WEBVTT - Ep 62 Leishmaniasis, Relationship Status: It's Complicated 0:00:01.360 --> 0:00:04.080 On one burning day in April, in a village in Biha, 0:00:04.680 --> 0:00:08.200 Sushila Devy was worried about her sick child. Her decision 0:00:08.240 --> 0:00:12.160 to seek medical help required brave determination. There was the 0:00:12.240 --> 0:00:14.880 overpowering heat through which she would have to walk, carrying 0:00:14.960 --> 0:00:16.960 her sick child most of the eight miles to the 0:00:17.000 --> 0:00:20.680 government health center. The child was ill, but not emergency 0:00:20.720 --> 0:00:23.320 ill in any of the too familiar life threatening ways, 0:00:23.760 --> 0:00:27.480 the acute fever and coma of childhood malaria, the rapid 0:00:27.520 --> 0:00:31.160 wasting diarrhea and death of cholera, or the labored gasping 0:00:31.200 --> 0:00:35.040 of pneumonia. It was merely that the child seemed somewhat 0:00:35.080 --> 0:00:38.519 feverish this past month and was becoming emaciated despite a 0:00:38.560 --> 0:00:42.920 reasonably good appetite, with a distended abdomen. The young doctor 0:00:43.000 --> 0:00:47.120 was brusque, unfriendly, and uncommunicative. He told Sushila to put 0:00:47.120 --> 0:00:50.559 her frightened child on the bare wooden examination table. To 0:00:50.640 --> 0:00:53.760 the doctor, the constellation of signs and symptoms could point 0:00:53.840 --> 0:00:58.000 to only one diagnosis. The prolonged fever, the greatly enlarged 0:00:58.040 --> 0:01:02.000 liver and spleen, the anemia, the serum that jelled when 0:01:02.040 --> 0:01:07.880 mixed with formaldehyde all meant visceral leshmaniasis. Realizing the gravity 0:01:07.920 --> 0:01:10.800 of what he was about to tell Sushila, his pomposity 0:01:10.840 --> 0:01:14.920 fell away. Mother. He said, gently, your child is very 0:01:14.959 --> 0:01:18.120 ill with kala azar. It does not mean death. Your 0:01:18.200 --> 0:01:21.200 child can be cured. You must buy medicine. Then you 0:01:21.280 --> 0:01:23.959 must come here every day for twenty days so the 0:01:24.040 --> 0:01:27.440 nurse can inject the medicine. How much is it, Sushila 0:01:27.480 --> 0:01:30.600 asked fearfully, for you, I will give you a bottle 0:01:30.640 --> 0:01:33.440 of the drug enough for her whole treatment for three 0:01:33.480 --> 0:01:38.600 hundred rupees about fifteen dollars. It was an astronomical sum, 0:01:38.959 --> 0:01:42.360 more than the family's income for some months. Sushila picked 0:01:42.400 --> 0:01:44.440 up her child and began the long walk back to 0:01:44.480 --> 0:01:48.080 her village. Even if by some miracle they could buy 0:01:48.120 --> 0:01:50.720 the medicine, there was no way that Sushila and the 0:01:50.800 --> 0:01:53.280 child could travel these long miles to the health center 0:01:53.360 --> 0:01:57.480 for twenty consecutive days. No for the child, they would 0:01:57.520 --> 0:01:59.720 have to do the best they could. They would pray 0:01:59.760 --> 0:02:02.160 to the gods, they would consult the doctor in the 0:02:02.160 --> 0:02:03.200 adjoining village. 0:02:03.840 --> 0:02:04.400 In the end. 0:02:04.520 --> 0:02:07.960 As the weeks passed, the child became progressively more ill. 0:02:08.520 --> 0:02:12.200 She grew even more emaciated, her skin turned a dusky gray, 0:02:12.720 --> 0:02:16.760 her hair became brittle, Small bleeding sores covered her body, 0:02:17.200 --> 0:02:20.920 and the abdomen, burdened with a grossly enlarged liver, distended 0:02:20.960 --> 0:02:25.600 even further. One day, some three months after Sushila's visit 0:02:25.639 --> 0:02:28.560 to the health center, the child began to cough and 0:02:28.639 --> 0:02:32.360 gasp for breath. During the night, the little girl died, 0:02:33.160 --> 0:03:22.600 a fragment of life sacrificed for want of fifteen dollars. Ooh, 0:03:23.880 --> 0:03:26.239 that was rough to even read out loud. 0:03:26.680 --> 0:03:32.400 Yeah, that is from a book called The Malaria Capers 0:03:32.680 --> 0:03:34.560 by Robert S. Desowitz. 0:03:36.040 --> 0:03:36.240 Hi. 0:03:36.560 --> 0:03:38.280 I'm erin Welsh. 0:03:37.720 --> 0:03:39.760 And i'm erin allman updyke. 0:03:39.720 --> 0:03:43.400 And this is this podcast will kill you? It is. 0:03:43.840 --> 0:03:46.680 It's a depressing one today, erin. 0:03:46.960 --> 0:03:48.320 I mean, when are they not? 0:03:48.880 --> 0:03:52.480 Yeah? Could we ever, like maybe one time this season 0:03:52.560 --> 0:03:56.760 we could find a not depressing one just to try. 0:03:57.160 --> 0:04:01.800 We could try. Oh gosh, So, as you may have guessed, 0:04:01.880 --> 0:04:06.320 this week we are covering leshmaniasis, which includes not just 0:04:06.480 --> 0:04:09.920 visceral leshmaniasis as described in the first hand account, but 0:04:10.080 --> 0:04:13.880 also cutaneous and muco cutaneous leshmaniasis. 0:04:14.320 --> 0:04:14.880 Sure does. 0:04:15.200 --> 0:04:18.560 It's a lot more complex of a story than I 0:04:18.600 --> 0:04:19.000 think we. 0:04:19.080 --> 0:04:24.640 Realized really really complicated, a lot more than I ever knew. 0:04:25.160 --> 0:04:27.599 So it was good to learn this stuff. But also, 0:04:28.000 --> 0:04:30.760 oh my gosh, I hope that I do it even 0:04:30.839 --> 0:04:32.160 a shred of justice. 0:04:33.040 --> 0:04:37.960 I trust you, Oh gosh, I trust you well. Erin, 0:04:38.000 --> 0:04:40.440 I think we have a couple pieces of business to 0:04:40.560 --> 0:04:43.120 take care of, or at least one. 0:04:43.360 --> 0:04:46.279 Yep, is it that it's let me check quarantiny time. 0:04:46.560 --> 0:04:50.640 It is, indeed quarantine time. You are absolutely exactly right. 0:04:50.920 --> 0:04:52.440 What are we drinking today, Erin? 0:04:53.160 --> 0:04:56.080 Today we are drinking a sand fly in the ointment 0:04:56.520 --> 0:04:58.160 he oh so. 0:04:58.200 --> 0:05:02.120 Named, because this is a disease transmitted by sand flies. 0:05:03.800 --> 0:05:08.640 And in sand fly in the ointment there is lime juice, 0:05:08.839 --> 0:05:14.520 grapefruit juice, some simple syrup, all spice liqueur, so I 0:05:14.560 --> 0:05:16.800 finally get to use that stink and all spice liquor 0:05:16.880 --> 0:05:22.599 that's been on my shelf for ages, and some rum yum. Yeah. 0:05:22.640 --> 0:05:25.400 And we will post the full recipe to the quarantine 0:05:25.520 --> 0:05:28.240 as well as the non alcoholic place Barrita on our 0:05:28.240 --> 0:05:30.760 website This podcast will Kill You dot com, as well 0:05:30.800 --> 0:05:34.240 as all of our social media channels, so check it 0:05:34.279 --> 0:05:39.479 out there. Yeah. Any other business that we have I 0:05:39.640 --> 0:05:40.600 don't believe. 0:05:40.720 --> 0:05:44.960 So all right, then shall we just dive in season four, 0:05:45.040 --> 0:05:45.880 episode two? 0:05:46.279 --> 0:05:48.640 Oh my gosh, let's do it, okay. 0:05:49.480 --> 0:06:14.880 Right after this break. So, like we mentioned already, the 0:06:14.880 --> 0:06:20.839 biology of this disease is quite a lot. So I 0:06:21.040 --> 0:06:23.320 tried really hard, which is the opposite of what I 0:06:23.400 --> 0:06:25.800 normally do in my notes. I tried to really keep 0:06:25.800 --> 0:06:29.440 this organized so that we can go through it in 0:06:29.440 --> 0:06:33.760 a way that makes sense. Okay, So let me just 0:06:33.880 --> 0:06:37.760 go ahead and get started, all right. So, leshmaniasis, like 0:06:37.800 --> 0:06:41.120 you mentioned already, aarin, it's not just a single disease. 0:06:41.760 --> 0:06:45.279 It's a group of at least three different disease syndromes 0:06:45.920 --> 0:06:49.160 which are caused by a number of different species of 0:06:49.320 --> 0:06:53.600 protozoan parasites in the genus lesh Mania. 0:06:54.240 --> 0:06:57.040 It's kind of interesting that like they're all like when 0:06:57.080 --> 0:07:01.080 we say leshmaniasis, it's like means all of them. It 0:07:01.160 --> 0:07:04.479 means so many different types of diseases and so many 0:07:04.480 --> 0:07:07.200 different like caused by so many different species of parasites. 0:07:07.279 --> 0:07:11.400 Yeah, like overimplification. Yeah, yeah, I can't believe that we 0:07:11.440 --> 0:07:14.960 call this all the same disease. Quite honestly, it blows 0:07:15.000 --> 0:07:15.360 my mind. 0:07:15.520 --> 0:07:17.400 I mean historically we didn't, but we'll get to that. 0:07:17.560 --> 0:07:20.520 Oh any great, I can't wait. That makes a lot 0:07:20.520 --> 0:07:24.520 of sense actually, okay, yeah, so at least twenty different 0:07:24.560 --> 0:07:30.120 species of protozoan parasite transmitted by a whole number of 0:07:30.160 --> 0:07:34.000 different species of insect vectors. In this case, like we said, 0:07:34.040 --> 0:07:36.600 we're dealing with a new type of insect vector that 0:07:36.640 --> 0:07:38.760 we haven't dealt with on the podcast before, and that 0:07:38.920 --> 0:07:39.760 is the sand fly. 0:07:40.320 --> 0:07:43.600 Yeah, this is our first new vector. 0:07:43.840 --> 0:07:45.920 Yeah, we've only done mosquitos and ticks so far. 0:07:46.240 --> 0:07:48.000 How interesting. I didn't realize that. 0:07:48.160 --> 0:07:51.680 Yeah, so that's fun. So sandflies, for anyone who's not familiar, 0:07:51.720 --> 0:07:54.960 they're another sort of biting fly similar to mosquitoes. It's 0:07:55.040 --> 0:07:59.200 primarily the females who take blood meals, whereas both males 0:07:59.240 --> 0:08:03.320 and females also feed on like fluoral nectar and sugar water. 0:08:04.720 --> 0:08:07.480 So in this case, we're talking about sandflies in two 0:08:07.560 --> 0:08:14.360 different genera, Lutzomia and Phlebotomus. Okay, so so far we 0:08:14.480 --> 0:08:18.960 have over twenty species of parasite and two whole genera 0:08:19.000 --> 0:08:19.720 of sandfly. 0:08:20.120 --> 0:08:22.080 Okay, it's a lot. 0:08:22.320 --> 0:08:26.480 Uh huh. It's gonna get to be more. Because leshmaniasis 0:08:26.520 --> 0:08:29.400 affects humans, which is what we're going to talk about today, 0:08:29.600 --> 0:08:32.480 but it also affects like at least one hundred other 0:08:32.920 --> 0:08:36.760 mammal species. So in addition to different forms of the 0:08:36.760 --> 0:08:40.439 disease that we see in humans, there are different cycles 0:08:40.480 --> 0:08:43.240 of the disease. There is a zoonotic cycle of disease 0:08:43.440 --> 0:08:48.920 wherein humans become infected from vectors that got infected from animals, 0:08:49.000 --> 0:08:51.720 so from animal to vector to human. And then there's 0:08:51.800 --> 0:08:56.559 also anthroponotic cycles wherein humans are the dominant reservoir host 0:08:56.640 --> 0:08:59.360 and humans are infecting other humans through a vector. 0:09:00.440 --> 0:09:03.400 And it's not just mammals, right, isn't it also reptiles. 0:09:03.600 --> 0:09:06.000 I think that reptiles and some birds have been known 0:09:06.080 --> 0:09:08.320 to be infected. How much of a role they really 0:09:08.360 --> 0:09:12.080 play in the zoonotic disease in humans is pretty minimal 0:09:12.120 --> 0:09:12.800 as far as I know. 0:09:13.120 --> 0:09:14.720 Yeah, I don't think they do, but I think it 0:09:14.800 --> 0:09:18.920 is just amazing the sheer number of species I know 0:09:19.040 --> 0:09:21.840 a different, like very different groups of animals that it's 0:09:21.960 --> 0:09:24.720 these parasites can infect bananas truly. 0:09:26.559 --> 0:09:29.640 So yeah, okay, that's a lot already. 0:09:30.160 --> 0:09:32.480 Okay, yep, So for. 0:09:32.559 --> 0:09:35.720 This biology section, because that's so much, we are really 0:09:35.880 --> 0:09:39.840 going to focus on the disease or the three big 0:09:39.880 --> 0:09:43.599 disease states of leshmaniasis in humans. I'm not going to 0:09:43.679 --> 0:09:48.000 touch on leshmaniasis in animals because it's just going to 0:09:48.040 --> 0:09:52.040 make things more complicated. So let's get into this disease 0:09:52.080 --> 0:09:54.679 by going over the parasite life cycle, which will tell 0:09:54.720 --> 0:09:58.080 us how it's transmitted, and then we'll talk about how 0:09:58.960 --> 0:10:00.720 we see the disease mana fest in humans. 0:10:00.760 --> 0:10:01.920 Okay, sounds great. 0:10:02.720 --> 0:10:10.199 So leshmania species the parasite that causes leshmaniasis, like plasmodium 0:10:10.240 --> 0:10:15.240 parasites that cause malaria or tripanasoma parasites that cause Shaggas disease, 0:10:16.000 --> 0:10:21.800 are a eukaryotic, single celled parasite that has multiple different 0:10:22.240 --> 0:10:27.040 distinct life stages in their different hosts, whether a mammal 0:10:27.200 --> 0:10:31.520 or reptile and insect. In the case of leshmaniasis, they 0:10:31.520 --> 0:10:36.240 have two different forms, the a mastigote and the pro mastigot. 0:10:36.760 --> 0:10:39.640 One is a little ball that lives inside of our cells, 0:10:39.960 --> 0:10:45.080 and one is a cute, little kind of spermy shaped thing. 0:10:45.679 --> 0:10:47.959 I yes, maybe that doesn't sound cute, but it is 0:10:48.640 --> 0:10:52.160 with a little flagella tail that can swim. Okay, So 0:10:52.160 --> 0:10:55.120 a leshmania life cycle goes something like this, a sand 0:10:55.160 --> 0:10:59.320 fly takes a bite of an infected animal host in 0:10:59.480 --> 0:11:02.720 just a blood that contains the a mast goat form 0:11:03.040 --> 0:11:06.559 of the parasite. Those parasites travel through the gut of 0:11:06.600 --> 0:11:10.920 the sandfly, transform into the pro mastigotes, which have that 0:11:11.040 --> 0:11:16.080 flagella and can swim, and those parasites continue to divide. 0:11:16.200 --> 0:11:19.040 They make their way out of the gut of the 0:11:19.080 --> 0:11:23.120 sandfly and into their proboscis, which is the biting part 0:11:23.160 --> 0:11:26.679 of the fly. And then when that sandfly takes another 0:11:26.720 --> 0:11:31.040 blood meal, those parasites are regurgitated into that new host. 0:11:31.679 --> 0:11:34.199 In that host, let's say it's a human, since that's 0:11:34.200 --> 0:11:38.080 what we're talking about. Those pro mastagoats which are swimming 0:11:38.640 --> 0:11:43.800 are taken up by our white blood cells mostly are macrophages, 0:11:43.840 --> 0:11:47.680 which we've talked about a lot on this podcast. Those 0:11:47.720 --> 0:11:50.960 are a white blood cell that usually helps clear infection 0:11:51.160 --> 0:11:56.680 by like engulfing bacteria and parasites and killing them. Turns out, 0:11:56.840 --> 0:12:01.960 in the case of lesh mania, when a macrophage ingest it, 0:12:02.000 --> 0:12:05.040 that's actually where they become a master to goats and 0:12:05.120 --> 0:12:07.720 then continue to divide and reproduce. 0:12:09.720 --> 0:12:13.600 Yeah, so how do they avoid death? 0:12:14.160 --> 0:12:17.120 Oh, such a good question. Aaron, I wish that I 0:12:17.240 --> 0:12:22.600 had a full good answer to that. So leshmaniasis is 0:12:22.720 --> 0:12:27.000 a disease of what's called the reticulo endothelial system, So 0:12:27.000 --> 0:12:31.280 that means that it effects and replicates white blood cells, 0:12:31.520 --> 0:12:35.680 especially macrophages, and then affects in theory any organ where 0:12:35.679 --> 0:12:39.920 those white blood cells tend to congregate. So the exact 0:12:40.240 --> 0:12:44.920 mechanisms by which it evades our immune response are really 0:12:45.520 --> 0:12:50.680 really complicated To kind of sum it up in the 0:12:50.720 --> 0:12:56.959 simplest terms that I can, Gosh. 0:12:55.840 --> 0:12:58.240 Is it basically suppress the immune system overall? 0:12:58.559 --> 0:13:03.880 Exactly it it's press our immune system? And how exactly 0:13:03.920 --> 0:13:07.640 they're able to survive inside of macrophages, I don't fully know. 0:13:08.240 --> 0:13:11.920 But by living inside of macrophagis they evade any other 0:13:12.000 --> 0:13:13.240 of our immune responses? 0:13:14.000 --> 0:13:17.160 Okay? That makes sense and also very sneaky. 0:13:16.800 --> 0:13:22.640 And very very sneaky. Okay, And overall we know that 0:13:22.880 --> 0:13:27.240 infection with leshmaniasis it causes our body to mount an 0:13:27.240 --> 0:13:30.280 immune response, like we make antibodies to it, but those 0:13:30.320 --> 0:13:33.360 antibodies don't do much. It turns out that to develop 0:13:33.440 --> 0:13:38.480 immunity towards leshmaniasis, it's more about cell mediated So you 0:13:38.559 --> 0:13:41.600 need a strong t cell response to eventually kill those 0:13:41.640 --> 0:13:45.480 macrophages that are infected. Does that make sense? 0:13:45.800 --> 0:13:51.200 That does? And so basically the ant because it lives intracellularly, 0:13:51.760 --> 0:13:53.559 the antibodies don't even reach them. 0:13:54.160 --> 0:13:59.080 Right, Yeah, exactly. But yeah, overall infection with lesh mania 0:13:59.120 --> 0:14:04.520 species decreases our overall immune response. Okay, so there's really 0:14:04.520 --> 0:14:08.040 strong interactions going on between this parasite and our immune system, 0:14:08.080 --> 0:14:13.880 which is fascinating and complicated. Yeah, so let's get more complicated, 0:14:14.640 --> 0:14:17.920 all right. Like you mentioned, Aaron, there are three major 0:14:18.120 --> 0:14:22.760 forms and some others actually that we'll touch on. In 0:14:22.840 --> 0:14:25.680 terms of the disease that we know of as leshmaniasis, 0:14:26.120 --> 0:14:32.840 there's cutaneous, mucosal or mucosal cutaneous called a couple different things, 0:14:33.160 --> 0:14:38.680 and visceral. What type of disease a person gets depends 0:14:38.800 --> 0:14:42.800 on the parasite species. So some species generally cause a 0:14:42.920 --> 0:14:48.600 visceral leshmaniasis, while others generally cause cutaneous infection. But it 0:14:48.720 --> 0:14:52.520 also depends on host factors that we don't fully understand, 0:14:52.640 --> 0:14:58.680 whether that's genetics like genetic susceptibility, or overall immune response. 0:14:58.840 --> 0:15:02.840 Like if you have a poor cell mediated immune response 0:15:02.920 --> 0:15:06.000 to begin with, you might be more predisposed to infection, 0:15:07.040 --> 0:15:12.320 et cetera. So it's complicated. That's that's the subtitle of 0:15:12.360 --> 0:15:12.880 this episode. 0:15:12.920 --> 0:15:16.000 I was gonna say lash mania relationship status. It's complicated. 0:15:17.400 --> 0:15:18.080 I like it. 0:15:20.120 --> 0:15:25.640 So when you say generally this species causes visceral versus 0:15:25.640 --> 0:15:29.200 cutaneous whatever, what does that generally actually look like? Is 0:15:29.240 --> 0:15:32.200 it like ninety five percent? Or is it much? Is 0:15:32.240 --> 0:15:33.360 it more variable than that? 0:15:33.880 --> 0:15:37.600 Very good question. I don't have a solid number on it. 0:15:37.720 --> 0:15:43.080 So in most of the literature, for example, visceral leshmaniasis 0:15:43.400 --> 0:15:47.840 is most often caused by leshmania donovanni, but also by 0:15:47.920 --> 0:15:51.920 leshmania in phantom, which is also kind of the same 0:15:51.960 --> 0:15:56.720 thing as leshmania shagasai. Okay, those are the same thing, 0:15:56.960 --> 0:15:59.840 seem to be the same species. Okay, So those two 0:16:00.080 --> 0:16:04.920 species are the dominant species that cause visceral leshmaniasis. However, 0:16:05.280 --> 0:16:09.680 in a few cases, a couple of other species have 0:16:09.880 --> 0:16:14.440 been found to cause visceral leshmaniasis that normally cause cutaneous 0:16:14.720 --> 0:16:17.640 The rest of the species tend to only cause cutaneous 0:16:17.680 --> 0:16:21.320 leshmaniasis except in those cases. Does that answer your question? 0:16:21.920 --> 0:16:24.120 Yeah? And then what about muco cutaneous? 0:16:24.200 --> 0:16:26.720 So muco cutaneous will get into it tends to be 0:16:26.840 --> 0:16:30.120 a longer term consequence of cutaneous leshmaniasis. 0:16:30.600 --> 0:16:34.600 Oh yeah, and that but that is also associated with 0:16:34.880 --> 0:16:37.440 I assume some parasitic species more than others. 0:16:37.720 --> 0:16:39.040 Yes, yep, exactly. 0:16:39.480 --> 0:16:42.000 Okay, So like, okay, okay, interesting. 0:16:41.720 --> 0:16:44.760 Yeah, it's very interesting. And I fully did not know 0:16:44.840 --> 0:16:47.280 that before researching for this episode. Like I knew there 0:16:47.360 --> 0:16:50.560 was cutaneous and visceral, but I did not know that 0:16:50.640 --> 0:16:53.280 they were caused by two different species, and that was 0:16:53.320 --> 0:16:57.520 what distinguishes which one you get for the most part. Yeah, yeah, 0:16:57.600 --> 0:17:02.360 but it's got to get more complicated, of course, because 0:17:03.040 --> 0:17:06.800 some people can be infected with either the species that 0:17:06.840 --> 0:17:13.320 cause cutaneous or visceral leshmaniasis and be entirely asymptomatic. Yeah, okay. 0:17:13.560 --> 0:17:17.119 For infection with cutaneous species, it's generally about ten percent 0:17:17.160 --> 0:17:21.360 of people are asymptomatic. Whereas, and this is really interesting, 0:17:21.640 --> 0:17:26.760 asymptomatic infection with species that cause the disseminated visceral infection 0:17:27.280 --> 0:17:32.280 really varies depending on region, but not necessarily depending on species. 0:17:32.840 --> 0:17:38.280 What this is so much aarin that implies. 0:17:38.600 --> 0:17:39.880 I don't know what that implies. 0:17:40.000 --> 0:17:43.480 I don't buiere. Okay, hold on, So. 0:17:43.800 --> 0:17:50.840 In the people who are asymptomatic but infected, is the parasite, like, 0:17:51.000 --> 0:17:52.800 what is it doing in their body? 0:17:52.960 --> 0:17:53.640 Good question? 0:17:53.760 --> 0:17:57.680 I wish I knew, Okay, And do they do? They 0:17:57.720 --> 0:18:01.080 go through like a course of infection assent where it's 0:18:01.119 --> 0:18:02.560 there and then it's gone. 0:18:02.840 --> 0:18:08.160 They mount an immune response. Okay, So what exactly does 0:18:08.200 --> 0:18:08.680 that mean? 0:18:09.160 --> 0:18:14.600 Because immunity, as we'll talk about more later, increases with age, 0:18:14.680 --> 0:18:18.280 which likely has to do with repeated exposure eventually producing 0:18:18.320 --> 0:18:20.840 long lasting immunity. So in a lot of cases, it's 0:18:20.880 --> 0:18:23.880 not necessarily like one exposure and then boom your immune 0:18:24.000 --> 0:18:30.840 it's like repeated exposures, especially for cutaneous leshmaniasis. So what's happening? 0:18:31.040 --> 0:18:34.119 How many times could you be infected and be asymptomatic? 0:18:34.480 --> 0:18:37.960 It's also let's throw some more complex things in there. 0:18:38.800 --> 0:18:43.160 In all cases of leshmaniasis, the incubation period is very long, Okay, 0:18:43.359 --> 0:18:47.760 We're talking weeks to potentially months. So are people asymptomatic 0:18:48.040 --> 0:18:50.800 entirely or are they asymptomatic at the time that we 0:18:50.960 --> 0:18:54.119 test them to see if there have any evidence of parasites, 0:18:54.160 --> 0:18:57.600 but then many months later develop infection maybe for some 0:18:57.720 --> 0:19:04.520 portion of people. So in all three of these cases, cutaneous, mucocutaneous, 0:19:04.520 --> 0:19:09.960 and visceral leshmaniasis. These parasites are infecting macrophages. The clinical 0:19:09.960 --> 0:19:12.919 disease that we see depends on where they localize and 0:19:13.000 --> 0:19:15.600 whether or not they disseminate to the rest of your 0:19:15.640 --> 0:19:21.040 body and cause like a systemic infection. Okay, yeah, okay, 0:19:21.480 --> 0:19:26.080 So let's talk about the symptoms that we see. Cutaneous leshmaniasis, 0:19:26.200 --> 0:19:28.480 which is the most benign of the three. So that's 0:19:28.520 --> 0:19:31.720 what we'll talk about. And benign, by the way, does 0:19:31.760 --> 0:19:35.919 not mean that it's not severe. It can be debilitating, 0:19:36.760 --> 0:19:40.119 it can be extremely scarring, and as I'm sure you 0:19:40.280 --> 0:19:42.880 will talk about aaron, it's associated with a lot of stigma, 0:19:43.080 --> 0:19:46.000 but it just kills people less than the other reforms. 0:19:46.680 --> 0:19:46.920 Yep. 0:19:47.119 --> 0:19:50.600 So it's generally caused, like I said, by a number 0:19:50.640 --> 0:19:54.520 of different species of leshmania. The most common species are 0:19:54.600 --> 0:20:01.080 Leshmania mexicana, Braziliensis major and tropica, but there are a 0:20:01.119 --> 0:20:04.160 whole bunch more like thirteen or fifteen or something more. 0:20:05.760 --> 0:20:08.800 And cutaneous is exactly what it sounds like. It affects 0:20:08.840 --> 0:20:12.719 your skin, so it causes a more localized infection. It 0:20:12.840 --> 0:20:16.000 usually starts as what looks like a bug bite from 0:20:16.040 --> 0:20:20.200 where the sandfly bits someone, but it doesn't heal and 0:20:20.400 --> 0:20:23.800 over a long period of time, and the length of 0:20:23.840 --> 0:20:26.399 time depends a lot on the species, so we're talking 0:20:26.440 --> 0:20:32.920 anywhere from two months to fifteen months. This lesion where 0:20:32.960 --> 0:20:36.640 this sort of bug bite was begins to ulcerate, and 0:20:36.840 --> 0:20:40.800 it eventually leads to it can lead to pretty significantly 0:20:40.920 --> 0:20:45.639 large ulcers like open sores essentially, which from what I've read, 0:20:45.720 --> 0:20:51.240 are painless, but they look very painful. And then this 0:20:51.440 --> 0:20:57.000 is a localized and self limited infection. So generally these ulcers, 0:20:57.040 --> 0:21:00.080 over the course of weeks and months, they begin to 0:20:59.840 --> 0:21:04.320 heal via granulation. So like our normal body's healing process 0:21:04.400 --> 0:21:07.200 eventually kicks in, but it takes a really long time. 0:21:07.440 --> 0:21:10.280 And that's probably because as much as our body is 0:21:10.359 --> 0:21:13.920 trying to fight off this parasite, it's inside of our 0:21:13.960 --> 0:21:16.320 white blood cells, so it's really difficult for us to 0:21:16.480 --> 0:21:24.240 really fully eradicate this quickly. Yeah, And these ulcers lead 0:21:24.280 --> 0:21:28.880 to significant scarring. So the scar is generally a depressed 0:21:29.240 --> 0:21:32.240 and large like the size or a little bit smaller 0:21:32.240 --> 0:21:37.080 than how large the ulcer was scar and that can 0:21:37.080 --> 0:21:39.760 be very debilitating. Depending on where it is, it can 0:21:39.840 --> 0:21:43.560 be disfiguring and be associated with significant stigma, especially if 0:21:43.600 --> 0:21:46.359 it's on the face, which something like fifty percent of 0:21:46.480 --> 0:21:48.679 sandfly bites tend to be on the face, just because 0:21:48.720 --> 0:21:52.760 it's easily exposed. We don't generally have clothing on our face. 0:21:54.280 --> 0:21:57.720 So yeah, so that's cutaneous lashmaniasis. You can also imagine 0:21:57.720 --> 0:21:59.840 that since this is an open wound, you can get 0:21:59.840 --> 0:22:04.560 a secondary bacterial infection on top of it. Yep, which 0:22:04.560 --> 0:22:05.880 can lead to more complications. 0:22:06.240 --> 0:22:08.800 I'm starting to feel like Benign is not even coming 0:22:08.960 --> 0:22:11.480 close to accurately describing. 0:22:11.000 --> 0:22:13.959 Those It's not. It's just of these three, it is 0:22:14.000 --> 0:22:15.240 the least deadly. 0:22:15.840 --> 0:22:16.840 Okay, how about that? 0:22:16.920 --> 0:22:17.399 How about that? 0:22:17.520 --> 0:22:18.040 Okay? 0:22:19.119 --> 0:22:23.480 So next is mucosal or muco cutaneous leshmaniasis. This is 0:22:23.520 --> 0:22:27.320 a very destructive form of leshmaniasis that most of the 0:22:27.320 --> 0:22:32.639 time occurs after cutaneous leshmaniasis. It's most commonly associated with 0:22:32.840 --> 0:22:37.480 Leshmania braziliensis. Like you asked which species erin, but there 0:22:37.520 --> 0:22:41.199 are other species, Especially in people who are immunocompromised and 0:22:41.240 --> 0:22:44.919 don't have a good cell mediated immune response, then you 0:22:44.960 --> 0:22:50.040 can get mucosal leshmaniasis from other species as well. So 0:22:50.160 --> 0:22:56.960 this form of leshmaniasis presents often with nasal stuffiness, nose bleeds, 0:22:57.680 --> 0:23:00.520 sloughing off of tissue from inside your nose or mouth. 0:23:01.280 --> 0:23:06.240 It can result in erosion of any of your mucosal surfaces, 0:23:06.240 --> 0:23:09.119 so inside your mouth, your cheeks, your nose. Kind of 0:23:09.160 --> 0:23:12.160 the worst thing that can happen is it can essentially 0:23:12.200 --> 0:23:15.360 eat away through your nasal septum and completely destroy your nose. 0:23:15.400 --> 0:23:19.359 So it can be very disfiguring. And if it's associated 0:23:19.400 --> 0:23:21.880 with your trichia or epiglottis, for example, then it can 0:23:21.960 --> 0:23:26.080 cause respiratory compromise. So this form can be deadly, especially 0:23:26.119 --> 0:23:29.800 if it affects the mucosal surfaces that we use to breathe, 0:23:30.160 --> 0:23:34.000 for example. So that's depressing. Now let's move on to 0:23:34.000 --> 0:23:38.919 the most depressing and that is visceral leshmaniasis, which is 0:23:38.960 --> 0:23:42.560 also known as kala azar, which is Hindi for black fever. 0:23:42.800 --> 0:23:46.040 And that's what you heard in our first hand account. 0:23:46.840 --> 0:23:50.600 Like I mentioned earlier, it's most often caused by leshmania donovanni, 0:23:50.920 --> 0:23:55.960 but also leshmania in phantom and or shagasai, which are 0:23:56.000 --> 0:24:02.000 the same thing. And this is a truly horrible, horrible disease. 0:24:02.040 --> 0:24:03.919 I think that our first hand account did a lot 0:24:03.960 --> 0:24:06.760 more justice than I'm going to to describe just how 0:24:07.200 --> 0:24:11.640 awful it is. Clinically, what we see is a very slow, 0:24:12.160 --> 0:24:15.840 insidious over weeks to months where you have this fever 0:24:16.160 --> 0:24:20.879 and general malaise, just not feeling well. You have significant 0:24:20.880 --> 0:24:23.600 weight loss that leads to what we call cachexia, which 0:24:23.640 --> 0:24:28.080 is just like emaciation. Okay, But then on top of that, 0:24:28.200 --> 0:24:31.400 because this parasite is in our white blood cells that 0:24:31.720 --> 0:24:37.040 congregate in our spleen and liver, you get massive splenomegaly, 0:24:37.200 --> 0:24:41.679 so enlargement of your spleen, or hippatosplenomegaly, so enlargement of 0:24:41.720 --> 0:24:45.359 your spleen and liver. And because the other place that 0:24:45.400 --> 0:24:49.199 our white blood cells congregate is our bone marrow, this 0:24:49.320 --> 0:24:52.359 can lead to massive infection in your bone marrow that 0:24:52.440 --> 0:24:56.640 causes pan cytopenia, which means all of your bloodlines are depressed, 0:24:56.760 --> 0:24:59.719 so you're anemic. But also all your white blood cell 0:24:59.760 --> 0:25:03.680 count are very depressed, which means, as you can imagine, 0:25:03.760 --> 0:25:07.400 people are very susceptible to secondary infection because they have 0:25:07.520 --> 0:25:14.719 no immune defense. Essentially, visceral leishmaniasis is almost uniformly fatal 0:25:14.800 --> 0:25:18.159 if left untreated. Mortality is ninety five to one hundred percent. 0:25:19.720 --> 0:25:25.000 And is it caused typically by the parasitic infection directly 0:25:25.359 --> 0:25:27.440 or through secondary infections. 0:25:27.320 --> 0:25:29.399 Both, and I don't have a number on the exact 0:25:29.440 --> 0:25:33.359 percentage of which is which, but absolutely both are cause 0:25:33.440 --> 0:25:41.320 of death. Yeah, and leshmania Donovani. Like I mentioned earlier, 0:25:41.640 --> 0:25:44.600 there's kind of two different cycles of this disease. There's 0:25:44.640 --> 0:25:48.479 the anthroponotic, where humans are the main reservoir, and then 0:25:48.520 --> 0:25:52.560 there's the zoonotic where it's animals, whether domestic or wild, 0:25:53.240 --> 0:25:57.320 that are the major reservoirs for infection, and the main 0:25:57.760 --> 0:26:02.199 species that causes visceral leshmaniasis is also considered anthroponautics, So 0:26:02.320 --> 0:26:06.480 humans are the major reservoir rather than animals, right, Okay. 0:26:07.080 --> 0:26:10.960 Do you have a timeline specifically for muco cutaneous how 0:26:11.000 --> 0:26:15.040 long it takes for cutaneous to turn into the mucosal 0:26:15.680 --> 0:26:17.360 variety if it's going to go that way? 0:26:17.680 --> 0:26:19.400 Very good question. I think a lot of what I've 0:26:19.440 --> 0:26:21.520