually present infecting humans. And this was a pretty feared disease by colonists who had moved to affected regions, so British troops stationed in Egypt and the early nineteen hundreds were told to wear a con while bathing so as not to get infected. It's not going to help you.
I don't do anything, but no.
Eventually, in nineteen fifteen, a researcher named Robert Leiper showed experimentally that snails are the intermediate host of schistosomes, and also showed how the adult worms mature in mammals.
To be fair like, it's amazing that people figured that out because it is such a complicated life cycle.
It's incredibly complicated.
Like as much as it seems wild to say to be adamant that there is no intermediate host, it's also wild that they figured out what the intermediate host was and just how like they just figured out this complex life cycle oh so long ago, Like that's it's really incredible.
Absolutely. I mean yeah, you'd think, like, why why would you look at snail? Like what would lead you to look at snails? Yeah, for instance, So yeah, it is, it is cool. So then yeah, so nineteen fifteen was pretty much when like, okay, we can finally get to the nitty gritty of all the different stages of the parasite and uh and look, take a closer look at
the intermediate hosts. Bill Ar's, though, unfortunately, wouldn't live to see the life cycle figured out, because he died only like eleven years after his discovery of the worms of typhoid fever.
At least it wasn't shisto. I thought it was going to be shisto.
I wonder if he had shisto.
Probably, Oh that's sad though.
Oh I have a quick question. Can you get shisto from ingesting contaminated water?
Good question, Not as far as I know.
Okay, it's just through contact.
Yeah, okay, yeah, okay, because it wouldn't Yeah yeah, I mean I not as far as I know.
Okay. So bill Ar's work I think is actually pretty impressive that he was making a connection between a microscopic parasite and disease symptoms before germ theory was really a thing, which is pretty cool. And his significant contributions to the study of schistosomes is why schistisimiasis was also called belarcia or blarsiasis.
But that's what that's common harder to say, isn't.
Much harder at least for us. Yeah, and actually it is still called bilarcia in many parts of the world. But schistosome was proposed first from the Greek words for divided and body. But other names of the disease include redwater fever, snail fever, and big belly, big belly.
That's from the asides.
Yeah. While the debates for the parasites transmission and life cycle were going on, the parasites themselves were experiencing a huge growth in prevalence, especially in Egypt. Instead of basin or surface irrigation during so that's when the land is flooded to soak the crops, and that's an old method of irrigation and allowed for one crop harvest along the Nile.
But then perennial irrigation was introduced in Egypt and that allowed for water to be flowing year round, which was great news for cotton, which became the country's primary export, but it also meant tortuous working conditions and a steady source of snail and human hosts for schistosomes. Studies looking at how this new irrigation method increases to Semias's prevalence estimate anywhere from a tenfold increase to a growth from one to three percent prevalence to seventy five to eighty
percent prevalence. So it just like exploded in terms of prevalence. Oh yeah, the enormous growth of interest in justtosomes in the late eighteen hundreds and through World War Two didn't just happen in a vacuum. Wasn't just driven by curiosity In the case of shistosomes. The motive to understand the disease was essentially imperialism.
As it often is.
As it often is, Yeah, tropical medicine as a field essentially began so that the tropical regions of the world could be made suitable for white people to inhabit and invest in empire building essentially, like the search for malaria transmission treatment and yellow fever prevention are two perfect examples
of this that we've talked about on those episodes. Yeah, and so there's even a line in a scientific article in the British Medical Journal from eighteen ninety seven that says, quote, get rid of or avoid these disease germs, and we get rid of a principal obstacle to the colonization of the tropics by Europeans.
Wow, just straight up.
Uh huh, just wow.
There's so much anger brewing in.
Me, you know, I think it's Yeah, the good news is that today we have a lot of studies of neglected tropical diseases that are motivated not by colonization but by wanting to make the world a better place, or at least that's what the researchers.
Does that do. Is that why there is no funding for it? Though exactly so.
The researchers who are working on it, they want to make the world a better place. The funding agencies don't know. Oh. But also random piece of Trivia here. The first graduate school of parasitology in the US was established at the University of Illinois in nineteen oh nine.
I didn't know that.
Yeah, there's no longer a school of graduate school of parasitolic.
There's not a ton of There's some you know, some of us here, but not a lot of people studying parasites anymore. It seems like comparatively.
Comparatively, Yeah, So the Boer War in South Africa, many British troops were stationed there and they became infected and incapacitated by shisto. And the presence of British troops in Egypt during the late eighteen hundreds and early nineteen hundreds, these directly led to the discoveries that I talked about. This is why people had such a vested interest in figuring out what was going on with the parasites life cycle,
socalism and war imperalism in war. So, increasing efficiency and control in the Egypt meant reducing the prevalence of schistosome's, but primarily by reducing it in British troops. So, once Leper made the link between the snail and the schistosome, he proposed that if you control the snail, you control the schistosome, and he recommended drying out the canals for
a bit every year to kill the snails. This method of control doesn't actually work all that well, since all you would need is a few snails to keep pumping out millions of parasites.
Personnail per day from one like.
It's yeah, uh huh, Yeah, it's such a harder thing to try and do to control the snails.
Yep, But that was the primary control strategy for decades and is still i think a practice in some places.
I mean, it's still i think an important component of everything it is. It's definitely not going to be the only thing going to yeah yeah.
And this aiming just for the snails kind of shows again how early tropical medicine was concerned only with the parasites or pathogens themselves, without considering how cultural or behavioral practices may have an impact on disease transmission. Water filtration was also proposed, but this was limited to British troops.
It could because setting up infrastructure to get clean water going everywhere was way too expensive in their minds, So let's just focus on the important people and It also might have been that the discovery of an effective treatment for schistosmiasis discouraged any infrastructural changes to prevent the disease. In nineteen eighteen, antimony tart rate so tartar emetic, was found to be relatively successful in treating shisto, which is
around seventy percent cured. But it was also a poison so you had to be careful you didn't die, and the doses given to infected people were extreme. They also had to be given out over a period of like thirty days, so you had to return to a clinic every few days, and as you can imagine, the proportion of people who actually completed the course of treatment pretty low because a day of going to the clinic meant a day of lost wages and you know, also potential poisoning.
And that's something that like, so it's still so very relevant today in terms of like reducing the barriers for treatment or for just healthcare overall. Is like, let's not make it a decision between making the money that you need to live and you know, having good health anyway, So researchers then were like, okay, well, we need an easier solution for reducing the parasite, and so that's one of the reasons why snail killing continued at such a
large scale. And you know, the first large scale efforts to reduce snails throughout Egypt did seem to offer at least a short term reduction in snail populations, and it was striking enough that in nineteen thirty nine it was declared that just a samiasis could be eliminated from Egypt in twenty five years by clearing the canals.
I'm sorry, this was in wet year nineteen thirty nine, twenty five years years.
That did not happen, not at all. Many of the public health directors in these tropical countries that were overseen by European imperialist countries, these were aimed towards controlling infectious disease, either through infrastructure improvements limited to citizens of whatever European country, or through widespread treatment campaigns. But it became obvious that neither of these tactics would result in a lasting improvement
in actual public health. So gradually sanitation campaigns and improved living and working conditions were put in place. But this wasn't motivated just by like, oh, we want to make the world a better place. Again, the ruling countries simply realized that a healthy workforce is more efficient and productive, and that's where a lot of the effort ended was as long as you got them well enough to work,
then you leave, you drop it all. Often the medical officer of like a mine, for instance, was seen as almost this missionary savior of the quote savage or uncivilized natives, pulling them out of the filth and disease to which they had been accustomed. But in reality, the prevalence of many of these diseases in tropical countries increased tremendously during
imperialist rule. Of course, I mean scurvy accounted. I'm getting a little bit outside of schisto, but for example, scurvy accounted for thirteen and a half percent of all deaths in a mine in what is now Zimbabwe in nineteen oh eight. Scurvy like which we talked about and which you know could have been prevented, tuberculosis, pneumonia, silicosis, and of course just to semiasis became huge problems in these minds, among other diseases. And it wasn't just that crowded and
unsanitary conditions promoted the spread of schistosimiasis. It was also the nature of the work itself. Sugar plantations and cotton growing both meant exposure to contaminated water, and prevalences reached above fifty percent in many places, but the link between these conditions and disease wasn't really recognized, at least publicly, but instead the sentiment was much more that the indigenous populations were acting as a disease reservoir, putting the white
colonists in harm's way. And you can see this come through in the way that shistosomiasis is discussed in some of the public health reports in South Africa in the early nineteen hundreds, schistosimiasis quote seems well under control among Europeans, though of course the natives are commonly infected end quote, and attacking the disease quote might help to free the
country of infection and enable us to bathe safely. H Throughout the nineteen thirties, the focus on tropical medicine declined in the two main empire builders, so Britain and the US, But then World War II broke out, which meant that those Europeans or American station in the tropical war zones would face the scourge of the diseases there. In terms of numbers, things like malaria and STIs far outweighed shisto infections in American troops. But one campaign in the Philippines
saw an explosion of shisto cases. Medical researchers kind of like leapt on this outbreak and the funding that was provided for it to conduct research into shisto, the stages of disease like acute versus chronic, and treatment strategies, And this came at a pretty key time in the history of tropical medicine, which was a few that was almost dying around the same time as imperialism was on the decline decline. So remember that that nineteen thirty nine prediction
that schistos mayass could be eradicated within twenty five years. Yeah, well, the snail population did seem to be declining, but the shisto no. A bunch of kids born after the eradication campaign began were screened for the parasite and the prevalence of the parasite was found to be sixty three percent, incredibly high, and in other more rural villages that number was over ninety five percent. Wow, So obviously something was wrong.
The eradication campaign recognized this and changed their name from the Blarzia snail Destruction Section to the Bilarzia snail Control Section.
Also, snail destruction section is a name.
Ostractions meeting them like at a bar after work, like, oh, what do you do? Oh?
I just work for the snail destruction section.
I want that on my business card, mean too, like an embroidery on a zipper jacket. Yeah. They the people working in these destruction and control sections, They couldn't answer how low the infection prevalence had to be in snails in order to break the cycle of transmission in humans. So how could they even direct the campaign effectively?
Cannot?
Cannot. Meanwhile, Egypt was not the only country dealing with incredibly high prevalences of schistosimiasis. China faced a similar situation, and a mass campaign against the disease was started by the Nine Man just A Semias's Subcommittee, which are like the best names for these the nine Subcommittee UH. Starting in nineteen fifty eight, this set up prevention and treatment units across the country, as well as research institutes to
study the parasite. Treatment regimens were shortened to just a few days, but it seems that the majority of the campaign's efforts were concentrated in reducing the snail host. Latrines were repaired, swamp land drained, snails buried, grass burned, and chemicals applied. Within a year or two, several counties were
announcing that they had eradicated just asimiasis excellent. Mao Zidong wrote a poem called Farewell to the God of Plague in response to this news, and you can go read the poem in a book that I'll mention, but anyway, you can probably find it online. Anyway, the campaign against just a Semiasis seemed to be incredibly successful, if you believe the claims about the progress made. But was shisto
actually eradicated in these counties. Probably not, but it does seem that substantial progress had been made in the prevalence of infection. Obviously, you know, I'm sure you'll talk about what the prevalence is today. But one of the main problems, and maybe something that's affecting the parasite today, is that other mammals, especially cattle, were the main source of schistosome eggs in the environment. And as far as I read,
cattle themselves were not a target for treatment. So in the decades following World War Two, interest in schistosomias's grew for a number of reasons. One was the fear that soldiers returning back to the US or Britain would carry with them the parasites that could establish in native snail populations. Another was the fear of a looming food crisis. If enough food was going to be produced globally, people in the most productive agricultural regions had to be healthy enough
to work. But irrigation and dams had only led to an increase in schistosomias's prevalence. For example, in Ghana, in nineteen sixty five, a lake was created after damning a river. Within a year, the snail host of Shistosoma heematobium had appeared, and two years after that the prevalence of schistosomiasis was fifty percent in the population living around the lake.
Yeah, damser damns are not great for shisto shisto.
So so. Another reason for this increased interest was simply the increase in cases. In nineteen fifty one, shistasmiasis had been declared next in importance to malaria among the world's tropical diseases.
I think it remains.
I think it does. Yeah, which has been sort of contended in terms of is it truly the second most important?
But I think we'll talk about it.
Yeah, okay. But the control programs kind of went like this, first, kill the snails. Oh, that didn't work. All right, Well, let's try treating people. Oh, that didn't work either, because peop, we can't afford to miss a ton of work to go get a shot. And also side notes, so this is, you know, making another connection with the hepatitis C episode. These tartar emetic campaigns in Egypt throughout the nineteen fifties through the nineteen eighties. These were like huge campaigns to
get the treatment for sistsymiasis. They tended to reuse needles to save money, and this led to a massive spread of HEPC, which is only discovered decades later. I think even now Egypt has one of the highest prevalences of heptitis C.
Oh wow, perfections.
Yeah, huh, So, how do we improve the treatments or maybe we do a combination of treatment and molluscicides. But so far, it doesn't really seem like any of these strategies have been super successful. If the hundreds of millions of infections today is any indication, I'm sure you'll talk about it.
M hmm.
Okay, a wrap up now, But I want to say that before researching this episode, I hadn't really considered how a possible negative consequence of germ theory was that people kind of stopped considering the social aspects of diseases. So there was a pathogen or a parasite or a vector, and so the research concentrated more on understanding or controlling or treating those aspects rather than the underlying causes contributing to not just one specific disease, but a whole suite
of them. So like before it was recognized that tuberculosis was caused by a bacterium, it was known that like crowded conditions and this and that, and so instead of focusing on treating the disease itself, let's treat some of the underlying issues associated with its spread or establishment. So it's kind of that part is I mean, obviously germ theory was hugely important, but it is interesting how these
social aspects were neglected. Building that knowledge of the pathogen and parasite biology and treatments is obviously hugely important, but it does seem to have come at a cost to
social medicine. So like how social factors contribute to disease, especially for these neglected tropical diseases, And these were researched and described by Western scientists through their lens, and the vast majority of those doing the research did not have any knowledge of local customs, knowledge or beliefs, which may have given them not only a more full picture of the disease they were studying, but also clues to its control.
And I'm primarily referring to schistosoma in Africa when talking about this, and then later in South America and so over the past few decades there has been a push towards social medicine and constructing a fuller picture of these diseases which are so multifaceted. But the disproportionate disease burden around the globe definitely shows that there is still so much work to be done, plus the looming specter of
climate change because I had to sneak it in there. Yeah, it means that the distribution and prevalence of shistosomiasis will likely change in ways that are going to be difficult to predict. Since the African continent has the vast majority of schistosomiasis infections and is one of the most vulnerable regions for climate change and climate instability, there's a big push for predictive modeling for what the disease is going
to look like. But that's the future and there's still a whole lot of work that needs to be done. So I'm ready to hear about what's going on with shisto in the world today.
I'm ready to tell you right after this break. So it's just a semiasis today. The World Health Organization considers it, of course, a neglected tropical disease, which we've talked about a number of these in the past. It is estimated that globally, nearly eight hundred million people are at.
Risk of infection. Oh my gosh, Yeah, at risk of infection.
And it's thought that about two hundred and fifty million people are infected worldwide, and about two hundred million of these people live in on the African continent. So yeah, that's pretty massive. And you asked earlier about worm burden. Uh huh, So let's circle back to that. I don't know the exact numbers like how many worms do people get infected with? But by and large, children have the
highest worm burdens and are the most affected. And one thing that I think is really interesting is that it used to be thought that this was entirely behavioral. Kids play in the water, they run around, that's how they get infected, whereas adults have different behavioral patterns and so they are infected at less of a burden. But there's more research that shows that there's also likely a strong immunological component to this, because you do build up immunity slowly over time.
Interesting, so that, first of all, is.
Important because we'll talk in a minute about the potential for vaccination. If you can't build up immunity to this, then there's no point in a vaccine.
It wouldn't work.
But we can build immunity to it, it just takes a really long time, and we don't know exactly what the best targets are necessarily, So it's thought that that's part of the reason why we see less of a burden and less egg shedding in adults than we do in children. The adults who tend to have the highest burdens are people who who are frequently exposed to freshwater sources. So if you fish for a living, if you work in flooded rice patties and things like that for a living,
occupational exposure is where adults tend to get infected. Right, So, yeah, I think that's something important to keep in mind that we used to think it was entirely behavioral, but it's likely not entirely behavioral. But in addition to just the number of people infected, we know that this is a
chronic disease and it causes these chronic symptoms. And so when we look at something like shis a semiasis, one of the metrics that people use to estimate the overall burden are what we call disability adjusted life years, which we've talked about DALIS.
And trying to.
Get a hand on the Daly's Forcehossi semiasis is really difficult. We don't have really solid numbers on this.
Surprise surprise why though, I.
Think because it's kind of hard to estimate how much of an effect infection has on people.
Well, I guess because it's probably not like often there are co infections with a lot of other things too, absolutely separating those out, Yeah.
Absolutely, co infection is going to be huge but then also like the greater the worm burden is going to make a difference on how severe your infection is, So like infection severity is going to range how often you get reinfected, you know, if you have access to treatment, things like that. So it's it's complicated. So estimates kind of are all over the place. Twenty sixteen Global Burden of Disease estimated that it's about one point nine million dallis so disability adjusted life years.
Wow.
But there have been some other analyzes that suggested much higher estimates. And that's I think if you include the fact that there is under nutrition anemia, right, this just.
Feel like you should because of the mafestations, you absolutely should.
And so this is where I actually want to touch on something that is really important with a disease like shist a semiasis and neglected tropical disease, and that is this cycle of poverty. Right. I feel like we've talked about this in bits and pieces before, but with something like shista semiasis, it's really important to touch on just how huge of an impact socioeconomics have on this disease, and how much of an impact this disease can have
on socioeconomics. Right, So, a disease like shist a semiasis that causes chronic and severe symptoms, especially in children, this can cause malnutrition, impaired growth, and compromise cognitive development in children, especially when you consider you know, coinfection, generalized under nutrition and lack of access to nutrition and things like that.
On top of this, Okay, then in adults, this illness can lead to the reduced ability to work, which can have profound impacts on economics, especially because of how widespread it is. So on a population level, a disease like schistosimiasis takes a huge impact. It has a huge impact
on a populations and an individual's socioeconomic status. Then when you combine that with poor sanitation and poor water quality which means opportunity for reinfection and continued exposure which means continued disease, you have further reduced productivity, further reducing a person's ability to move out of posity feedback and basically perpetuating that cycle. It's a feedback loop.
Yeah, and it's the same thing that that we see also with hookworm and with many other geohelmets. Basically many other of these intestinal parasites or neglectrotropical diseases. That's like, that's part of the one of the hallmarks of.
A neglected tetropical diseases exactly.
Especially these ones that are that are chronic like this, you know, uh huh, yeah, So it's in that way. It's just as miss is, like, we have a huge long way to go. The mainstay of control at this point is mass drug administration, so treating entire populations of people even if you don't know for sure if they're infected.
So essentially the World Health Organization can go into an area and see what proportion of children are symptomatic or have for example, hematuria or eggs in their stool, and if more than fifty percent of children in an area are infected, which is a very high proportion, and everyone in that area will be treated. Yeah, and the treatment now is there's only one drug really that's approved for use. We can talk about the problems with that, but it's
called prosy quantal or prazy quantal. It's effective, asterisk, it's effective, and so you can administer this to entire groups of people and you know, essentially wipe out adult worms from that population. But there's the asterisk. This drug is only effective against adult worms, so it does nothing if the worms that are in your body are still in that
teenage stage marval stage. It does nothing for the eggs that are already in your body, right that those are the ones that are causing a lot of the symptoms that we see. And it does nothing for the environmental aspect of it, right, so it does nothing to prevent reinfection.
How long is this treatment? Is it just a one time thing?
It is.
It's a one time dose, which is great, pretty effective at this point.
Is there any resistance?
That's why I said, at this point, ah, so there As with any drug, there is certainly concern for drug resistance. There isn't at this point a lot of evidence for resistance in the field, so it seems to still be pretty effective in the field. There is some evidence in mouse models, and I think this is really interesting and terrifying.
There's evidence in mouse models that immature schistosomes, so like the teenage versions in your liver that are exposed to praziquantal, are more likely to be resistant as adults, and that this tends to increase resistance through generations. So like if because it doesn't kill those larval stages in mouse models. If those larval stages are exposed to this drug as adults, they're more likely to be resistant.
How does that work mechanistically?
Probably some kind of epigenetics thing. Okay, it's like turning on or off genes that they might already have in place.
That's really interesting.
Yeah, it's it's only in mouse models, so it's unclear whether this is happening in real life.
There isn't at this point a lot of.
Evidence for resistance in human populations with this drug.
It's still an effective drug, okay, good, Yeah, but.
It also can't be used for like chemoprophylaxis because it doesn't do anything for those larval stages. It doesn't prevent you from getting infected in any way, and it has a really short half life. So it basically is like, you take one dose of this drug, it kills the adult worms.
End of story.
Cool the end, okay, okay, So we.
Need something better is pretty much the long and short of it. Right. So, there's a lot of work being done to try and develop a vaccine, in part by none other than our good friend Peter Hotez.
Yeah, Peter, Hotez Doctor Peter Hotez.
His group in Texas, as well as a number of other groups are working on vaccines. There are a number of challenges, largely in that we don't sort of develop classical immunity to this parasite the way that we do to other viruses or bacteria kind of a thing, so
it's a more difficult target essentially. But basically there's a lot of mathematical modeling that show that any vaccine that can overall reduce egg output and can last so can actually prevent reinfection and prevent egg output from going up again, can massively help to interrupt transmission.
I mean that makes sense, yeah.
Right, So that's kind of going to be one of the main things going forward, is trying to develop a vaccine that can do that. There are at least three vaccines right now in clinical trials. They are component vaccines, so they're made up of specific antigens of Schistosoma mansoni
or mansoni along with adjuvants. Because one of the big things is that because this is a parasite that we know can elicit an immune response, it takes a very long time, so we have to include adjuvants in these vaccines to elicit a stronger immune response so that your body can actually then fight off any further infection with this parasite.
Does that make sense?
Yeah, yeah, So there's a long way to go, but there is a lot of really great work being done by people to try and develop a vaccine for this, which is great.
That's awesome. Yeah, yeah, cool, it's always I think good to hear after a very depressing history section and a little bit daunting, not even daunting, but like horrifying numbers of people infected around the world, some promising future for the disease that we talk about.
Yeah, and World Health Organization, I will say, has a lot of goals in terms of trying to reduce morbidity and mortality from shisasmiasis, So they really are trying to get prosi quanto, the drug to as many people as possible. In twenty eighteen, about forty percent of people who needed treatment were actually reached and about sixty two percent of
children were being treated who needed to get treated. So we still have a ways to go there, but again, there are people really working hard to try and get people access to drugs as well as developed vaccines for this.
Horrible disease.
Truly.
So yeah, that's just asmisis.
Tropical A good a good turn for tropical medicine. It's not changed changed its intent and that's great.
Yeah, So sources, sources.
I want to shout out, first of all, a book called Belarzia, A History of Imperial Tropical Medicine by John Farley. Fantastic book, really thorough, is very very fascinating, great resource. And then I also want to shout out a few other papers that I read, Where do human just toems
come From? By Claude Comb's nineteen ninety by DiBella at All, twenty eighteen, History of Semiasis and Humans from Egyptian medical papyri to molecular biology on mummies, and finally by my Mood two thousand and four, A Semiasis from Antiquity to the Present. And there I've got a whole bunch more that I'll post on the website.
If you would like a really really comprehensive overview of schrissmiasis biology and ecology. There's a great primer in Nature Reviews Disease Primers by Donald McManus from twenty eighteen. And then I have a number of other review articles and papers about the vaccine development. We'll post all of our sources on our website, This podcast will Kill You dot com under the episodes tab where you can find all our sources for this and every single episode we've ever done, so check those out.
Yeah, thank you so much for listening and for letting us do this podcast because it's the most fun thing and honestly, I can't believe that we get to do it.
It's so fun.
And thank you to Bloodmobile for the music in this episode and all of our episodes.
And finally, until next time, wash your hands you feel the animals.
Um um um um