This Podcast Will Kill You - Ep 47 Schistosomiasis: A Snail's Pace

Episode Date: March 31, 2020

It’s back to your regularly scheduled programming this week with an episode on schistosomiasis (aka bilharzia), that scourge both ancient and modern. We kick off the episode by walking you through the amazingly complex life cycle of these blood flukes and the myriad of symptoms they and their eggs can cause, including a “check out the reproductive output on this one!” moment.  We then trace its early appearances in mummies (of course) and ancient writings, following that up with an overview of how imperialism drove the field of tropical medicine in its early days. To wrap up this wormy episode, we discuss the current, staggering numbers on schisto around the globe. See omnystudio.com/listener for privacy information.

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Janice Torres here. And I'm Austin Hankwitz. We host the podcast, Mind the Business, Small Business Success Stories, produced by Ruby Studio, in partnership with Intuit QuickBooks. We're back for season four to talk to some incredible small business owners. The big thing about working at tech is that it's ever evolving, ever changing. everyone's a rookie. That's how fast the industry is changing. So what I'm really excited about is to be part of that change. So listen on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. 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 wife's tail, but into something more wonderful, a trematode with divided sex. I performed an autopsy on a boy who died of meningitis. Upon opening the urinary bladder, we found lentil-to-pea-sized soft, spongy excrescences. When I cut through the largest of the excresences, 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 Dr. 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 Dr. Grisinger encouraged me to examine the pathologic changes of the bladder, which were so similar to those found in dysenteric degeneration 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-hibitobium stands in the same relation to dysentery as Akara-Skabi does to the itch. Right then.

So that was from excerpts from letters from Theodore Billars to his supervisor, Von Siebold, while conducting research in Egypt. And this was essentially the discovery of schistosoma hematobium. The subject of today's episode. One of the subjects. Shistosomiasis in Jen. Hi, I'm Erin Welsh. And I'm Erin Alman Updike. And this is, this podcast will kill you.

Yeah. Welcome to schistosomyasis. Schistosemiasis. My first true love of disease. I like the qualifier there. Not just true love? Yeah, I'm excited too. I mean, we love a good multi-host parasite.

Yeah, we do. It's 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 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 histories. Blood products, etc. Hey now. No, that was great. No, true. Okay, so what are we drinking this week? We're drinking just a fluke. Because also schistocones are known as flukes.

Flukes. Yeah. It's a type of flatworm. Yeah. And in Just a Fluke 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, we'll post the full recipe for this quarantini as well as our non-earned. alcoholic placebo rita on our social media and our website. So you can check it out there. Yeah.

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Quince.com slash this podcast. So schistasemiasis also called Bill Harcia. Yeah. Because of, as you mentioned from our first-hand account, the person who discovered it. Theodore Billars. Can we call him Teddy? Do you think you went by Teddy? I have no way of knowing.

There probably is Google, actually. Teddy Billars? That's a cute name. I like it. I like the name Teddy. So schistosomyasus, aka Bill Harsia, it's caused by a worm. We haven't done a ton of worms, so this is exciting. It's a flat worm 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 schistosomes that infect humans, the three most common are schistosoma mansini, 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, Mansonai, Joponacum, and hematobium. It's kind of like the special one. So what we're going to do is talk about the general life cycle and pathway first as a group, like all the schistosomes, 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 etymology. 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 fish. Little flounders.

I can see that. Cool. Thanks, Erin, for 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 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 freshwater, okay? And out of these eggs hatch these little myricidia is what they're called. but we'll call them baby schisto. Okay. So baby schisto have all these little cilia 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 does I write crab? What God. That is incorrect. That is incorrect. It is 100% incorrect. I can't believe I wrote crab. How funny.

So with these little swimmers, they see. 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 schistos begin to multiply asexually. Okay. 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 snail's little fleshy body parts? Yeah, okay.

But they, so they replicate asexually, which is wild considering in the firsthand account, we learn that there's... Oh, Erin. We'll get there. Okay, don't you worry. These are baby schistos. These are baby schistow. We're going through life stage by life stage. So the baby schistos swam their way into a snail. they begin to replicate asexually, so multiply and multiply, and then they change into what are called

Circarei. And these are kind of like a kid schistow, okay, kiddo schistos. They look kind of like sperms, 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 schistos, sperm-y-looking things, swim, burrow their way back out of the snail and are released again into fresh water. And then they use that tail to swim around through fresh water. Over how many days or how long do they replicate in the snail?

I knew you were going to 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 schistos make it into the snail, it takes four to six weeks before they start shedding the kiddo schistos, the Circairia. It's a long time. It is. And now these circarii can live in the environment for up to 72 hours. So they're swimming around.

That's a short time. They're swimming around in freshwater. And now here you come as a human mammal walking around for a nice walk through these freshwater. ponds or whatever. You're obviously barefoot because you wouldn't want to get your shoes wet. And these little kiddo chistos 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. 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 vein is 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. Oh. And where they go from there is actually they make their way from your heart to your liver. Okay. This is a very complicated root. 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. Yeah. Or no, not 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 bloodstream. So they're basically just riding your blood flow all the way to your liver. That's their target destination for now. Okay. Then in your liver, and this is 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 going to leave that 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 schistosomes. And like you mentioned, in the firsthand account, they now have male and female. schistos, 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, they're going to couple up, okay, and sleep in the same bed together. Just kidding. What happens is the female chistosome literally wedges, to a canal in the male schistosome called a gyna cipheral canal, and then as a pair, they travel

together to their final destination. Okay. For schistosoma mancini and japonicum, this final destination is the venous plexus around your intestines, the mesenteric veins. For schistosoma hematobium, it's the venous plexus around your bladder. Huh. Okay. I don't know why. 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 schistosoma 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, 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 burrow their way all the way through your bladder, which is a really thick organ, like it has a thick wall, into your bladder. And then you pee them out.

Okay. Okay. Is there ever any recoupling? Recopling? Recopling? Aaron, I practiced for like 10 minutes last night how to say, Coupe up. And I think I still did a terrible job of it.

Do you mean you watch 10 episodes of Love Island UK? I literally sat with Brett saying the words, couple up, like for 10 solid minutes, trying to get a good accent. Anyways, time well spent. So that's the life cycle of Shistosama. 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 body. That's impressive. Just laying eggs, laying eggs, laying eggs. Okay. That also makes it very difficult to get rid of environmental. schistosome. Do you want to know what? The theoretical reproductive potential of one schistosome pair is 600 billion schistosomes. Oh my. Because not only are the adults living in you shedding for years,

but one single meridium 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, 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 schistosomyasis 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, microperations, 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. 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 like your tissue essentially is it causes a massive inflammatory response in your body. 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. Oh. It's what happens in your lungs. Yeah. So that happens as well in

in chistosomyasis. And in the bladder wall, this can cause chronic inflammation. So one of the hallmark symptoms is bleeding in your pee. So hematuria. 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 flows in your veins, 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 is 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 hepatospenomegaly. 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? Let's see. Was it Hep C? No, because Hep C doesn't cause spleen. Dengay? Dengay.

It was dengue, okay. Yeah, dengue. Cool. Yeah. So fun. Connections. Yep. So it can cause hepatospinalamagally.

It can also cause what we did talk about with hepatitis C, which is fibrosis of the liver, especially. Now, any time that you have veins being close. like we talked about in the Hep C 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 ascites, fluid being filled up in your belly. You can get esophageal varicase, so varicose veins in your esophagus, which can cause massive bleeding if they rupture. Oh my gosh. Yeah. Yeah. 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 body's mounting a massive immune response to try and wall these eggs off. Mm-hmm. 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 circaria themselves. And that is an itch where those little spermies penetrate your body.

Okay. This is sometimes called swimmer's itch. It's also really funny to me that you're calling them little spermies because of something that I'll talk about in the history section. Oh, really? Yeah, yeah. Okay. 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 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 schistosoma, Mansonai, 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. Okay. 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 eocinophilia, which is, I think, another fun word. It's a great word. So that means an elevation in the number of eocinophils, which is a specific type of white blood cell that we have, that we use, to fight off parasitic infections. Uh-huh. 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 for 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 schistone 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. 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 what it's called. And yeah, that's sort of the acute, it doesn't, In endemic areas where schistosoma, Mansonai and hematobium are the primary causes, this isn't a disease you tend to see very often. Right. Which is very interesting. So the majority of problems associated with chistosomiasis 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 we'll 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 anemia. 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 ascites, portal hypertension, liver fibrosis, all of that kind of stuff. In your urinary tract, bloody urine hematuria, is kind of the hallmark sign of schistocymiasis, especially in children. Okay. Especially in children. Yeah. There's really no, like there's no other, well, in endemic areas, if there is a kid with

bloody urine, it's schistosomyosis, essentially. Okay. Okay. What's very interesting is that in adults, chronic infection with schistosoma hematobium that affects the urinary tract is associated with an increased risk of bladder cancer. Because of the inflammation, essentially? Yeah, it's thought that 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 smoking and things like that. Okay. So it's not entirely clear whether it's like, but overall, yeah, it's inflammation, right?

Yeah, right, right. Yeah. And now here's the other really important thing about schistosomahemotobium. 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 genitoneary chistosomyasis. So it can affect, it can affect the prostate, the seminal vesicles. So you can see things like hematospemia, 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 genitoneone chistosomyasis 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 10 and it was just like picture after picture of Eurogenitor, wow, of Eurogenital schistocymiasis. And yeah. Yeah. It's terrible.

It's horrible. It's horrible. Now, because this is something that's in your 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 granulomatous changes that we saw in everywhere else in the liver, in the bladder, etc. 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.

Oh my gosh. 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 pulmonary. 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 eggs 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 worm pairs that you have, the more eggs they're 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? It can.

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 brain. your bowels. So it can break its way into your central nervous system and cause neurosisomysis, which can cause seizures, other neurodegenerative type symptoms. Yeah, it's gnarly. That's schistomyasis. Wow. That's a very complicated story. Super, super complicated. And a lot of bad manifestations. Yeah, it's a really gnarly disease. Yeah.

What the heck, Aaron? What the heck? Where did this thing come from? How did it get here? Why did it take us 45 minutes to talk about? Oh, good God. Well, let's dive into the very long history of Shisto right after this break. Awesome. Anyone who works long hours knows the routine. Wash, sanitize, repeat.

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We host the podcast, Mind the Business, Small Business Success Stories, produced by Ruby Studio, in partnership with Intuit QuickBooks. And we are back for season four. We're talking to small business owners who are doing incredible things in their industries, achieving their dreams, being their own bosses, putting in the work, and enjoying all the benefits that come with it. This is our most exciting season yet. We're talking to more entrepreneurs about how they launched their vision,

and more importantly, how QuickBooks on the Intuit platform helps them do more in less time. Working in QuickBooks just makes it easier to run the business, right? There's so much that you need to do when it comes to running a business, building products, setting up marketing campaigns. And to run a business, you have to make sure that your finances are in order. So it removes my anxiety from one side of it so that I can focus on everything else. Whether you're a long-time listener or just getting started, tune in and join. us. You'll be so glad you did. Listen on the IHeart Radio app, Apple Podcasts, or wherever you get your

podcasts. 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 do we get? get here. But I want to change that question a little bit by asking and hopefully answering, how did we get from there to here? But first, what is there? Basically, where did schistosomes come from? And how did some of them become parasites of humans? So you mentioned that schistosomes are a super diverse group. There is about a 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, but of the ones that infect mammals, which is around 23 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, etc. And some of the ones that infect humans vary in their specificity to humans. So for instance, schistosoma japonicum, is that how you been saying it? I said japonicum, but I don't know. Just as some of japonicum, which has an Asian origin, can infect a wide range of mammals, which suggests that maybe only recently on an evolutionary time scale 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 schistosomes 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 Americas, Australia, Antarctica. Antarcticaica. I'm glad we can roll that one out.

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, Shistosome's 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, schistosoma Mansoni, and schistosoma hematobium. That divergence

occurred as much as four million years ago or as recently as 300,000 years ago. But again, it's not entirely clear. We don't know. Yeah. But what's cool about this evolutionary history of schistosomes 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 schistosomes 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 schistosoma hematobium and schistosoma 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 Mansoni. What did you say? Mansonai. Mansonai?

Honestly, I mean, your guess is as good as mine. People must hate me, I think. No, people must hate our pronunciations. Yeah. Mansonai, Mansoani, 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. All right. Are you ready to talk ancient Egypt? Always, Aaron. I live for it. For hundreds of thousands of years, humans and 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. Uh-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 8,000 years ago is when we see these earliest settlements.

And just a few thousand years after that, these communities had developed extensive irrigation systems and canal 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. Mm-hmm.

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. Mm-hmm. And we see physical evidence for this in mummies from the time. Mommies. Mammies. The earliest known case of schistosomiasis actually appears

in a mummy from modern-day 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 1910, and it was a case of schistosomyasis in a 3,000-year-old Egyptian mummy. In 1910, they were able to sit. Wow. Yeah. So that's amazing. That's when paleoepidemiology got its start, essentially. Wow.

And so paleo-epidemiological studies of mummies from the area on the border of Sudan and Egypt shows a 65% prevalence of Shisto. Right? Everyone had it. Everyone had it. Wow. I mean, hearing about the biology, I'm like, well, how is that not 100%? Yeah, it's true. We can talk about it actually.

Oh. This is a fun episode. This is. The finding of fossilized snails that are the host species in these areas and beyond, like into Mesopotamia and Palestine, also suggest that the disease was there as well. What about any physical evidence in Eastern Asia? Yeah. So schistosome eggs of schistosoma japonicum were found in a preserved corpse in China, dating to 2100 BCE. So, again, very old.

Long time ago. And so we have, yeah, we've got 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 Ebers Papyrus. Yeah.

So in the Evers Papyrus, 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 schistosomyasis 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 interpretation has been disputed more recently. Okay. Okay. Moving on. Okay. So Herodotus observed that Egypt is the land where men menstruate, which people have taken to mean hematuria, which is caused by schistisoma 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 schistow since it was thought that the disease could enter the body through the penis. Oh, that's too bad. Yeah.

But this interpretation has also been 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 chistosomyasis. That's really, that's really interesting, though.

Yeah. Hmm. There's, so there's a relief, like a picture from an Egyptian tomb from like 2400 BCE that shows someone performing circumcisions with the caption, I will do you good. Hmm. But that also has been challenged. Okay. Okay.

So basically, in ancient Egypt, there are a lot of possible references to, to schisticemiasis, 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. We 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? For sure. There's a song about it. Yeah. Exactly. Yeah.

So Jericho was an old walled city, like one of the oldest in the world, 11,000 years old, maybe. Wow. 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 schistosoma hematobium may obstruct fallopian tubes. Yep. And seminal tubes as well.

Yeah. Yeah. And so the city was abandoned after its destruction. And there's actually archaeological evidence to support its abandonment. The curse on the town was removed when Elisha went forth unto 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 Shastasema will.

But also, I feel like if you salt your drinking water, It's not going to be good for you. It's going to 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. Of course.

You mentioned Katayama disease, and symptoms resembling this can be found in old Chinese medicine writings dating back to around 400 BCE. So that's all I got for that. But basically all of these little bits of evidence here and there suggest that Shistisimaias was widespread and probably pretty dang prevalent across much of the tropical and sub-tropical old world. Makes sense. The new world seems to have been schistow-free until the slave trade began in the 16th century when Shistosoma Manso was brought over.

And so that species was able to establish where indigenous snail hosts could maintain the parasites' life cycle, so like Brazil, Suriname, Venezuela, and some Caribbean islands. All right, so now we're caught up on the origins of schistosomes and the evidence for human infection and antiquity. But when did people discover the parasite? So like that first-hand account. Well, there are descriptions of a disease resembling some of the manifestations of schistosomyasis in Italy in the 16th century, but no one really took much note of that. And it wasn't really until Napoleon's army invaded Egypt in 1798 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 50 years later, researchers on two separate continents began to take a closer look at this disease. In Japan in 1847, a researcher named Dr. Yoshinau 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. The acute schistow 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 infection with schistosomes. It would be decades, though, before the parasite causing this Katayama disease was discovered in Japan. In 1851, a guy named Theodore Billars. Teddy B. Teddy B. 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. Okay. This is like in 1851. Yeah, 1850s. And people started trying to figure out the transmission cycle of this parasite, but were

thwarted, partly because Bill Ars 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 other worms that show, yeah, I know, but he was very, had a lot of conviction, which is a dangerous thing in science when you close your mind off. During the 60 years following Billars' 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 in the early 1900s were told to wear a condom while bathing so as not to get infected. It's not going to help you at all. It's not going to do anything, but... No. Eventually, in 1915, 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 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, yeah. Like that's, it's really incredible.

Absolutely. I mean, yeah, you'd think like, why would you look at snails? Like, what would lead you to look at snails? Yeah. For instance. So, yeah, it is, it is cool. Yeah, so 1915 was pretty much when, like, okay, we can finally get to the nitty-gritty of all the different stages of the parasite and take a closer look at the intermediate hosts.

Billars, though, unfortunately, wouldn't live to see the life cycle figured out because he died only like 11 years after his discovery of the worms of typhoid fever. Oh, at least it wasn't Shisto. I thought it was going to be Shisto. I wonder if he had schistow, probably. Oh, that's sad, though. Oh, I have a quick question. Mm-hmm.

Can you get schistow 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 Ars' work, I think, is actually pretty impressive, considering 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 schistocymiasis was also called bilarsia or balarciaesis. But that's less common. That's harder to say. It's much harder, at least for us. Yeah. And actually it is still called Belarzia 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 ascites. 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 torturous working conditions and a steady source of snail and human hosts for schistosomes. Studies looking at how this new irrigation method increased schistosomias as prevalence estimate anywhere from a tenfold increase to a growth from 1 to 3% prevalence to 75% to 80% prevalence. So it just like exploded in terms of prevalence. Oh yeah. The enormous growth of interest in schistosomes.

in the late 1800s and through World War II didn't just happen in a vacuum. It wasn't just driven by curiosity. In the case of schistosomes, 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 1897 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 want to do is that why there is no funding for it though exactly yeah so the researchers who are working on it they want to make the world a better place

the funding agencies don't know uh oh um but also random piece of trivia here the first graduate school of parasitology in the u.s was established at the university of illinois in 1909 I didn't know that. Yeah. There's no longer a school of graduate school of parasitology. 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. 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 1800s and early 1900s, 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. So imperialism and war, as usual. So increasing efficiency and control in Egypt meant reducing the prevalence of schistosomes,

but primarily by reducing it in British troops. So once Leiper 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. Thousands per snail per day from one. Like, it's, yeah.

Uh-huh, yeah. It's such a harder thing to do. 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 that's not going to do it. 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. 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 schistisomyasis discouraged any infrastructural changes to prevent the disease. In 1918, antimony tartrate, so tartar emetic, was found to be relatively successful in treating schistow, which is around 70% 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 30 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 was pretty low. Right.

Because a day of going to the clinic meant a day of lost wages and, you know, also potential poisoning. Right. 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 health care overall. all 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 1939, it was declared that schistosomiasis could be eliminated from Egypt in 25 years by clearing the canals. I'm sorry, this was in what year? 1939. 1939. 25 years. Cool, cool, cool.

How'd that work out? That did not happen. Not at all. Many of the public health directives 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. make the world a better place again, the ruling countries simply realize that a healthy workforce is more efficient and productive. And that's where a lot of the effort ended. It 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 schistow, but for example, scurvy accounted for 13 and a half percent of all deaths in a mine in what is now Zimbabwe in 1908. Scurvy. Like, which we talked about and which, you know, could have been prevented. Tuberculosis, pneumonia, silicosis, and of course, schistosin, and of course schistosemiasis became huge problems in these minds, among other diseases. And it wasn't just that crowded and unsanitary conditions promoted the spread of schistosomyasis.

It was also the nature of the work itself. Sugar plantations and cotton growing both meant exposure to contaminated water, and prevalence is reached above 50% 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 schistisomyasis is discussed in some of the public health reports in South Africa in the early 1900s. Schistisomyasis, 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. Oh. Mm-hmm. Throughout the 1930s, the focus on tropical medicine declined in the two main empire builders, so Britain and the U.S. 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 STI's far outweighed schistow infections in American troops, but one campaign in the Philippines saw an explosion of schistow cases. medical researchers kind of leapt on this outbreak and the funding that was provided for it to conduct research into schisto, 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

field that was almost dying around the same time as imperialism was on the decline. So remember that that 1930s. 39 prediction that schistisomyasis could be eradicated within 25 years. Yeah. Yeah. Well, the snail population did seem to be declining, but the schisto, 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 63%.

Incredibly high. And in other more rural villages, that number was over 95%. Wow. So obviously something was wrong. The eradication campaign recognized this and changed their name from the Belarzia snail destruction section to the Belarzia snail control section. Also snail destruction section is a gnarly name. Total destruction. Meeting them 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. Me too. Wanted on like an embroidery on a zipper jacket. Yeah, 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. Right.

So how could they even direct the campaign effectively? Cannot. Cannot. Meanwhile, Egypt was not the only country dealing with incredibly high prevalences of schistosomyasis. China faced a similar situation, and a mass campaign against the disease was started by the nine-man schistosemiasis subcommittee, which are like the best names for these, the nine-man chistisemiasis subcommittee, starting in 1958. 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 schistisomyasis. Excellent. Mao Zedong 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 could probably find it online anyway. The campaign against Chistisomyasis seemed to be incredibly successful if you believe the claims about the progress made. But was Chistow 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. Right. And as far as I read, cattle themselves were not a target for treatment. So in the decades following World War II, interest in schistosomiasis grew for a number of reasons. One was the fear that soldiers returning back to the U.S. 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 Chistasmaeus' prevalence. For example, in Ghana in 1965, a lake was created after damning a river. Within a year, the snail host of Shistosoma hematobium had appeared, and two years after that, the prevalence of Shistosomyasis was 50% in the population living around the lake. Yeah, dams are not great for Shisto. So another reason for this increased interest was simply the increase in cases. In 1951, schistis had been declared next. 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. 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 people can't afford to miss a ton of work to go get a shot. And also side note, so this is, you know, making another connection with the hepatitis C episode, these tartar emetic campaigns in Egypt throughout the 1950s through the 1980s, these were like huge campaigns to get the treatment for chistosomyasis. They tended to reuse needles to save money, and this led to a massive spread of hep C, which was only discovered decades later.

I think even now Egypt has one of the highest prevalences of hepatitis. see infections. Yeah. So how do we improve the treatments? Yeah. Or maybe we do a combination of treatment and molluscusides. 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. Okay. I'm wrapping 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 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. Yeah.

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. Yeah. 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 schistosomyasis will likely change in ways that are going to be difficult to predict. Since the African continent has the vast majority of schistisomyasis 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 schistocymiasis 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 800 million people are at risk of infection. Oh my gosh. Yeah, at risk of infection.

And it's thought that about 250 million people are infected worldwide. And about 200 million of these people live 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. Okay. The adults who tend to have the highest burdens are people who work, 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 schistosomiasis, 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 Dallies. And trying to get a handle on the Dallies-forciusisomyasis 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. Absolutely. Co-infection is going to be huge. But then also like the greater the worm burden is going to make a difference on 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. 2016 global burden of disease estimated that it's about 1.9 million dallies, so disability-adjusted life years. Wow. But there have been some other analyses that suggested much higher estimates. Uh-huh. And that's, I think, if you include the fact that there is undernutrition, anemia. Right.

Which I feel like you should because that's manifestations of the disease. You absolutely should. And so this is where I actually want to touch on something that is really important with a disease like schistosomyasis 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 schistosemiasis, 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 schistosomyasis 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, co-infection, 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 schistocymiasis takes a huge impact. It has a huge impact on a population's 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 poverty. It's a feedback loop. And basically perpetuating that cycle. It's a feedback loop. Yeah. And it's the same thing that we see also with hookworm and with many other geohelments, basically, many other of these intestinal parasites or neglected tropical diseases. That's like, that's part of the one of the hallmarks of neglected tropical diseases. Exactly. Especially these ones that are that are chronic like this, you know? Uh-huh.

Uh-huh. Yeah. So it's, in that way, schistisomyces is like, we have a huge long way to go. The main, 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 50% of children in an area are infected, which is a very high proportion,

then everyone in that area will be treated. And the treatment now is a, there's only one drug, really, that's approved for use. We can talk about the problems with that. But it's called prosaquantle or praziquantle. 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, larval stage. It does nothing for the eggs that are already in your body, right? 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 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.

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 prosaquantal, 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 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 chemoprophylaxus 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. That's 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 Hote's? Yeah, Peter Hotez, Dr. 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 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 mansini or Mansoni, along with adjuvants. Because what 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. 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 schistisomyasis. So they really are trying to get prosaquantle the drug to as many people as possible. In 2018, about 40% of people who needed treatment were actually reached, and about 62% of children were being treated. Okay. 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 develop vaccines for this horrible disease. Yeah, truly. So, yeah, that's just a psomyasis. Tropical, a good turn for tropical medicine. It's now changed. Yeah. 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. It's very, very fascinating, great resource. And then I also want to shout out a few other papers that I read. Where Do Human Chistosomes come from? By Claude Combs, 1990. By DeBella at all 2018, history of schistosomyasis and humans from Egyptian medical papyri to molecular biology on mummies.

And finally, by Mahmoud 2004, Shistosomiasis from antiquity to the present. And I've got a whole bunch more that I'll post on the website. If you would like a really, really comprehensive overview of Shistosomyasis, biology, and ecology, there's a great primer in Nature Review's disease primers by Donald McManus from 2018. 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.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 filthy animals. This is Bethany Frankel from Just Be with Bethany Frankel.

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