This Podcast Will Kill You - Ep 71 Onchocerciasis/River Blindness: So many mysteries

Episode Date: April 20, 2021

In this classic TPWKY episode we travel down rivers and into worm-laden nodes as we take a look at the complex world of Onchocerca volvulus, the vector-borne parasite that causes river blindness. Join us as we learn why the name ‘river blindness’ captures only one dimension of the devastation caused by this parasite, how the short evolutionary history of this worm is at once surprising and enlightening, and why grasping the disease ecology of this system has been crucial in successful control efforts. As a bonus, if you tune in, you’ll get to hear how on earth The J. Geils Band fits into this story and the integral role that dog digestion has played in the history of this parasite. See omnystudio.com/listener for privacy information.

This is exactly right. There are already enough things charging your card every month. Dinner should not be one of them, which is exactly why Blue Apron is now subscription-free. You heard that right, Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another recurring charge. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients, so there's no meal planning and no extra grocery trip. Order now at Blue Apron.com. Get 50% off your first two orders plus free shipping with code this podcast 50.

Terms and Conditions Apply. Visit blueapron.com slash terms for more information. This is Jacob Goldstein from what's your problem. When you buy business software from lots of vendors, the costs add up and it gets complicated and confusing. Odu solves this. It's a single company that sells a suite of enterprise apps that handles everything from accounting to inventory to sales. Odu is all connected on a single platform. in a simple and affordable way.

You can save money without missing out on the features you need. Check out Odu at ODO.O-D-O-O-O-com. That's O-D-O-O-O-com. The greatest to ever play the game. Return to finish what they started. Welcome to Survivor 50. I wanted one more shot. I played the game that I fell in love with 25 years ago.

I want to win against the best of the best. I chickened out at the final tribal. He's in 50. It's an honor. Light your torch. I've got some unfinished business. Be part of history. I have more to play for this time.

Bigger than ever. Survivor 50. New milestone season begins CBS tonight at 87 Central. It just went completely white. This is how fishermen Akoyo Osumaka describes going blind in 2011 in the remote village of Babagulu in the Democratic Republic of Congo. It was a slow, creeping blindness that began a year earlier. It robbed him of his livelihood and threw his family life into disarray.

Tragically, Akoyo had once fought against the disease that eventually robbed him of his sight by volunteering to distribute drugs that help prevent transmission of river blindness. The river Onane runs through Babagulu and is a perfect breeding ground for the black flies that swarm through the village, infecting people with filarial worms that cause river blindness. Akoyo is one of the many living in the village with the disease, community leaders think that up to 3% of the community is blind. Akoyo felt the need to help, so he volunteered to help distribute Ivermectin. These programs rely solely on unpaid drug distributors to work within their communities.

He would travel to neighboring villages, often deep in the bush, to distribute the drugs. He was often bitten during his travels. One day his village had a stockout of the drug, and he stopped taking it. I was told to deliver all the drugs, and then I would take it later, once I started to symptoms, he remembers. But then there were no more drugs to take. He then ended up missing distribution programs in his village because he was out fishing in forest streams. In 2010, Okoyo started to have difficulty seeing, and in 2011 he went completely blind. His son Aito does not go to school and had to quit his job because of the stress of caring for his father. Iato has a number

of nodules on his torso and forehead. The adult worms that cause river blindness live in these fibrous nodules. Taking care of his father is a full-time job. Ito also suffers from epileptic seizures about four times a month. Researchers have noted a potentially causal relationship between oncosarcaeus infection and forms of epilepsy found in Africa. I depend totally on my wife. She feeds and dresses me, says Akoyo. Even my wife doesn't have a job. After I lost my sight, we couldn't send any of our children to school. Oof, that's horrible. Yeah, it's a tough and unfortunately not uncommon story.

Mm-hmm, yes. So that was adapted from an article titled Revealing the Neglect, Riverblindness, from March 30th, 2018, on the website for Drugs for Neglected Diseases Initiative. And we will link to that story on our website. And you should definitely check it out because not only is there more story to it, but there's also a really cool video, which is the story animated along with a traditional song recorded in a koyo's region about river blindness. So definitely check that out. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is This Podcast Will Kill You.

Welcome. Welcome to another parasitic disease episode of our podcast. I'm very excited about another. another parasitic disease, another vector-borne disease. Yeah, me too. It's super complicated, which gives us an opportunity to talk about all kinds of different aspects of this parasite, of this vector, of the human side of disease, of the history. It's, I think, complex is one word to describe it.

I think it's classic TPWKY, Erin. Yeah, actually, it really is. It really is. Yeah. So what are we even covering this week, Aaron? We're covering Oncocirciciasis, aka River Blindness. Yeah. Yeah.

It is truly a very classic TPWKY episode in so many ways. And speaking of classic TPWKY, we have to start this episode with a quarantini. A quarantini. What are we drinking this week? We're drinking as the worm turns. This is one of my favorite quarantini names. We went back and forth for a long time, but Aaron won out. It is very good. Well, and so I think that we were like, well, we should save this because we're going to do more

wormy parasites in the future, and this is a really good name. Should we do something else for this? But I found a quote from a researcher who was describing these that describes the worms as being undulating and terny. And so, like, you know, it was just too good to pass up. I mean, they are very turny worms. Like, definitely. They are. And also, I really feel like now that we're getting into the whole like worm and world swapping out those two words and idioms or whatever, we've got a whole host of opportunities for future quarantini names. Exactly. This is not going to be the end of the wormy world phrases. Not at all. It's a small worm after all. I can't remember the other ones sitting on top of the worm. Keep an ear out. Erin, what is in as the worm turns? Okay, yes.

Let's do that. In as the worm turns is cognac, ginger simple syrup, lemon juice, and a splash of sparkling water, and you garnish it with some candied ginger. It's actually really refreshing and good. Yeah, it sounds really good. It sounds both like warming and refreshing somehow at the same time. Yeah. And we will post the full recipe for this quarantini as well. well as our non-alcoholic placebo-rida on our website, this podcast will kill you.com, as well as

on all of our social media channels. So make sure you follow us there. Excellent. Any other business that we should attend to before we dive into this very interesting episode? There's the usual stuff. Go to our website. It contains links for merch, for bookshop.org affiliate account, for Goodreads reading list, for transcripts, for alcohol-free episodes, for anything, Any source you ever want to find that we reference on this podcast, you can find it there. Yeah, definitely check out our website. Okay. Is there anything else, Erin?

I think that you pretty much covered it quite well. Wonderful, wonderful. Well, in that case, should we dive into the episode? Yeah, let's take a quick break and then we'll dive into the biology. 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. Just heat them in the oven or microwave, and dinner is ready. And here's the exciting news. Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another recurring charge. Order now at blue apron.com.

Get 50% off your first two orders plus free shipping with code this podcast 50. Terms and conditions apply. Visit blue apron.com slash terms for more information. 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 lied 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. Texting privacy policy and terms and conditions posted at texting terms. Terms.us. Texting enrolls you for occurring automated text marketing messages. Message and data rates may apply or apply or place. Stop, opt out. Visit ISSA online for details. Excuse me, what do you do for a living? Weight tables. You like it?

Not really. Do you work out? Every day. Best part of my day. Would you like to get paid to work out? Are you kidding me? How? With ISS, you could become a certified personal trainer in as little as six weeks. Once you're certified, you can start your own business. Work at a gym or just do it as a side hustle.

Some trainers are making as $100 an hour. $100 an hour. Yes, please. but how do I even find a job as a trainer? That's the best part. There's such a huge demand for personal trainers that ISS guarantees you'll get a job. I'm in. How do I get started?

Just send them a text. Get your free personal training evaluation kit today. Just text Jim to 3232.32 right now. Get certified in as little as six weeks. And ISS guarantees you'll get a job. Text Jim to 3232. 3232. Text Jim to 32 32 32.

2.32. Jim to 32.32.32. So, Oncocirchiasis is a disease that is caused by a nematode, a round worm, named Oncocirca vulvulus, which is a type of worm known as a filarial worm, which means it's a nematode transmitted by an arthropod vector. In this case, oncocirchiasis is also the second leading cause of infectious blindness worldwide after trachoma, which is a bacterial disease caused by chlamydia trachomidus. So since this is a arthropod vectored worm, let's jump straight into talking about the transmission and life cycle of this parasite, shall we? Let's do it. So the overall life cycle of this parasite is not very dissimilar from a number of vector-borne diseases that we've covered on this podcast, but it is a different vector species than we've seen before.

In this case, it's a blackfly in the genus Simulium. The blackfly bites your skin. Generally, much like mosquitoes, it's female blackflies that bite a human, take a blood meal, and in that blood meal, ingest microfilariae, which are the earliest teeny teeny teeny baby, newly hatched larval stages of oncocirca volvulus. These microfileriae travel through the fly's gut. This is where it gets weird. They penetrate the gut walls, which we've seen other parasites do. But in this case, they migrate to the flight muscles of the fly.

Very weird. Very weird. I just have to imagine there's a lot of like glucose happening because those are important powerful muscles, but I don't know. So in these flight muscles, they live for a short time, and in that time, they mature into a second stage larva. And then from there, they make their way down into the salivary glands near their proboscis. They mature one more time into a third stage larva and are now infectious, so that when the blackfly takes its next bite of human flesh, they can be spit out, spit out those third stage larvae just under our skin.

So that whole process in the blackfly takes about a week, give or take. And now in the human, these larvae that have been injected just under our skin will worm and twirl as the worm twirls. As the worm turns. They'll worm their little way into our subcutaneous tissue. And that is where they will live. They'll make a little home for themselves in these little subcutaneous nodules that they kind of build and create. And they're they're pretty well protected from our immune system, which will become important later on. They feed off of our blood and both by like actively feeding but also just by soaking up nutrients through their cuticle.

And over a period of about 10 to 15 months or so, they mature into a adult. adult worms, they mate, and then begin releasing thousands of eggs, which quickly hatch into microfalierre every day. During the day, these little microfilariere worm their way back up to the skin surface, where they can then be ingested by blackflies, which coincidentally bite during the day, thus completing their life cycle. Question. I know. So you said that when the L3 larvae are injected into a person and they form this little

subcutaneous nodule that in which they're fairly protected from the immune system, how? Like, why are they fairly protected there? Because a lot of things could be injected into our skin and not be protected from our immune system. It's a very good question. And it's a question that I don't have a good answer to. I will talk in a lot more detail about what causes an immune reaction to us, but the question of why is it that living worms don't provoke much of an immune response in us is a very good one and not one that I have a good answer to.

And is that universally, or are there people that do show immune responses and are like more protected from this parasite than others? So people don't tend to show immune responses to the living worms. aside from the formation of these nodules, which you could think of as some kind of immune response because it's kind of like, you know, making a little fibrous sheath around those worms and kind of walling them off from the body in some ways. But otherwise, there's not much of an immune response that's provoked by the presence of the live worms themselves. That's wild. I know. It gets wilder. And so like the immune system isn't even showing like elevated antibodies or it's

Is it suppressed? Like, are people who are infected with this worm? Are they more susceptible to other infections? Sorry, I'm kind of going like down the rabbit hole of questions here. You're going so many miles a minute. Let me keep going. And I'm not sure if I'm really going to answer your questions or if I'm just going to bring up even more questions. Well, let's find out. I'm along for the ride either way. Excellent. Good. I'm so glad. Okay. So these adult worms that are living in these nodules. They can live for years. We're talking 10 to 15 years or more. Oh, yeah. Okay. And this whole time, they're producing thousands, if not millions of microflaree that whole time. Not continuously. They kind of cycle like every two to four months or so, they'll have a cycle. But anyways, 10 to 15 years.

I have an estimate that I wrote down because I was so horrified. Totally. Totally. The number of microfilere released from one female adult worm during its life of 10 to 15 years is estimated to be greater than 10 million. Yeah, that seems about right. Because it's like 2 to 300,000 per cycle. Yeah. Yeah.

That's a lot of things. It really is. Okay. And so before we get into what the same. symptoms of this disease are. What I want to tell you, you're going to get mad at this. All of the symptoms that we see stem not from the worms themselves, but from our immune response to the worms. Oh, but hold on. You made a very strong point of saying the living worms. So I'm guessing these are dead worms. You are exactly right. But you're right. I was like,

wait a second, Aaron, then I remember. I know. So it turns out that they do not trigger these intense immune reactions until they die. So of course we have to answer the question, why the heck and how the heck. So it's thought that the immune response that is triggered is in part due to proteins and other like inflammatory markers that are released by the dying worms themselves. So proteins and things that are inside the worms, but then not. accessible to our immune system until that worm dies.

Okay. But far more importantly and interestingly, it's also thought to be due largely to the release of the bacterial endosymbiance that they harbor. Say what? It's so strange. Wollbachia has so many mysteries that surround it. So many mysteries. So many mysteries.

So we have talked about Wobah. Bocchia on this podcast before briefly in, I think, our Dengue episode, because they're important in the context of mosquitoes that transmit Dengue and other arbiviral diseases. But basically, as a recap, Wolbachia are a genera of bacteria that often inhabit the guts of insects and other invertebrates. But it turns out that in filarial nematodes like Oncocerca volvulus, but also wucheraria bancroftiaei, which is the causative agent of lymphatic filariasis, and other nematodes. These bacteria are essential endosimbionts.

So without these bacteria, the nematodes cannot survive or reproduce. We still don't know exactly what it is that they are doing necessarily, but we do know that they are essential to the process of embryogenesis. So eggs can't develop into worms without the presence of these bacteria, which are transmitted transovarially. That is so interesting. I know. And it seems that, based on a lot of data, the release of these bacteria from dead worms is thought to be a major part of the trigger for our immune response.

And so how does this trigger look different compared to like other parasitic infection triggers? So that's what's so interesting. is that what we see is still a lot of eocinophil response, which is what you would expect with a parasitic disease. Not solely, though, antibodies have a large role as well in the inflammation and the immune response to oncocirchiasis, as do neutrophils and other lymphocytes, and these are all different types of white blood cells.

But you still do see a really large eocinophil response, which is interesting. So maybe those are responding to the worm, parts and it's the neutrophils and lymphocytes and antibodies that are responding to the bacteria. Who knows? We don't fully know. But I'm also going to put a pin in that. And I just want for us to remember how important Wolbachia are, because we'll talk more about them in the current event section. Oh, yeah. Yes. All right. So then what does this disease actually look like? In its mildest form, it's possible that the only symptoms that you would have are these nodules that we've talked about.

So these nodules are very kind of hard, deep, subcutaneous lumps, I guess is the best word. Often around the hip girdle, but you can also have them really anywhere throughout your body. They tend to be most prominent where you have like a bone just because then you have less subcutaneous tissue between your bone and your skin. But in terms of symptoms that we see, in the mildest symptoms present as a skin rash, which is usually what we call maculopular. That means a flat area of rash with a lot of little bumps on it that is incredibly itchy. Right. I think it's hard. The word itchy, I feel like doesn't quite do it justice.

Right. It doesn't invoke, I think, the response that this. really deserves. No. Yeah. So it's, yeah, I wish I had a better word than just incredibly itchy. So this rash can resolve in some cases, although the disease itself does not resolve, like we said, these worms can live for years. But more commonly, this rash can become chronic and can actually generalize across the body instead of being present in just discrete patches. And this, as you can imagine leads to even more severe itching. And then as our immune response ramps up, the way that our skin kind of heals results in very severe scarring. It's what's called lichenification,

like a lichen that grows on a tree. Yeah. So it's like our skin becoming really thick and leathery. At this stage, it can lead to hyperpigmentation of the skin, so it becomes very, very dark in patches. And like we talked about in our lush moniasis episode, these type of skin manifestations can be associated with a lot of stigma. And so they can be debilitating not only in the physical sense, like the amount of itching. I saw it described where some people couldn't even sleep except for on their knees and elbows because of the pain of the itching. Yeah, I saw some descriptions of people literally like burning their skin because it was so horrifying. itchy. Itchy. But it can also be debilitating in the way that it is stigmatizing as well. And then over years of this infection, the changes can become even more chronic. And the descriptors of these changes in the literature, I think, are also pretty stigmatizing. But basically what can happen is the skin can end up with its elasticity completely destroyed because of all of that damage to the kind of mid layers of the skin. So then the, the skin, the,

the very top layers become really thinned out. They become atrophied. They're quite wrinkly and they can just sort of hang off of the body. You can lose pigment entirely in those areas because of all the atrophy. And so the skin manifestations can be severe. And this whole time, even as it becomes chronic, that itching persists. And, okay, question real quick again about the nodules. when, like where those nodules exist is where the blackfly has bitten you?

Or like how much variation is there? Yeah, there's quite a lot of variation, which is so interesting. So from what I read, Blackflies often like to bite on lower extremities. So they really bite a lot on legs. But these nodules tend to be present on the hips or even the forehead and on the head. So that would suggest that these adult worms can travel and decide where they're going to make their nodule home. But it also means that the microfilare, which are traveling to the skin surface, can also travel a really long way. They can go pretty much anywhere in our body.

Right. Yeah. And I also thought I read somewhere too about like because, and I know you haven't gotten to this part yet, but the Americas versus Africa in terms of the location. and frequency of the skin nodules, black flies have different biting patterns, right? On like, they bite more on the upper half of the body and the Americas compared to Africa where it's on the lower parts of the body. I would believe that because I did read about a lot more forehead nodules and things in the Americas compared to in Africa.

Yeah. Okay. Okay. So that's kind of all of the skin manifestations, which is one of the most important parts of this disease. The other is, of course, the ocular or the eye manifestations. Well, that's where it gets the common name river blindness. So as these microfalier travel out of nodules and towards the skin, some of them can travel to the eye.

In the eye, the microfalier that die also cause a localized inflammatory reaction. And this results in a number of different manifestations. Kind of the most common one is called sclerosing keratitis, which is where the corneousy of your eye, which is the part that covers like your iris and your pupil, that becomes inflamed, and then we'll scar over. So this starts with a haziness around the edges of the cornea, and then we'll eventually go in to encompass the entire thing causing complete blindness. Oh, yeah. It's not only sclerosyn carotitis, because you can have these worms that end up in the posterior part of your eye, which can cause inflammation of the retina and similar kinds.

of damage due to inflammation in all parts of the eye. And I think it's also important to point out that these microfalaria can travel kind of throughout the body and invade, for example, our lymphatic system. And they've been found in a number of different organs. Like if you sample organs from someone who's died who was infected with onchocirchiasis, you can find microflaria in a number of different organs. but we don't really have a good handle on what kind of disease might be caused by that. It's really the skin and the eye that are the two most common organs affected.

Right. So, yeah, I also want to mention because it's important, but also because it was brought up in our firsthand account, there does seem to be increasing evidence that infection with oncocirchiasis is also associated with an increased risk of epilepsy. see. Is there any suggestion as to what the mechanism could be? None at all, which is the hardest part. So there's a lot of epidemiological evidence of association, but there's not really any data on what could be the cause or the mechanism. So we don't really know if it is, in fact, oncocirchiasis or something else. But there's epidemiological evidence for this association.

So I thought it was important to mention. Yeah, definitely. Yeah. Yeah. So, yeah, that's kind of the basic overall picture. I think it's interesting that there does seem to be some strain differences. So in parts of West Africa, it's long been noticed that in the savannah regions, the rates of blindness due to Oncocirca were much higher than in forested regions of West Africa. And in those savanna regions, the rates of blindness really strongly correlate with the intensity of infection. So the more heavily infected somebody is, the higher their risk of ocular complications. But in other areas, like in forested regions, that doesn't seem to be the

case. And so it turns out that there are different strains of oncocercovolvulus, but what I think is so interesting about this is that there's also some evidence that part of the differences in these strains is how much Wolbachia they carry, Erin. It's, well, and it's not, it doesn't seem to be just that as I'll get into, but it's really, yeah, that's definitely an interesting component for sure. Yeah. Oh my gosh. So that's pretty much the whole biology aside from treatment. Do you have any questions, Aaron, before I talk briefly about treatment? Did you say already how long these worms are? No, I was just about two.

Okay. These worms, the adult females, get to be up about 30 centimeters, 30 to 80 centimeters long, which is over a foot or two. That is very long. And yeah, wow. And then in each nodule, you'll also have one or two males, but what is fascinating is that these males travel around nodule to nodule. They go like, beep, boop, boop, boop, traveling along. because the females have to be re-inseminated every time they have a reproductive cycle. Hmm. Interesting.

Is that cool? By the way, the microfilier are so, so, so tiny. They're like two to 300 microns, which is about the length of two sheets of paper is wide. That makes sense. Very tiny, yes. It's very small. And then they grew up to be quite large. Yeah.

Yeah. Okay, so what do we do about it? Yeah. We do have something that we can do, which is phenomenal. Treatment, though, like I said, we can't just kill all of the adult worms outright because that would trigger a huge immune response. So treatment is actually via a drug called ivermectin, which is an antiparic that is very effective at reducing the load of microfaleriate in the skin for seven. several months at a time, which helps not only with symptoms, but it also reduces the risk of complications like blindness. It doesn't, though, kill the adult worms at all, not even slowly.

What's so fascinating is that ivermectin is a neurotoxin, and it works on channels that we have as vertebrates, as mammals, but we have a blood-brain barrier, so in us it doesn't have the same effects. Oh. Isn't that cool? So it's actually a very safe drug, which is awesome. Yeah. For humans.

Not for worms. But while it causes a flaccid paralysis and eventual death in the microfilariae, in the adult worms, what it does is just kind of block them from releasing eggs for a short period of time. So it's thought to kind of paralyze their reproductive tract, but not much else. Okay. Which is so fascinating. I tried so hard to get the like, why, why can't this kill an adult worm?

But I don't have the answer to that. I don't know. Yeah, that's very interesting. It's so interesting. Yeah. But that's the biology of aqua sarcasis. Oh, it's a big one. It's a big one.

It's so complicated. It's so interesting. There's so many steps and there are so many different components and that's sort of the theme also that I will talk about in the history. Would you please? Would you please? I'd love to hear it. Let's take a quick break first and then I'll dive right in. 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. Texting privacy policy and terms and terms.us. Texting enrolls you for recurring automated text

marketing messages. Message and data rates may apply or apply stop, dot, dot, Visit ISSA online for details. Excuse me, what do you do for a living? Weight tables. You like it? Not really. Do you work out? Every day.

Best part of my day. Would you like to get paid to work out? Are you kidding me? How? With ISSA, you could become a certified personal trainer in as little as six weeks. Once you're certified, you can start your own business. Work at a gym or just do it as a side hustle. Some trainers are making as much as $100 an hour.

$100 an hour. Yes, please. But how do I even find a job as a trainer? That's the best part. There's such a huge demand for personal trainer. that ISSA guarantees you'll get a job. I'm in. How do I get started? Just send them a text.

Get your free personal training evaluation kit today. Just text, Jim to 323232 right now. Get certified in as little as six weeks. And ISS guarantees you'll get a job. Text Jim to 323232. Text Jim to 3232. Jim to 3232. Lately, car buying has become a pretty dull experience.

But on eBay, behind every car in part, a story waiting to be shared. There was a guy who bought a 2020 Porsche Cayman GT4 on eBay. It was well loved. There are plenty of Cayman's in great condition on eBay, but this one needed some work. That's just the start of the story. So after this guy gets a great deal on his dream car, he rebuilds the whole thing with all these parts he found on eBay. Performance brakes, suspension, body panels, the works, guaranteed to fit. Next thing you know, this nearly scrapped Cayman was out there on the track as a full-blown race car. You're ready to go daily driver.

Your next, Restamad. Hello, Lotus Alon. Hand the parts to finish it. eBay has thousands of cars and is the largest online selection of vehicle parts and accessories. eBay. Things people love. I feel like I start off most of these histories, or at least a lot of these histories, especially in episodes about parasites, saying that, you know, this disease has been around forever, like millions of years forever. And then I go on.

to talk about how there was this fossilized poop found or evidence of infection in a mummy. And so I was surprised when I started researching for this episode that I wasn't finding any of that for oncocirychiasis. None of it. Where were my ancient Egyptian papyri? Where were my coprolites? None of it. Maybe they are out there still waiting to be found, either by me in a literature or by a budding

paleo-epidemiologist or something like that. Let us know if you find anything. But most articles I read discussed the early history of onchocychiasis as starting either at the evolutionary roots of the parasite that causes the disease, or they jumped ahead to the early scientific work classifying this parasite in detailing its transmission root and disease characteristics. And so we'll get to that part eventually. But first, I will want to go back, of course, to the evolutionary ecology of this parasite. Yes. Where did it come from?

How did it get to be distributed the way it currently is? And what role does the ecology of this complex parasitic infection play in its establishment and continued persistence? Yeah. Okay, here we go. This disease, onchostarchiasis, exists in two main areas of the world, Africa, where 99% of cases occur and Central and South America, where it's a lot more localized and less prevalent, partly because of control efforts that I'll go into later, and partly because of the history

and ecology of the parasite itself. And so based on this distribution, it's probably not that surprising that the parasite evolved in Africa and then was brought to the Americas at some point during the slave trade, beginning in the early 16th century. Makes sense. But what may be surprising is that although the genus Ancocirca is likely millions of years old and also originated in Africa, the species that causes river blindness, Oncocirca vulvulus, is a relatively recent parasite of humans. Okay, I saw that somewhere and I was like, what? I didn't mean anymore because I wanted to tell me about it. Well, because genetic analyses that have compared like many different species in the Ancocirca genus

show that Ancocirca Vulvulus likely evolved from the ancestor of Ancocirca Ocengi, which is a parasite of African savannah bovids. Okay, but I'm so confused by that, Aaron, because Oncocirca vulvulus is pretty much a human-specific parasite. Yes. So that doesn't make sense. This evolutionary pathway, like this speciation, is supposed to have occurred only within the last 10,000 years or so?

Because it's supposed to correspond to the period when cattle were domesticated and that's when humans would have come into contact. What are you telling me? Well, and there's a side note too. Cattle were domesticated between like 10,000 and 37,600 years ago in parts of Asia, but domestication is actually thought to take place later in Africa, like maybe between 4,000 or 1,500 years ago. What?

And so it might be that this parasite evolved so rapidly. Yeah. That's bananas. I know. And there's more on this too. Oh, my gosh. So for much of that 10,000 year history, let's just call it 10,000 years. Okay.

This parasite stayed in Africa. It drove human settlement patterns in such a way that perhaps people would settle near a river or a lake. and then as more and more people developed this horrifically itchy skin condition or they lost their vision, they moved away to land that was further away from these sources of water. So the land was often less arable. It was more susceptible to erosion. And by the way, this is still happening today. Like, for example, in parts of Ghana, where people have moved away from these high onchusarchaeus' prevalence areas

to more crowded, less arable areas that have led to an increase in nutritional deficiency, and food instability. But I'm getting ahead of myself. So, yeah, so let's go back to this remarkably short evolutionary history. This is an obligately human parasite. Yeah. Like they have shown, you know, incidental infections in a gorilla, I think I've seen, or in some other animals, but it is human specific. There's no animal reservoirs for oncocerca volvulus. It's a human disease. Right. And so within a relatively short time span, like let's say conservatively 10,000 years, this parasite went from a bovine host to just humans as hosts. That's truly remarkable. This definitely seems like there were some strong forces that drove speciation.

Yeah. And there's also some evidence that suggests that there might be speciation happening currently within the parasite species onca-circovolvulus. Stop it. Yes. And you touched on a little bit of this and talking about the strains. Oh, okay. And I want to talk a little bit more about that and about the ecology of this system overall. Okay. So as you mentioned, this parasite species is transmitted by multiple species of simulid blackflies. And the distribution and habitat preferences of these black flies varies quite a bit. And warning, this is going to be oversimplified.

Okay. But in Africa, for instance, you have some blackfly species that are savanna dwelling and those that are forest dwelling. And you mentioned that there are savanna strains of the parasite and forest strains of the parasite. And these different blackfly species transmit those corresponding strains of Ancocircovolvulus. Yeah. And what happens when researchers try to take a savanna strain of the parasite, and put it in a forest-dwelling blackfly, they found that the parasite developed poorly or not at all.

And the same thing happened with the forest drain of the parasite in the savannah-dwelling blackfly. What, Aaron? Yes. And there's some regions that they can be co-infected. So is that maybe, like, I'm getting too complicated. Well, what it seems is that that's fairly uncommon. Like it's happening more today, possibly because of control efforts and how that sort of changed the landscape of disease in this case.

But at least, like, historically, it really does seem that there has been sort of this something, some sort of barrier preventing the mixing of this like savanna strain and this forest strain of the parasite. What? And so what some researchers think is that these different parasite strains may actually be diverging from one another. So we're going to end up with two species? Mm-hmm. Possibly. Oh, my gosh. I mean, and it also makes sense because these parasites rely so heavily on these flies for their transmission and development that they may become, in a sense, reproductively isolated quite easily.

So basically, how I was thinking of it is that, like, the adaptations that these parasites have to survive and develop in one black fly species might not be the same ones that would allow them to. do the same in others. And for what it's worth, these parasites don't seem to be harmless hitchhikers for these flies. At least for some of the species or vector parasite complexes. And there have been some studies confirming that some black flies show innate and acquired resistance to filarial infection. I love that. I love when insect vectors have responses and fight back. Yeah. And so because. there's such like, let's call it a tenuous relationship between the parasite and vector, it might be that putting all of your like, you know, adaptive eggs in one blackfly basket

might be a favored strategy in terms of evolution. Yeah, you get really well adapted to that specific immune response. Mm-hmm. Mm-hmm. In any case, this diversity of blackfly species and the complicated interactions between different strains of the parasite and different, species of fly is just one example of the incredibly complex disease ecology of this parasitic infection. And I also think that this episode is a great opportunity to talk a bit about disease ecology in this context. Yeah. Because we get a lot of emails from people asking us the difference between epidemiology and disease ecology. And I feel like even though I technically have a degree, kind of in both. I still don't feel very qualified to go into those differences.

Same. But I'm going to try. So there's a lot of overlap between these two fields. And I think that this disease is a good way to show at least some examples in ways that the approaches or research questions could be different. And so overall, epidemiology is often defined very broadly as the study of patterns of disease and health in populations. And disease ecology is more concerned with the role that the environment and evolution play in the interactions between host and parasite. And so, for example, in the case of oncapsychiasis, the transmission of the parasite depends on so many things that are influenced by the environment. Right. Which vector species is present? How abundant is that vector species?

What are the things that determine its abundance? What season it is? What habitat it's in? and within a certain season or even a certain time of day, things like relative humidity, temperature, wind velocity, light intensity, rainfall, all of which could influence transmission in some way. And there's evidence to suggest that a lot of these factors do. And so a disease ecologist might ask something like, how does the seasonal biting activity of different simulid blackfly species change across these different environments? and how is that associated with the output of L3 larvae by those black flies? Like all of these things are sort of what role does the environment play in the transmission?

And getting a better sense of the different factors at play can help to focus control efforts in a lot of ways to make them more impactful or more efficient. Like for instance, is there a distinct wet season, like a distinct wet and a distinct dry season? and should one of those seasons be targeted more for breeding sites for the flies? And should that time of year be targeted more for, you know, habitat removal or habitat spraying? And an epidemiologist, conversely, might ask about the geographical variation in infection prevalence and how these prevalences might be associated with past spraying or ivermectin campaigns. And a lot of these epidemiological questions, the way I look at it is that they help to get a sense of the extent of the disease, how human behavior or experience plays a role in the exposure or to measure progress in

control efforts. Aaron, did I miss anything with disease ecology? That was really good. Also, how fun to get to talk about, like, just broadly, disease ecology and epidemiology. Well, it's really fun because as I was reading about the ecology of this system, and I didn't do a very comprehensive job of explaining it, but I was. by the number of questions that you could ask about how is the black fly, you know, feeding, like at what time of day? What part of the body is it feeding on? What time of year? How does that,

how does the current filarial load in the fly influence behavior? Like all of these things. I know, another PhD, PhD take two. It's just so funny, Erin, because as you're talking about all that, like, I can hear how excited you are and I am also getting so excited. And so it's just so funny that like of course this is a disease that would get us so like excited to be asking these questions and like that's why we did the degrees that we did like it's just it all comes full circle like yep yep and i love too like this is such a good example of you know the ways in which that that barrier between epidemiology and disease ecology isn't really a barrier at all it's very fluid you know eco epidemiology yo you know there we go

And so it's really cool to see how, you know, the data derived from these two different fields in terms of research questions could be used synergistically or in the same, in the same, like, applications. Well, I'm also like, can we get some immunologists to join this party too? Because I still can't get over that this is a newly evolved human-specific parasite that is so good at evading our immune response. Like, are you kidding me? I know. We should get back to Anka Syraciasis.

Let's get back to Ankaeis. Yeah, we do need to do a careers episode one day. Yeah, we do. We want to have other people define what an epidemiologist does and what a disease ecologist does. But yeah, I just wanted to kind of go through this because I think Anka Syracias is with its, you know, three-player cast of human parasite vector and its super close ties to environmental factors is a great way to think about how the environment ends up shaping transmission patterns leading to human disease.

Absolutely. Okay, so I've talked for a very long time about evolutionary history and disease ecology in general, but I haven't even started on the written history of onchocychiasis. Well, let's get started. But don't worry. I mean, it's a pretty straightforward story. So it's much more straightforward than it's ecology. I'll say that.

Before I begin, I also want to acknowledge that before the quote-unquote discoveries of Western scientists regarding this disease, the people who lived in Africa among this disease for thousands of years were already well aware of several aspects of oncocirchiasis, including the association with rivers or bodies of water, the role of the blackfly and transmission, and both the skin and blindness manifestations of disease. But, you know, this longstanding knowledge is rarely, if ever, noted in the official histories of scientific achievements, not just in terms of oncosychiasis, but in terms of many, many diseases that we have covered or will cover. Right. So taking that into consideration, where do these official histories begin? In 1874, there was a British naval surgeon by the name of John O'Neill, who was assigned to the HMS Decoy, off the coast of what is now Ghana. He noticed several people living along the

western coast of Africa had an itchy and irritating skin disease with nodules and puscioles. Locally, it was called craw-craw. And he thought at first, could this be scabies? And so he examined some of these nodules under a microscope and, quote, succeeded at length in discovering a philaria, which I believe to be the immediate cause of complaint. Threadlike in form, at one time undulating, and now twisted as if into an inexplicable knot. Then, having rapidly untwined itself, it curls up into many loops. It's a very poetic description of a phileria, yeah. O'Neill's observations of this parasite were followed pretty closely by Rudolph, Lucart,

who in 1890 received a nodule of worms the size of a pigeon's egg. that an unnamed German surgeon had removed from someone also in the Gold Coast, what is now Ghana. Actually, how big is a pigeon's egg? Actually, that's a great question. Let me look it up. A pigeon egg is smaller than a chicken egg. Looks like to me, it's like half the size to two-thirds the size. Yeah, I would say that.

So, yeah, he received this nodule, the size of this. pigeon's egg, from this guy who had sent it to him asking for identification. And Lucart looked into it, and he didn't make any announcement of his own regarding the description of the adult form of this worm, but he did tell the famous parasitologist Sir Patrick Manson, who published a note in which he gave Lucart credit for both the discovery as well as the naming of the worm, which eventually became Oncocirca vulvulus. Ancocerca, from the Greek words meaning barbed tail, and volvulus from the Latin for to roll or turn as the worm turns.

By this time, several other helmet species had been discovered in Africa and elsewhere, and Anka-Circovolvulus didn't really seem to attract any particular interest, which I find interesting. Yeah. I mean, they simply noted it as, you know, it's probably this old disease. And also, they seem to think that it was more of a rare, curiosity rather than a common occurrence, but that belief would later be turned on its head. So despite the much higher prevalence of river blindness in Africa compared to Central and South

America, a good chunk of the big leaps forward in terms of understanding this disease were made by Rodolfo Robles in Guatemala. In 1917, he published a report linking the parasite to blindness as well as the dermatitis that had previously been observed. And the link between blindness and the parasite wouldn't be discovered in Africa for another decade or longer by researchers working there, which I find very interesting. Yeah. And I wonder if one of the reasons for that

is because of the biting preferences of the black flies in Central and South America compared to Africa. Like that they were more kind of visible? More visible, more. No, I mean, like in terms of the blindness, that there happened to be more nodules on the face and head compared to Africa. So I don't know. But Robles also suggested that simuladay blackflies might be responsible for transmission of the filarié and that removal of the nodules might provide relief in symptoms. And speaking of nodules, in his quest to see whether these parasitic worms were the same species as on.

Anka-Ca-Cirka-Volvulus or if they were a new world species. Spoiler alert, they're the same species. He was wrong. He had a hard time getting the worms out of the nodule intact. And so he used, quote, the novel technique of removing the fibrous tissue by active digestion in the stomach of a living dog. Yeah. That's all the explanation that I found for that one. So he fed the...

He fed the dog. The nodules to a dog. Who then presumably pooped out worms. Pooped out worms? Or did he like induce vomiting or something? Oh, that's another possibility. I don't know. I don't know either.

Yep. It's weird that it was effective, honestly. It's weird that he thought of it. There's a lot that's weird. There's a lot that's weird. And the next big jump in Onka-Sarchiasis research was when Donald Blacklock made the link that blackflies were responsible for transmitting the parasites through observations of the guts of simulium blackflies. Robles had just suggested it, but Blacklock actually did the experiments.

Although, again, this link, I want to say, was well known among people who had been living there. Right. By the 1930s, interest in Oncustarchiasis had picked up, and scientists had started to realize that it was much more widespread than previously thought. but they were still missing one big piece of the puzzle, the piece that Robles had found nearly 20 years before, the link between the parasite and blindness. In 1931 or 1932, I can't remember, a researcher named Jean Hissette published a report that showed that in a part of the Democratic Republic of Congo, 20% of the people with oncocirchiasis were blind. and 50% of that population suffered from eye troubles. Unlike in many other places in Africa, the nodules and cysts were concentrated on the head

rather than lower down the body, which was also kind of the pattern in the Americas. And although Hissette's work seemed to show a clear connection, including he found microfaleri throughout the eye, the link wouldn't be widely accepted until the mid-1940s at the earlier. Wow. Which also coincided with this period of increased European troop presence in Onchusarchias' prevalent areas. Not unsurprising.

Not unsurprising. As researchers got a better handle on the scope of the disease and the devastating effects that it could have, campaigns to control or eliminate the disease were started. The earliest campaigns targeted the vectors of the parasite, relying on the use of DDT, which was developed in 1941 and found to be extremely effective as an insect killer. And also, as Rachel Carson has made us all aware, as a killer of many other things. Some of these early control programs seem to actually be quite effective. So, for instance, in the Coderra region of Kenya, which had been nicknamed the Valley of the Blind,

due to a prevalence of Onchocercaeus of 70%. Oh, my gracious. DDT applications over a six to seven month period led to eradication of the blackfly vector in that area. Wow. Mm-hmm. I know. It feels weird to be like, wow, DDT worked really well, but it did until it didn't. And then until it did until it didn't.

Yeah. Killed a lot of other things. Yeah. Yeah. Leading into the 70s, which is when probably the largest campaign began, the WHO onker Syracayas's control program, OCP, still the strategy for control focused on interrupting transmission by vector elimination. In this program, which targeted initially seven countries around the Volta Basin of West Africa, with additional areas or countries added later on, insecticide was applied either on the ground or arreally.

And the plan was to continue these types of vector control activities for 20 years, the length of a female worm's life, like the maximum length. Yeah, that makes sense. But there were several challenges that emerged that either interrupted or slowed down progress. And one was that several areas were reinvated by adult flies from outside the target areas. Studies show that some flies in the simulium damnosum species complex could migrate up to 500 kilometers. Yeah. They forgot that miles.

They're really far flyers, which makes it so much more complicated. So much more difficult. And another issue was insecticide resistance. So the OCP adapted to overcome these challenges by rotating different insecticides to reduce the likelihood of resistance. And there was another development that actually helped to overcome these challenges as well. And that was the discovery of ivermectin, which was developed in 1975 and provided for free by Merck starting in 1988. and its developers were actually awarded a Nobel Prize in 2015. Yeah.

Yeah. That was like really changed the landscape of control. This one-two punch of insecticide and treatment allowed the OCP to make incredible strides in Oncocirchiasis control. So by 2002, it was estimated that the OCP had rid 250,000 square kilometers of farmable land of Oncocircichiasis. with 40 million people having been protected and 600,000 cases of blindness prevented in at least seven countries. In the incredible amount of work done by this program not only greatly reduce the burden of disease in some areas, but also led to a huge amount of knowledge being gained about the ecology and the epidemiology of this disease, which could then be integrated into future control efforts.

And I just want to make a little note. Another bright moment during the OCP era happened in 1981 with the release of the J. Giles band song River Blindness. I'm going to redo the first two verses. Okay. You're not going to sing them? I'm not going to sing them. I actually haven't listened to the song yet, which is so bad, but I found it like right before we started to record. Okay.

Okay. Human kindness, river blindness. Black flies rise as the water flows. Human kindness, river blindness, angels cry as the fever grows. Indications, demographics, control of the basics is all you see. Correlations, disintegrations, cessation of life expectancy. We need to ask if we can get permission to play that song on the pod because, please. I know, I know.

I had no idea. It was on like a 10 things you probably didn't know about. for blindness. And I was like, you're right. I did not know about this. The J. Giles band song. The only other song that I know by the J. Giles band is centerfold. Like, my angel is a centerfold. Wait, I know that song. Yeah. So I think it's very funny in their repertoire of songs. One is centerfold and the other is river blindness. Wow. Fascinating. There we go. Okay. Anyway, After the OCP ended, OECAAS's control was headed up individually by many of the countries involved in the OCP, and since the mid-90s, there have been many other control programs started in countries that had not been involved in OCP.

And on the other side of the Atlantic, other elimination campaigns had started up in the Americas. And these were slightly different than those in Africa due to the ecology of the disease. So whereas in Africa, large parts of 31 countries are affected. by Ankapsychiasis, in the Americas, the distribution is much more limited or focused and has been. And so in those areas, mass drug administration with Ivermectin seemed to be the ticket. And in 1993, the Onka Syraciasis elimination program for the Americas began, and there have been many success stories there. For instance, and I hope I'm not stepping on your toes, Aaron, but rather setting you up to wrap up the story.

I love it. Anka Syraciasis was declared eliminated in Colombia in 2013, in Ecuador in 2014, in Mexico in 2015, Guatemala in 2016, and parts of Venezuela in 2017. And from what I can tell, the areas where most of the transmission still happens is the southern parts of Venezuela and the northern part of Brazil, where they border one another in sort of like the Amazon area. So, Aaron, it seems like there's been a great deal of progress in the control. of this disease, but it still seems like we have a long way to go based on some prevalence numbers I saw. So take me through where we stand and what we have left to do with this neglected tropical disease. I would love to. We'll take a quick break and then get into it. So World Health Organization estimates based on data from 2017, which is the most recent data that they have listed,

estimates that worldwide almost 21 million people are currently infected and living with Oncocirca volvulus. It's so many people. It's still a very, very large number. Yes. It's estimated that of those 21 million people, about 14.6 million of them have active skin manifestations. Wow. So they have active disease. And about 1.15 million have.

some degree of vision loss, if not complete blindness. Will everyone who is infected with this parasite develop blindness? Is it just an inevitability? Great question. No, definitely not. And not everyone would even necessarily have all of the skin manifestations. Okay. But I could not find a solid number on like what that percentage or proportion is.

Okay. I think it largely has to do with disease burden. So the higher the intensity of burden, the more likely you are to have severe disease including vision loss. Right. Okay. Yeah. Like you said, Aaron, already, it is still the case that over 99% of those who are currently living with oncocirchis live in 31 countries across Africa. The other 1% are located in FOSI in Latin America as well as Yemen.

And the thing is that oncocirchiasis doesn't kill. people outright. But it is no less debilitating and it does reduce life expectancy even though it doesn't kill people directly. So like you mentioned, Aaron, before control efforts ramped up, in some endemic areas, up to 35 or 46 percent of people would become blind eventually. That is just, yeah. And in many areas where oncocirchiasis was endemic, up to 10 percent of the adult population would become blind, just depending on the overall worm burden in the area. And even without considering permanent disability like blindness, these skin lesions, I really can't underestimate how debilitating the itchiness can be. People can't sleep. They can't work.

So if we look at the disability-adjusted life years, which is an imperfect measure, but still a measure of overall disease burden. Onco-psychiasis is estimated to account for between 1 million and 1.5 million disability-adjusted life years annually, depending on which paper you look at. And the itching and skin manifestations account for over 60% of these. So it's not just the blindness. I think that with a common name like river blindness, it can be overlooked how impactful the skin disease really is as well. Right. I think that's definitely the case. Yeah. And also, these skin manifestations can result in open wounds and just as well, Aaron, you asked really early on whether people become immunosuppressed in some ways. When you have a very, very high worm burden, it does cause your immune system

to be more likely to have other infections. Okay. On top of having potentially open wounds on your skin that can be an area where you can become infected. So overall, it's estimated that oncocirchiasis, though it doesn't kill people, it does reduce overall life expectancy by 13 years. That's, yeah, that's not insubstantial at all. Right, not in the slightest. But the good news is that control efforts have been ongoing for decades now. Early on, Erin, like you talked about, they relied on a lot of integrative approaches using both vector control pest management as well, as Ivermectin, most of the programs that are out there today really just rely on community directed treatment with Ivermectin annually. This has worked very, very well in some areas,

like in the Americas. It has not worked as well in very, very highly endemic areas in Africa, largely because it doesn't kill these adult worms. And you administer Ivermectin annually, but it really only reduces symptoms and slows the transmission for a few months. So ivermectin alone is unlikely to completely control or eradicate oncocirchiasis. And in terms of how it's only given once a year, is administering it more frequently bad for you? So it's a great question. It's a possibility and there's some data that suggests that maybe in these hyperendemic areas, that could be a good option to administer it bi-annually instead of annually.

But the data doesn't suggest that that would actually result in that big of a decrease. Because annually does make a really big difference. It's just that in places where this is hyperendemic, it's just not quite enough, essentially. Well, and I think it's also interesting, too, going a little bit back to the ecology, is that I saw a few, like, line graphs looking at the biting frequency and how it does peak at certain times of year. And so if you reduce the microfluaria presence during those times and time the drug administration then, then. Precisely, exactly. Yeah.

So kind of targeted administration as well. But overall, in 2017, 145 million people, which is about 70% of the estimated population at risk, were treated with Ivermectin through these various control programs, which is phenomenal. It's not quite where we need to be because in every region you would need at least 80 to 85%. treatment to really help reduce an interrupt transmission. But it's good progress. But the big question is, can we do better? We've been doing this now for decades. Can we do better, especially as it relates to actually curing disease rather than just treating symptoms or halting progression, which requires treatment for 10 to 15 years or more, right? Right. Enter Wolbachia. Oh, Yay. I'm excited for this. I told you we'd come back to them. So like I said in the biology section,

the more that we know about the disease pathophysiology of oncocirchiasis, the more it becomes clear that Wolbachia play a very important role. But we already know that we can't just kill the adult worms outright because then the Wobokia that are in them would make us really sick, right? So some researchers have wondered, what if we just kill the Wolbachia bacteria inside of these worms instead? How do we do that? Great question, Erin. We can do it. Okay. Treatment with doxycycline, which is an antibiotic. It's a relatively common one that we use for a lot of diseases, including tick-borne diseases like rickettsias, which Wolbachia are relatively closely related to Rickettsias? They are indeed. So treatment with doxycycline can interrupt embryogenesis, stop adult

worms from being able to reproduce for at least a year, if not two years, which is far longer than the few months that ivermectin can do. That's incredible. So it's unclear whether treatment with doxycycline can fully just kill the adult worms very slowly. I think in some studies it suggests that these adult worms will then die. But certainly it stops their reproduction. It stops the production of microfilariate for years. That's a wonderful news. So why aren't we mass administering this?

Yeah. Yeah. It's a little tough. So ivermectin is a one single dose treatment. One dose once a year and you have effect. Doxycycline, on the other hand, requires 100 to 200 milligrams per day every day for four to six weeks at a time. There's also a pretty large range of people, including pregnant people, breastfeeding

people, children under nine who can't take doxycycline for various reasons. So there are groups that are doing research to try and find other compounds and drugs that might have the same effect but be administered in a more practical way, so not needing people to take drugs for six weeks at a time, but also to a wider range of people who are at risk of infection or who are living with infection. But what's really cool is I saw some papers that were suggesting that this could be something that's particularly beneficial in those areas that are hyperendemic, where we've been treating with ivermectin, but it doesn't seem to be having the effect. Or also in areas where you have a high burden of disease, but you also have

Loa Loa, which is another filarial parasite. that if people are co-infected with Oncocirca and Loa Loa, you cannot treat them with Ivermectin because the Loa loa loa worms will also die, but they are larger and they can block blood vessels and cause brain damage and death. Yeah. So that's bad. Yeah. But Loa Loa Loa don't have Wolbachia. Interesting. So doxycycline and drugs that work like it don't affect them.

So that's a pretty promising area. of research for that reason as well, because areas where both Anco-Sirka and Loa Loa are present have been very difficult to do control strategies. We need to, like, keep a list of, like, at the end of these episodes, we're like, oh, like all these future directions, let's keep an eye on how these things are progressing. There's a lot, I feel like. There was a lot in, like, the Dengue episode where it was like, this is happening now. Right, right.

But it's pretty awesome. I think there's some good research that's going on. I think that overall things are not great in terms of oncocirchiasis, but they're a lot better than I expected, quite honestly. They're a lot better than I expected. And I think that, like, the, you know, the past 50 years or so of control efforts have really shown that a lot of progress can be made. Exactly. Yeah. Like, we've made massive progress.

It's just that because the life cycle of these parasites is so long, you still have really high prevalence of disease. Right. Right. But yeah, we've come a really long way, so we can end on kind of a positive note. Yay. I like when that happens. Me too. Sources? Sources. So I have a thousand different articles, not that many, but I have a lot of different articles. I'll shout out a couple. One resource that was great is a book called A History of Human Hell mythology by David Grove. and in terms of papers, I want to shout out a few, one by Basayas et al 2009, another by Crump at all 2012, Kruger at all 2007, and Lefoulon at all 2016, and those were all really great papers.

I will post these papers as well as all the other ones I didn't mention on our website. Same. I have a very long list of recommended reading, everything from the specific biology and pathophysiol to a lot more details on the role of Wolbachia and ivermectin. It's a really fascinating drug. If you want to read more about it, you can find all our sources for this episode and every one of our episodes on our website. This podcast will kill you.com under the episodes tab. Absolutely. Well, thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to the exactly right network of whom we are very proud to be members. And thank you to you listeners for allowing us to make this podcast and for listening.

Even if we talk about like really, I don't know, scary subjects or really weird subjects, we're glad to have you along for the ride. Yeah, this is really fun. We hope you enjoyed this episode. Yeah. Well, until next time, wash your hands. You filthy animals. Success starts with your drive.

An American Public University is here to fuel it. With affordable tuition and over 200. flexible online programs, APU helps you gain the skills and confidence to move forward. Whether you're changing careers, starting fresh, or pursuing a lifelong passion, our programs are designed for people who never stop. You bring the fire, APU will fuel the journey. Learn more at APU.APUS.edu.

Get a little out there, into the big heart of Nevada, where you can go off road and off the map, on two lakes or on horseback. Dip into hot springs and dive into deserts. Climb a mountain or make your best effort. See thousands of stars in some of the darkest skies. Stake out haunted hotels. Can you make it to sunrise? There's always something new to see because we've got plenty of space to just be.

Plan your trip at travel Nevada.com. You see it instantly. It's Coldwater Creek, the mark of exceptional workmanship, and signature touches inspired by a mountain west heritage. distinctive styles created from quality fabrics, silhouettes perfected with just the right drape, feel-good fits offering ease of movement, and thoughtful details to elevate your look.

For a wardrobe you can count on season after season, visit coldwater creek.com. Shop the new spring collection at 20% off $75 or more with code IHeart 20.