Speaker 1: The case was under the care of doctor During in Philadelphia,
Speaker 1: by whom it was diagnosed clinically as a typical example
Speaker 1: of chronic scrophuloderma. By his courtesy, I received a portion
Speaker 1: of the disease tissues, but was unable to demonstrate the
Speaker 1: presence in it of the tubercule bacillus. In the course
Speaker 1: of the examination, however, numerous curious bodies were found, distributed
Speaker 1: here and there throughout all the sections. They presented the
Speaker 1: appearance of parasites and the discovery rendered the case one
Speaker 1: of peculiar interest. Unfortunately, the matter could not be followed
Speaker 1: out as closely as could have been desired, as no
Speaker 1: more material could be obtained, the patient having been operated
Speaker 1: upon and the whole lesion having been removed. Three months
Speaker 1: after our first brief report, Otto Bousse published a case
Speaker 1: in which apparently similar bodies were demonstrated. Still later, other
Speaker 1: observers have found lesions in animals, horse, guinea pigs, etc.
Speaker 1: In Which very similar bodies have played a pathogenic role,
Speaker 1: but the present appears to be the first recorded case
Speaker 1: in which they have given rise to pathological processes in man.
Speaker 1: In reporting the case before the American Dermatological Society. I
Speaker 1: expressed the opinion that these bodies, in all probability would
Speaker 1: be found to belong to plant rather than to animal life,
Speaker 1: and further examination appeared to verify the conclusion that they
Speaker 1: might be classed as blastomycedes.
Speaker 2: I'm so curious to see where they went after that, I.
Speaker 1: Mean, blastamycosis. Maybe they named They named it eventually. So
Speaker 1: that is from TC Gilcrest eighteen ninety six in a
Speaker 1: report titled a Case of Blastomycetic Dermatitis in Man and
Speaker 1: it was.
Speaker 2: The first.
Speaker 1: Description clinical description of what we now know is blastomycosis.
Speaker 2: I love it.
Speaker 1: Yeah, you know, just go to the OG source.
Speaker 2: Straight to the source, why not. Yeah.
Speaker 1: Hi, I'm Aaron Welsh and I'm Erin allman up and
Speaker 1: this is this podcast will kill you today.
Speaker 2: We're talking fungus.
Speaker 1: We are uh huh. We haven't done this often, not
Speaker 1: in a while.
Speaker 2: Yeah.
Speaker 1: Yeah, I'm excited by that, me too.
Speaker 2: It's gonna be a good one.
Speaker 1: And I think that blastomycosis is strange. And I am
Speaker 1: especially curious about the current research.
Speaker 2: Oh yeah, yeah, me too. I am excited about it
Speaker 2: because we don't yeah, we haven't covered a lot of
Speaker 2: fung guy, I don't feel like they get enough attention.
Speaker 1: They don't, and many papers that I read started out
Speaker 1: that way. Yeah, medical micology is an overlooked field. It
Speaker 1: really is, despite the large burden of disease that agree,
Speaker 1: pathogenic fungi, whatever, et cetera.
Speaker 2: So let's just fill in that etcetera today, shall we hear?
Speaker 2: Let's do it, but first, it's quarantiney time.
Speaker 1: Yes, yes, yes, my favorite time. What are we drinking
Speaker 1: this week?
Speaker 2: We're drinking Blast from the Past.
Speaker 1: I mean, you know, there were so many Quarantini name
Speaker 1: options with this one blast. I'm sure that our title
Speaker 1: will have Blast in it at some point or another.
Speaker 2: We'll find out.
Speaker 1: Yeah, but I like blash in the past too, because,
Speaker 1: as you'll hear in the history section, I'm going kind
Speaker 1: of way way, way way back.
Speaker 2: I love it and I'm excited about it. Are we
Speaker 2: going in deep time again? Aaron?
Speaker 1: I don't know what the exact definition of deep time is,
Speaker 1: but it feels pretty deep. Okay, let's get into the recipe.
Speaker 2: Sow. Oh yeah, I really do. Un what's been a
Speaker 2: blast to the past, Aarin? It is so delicious.
Speaker 1: It's kind of a take on like a bourbon smash,
Speaker 1: but instead of bourbon, it's right whiskey, and we're doing
Speaker 1: peaches and ginger beer of course, lemon juice and basil.
Speaker 1: Oh so ym it's really refreshing and delightful.
Speaker 2: You can find the full recipe for that quarantine and
Speaker 2: our non alcoholic plusy Brita on our website, this podcast
Speaker 2: with Killy dot com, and our social media.
Speaker 1: Now for website stuff, there's lots of things. I have
Speaker 1: the website right here, fortunately, so let's just go through
Speaker 1: some of these tabs. Well, we've got the sources for
Speaker 1: each and every one of our episodes. We've got links
Speaker 1: to our bookshop dot org, affiliate account, our Goodreads list,
Speaker 1: our merch some pretty sweet merch there. We've got links
Speaker 1: to music by Bloodmobile, Patreon, submit your first hand account, form, transcripts,
Speaker 1: and stuff about us that we probably should update.
Speaker 2: We probably should actually yeah someday. Okay, then any other
Speaker 2: business that we should deal with.
Speaker 1: I don't think so. I think that we should just
Speaker 1: dive right into the episode.
Speaker 2: Okay, let's take a quick break and get into it.
Speaker 2: Blastomycosis is the name of the disease caused by the
Speaker 2: fungus blastomics dermatitidis, which I looked up how to say,
Speaker 2: like a hundred times, so hopefully that's right.
Speaker 1: I mean the spelling of it. I was like, this
Speaker 1: must be a typo. I kept being like, there are
Speaker 1: way too many eyes and teas.
Speaker 2: And your eyes and t's and d's and eyes blastomics dermatititis.
Speaker 2: The other major species is Blastomyces gilchristii, which you said
Speaker 2: that that first hand account came from doctor Gilchrist himself.
Speaker 2: Sure did, Okay, there's a story there, history over, and
Speaker 2: blastomycosis is a disease of so much more than just humans.
Speaker 2: This is a fungus that has been found causing disease
Speaker 2: and death in humans, but also canids, including wolves and coyotes.
Speaker 2: And from what I read, it's estimated that in like
Speaker 2: our domestic dogs, infection rates are likely eight to ten
Speaker 2: times higher than what they are in humans, so we'll
Speaker 2: come back to that eventually, but also in sea lions, dolphins, ferrets, lions, bears, lemurs, bats.
Speaker 2: This thing has been around the block.
Speaker 1: It's fascinating. I was gonna say it's cool, but.
Speaker 2: Like ooh ooh, interesting choice of words, because it's a
Speaker 2: thermally dimorphic fungus.
Speaker 1: Which I had to look up what that was. Yeah,
Speaker 1: and now I'm like, there's a whole world of these
Speaker 1: Why did this evolve?
Speaker 2: This is fascin So this is a characteristic of some
Speaker 2: of the fungi in the phylum Askomycoda, And this basically
Speaker 2: means that these fungi exist in different states or different forms,
Speaker 2: depending on the temperature, the ambient temperature and other factors
Speaker 2: as well. But in the environment, Blastomyces exists as a
Speaker 2: mold like the mold on your bread or your cheese,
Speaker 2: kind of if you looked at it under the microscope,
Speaker 2: it would have these long filaments that are called hyphi.
Speaker 2: And this form, this mold form reproduces asexually by making
Speaker 2: these things called canidia, which are spores that can go
Speaker 2: out and disperse long distances. The way that we get
Speaker 2: exposed to Blastomyces is via these spores, the canidia, sometimes
Speaker 2: directly from the high fee if like little bits get
Speaker 2: broken off and we inhale them when they're aerosolized with
Speaker 2: soil particles, or less commonly, we can get inoculated with
Speaker 2: the spores or the high feet in our skin. If
Speaker 2: we get a scratch from say like a plant or
Speaker 2: something ooh. And then what happens is that we humans
Speaker 2: are generally much warmer than soil, and in the warm,
Speaker 2: wet gooiness that is our body environment, this fungus transforms
Speaker 2: into a budding yeast, yeast being a unicellular type of
Speaker 2: fungus like the kind that you make bread with, except
Speaker 2: it's not at all like your bread yeast, and so
Speaker 2: that's what it means to be dimorphic. It has this
Speaker 2: yeast form that exists inside of us or inside of
Speaker 2: ho ghosts at higher temperatures, and a mold form that
Speaker 2: exists in the environment. Coxidioidomycosis that we covered on this
Speaker 2: podcast is also thermally dimorphic.
Speaker 1: Great pronunciation, thank you.
Speaker 2: I practice, as is histoplasmosis, which I'm sure will cover eventually.
Speaker 2: And it turns out quite a lot of fungi of
Speaker 2: medical importance are thermally dimorphic. And it's not only temperature
Speaker 2: that triggers this dimorphism. It's also things like how much
Speaker 2: carbon dioxide they're exposed to, which of course is much
Speaker 2: higher in our lungs than in our air. So once
Speaker 2: we inhale these spores and they're inside of us, they
Speaker 2: get eaten up by macrophages, which again are one of
Speaker 2: our white blood cells that are good at gobbling things
Speaker 2: that don't belong in us. And then they do this
Speaker 2: transform in to yeast thing and start butting as a
Speaker 2: yeast does in order to make more of itself. That's
Speaker 2: the way that it reproduces. And what's so fascinating is
Speaker 2: that in this process, during this transformation into yeast, what
Speaker 2: this fungus starts to do is up regulate all of
Speaker 2: these genes that, like, why do they have these genes?
Speaker 2: These genes that are specifically good at evading our immune system.
Speaker 2: So these are things like adhesions and calcium binding proteins
Speaker 2: and outer wall glycoproteins, all of these boring names of
Speaker 2: things that basically help this yeast stick to our cells
Speaker 2: and actively evade our immune defenses. Uh huh, it's amazing,
Speaker 2: it's so cool. So all of these genes are doing
Speaker 2: things like inhibiting major cytokines that we use in our
Speaker 2: defense like TNF alpha, we'll come back to it, and
Speaker 2: inhibiting the activation of our t lymphocytes. Like it's it's
Speaker 2: incredible what this yeast, this fungus is able to do. Yeah,
Speaker 2: and when they do this. On top of all of that,
Speaker 2: they also have to rearrange all of their cell walls,
Speaker 2: and in doing this, in this transformation from hyphi to yeast,
Speaker 2: it's yet another way to further confuse our immune system
Speaker 2: and make it harder to block this infection.
Speaker 1: You know, Okay, I love this and I can't like
Speaker 1: This ties in so well with what I'm.
Speaker 2: Going to be talking about. Yeah, I'm excited about it.
Speaker 2: I'm excited. Good, we too.
Speaker 1: We feel like this is going to be much more
Speaker 1: of a mind blowing episode, I hope, or at least
Speaker 1: it was for me, and it is right now in
Speaker 1: hearing you talk about it. Oh, good than I ever
Speaker 1: thought a fungal infection could be.
Speaker 2: I can't now, I'm like even more excited for the
Speaker 2: history section. Wow. But so, that is one of the
Speaker 2: things that makes blastomycosis specifically not considered just an opportunistic infection.
Speaker 2: A lot of fungal infections we think of as mostly
Speaker 2: being a problem for people who have various degrees of
Speaker 2: immunal compromise, and it's definitely true that for people with
Speaker 2: things like deficiencies in their T cell function, for example,
Speaker 2: in advanced HIV or AIDS, or people who are maybe
Speaker 2: on TNF alpha inhibitors, that important cytokine, those people are
Speaker 2: potentially at much higher risk of severe infection. But this
Speaker 2: is a fungus that can infect all of us da dadoo.
Speaker 2: So it's fascinating. It turns out that it's about fifty
Speaker 2: to fifty whether you actually are going to have symptoms
Speaker 2: from exposure to Blastomyces. Okay, and that is a little
Speaker 2: more than I expected for a fungus.
Speaker 1: Yeah, Like, how has that number been calculated with? Like,
Speaker 1: is it just from known outbreaks or known exposures?
Speaker 2: I think so, good question. Okay, Yeah, my guess is yes,
Speaker 2: it's from like various studies where they've tried to actually
Speaker 2: look at you have an outbreak, and then you try
Speaker 2: and look at a larger population. How many people do
Speaker 2: you find infected that never had symptoms? Right?
Speaker 1: Who who might have been at the pond near the
Speaker 1: rotting wood that day?
Speaker 2: Also exactly? And when it comes to symptoms, there are
Speaker 2: two main classes of symptoms. There's pulmonary and there's extra
Speaker 2: pulmonary aka everywhere else in your body. And like many
Speaker 2: fungal infections, this is a slow growing pathogen. Symptoms can
Speaker 2: take anywhere from three weeks to three months or more
Speaker 2: to develop after exposure.
Speaker 1: Okay, So I have a question, uh huh, because from
Speaker 1: and maybe this is just because I was reading older papers,
Speaker 1: but I thought that the environmental sources of Blastomyce's dermatititis
Speaker 1: is not they haven't been super well characterized and it's
Speaker 1: not reliably isolated from the environment. So how you know
Speaker 1: if an exposure was three weeks ago or three months ago.
Speaker 2: That's such a good question, especially if you're living in
Speaker 2: an endemic area. Right, I don't think we know, Okay,
Speaker 2: because also three weeks and three months is a very
Speaker 2: wide range. Yeah, it's very wide. So is the range
Speaker 2: really that wide or do we just not know that? Well?
Speaker 1: Right, it's like, well, I think three months ago, I
Speaker 1: guess I went camping there. But right, that's but maybe
Speaker 1: you forgot about something that was not camping that could
Speaker 1: have been an exposure.
Speaker 2: Okay, And maybe we have slightly better data from people
Speaker 2: who go to an endemic area and become exposed and
Speaker 2: then leave that endemic area and then have symptoms later. Okay,
Speaker 2: But yeah, you're right, a lot of this is a
Speaker 2: little bit messy. As you'll see, we don't have the answers.
Speaker 1: We're so not used to that on this podcast.
Speaker 2: It's never happened before. Oh yeah, So let's get into
Speaker 2: what this disease looks like when people are symptomatic. So
Speaker 2: for those fifty percent of people who are going to
Speaker 2: show some kind of symptoms, over eighty percent will have
Speaker 2: some type of pulmonary infection because again, most of the
Speaker 2: time we're being exposed by inhaling spores or inhaling hyphie.
Speaker 2: But even this pulmonary infection can be very broad in
Speaker 2: terms of symptoms. For some people it's a relatively minor pneumonia,
Speaker 2: for others, it can be as severe as acute respiratory
Speaker 2: distress syndrome that can lead to death. So in the
Speaker 2: case of more mild infections, like just a run of
Speaker 2: the mill pneumonia, we're looking at things like fevers. You
Speaker 2: might have chills, a cough, some difficulty breathing, chest pain.
Speaker 2: These are symptoms that are easy to confuse with any
Speaker 2: other kind of community acquired pneumonia, And when we look
Speaker 2: at an X ray, it's usually pretty indistinguishable from that
Speaker 2: perspective as well from any other bacterial cause there's nothing
Speaker 2: that makes a Blastomyce's pneumonia stand out necessarily, and that
Speaker 2: is one of the first problems, right, because that's going
Speaker 2: to make it a lot harder to diagnose. And so
Speaker 2: because of this, a relatively minor pneumonia can easily progress
Speaker 2: to a chronic pneumonia that just kind of persists because
Speaker 2: it's not going to be treated with whatever antibiotics somebody
Speaker 2: might take, or it can progress to an acute reread
Speaker 2: inspiratory distress syndrome or ards.
Speaker 1: And can it spontaneously resolve.
Speaker 2: It's a good question. I don't know, Okay, yeah, So
Speaker 2: on the chronic end of things, it could certainly be
Speaker 2: very mild symptoms for a long time. This is something
Speaker 2: that can mimic tuberculosis or even lung cancer, and so
Speaker 2: a lot of times those diseases might have very long
Speaker 2: periods where the symptoms are mild enough that people might not,
Speaker 2: you know, seek care in that way, or maybe not
Speaker 2: have access to care. But I didn't read anything about
Speaker 2: like spontaneous resolution necessarily. Okay, if you progress to the
Speaker 2: point where you're having symptoms, right, yeah, okay, yeah, it's
Speaker 2: a good question. But yeah, so in a chronic infection,
Speaker 2: people might have night sweats, they might have some weight loss,
Speaker 2: a persistent cough. They might even progress to coughing up
Speaker 2: blood or hemoptosis. But again, even in this case, the
Speaker 2: X ray findings are not very specific. They can look
Speaker 2: like cancer, they could look like tuberculosis. So unless somebody
Speaker 2: has a very clear risk factor like working construction in
Speaker 2: the Ohio River Valley or something like that, or the
Speaker 2: diagnostic team thinks to check for blastomycosis, which is more
Speaker 2: likely to happen in an endemic area than in a
Speaker 2: place where blastomycosis doesn't exist, it might take months before
Speaker 2: the correct diagnosis is reached in those cases. But the
Speaker 2: scary part is if it progresses to acute respiratory distress syndrome,
Speaker 2: and this is something that can happen even just after
Speaker 2: an acute pneumonia, within a few weeks, and has the
Speaker 2: potential for a greater than fifty percent mortality rate even
Speaker 2: with treatment. I think even with treatment, because it can
Speaker 2: be so rapid if it progresses in this direction, not
Speaker 2: a fifty percent mortality rate for just a chronic infection,
Speaker 2: but if it gets to the point where you basically
Speaker 2: have your lungs filling up with fluid because of how
Speaker 2: much inflammation there is. Then yes, it's a fifty percent
Speaker 2: mortality rate because, as we'll see, treatment for fungal infections
Speaker 2: in general and blastomycosis specifically is really prolonged. It takes
Speaker 2: months and months of antifungal treatment to clear this infection.
Speaker 2: So that's the kind of pulmonary syndrome of blasteromycosis. But
Speaker 2: of course this fungus is among us. I was really
Speaker 2: trying to throw that in there. Some whort is very
Speaker 2: well shoehorn in right there. Thank you, just made it work.
Speaker 2: It's not limited to our lungs because once these blastomyces
Speaker 2: transform into their yeast form, our bodies have a really
Speaker 2: hard time doing anything about them, and so then they
Speaker 2: can just disseminate either through our blood stream or through
Speaker 2: our lymphatics and just cause disease theoretically anywhere, but there's
Speaker 2: a few places that tend to be the most common.
Speaker 2: So the second most common place of infection outside of
Speaker 2: the lungs is the skin. Forty to eighty percent of
Speaker 2: people that have disseminated disease, So any disease outside of
Speaker 2: the lungs have some type of skin manifestation, and these
Speaker 2: can vary a lot in what they look like, but
Speaker 2: they're often fairly gnarly. They can look like these like nodules.
Speaker 2: Sometimes it's like a purplish nodule, or like a plaque,
Speaker 2: which is like a large, several centimeter wide kind of
Speaker 2: circle raised on your skin that can progress to like
Speaker 2: an ulcer or even an abscess, and they can continue
Speaker 2: to progress to these very large, necrotic or completely dead
Speaker 2: tissue usions that can lead to permanent scarring if they're
Speaker 2: not treated nice. Yeah. And after skin, the second most
Speaker 2: common sight of dissemination is our bones. And this can
Speaker 2: happen either directly from a skin infection that then just
Speaker 2: kind of makes its way into the bone, or it
Speaker 2: can just go from your lungs straight to the bone
Speaker 2: through your bloodstream.
Speaker 1: How does something go into our bones?
Speaker 2: Oh? I mean lots of infections can go into your bones.
Speaker 2: Your bones are a living things.
Speaker 1: I remember, was it tuberculosis episode? I can't remember, but
Speaker 1: that sounds right. Why? How?
Speaker 2: Yeah? Well why I think why is a more interesting
Speaker 2: question than how, because how it's just like, oh, it's
Speaker 2: our bloodstream, but why, like why is it so good
Speaker 2: at getting into our bones when other infections aren't exactly
Speaker 2: I don't know. It's a good question, though, Wow, but
Speaker 2: this is not uncommon. About five to twenty five percent
Speaker 2: of cases of disseminated blastomycosis can cause an osteomyelitis. And
Speaker 2: then this, once it's in the bone, can then extend
Speaker 2: into our joints or into the soft tissues like muscles
Speaker 2: and ligaments and result in a septic arthritis or deep
Speaker 2: deep abscesses.
Speaker 1: So the lesions are an indication of disseminated disease regardless
Speaker 1: of whether it's just one lesion or lesions all over
Speaker 1: your body.
Speaker 2: Excellent question. Most of the time. Yes, it is possible
Speaker 2: to have just a skin infection if you got exposed
Speaker 2: via inoculation in the skin, that is possible, but it's
Speaker 2: much less common because pulmonary infection is so much more common. Overall,
Speaker 2: it's more likely that there was a pulmonary infection that
Speaker 2: made it through the bloodstream and then made it to
Speaker 2: the skin, even if there's only one skin lesion. Okay, yeah, yeah,
Speaker 2: it's a good question. Beyond our skin and our bones,
Speaker 2: the two other places that are most common, And again,
Speaker 2: why such a good question, I don't know. But the
Speaker 2: two other places that are most common to see blastomycosis.
Speaker 2: Infections are the genito urinary tract, and this means any part.
Speaker 2: It can be an epididymitis, it can be a prostatitis,
Speaker 2: it can be an endometritis, it can be cystitis, which
Speaker 2: is your bladder. So this is just literally any organ
Speaker 2: involved in the genitourinary system. And then there is the
Speaker 2: central nervous system infection, so that's brain and spinal cord.
Speaker 2: And this can happen either from bloodborne spread crossing over
Speaker 2: that blood brain barrier, or from an osteomylitis so a
Speaker 2: bone infection in the skull that then progresses. Sorry, your
Speaker 2: face does not like that muntal image, I know. And
Speaker 2: as with many infections that we've talked about that can
Speaker 2: infect our brain or our spinal cord, the symptoms here
Speaker 2: can really range. They can be a headache, they can
Speaker 2: be confusion, they could be any range of neurologic deficits
Speaker 2: like seizures or visual disturbances. It's a really really wide
Speaker 2: range of potential nervous system symptoms.
Speaker 1: These different roots that a disseminated infection can take may
Speaker 1: or may not be affected by anti fungals, like whether
Speaker 1: or not it progresses to central nervous system involvement. Can
Speaker 1: you stop that? Or is it like, oh, we didn't
Speaker 1: know what this infection was. Suddenly now there's central nervous
Speaker 1: system involvement. Someone goes to the doctor and they're like, well.
Speaker 2: Yeah, that's a good question. I don't have like an
Speaker 2: exact answer for you. I can say that overall, the
Speaker 2: case fatality rate based on studies in hyperendemic regions is
Speaker 2: about four to six percent, and most of those likely
Speaker 2: had pretty severe infection, either widely disseminated in multiple organs
Speaker 2: or a central nervous system infection, or just a very
Speaker 2: bad ards or acute respiratory distress syndrome. It's not that
Speaker 2: it's impossible to treat if it's a disseminated infection. It's
Speaker 2: just that this is a difficult pathogen to treat regardless
Speaker 2: of where the infection is. So if it's already disseminated,
Speaker 2: you're likely dealing with a much larger fungal load that
Speaker 2: you have to deal with, right and the drugs that
Speaker 2: we use to treat fungal infections, namely amphotericin B. If
Speaker 2: it's a especially if it's a severe infection or various
Speaker 2: forms of connaisols like intriconoisol. These are not drugs without
Speaker 2: their own sets of risks. They can be pretty hard
Speaker 2: on the liver, pretty hard on the kidneys, have a
Speaker 2: lot of drug drug interactions. So, yeah, this is a
Speaker 2: disease that's difficult to diagnose and then difficult to treat,
Speaker 2: especially depending on how severe it's gotten to begin with. Yeah. Yeah,
Speaker 2: And while this is a disease that can infect and
Speaker 2: does infect immunal competent people, people with a fully functional
Speaker 2: immune system, in people with various degrees of immunal compromise,
Speaker 2: the risk of severe infection and the mortality rate can
Speaker 2: be significantly higher, in some cases, as high as forty
Speaker 2: percent in people with poorly controlled HIV or AIDS, or
Speaker 2: people with a history of a solid organ transplant who
Speaker 2: are often on a lot of immunosuppressive medications. So that's
Speaker 2: the biology eron of blastomycosis. It's this is a scary
Speaker 2: I think one of the things that makes fungal infections
Speaker 2: the most scary to me personally is how difficult they
Speaker 2: are to diagnose early mm.
Speaker 1: HM and how little we seem to know about their
Speaker 1: inner workings.
Speaker 2: Right, Yeah, yeah, because, Yeah, the early infection is usually
Speaker 2: pulmonary and usually looks like pneumonia until somebody gets really sick.
Speaker 1: And so this was sort of I guess going back
Speaker 1: to that question about pneumonia. Let's say that you are
Speaker 1: feeling sick, you think you might have pneumonia, you go
Speaker 1: to the doctor. What are the next things that happen?
Speaker 1: And then when is their exhaustive testing? Like do people
Speaker 1: test until they find a pathogen or until someone gets better?
Speaker 2: Ooh, that's like a question about the whole American healthcare system,
Speaker 2: isn't it. I have no pressure. I mean, it's going
Speaker 2: to really depend I also, I'm thinking more about your
Speaker 2: question that you asked on could you clear this infection
Speaker 2: on your own? And I feel like the answer has
Speaker 2: to be yes for some people because these case fatality
Speaker 2: rates in studies that we see are four to six percent.
Speaker 2: Presumably what we know of how many people get infected
Speaker 2: is likely a great underestimate. So presumably, yes, there are
Speaker 2: people who get infected, maybe even get treated with antibiotics
Speaker 2: that don't do anything for their fungal infection, but then
Speaker 2: they slowly get better and in fact their body took
Speaker 2: care of the blastomycosis infection itself, presumably, I guess. But
Speaker 2: to answer your actual question, are we testing for this,
Speaker 2: It really really is going to depend. It's going to
Speaker 2: depend on what part In the United States at least,
Speaker 2: which is where the vast majority of cases of blastomycosis
Speaker 2: are spoilers for the epidemiology section, it's going to depend
Speaker 2: on what part you live in. If you live somewhere
Speaker 2: where this is a known endemic disease, it's more likely
Speaker 2: that if someone is not getting better with normal antibiotics,
Speaker 2: that they're going to test for this infection. It's less
Speaker 2: likely perhaps in other areas. I think the biggest thing
Speaker 2: that will improve detection overall is more and more PCR
Speaker 2: based testing, because in any kind of PCR based testing,
Speaker 2: you can test for a whole bunch of different pathogens
Speaker 2: all at once. Right right now, it's mostly culture that's
Speaker 2: still the gold standard, and that takes potentially weeks to
Speaker 2: be able to grow this fungus in culture. There are
Speaker 2: urine tests that we can do, like we do for legionella,
Speaker 2: that look for the antigen like that look for various
Speaker 2: antigens of blastomyces, but those are imperfect tests as well,
Speaker 2: so Yeah, it really just depends on how sick somebody is,
Speaker 2: on where they are, on how much access they have
Speaker 2: to what kind of healthcare system, and how much people
Speaker 2: are thinking fungal infections versus not, et cetera.
Speaker 1: It is Yeah, this one is more intense than I
Speaker 1: thought it would be.
Speaker 2: It really is, isn't it. Yeah, So, Aarin, where did
Speaker 2: this fungus come from?
Speaker 1: Yeah, let's take a quick break and it all.
Speaker 2: I'll get into something.
Speaker 1: Okay, Arin, this is our one hundred and twenty fifth episode.
Speaker 1: Oh I didn't know that regular season episode. Oh, not
Speaker 1: including COVID or bonus episodes.
Speaker 2: Or anything like that.
Speaker 1: Okay, Yeah, first of all, congratulations.
Speaker 2: To us, Oh, pats on the back.
Speaker 1: But yet somehow I tallied it up. This is only
Speaker 1: the second fungal pathogen of humans that we've covered, right.
Speaker 2: We did coxidioid on mycosis, and what fungus did we
Speaker 2: do of non humans?
Speaker 1: We did white nose syndrome in backs, and we did
Speaker 1: a Kittrid episode.
Speaker 2: Oh yeah, Kittrid.
Speaker 1: And then in our Zombies episode way way back, we talked.
Speaker 2: About cordyceps a bit. Yep, just a little bit, just
Speaker 2: a little bit.
Speaker 1: But this is only the second time. I'm pretty sure, Like,
Speaker 1: I like it.
Speaker 2: I think that you're right, and we've been talking about
Speaker 2: doing another fungal episode for a while, but I think
Speaker 2: if we had done that mental math, we would have
Speaker 2: been like, whoops, yeah, we've done it sooner.
Speaker 1: Whoops indeed, but yeah, Like, maybe it's because I haven't
Speaker 1: gotten to think about fungi as often as I should,
Speaker 1: but researching blastomycosis got me thinking about fungal pathogens as
Speaker 1: a group, like human fungal pathogens as a group, and
Speaker 1: why this is only our second episode on a human
Speaker 1: fungal pathogen. It's not because we don't like fungi or
Speaker 1: find them interesting, Like we've talked about how psyches we
Speaker 1: are to like research this and talk about it. But
Speaker 1: I think that it really has to do more with
Speaker 1: the number of known fungal species that can cause disease
Speaker 1: in humans, whether that's through an environmental fungus invading our
Speaker 1: tissues like an accidental pathogen or an opportunistic pathogen, or
Speaker 1: through a part of our microbiome growing out of balance
Speaker 1: like dysbiosis, and that number of fungi pathogenic to humans
Speaker 1: pales in comparison to the more commonly featured stars of
Speaker 1: this podcast, bacteria and viruses, And then I started to
Speaker 1: think about, like why that is. Partly, it could be
Speaker 1: that fungal pathogens have received less research and less media
Speaker 1: attention compared to these other groups, and that the global
Speaker 1: burden of fungal infections and humans is actually an underestimate,
Speaker 1: which of course it is, but it's certainly not because
Speaker 1: the parasitic life cycle is unfamiliar to fungi. Of the
Speaker 1: two point two to three point eight million estimated species
Speaker 1: of fungi on this planet, about two hundred and seventy
Speaker 1: thousand are thought to be pathogenic to plants, and about
Speaker 1: fifty thousand are thought to be pathogenic to insects. Compare
Speaker 1: those numbers to the few hundred, Like, we're talking hundreds
Speaker 1: that are pathogenic to humans and other mammals. We're not
Speaker 1: in the thousands.
Speaker 2: Is it? Is it temperature?
Speaker 1: Well, okay, let's get into it. So in the first
Speaker 1: half it's actually like way more than half the history
Speaker 1: of blasto. It's very small. So I got way too
Speaker 1: excited about this part. I wanted to ask two primary questions,
Speaker 1: or try to answer two primary questions. Number one, what
Speaker 1: is it about humans and other mammals that keeps us
Speaker 1: mostly off limits from fungi. And number two, what's up
Speaker 1: with those special few fung gui that do infect humans?
Speaker 1: How do they do what they do? Yeah, the answer
Speaker 1: to the first question is pretty straightforward, and you hit
Speaker 1: it right on the head. Temperature, well, it's actually twofold.
Speaker 1: It's temperature being a big one.
Speaker 2: Warm.
Speaker 1: We're warm blooded as mammals. We are end of therms
Speaker 1: is the technical term. And number two is our immune
Speaker 1: systems in general just do a really good job of
Speaker 1: protecting us from systemic infections, largely through like macrophages, right,
Speaker 1: and other parts of our immune system. But what I
Speaker 1: really want to spend more time talking about today is
Speaker 1: our warm bloodedness, our endothermi, one of the key features
Speaker 1: of mammals as a group, and birds, but I'm not
Speaker 1: going to talk about birds, so sorry to all of.
Speaker 2: Our bird nerd friends office.
Speaker 1: But mammals maintain body temperatures at a constant rate, and
Speaker 1: we do this through producing our own heat using metabolic processes.
Speaker 1: This is called endothermi, and that constantly maintained body temperature
Speaker 1: tends to be warm relative to the environment. And since
Speaker 1: the vast majority of fungi are adapted to living at
Speaker 1: environmental temperatures. For instance, in soil, we mammals are simply
Speaker 1: too hot to handle if endotherms are on one end
Speaker 1: of a spectrum of strategies for regulating body temperature. At
Speaker 1: the opposite end are ectotherms, so called cold blooded because
Speaker 1: they rely on environmental sources of heat like the sun
Speaker 1: to adjust their body temperature. Reptiles, amphibians, fish all examples
Speaker 1: of ectotherms, although again it's a spectrum, and I have
Speaker 1: to mention that some species fall in between these two streams,
Speaker 1: like some fish I learned have regional endothermy where they
Speaker 1: can maintain temperature in certain regions of their body, like
Speaker 1: their brain areas.
Speaker 2: It's why they can swim really fast even where it's
Speaker 2: really cold yep, and really long distances. Fish are cool.
Speaker 2: Fish are really cool. Yeah.
Speaker 1: Or some mammals are more ectothermic than we tend to
Speaker 1: think of. Mammals like the thirteen lined ground squirrel or
Speaker 1: bats that drop their body temperature when going into torpor
Speaker 1: or hibernation.
Speaker 2: Okay, cool, cool cool.
Speaker 1: But generally speaking, ectotherms are more susceptible to infection from
Speaker 1: fungal pathogens. Because their body temperatures more closely match the
Speaker 1: environment at least part of the day, it's not as
Speaker 1: much of a stretch as it would be for most
Speaker 1: fungi infecting endotherms, unless, of course, you're a fungus infecting
Speaker 1: a bat who's in torpor, like we talked about in
Speaker 1: our episode on white no syndrome.
Speaker 2: I remember that now.
Speaker 1: A paper from two thousand and nine looked at thermal
Speaker 1: growth tolerance for several thousand fungal strains, basically how well
Speaker 1: they can grow at a range of different temperatures, and
Speaker 1: found that as you increase temperatures above thirty degrees celsius
Speaker 1: or eighty six degrees fahrenheit, fewer and fewer strains can
Speaker 1: hack it in the heat. Just having these warm bodies
Speaker 1: alone helps to protect us from fungal pathogens, which is
Speaker 1: a pretty awesome superpower, but it's one that comes at
Speaker 1: a cost. Endothermy is super energetically expensive, and I mean
Speaker 1: super It takes a whole lot of energy to maintain
Speaker 1: body temperature, and to keep up with that high rate
Speaker 1: of energy consumption, endotherms have to take in way more food,
Speaker 1: like ten times at least that of an ectotherm.
Speaker 2: Wow, yeah, that's why I'm always hungry, I know, right,
Speaker 2: that's that's why.
Speaker 1: Yeah, And we endotherms can't go as long without eating
Speaker 1: compared to most other ectotherms, with some endotherms needing to
Speaker 1: eat every hour otherwise they risk death. Meanwhile, some ectotherms
Speaker 1: can forego food for over a year. It's wow incredible.
Speaker 2: Huh.
Speaker 1: So for such a costly trait as endothermy, there's got
Speaker 1: to be a big payoff or payoffs pays off. I
Speaker 1: don't know which one. I think it's payoffs. You know
Speaker 1: what colds decide.
Speaker 2: Clods de sac.
Speaker 1: And the leading hypotheses for the rise of endothermy, which
Speaker 1: i've seen, estimates that it emerged between one hundred million
Speaker 1: years ago to two hundred and fifty million years ago.
Speaker 1: But these leading high potheses can be grouped into three
Speaker 1: primary models. Number one thermoregulation that maintaining constant body temperature
Speaker 1: even as the ambient temperature fluctuates, would have allowed early
Speaker 1: endotherms to be active at all times, giving them an
Speaker 1: advantage on a number of fronts. Right, you can expand
Speaker 1: your range into colder areas where ectotherms don't thrive as well.
Speaker 1: You can shift your behavior to being nocturnal to avoid
Speaker 1: the reptilian predators that are more active during the day.
Speaker 1: And even this thermoregulation may have allowed our brains to
Speaker 1: grow larger and more complex since they're being constantly fed
Speaker 1: that energy. Number two enhanced aerobic capacity endotherms can be
Speaker 1: more active over longer periods of time, giving them an
Speaker 1: edge if, for instance, a small endotherm was trying to
Speaker 1: escape from an ectotherm predator, many of which are sit
Speaker 1: in weight predators and who also didn't have the ability
Speaker 1: to sustain that kind of long term activity, or maybe
Speaker 1: it helped an endotherm predator chase after its endotherm prey.
Speaker 1: Endotherms just have more energy stores than ectotherms for aerobic activity.
Speaker 1: Number three parental care endothermy evolved because it allowed parents
Speaker 1: to incubate their developing young at a higher temperature, and
Speaker 1: then the enhanced aerobic capacity helped them to defend their
Speaker 1: offspring and collect food for them, increasing their survival.
Speaker 2: That's a fun one, Isn't that a fun one? Yeah?
Speaker 1: And I feel like I've said this for the past
Speaker 1: three episodes. Now as I go into like deep time
Speaker 1: and stuff that's not really related.
Speaker 2: To like the history of theory.
Speaker 1: Somehow, I'm really loving this, Like I hope that it's
Speaker 1: really fun like this.
Speaker 2: Yeah, I'm actually.
Speaker 1: Having so much fun talking about like these principles of
Speaker 1: what makes us human or viruses or anyway.
Speaker 2: Okay, I love it.
Speaker 1: But this, like I've said for the past few episodes,
Speaker 1: is an area of ongoing research. It's an active area
Speaker 1: of discussion, and it's probably an interplay among these drivers
Speaker 1: that led to the emergence of endothermy, and we may
Speaker 1: never know the full story. We probably won't. But there
Speaker 1: is one more hypothesis, not a leading one necessarily that
Speaker 1: has been mentioned here and there, which is that endothermy
Speaker 1: arose because higher body temperatures helped prevent infection with fungal pathogens.
Speaker 2: Wow.
Speaker 1: Okay, So, like I talked about in our last episode
Speaker 1: on the drivers of color vision in humans and other primates,
Speaker 1: this is another chicken and egg scenario. Did fungi drive endothermy?
Speaker 1: Or was escape from fungal infections? Just this added perk
Speaker 1: of endothermy. And there's not much by way of like
Speaker 1: fossil physical evidence for the former, but I did stumble
Speaker 1: upon some papers that laid out a scenario where the
Speaker 1: latter escape from fungal infections helped to usher in the
Speaker 1: age of the mammals.
Speaker 2: Okay, I'm listening.
Speaker 1: For nearly twenty years, a researcher of microbiology and immunology
Speaker 1: named Arturo Cassa Deval, along with some colleagues, has been
Speaker 1: working on a hypothesis called the quote fungal infection mammalian
Speaker 1: selection hypothesis.
Speaker 2: Oh Okay.
Speaker 1: Around sixty six million years ago, the Earth witnessed one
Speaker 1: of the largest cataclysmic losses of life, the Cretaceous Paleogene
Speaker 1: extinction event, when a massive asteroid slammed into the Yucatan Peninsula.
Speaker 1: And I feel compelled to mention that this is a
Speaker 1: hypothesis still, but like for there's pretty strong evidence that
Speaker 1: it was indeed an impact that coincided with the I
Speaker 1: don't know how much that's like a contentious issue. I
Speaker 1: don't think it is anyway. That's just like my Yeah.
Speaker 2: All of our toddler dinosaur books still mention it as
Speaker 2: like a hypothesis, but they're also like from my childhood,
Speaker 2: so they're kind of.
Speaker 1: Old when like Brontosaurus was still a thing. It's Brontosaurus
Speaker 1: still a thing.
Speaker 2: Yeah, no, Brachiosaurus is a thing. Brontosaurus is not.
Speaker 1: Oh see, yeah like that anyways, that's.
Speaker 2: How I learned. Anyway.
Speaker 1: The result of this impact was the die off of
Speaker 1: seventy five percent of species, including the extinction of all
Speaker 1: non avian dinosaurs, and of course enormous ecological collapse. This
Speaker 1: is familiar territory. The oceans acidified, the skies turned dark,
Speaker 1: forests burned and died off. Photosynthesis didn't occur for one
Speaker 1: to two years. The planet went into a cooling period
Speaker 1: of at least nine years, and much of the planet
Speaker 1: was basically turned into a giant pile of decomposing biomass.
Speaker 2: Sorry, no photosynthesis for.
Speaker 1: Two years that I've seen estimates from six months to
Speaker 1: two years, but most recently one to two years seems
Speaker 1: to be.
Speaker 2: Wow. Yeah, yeah, wow, okay okay.
Speaker 1: And so the end result of all this is that
Speaker 1: there was just a ton of dead things all around. Yeah,
Speaker 1: the planet was turned into a giant pile of decomposing biomass.
Speaker 2: Wow.
Speaker 1: And what loves decomposing biomass? What thrives on decomposing biomass?
Speaker 1: What puts the decompose in decomposing biomass? Fungus exactly right.
Speaker 1: Oh uh huh, And research supports this. A huge fungal
Speaker 1: peak has been observed following that asteroid impact, like around
Speaker 1: that same time, and it would have lasted a few years.
Speaker 2: Oh my god, I'm loving this so much. I'm so glad.
Speaker 1: But it would have been an incredible amount of fungui.
Speaker 2: Oh wow.
Speaker 1: The remaining ectotherms would have had a hard time regulating
Speaker 1: body temperature since the Sun was blotted out by dust
Speaker 1: clouds and the entire planet was experiencing this substantial period
Speaker 1: of cooling, and that cooling also would have skewed the
Speaker 1: sex ratios among reptiles.
Speaker 2: Oh my gosh.
Speaker 1: Right, I never thought of that me neither. Things were
Speaker 1: already not looking great for these guys. But then when
Speaker 1: you throw fungal proliferation into the mix, bad news, worse news,
Speaker 1: the worst possible news.
Speaker 2: Yep.
Speaker 1: The already struggling and probably malnutritioned ectotherms wouldn't have been
Speaker 1: able to raise their body temperature to induce fever to
Speaker 1: fight off a fungal infection since the sun was hiding
Speaker 1: and the eggs that they laid would have also been
Speaker 1: susceptible to the ever present fungi. Side note, Apparently fossilized
Speaker 1: hyphi have been found in fossilized dino eggs.
Speaker 2: Oh that's cool, isn't that.
Speaker 1: Casa Deval argues that this fungal bloom and its impact
Speaker 1: on ectotherms helped to pave the way for mammals to
Speaker 1: take over what because endotherms have fared much better in
Speaker 1: this global calamity. Being able to regulate body temperature would
Speaker 1: have protected them as the planet cooled and allowed them
Speaker 1: to move around more to collect food, and having embryos
Speaker 1: that developed inside you would have protected them much more
Speaker 1: from fungal diseases.
Speaker 2: I have to say I have gone through a lot
Speaker 2: of museum exhibits about dinosaurs and this extinction event, and
Speaker 2: read a lot of dino books, and they always just
Speaker 2: mentioned like and then the mammals mostly survived, and like
Speaker 2: nobody talks about why. And this is amazing, isn't it.
Speaker 1: I love this. I think it's just it's been so
Speaker 1: fun to read about. And I will say that, like,
Speaker 1: of course, I have to say, this is a hypothesis
Speaker 1: number one, number two. A lot of things were going on, right,
Speaker 1: Like even if you did didn't have the fungal bloom,
Speaker 1: not being able to like warm your body temperature enough
Speaker 1: to go.
Speaker 2: Find food, right would have been a problem. Not great.
Speaker 1: And then you know there's a lot of stuff that
Speaker 1: I didn't want to go into about sort of the
Speaker 1: relationship between endothermy and ectothermy and body size and like
Speaker 1: what is in terms of efficiency in terms of like
Speaker 1: food intake. So like there's more under the surface there.
Speaker 1: But you know, things were happening that somehow led to
Speaker 1: ectotherms starving and dying potentially from fungal infections, where endotherms
Speaker 1: just sort of prospered or were able to make it work.
Speaker 2: I'll say that, yeah, cool.
Speaker 1: And I don't know enough about this time period or
Speaker 1: the research in this area about what sort of led
Speaker 1: to the rise of mammals, especially not enough to say
Speaker 1: whether this is a well regarded hypothesis or whether this
Speaker 1: is like I don't know, has a lot of support
Speaker 1: or not. But I do think it's really fun and
Speaker 1: interesting to think about, especially since I feel like ecological
Speaker 1: research tends to even today neglect the effect that parasitism
Speaker 1: and infections can have on entire ecosystems unless you are
Speaker 1: a disease ecologist or a parasiticcologist and you're studying that
Speaker 1: thing directly.
Speaker 2: I agree. So future episode we're going to talk about
Speaker 2: how did crocodiles survive?
Speaker 1: Okay, yeah, I don't know, good question.
Speaker 2: I love it. I want to have to do a lot
Speaker 2: more reading. I'm excited about it.
Speaker 1: I have a book about dinosaurs I've been meaning to
Speaker 1: read for like a longs time. Here's your chance, completely
Speaker 1: forgot I have on my shelf. Yes, now it's my chance.
Speaker 2: Oh okay, I love this. The fungus is why we
Speaker 2: That's what I'm taking away from this. Oh gosh, I'm
Speaker 2: just kidding. What an interesting idea though, I love it.
Speaker 1: It's just really fun to think about.
Speaker 2: And I want to.
Speaker 1: Know if someone is out there who knows more about
Speaker 1: this or is just like, hey, I thought that was really.
Speaker 2: Cool, you know, let us know. Yeah, and also, I
Speaker 2: have a lot of.
Speaker 1: Sources to post about this, So if you want to
Speaker 1: do some more reading, have at it. Okay, So we
Speaker 1: endotherms are more protected against fungal infections thanks to our
Speaker 1: warm bodies and specialized immune systems, but we're not completely
Speaker 1: protected obviously, otherwise we wouldn't be doing this episode. So
Speaker 1: what is it about those select few fungi that allow
Speaker 1: them to wreak havoc on us with a billion one
Speaker 1: billion superficial fungal infections, one hundred and thirty five million
Speaker 1: mucosal fungal infections, twenty three point three million allergic fungal infections,
Speaker 1: and several million chronic and acute invasive fungal infections every
Speaker 1: year with more than one point six million deaths annually.
Speaker 2: WHOA rren. That's massive, right.
Speaker 1: I mean, it's bigger than I ever thought. These fungi
Speaker 1: that are causing this massive global burden of disease? Are
Speaker 1: there commonalities among them? Among the species causing disease, one
Speaker 1: feature of many, but not all, fungal infections lies in
Speaker 1: their opportunistic nature. Most of the time we see fungi
Speaker 1: causing secondary infections or primary infections in people who are compromised,
Speaker 1: or we see these accidental pathogens like Blastomyces dermatitidis. Rarely
Speaker 1: do we encounter fungi that are obligately pathogenic, right, Like,
Speaker 1: most fungi don't need a human host to complete their
Speaker 1: life cycle. It's just that these fungi pathogenic to humans,
Speaker 1: whether opportunistically or accidentally, possess traits that help them to
Speaker 1: succeed in their natural habitat, for instance tolerating higher temperatures
Speaker 1: because it allows them to expand where they live. And
Speaker 1: some of those traits also happen to help them colonize
Speaker 1: a human or other mammalian and a therm host. And
Speaker 1: because of this, human pathogenicity evolved many times across many
Speaker 1: lineages of the fungal tree of life. But is it
Speaker 1: that human pathogenicity evolved or is it that these traits
Speaker 1: evolved because they give the fungus a competitive edge in
Speaker 1: their natural habitat and they also happen to be the
Speaker 1: same traits that help the fungus infect humans. And the
Speaker 1: answer is it depends, and maybe it's like a more
Speaker 1: of a semantics thing like they might be able to
Speaker 1: be both. So there are a handful of obligately intracellular
Speaker 1: fungal parasites Microsporidia that probably coevolved with their hosts, but
Speaker 1: most of the known human fungal pathogens fall into the
Speaker 1: opportunistically or accidentally pathogenic category, blastomycosis being one of these
Speaker 1: as like an accidental pathogen. So let's think about what
Speaker 1: types of traits would help these fungi thrive in their
Speaker 1: natural habitat, say soil, which would be overflowing with microbial diversity,
Speaker 1: both competitors and predators. One thing I already mentioned was thermotolerance,
Speaker 1: being able to survive at higher temperatures that would help
Speaker 1: them maybe find food in a less populated area or
Speaker 1: escape from predators or pathogens who aren't as thermotolerant. Then
Speaker 1: there's the ability to adapt to varying levels of oxygen,
Speaker 1: which could be helpful for the same reasons. Maybe a
Speaker 1: fungus is great at evading amibe, which are common predators
Speaker 1: in soil environments, and if a fungus can escape amibe,
Speaker 1: then maybe that helps it evade macrophages in the human host.
Speaker 2: I love that so much erin right.
Speaker 1: And then finally, reproduction Blastomyces does this thing that you
Speaker 1: talked about aaron, where it switched from filamentous to yeast
Speaker 1: growth when in a human host, and that helps it
Speaker 1: evade host immune responses. And so I think it's so
Speaker 1: fascinating to think about these pathogenic traits in fungi because
Speaker 1: it forces us to recognize that they don't play by
Speaker 1: the same rules as the pathogens that we're used to,
Speaker 1: namely viruses and bacteria. And that could have bearing on
Speaker 1: how we treat these infections and how we assess risk.
Speaker 1: Understanding the ecology, like the natural ecology in these ecosystems
Speaker 1: and soil, for instance, of these medically relevant fungi also
Speaker 1: gives us opportunities to develop new anti fungal treatments by
Speaker 1: examining what other microbes or microbial products have an impact
Speaker 1: on this fungus's growth. Right if within a teaspoon of soil,
Speaker 1: there's a full on battle royale of microbes, like who's winning,
Speaker 1: who is releasing products that are knocking down blastomyces, what's
Speaker 1: eating blastomycees? What can Blastomyces not escape from? Maybe Blastomices
Speaker 1: isn't the greatest example because we don't know it's precise
Speaker 1: ecological niche, but you get the idea. Speaking of Blastomycees,
Speaker 1: I guess I should finally get into the history of
Speaker 1: this specific fungus.
Speaker 2: I want to hear all about it, but I'm having
Speaker 2: so much fun already. Good.
Speaker 1: Well, there's not much, at least that I could find
Speaker 1: in terms of the evolutionary history of Blastomyces as a genus.
Speaker 1: I read somewhere that the most recent common ancestor of
Speaker 1: the ana genals on a Jenales order which Blastomyces belongs to,
Speaker 1: that this most recent common ancestor emerged one hundred and
Speaker 1: fifty million years ago. And I also read that Blastomyces
Speaker 1: dermatitidis and Blastomyces gilchristie diverged about one point nine million
Speaker 1: years ago. Okay, yeah, that's all I got for that,
Speaker 1: And the prehistory of Blastomyces is similarly sparse. But I
Speaker 1: did come across a paper from nineteen seventy eight where
Speaker 1: researcher is studying the shild Mississippian Cemetery in Illinois, which
Speaker 1: is a prehistoric site, suggested that blastomycosis may have affected
Speaker 1: the community that they were studying, based on evidence from
Speaker 1: skeletal remains ranging from one to two thousand years.
Speaker 2: Old or so. Huh.
Speaker 1: Okay, yeah, I mean, and it does fit with what
Speaker 1: we know about the distribution of blastomycosis in North America.
Speaker 1: But it also, according to the authors, could have been tuberculosis, which,
Speaker 1: like you said, they're commonly mistaken for one another. Regardless,
Speaker 1: cases of blastomycosis probably occurred in at least the eastern
Speaker 1: half of North America long before dermatologist Thomas Casper Gilcrest
Speaker 1: identified the fungus in a tissue sample from an infected
Speaker 1: individual in eighteen ninety four, basically kind of what you
Speaker 1: heard in our first time account. At this time, the
Speaker 1: medical field was still sort of like it had been
Speaker 1: a few decades since germ theory had been introduced, but
Speaker 1: it took people a lot longer to recognize that fungi
Speaker 1: can be pathed genic to humans or other animals, and
Speaker 1: blastomycosis actually was one of like in within a span
Speaker 1: of a few years, the first that had been identified
Speaker 1: as causing disease in a human.
Speaker 2: This is a silly question, but in the late eighteen hundreds,
Speaker 2: did they know that a fungus was a fungus because
Speaker 2: I feel like he called it a plant. Yeah, the
Speaker 2: first hand account.
Speaker 1: So while okay, so I don't know about like the
Speaker 1: full breakdown of the taxonomy of fungi at the time,
Speaker 1: but I know that fungi weren't really separated out into
Speaker 1: their own kingdom until later, and so they were grouped
Speaker 1: in with plants. And it wasn't so much fungi were
Speaker 1: thought to be plants as it was that it was
Speaker 1: like animals and not animals and everything else.
Speaker 2: Okay, okay, okay, and so I think.
Speaker 1: That splitting happened later on. But in the later paper
Speaker 1: by Gilcrest, which just within a few years, when he
Speaker 1: found a second case, he did draw like the fungal
Speaker 1: cells and the fungal structure and stuff like that, and
Speaker 1: so I think that it was well recognized to be
Speaker 1: a fungus. It was just thought to be a type
Speaker 1: of plant.
Speaker 2: Yeah, yeah, that's that's interesting. Yeah. Yeah.
Speaker 1: Also in that firsthand account he mentioned that he thought
Speaker 1: it was a parasite in the very beginning, but later
Speaker 1: he was like, no, this is definitely a plant. And
Speaker 1: then that's when he named it, drew pictures of it,
Speaker 1: all of that, and he named it Blastomyces dermatitidis.
Speaker 2: And so really within the.
Speaker 1: First few decades first half of the twentieth century, other
Speaker 1: physicians reported an increasing number of cases of blastomycosis in
Speaker 1: the Midwest US, with the highest of cases in Chicago,
Speaker 1: which gave rise to the nickname Chicago disease. So you'll
Speaker 1: find that in some of the older literature on blastomycosis.
Speaker 1: Researchers also recognized that Blastomces dermatitidis could cause respiratory and
Speaker 1: systemic infections. Infect other animals besides humans, including dogs, and
Speaker 1: was not the exclusively North American disease they thought it was.
Speaker 1: Blastomycosis case is reported in Central and East Africa and
Speaker 1: India and probably other places that we just haven't found
Speaker 1: it yet. But it kind of reminds me of the
Speaker 1: Tulaimia episode in that way, where.
Speaker 2: This was the Chicago disease. Yeah, not quite like actually,
Speaker 2: well actually.
Speaker 1: Actually, and Aaron, I know that in a few minutes
Speaker 1: you're going to bring us up to speed on blasto
Speaker 1: epidemiology around the world today. But I don't think it'll
Speaker 1: be a spoiler to say that this isn't a super
Speaker 1: prevalent disease, right, but it can be, as we learned,
Speaker 1: a very deadly one, even with effective antifungal drugs. And
Speaker 1: I did find somewhere that prior to the introduction of
Speaker 1: drugs like ampheteris and b which you mentioned, the case
Speaker 1: fatality rate for chronic pulmonary and disseminated infection was one
Speaker 1: hundred percent. And part of what contributes to the deadliness
Speaker 1: or the apprehension surrounding blastomycosis is that its ecology still
Speaker 1: hasn't been fully resolved. Epidemiological studies suggest pretty strongly that
Speaker 1: the fungus probably resides near rotting wood and fresh water,
Speaker 1: but people haven't been able to reliably isolate it from
Speaker 1: environmental sources even when there's a recognized outbreak or cluster,
Speaker 1: and this represents a pretty major challenge in understanding or
Speaker 1: quantifying risk factors for this disease, both in the present
Speaker 1: day as as well as in the future, because if
Speaker 1: there's one thing that we know for certain, it's that
Speaker 1: this is an environmental fungus, and as an environmental fungus,
Speaker 1: its growth, survival, distribution, and exposure to humans and other
Speaker 1: animals that's all influenced by changes in its environment, changes.
Speaker 2: Like climate change now.
Speaker 1: Earlier in this history section, I talked about how our
Speaker 1: endothermy may have been mammals saving grace during the Cretaceous
Speaker 1: Paleogene extinction event when we could maintain high body temperatures
Speaker 1: to fend off fungal infections. But what happens as the
Speaker 1: global temperature continues to rise, selecting for fungi that can
Speaker 1: withstand the heat of this warming planet and thus are
Speaker 1: warmer bodies, will we see more cases of fungal infections
Speaker 1: or more fungal species that can cause infection. Well, Aaron,
Speaker 1: what do the experts say? Where do I stand with
Speaker 1: blast of my poses today? Oh?
Speaker 2: I can't wait to talk about it right after this break. So,
Speaker 2: like you mentioned already Erin, one of the problems when
Speaker 2: it comes to understanding this fungal pathogen is that we
Speaker 2: don't we don't really even yet know everything about its ecology.
Speaker 2: We do know that it seems to reside and thrive
Speaker 2: in damp, sandy soils with a cidic pH if you
Speaker 2: care about that part where there's a lot of rotting wood,
Speaker 2: often near lakes or rivers or other waterways. The vast
Speaker 2: majority of cases and most of what we know about
Speaker 2: blastomycosis comes from the United States, and specifically, this is
Speaker 2: a pathogen that's endemic in soils across the Midwest, the Southeast,
Speaker 2: the East, and a little bit in the south central
Speaker 2: US and up into Canada, classically described on like med
Speaker 2: school tests as the Ohio and Mississippi river valleys and
Speaker 2: around the Great Lakes and another river that I forgot
Speaker 2: to write down, Saint Lawrence. I think just some river
Speaker 2: in Canada we don't care goes through Canada and like
Speaker 2: another part of the US. Wow, Aaron that New England
Speaker 2: was a state for a long time. It's not. Yeah,
Speaker 2: but like you mentioned, cases have also been found across
Speaker 2: a very wide swath of the massive continent that is Africa,
Speaker 2: as well as in India. Overall, the reports across Africa
Speaker 2: and in India have been very rare. Less than ten
Speaker 2: cases confirmed in India and about one hundred cases across
Speaker 2: eighteen different countries in Africa, which is not a lot.
Speaker 2: Most of these cases, both in the US and in
Speaker 2: the other parts of the world where cases have been reported,
Speaker 2: tend to be sporadic, though there have been some occupations
Speaker 2: or situations that have led to some outbreaks in the past,
Speaker 2: like construction situations, hanging out in beaver dams apparently huh, yeah,
Speaker 2: that was reported. There was an outbreak, it was small.
Speaker 2: But part of the problem is that in the US,
Speaker 2: where this is most common, blastomycosis is not a reportable
Speaker 2: disease across most of its distribution. It's reportable right now
Speaker 2: in Arkansas, Louisiana, Michigan, Minnesota, and Wisconsin, but the rest
Speaker 2: of its distribution it's not considered a reportable disease. So
Speaker 2: we don't have a lot of data on it. Twenty
Speaker 2: nineteen was the last year that an MMWR report came
Speaker 2: out from the CDC, and in that report, they cited
Speaker 2: a total of two hundred and forty confirmed or probable
Speaker 2: cases of blastomycosis across the US, which resulted in one
Speaker 2: hundred and forty seven hospitalizations. So that's a pretty high
Speaker 2: rate of hospitalizations compared to the number of confirmed cases. Yeah,
Speaker 2: there are several regions in North America that tend to
Speaker 2: be hyper endemic where the overall incidents rate each year
Speaker 2: is significantly higher than in the rest of the area
Speaker 2: where it still can happen. Those places include part of
Speaker 2: Ontario where caseloads can be as high as one hundred
Speaker 2: and seventeen per one hundred thousand people per year, in
Speaker 2: Eagle River, Wisconsin and Villis County is how you say it, Wisconsin, sure,
Speaker 2: where cases can range between forty and one hundred per
Speaker 2: one hundred thousand, and a few other areas as well,
Speaker 2: But those are the biggest ones, and I would be
Speaker 2: remiss not to mention that there is an outbreak that
Speaker 2: happened this year in twenty twenty three. The most recent
Speaker 2: data I have on it is from April, but by
Speaker 2: that time, at least one hundred people had gotten sick
Speaker 2: and one person has died in an outbreak of blaster
Speaker 2: micosis at a paper mill in Michigan. That is the
Speaker 2: largest outbreak by far in a very long time, and
Speaker 2: apparently the first outbreak that's been specifically associated with like
Speaker 2: a workplace exposure rather than just like a construction site,
Speaker 2: where it was an environmental exposure.
Speaker 1: From the wood that they were processing.
Speaker 2: Right at the paper mill.
Speaker 1: Okay, interesting, and I feel like doing research on an
Speaker 1: outbreak like that will probably help answer some of the
Speaker 1: questions about environmental exposure, about asymptomatic versus symptomatic versus you know,
Speaker 1: what's the infectious dose, all of that type of stuff.
Speaker 2: Absolutely. Apparently this paper mill, at least according to the
Speaker 2: New York Times article that I read about it employs
Speaker 2: about eight hundred people. So that's a lot of people
Speaker 2: that got sick out of just that many people who
Speaker 2: work there. I know, gosh, I know. So we'll see
Speaker 2: how the rest of this comes out. I'm sure there'll
Speaker 2: be a lot of papers that come out of this outbreak. Yeah,
Speaker 2: but that's kind of what we know about the epidemiology
Speaker 2: of this disease. It's not a lot. There is seasonality
Speaker 2: to it. There tends to be highest case numbers in
Speaker 2: autumn and in spring, meaning that during the colder winter months.
Speaker 2: I don't know if it's just because people aren't outside
Speaker 2: as much or because the fungus is just not as
Speaker 2: active and maybe there's not as many spores in the environment,
Speaker 2: who knows, but there tends to be less infection during
Speaker 2: those colder winter months. Okay, and then that's when we
Speaker 2: have to come to how is this all going to
Speaker 2: change in our warming planet? Yeah? Yeah, The short answer
Speaker 2: is that we don't know, but we do know that
Speaker 2: undoubtedly there will be changes. Right, because this is an
Speaker 2: environmental pathogen, it is inevitable that the climate and weather
Speaker 2: conditions influence the growth and the dispersal of blastomyces. We
Speaker 2: have seen in the past that there have been outbreaks,
Speaker 2: much like with coxidioidomycosis, after you have a period of
Speaker 2: rainfall and then a dry period, right, thinking that after
Speaker 2: you have this big rain you get a lot of
Speaker 2: growth of the fungus and then the soil dries out
Speaker 2: and those spores are able to go on air currents
Speaker 2: and we breathe them all in. We know that large
Speaker 2: rainfall events and hotter conditions are things that are going
Speaker 2: to happen with climate change. The other thing is that
Speaker 2: there is a hypothesis in general that these fungal diseases
Speaker 2: that are already well adapted to mammals, like you talked
Speaker 2: a lot about aaron, especially these dimorphic thermally dimorphic fungi,
Speaker 2: many of which can infect humans, might be particularly well
Speaker 2: suited to this new warmer climate because they're already quite
Speaker 2: capable of surviving at higher temperatures. So we may see
Speaker 2: overall rises in this infection blastomycosis, as well as other
Speaker 2: similar infections cocidioidomycosis, histoplasmosis, paracoxidioides, There's a bunch more. We
Speaker 2: might also just see changes in the range and the
Speaker 2: distribution where it moves into areas that we hadn't seen
Speaker 2: blastomycosis before. We don't really know, but it's definitely a
Speaker 2: huge factor in considering the effects that global climate change
Speaker 2: have on our health, in the health of our animal pets, yeah,
Speaker 2: and wildlife.
Speaker 1: And wildlife and basically everything.
Speaker 2: I think. I think that's what's so.
Speaker 1: Fascinating I think about fungal pathogens is that, based on
Speaker 1: my very limited understanding of just doing that that research,
Speaker 1: if you could infect one mammal, you likely can infect
Speaker 1: all of them as long as there's an exposure route
Speaker 1: available to you.
Speaker 2: Yeah. Yeah, so I am sure that. Like with many
Speaker 2: pathogens we've covered, it feels like this season especially, we
Speaker 2: will probably see more and more blastomycosis the more we
Speaker 2: look for it. Yeah, seeking you shall find exactly so
Speaker 2: that aaron is blastomycosis.
Speaker 1: You know, we haven't really said any what a blast
Speaker 1: type jokes, but I did despite it all at a
Speaker 1: blast learning as well.
Speaker 2: Yeah, I mean I learned a lot about just how
Speaker 2: mammals exist. I'm just kidding, but kind of but.
Speaker 1: Not Well, if if you too would like to learn
Speaker 1: more and keep having a blast, I don't know, I've slate.
Speaker 1: I'm tired. Let's do sources.
Speaker 2: Sources. I have a lot.
Speaker 1: Like I said, I'm going to shout up three in particular,
Speaker 1: one for each of sort of like the themes that
Speaker 1: I covered in the history section. So the first is
Speaker 1: by Cascadeval and Dammen from twenty twenty called updating the
Speaker 1: fungal infection mammalian selection hypothesis. At the end of the
Speaker 1: Cretaceous period.
Speaker 2: And then in.
Speaker 1: Terms of the traits in fungi that help make them
Speaker 1: pathogenic to humans, there's a paper by Rokus from twenty
Speaker 1: twenty two called Evolution of the Human Pathogenic Lifestyle and Fungi.
Speaker 1: And then finally for the history of discovery, there's a
Speaker 1: book by al Dori and DiSalvo from twenty twelve called Blastomycosis.
Speaker 2: I had a few different papers. There's actually some really
Speaker 2: great overviews. One that was more broad about these types
Speaker 2: of fungi in general, called fungal dimorphism and virulence, Molecular
Speaker 2: mechanisms for temperature adaptation, immuneivation, and in vitro survival. Loved it.
Speaker 2: If that was a twenty seventeen paper, we'll post that.
Speaker 2: And then Clinical Manifestations and Treatment of Blastomycosis from Clinics
Speaker 2: and Chess Medicine, and then just Blastomycosis and Infectious Disease
Speaker 2: Clinics paper from twenty twenty one. Those were really good,
Speaker 2: just broad overviews of this infection. And then I have
Speaker 2: a bunch more about the maps, looking at where we've
Speaker 2: found blastomycosis, what we think might happen with climate change,
Speaker 2: and so much more. You can find all of our
Speaker 2: sources from this episode and every one of the other
Speaker 2: one hundred and twenty four plus episodes on our website
Speaker 2: this podcast so kill You dot com.
Speaker 1: Thank you to Bloodmobile for providing the music for this
Speaker 1: episode and all of our episodes.
Speaker 2: Thank you to Leanna Scuilachi for the incredible sound mixing.
Speaker 2: Thank you to Exactly Right, and thank you to you listeners.
Speaker 2: We hope you had a blast.
Speaker 1: Surely has to be more blast puns or idioms out
Speaker 1: there that we can use. You can't do it, no,
Speaker 1: not at this point in the night. But yeah, thank
Speaker 1: you so much for listening. And a huge, huge, thank
Speaker 1: you as always to our wonderful, generous patrons.
Speaker 2: We really just appreciate you so much, so much. Thank
Speaker 2: you well.
Speaker 1: Until next time, wash your hands, you filthy animals. Ou