WEBVTT - Ep 210 Histoplasmosis: Bats, birds, and budding yeast 0:00:00.440 --> 0:00:02.200 My name is Macy, and I'm a twenty five year 0:00:02.200 --> 0:00:05.560 old from southern Indiana. During my senior year of college, 0:00:05.559 --> 0:00:07.680 I started feeling pretty tired and chilly just a couple 0:00:07.720 --> 0:00:10.399 of days after I returned to campus after Thanksgiving break. 0:00:11.400 --> 0:00:13.440 I had a lot of final projects in studying to do, 0:00:13.560 --> 0:00:15.720 but I was feeling really exhausted, so I decided to 0:00:15.720 --> 0:00:18.120 give myself a break and lie down for a short nap. 0:00:18.560 --> 0:00:20.400 Not long after that, I realized that I might be 0:00:20.480 --> 0:00:22.960 running a fever. I took my temperature to find that 0:00:23.000 --> 0:00:25.800 it was just over one hundred degrees. It was twenty 0:00:25.800 --> 0:00:28.040 twenty two, so I took a quick at home COVID test, 0:00:28.160 --> 0:00:31.000 but it was negative. I figured I would keep an 0:00:31.000 --> 0:00:32.879 eye on it and see how things progressed over the 0:00:32.880 --> 0:00:35.760 next few days. But over the next week, my temperature 0:00:35.760 --> 0:00:39.120 steadily increased to just over one hundred one degrees. I 0:00:39.200 --> 0:00:42.560 wasn't experiencing a running nose, cough, body aches, or anything 0:00:42.560 --> 0:00:44.720 else you would expect with a cold. I had been 0:00:44.720 --> 0:00:46.760 feeling more tired and had started taking a nap each 0:00:46.840 --> 0:00:49.120 day after class, but I was still able to function 0:00:49.159 --> 0:00:52.239 almost like any other college did. By day twelve, my 0:00:52.280 --> 0:00:54.800 fear was reaching over one hundred three at times, and 0:00:54.840 --> 0:00:57.640 I was much more fatigued and sleeping even more. But 0:00:57.720 --> 0:00:59.600 now I was starting to notice some shortness of breath 0:00:59.640 --> 0:01:01.800 just walk from my apartment door to the elevators in 0:01:01.840 --> 0:01:04.440 my building. It was also getting a little uncomfortable to 0:01:04.440 --> 0:01:07.440 breathe deeply. At that point, I decided I should go 0:01:07.480 --> 0:01:09.800 to the doctor, but with as busy as urgent cares 0:01:09.800 --> 0:01:12.280 are in a big college town during flu season, I 0:01:12.360 --> 0:01:14.479 wasn't able to get in anywhere for a few days. 0:01:14.720 --> 0:01:16.960 I went into my urgent care appointment on day sixteen 0:01:17.000 --> 0:01:19.640 of this fever, expecting to be tested for a few infections, 0:01:20.000 --> 0:01:23.240 get an answer, and be sent home with a antibiotics instead. 0:01:23.280 --> 0:01:25.199 When the nurse practitioner came in to tell me about 0:01:25.200 --> 0:01:27.800 my results, she said that everything had come back negative. 0:01:29.040 --> 0:01:31.560 I do have a history of immunisuppression, though, so she 0:01:31.640 --> 0:01:33.640 chose to send me to the emergency department for further 0:01:33.720 --> 0:01:35.800 work up, just to be sure that she wasn't missing 0:01:35.840 --> 0:01:38.520 anything big. In the ED, the doctors told me that 0:01:38.560 --> 0:01:40.600 my chest X ray and CT showed some sort of 0:01:40.640 --> 0:01:43.600 pneumonia covering both lungs top to bottom. I was admitted 0:01:43.640 --> 0:01:45.319 and over the next few days, I was treated with 0:01:45.360 --> 0:01:47.640 empiric antibiotics while they tried to figure out what was 0:01:47.680 --> 0:01:50.480 causing this. In the meantime, I continued to run a 0:01:50.520 --> 0:01:53.120 fever and got more and more fatigued. Around day four 0:01:53.120 --> 0:01:55.440 in the hospital, they started treating me with oral anti 0:01:55.440 --> 0:01:57.840 fungals as they began to suspect that it was more 0:01:57.920 --> 0:02:01.400 likely to be a fungal infection. I was told definitively 0:02:01.480 --> 0:02:05.240 that I had pulmonary histoplasmosis. My doctors were somewhat stumped 0:02:05.280 --> 0:02:08.079 as we could not pinpoint any likely exposure event. They 0:02:08.160 --> 0:02:10.480 chalked it up to me being amina compromised and living 0:02:10.520 --> 0:02:13.520 in the Ohio River Valley. That evening, I was given 0:02:13.520 --> 0:02:15.639 ampho terras and B. They were planning to put in 0:02:15.680 --> 0:02:18.480 a pickline for continued infusions on discharge if I tolerated 0:02:18.520 --> 0:02:22.280 it well. But during that infusion, I experienced severe nausea, headache, 0:02:22.320 --> 0:02:24.200 and I spiked a fever for the first time that day. 0:02:24.600 --> 0:02:26.480 On my eighth morning in the hospital, they chose to 0:02:26.480 --> 0:02:28.959 go ahead and give me a second amphoterrasm B infusion 0:02:29.000 --> 0:02:32.000 before switching me to oral intriconaisole and sending me home. 0:02:32.320 --> 0:02:34.680 I was kept on interconisole for a full year. After that, 0:02:35.400 --> 0:02:37.840 I followed up with pulmonology for about three months and 0:02:37.880 --> 0:02:39.960 had to follow up with infectious disease for a couple 0:02:39.960 --> 0:02:42.240 of years. It has now been over three years since 0:02:42.280 --> 0:02:45.680 I was diagnosed with histoplasmosis and I'm fully recovered. I 0:02:45.800 --> 0:02:48.280 just have a few small pulmonary calcifications on my chest 0:02:48.360 --> 0:02:49.280 X ray to show for it. 0:03:35.200 --> 0:03:37.720 Macie, thank you so much for sharing your story with us. 0:03:37.840 --> 0:03:39.520 We really appreciate it. 0:03:39.920 --> 0:03:42.520 Yeah, it really does mean a lot. Thank you, Yeah, 0:03:42.560 --> 0:03:42.880 thank you. 0:03:44.080 --> 0:03:47.440 Hi. I'm Aaron Welsh and I'm Erin Alman Updank and 0:03:47.520 --> 0:03:49.320 this is this podcast will Kill You. 0:03:49.640 --> 0:03:51.720 Welcome to histo plasmosis. 0:03:52.200 --> 0:03:56.600 Histo plasmosis. It's taken us a while to do this, 0:03:56.760 --> 0:04:00.839 despite getting requests for it, and also this being one 0:04:00.880 --> 0:04:03.440 of the more abundant. 0:04:03.040 --> 0:04:07.320 Prevalent, much more common than other fungal pathogens that we've 0:04:07.320 --> 0:04:11.560 covered on the podcast, which I didn't really realize. Honestly 0:04:11.840 --> 0:04:12.600 I didn't either. 0:04:12.800 --> 0:04:15.640 I mean, I think when I saw the first time 0:04:15.680 --> 0:04:18.960 I read about how people in the Ohio River Valley 0:04:19.120 --> 0:04:23.680 like ninety percent have been exposed, I'm like, oh, I've 0:04:23.800 --> 0:04:27.560 lived there. That's where I grew up, I have been 0:04:27.600 --> 0:04:29.880 exposed to histo. It never occurred to me. 0:04:30.160 --> 0:04:32.720 Yeah, no, it's yeah, same, same. 0:04:32.800 --> 0:04:35.120 Yeah. I'm excited to learn more about the biology because 0:04:35.120 --> 0:04:38.479 I'm like, when does somebody find out anyway, there's so 0:04:38.560 --> 0:04:41.520 much to cover there. I'm so excited for this episode. 0:04:41.640 --> 0:04:45.480 So but so we got to get to through some things. First. 0:04:45.520 --> 0:04:48.320 We do, as always quarantin any time. 0:04:48.560 --> 0:04:50.039 Yeah, what do we drink in this week? 0:04:50.120 --> 0:04:53.719 We're drinking the Fungus among Us, which we're pretty sure 0:04:53.800 --> 0:04:56.520 was the title of our blast on my closest episode. 0:04:56.600 --> 0:04:58.640 But it's a great it's a great title. 0:04:58.920 --> 0:05:01.640 This is truly the fungus that is among. 0:05:01.440 --> 0:05:03.560 Us, way more so than blasto. 0:05:03.320 --> 0:05:05.360 At least for you know, the eastern half of the 0:05:05.480 --> 0:05:07.880 United States, but also other places. And it's also more 0:05:07.880 --> 0:05:09.840 broadly spread exactly, I know, I know. 0:05:09.920 --> 0:05:11.320 It's everywhere. It's everywhere. 0:05:13.480 --> 0:05:18.240 Fungus among us it is, it's going. We modeled it 0:05:18.320 --> 0:05:22.440 to look like maybe I shouldn't say that, I'll say 0:05:22.440 --> 0:05:28.559 the ingredients first. It has coconut cream, pineapple juice, lime juice. 0:05:28.600 --> 0:05:31.680 It's really good, and we did we used coconut cream 0:05:31.720 --> 0:05:34.920 because of the way that a lot of exposures to 0:05:35.640 --> 0:05:40.120 histol plasmosis occur, which is through that guano and bird excrement, 0:05:40.160 --> 0:05:42.080 So we wanted it to look a little bit poopy, 0:05:42.320 --> 0:05:43.520 like bird poopy. 0:05:43.640 --> 0:05:46.200 A little bit bird and batpoopy. 0:05:45.800 --> 0:05:49.560 In the spirit of Stow. Yeah. 0:05:49.720 --> 0:05:53.600 You can find the full recipe for that delicious quarantini 0:05:54.120 --> 0:05:56.159 on our website. This podcast will kill You dot com 0:05:56.200 --> 0:05:58.360 and all of our social medias. Are you following us 0:05:58.400 --> 0:06:00.120 on the socials because we're there. 0:06:01.000 --> 0:06:07.200 We are there. Make sure you follow, review, subscribe, rate, 0:06:07.760 --> 0:06:12.040 et cetera, and our website. Things that you can discover 0:06:12.360 --> 0:06:15.960 on there include transcripts, links to our bookshop, dot org 0:06:15.960 --> 0:06:20.960 affiliate page, our Goodreads list, music by Bloodmobile, a first 0:06:20.960 --> 0:06:25.719 hand account form, a contact us form, and links to 0:06:25.800 --> 0:06:26.680 merge Patreon. 0:06:27.000 --> 0:06:29.240 Wow so much, so much. 0:06:29.839 --> 0:06:33.360 Yeah, check it out sources because I have a lot 0:06:33.400 --> 0:06:37.160 of more sources than I anticipated for this and some 0:06:37.279 --> 0:06:40.120 really great ones that I am encouraging people to read. 0:06:40.520 --> 0:06:45.120 I am so excited. Also, apologies because my cat is 0:06:45.160 --> 0:06:47.080 being very loud in the other room right now. 0:06:47.360 --> 0:06:49.560 Is he hungry? Is it the kippie? 0:06:50.400 --> 0:06:53.279 He's always hungry and he's always been fed, so I 0:06:53.320 --> 0:06:55.440 don't know it anyways. 0:06:55.400 --> 0:06:57.040 He's just making himself known. 0:06:57.240 --> 0:06:57.400 Yep. 0:06:57.800 --> 0:07:02.040 Yeah, well, Aaron, should we get into this. 0:07:02.360 --> 0:07:05.520 Let's do it. Let's take a quick break and get started. 0:07:22.120 --> 0:07:26.480 Hytoplasmosis is the name for a disease caused by a 0:07:26.520 --> 0:07:33.080 fungus called Histoplasma capsulatum H. And it turns out that 0:07:33.080 --> 0:07:35.360 there's actually quite a lot of genetic diversity in this 0:07:35.440 --> 0:07:39.360 particular fungal species. There's probably I don't know, they might 0:07:39.400 --> 0:07:41.920 even be split into multiple species at some point. 0:07:42.600 --> 0:07:45.680 I don't know how fungal species differentiation works. 0:07:45.680 --> 0:07:48.640 Me neither, So I'm not going to get deep into 0:07:48.680 --> 0:07:51.680 it today. We're just going to kind of focus on 0:07:52.360 --> 0:07:58.239 the Histoplasma capsulatum group. Okay, right, And we have covered 0:07:58.320 --> 0:08:01.960 a relatively similar fungus at least in the kind of 0:08:02.120 --> 0:08:05.320 path of physiology of how it works in our bodies earlier, 0:08:05.440 --> 0:08:11.480 and that is blastomycosis caused by blastomics. But don't worry 0:08:11.520 --> 0:08:13.200 if you didn't listen to that episode or if you 0:08:13.200 --> 0:08:15.400 don't remember anything from it, because neither did I. 0:08:15.680 --> 0:08:19.360 So although it's a good episode, it is, remember it's 0:08:19.360 --> 0:08:23.480 a really good because there's deep time and dinosaurs and. 0:08:23.840 --> 0:08:28.720 Yeah, it's a really good episode. But unlike blastomics. The 0:08:28.720 --> 0:08:33.040 fungus that is the focus of today's episode, Histoplasma is 0:08:33.440 --> 0:08:38.880 extremely abundant in the environment, it turns out extraordinarily. So 0:08:39.360 --> 0:08:42.880 you mentioned aaron that classically in the US we associate 0:08:43.040 --> 0:08:47.680 histoplasmosis with the Mississippi and Ohio River valleys. That's like 0:08:47.760 --> 0:08:50.280 what we learn in med school. And I did look 0:08:50.320 --> 0:08:54.000 this up this time because I like kind of knew 0:08:54.120 --> 0:08:57.320 exactly where those were geographically, but let's be real, not 0:08:57.400 --> 0:09:01.360 everybody does. So the Mississippi River runs north south from 0:09:01.360 --> 0:09:04.120 like Minnesota all the way down and exits in the 0:09:04.160 --> 0:09:07.840 Gulf of Mexico. The Ohio River is one of its 0:09:07.920 --> 0:09:11.280 many tributaries that runs sort of east west ish from 0:09:11.280 --> 0:09:14.520 Pennsylvania to where it lets out in the Mississippi River. 0:09:15.600 --> 0:09:20.719 And so classically this is where most cases of histoplasmosis 0:09:20.800 --> 0:09:23.520 were seen. And so that is the kind of association 0:09:23.640 --> 0:09:25.480 in a lot of people's minds. And it's true that 0:09:25.520 --> 0:09:28.160 today the vast majority of cases in the US are 0:09:28.240 --> 0:09:33.480 centered in these regions. But it is not only these 0:09:33.520 --> 0:09:37.920 regions where this fungus can be found. This fungus exists 0:09:38.000 --> 0:09:42.640 in the soil as a mold, and it can be 0:09:42.720 --> 0:09:49.800 found on every continent except Antarctica. Yep. It loves humid, 0:09:50.320 --> 0:09:55.160 nitrogen and phosphorus rich soils, which means that it tends 0:09:55.160 --> 0:09:58.760 to grow very well where there's a lot of poop poop, 0:09:58.760 --> 0:10:00.960 bird poop and batpoop specifically. 0:10:01.240 --> 0:10:01.560 Yeah. 0:10:01.600 --> 0:10:04.560 Oh, I was trying to get deep into, like what 0:10:04.559 --> 0:10:09.800 what makes a bird poop different different amounts of nitrogen 0:10:09.840 --> 0:10:12.760 and phosphorus. I mean, I don't know the answer. I 0:10:12.840 --> 0:10:15.240 love that, but I was there was a period of time, 0:10:15.280 --> 0:10:16.920 there was like a few hours where I was like, 0:10:17.280 --> 0:10:19.080 bird poop composition. 0:10:18.679 --> 0:10:23.840 Composition, Yeah, different birds different I'm sure the composition's quite different, right. 0:10:24.040 --> 0:10:25.920 Right, And which one does histoplasma? 0:10:26.040 --> 0:10:29.080 Like, you know, I did know some of that, Yeah, exactly. 0:10:29.120 --> 0:10:30.720 I was gonna say, there are some papers with that. 0:10:31.040 --> 0:10:34.520 And it also seems like bats are a particularly important 0:10:34.559 --> 0:10:40.080 component of the hystoplasmosis cycle, especially because the fungus itself 0:10:40.120 --> 0:10:42.640 can also be found in the bats, and so then 0:10:42.720 --> 0:10:45.800 bat poop not only is good fodder in the soil 0:10:46.040 --> 0:10:48.840 for this mold to grow, but can actually contain the 0:10:48.880 --> 0:10:51.960 histoplasma so they can spread it as they poop around 0:10:51.960 --> 0:10:52.319 the world. 0:10:52.760 --> 0:10:52.920 Right. 0:10:53.160 --> 0:10:58.040 Yeah's although I did also hear so birds can't be infected, 0:10:58.120 --> 0:11:01.000 it seems. Yeah, but they're feather might be able to 0:11:01.040 --> 0:11:02.920 carry it because they're all poopy. 0:11:02.920 --> 0:11:07.000 Yes, because they're covered in spores. Yeah, and things so lovely. 0:11:08.000 --> 0:11:11.120 But Okay, if this fungus was just a mold living 0:11:11.120 --> 0:11:12.800 in the soil, then we wouldn't be talking about it 0:11:12.840 --> 0:11:14.679 on this podcast Will Kill You? Okay, well we might 0:11:14.760 --> 0:11:18.040 at some point maybe, but realistically, but it's probably. 0:11:17.840 --> 0:11:20.280 What it athogen So what makes that pathogenic. 0:11:21.040 --> 0:11:24.360 What makes it pathogenic is that this fungus, like blastomics 0:11:24.400 --> 0:11:28.480 that we've covered before, is what's called thermally dimorphic, which 0:11:28.559 --> 0:11:32.320 means it can exist in two different forms depending on 0:11:32.440 --> 0:11:36.840 the temperature, largely of the environment in which it exists in. 0:11:37.840 --> 0:11:40.520 So in the environment in the soil, which is going 0:11:40.600 --> 0:11:43.480 to be a cooler temperature like let's say ideally twenty 0:11:43.520 --> 0:11:46.960 five to thirty celsius, which is like seventies to eighties, 0:11:47.160 --> 0:11:50.360 that's their sweet spot. That's when we see this fungus 0:11:50.360 --> 0:11:53.600 existing as a fungus as a mold in this filamentous, 0:11:53.920 --> 0:11:58.600 branchy form, but it can also exist as a yeast, 0:11:58.679 --> 0:12:02.520 which is a single cell fungus when it is exposed 0:12:02.559 --> 0:12:07.079 to higher temperatures around thirty seven degrees celsius aka human 0:12:07.080 --> 0:12:09.319 body temperature ninety eight point six fahrenheit. 0:12:09.720 --> 0:12:13.280 Okay, so tell me how does that work? Like if 0:12:13.320 --> 0:12:16.360 you are exposed to the mold, can you can will 0:12:16.440 --> 0:12:18.800 it turn into a yea yeah, tell me about that. 0:12:18.840 --> 0:12:21.600 I would love to tell you about it. The answer 0:12:21.679 --> 0:12:25.400 is yes. So this is an example of an environmentally 0:12:25.440 --> 0:12:29.240 transmitted pathogen. So this is not something that's transmitted person 0:12:29.240 --> 0:12:32.040 to person. If I have histoplasmasis, I cannot give it 0:12:32.040 --> 0:12:36.520 to you, Aaron, especially not over the internet. And there 0:12:36.520 --> 0:12:41.319 aren't any like vectors directly involved. So yes, a human 0:12:41.400 --> 0:12:45.839 gets exposed via exposure to the mold form of this 0:12:45.920 --> 0:12:49.800 fungus that thrives in the soil. Okay, So little bits 0:12:49.880 --> 0:12:54.360 of these hyphie, this filamentous branching mold can break off 0:12:54.720 --> 0:12:58.840 in the soil. And the way that this form of 0:12:58.880 --> 0:13:03.520 the mold reproduced is it forms these spores called canidia, 0:13:04.000 --> 0:13:06.560 and those are what get dispersed into the environment so 0:13:06.600 --> 0:13:10.520 that this mold can continue to grow and move around 0:13:10.520 --> 0:13:13.959 the environment. So those spores, as well as little bits 0:13:14.000 --> 0:13:16.600 of the filaments themselves get mixed up in the soil 0:13:17.000 --> 0:13:19.920 and they can end up blown by the wind directly 0:13:19.960 --> 0:13:23.560 into our noses or many mammals noses where we're going 0:13:23.600 --> 0:13:26.640 to breathe them in, and once they are inside our 0:13:26.800 --> 0:13:32.559 warm human body, they're actually gobbled up almost immediately by 0:13:32.640 --> 0:13:37.320 our immune cells. They're gobbled up by cells like macrophages, 0:13:37.640 --> 0:13:39.880 which are kind of like one of the bouncers of 0:13:39.920 --> 0:13:42.480 our immune system that gobble things up that don't belong. 0:13:43.120 --> 0:13:51.319 And histoplasma is like well adapted to this process. Once 0:13:51.360 --> 0:13:54.760 it is engulfed by a macrophage in this warm environment, 0:13:55.480 --> 0:13:56.520 it switches. 0:13:57.760 --> 0:14:01.520 Because, oh my gosh. 0:14:00.480 --> 0:14:04.480 They completely transform. They rearrange the entirety of their cell 0:14:04.520 --> 0:14:10.120 walls and how they exist and how they reproduce and 0:14:10.240 --> 0:14:14.319 turn into this yeast form. Now, yeasts, which are single 0:14:14.440 --> 0:14:18.960 celled fungi, they don't reproduce by making spores. They reproduce 0:14:19.000 --> 0:14:21.280 by a process of budding, which basically just is like 0:14:21.360 --> 0:14:23.640 if you have one yeast cell, they kind of bloop, 0:14:23.720 --> 0:14:26.360 pinch off, and now there's two of them, and so 0:14:26.440 --> 0:14:33.000 on and so forth. Histoplasma does this inside of our macrophages, 0:14:33.360 --> 0:14:35.800 so it's like a virus our body. Yes, it's an 0:14:35.800 --> 0:14:37.160 intracellular pathogen. 0:14:37.720 --> 0:14:39.960 Okay, I did not know it was an intracellular pathogen. 0:14:40.080 --> 0:14:44.360 That is so okay, So then it re it buds 0:14:44.360 --> 0:14:47.360 and buds and buds inside this macrophage and then to 0:14:47.400 --> 0:14:50.040 the point where the macrophage bursts, Like does it eventually 0:14:50.120 --> 0:14:53.720 the macrophage to burst or does it go anywhere? Where? 0:14:53.720 --> 0:14:54.880 Does it go in your body? 0:14:55.040 --> 0:14:59.040 Yeah? Eventually it will kill this macrophag right, eventually it will. 0:14:59.440 --> 0:15:02.040 It will reproduce so much and so many times that 0:15:02.040 --> 0:15:05.480 these macrophages burst open and then now these yeasts are 0:15:05.520 --> 0:15:08.680 free to be gobbled up by other macrophages and continue 0:15:08.680 --> 0:15:09.480 this process. 0:15:09.560 --> 0:15:13.040 And so it's all macrophages is the intracellular part of it. 0:15:13.160 --> 0:15:15.720 There's other cells too, but macrophasis are one of like 0:15:15.760 --> 0:15:16.600 the main ones. 0:15:17.400 --> 0:15:17.720 Okay. 0:15:17.720 --> 0:15:21.240 Now, yeah, where this is happening is primarily in our 0:15:21.320 --> 0:15:24.440 lungs because we are exposed, yeah, by breathing it in, 0:15:24.520 --> 0:15:27.800 and so these tiny little spores that we've been exposed 0:15:27.840 --> 0:15:30.160 to get down into our lungs and that's where they 0:15:30.160 --> 0:15:34.520 are transforming into this yeast form. As our macrophagis are 0:15:34.520 --> 0:15:40.360 gobbling them up. They're trying to mount a typical immune response, 0:15:41.160 --> 0:15:44.040 and that means that they are flagging and telling other 0:15:44.120 --> 0:15:47.040 immune cells like our T cells to come in and 0:15:47.120 --> 0:15:50.760 get rid of this passagen, and for the vast majority 0:15:50.840 --> 0:15:53.200 of us, that is the end of the story. 0:15:53.680 --> 0:15:58.920 Okay, okay, so exposure, we have not gotten to infection yet. 0:15:58.960 --> 0:16:01.840 This is still like what exposure would look like that 0:16:01.880 --> 0:16:05.400 could potentially lead to infection. You're breathing in these spores, 0:16:05.440 --> 0:16:08.320 they turn into yeast, they start to replicate, and then 0:16:08.320 --> 0:16:10.520 at some point throughout this process, as more and more 0:16:10.520 --> 0:16:13.520 macrophages are infected, your two cells are like, we're shutting. 0:16:13.200 --> 0:16:19.120 This down absolutely unless unless they can't exactly. So for 0:16:19.200 --> 0:16:23.760 the vast majority of us, we will have exposure, some 0:16:23.840 --> 0:16:26.360 kind of immune response and it's you know, it's our 0:16:26.400 --> 0:16:30.800 whole entire immune system that's involved, and then goodbye fungus. 0:16:31.000 --> 0:16:31.400 The end. 0:16:31.720 --> 0:16:37.120 We do a really good job of clearing this fungus classically. However, 0:16:37.360 --> 0:16:42.040 also classically, fungi are really good at flying under the 0:16:42.160 --> 0:16:47.080 radar and can find ways to avoid being completely eradicated. 0:16:47.600 --> 0:16:51.760 So for some people, whether because they're immunal compromised or 0:16:52.000 --> 0:16:54.760 just because they were exposed to a really high dose 0:16:54.960 --> 0:16:58.920 right like they inhaled a whole face full of these spores, 0:16:59.600 --> 0:17:02.200 they could end up with a symptomatic infection. So let's 0:17:02.200 --> 0:17:05.360 talk about what that looks like, shall we. Yeah, if 0:17:05.400 --> 0:17:09.040 someone is going to have symptoms from exposure to histoplasma, 0:17:09.080 --> 0:17:12.080 the most common thing they're going to have is a pneumonia, 0:17:12.119 --> 0:17:14.439 which is unsurprising because again, this is all happening in 0:17:14.480 --> 0:17:18.400 our lungs. Usually this is only happening if you're exposed 0:17:18.400 --> 0:17:21.560 to a really high concentration of spores, and it's going 0:17:21.600 --> 0:17:24.560 to take some time because these youths aren't like really 0:17:24.600 --> 0:17:28.159 fast at reproducing, you know, take some time. Okay, So 0:17:28.320 --> 0:17:30.880 after an incubation period of usually a couple of weeks 0:17:31.000 --> 0:17:33.600 or so, but anywhere from like three to twenty one days, 0:17:33.600 --> 0:17:36.879 some of the papers I read said, you will start 0:17:36.920 --> 0:17:43.120 to have kind of non specific flu like symptoms, fever, headache, cough, 0:17:43.480 --> 0:17:48.320 maybe some chills, muscle aches. It'll look like a pneumonia. 0:17:48.760 --> 0:17:49.160 Okay. 0:17:49.600 --> 0:17:53.919 Many people might go to the doctor be treated for 0:17:54.480 --> 0:17:59.159 bacterial pneumonia, and then they might get better all on 0:17:59.200 --> 0:18:01.720 their own, and the animaliotics absolutely were not the thing 0:18:01.800 --> 0:18:04.399 that made them get better. But most people who have 0:18:04.720 --> 0:18:09.040 even an acute pneumonia from histoplasmosis are going to recover 0:18:09.440 --> 0:18:12.200 all on their own and get over this infection. 0:18:13.480 --> 0:18:15.760 Okay, for others. 0:18:15.359 --> 0:18:19.240 That maybe had a really even higher exposure or just 0:18:19.320 --> 0:18:22.280 are susceptible for one reason or another, they might have 0:18:22.320 --> 0:18:26.399 a more severe course. They might have increased inflammation, they 0:18:26.480 --> 0:18:29.719 might end up having like difficulty breathing, shortness of breath, 0:18:29.840 --> 0:18:33.920 or if you actually checked their oxygen concentration it might 0:18:33.960 --> 0:18:37.680 actually be low. And so in those cases people might 0:18:37.760 --> 0:18:43.040 actually get the diagnosis of histoplasmosis and then they might 0:18:43.080 --> 0:18:48.240 actually need treatment with antifungals. But that's not necessarily like 0:18:48.240 --> 0:18:53.000 a majority of people who are even having symptomatic acute 0:18:53.040 --> 0:18:59.119 pulmonary hystoplasmosis. But that is not the end of the 0:18:59.160 --> 0:19:02.080 story for some people. Okay, real quick though, Yeah, give 0:19:02.080 --> 0:19:02.399 it to me. 0:19:02.680 --> 0:19:06.080 How long on average does this last? If it is 0:19:06.119 --> 0:19:09.000 a self self what do you call it. 0:19:08.920 --> 0:19:10.080 A self limiting infection? 0:19:10.080 --> 0:19:10.880 Limiting infection? 0:19:11.040 --> 0:19:13.600 It's a good question. I don't have like a perfect timeline. 0:19:14.160 --> 0:19:17.359 I would expect it to be like within the within 0:19:17.440 --> 0:19:20.320 what would be a typical course of pneumonia for a 0:19:20.320 --> 0:19:22.879 lot of people, So maybe a couple of weeks max 0:19:23.040 --> 0:19:25.399 or so, But it all is just going to depend 0:19:25.440 --> 0:19:28.199 on what your immune response to it is, whether or 0:19:28.240 --> 0:19:32.160 not you get severely sick and things like that. It's 0:19:32.280 --> 0:19:33.560 very person dependent. 0:19:33.680 --> 0:19:38.199 And so most of these people are diagnosed based on 0:19:38.280 --> 0:19:43.359 symptoms and it is in they're diagnosed as having bacterial pneumonia. 0:19:43.560 --> 0:19:48.160 Yeah, it's very like we probably drastically underestimate the actual 0:19:48.200 --> 0:19:53.440 incidence of acute pulmonaryhystoplasmosis because so many cases are either 0:19:53.560 --> 0:19:57.080 never seen by a healthcare professional because they think it's 0:19:57.160 --> 0:20:00.880 just some other cold or flu, right, or yes, they're 0:20:00.880 --> 0:20:05.680 misdiagnosed as community acquired pneumonia treated with antibiotics and they 0:20:05.720 --> 0:20:07.639 get better, but not because of the antibiotics, and it 0:20:07.680 --> 0:20:09.080 was actually hytoplasmosis. 0:20:09.359 --> 0:20:14.600 Okay. I have two questions, Okay. The first is at 0:20:14.640 --> 0:20:18.960 what point does exposure become infections? Like, in order for 0:20:19.119 --> 0:20:22.439 an infection to count as infection, do there have to 0:20:22.480 --> 0:20:26.040 be symptoms? Yes, I don't know. 0:20:26.119 --> 0:20:29.080 It's a great question. Okay, I'm nodding because it's such 0:20:29.080 --> 0:20:30.959 a good question, but I don't have an answer for you. 0:20:31.200 --> 0:20:34.280 Okay. And then the other question is at what point 0:20:34.400 --> 0:20:38.320 does you know you said these diagnoses are often bacterial. 0:20:38.359 --> 0:20:42.600 At what point does does histoplasma become the horse and 0:20:42.680 --> 0:20:46.160 not the zebra? I guess yeah, Like, at what point 0:20:46.200 --> 0:20:48.920 do people start to say this is it's not resolving 0:20:48.920 --> 0:20:50.760 with antibiotics or like it's. 0:20:50.600 --> 0:20:53.120 Still Yeah, that's a really great questionnaire. And I don't 0:20:53.119 --> 0:20:57.480 know how either, because it's gonna so depend right on 0:20:57.640 --> 0:21:00.000 like what hospital you end up in, who you are, 0:21:00.359 --> 0:21:03.240 how sick you are, like how much people are looking 0:21:03.240 --> 0:21:05.440 into this. Are you getting worse and worse and worse 0:21:05.560 --> 0:21:08.320 or are you getting kind of better? Like do you 0:21:08.400 --> 0:21:11.960 have access to diagnostics? Do you not? Like right, there's 0:21:12.000 --> 0:21:13.600 so much that's going to play into. 0:21:13.400 --> 0:21:17.520 That risk factors that would exactly this is an opportunistic. 0:21:17.080 --> 0:21:19.600 Yeah, like I will say, I mean having worked in 0:21:19.600 --> 0:21:22.600 the hospitals, like, but not in a region that is 0:21:22.760 --> 0:21:26.000 common for histoplasmosis. I mean in med school I was, 0:21:26.080 --> 0:21:29.920 but I don't remember thinking that much about hystoplasmosis in 0:21:29.960 --> 0:21:32.520 med school. But like, whenever there was someone who's not 0:21:32.560 --> 0:21:34.439 getting better than one of the things at least that 0:21:34.520 --> 0:21:36.600 we would do would be to talk to the infectious 0:21:36.600 --> 0:21:38.400 disease folks. And this is often one of the first 0:21:38.440 --> 0:21:40.480 things that they would think of. And that's why it's 0:21:40.480 --> 0:21:43.359 so valuable to have access to infectious disease experts because 0:21:43.359 --> 0:21:46.000 they're going to think of things that other physicians might 0:21:46.080 --> 0:21:48.720 not remember as often or might not be top of 0:21:48.760 --> 0:21:52.040 mind when the symptoms are hard to kind of pinpoint, so. 0:21:52.000 --> 0:21:54.400 Or if you're not in the geographic region or exactly 0:21:54.400 --> 0:21:57.280 this is classically at histo Hystow zone. 0:21:57.440 --> 0:21:59.600 But as we know, as we'll talk about, it happens 0:21:59.640 --> 0:22:01.040 outside history. 0:22:01.320 --> 0:22:02.359 Yeah. 0:22:02.680 --> 0:22:05.439 So those are great questions though, And I like, how 0:22:05.600 --> 0:22:08.320 when does it considered an infection versus not? Is such 0:22:08.320 --> 0:22:10.879 an interesting question because we don't know. Most of the 0:22:10.920 --> 0:22:13.280 literature says that like less than one percent of people 0:22:13.440 --> 0:22:16.600 will have symptoms, but like that other ninety nine percent, 0:22:16.640 --> 0:22:19.680 do we consider them having been infected? 0:22:20.240 --> 0:22:20.480 Right? 0:22:20.560 --> 0:22:23.439 I mean if they mounted immune response, then yes, you 0:22:23.520 --> 0:22:26.680 do consider that, right, even if you are totally asymptomatic. 0:22:26.800 --> 0:22:29.280 So I think a lot of people had been have 0:22:29.440 --> 0:22:32.919 been infected, but just really very few of them end 0:22:32.960 --> 0:22:34.600 up actually having symptoms. 0:22:34.520 --> 0:22:38.560