Speaker 1: My name is Macy, and I'm a twenty five year
Speaker 1: old from southern Indiana. During my senior year of college,
Speaker 1: I started feeling pretty tired and chilly just a couple
Speaker 1: of days after I returned to campus after Thanksgiving break.
Speaker 1: I had a lot of final projects in studying to do,
Speaker 1: but I was feeling really exhausted, so I decided to
Speaker 1: give myself a break and lie down for a short nap.
Speaker 1: Not long after that, I realized that I might be
Speaker 1: running a fever. I took my temperature to find that
Speaker 1: it was just over one hundred degrees. It was twenty
Speaker 1: twenty two, so I took a quick at home COVID test,
Speaker 1: but it was negative. I figured I would keep an
Speaker 1: eye on it and see how things progressed over the
Speaker 1: next few days. But over the next week, my temperature
Speaker 1: steadily increased to just over one hundred one degrees. I
Speaker 1: wasn't experiencing a running nose, cough, body aches, or anything
Speaker 1: else you would expect with a cold. I had been
Speaker 1: feeling more tired and had started taking a nap each
Speaker 1: day after class, but I was still able to function
Speaker 1: almost like any other college did. By day twelve, my
Speaker 1: fear was reaching over one hundred three at times, and
Speaker 1: I was much more fatigued and sleeping even more. But
Speaker 1: now I was starting to notice some shortness of breath
Speaker 1: just walk from my apartment door to the elevators in
Speaker 1: my building. It was also getting a little uncomfortable to
Speaker 1: breathe deeply. At that point, I decided I should go
Speaker 1: to the doctor, but with as busy as urgent cares
Speaker 1: are in a big college town during flu season, I
Speaker 1: wasn't able to get in anywhere for a few days.
Speaker 1: I went into my urgent care appointment on day sixteen
Speaker 1: of this fever, expecting to be tested for a few infections,
Speaker 1: get an answer, and be sent home with a antibiotics instead.
Speaker 1: When the nurse practitioner came in to tell me about
Speaker 1: my results, she said that everything had come back negative.
Speaker 1: I do have a history of immunisuppression, though, so she
Speaker 1: chose to send me to the emergency department for further
Speaker 1: work up, just to be sure that she wasn't missing
Speaker 1: anything big. In the ED, the doctors told me that
Speaker 1: my chest X ray and CT showed some sort of
Speaker 1: pneumonia covering both lungs top to bottom. I was admitted
Speaker 1: and over the next few days, I was treated with
Speaker 1: empiric antibiotics while they tried to figure out what was
Speaker 1: causing this. In the meantime, I continued to run a
Speaker 1: fever and got more and more fatigued. Around day four
Speaker 1: in the hospital, they started treating me with oral anti
Speaker 1: fungals as they began to suspect that it was more
Speaker 1: likely to be a fungal infection. I was told definitively
Speaker 1: that I had pulmonary histoplasmosis. My doctors were somewhat stumped
Speaker 1: as we could not pinpoint any likely exposure event. They
Speaker 1: chalked it up to me being amina compromised and living
Speaker 1: in the Ohio River Valley. That evening, I was given
Speaker 1: ampho terras and B. They were planning to put in
Speaker 1: a pickline for continued infusions on discharge if I tolerated
Speaker 1: it well. But during that infusion, I experienced severe nausea, headache,
Speaker 1: and I spiked a fever for the first time that day.
Speaker 1: On my eighth morning in the hospital, they chose to
Speaker 1: go ahead and give me a second amphoterrasm B infusion
Speaker 1: before switching me to oral intriconaisole and sending me home.
Speaker 1: I was kept on interconisole for a full year. After that,
Speaker 1: I followed up with pulmonology for about three months and
Speaker 1: had to follow up with infectious disease for a couple
Speaker 1: of years. It has now been over three years since
Speaker 1: I was diagnosed with histoplasmosis and I'm fully recovered. I
Speaker 1: just have a few small pulmonary calcifications on my chest
Speaker 1: X ray to show for it.
Speaker 2: Macie, thank you so much for sharing your story with us.
Speaker 2: We really appreciate it.
Speaker 3: Yeah, it really does mean a lot. Thank you, Yeah,
Speaker 3: thank you.
Speaker 2: Hi. I'm Aaron Welsh and I'm Erin Alman Updank and
Speaker 2: this is this podcast will Kill You.
Speaker 3: Welcome to histo plasmosis.
Speaker 2: Histo plasmosis. It's taken us a while to do this,
Speaker 2: despite getting requests for it, and also this being one
Speaker 2: of the more abundant.
Speaker 3: Prevalent, much more common than other fungal pathogens that we've
Speaker 3: covered on the podcast, which I didn't really realize. Honestly
Speaker 3: I didn't either.
Speaker 2: I mean, I think when I saw the first time
Speaker 2: I read about how people in the Ohio River Valley
Speaker 2: like ninety percent have been exposed, I'm like, oh, I've
Speaker 2: lived there. That's where I grew up, I have been
Speaker 2: exposed to histo. It never occurred to me.
Speaker 3: Yeah, no, it's yeah, same, same.
Speaker 2: Yeah. I'm excited to learn more about the biology because
Speaker 2: I'm like, when does somebody find out anyway, there's so
Speaker 2: much to cover there. I'm so excited for this episode.
Speaker 2: So but so we got to get to through some things. First.
Speaker 3: We do, as always quarantin any time.
Speaker 2: Yeah, what do we drink in this week?
Speaker 3: We're drinking the Fungus among Us, which we're pretty sure
Speaker 3: was the title of our blast on my closest episode.
Speaker 3: But it's a great it's a great title.
Speaker 2: This is truly the fungus that is among.
Speaker 3: Us, way more so than blasto.
Speaker 2: At least for you know, the eastern half of the
Speaker 2: United States, but also other places. And it's also more
Speaker 2: broadly spread exactly, I know, I know.
Speaker 3: It's everywhere. It's everywhere.
Speaker 2: Fungus among us it is, it's going. We modeled it
Speaker 2: to look like maybe I shouldn't say that, I'll say
Speaker 2: the ingredients first. It has coconut cream, pineapple juice, lime juice.
Speaker 2: It's really good, and we did we used coconut cream
Speaker 2: because of the way that a lot of exposures to
Speaker 2: histol plasmosis occur, which is through that guano and bird excrement,
Speaker 2: So we wanted it to look a little bit poopy,
Speaker 2: like bird poopy.
Speaker 3: A little bit bird and batpoopy.
Speaker 2: In the spirit of Stow. Yeah.
Speaker 3: You can find the full recipe for that delicious quarantini
Speaker 3: on our website. This podcast will kill You dot com
Speaker 3: and all of our social medias. Are you following us
Speaker 3: on the socials because we're there.
Speaker 2: We are there. Make sure you follow, review, subscribe, rate,
Speaker 2: et cetera, and our website. Things that you can discover
Speaker 2: on there include transcripts, links to our bookshop, dot org
Speaker 2: affiliate page, our Goodreads list, music by Bloodmobile, a first
Speaker 2: hand account form, a contact us form, and links to
Speaker 2: merge Patreon.
Speaker 3: Wow so much, so much.
Speaker 2: Yeah, check it out sources because I have a lot
Speaker 2: of more sources than I anticipated for this and some
Speaker 2: really great ones that I am encouraging people to read.
Speaker 3: I am so excited. Also, apologies because my cat is
Speaker 3: being very loud in the other room right now.
Speaker 2: Is he hungry? Is it the kippie?
Speaker 3: He's always hungry and he's always been fed, so I
Speaker 3: don't know it anyways.
Speaker 2: He's just making himself known.
Speaker 1: Yep.
Speaker 3: Yeah, well, Aaron, should we get into this.
Speaker 2: Let's do it. Let's take a quick break and get started.
Speaker 3: Hytoplasmosis is the name for a disease caused by a
Speaker 3: fungus called Histoplasma capsulatum H. And it turns out that
Speaker 3: there's actually quite a lot of genetic diversity in this
Speaker 3: particular fungal species. There's probably I don't know, they might
Speaker 3: even be split into multiple species at some point.
Speaker 2: I don't know how fungal species differentiation works.
Speaker 3: Me neither, So I'm not going to get deep into
Speaker 3: it today. We're just going to kind of focus on
Speaker 3: the Histoplasma capsulatum group. Okay, right, And we have covered
Speaker 3: a relatively similar fungus at least in the kind of
Speaker 3: path of physiology of how it works in our bodies earlier,
Speaker 3: and that is blastomycosis caused by blastomics. But don't worry
Speaker 3: if you didn't listen to that episode or if you
Speaker 3: don't remember anything from it, because neither did I.
Speaker 2: So although it's a good episode, it is, remember it's
Speaker 2: a really good because there's deep time and dinosaurs and.
Speaker 3: Yeah, it's a really good episode. But unlike blastomics. The
Speaker 3: fungus that is the focus of today's episode, Histoplasma is
Speaker 3: extremely abundant in the environment, it turns out extraordinarily. So
Speaker 3: you mentioned aaron that classically in the US we associate
Speaker 3: histoplasmosis with the Mississippi and Ohio River valleys. That's like
Speaker 3: what we learn in med school. And I did look
Speaker 3: this up this time because I like kind of knew
Speaker 3: exactly where those were geographically, but let's be real, not
Speaker 3: everybody does. So the Mississippi River runs north south from
Speaker 3: like Minnesota all the way down and exits in the
Speaker 3: Gulf of Mexico. The Ohio River is one of its
Speaker 3: many tributaries that runs sort of east west ish from
Speaker 3: Pennsylvania to where it lets out in the Mississippi River.
Speaker 3: And so classically this is where most cases of histoplasmosis
Speaker 3: were seen. And so that is the kind of association
Speaker 3: in a lot of people's minds. And it's true that
Speaker 3: today the vast majority of cases in the US are
Speaker 3: centered in these regions. But it is not only these
Speaker 3: regions where this fungus can be found. This fungus exists
Speaker 3: in the soil as a mold, and it can be
Speaker 3: found on every continent except Antarctica. Yep. It loves humid,
Speaker 3: nitrogen and phosphorus rich soils, which means that it tends
Speaker 3: to grow very well where there's a lot of poop poop,
Speaker 3: bird poop and batpoop specifically.
Speaker 1: Yeah.
Speaker 2: Oh, I was trying to get deep into, like what
Speaker 2: what makes a bird poop different different amounts of nitrogen
Speaker 2: and phosphorus. I mean, I don't know the answer. I
Speaker 2: love that, but I was there was a period of time,
Speaker 2: there was like a few hours where I was like,
Speaker 2: bird poop composition.
Speaker 3: Composition, Yeah, different birds different I'm sure the composition's quite different, right.
Speaker 2: Right, And which one does histoplasma?
Speaker 3: Like, you know, I did know some of that, Yeah, exactly.
Speaker 3: I was gonna say, there are some papers with that.
Speaker 3: And it also seems like bats are a particularly important
Speaker 3: component of the hystoplasmosis cycle, especially because the fungus itself
Speaker 3: can also be found in the bats, and so then
Speaker 3: bat poop not only is good fodder in the soil
Speaker 3: for this mold to grow, but can actually contain the
Speaker 3: histoplasma so they can spread it as they poop around
Speaker 3: the world.
Speaker 1: Right.
Speaker 2: Yeah's although I did also hear so birds can't be infected,
Speaker 2: it seems. Yeah, but they're feather might be able to
Speaker 2: carry it because they're all poopy.
Speaker 3: Yes, because they're covered in spores. Yeah, and things so lovely.
Speaker 3: But Okay, if this fungus was just a mold living
Speaker 3: in the soil, then we wouldn't be talking about it
Speaker 3: on this podcast Will Kill You? Okay, well we might
Speaker 3: at some point maybe, but realistically, but it's probably.
Speaker 2: What it athogen So what makes that pathogenic.
Speaker 3: What makes it pathogenic is that this fungus, like blastomics
Speaker 3: that we've covered before, is what's called thermally dimorphic, which
Speaker 3: means it can exist in two different forms depending on
Speaker 3: the temperature, largely of the environment in which it exists in.
Speaker 3: So in the environment in the soil, which is going
Speaker 3: to be a cooler temperature like let's say ideally twenty
Speaker 3: five to thirty celsius, which is like seventies to eighties,
Speaker 3: that's their sweet spot. That's when we see this fungus
Speaker 3: existing as a fungus as a mold in this filamentous,
Speaker 3: branchy form, but it can also exist as a yeast,
Speaker 3: which is a single cell fungus when it is exposed
Speaker 3: to higher temperatures around thirty seven degrees celsius aka human
Speaker 3: body temperature ninety eight point six fahrenheit.
Speaker 2: Okay, so tell me how does that work? Like if
Speaker 2: you are exposed to the mold, can you can will
Speaker 2: it turn into a yea yeah, tell me about that.
Speaker 3: I would love to tell you about it. The answer
Speaker 3: is yes. So this is an example of an environmentally
Speaker 3: transmitted pathogen. So this is not something that's transmitted person
Speaker 3: to person. If I have histoplasmasis, I cannot give it
Speaker 3: to you, Aaron, especially not over the internet. And there
Speaker 3: aren't any like vectors directly involved. So yes, a human
Speaker 3: gets exposed via exposure to the mold form of this
Speaker 3: fungus that thrives in the soil. Okay, So little bits
Speaker 3: of these hyphie, this filamentous branching mold can break off
Speaker 3: in the soil. And the way that this form of
Speaker 3: the mold reproduced is it forms these spores called canidia,
Speaker 3: and those are what get dispersed into the environment so
Speaker 3: that this mold can continue to grow and move around
Speaker 3: the environment. So those spores, as well as little bits
Speaker 3: of the filaments themselves get mixed up in the soil
Speaker 3: and they can end up blown by the wind directly
Speaker 3: into our noses or many mammals noses where we're going
Speaker 3: to breathe them in, and once they are inside our
Speaker 3: warm human body, they're actually gobbled up almost immediately by
Speaker 3: our immune cells. They're gobbled up by cells like macrophages,
Speaker 3: which are kind of like one of the bouncers of
Speaker 3: our immune system that gobble things up that don't belong.
Speaker 3: And histoplasma is like well adapted to this process. Once
Speaker 3: it is engulfed by a macrophage in this warm environment,
Speaker 3: it switches.
Speaker 2: Because, oh my gosh.
Speaker 3: They completely transform. They rearrange the entirety of their cell
Speaker 3: walls and how they exist and how they reproduce and
Speaker 3: turn into this yeast form. Now, yeasts, which are single
Speaker 3: celled fungi, they don't reproduce by making spores. They reproduce
Speaker 3: by a process of budding, which basically just is like
Speaker 3: if you have one yeast cell, they kind of bloop,
Speaker 3: pinch off, and now there's two of them, and so
Speaker 3: on and so forth. Histoplasma does this inside of our macrophages,
Speaker 3: so it's like a virus our body. Yes, it's an
Speaker 3: intracellular pathogen.
Speaker 2: Okay, I did not know it was an intracellular pathogen.
Speaker 2: That is so okay, So then it re it buds
Speaker 2: and buds and buds inside this macrophage and then to
Speaker 2: the point where the macrophage bursts, Like does it eventually
Speaker 2: the macrophage to burst or does it go anywhere? Where?
Speaker 2: Does it go in your body?
Speaker 3: Yeah? Eventually it will kill this macrophag right, eventually it will.
Speaker 3: It will reproduce so much and so many times that
Speaker 3: these macrophages burst open and then now these yeasts are
Speaker 3: free to be gobbled up by other macrophages and continue
Speaker 3: this process.
Speaker 2: And so it's all macrophages is the intracellular part of it.
Speaker 3: There's other cells too, but macrophasis are one of like
Speaker 3: the main ones.
Speaker 2: Okay.
Speaker 3: Now, yeah, where this is happening is primarily in our
Speaker 3: lungs because we are exposed, yeah, by breathing it in,
Speaker 3: and so these tiny little spores that we've been exposed
Speaker 3: to get down into our lungs and that's where they
Speaker 3: are transforming into this yeast form. As our macrophagis are
Speaker 3: gobbling them up. They're trying to mount a typical immune response,
Speaker 3: and that means that they are flagging and telling other
Speaker 3: immune cells like our T cells to come in and
Speaker 3: get rid of this passagen, and for the vast majority
Speaker 3: of us, that is the end of the story.
Speaker 2: Okay, okay, so exposure, we have not gotten to infection yet.
Speaker 2: This is still like what exposure would look like that
Speaker 2: could potentially lead to infection. You're breathing in these spores,
Speaker 2: they turn into yeast, they start to replicate, and then
Speaker 2: at some point throughout this process, as more and more
Speaker 2: macrophages are infected, your two cells are like, we're shutting.
Speaker 3: This down absolutely unless unless they can't exactly. So for
Speaker 3: the vast majority of us, we will have exposure, some
Speaker 3: kind of immune response and it's you know, it's our
Speaker 3: whole entire immune system that's involved, and then goodbye fungus.
Speaker 2: The end.
Speaker 3: We do a really good job of clearing this fungus classically. However,
Speaker 3: also classically, fungi are really good at flying under the
Speaker 3: radar and can find ways to avoid being completely eradicated.
Speaker 3: So for some people, whether because they're immunal compromised or
Speaker 3: just because they were exposed to a really high dose
Speaker 3: right like they inhaled a whole face full of these spores,
Speaker 3: they could end up with a symptomatic infection. So let's
Speaker 3: talk about what that looks like, shall we. Yeah, if
Speaker 3: someone is going to have symptoms from exposure to histoplasma,
Speaker 3: the most common thing they're going to have is a pneumonia,
Speaker 3: which is unsurprising because again, this is all happening in
Speaker 3: our lungs. Usually this is only happening if you're exposed
Speaker 3: to a really high concentration of spores, and it's going
Speaker 3: to take some time because these youths aren't like really
Speaker 3: fast at reproducing, you know, take some time. Okay, So
Speaker 3: after an incubation period of usually a couple of weeks
Speaker 3: or so, but anywhere from like three to twenty one days,
Speaker 3: some of the papers I read said, you will start
Speaker 3: to have kind of non specific flu like symptoms, fever, headache, cough,
Speaker 3: maybe some chills, muscle aches. It'll look like a pneumonia.
Speaker 2: Okay.
Speaker 3: Many people might go to the doctor be treated for
Speaker 3: bacterial pneumonia, and then they might get better all on
Speaker 3: their own, and the animaliotics absolutely were not the thing
Speaker 3: that made them get better. But most people who have
Speaker 3: even an acute pneumonia from histoplasmosis are going to recover
Speaker 3: all on their own and get over this infection.
Speaker 2: Okay, for others.
Speaker 3: That maybe had a really even higher exposure or just
Speaker 3: are susceptible for one reason or another, they might have
Speaker 3: a more severe course. They might have increased inflammation, they
Speaker 3: might end up having like difficulty breathing, shortness of breath,
Speaker 3: or if you actually checked their oxygen concentration it might
Speaker 3: actually be low. And so in those cases people might
Speaker 3: actually get the diagnosis of histoplasmosis and then they might
Speaker 3: actually need treatment with antifungals. But that's not necessarily like
Speaker 3: a majority of people who are even having symptomatic acute
Speaker 3: pulmonary hystoplasmosis. But that is not the end of the
Speaker 3: story for some people. Okay, real quick though, Yeah, give
Speaker 3: it to me.
Speaker 2: How long on average does this last? If it is
Speaker 2: a self self what do you call it.
Speaker 3: A self limiting infection?
Speaker 2: Limiting infection?
Speaker 3: It's a good question. I don't have like a perfect timeline.
Speaker 3: I would expect it to be like within the within
Speaker 3: what would be a typical course of pneumonia for a
Speaker 3: lot of people, So maybe a couple of weeks max
Speaker 3: or so, But it all is just going to depend
Speaker 3: on what your immune response to it is, whether or
Speaker 3: not you get severely sick and things like that. It's
Speaker 3: very person dependent.
Speaker 2: And so most of these people are diagnosed based on
Speaker 2: symptoms and it is in they're diagnosed as having bacterial pneumonia.
Speaker 3: Yeah, it's very like we probably drastically underestimate the actual
Speaker 3: incidence of acute pulmonaryhystoplasmosis because so many cases are either
Speaker 3: never seen by a healthcare professional because they think it's
Speaker 3: just some other cold or flu, right, or yes, they're
Speaker 3: misdiagnosed as community acquired pneumonia treated with antibiotics and they
Speaker 3: get better, but not because of the antibiotics, and it
Speaker 3: was actually hytoplasmosis.
Speaker 2: Okay. I have two questions, Okay. The first is at
Speaker 2: what point does exposure become infections? Like, in order for
Speaker 2: an infection to count as infection, do there have to
Speaker 2: be symptoms? Yes, I don't know.
Speaker 3: It's a great question. Okay, I'm nodding because it's such
Speaker 3: a good question, but I don't have an answer for you.
Speaker 2: Okay. And then the other question is at what point
Speaker 2: does you know you said these diagnoses are often bacterial.
Speaker 2: At what point does does histoplasma become the horse and
Speaker 2: not the zebra? I guess yeah, Like, at what point
Speaker 2: do people start to say this is it's not resolving
Speaker 2: with antibiotics or like it's.
Speaker 3: Still Yeah, that's a really great questionnaire. And I don't
Speaker 3: know how either, because it's gonna so depend right on
Speaker 3: like what hospital you end up in, who you are,
Speaker 3: how sick you are, like how much people are looking
Speaker 3: into this. Are you getting worse and worse and worse
Speaker 3: or are you getting kind of better? Like do you
Speaker 3: have access to diagnostics? Do you not? Like right, there's
Speaker 3: so much that's going to play into.
Speaker 2: That risk factors that would exactly this is an opportunistic.
Speaker 3: Yeah, like I will say, I mean having worked in
Speaker 3: the hospitals, like, but not in a region that is
Speaker 3: common for histoplasmosis. I mean in med school I was,
Speaker 3: but I don't remember thinking that much about hystoplasmosis in
Speaker 3: med school. But like, whenever there was someone who's not
Speaker 3: getting better than one of the things at least that
Speaker 3: we would do would be to talk to the infectious
Speaker 3: disease folks. And this is often one of the first
Speaker 3: things that they would think of. And that's why it's
Speaker 3: so valuable to have access to infectious disease experts because
Speaker 3: they're going to think of things that other physicians might
Speaker 3: not remember as often or might not be top of
Speaker 3: mind when the symptoms are hard to kind of pinpoint, so.
Speaker 2: Or if you're not in the geographic region or exactly
Speaker 2: this is classically at histo Hystow zone.
Speaker 3: But as we know, as we'll talk about, it happens
Speaker 3: outside history.
Speaker 2: Yeah.
Speaker 3: So those are great questions though, And I like, how
Speaker 3: when does it considered an infection versus not? Is such
Speaker 3: an interesting question because we don't know. Most of the
Speaker 3: literature says that like less than one percent of people
Speaker 3: will have symptoms, but like that other ninety nine percent,
Speaker 3: do we consider them having been infected?
Speaker 2: Right?
Speaker 3: I mean if they mounted immune response, then yes, you
Speaker 3: do consider that, right, even if you are totally asymptomatic.
Speaker 3: So I think a lot of people had been have
Speaker 3: been infected, but just really very few of them end
Speaker 3: up actually having symptoms.
Speaker 2: And you can become re exposed and reinfected.
Speaker 3: Absolutely, yes, yeah, yeah, And along those lines, arn this
Speaker 3: acute like limited infection is not the end of the
Speaker 3: story for a lot of people, because this fungus can
Speaker 3: continue to grow even as we are mounting an immune
Speaker 3: response to it. And if that happens. There's kind of
Speaker 3: like two main ways that it can go in the
Speaker 3: long term or not even the long term, but there's
Speaker 3: two kind of ways that it can grow. One is
Speaker 3: that this yeast can continue to replicate, but our immune
Speaker 3: system can be kind of fighting back at the same time, okay,
Speaker 3: and so it can do this thing that we do
Speaker 3: with a lot of infections that are really hard to eradicate,
Speaker 3: where our immune system kind of decides, look, we can't
Speaker 3: really get rid of this thing entirely, so let's wall
Speaker 3: it off. Ah. And so that results in the formation
Speaker 3: of these things called granulomas. And that's these like inflammatory
Speaker 3: little pockets of fungus and immune cells that kind of
Speaker 3: can just like sit there.
Speaker 2: This we've we've encountered this before. Because I feel like
Speaker 2: I made some bad a cask of amontiao Edgar Allan
Speaker 2: Poe joke about walling off.
Speaker 3: Probably nothing else familiar. Yeah, no idea, what episode that was.
Speaker 3: I mean, it could have been blastoma, could have been TB,
Speaker 3: but that was so long ago. I don't know. But
Speaker 3: these you can see things like this in tuberculosis, absolutely,
Speaker 3: and histoplasmosis is easy to conflate with tuberculosis. In a
Speaker 3: lot of cases. And what's interesting is that this can happen.
Speaker 3: This process of this granuloma formation can happen even without
Speaker 3: any clinically apparent disease. So even without having had any
Speaker 3: known symptoms, you can end up with these granulomas in
Speaker 3: your lungs that you might find on say a CT
Speaker 3: scan decades later.
Speaker 2: Decades later.
Speaker 3: It's actually quite a common cause of pulmonary nodules, like
Speaker 3: asymptomatic pulmonary nodules, what.
Speaker 2: And so that would just be like a random finding
Speaker 2: or would you be going in for something else.
Speaker 3: It's really common that we have just incidental pulmonary nodules.
Speaker 3: They're like, oh, like what digital is there? Yeah, okay,
Speaker 3: So these these malmas can do two sorts of things.
Speaker 3: One is they can just sit there and be an
Speaker 3: incidental nodule that never causes a problem, or they could
Speaker 3: result in a chronic sort of disease that may or
Speaker 3: may not have symptoms and that may or may not
Speaker 3: be able to reactivate. We see this chronic pulmonary histoplasmosis
Speaker 3: much more commonly in people that have pre existing lung
Speaker 3: conditions like COPD, and it can really mimic tuberculosis. Because
Speaker 3: it tends to be in the upper lobes of the
Speaker 3: lungs where we see these granulomas, and they can really
Speaker 3: progress with time to where eventually they kind of really
Speaker 3: cause significant damage throughout the lungs, but it's usually only
Speaker 3: in lungs that already have underlying structural damage.
Speaker 2: Gotcha.
Speaker 3: So that's one way that this disease, or that this
Speaker 3: fungus can kind of proliferate in our lungs sort of
Speaker 3: low level. But the second way is that this fungus,
Speaker 3: this yeast could continue to grow unchecked and can invade
Speaker 3: our lymphatic system or our blood stream and then end
Speaker 3: up causing a disseminated infection where it can spread because
Speaker 3: it's inside of our blood cells, inside of our white
Speaker 3: blood cells, to literally any organ in our body, our eyes,
Speaker 3: our spleen, our liver, our bones, our skin, our nervous system,
Speaker 3: almost any organ really, any organ, our colon is actually
Speaker 3: a really big one. And this disseminated histoplasmosis is what
Speaker 3: we tend to see in people with immunal compromise like
Speaker 3: uncontrolled HIV, or like a solid organ transplant who's on
Speaker 3: immunosuppressive medications, or a congenital immune deficiency, or especially today,
Speaker 3: people who are on medications like TNF alpha inhibitors, which
Speaker 3: are a class of medications that's used to treat a
Speaker 3: really wide variety of autoimmune conditions like rheumatoid arthritis or
Speaker 3: all sort of colitis and things like that.
Speaker 2: So there can be these these nodules and there can
Speaker 2: be disseminated disease. How long does it take for disseminated
Speaker 2: disease to develop? And can it kind of bypass these
Speaker 2: other stages and just sort of be disseminated.
Speaker 3: Yes, those are really great questions. So to answer the
Speaker 3: first question, I don't have an exact timeline because we
Speaker 3: don't really have at least from what I read, And
Speaker 3: so if I missed it, someone please let me know.
Speaker 3: But there's not like really great like, oh, here's an
Speaker 3: exposure versus here's disseminated disease like timelines out there, if
Speaker 3: that makes sense. So it's going to really depend on
Speaker 3: who the person is and how sick they were or
Speaker 3: how compromise their immune system was to begin with. But
Speaker 3: then yes, they absolutely could have disseminated disease without having
Speaker 3: like a pneumonia type infection. First, if that makes sense.
Speaker 2: And then what are the symptoms of disseminated disease?
Speaker 3: Great question. They can be really non specific, which can
Speaker 3: make them really hard to identify. What you end up
Speaker 3: seeing are these same kind of grand and yulomitis lesions
Speaker 3: wherever this yeast has disseminated too, the lungs, the liver,
Speaker 3: the brain, the colon, and so it really depends on
Speaker 3: how far this has progressed and what organs it has
Speaker 3: invaded to know what the symptoms are going to be.
Speaker 3: But often what we see are fevers, and especially fevers
Speaker 3: that don't respond to antibiotics right or that we can't
Speaker 3: find a source of a bacterial infection, we can find
Speaker 3: weight loss because this tends to be like a really
Speaker 3: progressive disease. When you look at people's blood, like when
Speaker 3: you know they're in the hospital because they're sick and
Speaker 3: you're checking their blood, we see that all of their
Speaker 3: blood counts so like white blood cells, red blood cells,
Speaker 3: platelets tend to go down, down and down, and that's
Speaker 3: what we call pan cidopenia. That's a pretty bad prognosis
Speaker 3: in histoplasmosis. I don't know the exact mechanism of it, Okay,
Speaker 3: and yeah, beyond that, the symptoms can be just really nonspecific.
Speaker 3: If someone has a lot of lung involvement, they might
Speaker 3: have symptoms that look like pneumonia, but again they're not
Speaker 3: getting better with antibiotics. We can often see and this
Speaker 3: is when it gets really extreme, like colon perforations and things,
Speaker 3: which of course is like a surgical emergency. And that's
Speaker 3: if the colon is very involved. If it's in the brain,
Speaker 3: then you might have symptoms similar to meningitis. If it's
Speaker 3: in the eye, then you might have damage to the eye,
Speaker 3: including vision loss. So it really just it's so so
Speaker 3: varied and it really just depends on where it has
Speaker 3: disseminated too.
Speaker 2: Yeah that makes sense. Yeah, is there okay too? Sorry,
Speaker 2: I feel like I'm like just pre empty.
Speaker 3: I love it. I love it.
Speaker 2: Keep going. What is the breakdown of let's say, you know,
Speaker 2: one hundred people are are become infected with histoplasma every year.
Speaker 2: What proportion of those are like asymptomatic, What proportion are
Speaker 2: symptomatic and self resolve? What are the ones that are nodules,
Speaker 2: what are the ones that are just saying dominated?
Speaker 3: Yeah, yeah, this is such a great question. I don't have.
Speaker 3: I wanted to find like exact stats on that, but
Speaker 3: the best that I got is that a lot of
Speaker 3: the papers say that one percent of people, so one percent,
Speaker 3: one out of that one hundred would have a symptomatic infection.
Speaker 3: So we're gonna have to go bigger. We'll go like
Speaker 3: a thousand, Okay, Yeah, and then sixty percent of people
Speaker 3: who have a symptomatic infection will have respiratory symptoms, So
Speaker 3: that's more that like acute pulmonary infection. Of the rest
Speaker 3: of the forty percent, I don't know what that breakdown is.
Speaker 3: How much of that forty percent is like a chronic
Speaker 3: pulmonary histoplasmosis versus a disseminated someone with immuno compromise having
Speaker 3: a disseminated infection.
Speaker 2: I don't have it.
Speaker 3: I don't have a breakdown on that other forty percent
Speaker 3: of the one percent of the one percent of the
Speaker 3: one percent.
Speaker 2: Okay, and treat men.
Speaker 3: Yeah, So before I talk about treatment, I want to
Speaker 3: just mention that one of the big, big problems, and
Speaker 3: we kind of have alluded to this, but one of
Speaker 3: the big issues with histoplasmosis is being able to diagnose
Speaker 3: it to begin with. Okay, because if it's an acute infection,
Speaker 3: then it looks a lot like a bacterial pneumonia. Right,
Speaker 3: maybe an X ray would look a little bit different
Speaker 3: or a little bit more patchy rather than like you know,
Speaker 3: a low bar that we would see with a bacterial infection.
Speaker 3: But really it's not super different in those early stages
Speaker 3: for acute infections, and so in those cases it can
Speaker 3: be hard to diagnose because you're not thinking about it.
Speaker 3: Like you said, horses not zebras, right, But when it
Speaker 3: becomes chronic, it can just be so nonspecific that it's
Speaker 3: hard to think of. And then even when you think
Speaker 3: of it, the gold standard for diagnosis is always culture,
Speaker 3: but it can take six weeks to culture this fungus.
Speaker 2: At which point, at which point you need.
Speaker 3: To do something already. Right, So there is a lot
Speaker 3: of work being done, and there are a lot of
Speaker 3: other tests out there to look at, things like antigen detection,
Speaker 3: including in like urine, which is really great because that
Speaker 3: makes it cheap and easy. It's like very easy obviously
Speaker 3: to collect urine compared to like cerebrospinal fluid from people.
Speaker 3: And then there's also PCR based methods, but those are
Speaker 3: not available everywhere, so especially in places where histoplasmosis historically
Speaker 3: has been thought to be less common. There's a lot
Speaker 3: of issues with even having the tools in place to
Speaker 3: be able to detect this pathogen, which is a huge
Speaker 3: problem because if you can't diagnose it, then you can't
Speaker 3: treat it. Yeah, now, when it comes to treatment, not
Speaker 3: everyone ends up needing treatment, right, If this resolves on
Speaker 3: its own, then people don't need to be treated. And
Speaker 3: in fact, the guidelines from the Infectious Disease Society of America,
Speaker 3: which I think are under revision because they haven't been
Speaker 3: updated since two thousand and seven, really emphasize like trying
Speaker 3: to not treat it unles you really have to so
Speaker 3: unless somebody is really getting sick. And that's because fungal
Speaker 3: pathogens are really difficult to treat, and the anti fungal
Speaker 3: medications that we use tend to be pretty hard on
Speaker 3: our bodies and cause quite a lot of side effects.
Speaker 3: So the two main medicines that are used are amphoteresin
Speaker 3: b which like pokes holes in the fungus and then
Speaker 3: kills them, but also pokes holes in our own cell
Speaker 3: membranes because it binds to cholesterol in our cells, and
Speaker 3: so it can cause pretty severe kidney and liver damage
Speaker 3: in some cases. And then the other medicine that's uses ittriconasol,
Speaker 3: which is another antifungal medication, that also can have a
Speaker 3: lot of damage to the liver because of the way
Speaker 3: that it's metabolized. And in either case, people often need
Speaker 3: at least six to twelve weeks of therapy and sometimes
Speaker 3: six to twelve months of therapy. Okay, yes, that's.
Speaker 2: A long time to be with those side.
Speaker 3: Effects exactly exactly, so it requires quite a lot of
Speaker 3: close monitoring and everything. When it comes to the big,
Speaker 3: big picture of mortality from histoplasmosis, the mortality rates are
Speaker 3: actually quite high. They're five to eight percent, and that's
Speaker 3: in the US, Like that's based on US statistics, and
Speaker 3: even those statistics are really generalized across the board, like
Speaker 3: that's from all the symptomatic infections that we know of,
Speaker 3: But in certain subpopulations or in certain geographical regions, this
Speaker 3: mortality rate can be substantially higher. So, for example, in
Speaker 3: people with HIV who end up with disseminated histoplasmosis, the
Speaker 3: US mortality rate is closer to ten percent, is what
Speaker 3: I saw. But in some places, like in some areas
Speaker 3: of Brazil, it's up to forty percent.
Speaker 2: Oh my god.
Speaker 3: And a lot of that is due to delays in
Speaker 3: diagnosis and treatment and access and things like that. So
Speaker 3: it is not a minor disease when it becomes disseminated. Yeah, yeah,
Speaker 3: and that is hytoplasmosis sarin.
Speaker 2: Oh, it's a I mean, fungal infections in general are
Speaker 2: just harder.
Speaker 3: There's so much harder.
Speaker 2: They our body doesn't do as well recognizing them. Often,
Speaker 2: we have a harder time treating them. And then once
Speaker 2: they kind of establish a foothold, it seems really difficult.
Speaker 3: To They're really good at just sort of like resisting
Speaker 3: our clearance, you know. So yeah, tell me, Aaron, how
Speaker 3: did we get to hear? Where did this fungus among
Speaker 3: us come from?
Speaker 2: Great? Great questions. Our picture of histoplasmosis has taken shape
Speaker 2: over the past century and change. In fact, twenty twenty
Speaker 2: six marks one hundred and twenty years since it was
Speaker 2: first described.
Speaker 3: Oh wow.
Speaker 2: Yeah, and over that time it has transformed from a
Speaker 2: rare disease to one of abundance, not just in terms
Speaker 2: of the number of annual exposures, which is numbering in
Speaker 2: the hundreds of thousands, millions potentially, but also in terms
Speaker 2: of where it thrives. It loves nutrient rich soils like
Speaker 2: those that have been enriched by a bat, guano or
Speaker 2: bird excrement. I won't say contaminated. This theme of abundance
Speaker 2: is something that I'm going to come back to later on,
Speaker 2: but for now, let me take you through the history
Speaker 2: of this fungus okay, which oddly enough started out not
Speaker 2: as a fungus but as a protozoan according to the
Speaker 2: guy who first observed it.
Speaker 3: Oh yes, yeah, yeah, okay.
Speaker 2: In December nineteen oh five, Samuel Taylor Darling had freshly
Speaker 2: arrived in Panama in the Canal Zone, where he acted
Speaker 2: as a pathologist in the hospital where he was working.
Speaker 2: On December fifth, nineteen oh five, a twenty seven year
Speaker 2: old man, a Carpenter, checked himself into the hospital with
Speaker 2: when his illness, which had started a few months earlier
Speaker 2: as fever and vomiting, it took a turn for the worse.
Speaker 2: He was described as quote mildly delirious and incoherent with
Speaker 2: an enlarged spleen, but his lungs were clear and his
Speaker 2: blood did not contain any malaria parasites. Over the next
Speaker 2: twenty four hours, he steadily declined, and he died on
Speaker 2: the evening of the sixth of December. A preliminary diagnosis
Speaker 2: of milliary tuberculosis was given, which is when the tuberculosis
Speaker 2: bacteria have spread throughout the body, forming nodules and leading
Speaker 2: to these systemic symptoms, and initially the autopsy seemed to
Speaker 2: confirm this diagnosis. Quote the odor on opening thorax was
Speaker 2: suggestive of pulmonary tuberculosis. End quote.
Speaker 3: Interesting.
Speaker 2: I don't know, but he I mean, the way he
Speaker 2: wrote about that is just sort of like everyone.
Speaker 3: Knows what this everyone knows what this smells like. It
Speaker 3: smells like yeah, I mean, I guess that makes sense
Speaker 3: in that if you do something very often and you
Speaker 3: are exposed to I am, I am not surprised that
Speaker 3: the formation of a bunch of case eating granulum has
Speaker 3: a specific smell to it. Totally totally so interesting though, Wow.
Speaker 2: Yeah, I just have never encountered that, Like, yeah, yeah,
Speaker 2: I know that, like sea diiff has a particular smell,
Speaker 2: but like I didn't anyway, So but also quote the
Speaker 2: lungs on section were found studded with pale gray milliary
Speaker 2: tubercles tubercles from two to three millimeters in diameter end quote.
Speaker 2: But as Darling continued with the autopsy, he noticed several
Speaker 2: findings that contradicted the initial tuberculosis diagnosis, things like quote,
Speaker 2: the tubercles were not as closely packed or so numerous
Speaker 2: as is often found in miliary tuberculosis, and the general
Speaker 2: color of the lungs was quite red.
Speaker 3: Interesting.
Speaker 2: Yeah, and his suspicions were confirmed when he took a
Speaker 2: look at some blood smears under the microscope and found
Speaker 2: no tuberculosis bacteria, but instead quote enormous numbers of small bodies,
Speaker 2: generally oval or round. Most of them were intracellular in
Speaker 2: alveolar epithelial cells, while others appeared to be free in
Speaker 2: the plasma of the spleen and rib marrow end quote.
Speaker 3: I love that description, Aaron, And.
Speaker 2: To Darling's eye, which admittedly was limited by crude microscope equipment,
Speaker 2: these round bodies resembled protozoan parasites like those that cause leishmaniasis.
Speaker 3: Right. Yeah, And so he.
Speaker 2: Concluded that this was a new species of pathogenic species
Speaker 2: of protozoan, distinct enough to warrant a new name, Histoplasma capsulotum.
Speaker 3: Huh, that's how it got its name.
Speaker 2: That's how got its name.
Speaker 3: How interesting, Gary.
Speaker 2: Yeah, And this incorrect categorization as a protozoan, it didn't
Speaker 2: last all that long. It was just like five years
Speaker 2: later in nineteen twelve, after he published this paper, after
Speaker 2: he first saw it. Rather, another famous pathologist, Enrika Roschalima,
Speaker 2: published a report where he was like, are you sure
Speaker 2: it's a protozoan because I just compared with what hytoplasma
Speaker 2: looks like next to leishmania and yeast, and it looks
Speaker 2: a lot more like yeast than a protozoan parasite. All right, So,
Speaker 2: like it was corrected pretty shortly after confirmed a number
Speaker 2: you know, years later, But.
Speaker 3: Like, I just love that your description of that made
Speaker 3: it sound like he was so polite about it.
Speaker 2: I mean, it's sure.
Speaker 3: I'm so sorry, dude, but like I just I wanted
Speaker 3: you to just like make.
Speaker 2: Sure, like, can we just double check this again?
Speaker 3: Really cute.
Speaker 2: That's how I'm imagining, very gentlemanly about the thing.
Speaker 3: That's making me cry.
Speaker 2: Wow, your bar for jokes.
Speaker 3: I don't know what's going on.
Speaker 2: With this correction was ultimately, of course necessary, like it was.
Speaker 2: It had to happen, but it was kind of kind
Speaker 2: of inevitable, like someone was going to come to this
Speaker 2: conclusion sooner or later. And it didn't exactly like shake
Speaker 2: the mycology world to its core, right, Okay, hissto plasma
Speaker 2: was not widely known at all, and those who had
Speaker 2: heard of it thought of it as a rare tropical disease,
Speaker 2: so of limited interest. I would say, more of like
Speaker 2: a medical curiosity than something of like major, major importance. Okay. Yeah.
Speaker 2: The first inkling that it might be more than that, though,
Speaker 2: came in nineteen thirty two, and this is when doctor
Speaker 2: Catherine Dodd asked another physician at her university, doctor Edna Tompkins,
Speaker 2: to take a look at a blood smear that she
Speaker 2: had just taken from a with an unusual form of
Speaker 2: anemia a few years earlier. Doctor Tompkins, so the one
Speaker 2: that she had asked to look at the slide, had
Speaker 2: just so happened to attend a demonstration on hystoplasmosis given
Speaker 2: by a researcher who had visited doctor Samuel Darling to
Speaker 2: learn about the fungus. And so he came to this
Speaker 2: hostel and was like, here's this presentation. Here's how you
Speaker 2: look at it, or here's here's what it looks like.
Speaker 2: And so when she saw the blood smear, she was like,
Speaker 2: I've seen this before, hmm, right, Like this looks familiar.
Speaker 2: And so she reached out to this researcher who had
Speaker 2: presented this this demonstration to confirm her suspicions. And yes,
Speaker 2: it was hystoplasmosis. And so why this was a landmark
Speaker 2: moment in hystoplasmosis history is because this was the first
Speaker 2: time that someone had been diagnosed while they were still alive.
Speaker 3: Oh wow.
Speaker 2: Every case prior to this, which was not very many cases,
Speaker 2: had been diagnosed at autopsy. And so this gave researcher
Speaker 2: an opportunity to better culture and characterize the organism and
Speaker 2: also just to describe like symptoms while someone was still alive.
Speaker 2: And the work that was done on just this one
Speaker 2: case tied up many loose ends, at least in terms
Speaker 2: of the fungus itself. It fulfilled coxpostulates, it identified the
Speaker 2: best medium for growth, led to the development of a test,
Speaker 2: and hinted at a more widespread distribution of this organism
Speaker 2: in nature, like in the environment, something that would be
Speaker 2: confirmed in the following decades. Up until the nineteen forties,
Speaker 2: those who had heard of histoplasmosis considered it a rare,
Speaker 2: almost uniformly fatal disease, very different than the pathogen you
Speaker 2: described aaron, where it was, you know, one percent actually
Speaker 2: is symptomatic. Yeah, yeah, So what did it take to
Speaker 2: change that perception? Tuberculosis? Everything, everything is tuberculosis still happening.
Speaker 3: Yeah, okay.
Speaker 2: And so what was going on is that increasingly doctors
Speaker 2: were finding that some patients that seemed like they had
Speaker 2: tuberculosis had a negative TB skin test. Health exams during
Speaker 2: World War two laid the groundwork for this.
Speaker 3: Okay.
Speaker 2: X rays had become part of the screening process to
Speaker 2: see whether someone could enlist, and physicians began to notice
Speaker 2: these calcified regions, these nodules in the lungs on X
Speaker 2: ray without an accompanying positive TB test. Mapping out where
Speaker 2: this happened showed Kentucky, Tennessee, Ohio, North Carolina, West Virginia, Mississippi, Missouri, Indiana,
Speaker 2: and Illinois as the hotspots for this phenomenon. And this
Speaker 2: is where just I think I mentioned it earlier, but
Speaker 2: up to ninety percent of residents are estimated to be
Speaker 2: exposed during their lifetime.
Speaker 3: Yeah yeah yeah yeah, and like have evidence of prior
Speaker 3: like antibody response, gaining that they had an infection even
Speaker 3: though it was asymptomatic most likely yep, yep.
Speaker 2: And so a few years after this, so World War
Speaker 2: two on. Once these these draft screenings were over a
Speaker 2: few years later, by which point a hystoplasmosis test was available.
Speaker 2: The same phenomenon was observed in tuberculosis sanatoriums, and it
Speaker 2: pointed not towards an unusual form of tuberculosis, but a
Speaker 2: separate disease entirely.
Speaker 3: Wow. Okay yeah.
Speaker 2: A paper from nineteen sixty two looked at eighty one
Speaker 2: sanatoriums across the US, Canada, and Cuba and found that
Speaker 2: seven and a half percent of the forty five thousand
Speaker 2: patients screened were positive for hytoplasmosis.
Speaker 3: So like, they were in there being treated for tuberculosis,
Speaker 3: but they actually had histoplasmosis. Yeah, fascinating Aaron.
Speaker 2: Yep, yep. At least one quarter of those had active
Speaker 2: histoplasmosis wow, and few were so positive for tuberculosis.
Speaker 3: Wow.
Speaker 2: So how many people in sanatoriums actually had histo and
Speaker 2: not tuberculosis or and then developed TB during their time there,
Speaker 2: right of course, no right, no idea, but more than zero, yeah,
Speaker 2: especially in the areas that we tend to think of
Speaker 2: as the classic histoplasmosis region. So, for instance, more on
Speaker 2: that paper from nineteen sixty two, the percentage of people
Speaker 2: who were positive for histoplasmosis in Indiana, Kentucky, and Tennessee
Speaker 2: respectively was fifteen percent, fourteen percent, and thirteen percent, Like.
Speaker 3: Much higher than just the baseline. Oh wow, much.
Speaker 2: Higher than the seven and a half percent. Yeah, so
Speaker 2: this definitely pointed towards a tip of the Iceberg situation.
Speaker 2: Far from being a rare tropical disease, histoplasma probably led
Speaker 2: to millions of exposures every year and thousands of active
Speaker 2: cases in certain regions of the United States. But how
Speaker 2: were they getting it? A number of outbreaks throughout the
Speaker 2: nineteen fifties and the nineteen sixties helped to shed light
Speaker 2: on that question, and a pattern gradually emerged. Exposure to
Speaker 2: disturbed soil, like through construction or tornadoes. I saw a
Speaker 2: paper that was like tornadoes as as a spreader of histoplasmas.
Speaker 3: Totally makes sense, totally makes.
Speaker 2: Sense, and that is tornado zone like it's not quite
Speaker 2: all of Tornado Alley, but like there are tornadoes that
Speaker 2: absolutely happen there. Yeah, but even just like walking around
Speaker 2: right can disturb soil. And it's not just any soil.
Speaker 2: Soils enriched by batguano or bird excrement seemed particularly prone
Speaker 2: to harboring the fungus. Research demonstrated that, like we talked about,
Speaker 2: many bats can be cut or while many bats can
Speaker 2: become infected, birds cannot. But the poop of both animals
Speaker 2: is just stupendous for histo growth, and birds might be
Speaker 2: able to carry it in their feathers. Outbreak investigation often
Speaker 2: led to like a chicken coop or a roof where
Speaker 2: pigeons roosted, or a cave where bats lived. So, for instance,
Speaker 2: the nineteen seventy Earth Day outbreak where nearly yeah, ironically,
Speaker 2: where nearly three hundred students in faculty at a junior
Speaker 2: high school in Delaware, which was forty percent of the
Speaker 2: entire staff and students, they were symptomatic after cleaning up
Speaker 2: blackbird and pigeon roosting sites.
Speaker 3: They all were trying to clean up for Earthday, and
Speaker 3: then they all got hissed too. It's not funny.
Speaker 2: It's not funny, but it is just like, of course,
Speaker 2: of course you try to do something good. Yeah, but yeah.
Speaker 2: Histoplasma capsule atum was later isolated from the soil where
Speaker 2: they were doing the cleanup tracks. A paper from twenty
Speaker 2: sixteen by Benedict and Mody examined Histoplasmas's outbreaks in the
Speaker 2: United States and Puerto Rico since nineteen thirty eight and
Speaker 2: found that in the one hundred and five outbreaks that
Speaker 2: they examined, seventy seven percent were associated with bird or
Speaker 2: batpoop YEP and while earlier outbreaks tended to be rural
Speaker 2: and more limited, later outbreaks grew to be more urban
Speaker 2: and occasionally enormous. So, for instance, a couple of outbreaks
Speaker 2: in Indianapolis in the late nineteen seventies and early nineteen
Speaker 2: eighties resulted in an estimated two hundred thousand people becoming
Speaker 2: infected one hundred k in each outbreak. What yeah, yeah,
Speaker 2: that's what the estimates are.
Speaker 3: But that's not all symptomatic. That's like how total because
Speaker 3: of were against a symptomatic cases.
Speaker 2: This question of yeah, exposure versus infection and the epidemics
Speaker 2: both of these were associated with construction, So like there
Speaker 2: was a tearing down of an old amusement park along
Speaker 2: with construction of a new tennis stadium, and then the
Speaker 2: construction of like a swimming gym swimming pool gym thing
Speaker 2: on a university campus. So you got all that soil
Speaker 2: being disturbed and then winds carrying it throughout the city
Speaker 2: where which is densely populated, and boom like everyone is
Speaker 2: just breathing in histoto yep. And then the nineteen eighties
Speaker 2: and the AIDS pandemic ushered in the next era of histoplasmosis.
Speaker 2: Histo Plasmosis is a disease that you mentioned aaron disproportionately
Speaker 2: affects people with weakened immune systems, and over the course
Speaker 2: of the next few decades it proved to be devastating,
Speaker 2: like truly devastating for so many people infected with HIV
Speaker 2: who especially those living in endemic regions, with case fatality
Speaker 2: rates up to sixty percent in some situations, and effective
Speaker 2: treatments for histo back then were few and far between,
Speaker 2: and still relatively little was known about it, and so
Speaker 2: this period led to a big push for more research
Speaker 2: to better understand this infection and just growing awareness of
Speaker 2: the disease overall, as you might expeck, these years of
Speaker 2: research led to HISTO turning out to be much more
Speaker 2: prevalent and widespread than expected, not just restricted to the
Speaker 2: Mississippi Ohio River valleys, but elsewhere in North America, South America,
Speaker 2: parts of Africa, and Eastern Asia, and its range is
Speaker 2: shifting currently just as it once did. Histoplasma likely originated
Speaker 2: in South America and began it spread to these other
Speaker 2: regions about thirteen million to three and a half million
Speaker 2: years ago, something like.
Speaker 3: That, just a casual ten million year range, that's how
Speaker 3: it goes.
Speaker 2: But that is when the global the global climate was warmer,
Speaker 2: and it experienced a pause and kind of range contraction
Speaker 2: during the Pleistocene about like one hundred and one or sorry,
Speaker 2: about one point eight million years ago, when the climate cooled,
Speaker 2: and then as it warmed again, it re established itself,
Speaker 2: flourishing in warmer and wetter areas, oh really wetter, as
Speaker 2: always wetter in some places, as always. We can look
Speaker 2: towards the past to better predict our future. Ongoing human
Speaker 2: induced climate change is altering where this fungus can live
Speaker 2: and how we interact with it. As temperatures have risen
Speaker 2: Histoplasma has expanded northwards in North America and to other
Speaker 2: temperate regions where it historically has not really occurred or
Speaker 2: has not been that prevalent, such as northern Italy, parts
Speaker 2: of Argentina, and Turkey. This global warming might not only
Speaker 2: impact the range of this pathogen, but also how deadly
Speaker 2: it is. It might be selecting for more virulent and
Speaker 2: heat tolerant strains, meaning it could better infect us. It
Speaker 2: might be more infectious in humans or also animals like
Speaker 2: our pets or bats, enabling greater spread, or, in the
Speaker 2: case of bats, more harm on top of another fungal
Speaker 2: pathogen that they're currently dealing with, white nose syndrome. So
Speaker 2: what will the impact be We don't know.
Speaker 3: Time will tell, Time will tell.
Speaker 2: Will increasing construction and land use change affect exposure to
Speaker 2: this pathogen? Seems pretty likely.
Speaker 3: I'm gonna go Yes, that's my that's where my money is.
Speaker 2: Yep. What we do know is that histoplasma will continue
Speaker 2: to change in the coming years due to human intervention.
Speaker 2: And I want to wrap up today by talking about
Speaker 2: this change not in terms of a hypothetical future, but
Speaker 2: as a hypothetical past. What might histoplasmosis have looked like
Speaker 2: one hundred and fifty or two hundred years ago, particularly
Speaker 2: in the region that we think of as classic Histo country,
Speaker 2: the Ohio and Mississippi River valleys. Why would it have
Speaker 2: been any different than today? My answer? Okay, the passenger
Speaker 2: pigeon stop also known as ectopiestis migratorius. Okay, Errent, do
Speaker 2: you know about the passenger pigeon?
Speaker 3: I mean, I know that they were saying that people
Speaker 3: used to send messages and.
Speaker 2: Things different different pigeon.
Speaker 3: Oh, that's a different pigeon.
Speaker 2: I think that's the carrier pigeon.
Speaker 3: Okay, So what the heck is the passenger pigeon?
Speaker 2: Okay, Oh, the passenger pigeon. This might be my first
Speaker 2: tattoo ever.
Speaker 3: Okay.
Speaker 2: The passenger pigeon was once the most numerous bird in
Speaker 2: North America, with an estimated population of five to ten
Speaker 2: billion with a bee was before European invasion three to
Speaker 2: five billion, after, which means that at one point there
Speaker 2: were more passenger pigeons than humans on the planet.
Speaker 3: Wow. Wow, Okay.
Speaker 2: Over the eighteenth and nineteenth centuries, the passenger pigeon steadily
Speaker 2: declined until the sole remaining member of the species Martha
Speaker 2: died in the Cincinnati Zoo on September one, nineteen fourteen.
Speaker 2: She was twenty nine years old. Oh wow, her passing
Speaker 2: marked the end of an era. Never again would flocks
Speaker 2: of these birds, tens of millions strong, blot out the
Speaker 2: sun as they flew in search of food. This extinction
Speaker 2: served as a wake up call and inspiration for the
Speaker 2: modern conservation movement. And while researching for this episode, I
Speaker 2: saw a passing reference to the passenger pigeon in a
Speaker 2: textbook called One Health and Mycology, where the author just
Speaker 2: kind of almost in a throwaway line, suggests that this
Speaker 2: bird drastically impacted histoplasmosis distribution across the United States, And
Speaker 2: I was like, uh, what so okay, So, since most
Speaker 2: histo outbreaks are associated with exposure to bird or bat excrement,
Speaker 2: the presence of billions of birds and the untold amounts
Speaker 2: of their poop could have driven the spread of histoplasmosis
Speaker 2: across the landscape, or at least provided the nutrients necessary
Speaker 2: for their growth.
Speaker 3: Yeah.
Speaker 2: I've always had a soft spot for the passenger pigeon.
Speaker 2: Growing up in northern Kentucky, we would often go to
Speaker 2: the Cincinnati Zoo, where there's a statue of Artha and
Speaker 2: an exhibit on the passenger pigeon, and it always like
Speaker 2: struck me as horribly said, and also somehow like another era,
Speaker 2: like it is another era, and it Yeah, I've always
Speaker 2: had a soft spot, I guess. So when I saw
Speaker 2: that mention in that book, I had to pull on
Speaker 2: that thread and I was like, okay, where do we
Speaker 2: go from here? So, just to just to prepare you,
Speaker 2: I did not find any conclusive evidence of linking the
Speaker 2: passenger pigeon to histoplasmosis, but I did find plenty that
Speaker 2: is suggestive of a connection. And so if that's all
Speaker 2: right with you, I thought I'd spend the last bit
Speaker 2: of time just going through some of these observations and
Speaker 2: really just like this is my time to pay tribute too.
Speaker 3: I'm most amazing species.
Speaker 2: Yes me too. I'm so glad we get tattoos together.
Speaker 3: Okay, I've been trying to get you to do that
Speaker 3: for a long time.
Speaker 2: I know I know that first one won't be TPWKY.
Speaker 2: I don't be the passenger pitch.
Speaker 3: I don't know if mine's going to be the passenger pigeon.
Speaker 3: But maybe you're going to convince you, right.
Speaker 2: Now your favorite species driven to extinction by humans? Okay, okay.
Speaker 2: The passenger pigeon could be found throughout the eastern half
Speaker 2: of North America, basically east of the Mississippi River, halfway
Speaker 2: north into Canada and halfway or halfway into Canada on
Speaker 2: the northern side, and halfway down Florida, but its breeding
Speaker 2: range was primarily across the Ohio River Valley in Great
Speaker 2: Lakes Region, Indiana, Ohio, Michigan, Wisconsin, Kentucky. If you look
Speaker 2: at a map of Histoplasmosa's outbreaks and passenger pigeon distribution,
Speaker 2: it is almost spot on, like the Van diagram is
Speaker 2: a circle kind of Okay. Correlation is not causation, and
Speaker 2: there could be many reasons for that overlap, just like, hey,
Speaker 2: the both things like the same environment, right exactly other
Speaker 2: environment and humid. Yeah, but it is compelling nonetheless, especially
Speaker 2: when you consider the poop.
Speaker 3: The poop.
Speaker 2: John James Audubon described what he saw in the eighteen
Speaker 2: twenties and eight teen thirties. Quote the dung lay several
Speaker 2: inches deep, covering the whole extent of the roosting place,
Speaker 2: like a bed of snow. Many trees two feet in diameter.
Speaker 2: I observed were broken off at no great distance from
Speaker 2: the ground, and the branches of many of the largest
Speaker 2: and tallest had given way, as if the forest had
Speaker 2: been swept by a tornado. End quote.
Speaker 3: Because of how many birds are sitting on there. Oh
Speaker 3: my gosh.
Speaker 2: Yeah. Yeah, it's like hard to fathom until you listen
Speaker 2: to some of these descriptions. Because there's another one, this
Speaker 2: is also from Audubon quote the air was literally filled
Speaker 2: with pigeons. The light of noonday was obscured as by
Speaker 2: an eclipse. The dung fell in spots, not unlike melting
Speaker 2: flakes of snow to have the sun obscured. Yeah, these
Speaker 2: flocks were millions strong. That's not a small amount of dung,
Speaker 2: which also could have provided excellent substrate for histoplasmos to
Speaker 2: grow hystell plasmosis that could have been misdiagnosed as tuberculosis,
Speaker 2: especially since the diagnostic technology for tb X rays and
Speaker 2: tuberculin skin tests was only developed in the last years
Speaker 2: of the bird's existence. Wow. Perhaps it's a coincidence that
Speaker 2: high tuberculosis mortality in the late eighteen hundreds was observed
Speaker 2: in the histoplasmosis corridor, which was also the passenger pigeon
Speaker 2: breeding grounds. Perhaps not. I wish I knew. I really
Speaker 2: wish I knew. And maybe if I had like another
Speaker 2: few weeks slash do a PhD on this, then I could.
Speaker 2: But yeah, I really do wish that the information was
Speaker 2: out there somewhere, right, But I did find again, going
Speaker 2: back to just a few compelling statistics. So during World
Speaker 2: War One, so nineteen fourteen, nineteen eighteen, twenty three percent
Speaker 2: of draftees in Kentucky were rejected due to tuberculosis. And
Speaker 2: that was compared to the national APPA bridge of nine percent.
Speaker 2: Oh wow, which is kind of interesting. It could be
Speaker 2: for many different things. Could many different things could be
Speaker 2: you know, but it could be hista, could be histo. Maybe.
Speaker 2: Alexander Wilson, the founder of American Ornithology, described a breeding
Speaker 2: site in Kentucky that was several miles wide and nearly
Speaker 2: forty miles long by his estimate. Quote in this tract,
Speaker 2: almost every tree was furnished with nests wherever the branches
Speaker 2: could accommodate them. Several people informed me that the noise
Speaker 2: in the woods was so great as to terrify their horses,
Speaker 2: and that it was difficult for one person to hear
Speaker 2: another speak without bawling in his ear. It was dangerous
Speaker 2: to walk under these flying and fluttering millions from the
Speaker 2: frequent fall of large branches broken down by the weight
Speaker 2: of the multitudes above, and which in their descent often
Speaker 2: destroyed numbers of the birds themselves, while the clothes of
Speaker 2: those engaged in traversing the woods were completely covered with
Speaker 2: the excrements of the pigeons.
Speaker 3: And wow, yeah, I cannot imagine this.
Speaker 2: Doesn't it seem like fantastical? Yes, but it was real.
Speaker 2: I mean like real. Some of this was exaggerated, no doubt,
Speaker 2: but like you can't not all of it because this
Speaker 2: is also many, many, many, many, many different accounts of
Speaker 2: how many birds there were.
Speaker 3: Birds there were.
Speaker 2: Yeah. Interestingly, in August nineteen eighty, just I was like, oh,
Speaker 2: this sounds like similar settings to what happened in this
Speaker 2: nineteen eighty histo plasmosis outbreak when a group of people
Speaker 2: were traveling through it was a cross country wagon train
Speaker 2: and in nineteen eighty it was ford like a troubled
Speaker 2: youth camp thing. Yeah, And they were traveling through eastern
Speaker 2: Kentucky and eighty one percent of the eighty five people
Speaker 2: on the train developed histoplasmosis after stopping on the site
Speaker 2: of a former blackbird roost. It is interesting, and it
Speaker 2: wasn't even that they were doing a lot of digging.
Speaker 2: It was simply just like setting tents up.
Speaker 3: Oh wow, yeah.
Speaker 2: Can you imagine traveling through a passenger pigeon roosting site
Speaker 2: tens of miles long, no, or even just standing beneath
Speaker 2: a flock as it passed overhead. I've got one last
Speaker 2: quote from Wilson, also in Kentucky. Quote Happening to go
Speaker 2: ashore one charming afternoon to purchase some milk at a
Speaker 2: house that stood near the river, and while talking with
Speaker 2: the people within doors, I was suddenly struck with astonishment
Speaker 2: at a loud, rushing roar, succeeded by instant darkness, which,
Speaker 2: on the first moment I took for a tornado about
Speaker 2: to overwhelm the house and everything around in destruction. The people,
Speaker 2: observing my surprise, coolly said it is only the pigeons,
Speaker 2: and on running out, I beheld a flock thirty or
Speaker 2: forty yards in width. These continued passing for more than
Speaker 2: a quarter of an hour end quote.
Speaker 3: Fifteen minutes of so many you thought it was right?
Speaker 2: Birds numerous enough to be mistaken for a tornado, whose
Speaker 2: excrement was inches deep in roosting sites, where roosting sites
Speaker 2: left their mark on the forest for years. Passenger pigeons
Speaker 2: were a force on this continent, and their decline and
Speaker 2: ultimate extinction was a shock, although it really shouldn't have been.
Speaker 2: Since Europeans landed in North America and began to cut
Speaker 2: down enormous forests to make way for pasture land, the
Speaker 2: birds began to drop in abundance. By the early eighteen hundreds,
Speaker 2: they still numbered in the billions, but population growth and
Speaker 2: deforestation over that century contributed to their annihilation, along with
Speaker 2: the introduction of species that competed for resources like pigs
Speaker 2: and the free for all hunting in which quote wagonloads
Speaker 2: of the young birds could be easily obtained and quote
Speaker 2: tens of thousands, even over one hundred thousand killed at
Speaker 2: just for sport, like they just were. Many of them
Speaker 2: would just rot because people could only a lot of
Speaker 2: people ate them for food. But this type of a
Speaker 2: thing was just like a free for all. It's this
Speaker 2: complete waste. Yeah. And it's possible that also as they
Speaker 2: declined and their strength in numbers could no longer protect
Speaker 2: them from predators, including humans. They just couldn't recover year
Speaker 2: after year. Conservation as a concept was still in its infancy,
Speaker 2: and no one thought to create a captive breeding program
Speaker 2: which could have preserved the species. But without adequate continuous
Speaker 2: forest it's doubtful that they could have ever recovered to
Speaker 2: their billion strong numbers. And there is some talk from
Speaker 2: the Resurrection Company with all the dire wolf like overhype,
Speaker 2: but again, I feel like those resources could be better
Speaker 2: spent on actual conservation efforts rather than implying that like, oh,
Speaker 2: it's fine if it goes extinct, we can always bring
Speaker 2: it back and guess what, this technology is proprietary, so
Speaker 2: good luck.
Speaker 3: Yeah. No, Jeff Goldblooms said it best, Okay.
Speaker 2: Like, yeah, that's a whole I could that's that's a
Speaker 2: soap box that I should probably just at this point.
Speaker 3: That's exactly how I feel.
Speaker 2: But when when passenger pigeons were made extinct, North America
Speaker 2: lost a major ecosystem engineer. These birds preferentially fell on
Speaker 2: mast from red oaks, and the forests where they roosted
Speaker 2: were filled with broken branches and twigs and trees, leading
Speaker 2: to more intense and frequent forest fires part of the
Speaker 2: natural you know, like cycle of forest fires. These two
Speaker 2: things favored white oaks, which are more fire resistant, And
Speaker 2: when the passenger pigeon went extinct, the forest of eastern
Speaker 2: North America shifted from white oak to red oak, which
Speaker 2: is just kind of an interesting gosh.
Speaker 3: I love this makes me just love ecology so much,
Speaker 3: Like who's to you know, Like it's like the story
Speaker 3: of the otters and the sea urchins and the kelp
Speaker 3: and the like. It's the same keystone.
Speaker 2: Species, keystone species. Everything is connected, and everything is connected
Speaker 2: it is. It is just amazing also how little people
Speaker 2: have heard, Like it's also amazing at all. Yeah, and
Speaker 2: it was just over one hundred years ago that Martha died.
Speaker 2: But also of interest, Forrest lost a major seed distributor
Speaker 2: and tree masted consumer as well. So like acorns, like
Speaker 2: all of the stuff, the seeds and stuff that trees,
Speaker 2: these trees produced, and that opened up a niche for
Speaker 2: competitors like deer and rodents in their populations, which may
Speaker 2: have contributed to the rise of lime disease passenger prision extinction. Man,
Speaker 2: it's all connected. Did the extinction of passenger pigeon also
Speaker 2: reduce histoplasmosis across the landscape. It's possible. I don't know.
Speaker 2: I mean all of this is that the links between
Speaker 2: Histo and the passenger pigeon is speculation on my part.
Speaker 2: I'm just trying to connect the dots across these historical
Speaker 2: accounts of a lost bird and our modern understanding of
Speaker 2: this fungal disease. The discovery of Histoplasma capsulatum occurred just
Speaker 2: eight years before Martha's death and nine years after the
Speaker 2: last passenger pigeon in the wild was killed. Histoplasmosis is
Speaker 2: a disease of abundance, and it's possible that some of
Speaker 2: this abundance can be attributed to this once abundant bird.
Speaker 2: I'm not sure we'll ever know the relationship between the two,
Speaker 2: but we can't afford to ignore the role that we
Speaker 2: humans play in the rise and fall of species. So
Speaker 2: with that, Aaron, I'll turn it over to you to
Speaker 2: tell me where we are with Histo today. Oh and
Speaker 2: also I wanted to mention I wore this sweater. This
Speaker 2: has birds on it. Can you see this bird over here?
Speaker 3: I can?
Speaker 2: My little guy so cute. In honor of the passenger pigeon.
Speaker 3: I don't even want to say anything. I just want
Speaker 3: to put it there, but I will only because I
Speaker 3: already wrote it down. So listen, right, wrap this up
Speaker 3: real quick here. Oh gosh, that was so much I'm
Speaker 3: like still reeling. So his applisis has been described as
Speaker 3: the most common endemic mycosis in the Americas, and the
Speaker 3: fungus itself has been reported, like you mentioned, Darin, across
Speaker 3: the United States, especially in the eastern half, especially in
Speaker 3: the Mississippi Ohio River valleys, but also throughout a large
Speaker 3: portion of Latin America, including Central and South America. It
Speaker 3: has been found in Central and western Africa though there
Speaker 3: and this is what I said at the very beginning,
Speaker 3: there's like different sort of subspecies or like variants, and
Speaker 3: so there's a little confusion over there. And it's been
Speaker 3: found across a lot of Asia as well. Truly, this
Speaker 3: is a global pathogen. The more that we look for it,
Speaker 3: the more that we find it. In the US, which
Speaker 3: is where we have probably the most data on incidents
Speaker 3: and prevalence, the estimated incidence overall is between one to
Speaker 3: two cases per one hundred thousand people. Okay, I don't
Speaker 3: know if that is the incidence of symptomatic infection, but
Speaker 3: I anticipate that it is. So that's how many symptomatic
Speaker 3: cases we expect, because, like we've said numerous times now,
Speaker 3: it's estimated that anywhere from sixty to ninety percent of
Speaker 3: people who live in areas of high histoplasma in the
Speaker 3: soil they show evidence of prior infection.
Speaker 2: Yeah, and in.
Speaker 3: The US, this disease is only reportable in like fourteen
Speaker 3: states in those areas that we know histoplasmosis is more common,
Speaker 3: so our data isn't great across the rest of the country.
Speaker 3: And that one to two cases per one hundred thousand
Speaker 3: is averaged across the whole country. So it is higher
Speaker 3: incidents in places like Kentucky, Ohio, et cetera, where this
Speaker 3: is more common, right right, Yeah, Yeah, And so then
Speaker 3: how do we, like, how many cases are there in
Speaker 3: the US across like each year. We don't. We really
Speaker 3: don't have good numbers. There was a paper I found
Speaker 3: that looked at like Medicare data over a nine year
Speaker 3: period from two thousand seven to twenty sixteen that said
Speaker 3: there were seventy nine or so thousand cases that were reported.
Speaker 3: These are all going to be symptomatic cases. Of course,
Speaker 3: and those are just the ones that are reported wow,
Speaker 3: because it's not it's not reportable only in fourteen states,
Speaker 3: only in fourteen states across. So this was looking at
Speaker 3: like medicare data, like hospital data and things like that.
Speaker 3: So where there was like a histoplasmosis, you know, case documented,
Speaker 3: But another paper suggested that there could be upwards of
Speaker 3: five hundred thousand new infections each year in the US.
Speaker 2: I saw that because, I mean that makes sense if
Speaker 2: you think about it.
Speaker 3: You think about the asymptomatic infections.
Speaker 2: Or the people who recover even though they're in they're
Speaker 2: diagnosed with bacteria.
Speaker 3: Exactly one hundred percent, So that's including all of that,
Speaker 3: like you know, self limited disease or asymptomatic disease. So
Speaker 3: it suggested that like over forty million people in the
Speaker 3: US at least have been infected, and that's probably an underestimate.
Speaker 3: That is, it's like son so so common, and like
Speaker 3: I said, the more places that we look for it,
Speaker 3: the more places that we find it. In Central and
Speaker 3: South America there are cases reported year after year. We're
Speaker 3: seeing more and more case reports across Asia, especially in
Speaker 3: the Yanksee River Valley in China River valley for my
Speaker 3: pronunciation there, yeah, river valleys. But there's also been case
Speaker 3: reports in Thailand and South Korea and India. In Africa,
Speaker 3: it's been reported in Uganda, Tanzania, and South Africa. And
Speaker 3: one of the things that we talked about is the
Speaker 3: impact of this disease on people who are immunal compromised,
Speaker 3: especially in people living with HIV, especially in areas that
Speaker 3: lack access to either diagnosis and or treatment for HIV,
Speaker 3: especially in places where there's a lot of stigma associated
Speaker 3: with HIV still. So there are a number of papers
Speaker 3: out there that are looking at histoplasmosis specifically in people
Speaker 3: living with HIV, and one of the places that they're
Speaker 3: doing a lot of research on this is in Brazil.
Speaker 3: And in some cases, not only is the case fatality
Speaker 3: rate of histoplasmosis so high in people living with HIV,
Speaker 3: but there's estimates that the mortality rates in people living
Speaker 3: with HIV with histoplasmosis are equivalent to, if not exceeding,
Speaker 3: the mortality due to tuberculosis.
Speaker 2: That's oh my god, I know.
Speaker 3: So this is a hugely impactful disease, Like it is
Speaker 3: way more widespread and it is a much bigger concern
Speaker 3: certainly than I really totally, and with more and more
Speaker 3: people being put on medications like these TNF alpha inhibitors,
Speaker 3: And that's just one example, but there's a lot of
Speaker 3: like strong association between those types of drugs and fungal
Speaker 3: infections like histoplasmosis specifically, but those among other drugs that
Speaker 3: cause immunal compromise and immune suppression. Our understanding of histoplasmosis
Speaker 3: is more important than ever, right, that we're able to
Speaker 3: diagnose it, that we have access to a beoutur treatments,
Speaker 3: which we don't right now, like our treatments are ancient
Speaker 3: and not great great, Yeah, And like you mentioned, we
Speaker 3: might not have a current day passenger pigeon situation, but
Speaker 3: given how much land use change is happening, how rapid
Speaker 3: land use change is happening in places, the effects of
Speaker 3: climate change on fungal pathogens broadly, including histoplasmosis, like this
Speaker 3: is very likely to only continue to increase histoplasmos absolutely,
Speaker 3: So that's what I got.
Speaker 2: We should be talking more about it, We.
Speaker 3: Should be talking more about it, We should be talking
Speaker 3: more about it and.
Speaker 2: About the passenger pigeon. But that's my personal, my personal,
Speaker 2: Like I.
Speaker 3: Need to look up like images of the passenger pic.
Speaker 2: They're really like, I mean, it's certainly pigeon like, but
Speaker 2: it's it's I think it's quite beautiful. And there was
Speaker 2: a strong amount of sexual dimorphism, which not all pigeons
Speaker 2: have anyway.
Speaker 3: So cute. I love. That's my favorite thing I've learned.
Speaker 3: If you want to learn more, we'll tell you.
Speaker 2: We have. I have, Like I said, I really because
Speaker 2: of the rabbit hole pigeonhole. Again, you're showing how loo
Speaker 2: your bar.
Speaker 3: For jokes is sarin. I'm in a good mood, I guess.
Speaker 2: But the I have so many sources because I was like,
Speaker 2: and what about this one? About this? So anyway, let
Speaker 2: me take you through a couple on histo. There's a
Speaker 2: paper from nineteen fifty seven by Schwartz and Baum called
Speaker 2: the History of Histoplasmosis nineteen oh six to nineteen fifty six.
Speaker 2: It was a great sort of primer on like what
Speaker 2: people have discovered and where are we from here? From
Speaker 2: twenty twenty two by Taylor at All Considerations about the
Speaker 2: geographic distribution of Histoplasma species.
Speaker 3: Yeah, saw that one.
Speaker 2: And then if you would like to read about the
Speaker 2: Passenger pigeon. I read a book called A Message from
Speaker 2: Martha by Mark Avery. But there's there's like a number
Speaker 2: of passenger pigeon books out there. And I have a
Speaker 2: couple of papers about the genome anyway, it's it's And
Speaker 2: did I find one about its diet? I did find
Speaker 2: one about its diet. Yeah, anyway, gohead.
Speaker 3: So I had a number of papers as well, just
Speaker 3: a few that I'm going to shout out here that
Speaker 3: were really good overviews of histoplasmosis itself. One was by
Speaker 3: Linda and Kaufman from twenty nineteen in Current Fungal Infection
Speaker 3: Reports called Hytoplasmosis, Epidimology, Diagnosis and Clinical Manifestations. Another from
Speaker 3: twenty twenty four by Gandhi at All that was called
Speaker 3: Histoplasmosis Around the World, A Global Perspective on the presentation runs,
Speaker 3: Factors and Treatment of Hytoplasmosis. There's too many, and they're
Speaker 3: all just like really long titles. There's a whole bunch there, Okay.
Speaker 3: I had an interesting one that was comparing histoplasmosis to blastomycosis.
Speaker 3: So if you want more details on those the similarities
Speaker 3: and differences, we got them all on our website. This
Speaker 3: podcast wikill you dot com. Right under the episodes tab
Speaker 3: you can find the list of sources from this and
Speaker 3: every single one of our many episodes.
Speaker 2: Many episodes. Yeah, thank you again so much, Masie for
Speaker 2: sharing your story with us. We really appreciate it.
Speaker 3: We do.
Speaker 2: Thank you.
Speaker 3: Thank you.
Speaker 2: Thank you also to Bloodmobile for providing the music for
Speaker 2: this episode and all of our episodes.
Speaker 3: Thank you to Leanna and Tom and Pete and Mark
Speaker 3: and everyone at exactly Right for everything that you do.
Speaker 2: Thank you, thank you, and thank you to you listeners.
Speaker 2: If you find more info about the passenger pigeon and
Speaker 2: Histo or refuting the link, or things you want to
Speaker 2: know more about or whatever, let us know what you think.
Speaker 2: We all or you to know.
Speaker 3: If you already have a tattoo of a passenger pigeon,
Speaker 3: can you send it so that Aaron can get some inspouse.
Speaker 2: Please please, it's going to be that Tasmanian tiger.
Speaker 1: Oh.
Speaker 3: I love it. That's so cute. And as always, a
Speaker 3: special shout out to our patrons. Thank you so much
Speaker 3: for your support. It really does mean it really does
Speaker 3: mean a lot to us.
Speaker 2: It really does. It means so much to us. Thank you.
Speaker 2: Until next time wash your hands
Speaker 3: You feelthy animals.