This Podcast Will Kill You - Ep 58 Guinea worm: (Almost) Ancient History

Episode Date: September 15, 2020

You’ve heard about smallpox, and you’ve learned about rinderpest. Now it’s time to meet what may be the third disease to ever be eradicated: dracunculiasis, also known as Guinea worm disease. In this episode, we take you through the absolutely remarkable life cycle of this not-so-little worm and the nitty gritty of the havoc it wreaks on a person’s body throughout its journey. Then get out your TPWKY bingo cards, because the history of Guinea worm includes not only mummies and historic papyri but also ancient Rome and fun etymology. To bring us up to speed on the current status of Guinea worm today is Sarah Yerian, Senior Associate Director of the Guinea Worm Eradication Program at the Carter Center. Sara discusses not only how the reduction in prevalence of dracunculiasis has been achieved but also the challenges that remain to finally relegate this worm to the history books.To learn more about the Guinea Worm Eradication Program at the Carter Center, check out the website or follow them on social media: @CarterCenter. You can also find the link to our firsthand account here. See omnystudio.com/listener for privacy information.

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Terms and conditions apply. Visit blue apron.com slash terms for more information. This is Special Agent Regal, Special Agent Bradley Hall. In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world. The Sixth Bureau podcast is a story of the inner workings of the MSS, and how one man's ambition and mistake. opened its fault of secrets.

Listen to the Sixth Bureau on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. I'm Amanda Knox, and in the new podcast, doubt the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story? Evidence has been made to fit.

The moment you look at the whole picture, the case collapsed. What if the truth was disguised by a story we chose to believe? Oh, my God, I think she might be innocent. Listen to Doubt, the case of Lucy Letby, on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. When I was a young boy, I had two uncles. Both were heavily infected with guinea worms. And back then, no one here knew how guinea worm was transmitted.

People would become infected, and we just kept wondering why. During those years, we had some communal fighting, fighting between communities amid South Sudan struggle for independence. One day, fighting erupted in the evening, so everyone in my village ran away, but my uncles could not run. So they crawled to the garden to hide because no one could carry them. My mom could not carry them, and I had lost my dad during the struggle. So we had to leave them. There weren't any options. We just cried.

So warfare comes and fighters raid our cows and kill some people and then go back where they came from. After that, when the people came back, we found that my uncles were gone. They had been killed. If it were not for guinea worm, they would have just joined us and trekked away from the danger. So I say that it was guinea worm that killed them indirectly. When I was young, I could not understand how the guinea worm killed my uncles. But as time goes on, I have come to know, this is our story. Later, we were living at a refugee camp, and we were given pipe filters from the Carter Center. I didn't know why people were given pipe filters, so I refused to use mine. My mom is educated, and she told me these were for guinea worm. and now she began to tell me this story, and I finally could see the connection between the guinea worm and the loss of my uncles. I said, okay, there are people that are working for this, and that was when I committed to working for guinea worm eradication,

because guinea worm had done something bad to me. And even if it had not been me, what of the rest of the community? That's what inspired me to work for the eradication of guinea worm. So I went away to school, and when I came back, I looked for this work. When I found the man who would be my director, I told him, I will never let you and my country down. I just need to relate to my community and see how this guinea worm is cruel to my community. I want my community to be free. And that's why, you see, I am doing this work. It is very difficult. If you want to work for guinea worm, you need to leave the good things in your life behind and become part of the community.

That way you come to understand the dynamic of how to help the community to eliminate the Giniworm. And that's been very effective. I've been there and I've worked and I've seen how the guinea worm can go to nothing. And I have hope that one day we will be free and able to say that guinea worm is gone. It will be a very great achievement. I thank the Carter Center for helping us achieve it. Wow. That was, that was, wow. That was an amazing story. Yeah, yeah. So that was from Daniel Deng and he wrote that story called Guinea Worm Killed My Uncles

which we found on the Carter Center blog. So that's who that was from. Yeah. Hi, I'm Erin Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. And if you haven't guessed, today we're talking about Guinea Worm.

Guinea Worm. Trachankuliasis. I am really excited for this episode, which I know we say that every episode. Every episode, but we're always excited. So it's always excited. I feel like it's been a while since we've done a parasitic disease. So that's always interesting, you know.

And the other reason that I'm super excited for this episode is that we have an incredible guest. Yes. We were fortunate enough to interview Sarah Urien, who is the Senior Associate Director of the Guinea Worm Eradication Program at the Carter Center. How amazing. I know. So we got to talk with her a bit about her experience. on the ground, as well as some of the more like, you know, the logistical finer points of how eradication is actually achieved. So keep an ear out for that later in the episode. Yeah,

we're really excited about it. But first, oh, what, what time is it? I think it's, I think it, it must be quarantini time if I'm not mistaken. You're right. I just, it's quarantine time. I checked my watch and everything. Well, Erin, what are we drinking this week? We're drinking the littlest dragon. I love this name, but it does require maybe a bit of explanation. Just a touch. So the species' name for guinea worm is draconculus metanensis, and dracunculus means little dragon.

And so it's like the littlest dragon. Just the tiniest little dragon. It's a cute name for a not-so-cute worm. I have to admit it's not the cutest of one. worms. You know, are there cute worms out there? Absolutely. Oh, okay. Yeah. I don't know any by name, but I'm sure. I'm sure that there are. Like oceanic worms, actually. There's some cute ones in the ocean. Yeah. Yeah. So what's in the The Littleest Dragon? The Littleest Dragon is actually quite a delicious cocktail. So it has Blue Curacao. It has rum, pineapple juice, cream of coconut. And, um,

The most crucial part is that you garnish it with a toothpick with a sour gummy worm wrapped around the toothpick for reasons that will become clearer later in the episode. Yes. And we'll post the full recipe for that quarantini as well as our non-alcoholic placebo rita on our website. This podcast will kill you.com and all of our social media channels as well. Yes. So I think we have a couple other pieces of business to take care of. We do. So first of all, I finally checked our PO box after months of not going to the post office because of Corona. And I'm thrilled for, we got a couple of really, really kind presents that we wanted to say thank you for. So first, I want to say thank you so much to Kira, who sent us not only the most adorable sweet, just the sweetest letter, but also a handmade, like, Matt coaster for our quarantinies that looked. looks like the coronavirus. Oh my gosh. It is incredible. Kira, thank you so much. It's so sweet of you. And yeah, that letter made us like, oh, it's just like, we're like, we don't deserve this.

This is too nice. And also thank you so much to Melanie who made us handmade masks with little germs on them. Oh my gosh. They're so cool. Thank you so much, Kira and Melanie. We appreciate it so very much. So much, really. Amazing. Well, I think the only other business is that we've got, you know, merch as per usual. Go to this podcast, We'll Kill You.com and click on the merch tab. Shout out to Abigail Irvin Penner, who designed all of our new merch. We love it so much. Oh, my gosh. I mean, I'm obsessed. Seriously. And we also have a bookshop affiliate account. So you can find all of the books that we talk about on our podcast there. and also Goodreads list. So check those out. You can find all of those things on our website. Awesome. Is that all? I think that's all.

Excellent. Shall we dive right into the biology of this little worm? Let's do it. Right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals, take about five minutes of hands-on prep. Just spread the pre-chopped ingredients on a sheet pan, put it in the oven, and that's it. And if there's truly no time to cook, dish by Blue Apron meals are fully prepared.

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Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly.

A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside.

We're offering our listeners 15% off their first order of O'Keef's. Just visit O'Keef's Company.com slash this podcast and code this podcast at checkout. China's Ministry of State Security is one of the most mysterious and powerful spy agencies in the world. But in 2017, the FBI got inside. This is Special Agent Regal, Special Agent Bradley Hall. This MSS officer has no idea the U.S. government is on to him. But the FBI has his chats, texts, emails, even his personal diary. Hear how they got it on the Sixth Bureau podcast.

I now have several terabytes of an MSS officer, no doubt, no question, of his life. And that's the unicorn. No one had ever seen anything like that. It was unbelievable. This is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app,

Apple Podcasts, or wherever you get your podcasts. Guinea Worm, or, as you mentioned, Aaron, draconculus medinensis, right? I think that's how you say it. I even Googled how to make sure I pronounced Dracunculus properly because I've never been able to pronounce it, but everyone knows I have issues with pronunciation. What do you mean? Coughcough, Girardia? Anyways, Dracunculus metanensis is a nematode or a roundworm.

So this is the same phylum as hookworm. This is our second nematode. Okay? Uh-huh. Uh-huh. Gotta love them. Gotta love them. That's their tagline. So, okay, because this is a complex parasite, we obviously have to start with the life cycle, okay? Excellent.

We're going to start with the first stage larva so that when we end the cycle, we'll end with the human part of the life cycle. Okay? Okay. So the first stage larva, if Dracunculus are tiny dragons, these are the tiniest dragons, the babies, they're found in water sources, freshwater or brackish water sources, they swim and they thrash about in this water the way that worms like to do, and then they find tiny little copepods. Okay, a copepod is a little crustacean, think plankton from SpongeBob. They're really cute. Really cute. Yeah, they're very adorable. These copepods swallow this first stage larva of the guinea worm. And then within the body of the copepod, the larva kind of burst out of their stomach and begin to develop and grow. Question. Yes, I know. It's starting early.

Okay, so the first stage larva, it is ingested by the copepod. Does it have any movement towards the copepod? Like, you know what I mean? Does it have any directional movement? They have certainly movement. I don't know if they have directional movement towards copepods. I didn't see anything about that in the literature that I read. But that's a really interesting question.

Okay. Gotcha. Okay. So now they've molted, they've grown inside of, this copepod and then a human comes along and fills up their water container from the well or the pond or whatever that this copepod has been living in and they've been walking for a while so they take a big old swig of that water and they swallow these tiny little plankton copepods and then inside our stomach the copepods die because of all of the acid and they're obliterated

And the larva come forth, burst free, survive somehow in our stomach, travel down into our small intestine, and then burrow their way out of the small intestine and into the wall of our abdomen. What? It's terrifying. It is truly like the movie Alien. Yes. But just on a much smaller scale. The tiniest dragon of scale. Which is actually really funny because there's a documentary I watched, which is narrated by a Sigourney Weaver.

About Guinea worm? Yeah. Oh my gosh. That's phenomenal. Okay. So now these tiny larval worms are in basically like the connective tissue layers of your abdominal wall, your belly wall. And there is where they will begin to mature into fully adult worms. And these worms have male worms and female worms.

and they will mate, and then the females will grow and grow and grow and grow and become all full of millions of eggs. And this is a process that takes many, many months. And then over the course of these months, as her eggs mature into embryos, she will then travel down through our connective tissue down and down and down to the lower limbs, like your leg, usually your ankle or your foot, although she could travel anywhere because she's basically just under your skin, just like in the fatty tissue underneath your skin. And these little worms are migrating through down into your lower extremities, and then 10 to 14 months after somebody drinks these copepods, this fully engorged fema-pods, this fully engorged

female worm, which is now 70 to 100 centimeters long. That's up to a meter long. It's very long. It's very long. It started in like microscopic and now it's a meter long. Okay. Then they come all the way forth to the surface of your skin. And in doing so, it produces a blister. And this blister is incredibly, incredibly itchy, like unbearably itchy, and it's burning and it's really uncomfortable, so much so that the only thing you want to do to try and stop the itch is submerge your foot in cool, cool water. So you find a pond and you do that. And as soon as your foot enters the pond, that worm contracts and she pushes up and she bursts forth and literally pushes open part of her her gravid uterus out of the blister bursts open and expels upwards of 500,000 larval

worms into the water, thus completing her life cycle. It's incredible. It is so, seems like otherworldly. Absolutely. Seems like this is, everything about it is mind blowing. It's, it really is. Nematodes in general, I think, are absolutely mind. blowing creatures. Like I genuinely am fascinated by them. Same. So I said that she bursts forth and releases

all these larval worms. That's not the end of her story. That's just what happens the very first time that she comes into contact with water. But now she is partially freed from your skin. Literally part of this female worm is sticking out of you. And then every time that she's submerged in water, she'll release more larva. And the part that's outside of your body, kind of just shrivel up and die and then a little bit more of her will emerge every day, every day, every day, every day until finally she is completely gone and has released, I don't know, more than like three million larval worms into the environment. Mm-hmm. Whoa.

Mm-hmm. It's a journey, yeah. It's a real journey. Okay. So number one, what happens to the male? Oh, great question. Because he's just floating around in there somewhere? He's pretty much just floating around, yeah.

You can sometimes get like a small inflammatory response from wherever he ends up, but usually he just sort of, your body will just sort of calcify him, and then you'll just have a little like boop of calcium sum deposits somewhere in your body. Nothing much. Does the where he ends up dying, can that be problematic in terms of like if he ends up in a joint? Oh, Aaron, you are getting so far ahead. Okay. We'll just put a pin in it.

Put a pin. All right. My next question then is, how does the female know where to go? No idea. Great question. I don't. It is the weirdest. It is the weirdest thing.

And all of the things that I read were just like, yeah, most of the time it's from the lower limbs. But it could be anywhere. I think that there's some thought that they travel in part along like lymphatic routes. So if they just get on the right lymphatic tract in your abdomen, a lot of your lymphatics are going to be draining down to your legs or like your lymphatics from your legs are going to be draining up towards your abdomen. So it kind of makes sense if they're if they're in your lower abdomen already that they just sort of end up going down to your legs. Gotcha. Gotcha. Yeah. Okay. My other question pertains to the longevity. of these worms. So 10 to 12 months, and that's typically just in correspondence with like a rainy dry season in the places where these are most abundant, prevalent. Good question. Very good question. Yeah, so there is definitely seasonal dynamics in terms of transmission, but whether people are more likely to get infected in the wet or the dry season depends on where they live and what region. So in some parts of the world, transmission is highest during the rainy season if it's areas

where people are primarily using ponds as their water sources that are otherwise dry during the dry season, right? Okay. But in other places that are maybe more wet in general, where you have step wells or other types of cisterns, then transmission tends to be highest in the dry season or right before the rainy season starts at the very end of the dry season, because at that time, the water quality supports higher numbers of copepods. The water is less turbid, and there's not as many streams washing things away. So the copepods aren't as dilute as they would be during the rainy season when water levels are high. That makes sense. Isn't it? Ecology. There you go. It's so cool. It's very interesting. Okay, but that didn't answer your question. So the worms live a long

time. Yeah. Yeah, I guess I'm thinking like other species of nematodes, they mature a lot more quickly. Right. Yeah. Than that. And so I'm wonder whether it does seem to be more in correspondence with like the timing of the dry and the rainy season. Yeah, yeah, that makes sense because pretty much across the board, even though in some places it's the wet season and in some places it's the dry season, either way, we definitely see seasonal trends. So that does make sense. Yeah. Cool. Yeah. All right. Okay. So that was just the worm, right? Right. That was just the life cycle of the worm. We're missing like the human part of it, right? These are humans that are being infected. So what the heck is going on in you? Let's find out. Tell me. Okay. So for some people, the first sign of infection might be noticing the worm itself, right? Just kind of beneath the skin a few. days before it emerges kind of as it's traveling down. For others, and very commonly, it's kind of a more generalized, kind of allergic type symptoms. So maybe hives, maybe a bit of a fever,

some swelling under your eyes, kind of like you might think I have an allergy to something. But all of this would be still around the time of its emergence. Of its emergence, right, not of when you get infected. Pretty much there's basically no symptoms. when you first get infected. So this is a year after you drink the larva. Okay? But for most people, the very first indication of infection is the blister. And like we said already, 80 to 90% of the time it's on the legs or the feet.

And it usually starts pretty small, but it grows fairly rapidly. It can grow over a number of hours or over a couple of days. And the blister before it opens is sterile. So it's not filled with like pus and bacteria like a pimple kind of blister. Right. It's just clear liquid. Yeah. It's inflammatory fluid and it's filled, filled with larval worms.

So the female starts to release larval worms underneath your skin as part of the formation of the blister. So we're not. It's not quite sterile, is it? Well, yeah, it doesn't grow bacteria, is what we mean by sterile. And what's so interesting is that it's not entirely clear, like, pathologically, what causes the formation of the blister, like whether it's the adult worm releasing enzymes that cause tissue death, or whether it's the embryos, the larva themselves, that are causing the tissue damage, which I think is really, interesting that we still just don't quite understand. Well, I also think, you know, to jumping

ahead a little bit, but that there's probably a lot that we don't know about the biology or the ecology of this simply because it's not directly relevant to the control of the parasite. Exactly. I think there is so much of this that we just don't know because it hasn't been studied because we didn't technically need to, quote unquote, to get it under control. Right. Yeah. Okay. So now you have this blister and then it'll start to open. So very often it opens at first in contact with water because that does produce in the female worm this intense contraction where she pushes herself forth. But it is possible to have the blister break open even if you don't put your feet in water. So now you have this female worm half a little bit. sticking out of a wound in your foot. And basically, the only way to get her out is to slowly pull her out in a process that can take usually at least a month where you slowly twist the worm around a small stick.

Yep. And that's why we have a gummy worm in our quarantini. It is indeed. If anyone still even wants to make it after that description. Of a worm coming out of your foot that you're wrapping around a stick slowly over the course of a month. Okay. And that is the best case scenario. Right.

That's not what always happens. More than 50% of the time, the wound itself is like. complicated by a secondary bacterial infection. And there's a whole bunch of different ways that this can happen. Okay. So when the worm is happily living under the surface of your skin in your subcutaneous tissue, it's in this little worm house. Okay. So it forms like this little fibrous worm sheath around itself. And that's how it can move without getting stuck to your tissues, like because of our inflammatory response. Okay. Whoa.

Yeah. That's really cool. Which I think is probably part of why it takes so long to travel down, right? It's not just like swimming through. It's like slowly moving its little sheath within its sheath. It's like, oh my God. I know. Okay.

Wow. Yeah. But once it starts to emerge and it breaks through our skin, then our inflammatory response can really start to kick in. And it can form adhesions to the worm itself. rather than the sheath, which can complicate the removal and make it harder because it's stuck to our tissues. So if the worm gets broken during the extraction process, because it's quite a fragile little worm, then what's left of the worm in your body kind of withdraws back into its little sleeping bag, and it brings with it all the bacteria from the outside of your skin.

So staphoreas, e-coli, anything living there. So then you can get deep tissue infections because of that. that. But you also could get an infection even if you don't break off the worm, right? Just because you have this open wound and it's on a place like your foot or your ankle that's in contact with like the environment, right? Tetness is also a very real and very common complication. So secondary infection with a Clostridium species that produces tetanus toxin and then you end up with tetanus because of this. So that's kind of the most common. complication of guinea worm infection, but it's also possible, like you mentioned, Aaron, in your

jumping ahead, for the worm to get a little bit lost on its way to try and emerge. So whether that means it makes it to your skin, but for some reason can't quite penetrate through your skin, which can happen, then what will happen there is the worm just kind of becomes calcified with our own immune response, which wouldn't be a problem if it's just like, say, in the subcutaneous tissue of your abdomen or your arm, but if it's in an important organ, like your pancreas, or your heart, or like you mentioned, Aaron, in your joint space, then you could end up with arthritis. It can also lead to deep abscesses. So even though I said that this blister is sterile, quote unquote.

Quote unquote. If the worm begins to release the embryos or the larva in your deep tissue, it will cause a really dramatic inflammatory response. And that will lead to a serious abscess where you would find a lot of pus and white blood cells and things like that. You still wouldn't find bacterial infection, but it would be full of larva. Right. And so overall, the reported period of kind of incapacitation due to this infection on average is eight and a half weeks.

But that range is from two to 16 weeks or even longer. And it really depends on how many worms you're infected with or whether you get a secondary infection and things like that. because, P.S., getting infected with one worm doesn't prevent you from getting infected with multiple worms. Right. There's no immunity. Yeah, exactly. So usually, most of the time, people get infected with, like, one to three worms that emerge

at a time. But some reports have found up to 40 worms emerging from one person at a time, which just sounds unimaginably awful. Yeah. Yeah. Yeah. Because even like I said in the best case scenario where you have a worm that emerges without any complications or infection, this is a very painful process. You're slowly winding a worm, a living worm out of your tissue in your leg.

There's nerve pain. There's itching. There's burning. It's extremely painful. Yeah. Just even getting around. Like even not just the process of pulling. the worm out, but like walking?

Yeah. It's really painful and challenging. Very painful. Yep. That's it. Aaron, that's a polyology. Okay. Do you have any other questions for me? I don't think so. Well, good.

So, Aaron, where did this worm come from? Why? Why? I didn't mention this, but it only infects humans for the most part. Why? How did it find? us, where did it come from? What are we doing about it? What? Tell me everything. I can't wait to right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working

hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters. when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside.

We're offering our listeners 15% off their first order of O'Keef's. Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. In 2023, a story gripped the UK, evoking horror and disbelief. The nurse who should have been in charge of caring for tiny babies is now the most prolific child killer. in modern British history. Everyone thought they knew how it ended. A verdict? A villain.

A nurse named Lucy Lettby. Lucy Lettby has been found guilty. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses. I'm Amanda Knox, and in the new podcast, doubt the case of Lucy Lettby, we follow the evidence and hear from the people that lived it. To ask what really happened when the world decided who Lucy Lettby was. No voicing of any skepticism or doubt.

It'll cause so much harm at every single level of the British establishment of this is wrong. Listen to Doubt, the case of Lucy Letby on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. China's Ministry of State Security is one of the most mysterious and powerful spy agencies in the world. But in 2017, the FBI got inside. This is Special Agent Regal, Special Agent Bradley. whole. This MSS officer has no idea the U.S. government is on to him. But the FBI has his chats, texts, emails, even his personal diary. Hear how they got it on the Sixth Bureau podcast. I now have several terabytes of an MSS officer, no doubt, no question, of his life. And that's

a unicorn. No one had ever seen anything like that. It was unbelievable. This is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the sixth bureau on the IHeart radio app, Apple Podcasts, or wherever you get your podcasts. All right. It's kind of funny that you ask me, where does it come from? And why does it only infect humans and, et cetera? Because to be honest, I couldn't find a ton on the evolutionary history of it, except for just like, here's the phylogeny of these worms. And so, you know, to answer those questions, I don't really know. I know that it's been with humans for a very, very long time.

And it actually does seem to infect other animals, maybe not as readily as it does humans. Right. But the infection in dogs seems to be a problem that's contributing to some of the difficulties in the complete eradication. Yes. Yeah. Yeah, I don't know. Anyway, I'm sorry, I wish I had more. If anyone has any great evolution Dracunculus Menonensis evolution papers, please send them our way. I'd like to know. Yeah. Okay, so, but the history of guinea worm has got all of the other usual suspects, mummies, fun etymology, imperialism, and more. And it's maybe the most classic disease

quote unquote that we've had in a while. Yeah. So if you're playing TPWKY bingo, get your cards ready. I love it. All right. Let's begin. Ancient Rome. To Rome.

To ancient Rome. No, actually, let's go back even earlier, Erin. Because this worm seems to have been known to humans for basically all of written history. And it makes an appearance. in, you might guess, the Iber's papyrus. Iber's papyrus. Bingo. There we go. Bingo number one. That's from around 1550 BCE, by the way. So it's very old. Very old. And so researchers think that the rare and obscure verb DQR, which is just like all one word

together, refers to the pulling and spinning of the worm for its removal. Huh. Interesting. Like they had a specific verb that meant that. Right. And so, like, researchers were like, well, it kind of looks like it's referred to with, like, a spindle against one's leg, but it's also meant to something beneath the surface. And so they think it refers to the removal of the guinea worm using that method. And there's also evidence to support this or to support at least the fact that guinea worm was present in ancient Egypt because a calcified worm was found in a mummy of a 13-year-old female from 1,000 BCE, roughly. who had died shortly after her lower legs had been amputated. Oh. Right, which some researchers have speculated was done to try to save her from the secondary infections that you mentioned caused by the worms. Wow.

Yeah. And then, of course, there's the biblical mention. So in the Old Testament, in Numbers 21, 6, which is thought to have been written around the 8th century BCE, there's this line. Then the Lord sent fiery serpents among the people, and they bit the people so that many people of Israel died. And so this is where the worm gets its fiery serpent nickname that you probably come across. So that they think is draconculus, guinea worm. Fascinating. Uh-huh.

Yeah, and the Iber's papyrus and the Bible aren't the only ancient text to mention guinea worm. There's also talk of the worm in ancient Greece and ancient Rome. For instance, there's this from around 46 to 120 CE. Quote, the people who live near the Red Sea are tormented by an extraordinary and hitherto unheard of disease. Small worms issue from their bodies in the form of serpents which gnaw their arms and legs. When these creatures are touched, they withdraw themselves and insinuating themselves between the muscles give rise to who. horrible sufferings. A hundred percent guinea worm.

100 percent. And it was Galen who gave the infestation its first name, dracontiasis. And one more thing. Are you getting to my favorite part yet? I think it might be right now. Okay, good. This might be it. I'm sure you've heard it said before that the staff of Asclepius, how do you say there?

Asclepius. Yes. Which is that symbol that you often see associated with medicine and medical things. It's basically a singular snake winding around a rod. Yes. It's been said that the snake actually represents a guinea worm. Some people hypothesize. That's my favorite.

It's my absolute favorite. It's so much better than it being like just a random snake. Like it has to be guinea worm. Of course it's guinea worm. Well, there are other hypotheses. Yeah, I know. So before I get to those, the W. The WHOHO logo actually has the staff of Asclepius on it.

And side note, a lot of the times you'll see, and I was always confused that the caduceus, which is like two snakes and the wings, that's actually something else. That's Hermes. That's Hermes. Not Asclepius. Right. And so that refers to more like messaging or trade or commerce, information flow, et cetera. But the other thing that I think is really interesting about the staff of Asclepius or the rod of Asclepius. is that Asclepius was this Greek god that was associated with medicine and healing.

And so some people hypothesized that the snake was like part of the healing process is shedding of the skin and becoming like that renewal. And so that's why they think the snake might represent besides getting warm. I don't like it as much. I'm just, you don't have to like it. You're just the messenger. I'm just the Hermes of this. Okay, so whether or not the Radoesclepius truly represents guinea worm, from all of these ancient references to the parasite, we can at least tell that it was pretty prevalent across the tropical and parts of the subtropical regions of the old world. And while most of these ancient folks seem to recognize it as a parasite, so as like an animal, a creature that has somehow invaded your body and is now causing you harm, others, including the famous,

Avicenna weren't as convinced. Instead, claiming it was actually a vein gone awry. Interesting. Mm-hmm. Yeah. He did give it a name that would stick with the worm until present day, though. The Medina sickness or the Medina vein, because apparently it was quite prevalent in Medina, which is a city in Western Saudi Arabia. Oh, like that funky cold Medina? The funky worm from Medina. There you go.

Oh, okay. Anyway, so the scientific name of guinea worm, which was given by Linnaeus in the mid-1700s, is Dracunculus Medinensis. Right. So, as we mentioned, from the Latin, Draco, meaning dragon or serpent, and medinensis, meaning from funky cold Medina. Wait, Draco means serpent? Like, Draco Malfoy meant literally serpent? Or dragon, yeah. I never knew that. Okay, sorry.

Yeah. No, I didn't know that either. Yeah, so basically its scientific name means Little Dragon from Medina. Okay. It's kind of cute. Yeah. As travel and trade expanded throughout the 16th and 17th centuries, reports of the worm became more numerous. As did hypotheses about its nature. Was it an animal or was it just part of your body?

It's life cycle and how a person became infected in the first place. And it was also during this time that it was first called Guinea Worm, as it was seen in super high numbers along the west coast of Africa. The transatlantic slave trade also led to the introduction of the worm in parts of north, central, and South America. But it doesn't seem that local transmission was sustained for very long after the mid-1800s, possibly because of environmental conditions, possibly because the right Copepod species weren't there. I don't really know for sure. Okay, okay. But throughout the 1800s and early 1900s, the rapid expansion of travel and in particular colonization led to a heightened interest in the parasite. In India and parts of Africa, for instance, British officers reported seeing cases of infestation among the military serving there.

And so, as you might expect, this led to calls for doing something about this skinny worm problem. Although the association between the parasite and water had long been recognized, especially in places where it had been prevalent for basically all of human history, there still wasn't a very clear understanding of how exactly they were connected and whether there were any other players in the game. Okay. In the 1870s, a Russian parasitologist named Alexei Fedchenko getting his start just as the field of parasitology was taking off,

What an exciting time. We would never have been allowed to pursue this career. So Fanchanko was encouraged by leading hell mythologist Rudolf Luchart to look at the possibility that infected copepods might be harboring the larvae of the worm. In 18 what now, Aaron? 1870s. They were like, hmm, pretty sure it's a copepot. What? Well, so this guy, Rudolph Luchart, he had either discovered this or.

learned about this in another species of worm that was using copepods as an intermediate host. Yeah. It's, yeah. Like, I know that we've talked about, like, early discoveries like this before, but it still blows my mind that people could figure out a life cycle as complex as this. Oh, just you wait. Oh, gosh. Okay.

Just you wait. Okay. So, so, yeah. So Fedchenko looked. and sure enough, within some species of cyclops copepods that he had found in contaminated drinking water, he found larval worms that he thought might be the intermediate stage of guinea worm. There you go. Incredible.

And then he was like, all right, you know what? Humans probably become infected when they drink water containing these infested copepods. Because that's logical. Yeah. And he was like, I'm going to try to show this experimentally. So I'm going to give some infected copepods to cats and dogs. But they never developed the infection. They didn't.

And so his hypothesis just kind of sat there quietly in the parasitology journals for a couple of decades, while others argued that it infected humans by boring into their skin directly, kind of like a la hookworm. A la hookworm. Meanwhile, in Britain's colonies in Africa, guinea worm continued to pose a threat to productivity and political stability. Oh, gosh. And so the committee of the London School of Tropical Medicine asked, fresh out of medical

school with basically no research training, 24-year-old parasitologist Robert Leiper, whom you may remember from our Shistosomiasis episode. That's okay. I just remember the name, and that's it. And now I'm wondering, did I pronounce it differently in that episode? So anyway, they asked Lyper to head to Akra in Ghana to learn more about the parasite so that it could be controlled. And he, you know, entered this field of conflicting hypotheses and big egos and made, frankly, incredible progress towards understanding the key components of the parasite that would allow for its dramatic decline in prevalence over the next 100 years. Wow.

Most of that decline was concentrated in the last couple decades. But anyway, first of all, he demonstrated that, no, the larval worms do not burrow into your flesh. He fed a monkey bananas that contained infested copepods. And then he waited six months and carried out a postmortem that showed that, yes, indeed, there were some draconculus metanensis in the monkey. Mm-hmm. Next. Are you laughing at the banana? Yeah, the banana.

I don't know why that's so funny. I don't know either. I don't know either. Like you can't just put it in this water. Like, you've got to add it to the banana. That's what made me include that detail. I was like, it's not just feeding them infested copepods. It's the banana.

The banana. Oh. Well, and then next Lyper rules. ruled out that it was any other intermediate host besides copepods. He then decided to do a series of experiments showing under what environmental conditions the larvae can live, the timeline of their maturation, and he mimicked conditions of the human stomach. He, like, made an acidic solution to show how the copepods are killed, allowing the larvae to burst forth and then, like, continue. their passage through the human body. He did this in what year now? 1905. What on earth? And so from all of this, he concluded that, quote, the young larvae must be

discharged directly into freshwater soon after the parent worm has succeeded in creating a break in the overlying skin and before the wound has become markedly septic. Wow. The embryos must find a cyclops within a few days. They must, moreover, succeed in entering its body cavity. Five weeks later, they will have developed into mature larvae. They must, therefore, be taken into a human stomach and having been set free from their host by the gastric juice, reach the connective tissues by penetrating the gut wall. Wow. That's everything I described. Everything. And so basically within two years of his arrival, the 24-year-old had essentially laid out in impressive detail the life cycle of this parasite.

Also, he didn't stop there. Mm-mm. They never do. Never. Leiber took this information and made recommendations for its control. Basically, clean the water to eliminate the worm. He also stressed the importance of knowing the seasonality. of infection. The timing of dry seasons and wet seasons and where people get water as crucial in

knowing where and when water supplies are most likely to be infested. Oh my goodness. Uh-huh. He also recommended filling in surface water and shallow wells, getting rid of step wells, where people have to descend to get water and instead using draw wells, artesian wells, or pipes from rapidly flowing streams. Wow. And finally, just the cherry on top, he suggested that certain fish species might be a great way to naturally control the copepods and hence the disease. Oh my gracious. Wow. And so all of this he did in a couple years and then he like wrote a couple of papers and then didn't do anything with guinea worm ever again. He's like, I did it all. I'm done guys. I solved it. Just do it. I mean, kind of. I mean.

If, I mean, he wasn't wrong. Yeah, and so after that, he just went to hookworms and schistow. Wow. That was it. And yeah, so I think that's one thing that I find so fascinating about guinea worm is that so much of the information that we use today to control guinea worm is literally ancient or at the very least like old knowledge. Right. Like over 100 years old. Over 100 years old.

Sometimes over 3,000 years old. Wow. Yeah. In the early 1900s, the development of certain arsenical treatments for other wormy parasites led to some researchers trying them out on guinea worm, but none worked very well. Or they caused greater problems because then the worm would die in a joint or something. And then, as you mentioned, all of the horrible effects that can come from that. Right, like on its way down. Mm-hmm. And then even if those side effects weren't an issue, there was the aspect of getting access to any potential treatments and the financial aspect of that as well.

The method described in the Ebers papyrus from 1550 BCE of winding the worm around a stick to remove it, that's what we use today. 2020. 2020. I mean, that's incredible to me. Yeah. Yeah. The connection between water and the parasite was long known in the areas where the parasite has been historically most abundant, even while Western researchers were fighting amongst themselves over whether it was from water or from the grass or from this or that. And the larger scale control efforts that we use still follow the same principles that Robert Leiper laid out in 1907, which brings me.

to the last part of the history. Yes, the eradication campaign. Although by the early 1900s, the information needed to make serious progress towards controlling guinea worm was there, the disease remained neglected for almost seven decades, receiving little to no priority in national or international health campaigns for many reasons. Certainly part of it was that the populations that were most affected were often poverty-stricken in rural hard-to-reach areas. But another aspect is that there were or are often many other diseases that had higher mortality rates or prevalence or both. And so this was just lower on a priority chain. Yeah. There were some regional eradication efforts made during those 70 years and other places

made larger infrastructural changes to the water supply that essentially eliminated guinea worm, even if that was not one of the primary intended goals. But it was only in 1981 when the United Nations added guinea worm to the United Nations International Drinking Water Supply and Sanitation Decade. Huh. It was only in that year that the parasite was featured in an international elimination plan. Huh. And so the Carter Center was founded a year after this was added to this elimination plan in 1982.

And one of its goals was the eradication of Guinea-Wermin. worm, a cause that former president Jimmy Carter became very interested in after a trip to West Africa in their early 1980s in which he witnessed some of the devastating effects of the infection. With the Carter Center's involvement, in 1986, the WHO added support to the campaign to eradicate the infection. But one of the biggest challenges in this plan was the lack of accurate surveillance data. A survey in 1986 revealed, revealed that the disease was endemic in 20 countries, most of which were in Africa, and there were an estimated 3.5 million cases. The economic strain caused by the infection as well as the

relatively inexpensive methods of control led to both continued support of the initiative, as well as rapid progress in the control of the parasite. Still, setbacks occurred in the shape of logistical difficulties, political instability, financial or technological shortcomings. But Despite these, within four years, the number of estimated cases fell from $3.5 million in 1986 to $892,000 in 1990, and then in 2015, 22. Oh, oh. Okay. Yeah. I know.

There's more to that story, which you're going to pick up on. Yeah. But, and so, although, you know, 2015, it sounds pretty great to only have 22 cases. and each year seems to bring an article with the headline guinea worm eradication. Could it be this year? But complete elimination has remained just out of grasp. And so, Erin. Yeah.

That's where I'll leave off and leave it to you. Okay. To tell us what's going on with guinea worm today. Right after this break. So, Aaron, you asked for me to tell you what's going on. with guinea worm today, but I'm not going to do that. Because as we mentioned in our intro, we were fortunate enough to talk with Sarah Eurion, the senior associate director for the Guinea Worm Eradication Program at the Carter Center,

who obviously knows a lot more than I do about what's going on today. So I am thrilled to introduce her and we'll let her tell us all what's been going on. Awesome. My name is Thayeri Urien and I am the Senior Associate Director for the Guinea Worm Eradication Program at the Carter Center. And I started this job about a year ago following six years working with the Carter Center and the getting room eradication program in South Sudan. A few years as a technical advisor in the field and then my last three years in South Sudan as the country representative for the program in South Sudan. And so now here at headquarters, I work with the team here to provide support to the country programs in the remaining endemic countries, which is Chad, South Sudan, Ethiopia, Mali, and now

Angola. Awesome. Thank you so very much for taking the time to chat with us. We really appreciate it. So could you start us off by telling us a little bit about the history of the Guinea Warmer Redication Program and sort of. what kind of work was being done in the early days there in terms of systems that were put into place for surveillance or direct care and field work, those sorts of things?

So guinea worm, though it's not a deadly disease, it does cause debilitating pain when it's emerging from the body, and then also during the healing process, and particularly if there has been a secondary infection associated with the emergence of that worm. And so this disease is something that was devastating communities. And there were even parts of West Africa where it was called the disease of the empty granary. And so with simultaneously we're having the success of the smallpox eradication campaign in the late 1970s. The global community was looking for what might be next. And so now you have guinea worm disease, which is devastating communities.

And it's also a disease that potentially, meets the criteria for eradications. And also, you know, there was an assessment done by the World Bank where they determined that actually the cost of the eradication campaign would be less than the costs that are associated with the socioeconomic impact of not eradicating Giniworm. And I think that's a critically important part of that consideration. And there's also, there was also sufficient funding and sustained political will. And so with all of that factors and the devastating impact of guinea worm on communities, that's how it was taken on as the next disease to try to eradicate.

When we talk about setting up a surveillance system to address guinea worm, we're talking about kind of two phases of guinea worm eradication. The first is breaking transmission, and then the second is certifying a country as guinea worm-free. And so currently, you know, we have a lot of, gone from over 21 endemic countries in Africa and Asia in the 1980s to five now. We have South Sudan, Mali, Ethiopia, Chad, and Angola that remain endemic for guinea worm. And they are still working to break transmission.

And so endemic countries have to establish active community-based surveillance, and the foundation of this community-based surveillance structure is the village volunteer. So at every endemic village, the volunteer actually walks house to house on a daily basis searching for possible cases of guinea worm and providing health education to the community residents and then treating any potential cases of guinea worm that are detected. And these volunteers are also supported by a hierarchy of other health workers who support their work and the implementation of a package of interventions to stop transmission. But at this point, we know now that we have a suite of interventions that when applied together

can be successful in stopping transmission. And that includes searching for cases and treating them. And also, you know, another intervention is health education to the communities on transmission and prevention of guinea worm. We also distribute nylon filters so that the communities can filter their drinking water. And we've also over the years have developed a pipe or a straw filter. And finally, treating water sources with a chemical that's safe for drinking water, but that reduces the presence of cyclops in the water and therefore the population of infective guinea worm larva in the water.

You know, guinea worm is about behavior change. and that requires a constant presence from program staff in affected villages. And it requires building trust. And that's something that takes time and it's not going to be able to be bought with any amount of money. And so, you know, I think the success of this campaign is really credited to the endemic communities themselves and the actions that they've taken to stop Giniworm in their communities. And so after transmission is broken, the second kind of phase of the eradication campaign takes place in a country. And so after they've reported zero, they go three years without reporting

another case of guinea worm. And then they can apply for certification as guinea worm free from the ICCDE, which is the International Commission for the Certification of Dracongoliasis eradication. Gotcha. Awesome. So, you know, one thing I wanted to do. One thing I wanted to to ask was about how there are these certain large-scale infrastructural changes that would make not only guinea worm eradication more possible, but would also greatly reduce the prevalence of other diseases, particularly waterborne infectious diseases. So how do you strike that balance between investing in the underlying infrastructure, such as like a consistently clean water supply, versus a more targeted approach, like the use of those filters that you mentioned that prevent

guinea worm transmission, but not of other waterborne pathogens. So two things here. One, the guinea worm, as you've said, the guinea worm program has to remain targeted on guinea worm disease in order to be able to demonstrate success. But at the same time, the program is training and developing a group of volunteers and health workers who will be prepared to provide other health services once skinny worm is eliminated in that country. And in some countries, we've seen that these health workers and volunteers have gone on to be involved in programs such as river blindness or trachoma control.

And some places they've even been absorbed into the National Ministry of Health's health system once skinny worm is gone. So I think that's one good example of, of some of the effects of the campaign that are beyond just the targeted disease eradication. And the other thing is guinea worm, because it's a waterborne disease, the presence of guinea worm or endemic communities has been an opportunity to leverage access to safe water. And so the guinea worm program in many countries has been able to work with ministries of and UNICEF and others to prioritize certain villages or locations for provision of safe water because guinea worm is an indicator that safe water is not present in that location.

Gotcha. Okay. Yeah, that makes a lot of sense. So throughout the history of the program, there has been an absolutely incredible amount of progress made towards eradication. So for millions of cases in the 1980s to just like, you know, dozens in the last few years. So can you bring us up to speed a bit with the latest numbers and especially the biggest hurdles that remain? So as you've said since the 1980s, we've seen a 99% reduction in cases, which is phenomenal. So we've had 21 cases so far in 2020, which is a 56% reduction compared to the same period in 2019. And at this point in the campaign, really our biggest challenge is transmission in animals and mostly in domestic dogs in Chad. And just to give you a sense

of the numbers, in 2019, we had almost 2,000 infected dogs that were detected globally and only 11 that were detected outside of Chad. You know, we've talked about getting anywhere being transmitted through drinking infected water, but we also have some evidence that dogs in particular could be getting infected by eating aquatic animals or aquatic animal waste that contains infective larva. And so as we're tackling the problem with dogs, we've had to kind of think outside the box a little bit and try to tailor some of our interventions to better target dog infections. And so the program is also working with the communities to kind of figure out what works best

in each location, but to provide supplemental food to the household so that to feed the dog with, and then also access to veterinary care and good access for the dogs to exercise. And so far, you know, this is something that has been a very recent intervention, but we are encouraged by the 26% reduction in dog infections in Chad that we've seen so far. in 2020. And so while we may not have all of the answers or a perfect intervention or a silver bullet just yet, we are excited about some evidence that these new interventions to target dogs might be working. Yeah, it's fascinating. I think there's a lot to uncover there, which is really cool. And so the last question that I want to ask is about you. So how did you get involved

with the Guinea Wormer Education Program? And I was wondering, you could share with us any memorable experiences that you've had while working with the Carter Center. When I was doing my master's in public health at the Rollins School of Public Health at Emory University, there was a professor, Stan Foster, who had been a big part of the smallpox eradication campaign. And one day, I was in his office. We were talking about something else. And he said, you know, I think you could do it. I said, do what? And he said, I think you could be a technical advisor for guinea worm. And so a few months later, I found myself signing up for a six-month contract with the Guinea Worm Eradication Program working in South Sudan that turned into six years working with

the program there and then now in this role here, a total of seven years later. And I think for me, you know, initially going into this, what interested me was that this really seemed like an opportunity to apply field epidemiology. You know, you're collecting data and making decisions in real time. And it's really an honor and it's really a privilege to be part of a program and to work in places where the community has invited the program to work there with them. And the governments themselves indeed have invited the support of Carter Center and other partners in their national eradication campaigns. And so I think that level of discipline and diligence that's required from everyone in the program is really incredible. And to just imagine how many, you know, tens of

thousands of volunteers and health workers around the world that have all displayed that level of commitment to support their communities to get rid of Guinea Worm is. is, I think, truly remarkable. And for me, as I said, has been a real privilege to be part of that. That was so great. Thank you so much, Sarah, for taking the time to chat with me about guinea worm. It was great. It was great. It's how amazing that we get to interview people who have actual experience working on these things. Like, that's incredible. It blows my mind. Thank you so much for taking the time. Yeah. It's kind of nice that we get to end this. episode on a happy note. It's not often that we get to do that when we discuss diseases,

particularly neglect of tropical diseases. Yeah, it's a really thing. And do you know, we could actually make this episode even a little happier if we wanted to. We, of course, did an episode on polio way back in, was it 2017? I think it was. Yeah, our first season. And there's been some new news on the polio eradication front that is absolutely thrilling. So we now are even closer to polio eradication because as of 2020, the World Health Organization African region has been declared free of wild polio. They haven't had a single case of wild polio on the continent in the last four years. That is remarkable. I mean, to hear that it is on the verge of eradication is. is absolutely incredible. There's only two countries left in the entire world that are still left

to be eradicated. Pakistan and Afghanistan, so incredible. Like, wow. We're so close. We're so close. Oh, that's very cool. Yeah. Awesome. So. So is that it? Should we dive right into sources? I think we ought to, yes. Okay, cool. So I read a few things. One was a couple chapters in a book called A History of Human Helm Anthology by David Grove. And then a few papers that I found super helpful were DQR spinning and treatment of Gini Worm by Miller in 1989. And by Taya et al, 2017, Guinea Worm from Robert Leiper to eradication. And then I also wanted to shout out a couple of really interesting papers by Amy Morin Thomas,

one titled A Salvage Ethnography of the Guinea Worme. and another called the creation of emergency and afterlife of intervention. And these, I thought, were very interesting discussions on sort of the merit of targeted approaches to disease eradication or elimination versus like a more integrative, bigger scale infrastructure approaches. Very, very interesting papers. I feel like those are really sort of important discussions to have in the context of these kind of eradication campaigns. So definitely shout out those papers. Awesome. I have a number of papers for the biology as well. We'll post the full list of all of our sources

for this episode and every episode on our website. This podcast will kill you.com. Just click on the episodes tab and you can find all of our sources there. Thanks again to Sarah for taking the time to chat with us about guinea worm. And also thank you to Emily for helping set that up. Yeah, that was really incredible. And thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to you, listeners, for still tuning in and listening to us talk about disease. We really appreciate it. We hope this could be like a small little ray of sunshine in your September 2020. Yeah, yeah. Well, okay, until next time, wash your hands. You filthy animals. Regal, Special Agent Bradley Hall.

In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world. The Sixth Bureau podcast is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. I'm Amanda Knox, and in the new podcast, Doubt, the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story?

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