Speaker 1: It just went completely white. This is how fishermen A
Speaker 1: Coo yo Osumaka describes going blind in twenty eleven in
Speaker 1: the remote village of Babagulu in the Democratic Republic of Congo.
Speaker 1: It was a slow creeping blindness that began a year earlier.
Speaker 1: It robbed him of his livelihood and threw his family
Speaker 1: life into disarray. Tragically, A Koyo had once fought against
Speaker 1: the disease that eventually robbed him of his sight by
Speaker 1: volunteering to distribute drugs that help prevent transmission of river blindness.
Speaker 1: The River Onane runs through Babagulu and is a perfect
Speaker 1: breeding ground for the black flies that swarm through the village,
Speaker 1: infecting people with filarial worms that cause river blindness. A
Speaker 1: Koyo is one of the many living in the village
Speaker 1: with the disease. Community leaders think that up to three
Speaker 1: percent of the community is blind. A Koyo felt the
Speaker 1: need to help, so he volunteered to help distribute ivermectin.
Speaker 1: These programs rely solely on unpaid drug dishries readers to
Speaker 1: work within their communities. He would travel to neighboring villages,
Speaker 1: often deep in the bush, to distribute the drugs. He
Speaker 1: was often bitten during his travels. One day, his village
Speaker 1: had a stock out of the drug and he stopped
Speaker 1: taking it. I was told to deliver all the drugs
Speaker 1: and then I would take it later once I started
Speaker 1: to have symptoms, he remembers, but then there were no
Speaker 1: more drugs to take. He then ended up missing distribution
Speaker 1: programs in his village because he was out fishing in
Speaker 1: forest streams. In twenty ten, a Koyo started to have
Speaker 1: difficulties seeing, and in twenty eleven he went completely blind.
Speaker 1: His son, Ato, does not go to school and had
Speaker 1: to quit his job because of the stress of caring
Speaker 1: for his father. Itto has a number of nodules on
Speaker 1: his torso and forehead. The adult worms that cause river
Speaker 1: blindness live in these fibrous nodules. Taking care of his
Speaker 1: father is a full time job. Ito also suffers from
Speaker 1: epileptic seizures about four times a month. Researchers have noted
Speaker 1: a potentially causal relationship between UNCO Sarkaiais infection and forms
Speaker 1: of epilepsy found in Africa. I depend totally on my wife.
Speaker 1: She feeds and dresses me, says a ko Yo. Even
Speaker 1: my wife doesn't have a job. After I lost my sight,
Speaker 1: we couldn't send any of our children to school.
Speaker 2: That's horrible.
Speaker 1: Yeah, it's a tough and unfortunately not uncommon story.
Speaker 2: Yes, so that was adapted from an article titled Revealing
Speaker 2: the Neglect river Blindness from March thirtieth, twenty eighteen on
Speaker 2: the website for Drugs for Neglected Diseases Initiative, and we
Speaker 2: will link to that story on our website. And you
Speaker 2: should definitely check it out because not only is there
Speaker 2: more story to it, but there's also a really cool
Speaker 2: video which is the story animated along with a traditional
Speaker 2: song recorded in a Koyo's region about river blindness. So
Speaker 2: definitely check that out. Hi, I'm erin Welsh and I'm
Speaker 2: erin alman Updike and this is this podcast will kill you. Welcome,
Speaker 2: Welcome to another parasitic disease episode of our podcast.
Speaker 1: I'm very excited about another parasitic disease, another vector born disease.
Speaker 2: Yeah, me too. It's super complicated, which gives us an
Speaker 2: opportunity to talk about all kinds of different aspects of
Speaker 2: this parasite, of this vector, of the human side of disease,
Speaker 2: of the history it's I think complex is one word.
Speaker 1: I think it's I think it's classic TPWKY.
Speaker 2: Aaron, Yeah, it actually it really is. It is. Yeah,
Speaker 2: So what are we even covering this week?
Speaker 1: Erin we are covering oncossarchiasis.
Speaker 2: Aka river blindness.
Speaker 1: Yeah.
Speaker 2: Yeah.
Speaker 1: It is truly a very classic TPWKY episode in so
Speaker 1: many ways.
Speaker 2: And speaking of classic TPWKY, we have to start this
Speaker 2: episode with a quarantiny A quarantiney. What are we drinking
Speaker 2: this week?
Speaker 1: We're drinking as the worm turns.
Speaker 2: This is one of my favorite quarantine names.
Speaker 1: We went we went back and forth for a long time,
Speaker 1: but Aaron went out, it is very good.
Speaker 2: Well, and so I think that we were like, well,
Speaker 2: we should save this because we're gonna do more wormy
Speaker 2: parasites in the future, and this is a really good name.
Speaker 2: Should we do something else for this? But I found
Speaker 2: a quote from a researcher who was describing these that
Speaker 2: describes the worms as being undulating and turny, and so, like,
Speaker 2: you know, it was just too good to pass up.
Speaker 1: I mean, they are very turny worms, Like, definitely they are.
Speaker 2: And also I really feel like now that we're getting
Speaker 2: into the whole like worm and world. Swapping out those
Speaker 2: two words and idioms or whatever, We've got a whole
Speaker 2: host of opportunities for future quarantine names exactly.
Speaker 1: This is not going to be the end of the
Speaker 1: worm me world phrase at all.
Speaker 2: It's a it's a small worm, after all, I can't
Speaker 2: remember the other ones sitting on top of the worm.
Speaker 3: Keep an ear out, Aaron. What is in as the
Speaker 3: Worm turns? Okay, yes, let's let's do that. In as
Speaker 3: the Worm Turns is cognac ginger, simple syrup, lemon juice,
Speaker 3: and a splash of sparkling water, and you garnish it
Speaker 3: with some candy ginger. It's actually really refreshing and good.
Speaker 1: Yeah, it sounds really good. It sounds both like warming
Speaker 1: and refreshing somehow.
Speaker 2: Yeah. And we will post the full recipe for this
Speaker 2: quarantini as well as our non alcoholic plus sy burrita
Speaker 2: on our website This podcast will kill You dot com
Speaker 2: as well as on all of our social media channels,
Speaker 2: so make sure you follow us there.
Speaker 1: Excellent. Any other business that we should attend to before
Speaker 1: we dive into this very interesting episode.
Speaker 2: There's the usual stuff. Go to our website. It contains
Speaker 2: links for merch for bookshop dot Org affiliate account for
Speaker 2: Goodreads reading list, for transcripts, for alcohol free episodes, for anything.
Speaker 2: Any source you ever want to find on that we
Speaker 2: reference on this podcast, you can find it there.
Speaker 1: Yeah, definitely check out our website.
Speaker 2: Okay, is there anything else, Sarin?
Speaker 1: I think that you pretty much covered it quite well.
Speaker 2: Wonderful, wonderful. Well. In that case, should we dive into
Speaker 2: the episode.
Speaker 1: Yeah, let's take a quick break and then we'll dive
Speaker 1: into the biology. So, Ancosarchiasis is a disease that is
Speaker 1: caused by a nematde around worm named Anco circa volvulus,
Speaker 1: which is a type of worm known as a filarial worm,
Speaker 1: which means it's a nema toad transmitted by an arthropod vector.
Speaker 1: In this case. Oncopsychiasis is also the second leading cause
Speaker 1: of infectious blindness worldwide, after trachoma, which is a bacterial
Speaker 1: disease caused by chlamydia trichomitis. So, since this is a
Speaker 1: arthropod vectored worm, let's jump straight into talking about the
Speaker 1: transmission and life cycle of this parasite, shall we.
Speaker 2: Let's do it.
Speaker 1: So, the overall life cycle of this parasite is not
Speaker 1: very dissimilar from a number of vector born diseases that
Speaker 1: we've covered on this podcast, but it is a different
Speaker 1: vector species than we've seen before. In this case, it's
Speaker 1: a black fly in the genus Stimulium. The black fly
Speaker 1: bites your skin generally much like mosquitoes. It's female blackflies
Speaker 1: that bite a human, take a blood meal, and in
Speaker 1: that blood meal ingest microfilaria, which are the earliest teeny
Speaker 1: teeny baby newly hatched larval stages of Onco circa volvulus.
Speaker 1: These microfilariae travel through the fly's gut. This is where
Speaker 1: it gets weird. They penetrate the gut walls, which we've
Speaker 1: seen other parasites do, but in this case they migrate
Speaker 1: to the flight muscles of the fly like very weird,
Speaker 1: very weird. I just have to imagine there's a lot
Speaker 1: of glucose happening, because those are important, powerful muscles, but
Speaker 1: I don't know. So in these flight muscles they live
Speaker 1: for a short time and in that time they mature
Speaker 1: into a second stage larva, and then from there they
Speaker 1: make their way down into the salivary glands near the proboscis.
Speaker 1: They mature one more time into a third stage larva
Speaker 1: and are now infectious, so that when the black fly
Speaker 1: takes its next bite of human flesh, they can be
Speaker 1: out spit out those third stage larva just under our skin.
Speaker 1: So that whole process in the blackfly takes about a week,
Speaker 1: give or take. And now in the human these larvae
Speaker 1: that have been injected just under our skin will worm
Speaker 1: and twirl. As the worm twirls the worm turn, they'll
Speaker 1: worm their little way into our subcutaneous tissue and that
Speaker 1: is where they will live. They'll make a little home
Speaker 1: for themselves in these little subcutaneous nodules that they kind
Speaker 1: of build and create, and they are pretty well protected
Speaker 1: from our immune system, which will become important later on.
Speaker 1: They feed off of our blood and both by actively
Speaker 1: feeding but also just by soaking up nutrients through their cuticle,
Speaker 1: and over a period of about ten to fifteen months
Speaker 1: or so, they mature into adult worms. They mate and
Speaker 1: then begin really leasing thousands of eggs which quickly hatch
Speaker 1: into microfilaria. Every day during the day, these little microfilaria
Speaker 1: worm their way back up to the skin's surface, where
Speaker 1: they can then be ingested by blackflies, which coincidentally bite
Speaker 1: during the day. Thus completing their life cycle.
Speaker 2: Question. I know, so you said that the when the
Speaker 2: L three larvae are injected into a person and they
Speaker 2: form this little subcutaneous nodule that in which they're fairly
Speaker 2: protected from the immune system. How like, why are they
Speaker 2: fairly protected there? Because a lot of things could be
Speaker 2: injected into our skin and not be protected from our
Speaker 2: immune system.
Speaker 1: It's a it's a very good question, and it's a
Speaker 1: it's a question that I don't have a good answer to.
Speaker 1: I will talk in a lot more detail about what
Speaker 1: causes an immune reaction to us, but the question of
Speaker 1: why is it that living worms don't provoke much of
Speaker 1: an immune response in us is a very good one
Speaker 1: and not one that I have a good answer to.
Speaker 2: And is that universally or are there people that do
Speaker 2: show immune responses and are like more protected from this
Speaker 2: parasite than others?
Speaker 1: So people don't tend to show immune responses to the
Speaker 1: living worms aside from the formation of these nodules, which
Speaker 1: you could think of as some kind of immune response,
Speaker 1: because it's kind of like, you know, making a little
Speaker 1: fibrous sheath around those worms and kind of walling them
Speaker 1: off from the body in some ways. But otherwise there's
Speaker 1: not much of an immune response that's provoked by the
Speaker 1: presence of the live worms themselves.
Speaker 2: That's wild I know, it gets wilder and so like
Speaker 2: the immune system isn't even showing like elevated antibodies or
Speaker 2: it's not is it suppressed? Like are people who are
Speaker 2: infected with this worm? Are they more susceptible to other infections?
Speaker 2: Of going like down the rabbit hole of questions here.
Speaker 1: You're going so many miles a minute. Let me, let
Speaker 1: me keep going, and I'm not sure if I'm really
Speaker 1: going to answer your questions or if I'm just gonna
Speaker 1: bring up even more questions. Let's find out.
Speaker 2: Okay, I'm along for the ride either way.
Speaker 1: Excellent, good, I'm so glad. Okay, So these adult worms
Speaker 1: that are living in these nodules, they can live for years.
Speaker 1: We're talking ten to fifteen years or more. Oh yeah, okay,
Speaker 1: and this whole time they're producing thousands, if not millions,
Speaker 1: of microflaria that whole time, not continuously. They kind of cycle,
Speaker 1: like every two to four months or so, they'll have
Speaker 1: a cycle. But anyways, ten to fifteen years.
Speaker 2: I have an estimate that I wrote down that because
Speaker 2: I was so horrified. So, the number of microfilaria released
Speaker 2: from one female adult worm during its life life of
Speaker 2: ten to fifteen years is estimated to be greater than
Speaker 2: ten million.
Speaker 1: Yeah that seems about right, because it's like two to
Speaker 1: three hundred thousand per cycle. Yeah. Yeah, that's a lot
Speaker 1: of lost, it really is. Okay, And so before we
Speaker 1: get into what the symptoms of this disease are, what
Speaker 1: I want to tell you. You're going to get mad
Speaker 1: at this. All of the symptoms that we see stem
Speaker 1: not from the worms themselves, but from our immune response
Speaker 1: to the worms.
Speaker 2: Oh but hold on. You made a very strong point
Speaker 2: of saying the living worms. So I'm guessing these are
Speaker 2: dead worms.
Speaker 1: You are exactly right.
Speaker 2: But you're right. I was like, wait a second, errand
Speaker 2: then I remember.
Speaker 3: I know.
Speaker 1: So it turns out that they do not trigger these
Speaker 1: intense immune reactions until they die. So of course we
Speaker 1: have to answer the quiet why the heck? And how
Speaker 1: the heck? So it's thought that the immune response that
Speaker 1: is triggered is in part due to proteins and other
Speaker 1: like inflammatory markers that are released by the dying worms themselves.
Speaker 1: So proteins and things that are inside the worms, but
Speaker 1: then not accessible to our immune system until that worm dies. Okay,
Speaker 1: but far more importantly and interestingly, it's also thought to
Speaker 1: be due largely to the release of the bacterial endosymbiants
Speaker 1: that they harbor.
Speaker 2: Say what, it's so strange. Wolbachia has so many mysteries
Speaker 2: that surround it.
Speaker 1: So many mysteries. So we have talked about wolbachia on
Speaker 1: this podcast before, briefly in I think our dengay episode,
Speaker 1: because they're important in the context of mosquitoes that transmit
Speaker 1: dungay and other arboviral diseases. As a recap Willbakia are
Speaker 1: a genera of bacteria that often inhabit the guts of
Speaker 1: insects and other invertebrates. But it turns out that in
Speaker 1: filarial nematodes like oncocercavolvulus, but also Wucheria bancroftyi, which is
Speaker 1: the coosative agent of lymphatic philoriasis and other nematodes, these
Speaker 1: bacteria are essential endosymbionts. So without these bacteria, the nematodes
Speaker 1: cannot survive or reproduce. We still don't know exactly what
Speaker 1: it is that they are doing necessarily, but we do
Speaker 1: know that they are essential to the process of embryogenesis.
Speaker 1: So eggs can't develop into worms without the presence of
Speaker 1: these bacteria which are transmitted transovarially.
Speaker 2: That is so interesting.
Speaker 3: I know.
Speaker 1: And it seems that based on a lot of data,
Speaker 1: the release of these bacteria from dead worms is thought
Speaker 1: to be a major part of the trigger for our
Speaker 1: immune response.
Speaker 2: And so how does this trigger look different compared to
Speaker 2: like other parasitic infection triggers.
Speaker 1: So that's what's so interesting is that what we see
Speaker 1: is still a lot of eosinophil response, which is what
Speaker 1: you would expect with a parasitic disease, not solely though.
Speaker 1: Antibodies have a large role as well in the inflammation
Speaker 1: and the immune response to acopsychiasis, as do neutrophils and
Speaker 1: other lymphocytes, and these are all different types of white
Speaker 1: blood cells. But you still do see a really large
Speaker 1: eosinophil response, which is interesting. So maybe those are responding
Speaker 1: to the worm parts, and it's the neutrophils and lymphocytes
Speaker 1: and antibodies that are responding to the bacteria. Who knows,
Speaker 1: We don't fully know. But I'm also going to put
Speaker 1: a pin in that, and I just want for us
Speaker 1: to remember how important while bakia are because we'll talk
Speaker 1: more about them in the current events section. Oh yeah, yes,
Speaker 1: all right, So then what does this disease actually look
Speaker 1: like in its mildest form. It's possible that the only
Speaker 1: symptoms that you would have are these nodules that we've
Speaker 1: talked about. So these nodules are very kind of hard,
Speaker 1: deep subcutaneous lumps, I guess is the best word, often
Speaker 1: around the hip girdle, but you can also have them
Speaker 1: really anywhere throughout your body. They tend to be most
Speaker 1: prominent where you have like a bone, just because then
Speaker 1: you have less subcutaneous tissue between your bone and your skin.
Speaker 1: But in terms of symptoms that we see in the
Speaker 1: mildest symptoms present as a skin rash, which is usually
Speaker 1: what we call maculo popular. That means a flat area
Speaker 1: of rash with a lot of little bumps on it
Speaker 1: that is incredibly itchy. Right, I think it's it's hard.
Speaker 1: The word itchy. I feel like it doesn't do. It
Speaker 1: doesn't right, it doesn't invoke I think the response that
Speaker 1: that this really deserves no. Yeah, so it's yeah, I
Speaker 1: wish I had a better word than just incredibly itchy.
Speaker 1: So this rash can resolve in some cases, although the
Speaker 1: disease itself does not resolve, like we said, these worms
Speaker 1: can live for years. But more commonly, this rash can
Speaker 1: become chronic and can actually generalize across the body instead
Speaker 1: of being present in just discrete patches. And this, as
Speaker 1: you can imagine, leads to even more severe itching. And
Speaker 1: then as our immune response ramps up, the way that
Speaker 1: our skin kind of heals results in very severe scarring.
Speaker 1: It's what's called like henification, like a like a lichen
Speaker 1: that grows on a tree. Yeah, so it's like our
Speaker 1: skin becoming really thick and leathery. At this stage, it
Speaker 1: can lead to hyper pigmentation of the skin, so it
Speaker 1: becomes very very dark in patches. And like we talked
Speaker 1: about in our leshmaniasis episode, these type of skin manifestations
Speaker 1: can be associated with a lot of stigma, and so
Speaker 1: they can be debilitating, not only in the physical sense,
Speaker 1: like the amount of itching I saw it described where
Speaker 1: some people couldn't even sleep except for on their knees
Speaker 1: and elbows because of the pain of the itching.
Speaker 2: Yeah. I saw some descriptions of people literally like burning
Speaker 2: their skin because it was so horrifyingly itchy.
Speaker 1: Itchy, but it can also be debilitating in the way
Speaker 1: that it is stigmatizing as well. And then over years
Speaker 1: of this infection, the changes can become even more chronic,
Speaker 1: and the descriptors of these changes in the literature I
Speaker 1: think are also pretty stigmatizing. But basically what can happen
Speaker 1: is the skin can end up with its elasticity completely
Speaker 1: destroyed because of all of that damage to the kind
Speaker 1: of mid layers of the skin. So then the very
Speaker 1: top layers become really thinned out, they become atrophied, they're
Speaker 1: quite wrinkily, and they can just sort of hang off
Speaker 1: of the body. You can lose pigment entirely in those
Speaker 1: areas because of all the atrophy, and so the skin
Speaker 1: manifestations can be severe and this whole time, even as
Speaker 1: it becomes chronic that itching persists.
Speaker 2: And okay, question real quick again about the nodules when
Speaker 2: like where those nodules exist is where the blackfly has
Speaker 2: bitten you, or like how much how much variation is there?
Speaker 1: Yeah, there's quite a lot of variation, which is so interesting.
Speaker 1: So from what I read, black flies often like to
Speaker 1: bite on lower extremities, so they really bite a lot
Speaker 1: on legs, But these nodules tend to be present on
Speaker 1: the hips or even the forehead and on the head.
Speaker 1: So that would suggest that these adult worms can travel
Speaker 1: and decide where they're going to make their nodule home.
Speaker 1: But it also means that the microfilaria which are traveling
Speaker 1: to the skin surface can also travel a really long way.
Speaker 1: They can go pretty much anywhere in our body, right, Yeah.
Speaker 2: And I also thought I read somewhere too about like
Speaker 2: because and I know you haven't gotten to this part yet,
Speaker 2: but the Americas versus Africa in terms of the location
Speaker 2: and frequency of the skin nodules blackflies have different biting
Speaker 2: patterns right on, Like, they bite more on the upper
Speaker 2: half of the body and the America's compared to Africa,
Speaker 2: where it's on the lower parts of the body.
Speaker 1: I would believe that because I did read about a
Speaker 1: lot more forehead nodules and things in the Americas compared
Speaker 1: to in Africa. Yeah, okay, okay, So that's kind of
Speaker 1: all of the skin manifestations, which is one of the
Speaker 1: most important parts of this disease. The other is, of course,
Speaker 1: the ocular or the eye manifestations. Well, that's where it
Speaker 1: gets the common name river blindness. So as these microfilaria
Speaker 1: travel out of nodules and towards the skin, some of
Speaker 1: them can travel to the eye. In the eye, the
Speaker 1: microfilaria that die also cause a localized inflammatory reaction and
Speaker 1: this results in a number of different manifestations kind of
Speaker 1: The most common one is called sclerosing keratitis, which is
Speaker 1: where the cornea of your eye, which is the part
Speaker 1: that covers like your iris and your pupil that becomes
Speaker 1: inflamed and then will scar over. So this starts with
Speaker 1: a haziness around the edges of the cornea and then
Speaker 1: will eventually go in to encompass the entire thing, causing
Speaker 1: complete blindness. Oh yeah, it's not only sclerosing keratitis, because
Speaker 1: you can have these worms that end up in the
Speaker 1: posterior part of your eye, which can cause inflammation of
Speaker 1: the retina and similar kinds of damage due to inflammation
Speaker 1: in all parts of the eye. And I think it's
Speaker 1: also important to point out that these microfilaria can travel
Speaker 1: kind of throughout the body and invade, for example, our
Speaker 1: lymphatic system, and they've been found in a number of
Speaker 1: different organs. Like, if you sample organs from someone who's
Speaker 1: died who was infected with ancosirchiasis, you can find microflaria
Speaker 1: in a number of different organs, but we don't really
Speaker 1: have a good handle on what kind of disease might
Speaker 1: be caused by that. It's really the skin and the
Speaker 1: eye that are the two most common organs affected, right,
Speaker 1: So yeah, I also want to mention because it's important,
Speaker 1: but also because it was brought up in our first
Speaker 1: hand account. There does seem to be increasing evidence that
Speaker 1: infection with unchosirchiasis is also associated with an a increased
Speaker 1: risk of epilepsy.
Speaker 2: Is there any suggestion as to what the mechanism could be?
Speaker 1: None at all, which is the hardest part. So there's
Speaker 1: a lot of epidemiological evidence of association, but there's not
Speaker 1: really any data on what could be the cause or
Speaker 1: the mechanism. So we don't really know if it is
Speaker 1: in fact oncosyarchiasis or something else. But there's epidemiological evidence
Speaker 1: for this association, so I thought it was important to mention.
Speaker 2: Yeah, definitely.
Speaker 1: Yeah, So yeah, that's kind of the basic overall picture.
Speaker 1: I think it's interesting that there does seem to be
Speaker 1: some strain differences. So in parts of West Africa, it's
Speaker 1: long been noticed that in the savannah regions the rates
Speaker 1: of blindness due to Anco circa were much higher than
Speaker 1: in forested regions of West Africa. And in those savannah regions,
Speaker 1: the rates of blindness really strongly correlate with the intensity
Speaker 1: of infection. So the more heavily infected somebody is, the
Speaker 1: higher their risk of ocular complications. But in other areas,
Speaker 1: like in forested regions, that that doesn't seem to be
Speaker 1: the case. And so it turns out that there are
Speaker 1: different strains of Anco cercovolvulus. But what I think is
Speaker 1: so interesting about this is that there's also some evidence
Speaker 1: that part of the differences in these strains is how
Speaker 1: much wolbakia they carry erin.
Speaker 2: It's well, and it's not it doesn't seem to be
Speaker 2: just that, as I'll get into, but it's really Yeah,
Speaker 2: that's definitely an interesting component for sure.
Speaker 1: Oh my gosh. So that's pretty much the whole biology,
Speaker 1: aside from treatment. Do you have any questions arin before
Speaker 1: I talk briefly about treatment.
Speaker 2: Did you say already how long these worms are?
Speaker 1: No, I was just about to Okay, these worms that
Speaker 1: adult females get to be up about thirty centimeters thirty
Speaker 1: to eighty centimeters long, which is over a foot.
Speaker 2: That is two very long, and yeah wow.
Speaker 1: And then in each nodule you'll also have one or
Speaker 1: two males. But what is fascinating is that these males
Speaker 1: travel around nodule to nodule. They go like beg boop
Speaker 1: boop boop, traveling along because the females have to be
Speaker 1: reinseminated every time they have a reproductive cycle.
Speaker 2: Hmmm. Interesting. Cool.
Speaker 1: By the way, the microfilaria are so so so tiny.
Speaker 1: They're like two to three hundred microns, which is about
Speaker 1: the length of two sheets of paper is wide, that
Speaker 1: makes sense.
Speaker 2: Very tiny, Yeah, it's very.
Speaker 1: Small, and then they grow up to be quite large.
Speaker 1: Yeah yeah, okay, So what do we do about it? Yeah,
Speaker 1: we do have something that we can do, which is
Speaker 1: phenomenal treatment. Though, like I said, we can't just kill
Speaker 1: all of the adult worms outright because that would trigger
Speaker 1: a huge immune response. So treatment is actually via a
Speaker 1: drug called ivermectin, which is an anti parasitic that is
Speaker 1: very effective at reducing the load of microfilaria in the skin.
Speaker 1: For several months at a time, which helps not only
Speaker 1: with symptoms, but it also reduces the risk of complications
Speaker 1: like blindness. It doesn't, though, kill the adult worms at all,
Speaker 1: not even slowly. What's so fascinating is that ivermectin is
Speaker 1: a neurotoxin and it works on channels that we have
Speaker 1: as vertebrates as mammals, but we have a blood brain barrier,
Speaker 1: so in us it doesn't have the same effects. Oh,
Speaker 1: isn't that cool. So it's actually a very safe drug,
Speaker 1: which is awesome, yeah for humans, not for worms. But
Speaker 1: while it causes a flaccid paralysis and eventual death in
Speaker 1: the microfilaria, in the adult worms, what it does is
Speaker 1: just kind of block them from releasing eggs for a
Speaker 1: short period of time, so it's thought to kind of
Speaker 1: paralyze their reproductive tract, but not much else. Okay, which
Speaker 1: is so fascinating. I tried so hard to get the like,
Speaker 1: why why can't this kill an adult worm? But I
Speaker 1: don't have the answer to that. I don't know.
Speaker 2: Yeah, that's very it's so interestrange.
Speaker 1: Yeah, but that's the biology of ancosnychiasis.
Speaker 2: Oh, it's a it's a big one. It's a big
Speaker 2: it's so interested, it's so interesting. There's so many steps,
Speaker 2: and there are so many different components. And that's sort
Speaker 2: of the theme also that I will talk about in
Speaker 2: the history.
Speaker 1: Would you please, would you please? I'd love to hear it.
Speaker 2: Let's take a quick break first, and then I'll dive
Speaker 2: right in. I feel like I start off most of
Speaker 2: these histories, or at least a lot of these histories,
Speaker 2: especially in episodes about parasites, saying that you know, this
Speaker 2: disease has been around forever, like millions of years forever,
Speaker 2: and then I go on to talk about how there
Speaker 2: was this fossilized poop found or evidence of infection in
Speaker 2: a mummy. And so I was surprised when I started
Speaker 2: researching for this episode that I wasn't finding any of
Speaker 2: that for uncosychiasis. Where were my ancient Egyptian papyri, Where
Speaker 2: were my coprolites? None of it. Maybe they are out
Speaker 2: there still waiting to be found, either by me in
Speaker 2: the literature or by a budding paleo epidemiologist or something
Speaker 2: like that. Let us know if you find anything. But
Speaker 2: most articles I read discussed the early history of uncosirchiasis
Speaker 2: as starting either at the evolutionary roots of the parasite
Speaker 2: that causes the disease, or they jumped ahead to the
Speaker 2: early scientific work classifying this parasite and detailing its transmission
Speaker 2: route and disease characteristics. And so we'll get to that
Speaker 2: part eventually, But first I want to go back, of course,
Speaker 2: to the evolutionary ecology of this parasite. Yes, did it
Speaker 2: come from? How did it get to be distributed the
Speaker 2: way it currently is, and what role does the ecology
Speaker 2: of this complex parasitic infection play in its establishment and
Speaker 2: continued persistence. Okay, here we go. This disease, ancosarchiasis exists
Speaker 2: in two main areas of the world, Africa, where ninety
Speaker 2: nine percent of cases occur in Central and South America,
Speaker 2: where it's a lot more localized and less prevalent, partly
Speaker 2: because of control efforts that I'll go into later, and
Speaker 2: partly because of the history and ecology of the parasite itself.
Speaker 2: And so based on this distribution, it's probably not that
Speaker 2: surprising that the parasite evolved in Africa and then was
Speaker 2: brought to the Americas at some point during the slave
Speaker 2: trade beginning in the early sixteenth century.
Speaker 1: Makes sense, But what.
Speaker 2: May be surprising is that although the genus Anco circa
Speaker 2: is likely millions of years old and also originated in Africa,
Speaker 2: the species that causes river blindness, Anco Circa volvulus, is
Speaker 2: a relatively recent parasite of humans.
Speaker 1: Okay. I saw that somewhere, and I was like, what,
Speaker 1: I didn't mean anymore because I wanted to.
Speaker 2: Okay, Well, because genetic analyzes that have compared like many
Speaker 2: different species in the Anca cerca genus show that Anca
Speaker 2: circa volvulus likely evolved from the ancestor of Anca Circa ochngi,
Speaker 2: which is a parasite of African savannah bovids.
Speaker 1: Okay, but I'm so confused by that, Aaron, because Anco
Speaker 1: circa volvulus is pretty much a human specific parasite.
Speaker 2: Yes, So that is since this this evolutionary pathway, like
Speaker 2: this speciation is supposed to have occurred only within the
Speaker 2: last ten thousand years or so, because it's supposed to
Speaker 2: correspond to the period when cattle were domesticated, and that's
Speaker 2: when humans would have come into contact.
Speaker 1: What are you telling me?
Speaker 2: Well, and there's a side note too. Cattle were domesticated
Speaker 2: between like ten thousand and thirty seven thousand, six hundred
Speaker 2: years ago in parts of Asia, but domestication is actually
Speaker 2: thought to take place later in Africa, like maybe between
Speaker 2: four thousand or fifteen hundred years ago. What And so
Speaker 2: it might be that this parasite evolved so rapidly.
Speaker 1: Yeah, that's bananas.
Speaker 2: I know. And there's more on this too, Oh my gosh.
Speaker 2: So for much of that ten thousand year history, let's
Speaker 2: just call it ten thousand years, this parasite stayed in Africa.
Speaker 2: It drove human settlement patterns in such a way that
Speaker 2: perhaps people would settle near a river or a lake.
Speaker 2: And then as more and more people developed this horrifically
Speaker 2: itchy skin condition or they lost their vision, they moved
Speaker 2: away to land that was further away from these sources
Speaker 2: of water. So the land was often less arable, it
Speaker 2: was more susceptible to erosion. And by the way, this
Speaker 2: is still happening today, like, for example, in parts of Ghana,
Speaker 2: where people have moved away from these high anchro psychiasis
Speaker 2: prevalence areas to more crowded, less arable areas that have
Speaker 2: led to an increase in nutritional deficiencies and food instability.
Speaker 2: But I'm getting ahead of myself. So yeah, so let's
Speaker 2: go back to this remarkably short evolutionary history. This is
Speaker 2: an obligately human parasite. Yeah, like they have shown, you know,
Speaker 2: incidental infections in a gorilla I think I've seen, or
Speaker 2: in some other animals, but it is human specific.
Speaker 1: There's no animal reservoirs for Anco circa volvulis. It's a
Speaker 1: human disease.
Speaker 2: Right, And so within a relatively short time span, like
Speaker 2: let's say, conservatively ten thousand years, this parasite went from
Speaker 2: a bovine host to just humans as hosts truly, and
Speaker 2: so this definitely seems like there were some strong forces
Speaker 2: that drove speciation. And there's also some evidence that suggests
Speaker 2: that there might be speciation happening currently within the parasite
Speaker 2: species on Cacerco vulvulis.
Speaker 1: Stop it.
Speaker 2: Yes, and you touched on a little bit of this
Speaker 2: and talking about the strains, okay, and I want to
Speaker 2: talk a little bit more about that and about the
Speaker 2: ecology of this system overall. So, as you mentioned, this
Speaker 2: parasite species is transmitted by multiple species of simuliad blackflies,
Speaker 2: and the distribution and habitat preferences of these blackflies varies
Speaker 2: quite a bit. And warning this is going to be oversimplified, okay,
Speaker 2: But in Africa, for instance, you have some blackfly species
Speaker 2: that are savannah dwelling and those that are forest dwelling.
Speaker 2: And you mentioned that there are vana strains of the
Speaker 2: parasite and forest strains of the parasite, and these different
Speaker 2: blackfly species transmit those corresponding strains of unca cercovulbulus. Yeah,
Speaker 2: and what happens when researchers try to take a savannah
Speaker 2: strain of the parasite and put it in a forest
Speaker 2: dwelling black fly, They found that the parasite developed poorly
Speaker 2: or not at all, And the same thing happened with
Speaker 2: the forest strain of the parasite in the savannah dwelling blackfly.
Speaker 2: What ain, Yes.
Speaker 1: And there's some regions that they can be coinfected. So
Speaker 1: is that maybe like I'm getting too too complicated.
Speaker 2: Well matter, what it seems is that that's fairly uncommon,
Speaker 2: like it's happening more today, possibly because of control efforts
Speaker 2: and how that sort of changed the landscape of disease
Speaker 2: in this case, but at least like historically, it really
Speaker 2: does seem that there has been sort of this something,
Speaker 2: some sort of barrier preventing the mixing of this like
Speaker 2: savannah strain and this forest strain of the parasite. What
Speaker 2: and so, what some researchers think is that these different
Speaker 2: parasite strains may actually be diverging from one another.
Speaker 1: So we're gonna end up with two species.
Speaker 2: Mm hmmm, possibly, Oh my gosh. I mean. And it
Speaker 2: also makes sense because these parasites rely so heavily on
Speaker 2: these flies for their transmission and development that they may
Speaker 2: become in a sense, reproductively isolated quite easily. So basically
Speaker 2: how I was thinking of it is that like the
Speaker 2: adaptations that these parasites have to survive and develop in
Speaker 2: one black fly species might not be the same ones
Speaker 2: that would allow them to do the same in others.
Speaker 2: And for what it's worth, these parasites don't seem to
Speaker 2: be harmless hitchhikers for these flies, like at least for
Speaker 2: some of the species or vector parasite complexes. And there
Speaker 2: have been some studies confirming that some blackflies show innate
Speaker 2: and acquired resistance to filarial infection.
Speaker 1: I love that. I love when insect vectors have fight responses.
Speaker 2: Oh yeah, and so because there's such like let's call
Speaker 2: it a tenuous relationship between the parasite and vector. It
Speaker 2: might be that putting all of your like, you know,
Speaker 2: adaptive eggs in one blackfly basket might be a favored
Speaker 2: strategy in terms of evolution.
Speaker 1: Yeah, you get really well adapted to that specific immune response.
Speaker 2: Mm hmmmm hmm. In any case, this diversity of blackfly
Speaker 2: species and the complicated interactions between different strains of the
Speaker 2: parasite and different species of fly is just one example
Speaker 2: of the incredibly complex disease ecology of this parasitic infection.
Speaker 2: And I also think that this episode is a great
Speaker 2: opportunity to talk a bit about disease ecology in this context. Yeah,
Speaker 2: because we get a lot of emails from people asking
Speaker 2: us the difference between epidemiology and disease ecology, and I
Speaker 2: feel like, even though I technically have a degree kind
Speaker 2: of in both, I still don't feel very qualified to
Speaker 2: go into those differences same, but I'm gonna try. So
Speaker 2: there's a lot of overlap between these two fields, and
Speaker 2: I think that this disease is a good way to
Speaker 2: show at least some examples in ways that the approaches
Speaker 2: or research questions could be different. And so overall, epidemiology
Speaker 2: is often defined very broadly as the study of patterns
Speaker 2: of disease and health in populations, and disease ecology is
Speaker 2: more concerned with the role that the environment and evolution
Speaker 2: play in the interactions between host and parasite. And so,
Speaker 2: for example, in the case of onchosychiasis, the transmission of
Speaker 2: the parasite depends on so many things that are influenced
Speaker 2: by the environment. Which vector species is present, how abundant
Speaker 2: is that vector species, what are the things that determine
Speaker 2: its abundance, what season it is, what habitat it's in,
Speaker 2: and within a certain season or even a certain time
Speaker 2: of day, things like relative humidity, temperature, wind velocity, light intensity, rainfall,
Speaker 2: all of which could influence transmission in some way, And
Speaker 2: there's evidence to suggest that a lot of these factors do.
Speaker 2: And so a disease ecologist might ask something like, how
Speaker 2: does the seasonal biting activity of different Simulia blackfly species
Speaker 2: change across these different environments, and how is that associated
Speaker 2: with the output of L three larvae by those blackflies?
Speaker 2: Like all of these things are sort of what role
Speaker 2: does the environment play in the transmission and getting a
Speaker 2: better sense of the different factors at play can help
Speaker 2: to focus control efforts in a lot of ways to
Speaker 2: make them more impactful or more efficient, like, for instance,
Speaker 2: is there a distinct wet season, like a distinct wet
Speaker 2: and a distinct dry season, and should one of those
Speaker 2: seasons be targeted more for breeding sites for the flies?
Speaker 2: And should that time of year be targeted more for
Speaker 2: habitat removal or habitat spraying. And an epidemiologist, conversely might
Speaker 2: ask about the geographical variation in infection prevalence and how
Speaker 2: these prevalences might be associated with past spraying or ivermectin campaigns,
Speaker 2: and a lot of these epidemiological questions. The way I
Speaker 2: look at it is that they helped to get a
Speaker 2: sense of the extent of the disease, how human behavior
Speaker 2: or experience plays a role in the exposure, or to
Speaker 2: measure progress in control efforts. Aaron, did I miss anything withology.
Speaker 1: That was really good? Also? How fun to get to
Speaker 1: talk about, like just broadly disease ecology and epidemiology.
Speaker 2: Well, it's it's really fun because as I was reading
Speaker 2: about the ecology of this system, and I didn't do like,
Speaker 2: I didn't do a very comprehensive job of explaining it.
Speaker 2: But I was struck by the number of questions that
Speaker 2: you could ask about, how is the black fly, you know, feeding,
Speaker 2: like at what time of day, what part of the
Speaker 2: body is it feeding on? What time of year? How
Speaker 2: does that? How does the current filarial load in the
Speaker 2: fly influence behavior? Like all of these things, I know
Speaker 2: another PhD PhD Take two.
Speaker 1: It's just so funny erin because as you're talking about
Speaker 1: all that, like I can hear how excited you are,
Speaker 1: and I'm also getting so excited, and so it's just
Speaker 1: so funny that like, of course, this is a disease
Speaker 1: that would get us so like excited to be asking
Speaker 1: these questions, and like that's why we did the degrees
Speaker 1: that we did. Like it's just it all comes full circle,
Speaker 1: like yep.
Speaker 2: And I love too, Like this is such a good
Speaker 2: example of, you know, the ways in which that that
Speaker 2: barrier between epidemiology and disease ecology isn't really a barrier
Speaker 2: at all. It's a very fluid you.
Speaker 1: Know, eco epidemiology. Yo, there we go.
Speaker 2: And so it's really cool to see how, you know,
Speaker 2: the data derived from these two different fields in terms
Speaker 2: of research questions could be used synergistically or in the
Speaker 2: same in the same like applications.
Speaker 1: Well, I'm also love it. Can we get some immunologists
Speaker 1: to join this party too, because I still can't get
Speaker 1: over that this is a newly evolved human specific parasite
Speaker 1: that is so good at evating our immune response, Like,
Speaker 1: are you kidding me? I know we should get back
Speaker 1: to ancos chiasis.
Speaker 2: Let's get back to anchoerchiasis. Yeah, we do need to
Speaker 2: do a career's episode one day, we have. We want
Speaker 2: to have other people to find what an epidemiologist does
Speaker 2: and what a dizzas ecologist does. But yeah, I just
Speaker 2: wanted to kind of go through this because I think
Speaker 2: ancoserchias is with its you know, three player cast of
Speaker 2: human parasite vector and its super close ties to environmental factors,
Speaker 2: is a great way to think about how the environment
Speaker 2: ends up shaping transmission patterns leading to human disease.
Speaker 1: Absolutely.
Speaker 2: Okay, So I've talked for a very long time about
Speaker 2: evolutionary history and disease ecology in general, but I haven't
Speaker 2: even started on the written history of anchoschiasis.
Speaker 1: Well let's get started.
Speaker 2: But don't worry. I mean, it's a pretty straightforward story
Speaker 2: so much. It's much more straightforward than it's ecology. I'll
Speaker 2: say that before I begin. I also want to acknowledge
Speaker 2: that before the quote unquote discoveries of Western scientists regarding
Speaker 2: this disease, the people who lived in Africa among this
Speaker 2: disease for thousands of years were already well aware of
Speaker 2: several aspects of anarchiasis, including the association with rivers or
Speaker 2: bodies of water, the role of the blackfly and transmission,
Speaker 2: and both the skin and blindness manifestations of disease. But
Speaker 2: you know, this long standing knowledge is rarely, if ever
Speaker 2: noted in the official histories of scientific achievements, not just
Speaker 2: in terms of uncles psrachiasis, but in terms of many
Speaker 2: many diseases that we have covered or will cover. So
Speaker 2: taking that into consideration, where do these official histories begin?
Speaker 2: In eighteen seventy four, there was a British naval surgeon
Speaker 2: by the name of John O'Neill who was assigned to
Speaker 2: the HMS Decoy off the coast of what is now Ghana.
Speaker 2: He noticed several people living along the western coast of
Speaker 2: Africa had an itchy and irritating skin disease with nodules
Speaker 2: and pustules. Locally it was called craw craw, and he
Speaker 2: thought at first could this be scabies? And so he
Speaker 2: examined some of these nodules under a microscope, and quote
Speaker 2: succeeded at length in discovering a filaria, which I believe
Speaker 2: to be the immediate cause of complaint, threadlike in form,
Speaker 2: at one time undulating and now twisted as if into
Speaker 2: an inexplicable knot, then having rapidly untwined itself, it curls
Speaker 2: up into many loops. It's a very poetic description of
Speaker 2: this hilaria. Yeah. O'Neill's observations of this parasite were followed
Speaker 2: pretty closely by Rudolph Lukart, who in eighteen ninety received
Speaker 2: a nodule of worms the size of a pigeon's egg
Speaker 2: that an unnamed German surgeon had removed from someone also
Speaker 2: in the Gold Coast. What has now goneah? Actually?
Speaker 1: And how big is a pigeons egg?
Speaker 2: Actually, that's a great question. Let me look it up.
Speaker 2: A pigeon egg is smaller than a chicken egg. Looks
Speaker 2: like to me, it's like half the size to two
Speaker 2: thirds the size.
Speaker 1: Yeah, I would say that.
Speaker 2: So, yeah, he received this nodule the size of this
Speaker 2: pigeons egg from this guy who had sent it to
Speaker 2: him asking for identification, and Lucart looked into it, and
Speaker 2: he didn't make any announcement of his own regarding the
Speaker 2: description of the adult form of this worm, but he
Speaker 2: did tell the famous parasitologist Sir Patrick Manson, who published
Speaker 2: a note in which he gave Lucart credit for both
Speaker 2: the discovery as well as the naming of the worm,
Speaker 2: which eventually became Oncacerca volvulus on caa circa from the
Speaker 2: Greek words meaning barbed tale and volvulus from the Latin
Speaker 2: for to roll or turn as the worm turns. By
Speaker 2: this time, several other helmet species had been discovered in
Speaker 2: Africa and elsewhere, and Oncacerca volvulust didn't really seem to
Speaker 2: attract any particular interest, which I find interesting. Yeah, I mean,
Speaker 2: they simply noted it, as you know, it's probably this
Speaker 2: old disease. And also they seem to think that it
Speaker 2: was more of a rare curiosity rather than a common occurrence.
Speaker 2: But that belief would later be turned on its head. So,
Speaker 2: despite the much higher prevalence of river blindness in Africa
Speaker 2: compared to Central and South America. A good chunk of
Speaker 2: the big leaps forward in terms of understanding this disease
Speaker 2: were made by Ridolfo Roblis and Guatemala. In nineteen seventeen,
Speaker 2: he published a report linking the parasite to blindness as
Speaker 2: well as the dermatitis that had previously been observed, and
Speaker 2: the link between blindness and the parasite wouldn't be discovered
Speaker 2: in Africa for another decade or longer by researchers working there,
Speaker 2: which I find very interesting. Yeah, and I wonder if
Speaker 2: one of the reasons for that is because of the
Speaker 2: biting preferences of the black flies in Central and South
Speaker 2: America compared to Africa, like.
Speaker 1: That they were more kind of visible.
Speaker 2: More visible more no, I mean like in terms of
Speaker 2: the blindness, that there happened to be more nodules on
Speaker 2: the face and head compared to Africa. So I don't know.
Speaker 2: But Roeblis also suggested that Simulidae blackflies might be responsible
Speaker 2: for transmission of the filaria and that removal of the
Speaker 2: nodules might provide relief in symptoms. And speaking of nodules,
Speaker 2: in his quest to see whether these parasitic worms were
Speaker 2: the same species as Anca Cerca volvulus, or if they
Speaker 2: were a New World species, spoiler alert, they're the same species.
Speaker 2: He was wrong. He had a hard time getting the
Speaker 2: worms out of the nodule intact, and so he used
Speaker 2: quote the novel technique of removing the fibrous tissue by
Speaker 2: active digestion in the stomach of a living dog. Yeah,
Speaker 2: that's all the explanation that I found for that one. See,
Speaker 2: he fed the he fed the dog nodule to a
Speaker 2: dog who then presumably post worms.
Speaker 1: Pooped out worms or did he like induce vomiting or something.
Speaker 2: Oh, that's another possibility. I don't know.
Speaker 1: I don't know either. Yep. It's weird that it was effective.
Speaker 2: Honestly, it's weird that he thought of it.
Speaker 1: There's a lot that's weird.
Speaker 2: There's a lot that's weird. And the next big jump
Speaker 2: in Ancaserkias's research was when Donald Blacklock made the link
Speaker 2: that blackflies were responsible for transmitting the parasites through observations
Speaker 2: of the guts of simulium blackflies. Roblaze had just suggested it,
Speaker 2: but Blacklock actually did the experiments. Although again, this link
Speaker 2: I want to say was well known among people who
Speaker 2: had been living there right By the nineteen thirties, interest
Speaker 2: in ancastrakias's had picked up, and scientists had started to
Speaker 2: realize that it was much more widespread than previously thought.
Speaker 2: But they were still missing one big piece of the puzzle,
Speaker 2: the piece that Roblaze had found nearly twenty years before
Speaker 2: the link between the parasite and blindness. In nineteen thirty
Speaker 2: one or nineteen thirty two, I can't remember, a researcher
Speaker 2: named Gene Hassett published a report that showed that in
Speaker 2: a part of the Democratic Republic of Congo, twenty percent
Speaker 2: of the people with uncoserkiasis were blind and fifty percent
Speaker 2: of that population suffered from eye troubles. Unlike in many
Speaker 2: other places in Africa, the nodules and systs were concentrated
Speaker 2: on the head rather than lower down the body, which
Speaker 2: was also kind of the pattern in the Americas. And
Speaker 2: although Hisssett's work seemed to show a clear connection, including
Speaker 2: he found microfilaria throughout the eye, the link wouldn't be
Speaker 2: widely accepted until the mid nineteen forties at the earliest WOW,
Speaker 2: which also coincided with this period of increased European troop
Speaker 2: presence in uncleserciasis prevalent areas, so not unsurprising. Unsurprising. As
Speaker 2: researchers got a better handle on the scope of the
Speaker 2: disease and the devastating effects that it could have, campaigns
Speaker 2: to control or eliminate the disease were started. The earliest
Speaker 2: campaigns targeted the vectors of the parasite, relying on the
Speaker 2: use of DDT, which was developed in nineteen forty one
Speaker 2: and found to be extremely effective as an insect killer
Speaker 2: and also, as Rachel Carson has made us all aware,
Speaker 2: as a killer of many other things. Some of these
Speaker 2: early control programs seemed to actually be quite effective. So,
Speaker 2: for instance, in the Coodera region of Kenya, which had
Speaker 2: been nicknamed the Valley of the Blind due to a
Speaker 2: prevalence of acosarchiasis of seventy percent. Oh my gracious, DDT
Speaker 2: applications over a six to seven month period led to
Speaker 2: eradication of the blackfly vector in that area.
Speaker 1: Wow mm hmm, I know.
Speaker 2: It's like feels weird to be like wow, DDT worked
Speaker 2: really well, But it did until it didn't, and then
Speaker 2: it did until it didn't. Killed a lot of other things.
Speaker 1: Yeah.
Speaker 2: Yeah, Leading into the seventies, which is when probably the
Speaker 2: largest campaign began, the WHO on Chris Archaius's Control Program OCP. Still,
Speaker 2: the strategy for control focused on interrupting transmission by vector elimination.
Speaker 2: In this program, which targeted initially seven countries around the
Speaker 2: Volta Basin of West Africa, with additional areas or countries
Speaker 2: added later on, insecticide was applied either on the ground
Speaker 2: or aerially, and the plan was to continue these types
Speaker 2: of vector control activities for twenty years, the length of
Speaker 2: a female worm's life like the maximum length.
Speaker 1: Yeah, that makes sense.
Speaker 2: But there were several challenges that emerged that either interrupted
Speaker 2: or slowed down progress, and one was that several areas
Speaker 2: were reinvaded by adult flies from outside the target areas.
Speaker 2: Studies showed that some flies in the Simuleum damnosum species
Speaker 2: complex could my grate up to five hundred kilometers Yeah,
Speaker 2: three hundred and ten miles.
Speaker 1: They're really far flyers, which makes it so much more complicated, so.
Speaker 2: Much more difficult. And another issue was insecticide resistance. So
Speaker 2: the OCP adapted to overcome these challenges by rotating different
Speaker 2: insecticides to reduce the likelihood of resistance. And there was
Speaker 2: another development that actually helped to overcome these challenges as well,
Speaker 2: and that was the discovery of ivermectin, which was developed
Speaker 2: in nineteen seventy five and provided for free by Murk
Speaker 2: starting in nineteen eighty eight, and its developers were actually
Speaker 2: awarded a Nobel Prize in twenty fifteen. Yeah, Yeah, that
Speaker 2: was like really changed the landscape of control. This one
Speaker 2: two punch of insecticide and treatment allowed the OCP to
Speaker 2: make incredible strides in Uncas Archias's control. So by two
Speaker 2: thousand and two, it was estimated that the OCP had
Speaker 2: rid two hundred and fifty thousand square kilometers of farmable
Speaker 2: land of Bonker psychiasis, with forty million people having been
Speaker 2: protected and six hundred thousand cases of blindness prevented in
Speaker 2: at least seven countries in The incredible amount of work
Speaker 2: done by this program not only greatly reduced the burden
Speaker 2: of disease in some areas, but also led to a
Speaker 2: huge amount of knowledge being gained about the ecology and
Speaker 2: the epidemiology of this disease, which could then be integrated
Speaker 2: into future control efforts. And I just want to make
Speaker 2: a little note Another bright moment during the OCP era
Speaker 2: happened in nineteen eighty one with the release of the
Speaker 2: Jay Giles Band song river Blindness. I'm going to read
Speaker 2: you the first two verses.
Speaker 1: Okay, you're not going to sing them.
Speaker 2: I'm not going to sing them. I actually haven't listened
Speaker 2: to the song yet, which is so bad, but I
Speaker 2: found it like right before we started to record. Okay, okay,
Speaker 2: human kindness, river blindness. Blackflies rise as the water flows,
Speaker 2: human kindness, river blindness. Angels cry as the fever grows. Indications, demographics,
Speaker 2: control of the basics is all you see. Correlations, disintegrations,
Speaker 2: cessation of life, expectancy.
Speaker 1: We need to ask if we can get permission to
Speaker 1: play that song on the pod because police.
Speaker 2: I know, I know. I I had no idea. It
Speaker 2: was on like a ten Things you probably didn't know
Speaker 2: about river Blindness, and I was like, you're right, I
Speaker 2: did not know about this the Jay Giles Band song.
Speaker 2: The only other song that I know by the Jay
Speaker 2: Giles Band is Centerfold. Like my angel is wait, I
Speaker 2: know that song. Yeah, so I think it's very funny.
Speaker 2: In their repertoire of songs, one is Centerfold and the
Speaker 2: other is blindness.
Speaker 1: Wow, fascinating, there.
Speaker 2: We go, Okay. Anyway, after the OCP ended, Anca Cirkias's
Speaker 2: control was headed up individually by many of the countries
Speaker 2: involved in the OCP, and since the mid nineties there
Speaker 2: have been many other control programs started in countries that
Speaker 2: had not been involved in OCP, and on the other
Speaker 2: side of the Atlantic, other elimination campaigns had started up
Speaker 2: in the Americas, and these were slightly different than those
Speaker 2: in Africa due to the ecology of the disease. So
Speaker 2: whereas in Africa large parts of thirty one countries are
Speaker 2: affected by ancassrakiasis, in the Americas the distribution is much
Speaker 2: more limited or focused and has been and so in
Speaker 2: those areas, mass drug administration with ivermectins seemed to be
Speaker 2: the ticket, and in nineteen ninety three the Ancasrakiasis elimination
Speaker 2: program for the America's began and there have been many
Speaker 2: success stories there. For instance, and I hope I'm not
Speaker 2: stepping on your toes errand but rather setting you up
Speaker 2: to wrap up this story, I love it. Alcast rokiasis
Speaker 2: was declared eliminated in Colombia in twenty thirteen. In Ecuador,
Speaker 2: in twenty fourteen, in Mexico in twenty fifteen, Guatemala in
Speaker 2: twenty sixteen, and parts of Venezuela in twenty seventeen. And
Speaker 2: from what I can tell, the areas where the most
Speaker 2: of the transmission still happens is the southern parts of
Speaker 2: Venezuela and the northern part of Brazil where they border
Speaker 2: one another in sort of like the Amazon area. So
Speaker 2: aerin it seems like there's been a great deal of
Speaker 2: progress in the control of this disease, but it still
Speaker 2: seems like we have a long way to go based
Speaker 2: on some prevalence numbers I saw. So take me through
Speaker 2: where we stand and what we have left to do
Speaker 2: with this neglected tropical disease.
Speaker 1: I would love to. We'll take a quick break and
Speaker 1: then get into it. So World Health Organization estimates, based
Speaker 1: on data from twenty seventeen, which is the most recent
Speaker 1: data that they have listed, estimates that worldwide, almost twenty
Speaker 1: one million people are currently infected and living with Anco
Speaker 1: Cerca volvulus. It's so many, it's still a very very
Speaker 1: large number. Yes, it's estimated that of those twenty one
Speaker 1: million people, about fourteen point six million of them have
Speaker 1: active skin manifestations, so they have active disease, and about
Speaker 1: one point one five million have some degree of vision loss,
Speaker 1: if not complete blindness.
Speaker 2: Will everyone who is infected with this parasite develop blindness?
Speaker 2: Is it just an inevitability?
Speaker 1: Great question. No, definitely not, and not everyone would even
Speaker 1: necessarily have all of the skin manifestations. But I did
Speaker 1: not I could not find a solid number on what
Speaker 1: that percentage or proportion is. I think it largely has
Speaker 1: to do with disease burden. So the higher the intensity
Speaker 1: of burden, the more likely you are to have severe disease,
Speaker 1: including vision loss. Right, Okay, Yeah, like you said, Aaron, already,
Speaker 1: it is still the case that over ninety nine percent
Speaker 1: of those who are currently living with ancosarchiasis live in
Speaker 1: thirty one countries across Africa. The other one percent are
Speaker 1: located in Focai in Latin America as well as Yemen.
Speaker 1: And the thing is that acossarchiasis doesn't kill people outright,
Speaker 1: but it is no less debilitating and it does reduce
Speaker 1: life expectancy even though it doesn't kill people directly. So,
Speaker 1: like you mentioned, Aarin, before control efforts ramped up in
Speaker 1: some endemic areas up to thirty five or forty six
Speaker 1: percent of people would become blind eventually. That is just yeah, yeah,
Speaker 1: And in many areas where ancosyirchiasis was endemic, up to
Speaker 1: ten percent of the adult population would become blind, just
Speaker 1: depending on the overall worm burden in the area. And
Speaker 1: even without considering permanent disability like blindness, these skin lesions,
Speaker 1: I really can't underestimate how debilitating the itchiness can be.
Speaker 1: People can't sleep, they can't work. So if we look
Speaker 1: at the disability adjusted life years, which is an imperfect
Speaker 1: measure but still a measure of overall disease burden, alcocerciasis
Speaker 1: is estimated to account for between one million and one
Speaker 1: and a half million disability adjusted life heres annually, depending
Speaker 1: on which paper you look at, and the itching and
Speaker 1: skin manifestations account for over sixty percent of these. So
Speaker 1: it's not just the blindness. I think that with a
Speaker 1: common name like river blindness, it can be overlooked how
Speaker 1: impactful the skin disease really is as well.
Speaker 2: Right, I think that's definitely the case.
Speaker 1: Yeah, And also these skin manifestations can result in open wounds,
Speaker 1: and just as well the aarin you asked really early
Speaker 1: on whether people become immunosuppressed in some ways. When you
Speaker 1: have a very very high worm burden, it does cause
Speaker 1: your immune system to be more likely to have other infections. Okay,
Speaker 1: on top of having potentially open wounds on your skin,
Speaker 1: that can be an area where you can become infected.
Speaker 1: So overall, it's estimated that oncopsychiasis, though it doesn't kill people,
Speaker 1: it does reduce over life expectancy by thirteen years.
Speaker 2: That's yeah, that's not in substantial at all.
Speaker 1: Right, not in the slightest. But the good news is
Speaker 1: that control efforts have been ongoing for decades now. Early
Speaker 1: on AARIN, like you talked about, they relied on a
Speaker 1: lot of integrative approaches, using both vector control pest management
Speaker 1: as well as ivermectin. Most of the programs that are
Speaker 1: out there today really just rely on community directed treatment
Speaker 1: with ivermectin annually. This has worked very very well in
Speaker 1: some areas, like in the Americas. It has not worked
Speaker 1: as well in very very highly endemic areas in Africa,
Speaker 1: largely because it doesn't kill these adult worms and you
Speaker 1: administer ivermectin annually, but it really only reduces symptoms and
Speaker 1: slows the transmission for a few months. So ivermectin alone
Speaker 1: is unlikely to completely control or eradicate ancos orchiasis.
Speaker 2: And in terms of like how it's only given once
Speaker 2: a year, is administering it more frequently bad for year?
Speaker 1: So it's yeah, it's a great question. It's it's a possibility,
Speaker 1: and there's some data that suggests that maybe in these
Speaker 1: hyper endemic areas that could be a good option to
Speaker 1: administer it bi annually instead of annually, But the data
Speaker 1: doesn't suggest that that would actually result in that big
Speaker 1: of a decrease, because annually does make a really big difference.
Speaker 1: It's just that in places where this is hyper endemic,
Speaker 1: it's just not quite enough essentially.
Speaker 2: Well, and I think it's it's also interesting too, going
Speaker 2: a little bit back to the ecology, is that I
Speaker 2: saw a few like line graphs looking at the biting
Speaker 2: frequency and how it does peak at certain times of year,
Speaker 2: and so if you reduce the microfil area like presence
Speaker 2: during those times and time the drug administration then then.
Speaker 1: Precisely exactly Yeah, so kind of targeted administration as well.
Speaker 1: But overall, in twenty seventeen, one hundred forty five million people,
Speaker 1: which is about seventy percent of the estimated population at risk.
Speaker 1: We're treated with ivermectin through these various control programs, which
Speaker 1: is phenomenal. It's not quite where we need to be
Speaker 1: because in every region you would need at least eighty
Speaker 1: to eighty five percent treatment to really help reduce an
Speaker 1: interrupt transmission. But it's good progress. But the big question
Speaker 1: is like, can we do better? We've been doing this
Speaker 1: now for decades. Can we do better, especially as it
Speaker 1: relates to actually curing disease rather than just treating symptoms
Speaker 1: or halting progression, which requires treatment for ten to fifteen
Speaker 1: years or more. Right, enter wolbakia. Okay, I told you
Speaker 1: we come back to them. So, like I said in
Speaker 1: the biology section, the more that we know about the
Speaker 1: disease path of physiology of nco psychiasis, the more it
Speaker 1: becomes clear that Wilbakia play a very important role. But
Speaker 1: we already know that we can't just kill the adult
Speaker 1: worms outright, because then the Wolbachia that are in them
Speaker 1: would make us really sick. Right, So some researchers have wondered,
Speaker 1: what if we just kill the Wolbachia bacteria inside of
Speaker 1: these worms? How do we do that great question, Aaron,
Speaker 1: We can do it. Okay, treatment with doxycycline, which is
Speaker 1: an antibiotic, it's a relatively common one that we use
Speaker 1: for a lot of diseases, including tick born diseases like ricketsias,
Speaker 1: which Wolbachia are relatively closely related to ricketsias.
Speaker 2: They are. Indeed, so treatment.
Speaker 1: With doxycycline can interrupt embryogenesis, stop adult worms from being
Speaker 1: able to reproduce for at least a year, if not
Speaker 1: two years, which is far longer than the few months
Speaker 1: that ivermectin can do.
Speaker 2: That's incredible.
Speaker 1: So it's unclear whether treatment with doxycycling can fully just
Speaker 1: kill the adult worms very slowly. I think in some
Speaker 1: studies it suggests that these adult worms will then die,
Speaker 1: but certainly it stops their reproduction. It stops the production
Speaker 1: of microfilaria for years.
Speaker 2: That's a wonderful news.
Speaker 1: So why aren't we mass administering this? Yeah, yeah, it's
Speaker 1: a little tough. So ivermectin is a one single dose treatment,
Speaker 1: one dose once a year, and you have effect. Doxycycline,
Speaker 1: on the other hand, requires one hundred to two hundred
Speaker 1: milligrams per day every day for four to six weeks
Speaker 1: at a time. Yeah, there's also a pretty large range
Speaker 1: of people, including pregnant people, breastfeeding people, children under nine
Speaker 1: who can't take doxycycling for various reasons. So there are
Speaker 1: groups that are doing research to try and find other
Speaker 1: compounds and drugs that might have the same effect but
Speaker 1: be administered in a more practical way, so not needing
Speaker 1: people to take drugs for six weeks at a time,
Speaker 1: but also to a wider range of people who are
Speaker 1: at risk of infection or who are living with infection.
Speaker 1: But what's really cool is I saw some papers that
Speaker 1: were suggesting that this could be something that's particularly beneficial
Speaker 1: in those areas that are hyperendemic where we've been treating
Speaker 1: with ivermectin but it doesn't seem to be having the effect,
Speaker 1: or also in areas where you have a high burden
Speaker 1: of disease but you also have Loa loa, which is
Speaker 1: another filarial parasite that if people are coinfected with Anko
Speaker 1: circa and Loa looa, you cannot treat them with ivermectin
Speaker 1: because the loaaloa worms will also die, but they are
Speaker 1: larger and they can block blood vessels and cause brain
Speaker 1: damage and death.
Speaker 2: Yeah, so that's bad.
Speaker 1: Yeah, but loa looa don't have waalbakia. Interesting, so doxycycline
Speaker 1: and drugs that were like it don't affect them. So
Speaker 1: that's a pretty promising area of research for that reason
Speaker 1: as well, because areas where both ankocerca and loaloa are
Speaker 1: present have been very difficult to do control strategies.
Speaker 2: We need to keep a list of like things at
Speaker 2: the end of these episodes were like, oh, like all
Speaker 2: these future directions, let's keep an eye on how these
Speaker 2: things are progressing.
Speaker 1: There's a lot I feel like there was a lot
Speaker 1: in like the Dengae episode where it was like, this
Speaker 1: is happening now, Okay, right, but it's pretty it's pretty awesome.
Speaker 1: I think there's some good researches going on. I think
Speaker 1: that overall things are not great in terms of anchocerciasis,
Speaker 1: but they're a lot better than I expected. Quite honestly,
Speaker 1: they're a lot better than I expected.
Speaker 2: And I think that like the you know, the past
Speaker 2: fifty years or so of control efforts have really shown
Speaker 2: that a lot of progress can.
Speaker 1: Be made exactly. Yeah, like we've we've made massive progress.
Speaker 1: It's just that because the life cycle of these parasites
Speaker 1: is so long, you still have really high prevalence of disease, right,
Speaker 1: But yeah, we've come a really long waist, so we
Speaker 1: can end on kind of a positive note.
Speaker 2: Yay for a.
Speaker 1: While, like when that happens me too.
Speaker 2: Sources sources, So I have a thousand different articles, not
Speaker 2: that many, but I have a lot of different articles.
Speaker 2: I'll shout out a couple. One resource that was great
Speaker 2: is a book called A History of Human Heal Mythology
Speaker 2: by David Grove. And in terms of papers, I want
Speaker 2: to shout out a few, one by Basanyas at all
Speaker 2: two thousand and nine and another by Crump at all
Speaker 2: twenty twelve, Kruger at all two thousand and seven and
Speaker 2: Leifs Foulon at All twenty sixteen, and those were all
Speaker 2: really great papers. I will post these papers as well
Speaker 2: as all the other ones I didn't mention on our
Speaker 2: website same.
Speaker 1: I have a very long list of recommended reading, everything
Speaker 1: from the specific biology and path of physiology to a
Speaker 1: lot more details on the role of wellbakia and ivermectin.
Speaker 1: It's a really fascinating drug. If you want to read
Speaker 1: more about it, you can find all our sources for
Speaker 1: this episode and every one of our episodes on our
Speaker 1: website This podcast will Kill You dot Com under the
Speaker 1: episodes tab.
Speaker 2: Absolutely well. Thank you to Bloodmobile for providing the music
Speaker 2: for this episode and all of our episodes.
Speaker 1: Thank you to the Exactly Right Network, of whom we
Speaker 1: are very proud to be members.
Speaker 2: And thank you to you listeners for allowing us to
Speaker 2: make this podcast and for listening even if we talk
Speaker 2: about like really I don't know, scary subjects or really
Speaker 2: weird subjects, We're glad to have you along for the ride.
Speaker 1: Yeah, this is really fun. We hope you enjoyed this episode.
Speaker 2: Yeah, well, until next time, wash your hands.
Speaker 1: You feelthy animals. MBA, bum bum bum bum