WEBVTT - Ep 90 Human African Trypanosomiasis: A lot to unpack 0:00:02.080 --> 0:00:04.800 My name is a vet. I first fell ill in 0:00:04.880 --> 0:00:08.039 nineteen eighty seven. I started having back pain and was 0:00:08.080 --> 0:00:10.879 cold all the time, even when it was hot. Just 0:00:10.920 --> 0:00:13.640 taking a bath was an ordeal. I didn't know what 0:00:13.720 --> 0:00:16.760 was wrong. All the tests came out negative. I went 0:00:16.800 --> 0:00:19.800 to Fumetro and Mushi in nineteen ninety two. They performed 0:00:19.800 --> 0:00:22.840 a spinal tap and the result was negative. I continued 0:00:22.880 --> 0:00:26.720 to suffer. My bones ached terribly, I was extremely cold, 0:00:27.080 --> 0:00:30.240 I had fever but would never sweat. I was losing weight. 0:00:30.800 --> 0:00:33.720 I arrived here in ban Doondo in nineteen ninety nine 0:00:33.760 --> 0:00:36.360 in a very precarious state of health. I went to 0:00:36.400 --> 0:00:39.159 a health center where they performed another spinal tap. The 0:00:39.240 --> 0:00:42.040 result was still negative. I went to fo Metro in 0:00:42.120 --> 0:00:45.120 twenty ten, again the spinal tap. It seemed there was 0:00:45.159 --> 0:00:47.959 no solution to my problem. I could hardly stand up. 0:00:48.360 --> 0:00:52.360 I was nearly paralyzed, constant back pain, constantly sleeping in 0:00:52.360 --> 0:00:54.920 my bed. When I would go to prayer, I couldn't 0:00:54.920 --> 0:00:57.600 follow the preacher. I would just fall into a slumber. 0:00:58.160 --> 0:01:01.120 I insisted on getting the right test. Maybe I had 0:01:01.120 --> 0:01:04.119 sleeping sickness. They just kept telling me I was fine. 0:01:04.720 --> 0:01:08.360 I went to the hospital and still no diagnosis. Here 0:01:08.440 --> 0:01:11.640 at the general hospital, the test was negative, just malaria. 0:01:12.160 --> 0:01:16.280 I was totally confused. In the meantime, my health deteriorated. 0:01:16.800 --> 0:01:19.679 In twenty ten. In January, they brought me to Vanga. 0:01:19.959 --> 0:01:23.440 I was practically in agony. It was there finally that 0:01:23.520 --> 0:01:27.040 I discovered I had sleeping sickness. I was transferred back 0:01:27.080 --> 0:01:30.840 here to Vandundu for treatment. I knew nothing of all 0:01:30.880 --> 0:01:33.760 of this since I was unconscious. They started me on 0:01:33.800 --> 0:01:36.800 the treatment, although I had no idea what had been prescribed. 0:01:37.040 --> 0:01:39.080 I was crying all the time. I had to be 0:01:39.200 --> 0:01:42.480 carried and fed like a child. I was a complete disaster. 0:01:43.040 --> 0:01:45.840 I didn't think i'd ever walk again, but the treatment 0:01:45.920 --> 0:01:49.200 was effective. When I regained consciousness, I was discharged from 0:01:49.200 --> 0:01:52.480 the hospital, I started to walk again. I was so thrilled. 0:01:53.360 --> 0:01:56.360 My eldest sibling died from sleeping sickness in nineteen eighty 0:01:56.440 --> 0:01:59.120 in Mushi, in the city where I live. A friend 0:01:59.120 --> 0:02:03.200 of mine contracted the disease. She suffered complications. She had 0:02:03.240 --> 0:02:06.520 been treated with the shots. In the end, she died. 0:02:07.280 --> 0:02:09.840 The patients that were treated with the new treatment were healed, 0:02:10.400 --> 0:02:12.440 but most of those that were treated with the shots 0:02:12.480 --> 0:02:17.000 had enormous difficulties. Some are paralyzed for life. I was 0:02:17.040 --> 0:02:19.800 among the first patients to be treated with the new products. 0:02:20.320 --> 0:02:22.440 My opinion is that we have to keep using the 0:02:22.480 --> 0:02:25.200 new products. They are good and don't harm the patients. 0:02:25.680 --> 0:02:28.440 I was paralyzed and thanks to the new treatment, I 0:02:28.480 --> 0:03:17.200 can walk again. Wow. 0:03:17.440 --> 0:03:21.120 I honestly don't even know what to say. Yeah. 0:03:21.360 --> 0:03:26.480 Same, There is so much too unpack. I feel like 0:03:26.560 --> 0:03:31.480 in this story, just the horror of this disease and 0:03:31.919 --> 0:03:35.360 in many times the horror of the treatment itself too, 0:03:35.720 --> 0:03:36.440 as I'm. 0:03:36.280 --> 0:03:37.240 Sure we'll talk about. 0:03:37.680 --> 0:03:41.640 But yeah, yeah, So that was from a video titled 0:03:41.680 --> 0:03:45.240 a Life Saved by any ct VET Story of Sleeping 0:03:45.280 --> 0:03:48.560 Sickness from the Drugs for Neglected Diseases Initiative. 0:03:50.200 --> 0:03:50.400 Hi. 0:03:50.880 --> 0:03:54.360 I'm Aaron Welsh and I'm Erin alman Updyke. 0:03:54.200 --> 0:03:56.280 And this is this podcast will Kill You. 0:03:56.840 --> 0:04:01.400 Welcome Today we're talking about sleeping sickness. 0:04:01.640 --> 0:04:04.760 Aka human African tapanisimiasis. 0:04:05.280 --> 0:04:08.840 Yeah. Yeah, this is a. 0:04:11.080 --> 0:04:15.560 Like the exact type of disease that really got me 0:04:15.680 --> 0:04:20.600 interested in disease and medicine and public health and global 0:04:20.600 --> 0:04:25.159 health and all of the things because it's yeah. 0:04:24.920 --> 0:04:26.520 Yeah, it's it's a lot. 0:04:26.560 --> 0:04:30.920 It's it's a really complex disease system. It's a really 0:04:30.920 --> 0:04:35.120 complex disease history. And I you know, I think I 0:04:35.240 --> 0:04:38.400 now say this every time, but I was surprised by 0:04:38.480 --> 0:04:41.560 how much I absolutely had no idea. 0:04:41.640 --> 0:04:46.800 Oh about same. The biology was so much more complex. 0:04:47.040 --> 0:04:50.360 I mean, I knew that the kind of ecology was complex, 0:04:50.400 --> 0:04:53.520 but I had no idea about the complexity of the 0:04:53.640 --> 0:04:57.880 biology like in humans even And I know nothing still 0:04:57.920 --> 0:05:02.680 about the history. I can take some guesses. Yeah, it's 0:05:02.720 --> 0:05:04.359 badly it's gonna be a big episode. 0:05:04.760 --> 0:05:09.520 Yeah, but I think it'll be a very interesting one. 0:05:09.640 --> 0:05:12.880 Yeah, I think so too. I'm excited about it. Yeah, 0:05:13.200 --> 0:05:16.160 but before we get into too much detail, erin it 0:05:16.279 --> 0:05:17.760 is quarantiny time. 0:05:18.200 --> 0:05:19.960 It is Aaron. 0:05:20.040 --> 0:05:21.279 What are we drinking this week? 0:05:21.680 --> 0:05:23.440 We're drinking the Nightmare? 0:05:23.920 --> 0:05:28.679 We are I think a pretty appropriate name for this disease, 0:05:28.760 --> 0:05:32.240 because this disease truly does seem like a nightmare, and 0:05:32.320 --> 0:05:33.279 it is in many. 0:05:33.120 --> 0:05:34.120 Ways a nightmare. 0:05:34.200 --> 0:05:36.520 So ye, what's in a nightmare? 0:05:36.680 --> 0:05:42.120 Erin, great question? In the nightmare is laven or simple syrup, 0:05:42.480 --> 0:05:45.400 camimeal tea whiskey and a little bit. 0:05:45.279 --> 0:05:47.800 Of lemon juice de lish. 0:05:47.960 --> 0:05:50.200 Yeah, it's not a nightmare to drink. 0:05:51.360 --> 0:05:54.560 We'll post the full recipe for that quarantiny and our 0:05:54.600 --> 0:05:57.720 non alcoholic Placeiba Rita on our website. This podcast will 0:05:57.760 --> 0:06:00.880 kill you dot Com and all of our social media channels. 0:06:01.000 --> 0:06:08.279 We will other business includes our website, which has lots 0:06:08.360 --> 0:06:11.479 and lots of things. I promised myself last time that 0:06:11.520 --> 0:06:13.880 I was gonna do a post it note of all 0:06:13.920 --> 0:06:15.880 of the things on our website, and now I am 0:06:16.440 --> 0:06:19.040 so mad at myself for not following through. All right, 0:06:19.200 --> 0:06:22.920 well it comes to me anyway. Our website, you can 0:06:22.920 --> 0:06:24.960 find sources for where we get all of the info 0:06:25.040 --> 0:06:28.240 for each of our episodes. You can find transcripts. You 0:06:28.320 --> 0:06:33.400 can find links to Bloodmobile's music now on Spotify. You 0:06:33.440 --> 0:06:37.200 can find links to our Goodreads booklist and our bookshop 0:06:37.200 --> 0:06:40.400 dot org affiliate account. You can find our Patreon and 0:06:40.640 --> 0:06:42.200 some sweet sweet merch. 0:06:42.880 --> 0:06:47.839 Yes, oh real quick, I did remember one piece of business, 0:06:48.000 --> 0:06:51.360 oh wock I should cover. We have gotten a number 0:06:51.440 --> 0:06:57.000 of emails about our ceediff episode in which I didn't 0:06:57.040 --> 0:07:02.279 include the update that Closterdium difficile has been reclassified several 0:07:02.360 --> 0:07:06.440 years ago, I think around twenty sixteen to this species 0:07:06.600 --> 0:07:11.320 Claustritioides difficial seed iff is still sea diiff, but it's 0:07:11.320 --> 0:07:12.280 a different see. 0:07:12.920 --> 0:07:16.720 Yes, yeah, all right, let's let's talk about sleeping sickness. 0:07:16.720 --> 0:07:19.400 Now, let's let's do it, Okay, right after this break. 0:07:42.520 --> 0:07:45.640 For most listeners, this should be at least a little 0:07:45.640 --> 0:07:51.040 familiar sleeping sickness or human African tripennosamiasis, which like I 0:07:51.120 --> 0:07:55.360 might at some point just call tripenosimiasis or hat because 0:07:55.680 --> 0:08:00.600 it's shorter. It is caused by a trapanosome. We've talked 0:08:00.600 --> 0:08:05.000 about those once before, in the same genus as that 0:08:05.080 --> 0:08:06.760 which causes shagas disease. 0:08:08.080 --> 0:08:09.360 In this case it is a. 0:08:09.320 --> 0:08:13.440 Different species, and in fact it is two different subspecies. 0:08:14.040 --> 0:08:18.120 So today we're going to be talking about Tripanosoma brucei rhudesienc. 0:08:19.080 --> 0:08:25.280 And Tripanosoma brucei gambiency. I might just say gambiency and 0:08:25.480 --> 0:08:27.920 rhodesience because that's true. 0:08:28.360 --> 0:08:29.880 I do the same. It's a lot easier. 0:08:29.960 --> 0:08:34.760 Yeah. Sometimes you even just see like TBG or tb R. 0:08:35.600 --> 0:08:35.800 Right. 0:08:36.800 --> 0:08:43.079 So, tripanosomes as a recap are unicellular eukaryotes. They are 0:08:43.200 --> 0:08:45.880 shaped kind of like little if you look at them 0:08:45.960 --> 0:08:49.920 on a microscope slide like little commas or maybe little bananas. 0:08:50.080 --> 0:08:53.440 I don't know. They have a little flagellum that they 0:08:53.559 --> 0:08:59.720 use to swim around. Okay, t Brucei all the species 0:09:00.720 --> 0:09:04.040 because I didn't mention this, But there is yet another subspecies, 0:09:04.200 --> 0:09:10.120 Trypanosoma bruci brucei, which causes a disease in cattle called nagana. 0:09:10.240 --> 0:09:14.400 I believe is how you pronounce it. So Trypanosoma brucei 0:09:14.880 --> 0:09:18.640 is transmitted by yet another new vector species that we 0:09:18.760 --> 0:09:22.959 have never touched on in this podcast. It is the 0:09:22.960 --> 0:09:28.120 blood feeding setsi fly. Seats fly, sets fly. 0:09:28.440 --> 0:09:32.000 We've had discussions about this pronunciation, and we've looked up 0:09:32.040 --> 0:09:35.280 many videos and I. 0:09:35.200 --> 0:09:38.360 Think it's one of those that different people are going 0:09:38.440 --> 0:09:43.000 to pronounce differently. And that's okay. Yeah, so that seats flies, 0:09:43.800 --> 0:09:47.120 seats flies. I'm really excited to talk about these, but 0:09:47.280 --> 0:09:50.040 I promise I'm not gonna geek out quite as hard 0:09:50.120 --> 0:09:52.319 as like we did during the Typhus episode with lice. 0:09:53.360 --> 0:09:54.920 Yeah, Okay, we did pretty hard. 0:09:55.320 --> 0:09:58.840 H It's not gonna be quite as hard. But specifically 0:09:59.000 --> 0:10:02.360 that sets flies in genus Glossina is who we're talking 0:10:02.400 --> 0:10:06.040 about today. I want to geek out just a little 0:10:06.040 --> 0:10:14.240 bit These flies are fascinating. They are viviparous, yeah, which 0:10:14.320 --> 0:10:18.360 means they give live birth. They give birth to live 0:10:18.679 --> 0:10:20.040 little larval young. 0:10:20.640 --> 0:10:25.480 I had no idea that was a thing in insects 0:10:25.720 --> 0:10:30.720 until this. But I've never taken an entomology class, so I. 0:10:29.960 --> 0:10:33.320 Have a PhD in entomology, and I learned something new. 0:10:37.120 --> 0:10:41.920 So these female flies deposit their larva into the soil directly. 0:10:41.960 --> 0:10:46.080 They have eggs that they actually hold internally until they 0:10:46.120 --> 0:10:50.120 develop into I believe third in star larvae. They deposit 0:10:50.160 --> 0:10:53.640 those larvae into the soil where they burrow in. They 0:10:53.640 --> 0:10:56.840 then pupate and emerge as adult flies. 0:10:57.960 --> 0:11:02.160 It's so fascinating because like, first of all, I really 0:11:02.160 --> 0:11:05.680 want to know has this happened, has this evolved in 0:11:05.840 --> 0:11:08.840 other species of insects, and like what are the like 0:11:08.880 --> 0:11:12.760 what are the evolutionary pressures or pathways for this thing 0:11:12.800 --> 0:11:14.920 to be? Like I'm gonna spend all of my time 0:11:14.960 --> 0:11:18.440 and energy on. I mean, they're they're relatively long lived 0:11:19.200 --> 0:11:21.240 for flies, and so maybe that's part of it, but 0:11:21.280 --> 0:11:24.120 I just like I just want to know so much 0:11:24.120 --> 0:11:27.000 more about viviparous insects. 0:11:27.400 --> 0:11:31.000 I know, and I like specifically didn't deep dive on them, 0:11:31.040 --> 0:11:33.280 but like, use, we so could. 0:11:33.679 --> 0:11:36.359 Yeah, yeah, we really could, because. 0:11:36.120 --> 0:11:38.440 There is there's a lot, there's a lot there to unpack. 0:11:39.600 --> 0:11:41.480 But we're just gonna leave it at Aren't these flies 0:11:41.480 --> 0:11:45.880 so cool? Let's let's deep dive another time. Another important 0:11:45.960 --> 0:11:48.720 part about these flies is that both male and female 0:11:48.720 --> 0:11:53.680 flies blood feed as adults, and so here is how 0:11:54.400 --> 0:11:59.960 human African tripanosomiasis becomes a problem. When these flies feed 0:12:00.880 --> 0:12:03.640 on a human host or an animal host, they pick 0:12:03.679 --> 0:12:07.200 up this parasite, this tripanosome in the blood meal. These 0:12:07.240 --> 0:12:13.440 parasites enter the digestive tract of the fly. There they differentiate, 0:12:14.040 --> 0:12:18.720 they replicate, They burst out of the digestive tract, travel 0:12:18.800 --> 0:12:23.280 through the fly's body, enter into the salivary glands. In 0:12:23.400 --> 0:12:27.400 the salivary glands, they differentiate again into the infective form 0:12:27.480 --> 0:12:31.680 of tripanisome, continue to replicate, and then when that fly 0:12:31.880 --> 0:12:35.559 takes its next blood meal, their salivary glands are full 0:12:35.679 --> 0:12:39.199 of infective stages of this parasite that they can inject 0:12:39.520 --> 0:12:40.679 under their host's skin. 0:12:41.679 --> 0:12:46.360 Okay, interesting, Is this the way it is for all 0:12:46.880 --> 0:12:50.640 tripanisomes transmitted by setsuflies? 0:12:51.480 --> 0:12:55.520 As far as I know, Yes, And this process we 0:12:55.640 --> 0:12:59.480 have actually seen this process before. This is actually not 0:12:59.640 --> 0:13:04.680 a very uncommon way of vector transmission. Something like dangay 0:13:04.720 --> 0:13:08.600 fever is very similar, right, where the virus has to 0:13:08.760 --> 0:13:11.240 enter the GI tract, make its way out of the 0:13:11.280 --> 0:13:15.840 GI tract, through the body, and into the salivary glands. Importantly, 0:13:15.960 --> 0:13:19.720 this is very different than the other tripanisome we've talked about, 0:13:19.720 --> 0:13:23.119 which is Shaugus disease, which is transmitted just through the feces, 0:13:23.480 --> 0:13:26.240 so that parasite just travels kind of straight through the 0:13:26.320 --> 0:13:31.600 gut of the kissing bug. Here, this parasite not only 0:13:32.240 --> 0:13:35.000 has to migrate through the gut, through the gut wall, 0:13:35.160 --> 0:13:38.920 through the body into the salivary glands, but during this 0:13:39.040 --> 0:13:43.800 process it also differentiates multiple times and changes forms in 0:13:43.840 --> 0:13:48.640 a very complex way. And this whole process actually takes 0:13:48.640 --> 0:13:52.360 these trypanisomes about three to five weeks, which is a 0:13:52.480 --> 0:13:53.680 really long time. 0:13:54.440 --> 0:13:58.800 Yeah, that's a really long time. Yeah, that's a. 0:13:58.880 --> 0:14:02.360 Very long time. And like you mentioned, Aaron, this fly 0:14:02.960 --> 0:14:04.280 is very long lived. 0:14:04.960 --> 0:14:05.480 From what I. 0:14:05.440 --> 0:14:08.240 Read, its lifespan is at least two to three months, 0:14:09.440 --> 0:14:14.120 and they blood feed every three days or so. Likely 0:14:14.559 --> 0:14:19.000 largely because of this complexity, not only the complexity of 0:14:19.040 --> 0:14:22.800 the life cycle of this fly, but also the complexity 0:14:22.800 --> 0:14:26.240 of like the maturation process of these parasites within the fly. 0:14:27.240 --> 0:14:31.640 It's actually found that for the most part, the prevalence 0:14:31.680 --> 0:14:35.000 of tripanosomes in flies is actually very very low. Zero 0:14:35.000 --> 0:14:38.640 point one percent of flies in any given study area 0:14:38.960 --> 0:14:40.080 tend to be infected. 0:14:40.920 --> 0:14:45.520 That's bizarre, it is, So what's going on? 0:14:47.080 --> 0:14:48.480 I don't have a good answer for that. 0:14:49.240 --> 0:14:50.480 So because you. 0:14:50.400 --> 0:14:54.120 Would think that, like flies are so long lived, parasites 0:14:54.120 --> 0:14:56.360 seem to be in them for weeks at a time. 0:14:57.600 --> 0:14:59.280 But I think what it is is that a lot 0:14:59.280 --> 0:15:02.520 of those parasit even if a fly is picking up parasites, 0:15:02.680 --> 0:15:04.880 they don't necessarily make it all the way to an 0:15:04.920 --> 0:15:07.360 infective infection in the fly. 0:15:07.920 --> 0:15:10.680 Okay, So yeah, at any point in time, it's one 0:15:10.720 --> 0:15:15.760 percent of flies that are infected with infectious stage parasites. 0:15:15.840 --> 0:15:18.640 It's point one percent point one percent. 0:15:19.000 --> 0:15:21.360 Yeah, yeah, okay. 0:15:21.560 --> 0:15:24.240 And as far as I found, at least, this is 0:15:24.280 --> 0:15:27.400 not a parasite that's vertically transmitted. So even though these 0:15:27.440 --> 0:15:30.720 female flies have their young that develop in their bodies, 0:15:30.720 --> 0:15:33.160 they're not passing those parasites onto their offspring. 0:15:33.480 --> 0:15:34.560 Yeah, okay, gotcha. 0:15:35.280 --> 0:15:38.720 So there's a lot more to unpack there, I am sure, 0:15:38.760 --> 0:15:42.880 because this is a very interesting and complicated genus of bug. 0:15:44.040 --> 0:15:46.760 But that's where I'm gonna leave it. And let's get 0:15:46.760 --> 0:15:49.480 back to the life cycle of the parasite. So the 0:15:49.480 --> 0:15:52.560 parasite is now in the salivary glands. The fly takes 0:15:52.640 --> 0:15:57.160 another blood meal, and in so doing, through their little proboscis, 0:15:57.640 --> 0:16:01.640 deposits a whole bunch of parasite underneath our skin. Those 0:16:01.680 --> 0:16:05.680 parasites enter our lymphatic system and our bloodstream, and from 0:16:05.760 --> 0:16:09.640 there they're able to replicate. They differentiate again in us 0:16:09.680 --> 0:16:13.760 as well, and they travel to various organs and establish 0:16:13.880 --> 0:16:18.240 an infection. It gets even more interesting erin the biology 0:16:18.400 --> 0:16:22.240 of this parasite. There's so much here. I'm not going 0:16:22.280 --> 0:16:24.560 to do every aspect of it justice, but I do 0:16:24.680 --> 0:16:27.760 hope that I at least give a teaser of all 0:16:27.800 --> 0:16:31.800 of the different interesting parts of this parasite. That's my 0:16:31.880 --> 0:16:35.800 kind of goal here, Okay, I'm down. So our human 0:16:35.840 --> 0:16:40.040 immune system, when we see these parasites, is actually primed 0:16:40.160 --> 0:16:43.960 to recognize these parasites, and we do. Our immune system 0:16:44.120 --> 0:16:47.120 does we actually even have a protein in our bloodstream 0:16:47.440 --> 0:16:52.080 that's usually really good at eliminating other tripanosomes. That's called 0:16:52.200 --> 0:16:55.440 tripanosomelytic factor. Did you know that we had that? 0:16:55.960 --> 0:16:57.920 Uh? No, I have? Yeah? 0:16:57.960 --> 0:16:58.800 Okay, keep going. 0:17:00.120 --> 0:17:03.720 So if we get infected with most other species of tripanosome, 0:17:04.280 --> 0:17:06.680 not the two that we've talked about that cause disease 0:17:06.720 --> 0:17:09.600 in humans, here, we're able to fend off that infection 0:17:09.760 --> 0:17:15.119 like a lot of other animal tripanosomes. But Tripanosoma bruci 0:17:15.600 --> 0:17:23.119 subspecies Rhodesiency and gambiency specifically have resistance factors that render 0:17:23.320 --> 0:17:26.040 this particular protein that we have not useful. 0:17:26.800 --> 0:17:28.959 So my mind is blown because this is filling in 0:17:29.160 --> 0:17:32.600 so much of the evolution part that I researched, and 0:17:32.640 --> 0:17:35.000 I was like, but what does that mean about this 0:17:35.160 --> 0:17:38.679 and the history? But so this means that we are like, 0:17:38.920 --> 0:17:41.520 we can witness this as an arms race kind of 0:17:41.520 --> 0:17:44.560 a thing, right, Yeah, Oh my god, that's so cool. 0:17:44.800 --> 0:17:49.520 It gets even cooler. Okay. Tripanosomes have on their cell 0:17:49.600 --> 0:17:53.120 surface a lot of different proteins that our body uses 0:17:53.160 --> 0:17:56.600 to identify and recognize them as non self right, anigens 0:17:56.720 --> 0:17:59.800 essentially that we make antibodies against to remove them from 0:17:59.840 --> 0:18:03.720 our bodies, and we're really good at that. But the 0:18:03.760 --> 0:18:10.120 tripanosomes that cause human African tripanosomiasis T. BRUCEI, Rudi ziency, 0:18:10.400 --> 0:18:13.760 and gambiency. From now on, those are the only two 0:18:14.080 --> 0:18:15.119 that I'm going to talk about. 0:18:15.480 --> 0:18:15.800 Okay. 0:18:16.119 --> 0:18:21.560 They have hundreds, maybe a couple of thousand variants of 0:18:21.600 --> 0:18:26.560 these proteins, and they express them one at a time, 0:18:27.480 --> 0:18:31.160 and they constantly switch them up, so by the time 0:18:31.240 --> 0:18:35.240 our body manages to make antibodies against one of these glycoproteins, 0:18:35.680 --> 0:18:38.600 that one like barely even exists anymore, and they've changed 0:18:38.600 --> 0:18:40.560 to a new one. Here's the way that I think 0:18:40.600 --> 0:18:45.680 about this. These tripanosomes are me when I was like sixteen, 0:18:45.800 --> 0:18:49.080 sneaking into a movie, right, you with me here? 0:18:49.200 --> 0:18:50.800 Into an R rated movie. 0:18:51.119 --> 0:18:54.440 No, I wasn't that risk erin it was probably PG thirteen. 0:18:54.760 --> 0:18:57.760 You were sixteen sneaking into a PG thirteen movie. 0:18:58.200 --> 0:19:01.879 Let me tell you that I can finish my analogy. 0:19:02.320 --> 0:19:03.679 It's gonna make more sense. 0:19:04.040 --> 0:19:06.440 It's flawed from the start, but fine. 0:19:06.280 --> 0:19:08.320 No, no, no, I'm talking about like movie hopping, like 0:19:08.359 --> 0:19:09.800 you're trying to go to more than one movie. 0:19:09.840 --> 0:19:11.679 Oh oh my gosh. 0:19:11.720 --> 0:19:15.080 Okay, Okay, I see right, Okay, so that's this is 0:19:15.119 --> 0:19:18.359 what's happening. The trypanosomes are sneaking into movies and the 0:19:18.440 --> 0:19:21.160 security guards see them. They get on their walkie talkie 0:19:21.160 --> 0:19:24.560 and they're like, we've spotted the culprint. They're wearing a 0:19:24.720 --> 0:19:29.520 pink jacket that's a very flamboyant jacket. So by the 0:19:29.520 --> 0:19:32.919 time the security guards get into the theater, that tripanosome 0:19:33.560 --> 0:19:35.840 change their pink jacket out for a green one, and 0:19:35.880 --> 0:19:38.880 the security guards are like, Hm, there's no pink jacket here. Wait, 0:19:38.920 --> 0:19:41.359 who's that in the green? They look suspicious, And then 0:19:41.400 --> 0:19:44.159 that person slips into a different theater, and by the 0:19:44.160 --> 0:19:46.320 time the guards get to the next theater, they've changed 0:19:46.320 --> 0:19:49.199 their jacket again for like a cheetah print one, and 0:19:49.200 --> 0:19:51.439 the gods are like, look, there's no one here in 0:19:51.520 --> 0:19:54.240 pink or green. We're just gonna give up. We're gonna 0:19:54.280 --> 0:19:58.520 go get popcorn. It's like that, but at the same 0:19:58.600 --> 0:20:01.919 time as this, the tripanis is replicating unlike me in 0:20:01.920 --> 0:20:04.480 a movie theater, or you can think of it as 0:20:04.480 --> 0:20:06.480 like with letting a bunch of their friends in with 0:20:06.640 --> 0:20:07.840 different color jackets. 0:20:08.520 --> 0:20:10.200 It sounds totally overwhelming. 0:20:10.560 --> 0:20:13.600 I know, before you know it, our immune system literally 0:20:13.640 --> 0:20:16.240 just can't keep up. So we'll probably manage to kick 0:20:16.240 --> 0:20:18.399 out some of them that we're still wearing pink or 0:20:18.400 --> 0:20:21.280 green jackets, but the rest of them managed to escape 0:20:21.320 --> 0:20:26.600 our security guards. And that is how tripanasoma BRUCEI Rudy 0:20:26.680 --> 0:20:30.560 zienc gambiency can establish an infection in our bodies. 0:20:31.440 --> 0:20:35.560 Okay, that is very interesting and that I feel like 0:20:35.640 --> 0:20:40.879 has a lot of implications for vaccines and therapy. 0:20:40.880 --> 0:20:42.400 Sure does, erin, sure does? 0:20:43.119 --> 0:20:43.560 Oh boy? 0:20:43.680 --> 0:20:48.680 Okay, yeah, yeah, it makes the vaccines very difficult, if 0:20:48.720 --> 0:20:51.679 not nearly impossible, because it's very difficult to stop the 0:20:51.880 --> 0:20:53.119 establishment of an infection. 0:20:53.800 --> 0:20:57.679 Yeah, this is so interesting, okay, I yeah, I just 0:20:57.720 --> 0:21:00.560 want to keep gushing about how interesting this is also 0:21:00.560 --> 0:21:03.440 from an evolutionary perspective, because I think this really does 0:21:03.920 --> 0:21:07.920 kind of provide some insight into like if there are 0:21:08.320 --> 0:21:14.200 so many protein variants of the like, so much antigenic variation, 0:21:14.560 --> 0:21:17.840 right then this has to be like a long period 0:21:17.840 --> 0:21:18.920 of exposure to humans. 0:21:19.040 --> 0:21:26.600 Absolutely yeah wow, okay, Okay, speaking of exposure to humans, T. 0:21:26.760 --> 0:21:31.400 Bruce ei gambiency tends to be a primarily anthroponotic disease. 0:21:31.880 --> 0:21:35.920 So while this tripanistome can also infect animals, humans are 0:21:36.080 --> 0:21:39.240 the predominant reservoir so it's much more common to have 0:21:39.440 --> 0:21:43.760 human to human transmission via of course, the Glossina fly 0:21:45.280 --> 0:21:51.160 Tripanisoma brucie. Rhodiziency is generally a zoonotic disease that's often 0:21:51.200 --> 0:21:54.399 transmitted from animals to humans, especially cattle, which are a 0:21:54.520 --> 0:21:59.960 very important reservoir. And that's just one of the differences 0:22:00.200 --> 0:22:03.240 between these two subtypes, and we'll talk a little bit 0:22:03.280 --> 0:22:05.879 more in a minute about the differences in terms of 0:22:05.920 --> 0:22:12.280 their symptoms. But basically, the disease known as human African 0:22:12.280 --> 0:22:18.240 tripanosomiasis or sleeping sickness, has two phases. The first phase 0:22:18.440 --> 0:22:20.520 is when the parasite is in the blood or the 0:22:20.600 --> 0:22:24.479 lymphatics and making its way into various organs, and then 0:22:24.520 --> 0:22:27.760 the second phase is when it invades our central nervous 0:22:27.760 --> 0:22:30.520 system and results in the symptoms that have given it 0:22:30.560 --> 0:22:34.679 the name sleeping sickness. And we will get there, but 0:22:34.880 --> 0:22:38.120 first I want to talk briefly about the differences in 0:22:38.200 --> 0:22:43.199 the two subtypes, gambiency and rhodesience. The disease itself, for 0:22:43.240 --> 0:22:46.679 the most part, is the same or at least very 0:22:46.720 --> 0:22:50.560 similar between these two subtypes, but the big, big difference 0:22:51.040 --> 0:22:54.199 is that in gambiency, which again is the subspecies that 0:22:54.240 --> 0:22:57.920 tends to have humans as the primary reservoir rather than animals. 0:22:59.240 --> 0:23:02.920 In this subtype, the disease course tends to be prolonged. 0:23:03.680 --> 0:23:09.040 That first stage might last months or even years, and 0:23:09.080 --> 0:23:13.200 it can be more mild and have vague symptoms. That's 0:23:13.240 --> 0:23:15.479 not to say that it's a mild disease, because it's 0:23:15.560 --> 0:23:20.880 not at all. But the average duration of gambiency disease 0:23:21.600 --> 0:23:24.439 is about three years, and there's a huge amount of 0:23:24.480 --> 0:23:27.919 interperson variability. So like in our first hand account, what 0:23:28.000 --> 0:23:31.959 was described was a very prolonged disease, but in some 0:23:32.000 --> 0:23:35.000 people it might be a matter of months. On the 0:23:35.040 --> 0:23:39.040 other hand, disease caused by the subspecies Rudiesiency tends to 0:23:39.080 --> 0:23:43.040 have a much faster and more severe course, where over 0:23:43.359 --> 0:23:46.199 a few weeks or a couple of months, people end 0:23:46.280 --> 0:23:49.840 up very sick, progress to the second stage of disease 0:23:50.200 --> 0:23:53.119 and usually die within six months if they're untreated. 0:23:53.520 --> 0:23:55.800 Wow, and for. 0:23:55.800 --> 0:23:59.320 Both subtypes of this disease, almost all of the accounts 0:23:59.359 --> 0:24:02.720 report the the disease is almost universally fatal if it's 0:24:02.760 --> 0:24:06.320 left untreated, but there have been a handful of case 0:24:06.359 --> 0:24:12.240 reports of gambiency where people either recover or have like 0:24:12.280 --> 0:24:16.040 a self cure where they do actually recover from the infection, 0:24:16.760 --> 0:24:20.960 or of being relatively healthy carriers. Okay, yeah, but that's 0:24:21.040 --> 0:24:24.480 the very minority. It's like a few case reports, gotcha. 0:24:25.400 --> 0:24:29.840 In terms of the distribution, rhodesiency, the one with animals 0:24:29.880 --> 0:24:33.439 as the primary reservoir, accounts for about five percent of 0:24:33.480 --> 0:24:36.840 cases and is more prevalent in the eastern and southern 0:24:36.840 --> 0:24:40.680 parts of Africa, and gambiency accounts for about ninety five 0:24:40.680 --> 0:24:43.240 percent of cases and is more prevalent in the western 0:24:43.280 --> 0:24:45.239 and central parts of Africa. 0:24:45.359 --> 0:24:48.000 Does this is definitely jumping the gun? But does trevent 0:24:48.200 --> 0:24:51.560 work equally well on both of these some notpes? 0:24:51.640 --> 0:24:54.240 Okay, Nope, that is definitely jumping the gun, and we'll 0:24:54.240 --> 0:24:54.560 get there. 0:24:55.520 --> 0:24:55.920 Okay. 0:24:56.520 --> 0:25:00.280 Yeah, So let's first talk about what this disease actually 0:25:00.320 --> 0:25:04.840 looks like in these two different stages. First stage of 0:25:04.880 --> 0:25:09.439 this disease is really pretty generalized symptoms. Usually there's fever, 0:25:09.960 --> 0:25:13.439 and this fever is often intermittent, so it can last 0:25:13.560 --> 0:25:16.040