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