Speaker 1: My name is a vet. I first fell ill in
Speaker 1: nineteen eighty seven. I started having back pain and was
Speaker 1: cold all the time, even when it was hot. Just
Speaker 1: taking a bath was an ordeal. I didn't know what
Speaker 1: was wrong. All the tests came out negative. I went
Speaker 1: to Fumetro and Mushi in nineteen ninety two. They performed
Speaker 1: a spinal tap and the result was negative. I continued
Speaker 1: to suffer. My bones ached terribly, I was extremely cold,
Speaker 1: I had fever but would never sweat. I was losing weight.
Speaker 1: I arrived here in ban Doondo in nineteen ninety nine
Speaker 1: in a very precarious state of health. I went to
Speaker 1: a health center where they performed another spinal tap. The
Speaker 1: result was still negative. I went to fo Metro in
Speaker 1: twenty ten, again the spinal tap. It seemed there was
Speaker 1: no solution to my problem. I could hardly stand up.
Speaker 1: I was nearly paralyzed, constant back pain, constantly sleeping in
Speaker 1: my bed. When I would go to prayer, I couldn't
Speaker 1: follow the preacher. I would just fall into a slumber.
Speaker 1: I insisted on getting the right test. Maybe I had
Speaker 1: sleeping sickness. They just kept telling me I was fine.
Speaker 1: I went to the hospital and still no diagnosis. Here
Speaker 1: at the general hospital, the test was negative, just malaria.
Speaker 1: I was totally confused. In the meantime, my health deteriorated.
Speaker 1: In twenty ten. In January, they brought me to Vanga.
Speaker 1: I was practically in agony. It was there finally that
Speaker 1: I discovered I had sleeping sickness. I was transferred back
Speaker 1: here to Vandundu for treatment. I knew nothing of all
Speaker 1: of this since I was unconscious. They started me on
Speaker 1: the treatment, although I had no idea what had been prescribed.
Speaker 1: I was crying all the time. I had to be
Speaker 1: carried and fed like a child. I was a complete disaster.
Speaker 1: I didn't think i'd ever walk again, but the treatment
Speaker 1: was effective. When I regained consciousness, I was discharged from
Speaker 1: the hospital, I started to walk again. I was so thrilled.
Speaker 1: My eldest sibling died from sleeping sickness in nineteen eighty
Speaker 1: in Mushi, in the city where I live. A friend
Speaker 1: of mine contracted the disease. She suffered complications. She had
Speaker 1: been treated with the shots. In the end, she died.
Speaker 1: The patients that were treated with the new treatment were healed,
Speaker 1: but most of those that were treated with the shots
Speaker 1: had enormous difficulties. Some are paralyzed for life. I was
Speaker 1: among the first patients to be treated with the new products.
Speaker 1: My opinion is that we have to keep using the
Speaker 1: new products. They are good and don't harm the patients.
Speaker 1: I was paralyzed and thanks to the new treatment, I
Speaker 1: can walk again. Wow.
Speaker 2: I honestly don't even know what to say. Yeah.
Speaker 3: Same, There is so much too unpack. I feel like
Speaker 3: in this story, just the horror of this disease and
Speaker 3: in many times the horror of the treatment itself too,
Speaker 3: as I'm.
Speaker 2: Sure we'll talk about.
Speaker 3: But yeah, yeah, So that was from a video titled
Speaker 3: a Life Saved by any ct VET Story of Sleeping
Speaker 3: Sickness from the Drugs for Neglected Diseases Initiative.
Speaker 2: Hi.
Speaker 1: I'm Aaron Welsh and I'm Erin alman Updyke.
Speaker 2: And this is this podcast will Kill You.
Speaker 1: Welcome Today we're talking about sleeping sickness.
Speaker 3: Aka human African tapanisimiasis.
Speaker 2: Yeah. Yeah, this is a.
Speaker 1: Like the exact type of disease that really got me
Speaker 1: interested in disease and medicine and public health and global
Speaker 1: health and all of the things because it's yeah.
Speaker 2: Yeah, it's it's a lot.
Speaker 3: It's it's a really complex disease system. It's a really
Speaker 3: complex disease history. And I you know, I think I
Speaker 3: now say this every time, but I was surprised by
Speaker 3: how much I absolutely had no idea.
Speaker 1: Oh about same. The biology was so much more complex.
Speaker 1: I mean, I knew that the kind of ecology was complex,
Speaker 1: but I had no idea about the complexity of the
Speaker 1: biology like in humans even And I know nothing still
Speaker 1: about the history. I can take some guesses. Yeah, it's
Speaker 1: badly it's gonna be a big episode.
Speaker 3: Yeah, but I think it'll be a very interesting one.
Speaker 1: Yeah, I think so too. I'm excited about it. Yeah,
Speaker 1: but before we get into too much detail, erin it
Speaker 1: is quarantiny time.
Speaker 3: It is Aaron.
Speaker 2: What are we drinking this week?
Speaker 1: We're drinking the Nightmare?
Speaker 3: We are I think a pretty appropriate name for this disease,
Speaker 3: because this disease truly does seem like a nightmare, and
Speaker 3: it is in many.
Speaker 2: Ways a nightmare.
Speaker 1: So ye, what's in a nightmare?
Speaker 3: Erin, great question? In the nightmare is laven or simple syrup,
Speaker 3: camimeal tea whiskey and a little bit.
Speaker 2: Of lemon juice de lish.
Speaker 3: Yeah, it's not a nightmare to drink.
Speaker 1: We'll post the full recipe for that quarantiny and our
Speaker 1: non alcoholic Placeiba Rita on our website. This podcast will
Speaker 1: kill you dot Com and all of our social media channels.
Speaker 3: We will other business includes our website, which has lots
Speaker 3: and lots of things. I promised myself last time that
Speaker 3: I was gonna do a post it note of all
Speaker 3: of the things on our website, and now I am
Speaker 3: so mad at myself for not following through. All right,
Speaker 3: well it comes to me anyway. Our website, you can
Speaker 3: find sources for where we get all of the info
Speaker 3: for each of our episodes. You can find transcripts. You
Speaker 3: can find links to Bloodmobile's music now on Spotify. You
Speaker 3: can find links to our Goodreads booklist and our bookshop
Speaker 3: dot org affiliate account. You can find our Patreon and
Speaker 3: some sweet sweet merch.
Speaker 1: Yes, oh real quick, I did remember one piece of business,
Speaker 1: oh wock I should cover. We have gotten a number
Speaker 1: of emails about our ceediff episode in which I didn't
Speaker 1: include the update that Closterdium difficile has been reclassified several
Speaker 1: years ago, I think around twenty sixteen to this species
Speaker 1: Claustritioides difficial seed iff is still sea diiff, but it's
Speaker 1: a different see.
Speaker 3: Yes, yeah, all right, let's let's talk about sleeping sickness.
Speaker 1: Now, let's let's do it, Okay, right after this break.
Speaker 1: For most listeners, this should be at least a little
Speaker 1: familiar sleeping sickness or human African tripennosamiasis, which like I
Speaker 1: might at some point just call tripenosimiasis or hat because
Speaker 1: it's shorter. It is caused by a trapanosome. We've talked
Speaker 1: about those once before, in the same genus as that
Speaker 1: which causes shagas disease.
Speaker 3: In this case it is a.
Speaker 1: Different species, and in fact it is two different subspecies.
Speaker 1: So today we're going to be talking about Tripanosoma brucei rhudesienc.
Speaker 1: And Tripanosoma brucei gambiency. I might just say gambiency and
Speaker 1: rhodesience because that's true.
Speaker 2: I do the same. It's a lot easier.
Speaker 1: Yeah. Sometimes you even just see like TBG or tb R.
Speaker 2: Right.
Speaker 1: So, tripanosomes as a recap are unicellular eukaryotes. They are
Speaker 1: shaped kind of like little if you look at them
Speaker 1: on a microscope slide like little commas or maybe little bananas.
Speaker 1: I don't know. They have a little flagellum that they
Speaker 1: use to swim around. Okay, t Brucei all the species
Speaker 1: because I didn't mention this, But there is yet another subspecies,
Speaker 1: Trypanosoma bruci brucei, which causes a disease in cattle called nagana.
Speaker 1: I believe is how you pronounce it. So Trypanosoma brucei
Speaker 1: is transmitted by yet another new vector species that we
Speaker 1: have never touched on in this podcast. It is the
Speaker 1: blood feeding setsi fly. Seats fly, sets fly.
Speaker 3: We've had discussions about this pronunciation, and we've looked up
Speaker 3: many videos and I.
Speaker 1: Think it's one of those that different people are going
Speaker 1: to pronounce differently. And that's okay. Yeah, so that seats flies,
Speaker 1: seats flies. I'm really excited to talk about these, but
Speaker 1: I promise I'm not gonna geek out quite as hard
Speaker 1: as like we did during the Typhus episode with lice.
Speaker 2: Yeah, Okay, we did pretty hard.
Speaker 1: H It's not gonna be quite as hard. But specifically
Speaker 1: that sets flies in genus Glossina is who we're talking
Speaker 1: about today. I want to geek out just a little
Speaker 1: bit These flies are fascinating. They are viviparous, yeah, which
Speaker 1: means they give live birth. They give birth to live
Speaker 1: little larval young.
Speaker 3: I had no idea that was a thing in insects
Speaker 3: until this. But I've never taken an entomology class, so I.
Speaker 1: Have a PhD in entomology, and I learned something new.
Speaker 1: So these female flies deposit their larva into the soil directly.
Speaker 1: They have eggs that they actually hold internally until they
Speaker 1: develop into I believe third in star larvae. They deposit
Speaker 1: those larvae into the soil where they burrow in. They
Speaker 1: then pupate and emerge as adult flies.
Speaker 3: It's so fascinating because like, first of all, I really
Speaker 3: want to know has this happened, has this evolved in
Speaker 3: other species of insects, and like what are the like
Speaker 3: what are the evolutionary pressures or pathways for this thing
Speaker 3: to be? Like I'm gonna spend all of my time
Speaker 3: and energy on. I mean, they're they're relatively long lived
Speaker 3: for flies, and so maybe that's part of it, but
Speaker 3: I just like I just want to know so much
Speaker 3: more about viviparous insects.
Speaker 1: I know, and I like specifically didn't deep dive on them,
Speaker 1: but like, use, we so could.
Speaker 2: Yeah, yeah, we really could, because.
Speaker 1: There is there's a lot, there's a lot there to unpack.
Speaker 1: But we're just gonna leave it at Aren't these flies
Speaker 1: so cool? Let's let's deep dive another time. Another important
Speaker 1: part about these flies is that both male and female
Speaker 1: flies blood feed as adults, and so here is how
Speaker 1: human African tripanosomiasis becomes a problem. When these flies feed
Speaker 1: on a human host or an animal host, they pick
Speaker 1: up this parasite, this tripanosome in the blood meal. These
Speaker 1: parasites enter the digestive tract of the fly. There they differentiate,
Speaker 1: they replicate, They burst out of the digestive tract, travel
Speaker 1: through the fly's body, enter into the salivary glands. In
Speaker 1: the salivary glands, they differentiate again into the infective form
Speaker 1: of tripanisome, continue to replicate, and then when that fly
Speaker 1: takes its next blood meal, their salivary glands are full
Speaker 1: of infective stages of this parasite that they can inject
Speaker 1: under their host's skin.
Speaker 3: Okay, interesting, Is this the way it is for all
Speaker 3: tripanisomes transmitted by setsuflies?
Speaker 1: As far as I know, Yes, And this process we
Speaker 1: have actually seen this process before. This is actually not
Speaker 1: a very uncommon way of vector transmission. Something like dangay
Speaker 1: fever is very similar, right, where the virus has to
Speaker 1: enter the GI tract, make its way out of the
Speaker 1: GI tract, through the body, and into the salivary glands. Importantly,
Speaker 1: this is very different than the other tripanisome we've talked about,
Speaker 1: which is Shaugus disease, which is transmitted just through the feces,
Speaker 1: so that parasite just travels kind of straight through the
Speaker 1: gut of the kissing bug. Here, this parasite not only
Speaker 1: has to migrate through the gut, through the gut wall,
Speaker 1: through the body into the salivary glands, but during this
Speaker 1: process it also differentiates multiple times and changes forms in
Speaker 1: a very complex way. And this whole process actually takes
Speaker 1: these trypanisomes about three to five weeks, which is a
Speaker 1: really long time.
Speaker 2: Yeah, that's a really long time. Yeah, that's a.
Speaker 1: Very long time. And like you mentioned, Aaron, this fly
Speaker 1: is very long lived.
Speaker 2: From what I.
Speaker 1: Read, its lifespan is at least two to three months,
Speaker 1: and they blood feed every three days or so. Likely
Speaker 1: largely because of this complexity, not only the complexity of
Speaker 1: the life cycle of this fly, but also the complexity
Speaker 1: of like the maturation process of these parasites within the fly.
Speaker 1: It's actually found that for the most part, the prevalence
Speaker 1: of tripanosomes in flies is actually very very low. Zero
Speaker 1: point one percent of flies in any given study area
Speaker 1: tend to be infected.
Speaker 3: That's bizarre, it is, So what's going on?
Speaker 1: I don't have a good answer for that.
Speaker 2: So because you.
Speaker 3: Would think that, like flies are so long lived, parasites
Speaker 3: seem to be in them for weeks at a time.
Speaker 1: But I think what it is is that a lot
Speaker 1: of those parasit even if a fly is picking up parasites,
Speaker 1: they don't necessarily make it all the way to an
Speaker 1: infective infection in the fly.
Speaker 3: Okay, So yeah, at any point in time, it's one
Speaker 3: percent of flies that are infected with infectious stage parasites.
Speaker 2: It's point one percent point one percent.
Speaker 3: Yeah, yeah, okay.
Speaker 1: And as far as I found, at least, this is
Speaker 1: not a parasite that's vertically transmitted. So even though these
Speaker 1: female flies have their young that develop in their bodies,
Speaker 1: they're not passing those parasites onto their offspring.
Speaker 2: Yeah, okay, gotcha.
Speaker 1: So there's a lot more to unpack there, I am sure,
Speaker 1: because this is a very interesting and complicated genus of bug.
Speaker 1: But that's where I'm gonna leave it. And let's get
Speaker 1: back to the life cycle of the parasite. So the
Speaker 1: parasite is now in the salivary glands. The fly takes
Speaker 1: another blood meal, and in so doing, through their little proboscis,
Speaker 1: deposits a whole bunch of parasite underneath our skin. Those
Speaker 1: parasites enter our lymphatic system and our bloodstream, and from
Speaker 1: there they're able to replicate. They differentiate again in us
Speaker 1: as well, and they travel to various organs and establish
Speaker 1: an infection. It gets even more interesting erin the biology
Speaker 1: of this parasite. There's so much here. I'm not going
Speaker 1: to do every aspect of it justice, but I do
Speaker 1: hope that I at least give a teaser of all
Speaker 1: of the different interesting parts of this parasite. That's my
Speaker 1: kind of goal here, Okay, I'm down. So our human
Speaker 1: immune system, when we see these parasites, is actually primed
Speaker 1: to recognize these parasites, and we do. Our immune system
Speaker 1: does we actually even have a protein in our bloodstream
Speaker 1: that's usually really good at eliminating other tripanosomes. That's called
Speaker 1: tripanosomelytic factor. Did you know that we had that?
Speaker 2: Uh? No, I have? Yeah?
Speaker 3: Okay, keep going.
Speaker 1: So if we get infected with most other species of tripanosome,
Speaker 1: not the two that we've talked about that cause disease
Speaker 1: in humans, here, we're able to fend off that infection
Speaker 1: like a lot of other animal tripanosomes. But Tripanosoma bruci
Speaker 1: subspecies Rhodesiency and gambiency specifically have resistance factors that render
Speaker 1: this particular protein that we have not useful.
Speaker 3: So my mind is blown because this is filling in
Speaker 3: so much of the evolution part that I researched, and
Speaker 3: I was like, but what does that mean about this
Speaker 3: and the history? But so this means that we are like,
Speaker 3: we can witness this as an arms race kind of
Speaker 3: a thing, right, Yeah, Oh my god, that's so cool.
Speaker 1: It gets even cooler. Okay. Tripanosomes have on their cell
Speaker 1: surface a lot of different proteins that our body uses
Speaker 1: to identify and recognize them as non self right, anigens
Speaker 1: essentially that we make antibodies against to remove them from
Speaker 1: our bodies, and we're really good at that. But the
Speaker 1: tripanosomes that cause human African tripanosomiasis T. BRUCEI, Rudi ziency,
Speaker 1: and gambiency. From now on, those are the only two
Speaker 1: that I'm going to talk about.
Speaker 2: Okay.
Speaker 1: They have hundreds, maybe a couple of thousand variants of
Speaker 1: these proteins, and they express them one at a time,
Speaker 1: and they constantly switch them up, so by the time
Speaker 1: our body manages to make antibodies against one of these glycoproteins,
Speaker 1: that one like barely even exists anymore, and they've changed
Speaker 1: to a new one. Here's the way that I think
Speaker 1: about this. These tripanosomes are me when I was like sixteen,
Speaker 1: sneaking into a movie, right, you with me here?
Speaker 2: Into an R rated movie.
Speaker 1: No, I wasn't that risk erin it was probably PG thirteen.
Speaker 3: You were sixteen sneaking into a PG thirteen movie.
Speaker 1: Let me tell you that I can finish my analogy.
Speaker 1: It's gonna make more sense.
Speaker 3: It's flawed from the start, but fine.
Speaker 1: No, no, no, I'm talking about like movie hopping, like
Speaker 1: you're trying to go to more than one movie.
Speaker 3: Oh oh my gosh.
Speaker 1: Okay, Okay, I see right, Okay, so that's this is
Speaker 1: what's happening. The trypanosomes are sneaking into movies and the
Speaker 1: security guards see them. They get on their walkie talkie
Speaker 1: and they're like, we've spotted the culprint. They're wearing a
Speaker 1: pink jacket that's a very flamboyant jacket. So by the
Speaker 1: time the security guards get into the theater, that tripanosome
Speaker 1: change their pink jacket out for a green one, and
Speaker 1: the security guards are like, Hm, there's no pink jacket here. Wait,
Speaker 1: who's that in the green? They look suspicious, And then
Speaker 1: that person slips into a different theater, and by the
Speaker 1: time the guards get to the next theater, they've changed
Speaker 1: their jacket again for like a cheetah print one, and
Speaker 1: the gods are like, look, there's no one here in
Speaker 1: pink or green. We're just gonna give up. We're gonna
Speaker 1: go get popcorn. It's like that, but at the same
Speaker 1: time as this, the tripanis is replicating unlike me in
Speaker 1: a movie theater, or you can think of it as
Speaker 1: like with letting a bunch of their friends in with
Speaker 1: different color jackets.
Speaker 3: It sounds totally overwhelming.
Speaker 1: I know, before you know it, our immune system literally
Speaker 1: just can't keep up. So we'll probably manage to kick
Speaker 1: out some of them that we're still wearing pink or
Speaker 1: green jackets, but the rest of them managed to escape
Speaker 1: our security guards. And that is how tripanasoma BRUCEI Rudy
Speaker 1: zienc gambiency can establish an infection in our bodies.
Speaker 3: Okay, that is very interesting and that I feel like
Speaker 3: has a lot of implications for vaccines and therapy.
Speaker 1: Sure does, erin, sure does?
Speaker 2: Oh boy?
Speaker 1: Okay, yeah, yeah, it makes the vaccines very difficult, if
Speaker 1: not nearly impossible, because it's very difficult to stop the
Speaker 1: establishment of an infection.
Speaker 3: Yeah, this is so interesting, okay, I yeah, I just
Speaker 3: want to keep gushing about how interesting this is also
Speaker 3: from an evolutionary perspective, because I think this really does
Speaker 3: kind of provide some insight into like if there are
Speaker 3: so many protein variants of the like, so much antigenic variation,
Speaker 3: right then this has to be like a long period
Speaker 3: of exposure to humans.
Speaker 1: Absolutely yeah wow, okay, Okay, speaking of exposure to humans, T.
Speaker 1: Bruce ei gambiency tends to be a primarily anthroponotic disease.
Speaker 1: So while this tripanistome can also infect animals, humans are
Speaker 1: the predominant reservoir so it's much more common to have
Speaker 1: human to human transmission via of course, the Glossina fly
Speaker 1: Tripanisoma brucie. Rhodiziency is generally a zoonotic disease that's often
Speaker 1: transmitted from animals to humans, especially cattle, which are a
Speaker 1: very important reservoir. And that's just one of the differences
Speaker 1: between these two subtypes, and we'll talk a little bit
Speaker 1: more in a minute about the differences in terms of
Speaker 1: their symptoms. But basically, the disease known as human African
Speaker 1: tripanosomiasis or sleeping sickness, has two phases. The first phase
Speaker 1: is when the parasite is in the blood or the
Speaker 1: lymphatics and making its way into various organs, and then
Speaker 1: the second phase is when it invades our central nervous
Speaker 1: system and results in the symptoms that have given it
Speaker 1: the name sleeping sickness. And we will get there, but
Speaker 1: first I want to talk briefly about the differences in
Speaker 1: the two subtypes, gambiency and rhodesience. The disease itself, for
Speaker 1: the most part, is the same or at least very
Speaker 1: similar between these two subtypes, but the big, big difference
Speaker 1: is that in gambiency, which again is the subspecies that
Speaker 1: tends to have humans as the primary reservoir rather than animals.
Speaker 1: In this subtype, the disease course tends to be prolonged.
Speaker 1: That first stage might last months or even years, and
Speaker 1: it can be more mild and have vague symptoms. That's
Speaker 1: not to say that it's a mild disease, because it's
Speaker 1: not at all. But the average duration of gambiency disease
Speaker 1: is about three years, and there's a huge amount of
Speaker 1: interperson variability. So like in our first hand account, what
Speaker 1: was described was a very prolonged disease, but in some
Speaker 1: people it might be a matter of months. On the
Speaker 1: other hand, disease caused by the subspecies Rudiesiency tends to
Speaker 1: have a much faster and more severe course, where over
Speaker 1: a few weeks or a couple of months, people end
Speaker 1: up very sick, progress to the second stage of disease
Speaker 1: and usually die within six months if they're untreated.
Speaker 2: Wow, and for.
Speaker 1: Both subtypes of this disease, almost all of the accounts
Speaker 1: report the the disease is almost universally fatal if it's
Speaker 1: left untreated, but there have been a handful of case
Speaker 1: reports of gambiency where people either recover or have like
Speaker 1: a self cure where they do actually recover from the infection,
Speaker 1: or of being relatively healthy carriers. Okay, yeah, but that's
Speaker 1: the very minority. It's like a few case reports, gotcha.
Speaker 1: In terms of the distribution, rhodesiency, the one with animals
Speaker 1: as the primary reservoir, accounts for about five percent of
Speaker 1: cases and is more prevalent in the eastern and southern
Speaker 1: parts of Africa, and gambiency accounts for about ninety five
Speaker 1: percent of cases and is more prevalent in the western
Speaker 1: and central parts of Africa.
Speaker 3: Does this is definitely jumping the gun? But does trevent
Speaker 3: work equally well on both of these some notpes?
Speaker 1: Okay, Nope, that is definitely jumping the gun, and we'll
Speaker 1: get there.
Speaker 2: Okay.
Speaker 1: Yeah, So let's first talk about what this disease actually
Speaker 1: looks like in these two different stages. First stage of
Speaker 1: this disease is really pretty generalized symptoms. Usually there's fever,
Speaker 1: and this fever is often intermittent, so it can last
Speaker 1: a day or it can last up to a week.
Speaker 1: It can come and go every few days or even
Speaker 1: every few months. Does that sound familiar at all?
Speaker 2: Erin it does malaria.
Speaker 1: It sounds like malaria. Yeah, so the symptoms can overlap
Speaker 1: a lot with malaria, and as you can imagine, that
Speaker 1: can make the diagnosis really challenging since the distribution of
Speaker 1: these two diseases overlaps.
Speaker 2: Yeah.
Speaker 3: Is there any sort of like diurnal pattern, because I
Speaker 3: know that like tetsi flies have a behavioral pattern, like
Speaker 3: they're more active during the day than at night, for instance, right,
Speaker 3: and malaria is the same kind of thing, like they're
Speaker 3: more active, they're more crepuscular, Right, that wonderful word.
Speaker 1: Yeah, that's a good question. Not that I read and
Speaker 1: I anticipate that because the mechanisms of the fever with
Speaker 1: malaria are a little bit more like very specifically associated
Speaker 1: with the parasites and the infectivity and that kind of
Speaker 1: a thing. So I think that's probably why you see
Speaker 1: more of that in malaria than you would in this
Speaker 1: where it's a more generalized like you have fever for
Speaker 1: like a whole day or a whole week or something
Speaker 1: like that, rather than like at certain times of day.
Speaker 1: It's a good question, though other symptoms are equally general.
Speaker 1: Things like headache are very common sometimes itching, you commonly
Speaker 1: can get swelling of the lymph, nodes, and it tends
Speaker 1: to be different lymph nodes in the two different subtypes
Speaker 1: of disease. Hipatospleinomegaly one of our favorite TPWKY words, so
Speaker 1: swelling of the spleen and the liver. It can also
Speaker 1: cause abnormal menstrual bleeding or sometimes even spontaneous pregnancy loss
Speaker 1: just because of this kind of overwhelming infection. And this
Speaker 1: can kind of just go on and on, on and off,
Speaker 1: on and off, really, and it can do so for
Speaker 1: as long as it takes essentially to progress to the
Speaker 1: second stage of the disease, which is when the tripanosomes
Speaker 1: actually invade the central nervous system. So the second stage
Speaker 1: is how human African tripanasaimiasis got its name sleeping sickness.
Speaker 1: But it's not all about sleep. Once this parasite invades
Speaker 1: our central nervous system, it can cause a huge range
Speaker 1: of neuro psychiatric findings and histologically it causes a very
Speaker 1: generalized encephalitis or inflammation of the brain and the central
Speaker 1: nervous system. So the findings, I mean, there are almost
Speaker 1: anything that you can imagine that has to do with
Speaker 1: the nervous system. It can cause tremors, it can cause
Speaker 1: motor weakness. It can cause ataxias or that like discordinated
Speaker 1: motor movement that we've talked about in a few other episodes.
Speaker 1: It can cause behavioral changes that can range from anything
Speaker 1: from apathy to aggressive behavior to psychosis or manic episodes.
Speaker 1: It can cause confusion and dementia. And all of these
Speaker 1: various symptoms progress with the severity of the disease, so
Speaker 1: they might start out as more mild and then continue
Speaker 1: to change and progress as this parasite still persists in
Speaker 1: the nervous system.
Speaker 3: How predictable are these psychological manifestations, as.
Speaker 1: Far as I read, not very like it really can
Speaker 1: vary person to person. Certainly the more severe the symptoms
Speaker 1: likely the more severe the disease, okay.
Speaker 2: And the later the stage.
Speaker 1: Now, the effects on sleep are very characteristic and from
Speaker 1: what I can tell, and I didn't get like as
Speaker 1: good of a number on this as I really like
Speaker 1: to like this per percentage of people have the sleeping signs,
Speaker 1: but it seems like they happen in most cases if
Speaker 1: it progresses that far.
Speaker 2: Okay.
Speaker 1: So the infection with this parasite results in changes to
Speaker 1: our circadian rhythm such that people end up with disruptions
Speaker 1: in their REM and non REM sleep. So we have
Speaker 1: different cycles of sleep REM when we're dreaming and you
Speaker 1: have those rapid eye movements, and then non REM sleep.
Speaker 1: And what happens with tripanosomiasis is that your REM sleep
Speaker 1: happens at the beginning, like you fall asleep and you
Speaker 1: have what's called sleep on set REM instead of REM happening.
Speaker 1: After you have these periods of actually RESTful sleep of
Speaker 1: non REM sleep, and then you also have during the
Speaker 1: night episodes of wakefulness during the night, not being able
Speaker 1: to fall asleep, being up and active, and then sleepiness
Speaker 1: and frequent napping or just falling asleep like very rapidly
Speaker 1: the way you would in something like narcolepsy during the day.
Speaker 1: It's not typically a complete reversal like some older descriptions
Speaker 1: say people will completely reverse their cycles and sleep all
Speaker 1: day and be awake all night. It tends to not
Speaker 1: be that black and white, but it is a significant
Speaker 1: disturbance in our circadian rhythm that normally regulates how we
Speaker 1: wake and sleep.
Speaker 2: That is so fascinating.
Speaker 1: I can't even handle how interesting it is, and I
Speaker 1: will be completely honest. I read several really great papers
Speaker 1: about this there's one from Nature twenty eighteen that was
Speaker 1: called sleeping sickness is a circadian rhythm disorder. It goes
Speaker 1: into a lot more detail about it, but I would
Speaker 1: not do it justice to try and like explain all
Speaker 1: of the nuances of sleep and then the effects that
Speaker 1: this parasite has on sleep. But it has a lot
Speaker 1: of hormonal effects where it like actually changes the hormones
Speaker 1: that our body produces that affect sleep. It's so interesting.
Speaker 1: Erin and despite all of this disturbance in sleep and
Speaker 1: disruption of our circadian rhythms, the total amount of sleep
Speaker 1: that people get is actually similar in people with severe
Speaker 1: tripanasomiasis and in healthy controls.
Speaker 3: Oh interesting, it's just a different it's like different times.
Speaker 1: A completely different pattern of sleep.
Speaker 3: Yeah, Okay, why why does it do this?
Speaker 1: Great question? We still don't fully know, but we have
Speaker 1: a lot of clues. Okay, So one clue is that
Speaker 1: tripanosomes tend to localize to parts of our brain, and
Speaker 1: like the places that they enter into our central nervous
Speaker 1: system tend to be places that are like just outside
Speaker 1: our blood brain barrier. And many of those places are
Speaker 1: I either response or have a lot of neurons which
Speaker 1: travel through them, that are involved in the regulation of
Speaker 1: our sleep wake cycles, that are involved in our circadian rhythm.
Speaker 1: So tripanosomes localize to this part of the brain that
Speaker 1: allows them easier entry through that blood brain barrier, and
Speaker 1: it just so happens that those areas are involved in
Speaker 1: some way in our sleep wake cycles. We still don't
Speaker 1: know exactly what it is about these parasites that causes
Speaker 1: these changes. What we do know is that it is
Speaker 1: it requires two different things. It requires the presence of
Speaker 1: the parasite. It's not inflammation alone, despite the fact that
Speaker 1: inflammation is running rampant when you have this infection. But
Speaker 1: it's not inflammation alone because we don't see this with
Speaker 1: other kinds of inflammation or in studies where they induce
Speaker 1: similar inflammation but without the parasite. But we're not sure
Speaker 1: if it's the parasite itself or something that the parasite
Speaker 1: produces that has an effect on our hormones and metabolites.
Speaker 1: But it's also not direct damage to our central nervous system.
Speaker 1: And we know this because these sleep disturbances resolve with treatment.
Speaker 3: Which is really wonderful, really.
Speaker 1: Wonderful and fascinating. So it's something about the parasite and
Speaker 1: its interaction with our immune system and our hormonal regulation
Speaker 1: that then causes this massive disruption but doesn't cause any
Speaker 1: direct damage to the structures involved in our circadian rhythms.
Speaker 2: I have a hypothesis, Okay, give it to me.
Speaker 3: So this is not about the mechanism at all, but
Speaker 3: it's more about like the why this might be something
Speaker 3: that the parasite does. So if people are having sleep
Speaker 3: disruptions and they're napping more throughout the day, if they're
Speaker 3: infected with this, the day is when SETSI flies are
Speaker 3: the most active, and so if someone is sleeping, they're
Speaker 3: less likely to be able to fend off the flies. Right,
Speaker 3: that's a really good point erin yeah, I wonder if
Speaker 3: that's but why not have someone sleep all day?
Speaker 2: I mean, because evolution is not perfect, it's.
Speaker 1: But that's a really good point, Aaron, That's a really
Speaker 1: really interesting way to look at it.
Speaker 2: There's so much more.
Speaker 3: I want to ask a thousand questions, there's.
Speaker 1: So much reading. All of this really made me feel
Speaker 1: like we need to do an episode on sleep.
Speaker 2: Okay, yep, let's do it.
Speaker 1: We should probably do an episode on narcolepsi. Okay, Okay,
Speaker 1: so we've got a lot more learning to do.
Speaker 3: Yeah, and we have to do an episode on viviparous insects.
Speaker 3: Oh my gosh, I love that.
Speaker 1: I feel like May Berenbaum would be so proud.
Speaker 3: Oh my gosh, we'll have her on.
Speaker 1: So that is kind of the the basics of the
Speaker 1: biology of this disease.
Speaker 2: How does the treatment work?
Speaker 1: Yeah, I was wondering if you were going to ask
Speaker 1: or if you just wanted me to bring it up again.
Speaker 1: So the diagnosis and treatment of this are both important
Speaker 1: to talk about and both leave a bit to be
Speaker 1: desired at this point. And one thing that at least
Speaker 1: in the past, has posed a significant additional challenge when
Speaker 1: it comes to human African tapinosamiasis is that historically it
Speaker 1: was very important to distinguish between those first and second
Speaker 1: stages when you make the diagnosis, because the treatment was
Speaker 1: actually completely different if that central nervous system invasion had begun.
Speaker 1: And historically, as was briefly mentioned in our first hand account,
Speaker 1: the treatment for late stage central nervous system associated disease
Speaker 1: was actually like very gnarly for a really long time,
Speaker 1: very toxic medicine that caused really severe reactions in up
Speaker 1: to ten percent of people and was really like not
Speaker 1: a great drug. Yeah, the good news is that very
Speaker 1: recently there is a new treatment option available that, at
Speaker 1: least for tripanosoma brucie gambiency can be used to treat
Speaker 1: both stage one and stage two disease. And this means
Speaker 1: that not only do you have a medication that works
Speaker 1: and that works well, but it also means you don't
Speaker 1: necessarily have to distinguish between has this parasite made it
Speaker 1: into your brain or not, because that diagnosis is actually
Speaker 1: really challenging and there's not like a great, like perfect
Speaker 1: kind of gold standard to diagnose that essentially.
Speaker 3: And once someone is treated and recovers, they can become
Speaker 3: infected again.
Speaker 4: Right far as I know, Yes, Okay, unfortunately, Yeah, So
Speaker 4: the Yeah, that's the biology, Arin'.
Speaker 2: It's so interesting.
Speaker 1: It's a lot. It's a lot, and I know that
Speaker 1: I missed a lot of parts. Don't worry, we have
Speaker 1: lots of papers, Aaron.
Speaker 3: I have so many questions, Okay, I will do my
Speaker 3: best to answer every question you have about the history
Speaker 3: or at least what I know about the history of
Speaker 3: this disease.
Speaker 5: Right after this break.
Speaker 3: Okay, this story of sleeping sickness. Like I said, this
Speaker 3: is a big story, and to be honest, it wasn't
Speaker 3: the easiest to get a handle on, not because there's
Speaker 3: not a lot of information out there about it, because
Speaker 3: there certainly is, but because it's a complex story whose
Speaker 3: narrative seems to have changed over time, especially as it
Speaker 3: relates to the enormous epidemics in Uganda and the Congo
Speaker 3: Basin in the early twentieth century. And part of the
Speaker 3: reason for this change is because we've learned a lot
Speaker 3: more about the parasites and the vectors themselves and how
Speaker 3: the whole ecology of the system works, which has helped
Speaker 3: to fill in some of the picture of how sleeping
Speaker 3: sickness spread across the African continent in the late eighteen
Speaker 3: hundreds and early nineteen hundreds. But another big part of
Speaker 3: it is the gradual shift in what people have recognized
Speaker 3: as the primary drivers of these epidemics and in.
Speaker 2: How they talk about them.
Speaker 3: So because the history of sleeping sickness is so intertwined
Speaker 3: with the history of colonialism in Africa, and for a
Speaker 3: good chunk of time, the bulk of what was written
Speaker 3: about the disease was written by the people actively participating
Speaker 3: in colonialism.
Speaker 2: It can be.
Speaker 3: Hard sometimes to read through that imperialist rhetoric, like, for instance,
Speaker 3: take human movement. Human movement did play a role in
Speaker 3: increasing the distribution of sleeping sickness in these big epidemics.
Speaker 3: But was it because people could move around more freely
Speaker 3: in the newly peaceful continent thanks to the arbitrary partitioning
Speaker 3: by the European imperial powers, or was it actually because
Speaker 3: people had to move around more to escape the violence, famine,
Speaker 3: and oppressive conflict that these colonists seemed to bring with them. Spoilers,
Speaker 3: It's definitely more the latter than the former. But in
Speaker 3: a lot of the early texts, you're going to see
Speaker 3: a lot more of the former than the latter. Yeah,
Speaker 3: but I'm getting ahead of myself, And so maybe before
Speaker 3: we try to examine what actually went on with those
Speaker 3: sleeping sickness epidemics of the early twentieth century, we should
Speaker 3: figure out maybe where.
Speaker 2: These parasites came from in the first place. Yes, can
Speaker 2: we please?
Speaker 3: Well, we can try, because I have kind of vague answers,
Speaker 3: but actually vague answers that became a little bit clearer
Speaker 3: with the biology section, which is pretty fun.
Speaker 1: Love it when that happens.
Speaker 3: Arin, Yeah, okay, So let's start broadly with the group
Speaker 3: of tripanosomes that these two causative agents of human African
Speaker 3: tripanisamiasis are a part of.
Speaker 2: And like you said, Aaron, you know you.
Speaker 3: Made this distinction between the tripanisome that causes shagas disease
Speaker 3: and how it's transmitted through the feces of the kissing
Speaker 3: bug and these two subspecies that are transmitted through the
Speaker 3: bite of a Setsi fly. So, these subspecies that cause
Speaker 3: human African trypanism miasis, these are known as salavarian trypanosomes.
Speaker 3: Isn't that fun it? Yeah, because they're transmitted through the
Speaker 3: saliva of their insect vector.
Speaker 2: I don't know.
Speaker 1: Why that sounds like a like an alien life form
Speaker 1: or something.
Speaker 3: Salivarian, it sounds like, yeah, like an evil character in
Speaker 3: this character. Well, and then you know accompanied by stirkuan,
Speaker 3: which means transmitted through the feces.
Speaker 1: My other favorite word.
Speaker 3: Yeah. And so the salavarian trypanosomes, they're thought to have
Speaker 3: originated in Africa and split off from the other trypanosomes
Speaker 3: around three hundred million years ago, is one estimate. I
Speaker 3: saw so very long time, long time, and when they
Speaker 3: split off, this is the point at which they probably
Speaker 3: became gut commensals or maybe even parasites of these early insects.
Speaker 3: And there they stayed in the guts in these insects
Speaker 3: for a very very long time, which is how they
Speaker 3: got into setsiflies, who evolved around thirty five million years ago.
Speaker 3: And by got into setsiflies, I really mean that they
Speaker 3: were probably there from the beginning, like they evolved with
Speaker 3: these flies as the flies evolved. And it's not clear
Speaker 3: exactly when this group of tripanosomes began venturing out of
Speaker 3: their fly hosts into mammalian animals, but it certainly doesn't
Speaker 3: seem to have been a recent development, considering that many
Speaker 3: African wild animals show a degree of tolerance towards SETSI
Speaker 3: transmitted tripanosomes, suggesting like a long association. So in addition
Speaker 3: to Tripanosoma brucei and that whole species complex with those
Speaker 3: three subspecies, there are also a bunch of other species
Speaker 3: in the Tripanosoma genus that caused tripanasamias in wild animals
Speaker 3: and especially domestic livestock. So anyway, I just wanted to
Speaker 3: throw that out there.
Speaker 1: I actually had no idea just how many species there are,
Speaker 1: Like there's so many.
Speaker 3: So many, so many, And so the fact that a
Speaker 3: lot of these African wild mammals show a degree of
Speaker 3: tolerance towards these tripanosomes that kind of suggest this long
Speaker 3: association with those right, Like you would expect that like, oh,
Speaker 3: the longer they were together, the more likely it is
Speaker 3: for them to evolve some sort of tolerance.
Speaker 2: Or resistance mechanism.
Speaker 3: And the same goes actually, like you said Aaron for humans.
Speaker 3: So humans don't seem to be susceptible to those other
Speaker 3: species of tripanosomes that can cause disease in animals, which
Speaker 3: is fascinating.
Speaker 1: Because we're really good at just taking them out mm hm.
Speaker 3: And so, like I wrote in my notes that like
Speaker 3: maybe humans developed resistance, or maybe these tripanisomes didn't evolve
Speaker 3: any sort of mechanism to infect humans, But it's clear
Speaker 3: now from what you said that the humans actually developed resistance.
Speaker 3: And it's thought that this happened when the early ancestors
Speaker 3: of humans came down from the trees and began to
Speaker 3: live in the savannah where they would have encountered these parasites.
Speaker 3: And this is supported in part by the finding that
Speaker 3: primates that mostly live in trees still are susceptible to
Speaker 3: these parasites that humans and other ground dwelling primates rarely
Speaker 3: get infected with. Wow, so they lack the tripanosome killing protein,
Speaker 3: which is so interesting.
Speaker 1: Oh my gosh cool.
Speaker 3: And so, like you said, Aarin, this long exposure to
Speaker 3: tripanosomes has definitely left its mark on the human genome,
Speaker 3: right with these tripanalytic factors that we seem to have.
Speaker 3: But and this research is I think still a little
Speaker 3: bit under discussion, but I found it really interesting, so
Speaker 3: I wanted to include it. There seems to be variation
Speaker 3: even within those tripanalytic factors, right, with some being maybe
Speaker 3: more effective than others. And so there are two variants
Speaker 3: of a gene that seemed to be especially common in
Speaker 3: people of African descent. And these variants seem to show
Speaker 3: signs of positive selection, meaning like they've provided some sort
Speaker 3: of evolutionary advantage, and so they're at higher rates than
Speaker 3: we would expect them to be. And that's an interesting
Speaker 3: finding considering that these variants are also associated with an
Speaker 3: increased risk of kidney disease.
Speaker 2: And so it seems though.
Speaker 3: That a closer look at these variant proteins shows that
Speaker 3: they may be able to life tripanisomes, specifically tripanisoma bruceise Huh.
Speaker 3: So it might be kind of like in the way
Speaker 3: that sickle cell trait and malaria has this sort of like, well,
Speaker 3: this is beneficial to protect against this disease, but it
Speaker 3: also in you know, homozygous form might lead to an
Speaker 3: increased risk of other disease.
Speaker 1: That is very interesting. It's also interesting in the context
Speaker 1: and I didn't even get into this, but there are
Speaker 1: some slightly different descriptions of especially the early stages of
Speaker 1: the course of disease in people who travel to Africa
Speaker 1: versus people who live and were born in endemic regions.
Speaker 1: Interesting and I wonder if there if there's any component
Speaker 1: of differences in selection for some of those specific different
Speaker 1: kindism analytic factors that might that's so interesting.
Speaker 3: Yeah, again, there's there's definitely a lot more there, and
Speaker 3: I think it's still in like early stages, but I
Speaker 3: will post the articles for sure.
Speaker 1: Yeah.
Speaker 3: Okay, So historically these setsiflies associated trypanosomes, they probably had
Speaker 3: a wider distribution than they do today, reaching up at
Speaker 3: least into the Nile delta, but they probably didn't make
Speaker 3: it to all the places that setsiflies did, given the
Speaker 3: fact that domestic animals still seem to be very susceptible
Speaker 3: to most of these trypanosomes, and so if there was
Speaker 3: like a global distribution of them, than we would expect
Speaker 3: to see, you know, more resistance or tolerance like we
Speaker 3: do in wild mammals in Africa. And I'm not sure
Speaker 3: what limited these historical trypanosome distributions, if anything, but there
Speaker 3: is evidence of setsiflies well outside of Africa, like even
Speaker 3: here in Colorado there are family fossils.
Speaker 2: Yeah, and the fluorescent fossil.
Speaker 1: Beds so not active, but like in the past.
Speaker 2: In the past, in the past. Yeah.
Speaker 3: And it's thought though that climate is really the big
Speaker 3: factor in where it's set flies can make their home,
Speaker 3: which does you know, raise the question of future climate
Speaker 3: change and current climate change and sleeping sickness distributions. Okay,
Speaker 3: so that's a lot about the evolution of African tripanosomes
Speaker 3: in general, but what about the two subspecies that cause
Speaker 3: disease in humans? So I honestly couldn't find good timing
Speaker 3: on when this might have happened. But given that they
Speaker 3: seem to have this you know, there seems to be
Speaker 3: like we're in the process of an arms race. I
Speaker 3: would guess it's like a pretty long amount of time,
Speaker 3: whatever that means. And honestly, I mean the taxonomy and
Speaker 3: phylogeny of these two subspecies it seems to be under
Speaker 3: debate or at least discussion. Okay, because Tripanosoma bruceye gambience
Speaker 3: does seem to be distinct from Tripanosoma bruce brucei, which
Speaker 3: is one that does not cause disease in humans generally.
Speaker 3: But Rhodesiense and Brucei seem to be incredibly similar to
Speaker 3: one another, both morphologically as well as genetically, with one exception,
Speaker 3: and that is the gene that allows Rhodesia to infect humans. Wow.
Speaker 4: Yeah.
Speaker 2: And so this has.
Speaker 3: Led to questions about whether Rhodesiense could be just considered
Speaker 3: a variant of Tripanosoma bruce brucei that has an increased
Speaker 3: host range. Oh man, right, So if you look at
Speaker 3: it in just the picture of host range, and we're like, oh,
Speaker 3: this can infect X, Y and Z species, right, and
Speaker 3: this and this can infect W, X, Y and Z, Like, right,
Speaker 3: does the W matter?
Speaker 2: And it does?
Speaker 3: In a public health sense for sure. But it's just
Speaker 3: an interesting way to frame it, I think.
Speaker 1: Right, but does it does it qualify it as a
Speaker 1: different subspecies?
Speaker 2: Right?
Speaker 1: Oh? That is interesting erin.
Speaker 3: Yeah, So it's possible that we'll see the reshuffling and
Speaker 3: rearranging of the taxonomy or phylogeny or whatever of these
Speaker 3: parasites in the future, but not just because the evolutionary
Speaker 3: relationships don't seem to be represented in their current arrangement,
Speaker 3: because there's also been some discussion recently about decolonizing the
Speaker 3: species name. Tripanosoma brucei rhodesiense, so, like Tripanosoma brucei gambience,
Speaker 3: Wheredesiense was named after the region it was first found, Rhodesia,
Speaker 3: which is a historical region in Southern Africa, which got
Speaker 3: its name after white settlers began calling it that informally
Speaker 3: after Cecil Rhodes, the British mining magnate and managing director
Speaker 3: of the British South Africa Company and also owner of
Speaker 3: many diamond mines and the Dedber's Diamond Company. Rhodes was
Speaker 3: born in eighteen fifty three. And I'm not going to
Speaker 3: go into the biography here. There's plenty on I mean,
Speaker 3: just skim Wikipedia and you'll get the fear. But he essentially,
Speaker 3: long story short, turned out to be a huge white
Speaker 3: supremacist and imperialist, and over the past few decades there's
Speaker 3: been an increasing push to remove statues of him or
Speaker 3: his name from buildings or scholarships named after him, And
Speaker 3: in twenty twenty one, a paper also called for the
Speaker 3: renaming of the parasite that bears his name. And I
Speaker 3: think it's an interesting conversation because you know, we've talked
Speaker 3: about so many times on this podcast how names have
Speaker 3: meaning and power, and I think it's good to re
Speaker 3: examine why we name things the way we do, and
Speaker 3: whether there are less harmful or more accurate names that
Speaker 3: could be used instead. And the authors make the point
Speaker 3: that if Tripanasoma BRUCEI rudisience is just a variant of
Speaker 3: Tripanosoma bruce eye BRUCEI, then might it be most accurate
Speaker 3: to just completely strike out rhodesiense and just call it
Speaker 3: Tripanasoma Brucey BRUCEII.
Speaker 2: I don't know. Yeah, problem solved.
Speaker 3: I'll post that paper also on our website if you
Speaker 3: want to read more, but I'm going to move on
Speaker 3: for now. So I've mentioned that Although we don't know
Speaker 3: exactly when humans began getting sleeping sickness, it's probably been
Speaker 3: around for thousands and thousands of years. And you know,
Speaker 3: we can see this in some of the long standing
Speaker 3: practices that many people in Africa use to avoid conflict
Speaker 3: with the tetsiflies, and it's also reflected in early writings,
Speaker 3: one of which is from thirteen seventy three or thirteen
Speaker 3: seventy four CE, describing the death of the King of Molly. Quote,
Speaker 3: he told me that Jata had been smitten by the
Speaker 3: sleeping sickness, a disease which frequently afflicts the inhabitants of
Speaker 3: that climate, especially the chieftains, who are habitually affected by sleep.
Speaker 3: Those afflicted are virtually never awake or alert. The sickness
Speaker 3: harms the patient and continues until he perishes. He said
Speaker 3: that the illness persisted in just to humor for a
Speaker 3: duration of two years, after which he died in the
Speaker 3: year seven seventy five, which is actually like thirteen seventy three.
Speaker 3: Sleeping sickness gained more European recognition as the slave trade began.
Speaker 3: Medical officers who were supposed to inspect enslaved people noticed
Speaker 3: certain signs and symptoms of the disease, and also how
Speaker 3: deadly it could be. In seventeen forty two, it was
Speaker 3: described in an article about the neurological symptoms as a
Speaker 3: quote sleepy distemper, and in eighteen oh three the English
Speaker 3: physician Thomas Winterbottom published a report describing how the lymph
Speaker 3: glands on the back of the net were often swollen
Speaker 3: from this disease, which is something that would later be
Speaker 3: called Winterbottom sign. But even according to winter Bottom, this
Speaker 3: was not a new discovery, because apparently Arabian slave traders
Speaker 3: would use those swollen glands in the past to determine
Speaker 3: whether or not to buy and slap. So despite the
Speaker 3: recognition by some of these early physicians that this disease
Speaker 3: was not new, the prevailing notion during the beginning of
Speaker 3: the enormous imperialist efforts in Africa was that this was
Speaker 3: a sporadic disease that African people knew nothing about and
Speaker 3: had never seen before. Right, But like, all you had
Speaker 3: to do is just ask, But you know who was
Speaker 3: going to do that. Not only had this disease been
Speaker 3: at least present throughout big chunks of the continent for
Speaker 3: thousands of years, there was actually quite a bit of
Speaker 3: knowledge about it, of course, and about animal African tripanisamiasis
Speaker 3: as well. For instance, it was known that traveling with
Speaker 3: livestock through certain regions during the day it shouldn't be
Speaker 3: done because that's when Setsi flies were active, and it
Speaker 3: was better to travel at night. And this is actually
Speaker 3: what the explorer David Livingstone was told in the mid
Speaker 3: eighteen hundreds during his travels. And of course, there were
Speaker 3: many different names for the disease, and knowledge and practices
Speaker 3: to prevent the disease varied across different populations as well,
Speaker 3: such as like setting intentional fires to clear areas of
Speaker 3: flies and the animals that they fed on, simply avoiding
Speaker 3: infested areas, or isolating people with sleeping sickness. But however,
Speaker 3: sleeping sickness was traditionally kept at bay, or at least
Speaker 3: kept relatively at bay. All of those structures and practices
Speaker 3: essentially broke down or collapsed beginning with the widespread European
Speaker 3: colonization that began in the late eighteen hundreds, and the
Speaker 3: consequences of this for sleeping sickness were horrific. So I'm
Speaker 3: going to focus on the two big epidemics of sleeping
Speaker 3: sickness that occurred in Africa in the early nineteen hundreds,
Speaker 3: one in the Congo Basin and the other in parts
Speaker 3: of Uganda. Between eighteen ninety six and nineteen oh six.
Speaker 3: These epidemics killed over five hundred thousand people in the
Speaker 3: Congo Basin and two hundred and fifty to three hundred
Speaker 3: thousand people, which was about a third of the entire
Speaker 3: population in the affected area in Uganda. Yeah, so what
Speaker 3: caused these epidemics, what did we learn from them? What
Speaker 3: were some of the lasting impacts? And I'm going to
Speaker 3: try to answer these questions, starting with what researchers believe
Speaker 3: led to this surge in sleeping sickness. Unsurprisingly, it was
Speaker 3: really a combination of many different factors. There was famine,
Speaker 3: wide scale movement, often forced landscape alteration, and render pest
Speaker 3: render pest, and all of these were either directly caused
Speaker 3: by or exacerbated by the increasing colonialism that was going
Speaker 3: on in the late eighteen hundreds. European colonialism was in
Speaker 3: full swing and the so called Scramble for Africa had
Speaker 3: begun kicked off, especially with the Burn Conference in eighteen
Speaker 3: eighty four, where basically like the European power sat down
Speaker 3: and they were like, all right, who wants this chunk
Speaker 3: of the continent.
Speaker 2: Who wants this? Okay, you get this.
Speaker 3: Part of East Africa, you get this part of West Africa.
Speaker 3: And so you have like Britain, France, Germany and Portugal
Speaker 3: as some of the major players, you know, deciding who
Speaker 3: gets what. And a lot of East and West Africa
Speaker 3: had been sort of partitioned off, but much of Central
Speaker 3: Africa was still viewed as being up for grabs. And
Speaker 3: so King Leopold the Second of Belgium he threw his
Speaker 3: hat into the ring, and he didn't want to claim
Speaker 3: this big bit of the Congo basin for Belgium necessarily,
Speaker 3: like he didn't want to make it a colony, but
Speaker 3: he wanted to keep it as a private free state
Speaker 3: where he could sort of be the unquestioned ruler and
Speaker 3: make as much money as he possibly could, and also
Speaker 3: to keep trade open between Western and Eastern African states.
Speaker 3: And so I mentioned Leopold and the Congo Free State
Speaker 3: in particular because this is where that deadly epidemic occurred,
Speaker 3: and because it provides such a clear example of how
Speaker 3: sleeping sickness was spread, not because the European self proclaimed
Speaker 3: saviors made peaceful movement possible. But because the brutality and
Speaker 3: violence that was perpetrated by these colonial powers, it drove
Speaker 3: the disease to be more widespread and prevalent. So to
Speaker 3: set the stage for sleeping sickness, I need to start
Speaker 3: with another disease, render pest.
Speaker 1: Render pest by.
Speaker 3: The late eighteen hundreds, render pest, which is a cattle disease.
Speaker 3: It's a virus that kills cattle like kills ungulates, and
Speaker 3: it's viciously deadly.
Speaker 1: It's horrific. We did a whole episode on it. When
Speaker 1: was it, season two, three and three? Yeah, season three,
Speaker 1: check it out.
Speaker 3: It's been eradicated, but it's yeah, check it out. I'm
Speaker 3: going to go over a little bit of the just
Speaker 3: like a brief, you know, listener's digest, but because it's
Speaker 3: important to go into here. And so in the late
Speaker 3: eighteen hundreds, rinderpest was brought to Ethiopia, and from there
Speaker 3: it spread south rapidly across the continent and it killed
Speaker 3: I mean millions and millions, just unfathomable numbers of cattle
Speaker 3: and wild ungulates in some places, like ninety five percent
Speaker 3: just wiped them out, wiped out, and in our render
Speaker 3: Pest episode, I talked about how the spread of renderpest
Speaker 3: was in some places accompanied by a drought and then
Speaker 3: extreme rains bringing locusts that ate all the crops, and
Speaker 3: so by the mid eighteen nineties you've got this combination
Speaker 3: of livestock deaths, wild ungulate deaths, and crop failure that
Speaker 3: leads to a horrible famine in many regions. And we
Speaker 3: know from our Typhus episode how times of famine leave
Speaker 3: people super vulnerable to many infectious diseases. The loss of cattle,
Speaker 3: which for many people was either entirely or at least
Speaker 3: a huge part of their livelihood, meant that people had
Speaker 3: less autonomy and they had to turn to other ways
Speaker 3: to survive in these colonial states, like working in deadly
Speaker 3: mines or harvesting rubber. This shift in labor wasn't always voluntary.
Speaker 3: In Leopold's Congo Free State, people were forced threatened with
Speaker 3: death or mutilation either of themselves or family members if
Speaker 3: they didn't work or fill their quotas.
Speaker 2: As I mentioned in.
Speaker 3: Our Wnderpest episode, this panzootic was used by European colonial
Speaker 3: powers to extend their reach, and what they didn't accomplish
Speaker 3: in that regard through renderpest, they would.
Speaker 2: With sleeping sickness.
Speaker 3: So at the end of the renderpest epidemic around eighteen
Speaker 3: ninety six or so, the social, political, and natural landscape
Speaker 3: of much of Africa had changed substantially. Famine was widespread,
Speaker 3: more and more Africans had been forced to work in
Speaker 3: mines or collect rubber and not do subsistence farming, and
Speaker 3: the wild ungulate population had nearly disappeared, along with domestic cattle.
Speaker 3: And at first this could be viewed as a good
Speaker 3: thing in terms of sleeping sickness, because with the absolute
Speaker 3: annihilation of so many hosts, setsifly populations dropped.
Speaker 2: But then as the.
Speaker 3: Forest recovered and wildlife came back in, and as people
Speaker 3: began to bring livestock and settled into these newly setsifly
Speaker 3: free zones places where they couldn't before because of the
Speaker 3: risk of animal African tripanismiasis, that setsiflies then recovered, and
Speaker 3: they did so to a huge extent. And when they
Speaker 3: came back, the setsiflies found ample mammals to feed on,
Speaker 3: and their tripanosomes found plenty of hosts to replicate and
Speaker 3: differentiate in including humans.
Speaker 2: So it's not a.
Speaker 3: Coincidence really that the sleeping sickness epidemics began as the
Speaker 3: renderest panzootic ended. But it wasn't just that rinderpest suddenly
Speaker 3: meant that humans and setsiflies and trapanisomes were in contact
Speaker 3: more than they had been before. There was also the
Speaker 3: aspect of human movement, and this wasn't done just by
Speaker 3: renderpest either. In the Congo Free State, as I mentioned,
Speaker 3: Leopold had established a rule that was motivated by the
Speaker 3: ruthless pursuit of economic gain. Any resistance was met with
Speaker 3: extreme violence, burning villages outright slaughter, holding women in cattle hostage.
Speaker 3: So many people fled the brutality or had to travel
Speaker 3: farther and farther from their village in order to find
Speaker 3: enough wild rubber to meet this rubber tax that had
Speaker 3: been imposed on all of them. It was demanded of
Speaker 3: each person, you don't pay the tax, I'm going to
Speaker 3: chop off your hand, or just kill you, or chop
Speaker 3: off the hand of your family member. So they would
Speaker 3: be spending twenty one to twenty five days per month
Speaker 3: in the forest, far away from home and in excellent
Speaker 3: setsifly habitat. There's a lot more to the story of
Speaker 3: the Congo Free State and Leopold, and I highly recommend
Speaker 3: reading the book Leopold's Ghost. But to sum up, it's
Speaker 3: estimated that ten million people died in what was first
Speaker 3: the Congo Free State and then later the Belgian Congo
Speaker 3: under Leopold's reign. That was about half the population. Ten
Speaker 3: million people died, and they died due to these violent practices,
Speaker 3: due to famine and due to disease, and then also
Speaker 3: due to just like a drop in the overall birth
Speaker 3: rate because people were you not able to yeah.
Speaker 5: Just.
Speaker 3: Yeah, oh dear, there's a lot more to unpack there
Speaker 3: that I just don't I can't do it justice here. Yeah,
Speaker 3: but yeah, sleeping sickness did contribute a substantial amount to that,
Speaker 3: you know, horrifically enormous number. But the Belgian Congo wasn't
Speaker 3: the only place where a colonial rule led to forced
Speaker 3: labor and forced movement. Uganda was under British rule during
Speaker 3: the big sleeping sickness epidemic that affected the Busoga region
Speaker 3: along Lake Victoria, and they had put into place a
Speaker 3: so called hut tax where each household had to pay
Speaker 3: a certain amount in taxes, and that was often more
Speaker 3: than the building could actually be sold for. This need
Speaker 3: for cash shifted labor away from subsistence farming, and if
Speaker 3: someone couldn't pay the tax, they would have to do
Speaker 3: a month's labor, usually far away from their village. So
Speaker 3: it was just like suddenly here was stress and movement
Speaker 3: and disruption and like a complete lack of autonomy and
Speaker 3: everything was just.
Speaker 2: Yeah.
Speaker 3: And so how much did these movements contribute to the
Speaker 3: geographic spread of sleeping sickness and any changes in its distribution?
Speaker 3: And it's not really clear. So historically it was thought
Speaker 3: that sleeping sickness was brought to East Africa from the
Speaker 3: Congo basin, but now people suggest that the parasites both
Speaker 3: subspecies had probably been present everywhere the vectors could be found,
Speaker 3: and it just appeared to spread because of the rapid
Speaker 3: jump in cases. And I should also point out here
Speaker 3: that these epidemics have long been thought to be caused
Speaker 3: by the gambience subspecies, but more recently some researchers have said, oh, actually,
Speaker 3: maybe the Uganda one was rudisience because of the clinical picture. Okay, okay,
Speaker 3: So the combination of the ecological cascades of renderpest, increased
Speaker 3: movement under colonial rule, and the huge amount of stress
Speaker 3: from famine and brutality led to a situation where the
Speaker 3: t setsifly in its sleeping sickness, parasites could flourish. Okay,
Speaker 3: So now let's see what happened once sleeping sickness had
Speaker 3: awakened in Uganda and the Congo Free State in the
Speaker 3: late eighteen hundreds. European imperialists had long seen much of
Speaker 3: Africa as being held back by disease. But what that
Speaker 3: really meant, if you read between the lines of rhetoric,
Speaker 3: was that they felt that disease was preventing Europeans from
Speaker 3: taking control of the continent and exploiting people in resources
Speaker 3: the way they wanted to. So Quinine, which was introduced
Speaker 3: in the eighteen twenties, was helpful for treating malaria, but
Speaker 3: there were still many tropical diseases for which there was
Speaker 3: no treatment or cure, and not long after the birth
Speaker 3: of germ theory in the mid eighteen hundreds, researchers began
Speaker 3: to specialize in studying pathogens and parasites that were found
Speaker 3: in tropical regions of the world, many of which happened
Speaker 3: to also be targets for colonialism, and I think I've
Speaker 3: discussed this before in our leshmaniasis episode, or maybe our
Speaker 3: schistis isis episode. I didn't look back, I might have
Speaker 3: mentioned it in both. But the field of tropical medicine
Speaker 3: was motivated in large part by protecting the financial interests
Speaker 3: of European colonial powers and the health of Europeans.
Speaker 2: In those colonies.
Speaker 3: So when sleeping sickness began to appear in large numbers,
Speaker 3: there was this big push to try to understand what
Speaker 3: was causing it and how it was transmitted, so that
Speaker 3: it spread could be stopped or at least slowed. Microbiologists
Speaker 3: and parasitologists flocked to the shores of Lake Victoria or
Speaker 3: to the Congo Basin to try to make a name
Speaker 3: for themselves. Robert Koch was one of these, and another,
Speaker 3: John Lancelot Todd, who would later join this Liverpool expedition
Speaker 3: to study the disease in the Congo Free State, wrote
Speaker 3: home quote, trips are a big thing, and if we
Speaker 3: have luck, I may make a name. Yet there was
Speaker 3: even a poem published around this time in the British
Speaker 3: satire magazine Punch about sleeping sickness.
Speaker 2: Quote men of.
Speaker 3: Science, you that dare beard the microbe in his lair,
Speaker 3: tracking through the jungly thickness Afric's germ of sleeping sickness. Here, oh, here,
Speaker 3: my parting plea send a microbe home to me, Send
Speaker 3: a microbe home to me.
Speaker 1: AHM, what we all write.
Speaker 3: Yeah, of course, but many people did send a microbe home,
Speaker 3: or at least find luck with tripanosomes. The Scottish microbiologist
Speaker 3: David Bruce first observed one of the causative agents of
Speaker 3: nagana and cattle in eighteen ninety five. Six years later,
Speaker 3: in nineteen oh one, British colonial surgeon Robert michael Ford
Speaker 3: identified tripanosomes in the blood of a steamboat captain in
Speaker 3: the Gambia. Actually he thought they were worms at first,
Speaker 3: and a few months later English physician John Everett Dutton
Speaker 3: was like, no, man, these are definitely tripanosomes. I'm going
Speaker 3: to name them Tripanasoma gambience. They were all thought to
Speaker 3: be the three Tripanisaba, Brucii, Gambience and Rudisience were all
Speaker 3: thought to be separate species at the beginning. The next
Speaker 3: link was made that same year in nineteen oh one,
Speaker 3: when Italian physician Aldo Castellani observed tripanisomes and the cerebrospinal
Speaker 3: fluid of people with sleeping sickness and said, hey, these
Speaker 3: these might be the cause. And the last pieces of
Speaker 3: the puzzle fell into place when the setsifly was found
Speaker 3: to yes, indeed, transmit these trypanosomes that cause sleeping sickness.
Speaker 3: In nineteen ten, finally, the other subspecies of trypanosome that
Speaker 3: causes sleeping sickness, rhodesiense, was identified by John William Watson
Speaker 3: Stevens and Harold Benjamin Phantom, and a bunch of other
Speaker 3: animal trypanosomes were discovered in the meantime. But these efforts
Speaker 3: in tropical medicine, they weren't just about identifying the parasite
Speaker 3: and the vector. They were also about treatment. Robert Cooke
Speaker 3: and Paul Erlik, whose names certainly should sound familiar.
Speaker 1: I would hope so by now, they had.
Speaker 3: A hand in the development of the first drugs used
Speaker 3: to treat sleeping sickness around nineteen oh five. The first
Speaker 3: of these drugs, whose name was a toxl meaning non
Speaker 3: toxic oh gosh, was arsenic based and often led to death.
Speaker 3: In about five to ten percent of the people who
Speaker 3: were treated, and blindness in about thirty percent. The amount
Speaker 3: you needed to inject into someone to have like an
Speaker 3: effect on the parasitic infection was about the amount that
Speaker 3: someone could handle without just dying outright.
Speaker 1: Yeah that the arsenic based compounds were used for until
Speaker 1: relatively recently. Oh yeah, and I mean it's still used
Speaker 1: for dyes, yancy.
Speaker 2: They are still used. They are less deadly.
Speaker 1: They are less deadly.
Speaker 3: But but that's not saying all that all that much. No, like,
Speaker 3: they're not they're not good. So so what did people
Speaker 3: do with this new knowledge about sleeping sickness and a deadly.
Speaker 2: Drug to treat it well?
Speaker 3: It partly depended on where you were. Both colonial powers,
Speaker 3: of course use the declaration of an epidemic as a
Speaker 3: tool to gain even more power, But specific disease control
Speaker 3: efforts differed in Uganda and the Congo Free State, with
Speaker 3: a more ecological focus controlled the setsifly in Uganda and
Speaker 3: a more human focus control the human reservoir in the
Speaker 3: Congo Free State. What did this mean in practice?
Speaker 2: In Uganda?
Speaker 3: It meant often the burning of setsi habitat, the destruction
Speaker 3: of tripanistome animal hosts, and the forced relocation of people
Speaker 3: away from sleeping sickness infested areas, in particular the shores
Speaker 3: of Lake Victoria. There was some identify and isolate but
Speaker 3: not nearly as much as there was in the Congo
Speaker 3: Free state.
Speaker 2: There.
Speaker 3: Leopold had commissioned a survey of the entire country to
Speaker 3: create a map with labels of uninfected and infected regions.
Speaker 3: Armed soldiers patrolled the borders of uninfected zones, and the
Speaker 3: movement of people in and out of the zones was
Speaker 3: strictly controlled. On top of this, there were enormous efforts
Speaker 3: made for public health teams to go out and find
Speaker 3: every case of sleeping sickness, and the easiest way to
Speaker 3: do this was to see if the glands on the
Speaker 3: back of their neck were swollen. And someone was determined
Speaker 3: to be infected. Using this incredibly subjective method and not
Speaker 3: necessarily accurate, they were sent, sometimes forcibly, often forcibly, to
Speaker 3: a lazarette to receive treatment or just weigh out their illness.
Speaker 3: These lazarettes were basically like kind of prisons in a way,
Speaker 3: like you weren't allowed to leave, you weren't really allowed
Speaker 3: visitors often, and you were kind of just told wait
Speaker 3: here and die. They were poorly staffed, medical treatment was
Speaker 3: not at all guaranteed, and a lot of the time
Speaker 3: neither was food. They became known as death camps, and
Speaker 3: at some of these camps mortality rates reached twenty five
Speaker 3: to thirty percent. Even one of the doctors who worked
Speaker 3: at one of these lazarettes said that a sign should
Speaker 3: be put up on the entrance that said, abandon all
Speaker 3: hope he who enter here.
Speaker 2: Yeah.
Speaker 1: Yeah.
Speaker 3: Did these interventions do anything like the burning of habitat
Speaker 3: or the identification of human hosts?
Speaker 2: I mean it's possible.
Speaker 3: Yeah, I mean we don't really have any way of
Speaker 3: measuring now how much of the decline of the sleeping
Speaker 3: sickness epidemics was due to the availability of treatment, or
Speaker 3: the destruction of habitat, or any ecological shifts or something
Speaker 3: else entirely. But even though cases dropped by nineteen ten
Speaker 3: or so, sleeping sickness didn't just cease to be a problem,
Speaker 3: And the way that the ruling colonial powers handled these
Speaker 3: epidemics paved the way for future efforts, particularly in how
Speaker 3: public health services were organized. So historically, public health in
Speaker 3: European colonies in Africa meant health services for European residents only,
Speaker 3: and Sleeping Sickness marked a turning point where administrators realized
Speaker 3: that they needed to extend those services to Africans as
Speaker 3: well as Europeans, maybe partly due to a humanitarian intention,
Speaker 3: I can't rule it out entirely, but it was also
Speaker 3: the simple matter of labor. As more and more people
Speaker 3: became infected with the tripanosomes, that meant fewer and fewer
Speaker 3: people who could be forced to labor at the mines
Speaker 3: or deliver the rubber or maintain the roads. The sleeping
Speaker 3: sickness campaigns, which were really the first of their kind
Speaker 3: in parts of Africa, were aimed at preventing or controlling
Speaker 3: this one disease, and that kind of set the pattern
Speaker 3: for future health services to also be pretty targeted. And
Speaker 3: this is what's called a vertical health service approach. So
Speaker 3: with these vertical health services already in place, where it's like, okay,
Speaker 3: one program, one disease, it's harder to transition to something
Speaker 3: that's more broad or integrated in its organization, and so
Speaker 3: you end up with a bunch of these individual programs
Speaker 3: that may not really talk to one another and may
Speaker 3: end up being inefficient or even neglectful of certain things,
Speaker 3: and the legacy of this is still being felt, and
Speaker 3: it's part of the conversation that goes on today about
Speaker 3: some current disease or eradication campaigns that tend to be
Speaker 3: very targeted. But going back to sleeping sickness and wrapping
Speaker 3: up very quickly.
Speaker 2: After these two.
Speaker 3: Big epidemics, incidents of the disease did seem to go down,
Speaker 3: though both World wars saw a bit of an increase,
Speaker 3: especially as movement for more rubber and resources increased. The
Speaker 3: widespread use of DDT led to further declines and the
Speaker 3: setsifly populations as well as in tripanosomes, and so the
Speaker 3: overall trend in the first half of the century after
Speaker 3: these big epidemics was one of a general decline in
Speaker 3: sleeping sickness. However, in the second half, cases began to
Speaker 3: rise again, usually following political upheavals and conflicts that led
Speaker 3: to the displacement of many people and the breakdown of
Speaker 3: medical infrastructure in countries, many of which were newly independent,
Speaker 3: And by the nineteen seventies there was another big epidemic
Speaker 3: go over one million people happening in Angola, Congo, Southern
Speaker 3: Sudan and the West Nile District of Uganda. Since then,
Speaker 3: there have been other improvements in treatments for this disease
Speaker 3: and a lot of incredible accomplishments in actually eradicating it
Speaker 3: from certain regions. But the story of sleeping sickness definitely
Speaker 3: doesn't seem like it's over, especially with land use change
Speaker 3: and climate change happening. So Erin, can you fill me
Speaker 3: in on what's going on with sleeping sickness today?
Speaker 1: I can't wait to aerin right after this break Well, Aaron,
Speaker 1: like you alluded to, we finally get the chance to
Speaker 1: end on a semi happy note this season.
Speaker 2: I know.
Speaker 1: So World Health Organization, along with many partners, has been
Speaker 1: targeting sleeping sickness or human African japan semiasis for control,
Speaker 1: and then they change their targets to elimination as a
Speaker 1: public health problem by twenty twenty and further reduction towards
Speaker 1: total elimination by twenty thirty. And they've gotten shockingly close.
Speaker 1: They really have, really shockingly close. So after the kind
Speaker 1: of historical outbreaks that you mentioned, Aaron, there was a
Speaker 1: lows of tripanasimiasis for a while, and then another resurgence
Speaker 1: in the nineties. That resulted in World Health Organization and
Speaker 1: other public health institutions really focusing on tripanasimiasis even more,
Speaker 1: and it's been really effective. In two thousand and nine,
Speaker 1: the number of reported cases fell to below ten thousand
Speaker 1: for the first time since the nineteen sixties. Wow, right
Speaker 1: below ten thousand reported cases worldwide. And in twenty nineteen,
Speaker 1: so ten years after that, there were only nine hundred
Speaker 1: ninety two cases reported.
Speaker 3: That's amazing, it's incredible.
Speaker 1: Now does that mean that only nine hundred ninety two
Speaker 1: people were affected?
Speaker 2: Certainly not.
Speaker 1: Underreporting is of course a factor, as in any disease,
Speaker 1: but especially in neglected diseases, and especially for a disease
Speaker 1: such as sleeping sickness that largely affects remote populations. But
Speaker 1: the efforts that have been made to identify and treat
Speaker 1: cases have been phenomenal. So screening of about two point
Speaker 1: five million people takes place annually and that number hasn't
Speaker 1: really changed. So this drop in cases between twenty nine
Speaker 1: and twenty nineteen is with the same intensity of screening,
Speaker 1: if that makes sense. So it's a true drop even
Speaker 1: though under reporting exists.
Speaker 2: That's that's great news.
Speaker 1: It's incredible. Now, all that good news being said, it
Speaker 1: is estimated that sixty five million people live in areas
Speaker 1: that put them at risk for human African japanisimiasis or
Speaker 1: sleeping sickness because they are within the distribution of the ccfly.
Speaker 1: And of course climate change, displacement, political unrest, natural disasters,
Speaker 1: land use change, etc. The list goes on global respiratory
Speaker 1: viral pandemics for example. All of these things certainly threaten
Speaker 1: not just the distribution of this disease or the burden
Speaker 1: of this disease, but also threaten the surveillance and treatment infrastructure.
Speaker 1: And on top of that, we don't fully understand the
Speaker 1: role of wild and domestic animals in the transmission cycle
Speaker 1: or of potentially latent or long standing infections in humans
Speaker 1: and how that might affect like elimination long term limits.
Speaker 1: So I will link to an interesting mathematical modeling paper
Speaker 1: that was kind of trying to look at these two
Speaker 1: aspects of it, the latent infection in humans and these
Speaker 1: kind of silent reservoirs or more rare animal reservoirs, especially
Speaker 1: for gambience, human African tapanisimiasis, which is largely a human
Speaker 1: reservoir disease, but can be found in other animals as well,
Speaker 1: and just looking at those two factors in the context
Speaker 1: of these efforts towards elimination. The paper didn't really have
Speaker 1: any solid answers, but it just kind of underscores the
Speaker 1: importance of having a better understanding of these different reservoir
Speaker 1: populations and that we have a lot to learn. But
Speaker 1: we've come such a long way.
Speaker 2: Yeah, we have.
Speaker 3: That's amazing to think in one hundred years how much
Speaker 3: progress has been made in terms of actually helping people, and.
Speaker 1: Even between twenty nine and twenty nineteen, like what it's
Speaker 1: amazing that is diagnostic testing still does leave much to
Speaker 1: be desired, and that's one of the problems. Even with
Speaker 1: all of these screenings in place, that actually becomes even
Speaker 1: more important as prevalence of this disease drops, because the
Speaker 1: tests essentially become a little less reliable the more rare
Speaker 1: a disease is in the population, and so having access
Speaker 1: to very accurate but also rapid and easy to use
Speaker 1: testing is really important. And that's still an area for
Speaker 1: improved research.
Speaker 2: Okay, But like I.
Speaker 1: Did mention, we have had massive developments in the last
Speaker 1: just few years for treatment, so The new guidelines that
Speaker 1: were published in twenty nineteen included a treatment that not only,
Speaker 1: like I mentioned, can treat stage one and early stage
Speaker 1: two disease when it's caused by gambiency, but it also
Speaker 1: is an oral medication. And that's the first time that
Speaker 1: there's been an oral medication that doesn't have to be
Speaker 1: either an intramuscular injection or an IVY drug, which are
Speaker 1: of course a lot more difficult to administer. That's the
Speaker 1: first time that that's available for trepanosimiasis. So that's another
Speaker 1: really big step. It's huge, but lots of progress has
Speaker 1: been made in a relatively short amount of time, and
Speaker 1: that's something to be glad about.
Speaker 2: Agreed.
Speaker 1: Yeah, that's sleeping sickness, Eric.
Speaker 3: And if you want to know more, you don't have
Speaker 3: to wait all that long. You just have to wait
Speaker 3: one week to hear so much more about the drugs
Speaker 3: that are used to treat sleeping sickness and how we
Speaker 3: actually get them.
Speaker 2: To the people that need them.
Speaker 3: It's going to be a very fascinating bonus episode, So
Speaker 3: put it on your calendars.
Speaker 2: I am really excited about it.
Speaker 1: I can't wait.
Speaker 3: Should we do sources, we should, we should do sources. Okay,
Speaker 3: I have a ton. I'm going to shout out just
Speaker 3: a few here that I highlighted and used heavily. So
Speaker 3: one is by marnez Lyons. It's a book called the
Speaker 3: Colonial Disease, A Social History of Sleeping Sickness in Northern Zaiere.
Speaker 3: And then a few papers that I found really helpful.
Speaker 3: One is by Steve Ding from two thousand and eight
Speaker 3: called the History of African Tripanisemiasis. Another is by Balmer
Speaker 3: at All from twenty eleven Philogeography and Taxonomy of Trapanisambrusi.
Speaker 3: And finally by Hedrick from twenty fourteen Sleeping Sickness, Epidemics
Speaker 3: and Clonial Responses in East and Central Africa in nineteen
Speaker 3: hundred and nineteen forty excellent.
Speaker 1: I had a number of papers a few different Lancet reviews,
Speaker 1: one from twenty ten and then an update from twenty seventeen.
Speaker 1: Another review paper that was in the Lancet Neurology twenty
Speaker 1: thirteen that was more about it was titled Clinical Features,
Speaker 1: Diagnosis and Treatment of Human African Tapinasimiasis, a few years
Speaker 1: old but still had a lot of good information in there.
Speaker 1: Two of my favorites about the kind of neurologic and
Speaker 1: circadian rhythm effects were diagnostic and neuropathogenesis issues in human
Speaker 1: African tapanisimiasis, and that one I mentioned already, sleeping sickness
Speaker 1: is a circadian disorder from Nature Communications twenty eighteen. Really
Speaker 1: really loved those ones as well. We've got a lot
Speaker 1: more sources from this episode everyone of our episodes on
Speaker 1: our website, This podcast would kill you dot com? Have
Speaker 1: you checked it out yet? If this is the episode
Speaker 1: that we finally got you to check it out, I
Speaker 1: want to know.
Speaker 3: Also, there is one more source that I forgot to mention,
Speaker 3: and it's a video about this new oral pill for
Speaker 3: sleeping sickness, and it's so wonderful, it's beautiful. It's on YouTube.
Speaker 2: We'll post a link.
Speaker 3: It's called a Doctor's Dream, a pill for sleeping sickness,
Speaker 3: and it's again by the Drugs for Neglected Diseases Initiative.
Speaker 1: Awesome.
Speaker 3: Thank you to Blowmobile for providing the music for this episode.
Speaker 2: And all of our episodes.
Speaker 1: Thank you to Exactly Right, and thank you to you listeners.
Speaker 3: We hope you found this interesting and informative and you
Speaker 3: learn something new.
Speaker 2: I'm extra thank.
Speaker 1: You also, to our patrons like we can't even express
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Speaker 2: It's true.
Speaker 3: Oh well, until next time, wash your hands.
Speaker 1: You filthy animals.
Speaker 5: U