WEBVTT - Ep 71 Onchocerciasis/River Blindness: So many mysteries 0:00:02.200 --> 0:00:06.000 It just went completely white. This is how fishermen A 0:00:06.120 --> 0:00:10.479 Coo yo Osumaka describes going blind in twenty eleven in 0:00:10.560 --> 0:00:14.160 the remote village of Babagulu in the Democratic Republic of Congo. 0:00:15.440 --> 0:00:18.720 It was a slow creeping blindness that began a year earlier. 0:00:19.440 --> 0:00:22.200 It robbed him of his livelihood and threw his family 0:00:22.239 --> 0:00:26.439 life into disarray. Tragically, A Koyo had once fought against 0:00:26.480 --> 0:00:29.400 the disease that eventually robbed him of his sight by 0:00:29.480 --> 0:00:33.599 volunteering to distribute drugs that help prevent transmission of river blindness. 0:00:34.200 --> 0:00:37.400 The River Onane runs through Babagulu and is a perfect 0:00:37.440 --> 0:00:40.279 breeding ground for the black flies that swarm through the village, 0:00:40.520 --> 0:00:44.720 infecting people with filarial worms that cause river blindness. A 0:00:44.800 --> 0:00:47.280 Koyo is one of the many living in the village 0:00:47.280 --> 0:00:50.240 with the disease. Community leaders think that up to three 0:00:50.320 --> 0:00:53.880 percent of the community is blind. A Koyo felt the 0:00:53.920 --> 0:00:56.760 need to help, so he volunteered to help distribute ivermectin. 0:00:57.240 --> 0:01:00.600 These programs rely solely on unpaid drug dishries readers to 0:01:00.640 --> 0:01:04.280 work within their communities. He would travel to neighboring villages, 0:01:04.400 --> 0:01:07.760 often deep in the bush, to distribute the drugs. He 0:01:07.880 --> 0:01:11.279 was often bitten during his travels. One day, his village 0:01:11.280 --> 0:01:13.120 had a stock out of the drug and he stopped 0:01:13.120 --> 0:01:15.800 taking it. I was told to deliver all the drugs 0:01:15.800 --> 0:01:17.800 and then I would take it later once I started 0:01:17.800 --> 0:01:21.080 to have symptoms, he remembers, but then there were no 0:01:21.120 --> 0:01:24.200 more drugs to take. He then ended up missing distribution 0:01:24.319 --> 0:01:26.600 programs in his village because he was out fishing in 0:01:26.640 --> 0:01:30.600 forest streams. In twenty ten, a Koyo started to have 0:01:30.640 --> 0:01:34.040 difficulties seeing, and in twenty eleven he went completely blind. 0:01:34.680 --> 0:01:37.039 His son, Ato, does not go to school and had 0:01:37.040 --> 0:01:39.160 to quit his job because of the stress of caring 0:01:39.200 --> 0:01:42.440 for his father. Itto has a number of nodules on 0:01:42.480 --> 0:01:45.760 his torso and forehead. The adult worms that cause river 0:01:45.840 --> 0:01:49.360 blindness live in these fibrous nodules. Taking care of his 0:01:49.400 --> 0:01:53.160 father is a full time job. Ito also suffers from 0:01:53.160 --> 0:01:57.040 epileptic seizures about four times a month. Researchers have noted 0:01:57.040 --> 0:02:01.520 a potentially causal relationship between UNCO Sarkaiais infection and forms 0:02:01.520 --> 0:02:06.080 of epilepsy found in Africa. I depend totally on my wife. 0:02:06.280 --> 0:02:09.400 She feeds and dresses me, says a ko Yo. Even 0:02:09.440 --> 0:02:12.280 my wife doesn't have a job. After I lost my sight, 0:02:12.440 --> 0:02:14.520 we couldn't send any of our children to school. 0:03:01.960 --> 0:03:03.919 That's horrible. 0:03:04.520 --> 0:03:08.080 Yeah, it's a tough and unfortunately not uncommon story. 0:03:09.160 --> 0:03:14.119 Yes, so that was adapted from an article titled Revealing 0:03:14.120 --> 0:03:18.760 the Neglect river Blindness from March thirtieth, twenty eighteen on 0:03:18.919 --> 0:03:23.320 the website for Drugs for Neglected Diseases Initiative, and we 0:03:23.400 --> 0:03:27.000 will link to that story on our website. And you 0:03:27.000 --> 0:03:29.640 should definitely check it out because not only is there 0:03:29.760 --> 0:03:32.320 more story to it, but there's also a really cool 0:03:32.400 --> 0:03:36.240 video which is the story animated along with a traditional 0:03:36.320 --> 0:03:40.400 song recorded in a Koyo's region about river blindness. So 0:03:40.480 --> 0:03:44.640 definitely check that out. Hi, I'm erin Welsh and I'm 0:03:44.760 --> 0:03:49.360 erin alman Updike and this is this podcast will kill you. Welcome, 0:03:50.120 --> 0:03:54.720 Welcome to another parasitic disease episode of our podcast. 0:03:55.080 --> 0:03:59.400 I'm very excited about another parasitic disease, another vector born disease. 0:04:00.320 --> 0:04:04.320 Yeah, me too. It's super complicated, which gives us an 0:04:04.320 --> 0:04:07.839 opportunity to talk about all kinds of different aspects of 0:04:07.880 --> 0:04:11.800 this parasite, of this vector, of the human side of disease, 0:04:11.880 --> 0:04:16.120 of the history it's I think complex is one word. 0:04:16.600 --> 0:04:19.200 I think it's I think it's classic TPWKY. 0:04:19.279 --> 0:04:23.120 Aaron, Yeah, it actually it really is. It is. Yeah, 0:04:23.200 --> 0:04:25.520 So what are we even covering this week? 0:04:25.640 --> 0:04:29.800 Erin we are covering oncossarchiasis. 0:04:29.080 --> 0:04:30.600 Aka river blindness. 0:04:31.080 --> 0:04:31.599 Yeah. 0:04:31.720 --> 0:04:32.520 Yeah. 0:04:32.040 --> 0:04:38.000 It is truly a very classic TPWKY episode in so 0:04:38.040 --> 0:04:38.720 many ways. 0:04:38.960 --> 0:04:43.000 And speaking of classic TPWKY, we have to start this 0:04:43.120 --> 0:04:47.760 episode with a quarantiny A quarantiney. What are we drinking 0:04:47.839 --> 0:04:48.400 this week? 0:04:48.800 --> 0:04:52.160 We're drinking as the worm turns. 0:04:53.080 --> 0:04:56.160 This is one of my favorite quarantine names. 0:04:56.440 --> 0:04:58.440 We went we went back and forth for a long time, 0:04:58.440 --> 0:05:00.400 but Aaron went out, it is very good. 0:05:02.080 --> 0:05:04.240 Well, and so I think that we were like, well, 0:05:04.279 --> 0:05:06.680 we should save this because we're gonna do more wormy 0:05:06.720 --> 0:05:08.920 parasites in the future, and this is a really good name. 0:05:08.960 --> 0:05:12.520 Should we do something else for this? But I found 0:05:12.520 --> 0:05:16.760 a quote from a researcher who was describing these that 0:05:16.839 --> 0:05:20.760 describes the worms as being undulating and turny, and so, like, 0:05:21.520 --> 0:05:23.400 you know, it was just too good to pass up. 0:05:23.640 --> 0:05:26.760 I mean, they are very turny worms, Like, definitely they are. 0:05:27.680 --> 0:05:30.000 And also I really feel like now that we're getting 0:05:30.000 --> 0:05:34.720 into the whole like worm and world. Swapping out those 0:05:34.760 --> 0:05:37.360 two words and idioms or whatever, We've got a whole 0:05:37.440 --> 0:05:41.120 host of opportunities for future quarantine names exactly. 0:05:41.160 --> 0:05:42.920 This is not going to be the end of the 0:05:43.000 --> 0:05:45.839 worm me world phrase at all. 0:05:46.040 --> 0:05:49.880 It's a it's a small worm, after all, I can't 0:05:49.880 --> 0:05:52.400 remember the other ones sitting on top of the worm. 0:05:53.720 --> 0:05:56.240 Keep an ear out, Aaron. What is in as the 0:05:56.279 --> 0:06:01.159 Worm turns? Okay, yes, let's let's do that. In as 0:06:01.200 --> 0:06:06.479 the Worm Turns is cognac ginger, simple syrup, lemon juice, 0:06:06.960 --> 0:06:11.279 and a splash of sparkling water, and you garnish it 0:06:11.320 --> 0:06:15.360 with some candy ginger. It's actually really refreshing and good. 0:06:15.440 --> 0:06:17.880 Yeah, it sounds really good. It sounds both like warming 0:06:17.960 --> 0:06:19.400 and refreshing somehow. 0:06:19.839 --> 0:06:22.400 Yeah. And we will post the full recipe for this 0:06:22.520 --> 0:06:25.600 quarantini as well as our non alcoholic plus sy burrita 0:06:25.640 --> 0:06:27.839 on our website This podcast will kill You dot com 0:06:27.880 --> 0:06:30.200 as well as on all of our social media channels, 0:06:30.200 --> 0:06:31.680 so make sure you follow us there. 0:06:32.120 --> 0:06:36.040 Excellent. Any other business that we should attend to before 0:06:36.080 --> 0:06:38.960 we dive into this very interesting episode. 0:06:39.520 --> 0:06:42.160 There's the usual stuff. Go to our website. It contains 0:06:42.200 --> 0:06:47.120 links for merch for bookshop dot Org affiliate account for 0:06:47.440 --> 0:06:53.000 Goodreads reading list, for transcripts, for alcohol free episodes, for anything. 0:06:53.080 --> 0:06:55.560 Any source you ever want to find on that we 0:06:55.640 --> 0:06:58.120 reference on this podcast, you can find it there. 0:06:58.560 --> 0:07:00.720 Yeah, definitely check out our website. 0:07:01.520 --> 0:07:03.760 Okay, is there anything else, Sarin? 0:07:04.080 --> 0:07:06.160 I think that you pretty much covered it quite well. 0:07:06.440 --> 0:07:10.760 Wonderful, wonderful. Well. In that case, should we dive into 0:07:10.760 --> 0:07:11.320 the episode. 0:07:11.720 --> 0:07:13.600 Yeah, let's take a quick break and then we'll dive 0:07:13.640 --> 0:07:48.840 into the biology. So, Ancosarchiasis is a disease that is 0:07:48.920 --> 0:07:54.480 caused by a nematde around worm named Anco circa volvulus, 0:07:55.680 --> 0:07:58.640 which is a type of worm known as a filarial worm, 0:07:59.040 --> 0:08:02.440 which means it's a nema toad transmitted by an arthropod vector. 0:08:04.040 --> 0:08:08.680 In this case. Oncopsychiasis is also the second leading cause 0:08:08.720 --> 0:08:13.600 of infectious blindness worldwide, after trachoma, which is a bacterial 0:08:13.640 --> 0:08:18.560 disease caused by chlamydia trichomitis. So, since this is a 0:08:19.280 --> 0:08:24.240 arthropod vectored worm, let's jump straight into talking about the 0:08:24.240 --> 0:08:27.840 transmission and life cycle of this parasite, shall we. 0:08:28.320 --> 0:08:28.920 Let's do it. 0:08:29.360 --> 0:08:32.640 So, the overall life cycle of this parasite is not 0:08:32.880 --> 0:08:36.120 very dissimilar from a number of vector born diseases that 0:08:36.160 --> 0:08:39.720 we've covered on this podcast, but it is a different 0:08:39.800 --> 0:08:43.640 vector species than we've seen before. In this case, it's 0:08:43.679 --> 0:08:47.800 a black fly in the genus Stimulium. The black fly 0:08:48.160 --> 0:08:51.960 bites your skin generally much like mosquitoes. It's female blackflies 0:08:52.240 --> 0:08:56.200 that bite a human, take a blood meal, and in 0:08:56.240 --> 0:09:01.480 that blood meal ingest microfilaria, which are the earliest teeny 0:09:01.520 --> 0:09:07.120 teeny baby newly hatched larval stages of Onco circa volvulus. 0:09:08.400 --> 0:09:13.839 These microfilariae travel through the fly's gut. This is where 0:09:13.880 --> 0:09:17.839 it gets weird. They penetrate the gut walls, which we've 0:09:17.880 --> 0:09:21.040 seen other parasites do, but in this case they migrate 0:09:21.160 --> 0:09:26.080 to the flight muscles of the fly like very weird, 0:09:26.559 --> 0:09:28.880 very weird. I just have to imagine there's a lot 0:09:28.880 --> 0:09:33.080 of glucose happening, because those are important, powerful muscles, but 0:09:33.679 --> 0:09:37.120 I don't know. So in these flight muscles they live 0:09:37.240 --> 0:09:40.040 for a short time and in that time they mature 0:09:40.160 --> 0:09:43.959 into a second stage larva, and then from there they 0:09:44.000 --> 0:09:48.280 make their way down into the salivary glands near the proboscis. 0:09:48.800 --> 0:09:51.960 They mature one more time into a third stage larva 0:09:52.320 --> 0:09:55.600 and are now infectious, so that when the black fly 0:09:55.720 --> 0:09:59.080 takes its next bite of human flesh, they can be 0:10:00.200 --> 0:10:03.640 out spit out those third stage larva just under our skin. 0:10:04.600 --> 0:10:08.480 So that whole process in the blackfly takes about a week, 0:10:08.760 --> 0:10:11.960 give or take. And now in the human these larvae 0:10:12.040 --> 0:10:15.320 that have been injected just under our skin will worm 0:10:15.760 --> 0:10:21.080 and twirl. As the worm twirls the worm turn, they'll 0:10:21.120 --> 0:10:24.920 worm their little way into our subcutaneous tissue and that 0:10:25.240 --> 0:10:27.400 is where they will live. They'll make a little home 0:10:27.440 --> 0:10:31.120 for themselves in these little subcutaneous nodules that they kind 0:10:31.120 --> 0:10:36.079 of build and create, and they are pretty well protected 0:10:36.240 --> 0:10:39.560 from our immune system, which will become important later on. 0:10:41.160 --> 0:10:45.560 They feed off of our blood and both by actively 0:10:45.600 --> 0:10:48.880 feeding but also just by soaking up nutrients through their cuticle, 0:10:49.760 --> 0:10:53.560 and over a period of about ten to fifteen months 0:10:53.679 --> 0:10:59.160 or so, they mature into adult worms. They mate and 0:10:59.200 --> 0:11:03.800 then begin really leasing thousands of eggs which quickly hatch 0:11:03.960 --> 0:11:09.640 into microfilaria. Every day during the day, these little microfilaria 0:11:09.840 --> 0:11:13.200 worm their way back up to the skin's surface, where 0:11:13.240 --> 0:11:17.560 they can then be ingested by blackflies, which coincidentally bite 0:11:17.760 --> 0:11:20.600 during the day. Thus completing their life cycle. 0:11:23.040 --> 0:11:27.400 Question. I know, so you said that the when the 0:11:27.480 --> 0:11:30.959 L three larvae are injected into a person and they 0:11:31.040 --> 0:11:34.840 form this little subcutaneous nodule that in which they're fairly 0:11:34.880 --> 0:11:39.480 protected from the immune system. How like, why are they 0:11:39.520 --> 0:11:42.520 fairly protected there? Because a lot of things could be 0:11:42.559 --> 0:11:46.120 injected into our skin and not be protected from our 0:11:46.120 --> 0:11:46.840 immune system. 0:11:47.440 --> 0:11:49.520 It's a it's a very good question, and it's a 0:11:49.800 --> 0:11:52.240 it's a question that I don't have a good answer to. 0:11:52.920 --> 0:11:55.840 I will talk in a lot more detail about what 0:11:56.360 --> 0:11:59.840 causes an immune reaction to us, but the question of 0:12:00.080 --> 0:12:04.320 why is it that living worms don't provoke much of 0:12:04.320 --> 0:12:06.920 an immune response in us is a very good one 0:12:07.160 --> 0:12:08.840 and not one that I have a good answer to. 0:12:09.360 --> 0:12:12.680 And is that universally or are there people that do 0:12:12.800 --> 0:12:16.560 show immune responses and are like more protected from this 0:12:16.640 --> 0:12:17.600 parasite than others? 0:12:18.440 --> 0:12:21.320 So people don't tend to show immune responses to the 0:12:21.440 --> 0:12:25.200 living worms aside from the formation of these nodules, which 0:12:25.240 --> 0:12:27.760 you could think of as some kind of immune response, 0:12:27.800 --> 0:12:29.920 because it's kind of like, you know, making a little 0:12:29.960 --> 0:12:33.959 fibrous sheath around those worms and kind of walling them 0:12:33.960 --> 0:12:38.000 off from the body in some ways. But otherwise there's 0:12:38.040 --> 0:12:40.400 not much of an immune response that's provoked by the 0:12:40.440 --> 0:12:43.320 presence of the live worms themselves. 0:12:43.480 --> 0:12:48.160 That's wild I know, it gets wilder and so like 0:12:48.280 --> 0:12:52.080 the immune system isn't even showing like elevated antibodies or 0:12:52.120 --> 0:12:54.839 it's not is it suppressed? Like are people who are 0:12:54.840 --> 0:12:59.400 infected with this worm? Are they more susceptible to other infections? 0:13:00.200 --> 0:13:03.040 Of going like down the rabbit hole of questions here. 0:13:04.160 --> 0:13:07.439 You're going so many miles a minute. Let me, let 0:13:07.440 --> 0:13:10.760 me keep going, and I'm not sure if I'm really 0:13:10.760 --> 0:13:13.080 going to answer your questions or if I'm just gonna 0:13:13.080 --> 0:13:16.520 bring up even more questions. Let's find out. 0:13:16.559 --> 0:13:18.360 Okay, I'm along for the ride either way. 0:13:18.559 --> 0:13:22.760 Excellent, good, I'm so glad. Okay, So these adult worms 0:13:22.800 --> 0:13:27.360 that are living in these nodules, they can live for years. 0:13:27.640 --> 0:13:33.160 We're talking ten to fifteen years or more. Oh yeah, okay, 0:13:33.360 --> 0:13:37.319 and this whole time they're producing thousands, if not millions, 0:13:37.679 --> 0:13:42.840 of microflaria that whole time, not continuously. They kind of cycle, 0:13:43.000 --> 0:13:45.679 like every two to four months or so, they'll have 0:13:45.720 --> 0:13:49.000 a cycle. But anyways, ten to fifteen years. 0:13:49.160 --> 0:13:52.040 I have an estimate that I wrote down that because 0:13:52.040 --> 0:13:56.960 I was so horrified. So, the number of microfilaria released 0:13:56.960 --> 0:14:00.320 from one female adult worm during its life life of 0:14:00.360 --> 0:14:03.240 ten to fifteen years is estimated to be greater than 0:14:03.280 --> 0:14:03.959 ten million. 0:14:04.400 --> 0:14:06.920 Yeah that seems about right, because it's like two to 0:14:06.960 --> 0:14:12.079 three hundred thousand per cycle. Yeah. Yeah, that's a lot 0:14:12.080 --> 0:14:18.040 of lost, it really is. Okay, And so before we 0:14:18.080 --> 0:14:21.520 get into what the symptoms of this disease are, what 0:14:21.600 --> 0:14:23.640 I want to tell you. You're going to get mad 0:14:23.680 --> 0:14:28.040 at this. All of the symptoms that we see stem 0:14:28.480 --> 0:14:33.080 not from the worms themselves, but from our immune response 0:14:33.640 --> 0:14:34.680 to the worms. 0:14:35.640 --> 0:14:38.880 Oh but hold on. You made a very strong point 0:14:38.880 --> 0:14:42.360 of saying the living worms. So I'm guessing these are 0:14:42.840 --> 0:14:43.560 dead worms. 0:14:43.800 --> 0:14:45.840 You are exactly right. 0:14:47.040 --> 0:14:49.040 But you're right. I was like, wait a second, errand 0:14:49.600 --> 0:14:50.640 then I remember. 0:14:51.320 --> 0:14:51.680 I know. 0:14:52.440 --> 0:14:55.520 So it turns out that they do not trigger these 0:14:55.600 --> 0:14:59.200 intense immune reactions until they die. So of course we 0:14:59.280 --> 0:15:01.800 have to answer the quiet why the heck? And how 0:15:01.840 --> 0:15:06.480 the heck? So it's thought that the immune response that 0:15:06.600 --> 0:15:10.360 is triggered is in part due to proteins and other 0:15:10.640 --> 0:15:14.920 like inflammatory markers that are released by the dying worms themselves. 0:15:15.000 --> 0:15:17.640 So proteins and things that are inside the worms, but 0:15:17.680 --> 0:15:21.800 then not accessible to our immune system until that worm dies. Okay, 0:15:22.120 --> 0:15:27.960 but far more importantly and interestingly, it's also thought to 0:15:28.000 --> 0:15:33.520 be due largely to the release of the bacterial endosymbiants 0:15:33.720 --> 0:15:34.560 that they harbor. 0:15:34.920 --> 0:15:42.920 Say what, it's so strange. Wolbachia has so many mysteries 0:15:42.960 --> 0:15:43.880 that surround it. 0:15:44.400 --> 0:15:49.080 So many mysteries. So we have talked about wolbachia on 0:15:49.120 --> 0:15:53.200 this podcast before, briefly in I think our dengay episode, 0:15:53.480 --> 0:15:56.840 because they're important in the context of mosquitoes that transmit 0:15:56.920 --> 0:16:02.640 dungay and other arboviral diseases. As a recap Willbakia are 0:16:02.800 --> 0:16:06.600 a genera of bacteria that often inhabit the guts of 0:16:06.720 --> 0:16:11.440 insects and other invertebrates. But it turns out that in 0:16:11.440 --> 0:16:18.560 filarial nematodes like oncocercavolvulus, but also Wucheria bancroftyi, which is 0:16:18.640 --> 0:16:24.200 the coosative agent of lymphatic philoriasis and other nematodes, these 0:16:24.240 --> 0:16:30.680 bacteria are essential endosymbionts. So without these bacteria, the nematodes 0:16:30.720 --> 0:16:34.920 cannot survive or reproduce. We still don't know exactly what 0:16:34.960 --> 0:16:38.080 it is that they are doing necessarily, but we do 0:16:38.240 --> 0:16:42.320 know that they are essential to the process of embryogenesis. 0:16:42.360 --> 0:16:45.800 So eggs can't develop into worms without the presence of 0:16:45.800 --> 0:16:49.200 these bacteria which are transmitted transovarially. 0:16:49.720 --> 0:16:52.760 That is so interesting. 0:16:52.520 --> 0:16:52.840 I know. 0:16:53.400 --> 0:16:56.160 And it seems that based on a lot of data, 0:16:56.520 --> 0:17:00.880 the release of these bacteria from dead worms is thought 0:17:00.920 --> 0:17:03.920 to be a major part of the trigger for our 0:17:04.200 --> 0:17:05.440 immune response. 0:17:06.480 --> 0:17:11.080 And so how does this trigger look different compared to 0:17:11.640 --> 0:17:14.480 like other parasitic infection triggers. 0:17:14.720 --> 0:17:17.480 So that's what's so interesting is that what we see 0:17:17.600 --> 0:17:20.439 is still a lot of eosinophil response, which is what 0:17:20.480 --> 0:17:25.680 you would expect with a parasitic disease, not solely though. 0:17:25.760 --> 0:17:29.159 Antibodies have a large role as well in the inflammation 0:17:29.320 --> 0:17:35.080 and the immune response to acopsychiasis, as do neutrophils and 0:17:35.200 --> 0:17:37.520 other lymphocytes, and these are all different types of white 0:17:37.560 --> 0:17:41.720 blood cells. But you still do see a really large 0:17:41.720 --> 0:17:45.520 eosinophil response, which is interesting. So maybe those are responding 0:17:45.560 --> 0:17:48.720 to the worm parts, and it's the neutrophils and lymphocytes 0:17:48.760 --> 0:17:52.719 and antibodies that are responding to the bacteria. Who knows, 0:17:52.880 --> 0:17:56.479 We don't fully know. But I'm also going to put 0:17:56.520 --> 0:17:58.840 a pin in that, and I just want for us 0:17:58.880 --> 0:18:02.360 to remember how important while bakia are because we'll talk 0:18:02.359 --> 0:18:06.600 more about them in the current events section. Oh yeah, yes, 0:18:07.240 --> 0:18:09.920 all right, So then what does this disease actually look 0:18:10.000 --> 0:18:15.640 like in its mildest form. It's possible that the only 0:18:15.720 --> 0:18:18.280 symptoms that you would have are these nodules that we've 0:18:18.320 --> 0:18:21.960 talked about. So these nodules are very kind of hard, 0:18:22.960 --> 0:18:28.400 deep subcutaneous lumps, I guess is the best word, often 0:18:28.560 --> 0:18:30.960 around the hip girdle, but you can also have them 0:18:31.119 --> 0:18:33.600 really anywhere throughout your body. They tend to be most 0:18:33.680 --> 0:18:37.800 prominent where you have like a bone, just because then 0:18:37.840 --> 0:18:40.639 you have less subcutaneous tissue between your bone and your skin. 0:18:42.080 --> 0:18:45.840 But in terms of symptoms that we see in the 0:18:45.880 --> 0:18:50.760 mildest symptoms present as a skin rash, which is usually 0:18:50.800 --> 0:18:54.159 what we call maculo popular. That means a flat area 0:18:54.240 --> 0:18:56.320 of rash with a lot of little bumps on it 0:18:57.000 --> 0:19:02.480 that is incredibly itchy. Right, I think it's it's hard. 0:19:02.920 --> 0:19:05.920 The word itchy. I feel like it doesn't do. It 0:19:06.080 --> 0:19:10.120 doesn't right, it doesn't invoke I think the response that 0:19:10.119 --> 0:19:16.840 that this really deserves no. Yeah, so it's yeah, I 0:19:17.080 --> 0:19:19.919 wish I had a better word than just incredibly itchy. 0:19:20.800 --> 0:19:25.239 So this rash can resolve in some cases, although the 0:19:25.280 --> 0:19:27.800 disease itself does not resolve, like we said, these worms 0:19:27.840 --> 0:19:32.080 can live for years. But more commonly, this rash can 0:19:32.119 --> 0:19:36.240 become chronic and can actually generalize across the body instead 0:19:36.240 --> 0:19:40.320 of being present in just discrete patches. And this, as 0:19:40.320 --> 0:19:45.199 you can imagine, leads to even more severe itching. And 0:19:45.240 --> 0:19:48.960 then as our immune response ramps up, the way that 0:19:49.040 --> 0:19:53.200 our skin kind of heals results in very severe scarring. 0:19:53.720 --> 0:19:58.000 It's what's called like henification, like a like a lichen 0:19:58.080 --> 0:20:00.880 that grows on a tree. Yeah, so it's like our 0:20:00.920 --> 0:20:05.480 skin becoming really thick and leathery. At this stage, it 0:20:05.520 --> 0:20:07.960 can lead to hyper pigmentation of the skin, so it 0:20:08.000 --> 0:20:13.120 becomes very very dark in patches. And like we talked 0:20:13.160 --> 0:20:17.439 about in our leshmaniasis episode, these type of skin manifestations 0:20:17.440 --> 0:20:20.359 can be associated with a lot of stigma, and so 0:20:20.400 --> 0:20:23.679 they can be debilitating, not only in the physical sense, 0:20:23.800 --> 0:20:27.280 like the amount of itching I saw it described where 0:20:27.320 --> 0:20:30.280 some people couldn't even sleep except for on their knees 0:20:30.280 --> 0:20:33.000 and elbows because of the pain of the itching. 0:20:33.400 --> 0:20:37.120 Yeah. I saw some descriptions of people literally like burning 0:20:37.160 --> 0:20:41.840 their skin because it was so horrifyingly itchy. 0:20:41.600 --> 0:20:45.200 Itchy, but it can also be debilitating in the way 0:20:45.240 --> 0:20:49.639 that it is stigmatizing as well. And then over years 0:20:49.680 --> 0:20:52.920 of this infection, the changes can become even more chronic, 0:20:53.520 --> 0:20:56.720 and the descriptors of these changes in the literature I 0:20:56.720 --> 0:21:00.879 think are also pretty stigmatizing. But basically what can happen 0:21:01.000 --> 0:21:04.119 is the skin can end up with its elasticity completely 0:21:04.160 --> 0:21:08.200 destroyed because of all of that damage to the kind 0:21:08.200 --> 0:21:10.880 of mid layers of the skin. So then the very 0:21:10.920 --> 0:21:15.600 top layers become really thinned out, they become atrophied, they're 0:21:15.640 --> 0:21:18.040 quite wrinkily, and they can just sort of hang off 0:21:18.040 --> 0:21:22.520 of the body. You can lose pigment entirely in those 0:21:22.560 --> 0:21:26.639 areas because of all the atrophy, and so the skin 0:21:26.720 --> 0:21:30.160 manifestations can be severe and this whole time, even as 0:21:30.200 --> 0:21:32.919 it becomes chronic that itching persists. 0:21:35.040 --> 0:21:39.160 And okay, question real quick again about the nodules when 0:21:40.359 --> 0:21:44.840 like where those nodules exist is where the blackfly has 0:21:44.880 --> 0:21:50.280 bitten you, or like how much how much variation is there? 0:21:50.560 --> 0:21:53.680 Yeah, there's quite a lot of variation, which is so interesting. 0:21:54.160 --> 0:21:56.960 So from what I read, black flies often like to 0:21:57.000 --> 0:21:59.640 bite on lower extremities, so they really bite a lot 0:21:59.640 --> 0:22:03.359 on legs, But these nodules tend to be present on 0:22:03.440 --> 0:22:06.600 the hips or even the forehead and on the head. 0:22:07.400 --> 0:22:11.440 So that would suggest that these adult worms can travel 0:22:11.680 --> 0:22:14.639 and decide where they're going to make their nodule home. 0:22:14.960 --> 0:22:19.159 But it also means that the microfilaria which are traveling 0:22:19.359 --> 0:22:22.480 to the skin surface can also travel a really long way. 0:22:22.520 --> 0:22:26.680 They can go pretty much anywhere in our body, right, Yeah. 0:22:26.359 --> 0:22:29.320 And I also thought I read somewhere too about like 0:22:29.720 --> 0:22:31.920 because and I know you haven't gotten to this part yet, 0:22:31.920 --> 0:22:35.840 but the Americas versus Africa in terms of the location 0:22:36.520 --> 0:22:39.600 and frequency of the skin nodules blackflies have different biting 0:22:39.640 --> 0:22:42.040 patterns right on, Like, they bite more on the upper 0:22:42.080 --> 0:22:45.560 half of the body and the America's compared to Africa, 0:22:45.600 --> 0:22:47.800 where it's on the lower parts of the body. 0:22:48.000 --> 0:22:50.040 I would believe that because I did read about a 0:22:50.080 --> 0:22:52.919 lot more forehead nodules and things in the Americas compared 0:22:52.920 --> 0:22:57.600 to in Africa. Yeah, okay, okay, So that's kind of 0:22:57.640 --> 0:23:00.080 all of the skin manifestations, which is one of the 0:23:00.080 --> 0:23:03.639 most important parts of this disease. The other is, of course, 0:23:03.760 --> 0:23:07.800 the ocular or the eye manifestations. Well, that's where it 0:23:07.800 --> 0:23:12.680 gets the common name river blindness. So as these microfilaria 0:23:12.840 --> 0:23:15.639 travel out of nodules and towards the skin, some of 0:23:15.680 --> 0:23:19.399 them can travel to the eye. In the eye, the 0:23:19.440 --> 0:23:26.240 microfilaria that die also cause a localized inflammatory reaction and 0:23:26.320 --> 0:23:31.080 this results in a number of different manifestations kind of 0:23:31.119 --> 0:23:35.600 The most common one is called sclerosing keratitis, which is 0:23:35.640 --> 0:23:38.400 where the cornea of your eye, which is the part 0:23:38.480 --> 0:23:41.760 that covers like your iris and your pupil that becomes 0:23:41.800 --> 0:23:46.439 inflamed and then will scar over. So this starts with 0:23:46.520 --> 0:23:49.920 a haziness around the edges of the cornea and then 0:23:49.960 --> 0:23:53.080 will eventually go in to encompass the entire thing, causing 0:23:53.119 --> 0:23:59.159 complete blindness. Oh yeah, it's not only sclerosing keratitis, because 0:23:59.200 --> 0:24:01.800 you can have these worms that end up in the 0:24:01.800 --> 0:24:05.080 posterior part of your eye, which can cause inflammation of 0:24:05.080 --> 0:24:09.399 the retina and similar kinds of damage due to inflammation 0:24:09.760 --> 0:24:12.760 in all parts of the eye. And I think it's 0:24:12.800 --> 0:24:17.800 also important to point out that these microfilaria can travel 0:24:18.119 --> 0:24:21.000 kind of throughout the body and invade, for example, our 0:24:21.080 --> 0:24:24.320 lymphatic system, and they've been found in a number of 0:24:24.359 --> 0:24:27.640 different organs. Like, if you sample organs from someone who's 0:24:27.760 --> 0:24:32.360 died who was infected with ancosirchiasis, you can find microflaria 0:24:32.400 --> 0:24:35.399 in a number of different organs, but we don't really 0:24:35.480 --> 0:24:38.080 have a good handle on what kind of disease might 0:24:38.119 --> 0:24:41.720 be caused by that. It's really the skin and the 0:24:41.760 --> 0:24:45.520 eye that are the two most common organs affected, right, 0:24:46.160 --> 0:24:50.960 So yeah, I also want to mention because it's important, 0:24:50.960 --> 0:24:52.640 but also because it was brought up in our first 0:24:52.640 --> 0:24:55.880 hand account. There does seem to be increasing evidence that 0:24:56.040 --> 0:25:00.400 infection with unchosirchiasis is also associated with an a increased 0:25:00.520 --> 0:25:01.560 risk of epilepsy. 0:25:02.640 --> 0:25:06.959 Is there any suggestion as to what the mechanism could be? 0:25:06.960 --> 0:25:09.720 None at all, which is the hardest part. So there's 0:25:09.760 --> 0:25:13.760 a lot of epidemiological evidence of association, but there's not 0:25:13.920 --> 0:25:17.080 really any data on what could be the cause or 0:25:17.080 --> 0:25:19.560 the mechanism. So we don't really know if it is 0:25:19.640 --> 0:25:24.640 in fact oncosyarchiasis or something else. But there's epidemiological evidence 0:25:24.680 --> 0:25:27.360 for this association, so I thought it was important to mention. 0:25:27.880 --> 0:25:28.720 Yeah, definitely. 0:25:29.040 --> 0:25:35.640 Yeah, So yeah, that's kind of the basic overall picture. 0:25:35.800 --> 0:25:38.800 I think it's interesting that there does seem to be 0:25:38.840 --> 0:25:46.360 some strain differences. So in parts of West Africa, it's 0:25:46.600 --> 0:25:49.720 long been noticed that in the savannah regions the rates 0:25:49.760 --> 0:25:53.160 of blindness due to Anco circa were much higher than 0:25:53.200 --> 0:25:57.960 in forested regions of West Africa. And in those savannah regions, 0:25:58.040 --> 0:26:01.600 the rates of blindness really strongly correlate with the intensity 0:26:01.720 --> 0:26:05.159