Speaker 1: So my name is Tory and I'm from Utah. I
Speaker 1: had always been a healthy girl, with no serious ailments
Speaker 1: or illnesses. I spent most of my high school cycling, swimming, running.
Speaker 1: Exercise was my whole life, and I was always very healthy.
Speaker 1: At age nineteen, I created a plan to serve a
Speaker 1: religious mission and then come home and spend the rest
Speaker 1: of my life doing iron mans and one day making
Speaker 1: it to the Cone Ironman Championship. However, those plans would
Speaker 1: quickly change. In March of twenty fourteen, I left on
Speaker 1: a religious mission to Arizona for eighteen months, doing service
Speaker 1: outdoors and teaching. I ran nearly every day of this
Speaker 1: mission ended quite a lot of bike riding as well.
Speaker 1: Initially going out to Arizona, we were warned about valley fever.
Speaker 1: We were told always to stay inside if there was
Speaker 1: a dust storm or if it's extra dusty outside, because
Speaker 1: valley fever was in the spores of the spoiler of
Speaker 1: the dust. While we tried to stay inside from the
Speaker 1: dust storms, being outside was inevitable, and being around the
Speaker 1: dust was inevitable. Hello, it's Arizona, and we spent so
Speaker 1: much time outside. Fast forward, it was August twenty ninth,
Speaker 1: twenty fifteen. I was seventeen days away from going home
Speaker 1: and seeing my family again, and finishing this service, and
Speaker 1: that day my life would change forever. I woke up
Speaker 1: with a bit of chest tightness, but shrugged it off.
Speaker 1: I still went on our morning run, but could barely
Speaker 1: make it more than a quarter of a mile. When
Speaker 1: the chest pain became so intense, I ended up going
Speaker 1: to an urgent care and sitting in the waiting room
Speaker 1: for three hours, gasping for breath because their computer was down.
Speaker 1: I was in so much pain I could barely breathe.
Speaker 1: When the computers finally came up. I was able to
Speaker 1: get an X ray by the urgent care doctor. After
Speaker 1: analyzing the x ray, nothing of concerns showed up, so
Speaker 1: the doctor presumed that the only explanation was something similar
Speaker 1: to shingles because I didn't have a fever, I didn't
Speaker 1: have a cough, I didn't have a rash or anything else.
Speaker 1: I was given steroids, shots, and paid medications, and then
Speaker 1: sent on my way. After a few two days, I
Speaker 1: began to have a low grade fever and somebody aches. Progressively,
Speaker 1: the fevers got worse and the aches more extreme. To
Speaker 1: which point I felt unable to move my joints. Exactly
Speaker 1: one week from my initial trip to the urgent care,
Speaker 1: I was back again with fevers, nausea, a developing cough,
Speaker 1: consistent chest pain with absolutely no relief, and convinced this
Speaker 1: was more than shingles. I wanted to die with the
Speaker 1: pain I was experiencing. Luckily, the computers didn't have issues
Speaker 1: and I was able to get right into the doctor
Speaker 1: and he immediately ordered an additional chest X ray, again
Speaker 1: just to see I will never forget that x ray,
Speaker 1: as his assistants helped me stand up because I screamed
Speaker 1: in agony, trying to expand my joints and my chest,
Speaker 1: all of which were screaming back at me tenfold. When
Speaker 1: I was screaming out loud, the X ray came up
Speaker 1: on the scream starting from the bottom up. As I
Speaker 1: watched it, I saw spiderweb clouds covering my entire right lung.
Speaker 1: Even I knew something was wrong. In a week's time,
Speaker 1: my chest x ray had dramatically changed. The doctor spent
Speaker 1: what seemed like years just looking at the X ray
Speaker 1: and deemed it appropriate for me to go to the
Speaker 1: er and get a stat CT scan and be admitted.
Speaker 1: When I got there, my two SATs were in the
Speaker 1: eighties at best, and the CT scan that they quickly
Speaker 1: did showed fluid or on my entire right lung and
Speaker 1: beginning or on my lower left lobe. It was clear
Speaker 1: whatever I was experiencing was spreading quickly. I was quickly
Speaker 1: treated by teams of infectious disease doctors, pulmonologists, and respiratory therapists.
Speaker 1: Blood samples were taken and sent off to labs. In
Speaker 1: the meantime, I was treated for anything and everything. One
Speaker 1: of the first things they tested for was valley fever.
Speaker 1: The blood antigen tests that they did ended up coming
Speaker 1: back negative for valley fever, oddly enough, but they wanted
Speaker 1: to test part of my lung tissue to be sure.
Speaker 1: I was then presumed to maybe have tuberculosis and or
Speaker 1: a staff infection, and was primarily treated for that, along
Speaker 1: with anti fungals for the possible valley fever. In the
Speaker 1: coming days, I got sicker and weaker. My cough persisted
Speaker 1: and became more violent. So much water was in my
Speaker 1: lungs that each time I coughed, I felt like I
Speaker 1: was drowning because so much water came up. Every bone hurt,
Speaker 1: and my fever couldn't get under control. I remember multiple
Speaker 1: mornings being visited by the infected disease doctor and her
Speaker 1: sitting by the side of my bed, holding my hand
Speaker 1: and telling me she didn't sleep, worried I wouldn't make
Speaker 1: it through the night. On September twelfth, three days before
Speaker 1: I was supposed to return home to Utah, the concoction
Speaker 1: of medication that they had me on seemed to be
Speaker 1: stabilizing me, and my resting arrow two stats looked as
Speaker 1: if they could be stable for a short flight to home.
Speaker 1: By this day, the atrophy and emaciation of my once
Speaker 1: very strong, healthy body was shocking. I could no longer
Speaker 1: even sit up in my hospital bed without being winded
Speaker 1: or gasping for air. Standing up was a special task
Speaker 1: of its own that I could no longer fathom doing
Speaker 1: on my own. I was wheeled in a wheelchair through
Speaker 1: the airport to greet my family. The active, vibrant athlete
Speaker 1: they once knew returned home. It was beaten by an
Speaker 1: unknown cause. We later received a call from Arizona that
Speaker 1: the tissue biopsy did end up growing Valley fever, and
Speaker 1: that Valley fever was indeed the culprit. The year following
Speaker 1: this infection would be very trying, to say the least.
Speaker 1: I continued to be sick, returning to the hospital a
Speaker 1: few additional times. I lived on the couch, barely even
Speaker 1: able to get myself up for months, still coughing up water,
Speaker 1: continuously taking quick, shallow, frightening breaths, and two weeks to
Speaker 1: do much of anything on my own. Everything caused me
Speaker 1: to be out of breath, very different from what I
Speaker 1: grew up knowing. As it stands today, I still get
Speaker 1: a CT scan about once a year, sometimes every six months,
Speaker 1: depending on what my infectious disease doctor says. My lower
Speaker 1: two lobes of my right lung are dead, as well
Speaker 1: as the lower lobe of my left lung. I have
Speaker 1: the equivalent of one lung in my body. The remaining
Speaker 1: tissue eventually took up the task of providing my body
Speaker 1: within the oxygen to live a normal life. So when
Speaker 1: I was able to start moving again after many years,
Speaker 1: exercise became a daunting feed. Getting my heart right up
Speaker 1: was very difficult and typically resulted in a coughing attack.
Speaker 1: It took years for me to work up the stamina
Speaker 1: to ride a bike. To this day, I cannot run
Speaker 1: and am a mediocre athlete at best. I can enjoy
Speaker 1: movement for the most part and do what my lungs
Speaker 1: will allow. Walking up hills and stairs tend to be
Speaker 1: most difficult. I'm on forever anti fungals because for whatever reason,
Speaker 1: my body, being an anomaly, doesn't like to fight balley fever. However,
Speaker 1: today I'm grateful for a body that did fight. Though
Speaker 1: my goals and ambitions changed drastically, I survived and walked
Speaker 1: today with the equivalent of one lung.
Speaker 2: Thank you so much, Tori for sharing your story with us.
Speaker 3: Yeah, wow, thank you, thank you. Hi.
Speaker 2: I'm Aaron Welsh and I'm Erin Alman Updike and.
Speaker 3: This is this podcast will Kill You.
Speaker 2: And today we're talking about coccidioido micosis.
Speaker 3: Oh well done.
Speaker 2: Thank you.
Speaker 3: We think that's how we're supposed to say it.
Speaker 2: We've been practicing a lot.
Speaker 3: Yeah, if that's the wrong way to pronounce it, and
Speaker 3: it's really bothering you. It's gonna be a long episode
Speaker 3: for you, guys.
Speaker 2: It's gonna be terrible. It's gonna be worse than g
Speaker 2: a idea.
Speaker 3: But listen, I went to YouTube and I found like
Speaker 3: an actual clinical lecture on coxadioidomycosis. Nailed it hopefully, and
Speaker 3: this is how the person pronounced it, And so we
Speaker 3: got our pronunciations from a clinical lecture from like a
Speaker 3: school of public health.
Speaker 2: So we're trying our best as always. AKA. In case
Speaker 2: you have not heard of this, the other name for
Speaker 2: it is valley fever.
Speaker 3: Yes, this is going to be a cool one because
Speaker 3: it's our first human fungal pathogen.
Speaker 2: Which is just I can't believe it's taken us this long.
Speaker 2: We've done Kittred, we did Kittrid, and actually someone asked
Speaker 2: us recently if we've ever done courtyceps, which we haven't
Speaker 2: done on this podcast, but we did talk a lot
Speaker 2: about courtyceps on an episode of the Biology of Superheroes podcast. Yeah,
Speaker 2: so definitely check that one out if you haven't listened
Speaker 2: to that already.
Speaker 3: Oh yeah, but we're not talking about cordys ups today.
Speaker 3: We're talking about coxidioid of mycosis.
Speaker 2: But before we begin, it's quarantiny time.
Speaker 3: It is quarantiny time, my favorite time. What are we
Speaker 3: drinking this week?
Speaker 2: We're drinking the dust Devil.
Speaker 3: This is a fantastic name, and it's so fantastic that
Speaker 3: we cannot take credit for it. I actually found it.
Speaker 3: It was the title of a paper. Some of the
Speaker 3: papers I read for this episode have the greatest titles.
Speaker 3: This one is dust Devil, The Life and Times of
Speaker 3: the fungus that causes Valley Fever. Oh, I love it great,
Speaker 3: and that's by Lewis Bauers and Barker. Another one of
Speaker 3: my favorite papers paper titles for this episode was coxcidioido mycosis.
Speaker 3: What a long strange trip it's been, or something to
Speaker 3: that effect.
Speaker 2: It's like, hoorable.
Speaker 3: Yeah, that's great. Anyway, what is in the dust Devil?
Speaker 2: It's a tequila based pair cider situation.
Speaker 3: Yeah, it's tasty. It's got tequila, of course, it's got
Speaker 3: like pair juice. It's got a spiced simple syrup and
Speaker 3: we threw in some orange liquor. And anyway. We will
Speaker 3: post the full recipe for this quarantini as well as
Speaker 3: our non alcoholic plus suberrita on our website This podcast
Speaker 3: will Kill You dot com as well as on all
Speaker 3: of our social media channels, so make sure you follow
Speaker 3: us there.
Speaker 2: Definitely, what other business do we have to attend to aarin.
Speaker 3: We got some of the most incredible responses from our
Speaker 3: sweating sickness episode or after our sweating sickness episode.
Speaker 2: Yeah we did.
Speaker 3: Oh my gosh, so many people you know wrote to
Speaker 3: us or commented with their different hypotheses as to like
Speaker 3: what caused this, you know, super bizarre disease. And I
Speaker 3: wanted to shout out one in particular from someone who
Speaker 3: wrote us this like incredibly detailed email about how they
Speaker 3: went down into this deep rabbit hole looking into possible
Speaker 3: causes and came up with a walnut mold penetrum a
Speaker 3: as their hypothesis.
Speaker 2: Like I just love it, Like I love that there
Speaker 2: are people out there as nerdy as us doing these deep,
Speaker 2: deep dives on things like what caused sweating sickness?
Speaker 3: Yeah, and came beautiful a walnut mold And like, honestly,
Speaker 3: I'm I'm kind of I kind of buy it. It
Speaker 3: seems like quite plausible, like the symptoms lineup, a food
Speaker 3: borne toxin could very well move along trade routes like
Speaker 3: we talked about. And I just wanted to say thank
Speaker 3: you for everyone's responses and this email in particular, because
Speaker 3: I got such a kick.
Speaker 2: Out of it. I love it.
Speaker 3: Do we have more business?
Speaker 2: I did want to say I finally checked our po
Speaker 2: box that I'm really bad about checking. And I wanted
Speaker 2: to say thank you you to Sabrina for your thank
Speaker 2: you note. Oh my gosh, so adorable. She sent us
Speaker 2: a thank you card just to say thanks for making
Speaker 2: the podcast, so that she really likes it and I
Speaker 2: really like you.
Speaker 3: It was the sweetest thing.
Speaker 2: Anyways, that's all.
Speaker 3: Okay, okay, let's talk fungus, please please.
Speaker 2: We'll take a quick break and then dive into the
Speaker 2: biology of coxdioido my coases? Do I say it right
Speaker 2: that time?
Speaker 3: I think so?
Speaker 2: I think I did. Okay, coxiitu aido my coas aka
Speaker 2: valley fever akaur, first human fungal pathogen. It's actually two
Speaker 2: different species of fungi, Coxidioides imodus and Coxidioides pos odyssey,
Speaker 2: which are both endemic to desert areas in mostly the
Speaker 2: southwestern US, so Coxidioides immodus tends to be more prevalent
Speaker 2: in California and Coxidioides posodicy mostly in Arizona, but these
Speaker 2: fungi are also found throughout New Mexico, Utah, into Texas.
Speaker 2: We'll talk a little bit later about how maybe it's
Speaker 2: all the way up in Washington as well as down
Speaker 2: into parts of Mexico and Central and South America. So
Speaker 2: let's get into the disease that's actually caused by this fungus.
Speaker 2: This is a pathogen that is not contagious, so it
Speaker 2: has not been shown to be spread from person to
Speaker 2: person or from animal to person. Because this is also
Speaker 2: a fungus that can infect other animals aside from humans,
Speaker 2: especially dogs. But I am not really going to talk
Speaker 2: anymore about infection in animals like at all. But this
Speaker 2: is a fungus that's called dimorphic, so it has two
Speaker 2: entirely different forms that it exists in. And I have
Speaker 2: to confess that I know so little about fungus that
Speaker 2: I still have so many questions about how the heck
Speaker 2: this is possible, Like it's so fascinating. Okay, let's get
Speaker 2: into it. In the environment, this fungus exists as a mold.
Speaker 2: It's called a miceelium. So if you were to grow
Speaker 2: a whole bunch of it, like very concentrated in like
Speaker 2: a jar or something, and pick it up, it would
Speaker 2: look kind of like a little cotton puff like a
Speaker 2: little ball of white little wispies like cotton candy yum. Microscopically,
Speaker 2: if you look at these little wispies in more detail,
Speaker 2: they look they're called branching septate hiphie, what does that mean.
Speaker 2: They're kind of like, this is the way I'm gonna
Speaker 2: describe it. Arin, It's like a tree made out of
Speaker 2: toilet paper. So it's like long stringy bits that have
Speaker 2: branches like a tree wood, but then they're separated at
Speaker 2: certain points like the way that toilet paper is, so
Speaker 2: it has septations, Okay, And so what happens is that
Speaker 2: during times of drought or low precipitation, those like toilet
Speaker 2: paper squares, which in the fungus are called arthrocnidia or arthrospores,
Speaker 2: they dry out and then they break off super easily,
Speaker 2: Like if your house got toilet papered and then the
Speaker 2: wind picked up and broke off a bunch of little
Speaker 2: squares of toilet paper, and then toilet paper flew all
Speaker 2: around your neighborhood. Yeah, and then what happens is that you,
Speaker 2: as a human breathe those spores in. So that is
Speaker 2: kind of the life cycle in the environment. So you
Speaker 2: have these mycelia, these little long, branchy stringy bits that
Speaker 2: break off when they dry out and then can become
Speaker 2: borne on the wind in the soil.
Speaker 3: Excellent.
Speaker 2: Now you breathe them in, and now we have to
Speaker 2: talk about what happens in us because it's totally completely
Speaker 2: different than what happens in the environment. So when you
Speaker 2: breathe in a spore literally potentially just one, it only
Speaker 2: has to be one spore could potentially infect you. What
Speaker 2: happens is you breathe it in and it goes down
Speaker 2: into the bottom of your respiratory tract and lodges in
Speaker 2: your terminal alveoli, your terminal bronchioles, like right where gas
Speaker 2: exchange is supposed to be happening. And once it gets there,
Speaker 2: it begins to enlarge and it forms what's called a
Speaker 2: sphere youle, like a big sphere.
Speaker 3: Okay, I don't know why it's called that, like a
Speaker 3: beach ball in your lung.
Speaker 2: In this spherule, it begins to replicate and forms thousands
Speaker 2: of endospores ooh, within this sphere in the spherule, okay.
Speaker 2: And then eventually that spherule will rupture and release those
Speaker 2: thousands of endospores that can go on to travel form
Speaker 2: new spherules which make more endospores, et cetera, et cetera.
Speaker 3: That's cool. So it brings its own little like reproductive machinery.
Speaker 2: Yeah, it just it does it all on its own.
Speaker 2: It's asexually reproducing. Just boot boom, boom boom. Make it
Speaker 2: a bunch of little endospores. But that's completely different than
Speaker 2: how it lives and replicates in the environment, in the soil.
Speaker 2: And it gets even weirder because if, for example, you
Speaker 2: take a sample of someone's speutum like like gunk that
Speaker 2: they coughed up when they were infected with coxidioids, and
Speaker 2: that's a whole bunch of endospores inside a spheerule. If
Speaker 2: you left that on the counter, it would grow my celium,
Speaker 2: It would grow into the environmental form, which by the way,
Speaker 2: would be highly infectious if it dried out.
Speaker 3: So there's some kind of cues that it's using.
Speaker 2: Yeah, some kind of cues to know that it's in
Speaker 2: a host versus in the external environment.
Speaker 3: I wonder what those cues are.
Speaker 2: Me too, Aaron, me too, huh. But we're going to
Speaker 2: focus on what happens when it's inside of your body.
Speaker 2: If somebody is a fungus researcher, it would be awesome
Speaker 2: to know more details about that fungus because woboy. But
Speaker 2: in general, once this happens inside of our lungs, our
Speaker 2: body reacts to this fungus, it's going to induce an
Speaker 2: immune response. It's going to recruit a lot of inflammatory cells,
Speaker 2: and that's going to kind of result in the symptoms
Speaker 2: that we see. So let's talk about those. Yeah, if
Speaker 2: you have any symptoms at all, which about forty percent
Speaker 2: of people who get infected with coxidioids will sixty percent
Speaker 2: of people won't have any symptoms at all. If you
Speaker 2: have these symptoms, most commonly it presents as an acute pneumonia.
Speaker 2: And I think we've talked very peripherally about pneumonia in
Speaker 2: the past. I'm actually going to talk kind of a
Speaker 2: lot about pneumonia in this episode, which is exciting. Yeah,
Speaker 2: but pneumonia is basically just the way that we say
Speaker 2: there's an infectious cause of inflammation and fluid filling up
Speaker 2: the air sacs of the lungs. Okay, so it's inflammation
Speaker 2: of the lungs. But pneumonia is used specifically to mean
Speaker 2: an infectious cause of that inflammation. So with coxidioido micosis,
Speaker 2: did I get that right?
Speaker 3: I think so. Honestly, it's it's like we've said it
Speaker 3: and I've thought it so many times, and to sound.
Speaker 2: Weird, I know, one to three weeks after inhalation of
Speaker 2: the spores, you have basically pretty typical pneumonia symptoms. Fever,
Speaker 2: a cough that's quite productive of like gunk, very profound fatigue,
Speaker 2: like just feeling very exhausted, and probably chest pain, especially
Speaker 2: when you take really deep breaths. With coxidioid's infection, it's
Speaker 2: also really common to have a headache and the chest
Speaker 2: pain tends to be very severe. And with this type
Speaker 2: of pneumonia, the fatigue can last for months and months,
Speaker 2: so even as the pneumonia resolves, that fatigue can persist. Okay,
Speaker 2: if you were to take a chest X ray or
Speaker 2: a chest CT scan, which would be very likely to
Speaker 2: happen if you went to the er or the doctor's office,
Speaker 2: it would look like pretty much most other causes of pneumonia,
Speaker 2: which means it would look like there's fluid in some
Speaker 2: portion of your lung, either in just one lobe or
Speaker 2: maybe in like the middle region, which is called the
Speaker 2: high lar region around the trachea, like where the trachea divides,
Speaker 2: you might have some swollen lymph nodes along that region.
Speaker 2: That's a little bit more common with a cooxidioides pneumonia
Speaker 2: than other types of pneumonia. One other thing you might
Speaker 2: have that's not as common with other forms of pneumonia
Speaker 2: is you might have some skin changes, like some red,
Speaker 2: painful swollen bumps along your shins that are called erythema nodosum,
Speaker 2: or another red splotchy rash that can occur kind of
Speaker 2: across your body that's called arithema multiform.
Speaker 3: Question, Okay, what else causes those two things?
Speaker 2: So a number of different These are not specific to
Speaker 2: coxidioides infection. These are both caused by an immune response
Speaker 2: to this infection, not from a disseminated fungus. So there's
Speaker 2: actually a number of different infections that can cause similar
Speaker 2: findings viruses and bacteria.
Speaker 3: Okay, but I mean, like, I guess what's the mechanism,
Speaker 3: Like why does that happen in these different infections?
Speaker 2: That's a really good question that I don't know the
Speaker 2: specifics of it. Aside from the fact that whatever specific
Speaker 2: immune response is being generated, that's what then causes this.
Speaker 3: Okay, and this is only like an occasional mm hmm,
Speaker 3: it's not always sign of disease, okay.
Speaker 2: Yeah. Yeah, So it's also kind of person specific, like
Speaker 2: some people might be more likely to have this immune
Speaker 2: response than others. But most of these people with this
Speaker 2: presentation will recover and be pretty much fine with or
Speaker 2: without any treatment. And keep that in mind, ding ding
Speaker 2: ding with or without treatment, because it'll become really important
Speaker 2: later on. Okay, but some people won't. So there's a
Speaker 2: few other forms that this disease can take. Some people
Speaker 2: will go on to have a chronic form of pneumonia
Speaker 2: that's called chronic progressive pneumonia. And I had a hard
Speaker 2: time finding the exact percentage of people that go on
Speaker 2: to have like a chronic pneumonia, which basically would be
Speaker 2: all the same things that you had with this pneumonia,
Speaker 2: so cough potentially coughing up blood because you have so
Speaker 2: much inflammation and infection. You'd go on to have weight
Speaker 2: loss because you've essentially been sick for so long that
Speaker 2: you're just not eating. You feel really really bad, the
Speaker 2: fatigue is extreme, and on X ray you still see
Speaker 2: those same pneumonia changes. But what based on everything that
Speaker 2: I read, it seems like it's likely less than five
Speaker 2: percent of the time. But I didn't get a hard
Speaker 2: number on chronic pneumonia. Okay, But even if the pneumonia
Speaker 2: resolves or is treated and goes away, sometimes all of
Speaker 2: the fluid and gunk that's left behind from the infection
Speaker 2: can kind of persist. And what it does is contract
Speaker 2: into like a cavity that our body kind of walls
Speaker 2: off and it just stays there. And this can happen
Speaker 2: like five to ten percent of the time, So you'd
Speaker 2: still see like a nodule or a cavity if you
Speaker 2: looked at an X ray of a person with this.
Speaker 3: This is in their lung, in their lung.
Speaker 2: And now most of the time that's all and nothing
Speaker 2: ever happens beyond that. But in thirty to sixty percent
Speaker 2: of people with these nodules, they actually still have an
Speaker 2: active infection. It's just not spreading or doing anything. So
Speaker 2: if you tested them for coxidioides, you would find it.
Speaker 2: And so this could potentially reactivate or have like waxing
Speaker 2: and waning symptoms.
Speaker 3: Wait a second, so the fungus is still there in
Speaker 3: that nodule, hmm, but it's been walled off.
Speaker 2: It's been walled off.
Speaker 3: So it's like that Edgar Allan post story The Cask
Speaker 3: of a Mantiato do you ere talking about.
Speaker 2: I probably have read it, but I don't specifically remember it.
Speaker 3: It's the one where they wall the guy up inside.
Speaker 3: Oh yeah, they wall him up and like leave.
Speaker 1: Yeah.
Speaker 2: I was gonna say it's kind of like tb oh.
Speaker 2: But yeah, also that I feel like that says a
Speaker 2: lot about our personalities. Yeah, this is not uncommon in
Speaker 2: other fungal infections as well. Fungal infections are very difficult
Speaker 2: to kind of treat and deal with, and our immune
Speaker 2: system doesn't always do a great job of responding to them. Now,
Speaker 2: there's something else that can happen that gets a lot worse.
Speaker 2: So in somewhere between one and five percent of cases,
Speaker 2: the infection can spread beyond the lungs and result in
Speaker 2: what's called disseminated disease. So overall, if you look at
Speaker 2: everyone who gets infected with coxidioids, the percentages are like
Speaker 2: somewhere between one and five percent. But if you look
Speaker 2: just at people who are in some way immunal compromised,
Speaker 2: whether that's from HIV infection that has a low CD
Speaker 2: four k out or some kind of congenital immuno deficiency,
Speaker 2: someone who's on immunosuppressants because of an organ transplant or whatever.
Speaker 2: In this group, it's like thirty to fifty percent of
Speaker 2: people could go on to develop disseminated disease.
Speaker 3: Okay, So it's like, so.
Speaker 2: It's disproportionate who is like to get a disseminated infection,
Speaker 2: right right, But even in people who are otherwise immunocompetent,
Speaker 2: somewhere between like one to three percent of people will
Speaker 2: go on to develop this systemic infection.
Speaker 3: Okay.
Speaker 2: So once this fungus spreads from beyond your lungs, so
Speaker 2: it like makes its way from your alveo light out
Speaker 2: into your bloodstream. It can go literally anywhere and infect
Speaker 2: in theory any organ or any system. But there are
Speaker 2: a few places that it goes. Most commonly the skin
Speaker 2: is one of them, and this results in kind of
Speaker 2: ulcerations or nodules or big kind of like blisters that
Speaker 2: that burst open that you see on the skin. It
Speaker 2: can go to the lymph nodes, which would cause a
Speaker 2: lot of lymph swelling. It can go to the joints,
Speaker 2: which would cause a lot of joint pain. But the
Speaker 2: most severe and terrifying manifestation is if it goes to
Speaker 2: the meningis, which is the lining of our central nervous system.
Speaker 2: So this means it's managed to cross the blood brain
Speaker 2: barrier and result in meningitis, which if untreated, is fatal
Speaker 2: over ninety percent of the time. And this also tends
Speaker 2: to happen months or even years after an initial respiratory
Speaker 2: pneumonia type infection. Months or years. Yeah, So it's a
Speaker 2: long process of this fungus making its way through our
Speaker 2: body and wreaking havoc.
Speaker 3: So is it possible that somebody becomes infected and then
Speaker 3: doesn't know for years and years that this is what
Speaker 3: they have?
Speaker 2: I don't think for years and years, but put potentially yes,
Speaker 2: because for example, if they form like a nodule and
Speaker 2: they're otherwise immunocompetent, then their immune system can keep that
Speaker 2: at bay. If they then become immunosuppressed for some reason
Speaker 2: later on, this could be reactivated.
Speaker 3: Okay, yeah, gotcha.
Speaker 1: Yeah.
Speaker 2: So yeah, So that's kind of like the general overall
Speaker 2: biology of cocidioidomycosis. Well said, thank you. It is treatable
Speaker 2: with anti fungals. But the thing is, and I'll talk
Speaker 2: a little bit more about this in the current event section,
Speaker 2: it's a very underdiagnosed cause of pneumonia, even in regions
Speaker 2: where it's endemic, like where we know that it's definitely circulating.
Speaker 2: So a lot of people who present with pneumonia just
Speaker 2: get antibiotics and then they're sent on their way home.
Speaker 2: So that's why a lot of people just recover without
Speaker 2: ever actually getting the proper treatment, because they just got
Speaker 2: antibiotics and then they felt crappy for like three months
Speaker 2: and then they got better. Maybe that was a fungus.
Speaker 2: But there are guidelines for when you should treat versus
Speaker 2: when you don't necessarily need to treat if you think
Speaker 2: someone's going to clear it, but it's they're not clear.
Speaker 2: There's not a good consensus. We don't have good evidence
Speaker 2: based guidelines on exactly how to treat coxadyoidemic oasis.
Speaker 3: It seems interesting considering Well, I'll talk about the history
Speaker 3: a bit, but.
Speaker 2: Like, I can't wait to hear about the history, Aaron,
Speaker 2: can you please tell me all about it? Because I
Speaker 2: read like a tiny bit by accident, and I was like, what.
Speaker 3: Wait, are you ready now?
Speaker 2: Yes, I'm ready now.
Speaker 3: Oh okay, I'm not so let's take a quick break.
Speaker 4: First day.
Speaker 3: Prominently displayed at the Institute of Parasitology in Buenos Aires
Speaker 3: is a head a human head stored in formuline and
Speaker 3: labeled as Exhibit one.
Speaker 2: Oh gosh.
Speaker 3: When this preserved head was discovered in nineteen forty eight,
Speaker 3: there was no identifying card to describe who the head
Speaker 3: once belonged to, when it was removed for storage, and
Speaker 3: why it was preserved. I'm sorry, someone just came across
Speaker 3: a head like it in a jar in formulae. Yeah, okay,
Speaker 3: uh huh, not creepy at all. Well, and the guy
Speaker 3: who came across this head, doctor Flavio Ninho, didn't need
Speaker 3: any sort of card to tell him who it was.
Speaker 3: He recognized it immediately as being the head of Domingo Escura,
Speaker 3: removed and preserved after Escura's death fifty years prior.
Speaker 2: What aaron.
Speaker 3: Okay, so we've got the who and the when, but
Speaker 3: the why remains. Why was this head removed and placed
Speaker 3: in formulin in eighteen ninety eight and as far as
Speaker 3: I know, still on display in twenty twenty one. What
Speaker 3: because it turns out that this head's original owner, Domingo Escura,
Speaker 3: was the first described case of coxidioido micosis.
Speaker 2: So someone preserved his head.
Speaker 3: So someone preserved his head.
Speaker 2: Okay, Yeah.
Speaker 3: In January eighteen eighty eight, Domingo, who was then a
Speaker 3: thirty two year old member of the cavalry in Northern Argentina,
Speaker 3: he woke up from a nap and noticed what he
Speaker 3: thought was a spider bite on his right cheek. Spoiler alert,
Speaker 3: it's never a spider bite, never a spider bight, unless
Speaker 3: you're in Australia, that might be a different story, but like,
Speaker 3: it's never a spider bite.
Speaker 2: Never a spider bite. That's our, that's our title.
Speaker 4: That's our.
Speaker 3: He tried various treatments to heal the lesion, but nothing
Speaker 3: seemed to work. The original lesion grew larger and rougher,
Speaker 3: his lymph nodes swelled, and new lesions appeared all over
Speaker 3: his face and neck. Eventually, he sought help at the
Speaker 3: military hospital, where they promptly diagnosed him with lupus vulgaris
Speaker 3: and discharged him with a prescription for nitric acid. But
Speaker 3: Of course, the nitric acid didn't do anything, so when
Speaker 3: the lesions continued to get worse, he was sent to
Speaker 3: a hospital in Buenos Aires. This time he was diagnosed
Speaker 3: with micosis fungoides Aaron, What is that? Just like briefly
Speaker 3: I googled it and I can't remember now.
Speaker 2: It's a type of T celldomphoma. So it's a type
Speaker 2: of cancer of the skin that manifests with a lot
Speaker 2: of skin.
Speaker 3: Okay, it's interesting because it has mico in the and
Speaker 3: so it makes you think that it's fungus related, but
Speaker 3: it's also micosis fungoidies.
Speaker 2: I know, it's very confusing, but yes, it's a type
Speaker 2: of tea cellomphoma.
Speaker 3: Not infectious, not contagious, not whatever, okay, okay. And so
Speaker 3: these treatments once again failed, and then he was put
Speaker 3: under the care of Alejandro Posadas, who was a twenty
Speaker 3: one year old intern with a mustache that makes cellad
Speaker 3: Ali's look like tame. It is an incredible it might
Speaker 3: be the most incredible mustache I've ever seen. WHOA Yeah.
Speaker 3: At this point, when Pisadas first met Domingo, Domingo had
Speaker 3: a large, purple, fungal like mass covering his right cheek
Speaker 3: and vegetations on his nose, his arm, his trunk, and
Speaker 3: his extremities. He must have been in incredible discomfort, and Posadas,
Speaker 3: trying to find out what exactly was going on, put
Speaker 3: some of Domingo's lesions under the scope and noticed that
Speaker 3: it was riddled with multi nucleated giant cells and then
Speaker 3: some smaller cells with granular contents. He put two and
Speaker 3: two together and figured that these cells were a type
Speaker 3: of protozoan.
Speaker 2: Okay, they weren't.
Speaker 3: He tried, though, he tried, but that they were a
Speaker 3: proper be the ones responsible for Domingo's condition, Okay. And
Speaker 3: he published his findings in eighteen ninety two. So this
Speaker 3: is like the first time that what would later turn
Speaker 3: into coccidioido mycosis was described this unique but kind of
Speaker 3: like you know, lonely case and that it was singular, right,
Speaker 3: could have gone unnoticed for years. But and this is
Speaker 3: what just really gets me. It didn't like, I feel
Speaker 3: like so many times we've come across oh, and then
Speaker 3: you know, finally someone had to look back hundreds of
Speaker 3: years and I linked together all these cases.
Speaker 2: Yeah, like it was lost for decades or whatever. And
Speaker 2: then they found the same thing and then saw it
Speaker 2: in some record somewhere.
Speaker 3: Yeah. Yeah, but yeah, this case wasn't lost to time
Speaker 3: or whatever, because a couple of years before Domingo Eskura
Speaker 3: noticed his spider bite that wasn't actually a spider bite. Yeah,
Speaker 3: another guy by the name of Joas Furtado Silverie had
Speaker 3: immigrated from the Azoris to San Francisco, where he began
Speaker 3: working as a farm laborer, and soon after his arrival
Speaker 3: he noticed a sore on his neck that just wouldn't
Speaker 3: go away. He ended up seeking medical help. Nothing made
Speaker 3: it better, and he eventually deteriorated until he died much
Speaker 3: more quickly actually, than Domingo Escura. He had to endure
Speaker 3: much more horrifying treatments like carbolic acid, cauterization, bromine plus cocaine. Yeah,
Speaker 3: and seemed to suffer much more before his death in
Speaker 3: eighteen ninety five. And before he died, a couple of
Speaker 3: doctors popped a bit of tissue from his neck lesion
Speaker 3: under a scope and once again they saw giant cells
Speaker 3: and granulated cells of various sizes, which they realized were
Speaker 3: just like the ones that Pisadas had written about. They
Speaker 3: were like, Hey, that reminds me.
Speaker 2: I am this very impressed.
Speaker 3: I know, I know, and they did, though they did
Speaker 3: disagree with the diagnosis of micosis fungoides, but they did
Speaker 3: notice the connection between the two conditions and once again
Speaker 3: said these cells were likely responsible. They also believed that
Speaker 3: they were a new species of protozoin, which they weren't.
Speaker 3: It's fine, and thought that they looked similar to Coxidia,
Speaker 3: and so they named it coxidioidesh coxity alikes.
Speaker 2: Okay, yeah, And.
Speaker 3: These two researchers who were doing this study, Rixford and Gilchrist,
Speaker 3: presented all these findings at a meeting of the California
Speaker 3: Academy of Medicine in eighteen ninety four. Okay, and so
Speaker 3: begins the modern history of coxidioidomcosis. But before I keep
Speaker 3: going on that path, you know that I have to ask,
Speaker 3: but what about the not so modern history. So these
Speaker 3: two Domingo and Joas, we're not the first two people
Speaker 3: to get infected of course, this little fungus.
Speaker 2: Right, Okay, we've learned nothing from this podcast. We've learned
Speaker 2: that that is absolutely not the case, absolutely not the case. Okay,
Speaker 2: So we have to go back way way back. So
Speaker 2: you mentioned that coxidioid in mycosis is caused by these
Speaker 2: two species of fungus, Coxidiodes imatus and Coxidiodes pasodasy. And
Speaker 2: even though it was relatively recently that Coxidioides pasodasy was
Speaker 2: recognized to be a separate species, it was like two
Speaker 2: thousand and two, I think it turns out that this
Speaker 2: species is actually much older than Coxidioides imatus, and it's
Speaker 2: likely that immatus evolved from pasodasy.
Speaker 3: So, and there seems to be still a little bit
Speaker 3: of debate about the geographic origins of Coxidioides pasodasy, but
Speaker 3: most papers I read seem to agree that it is
Speaker 3: thought to have originated somewhere in southern Arizona or in
Speaker 3: northern Mexico, maybe around like eight hundred thousand years ago,
Speaker 3: and then more recently like well, not recently to us,
Speaker 3: but like more recently three hundred and sixty five thousand
Speaker 3: years ago. Cocidioides imatus, which is found most commonly and
Speaker 3: has the most diversity in the Central Valley of California,
Speaker 3: that's thought to have diverged from pasodicy when like the
Speaker 3: glaciers and the inland sea of that area of California retreated,
Speaker 3: so it kind of like trapped it there in this
Speaker 3: little like you know, only home.
Speaker 2: Exactly little allapatric speciation.
Speaker 3: There we go, keeping isolated by the Sierra Nevadas.
Speaker 2: Yeah.
Speaker 3: Yeah, And the next big moment in the evolutionary history
Speaker 3: of this little fungus is the arrival of humans in
Speaker 3: North America. And there's a cool paper from two thousand
Speaker 3: and one, so it might be a little bit out
Speaker 3: of date, but current papers still do reference it. And
Speaker 3: it traced the genomic diversity of different isolates of Coxidiodes
Speaker 3: pasodasy so the older one all throughout the regions that
Speaker 3: it's been found in North America and South America, and
Speaker 3: found that based on the types of and the levels
Speaker 3: of diversity in the South American isolates, it seems that
Speaker 3: during the Pleistocene, ancient humans who migrated down from North
Speaker 3: America to South America also brought the fungus with them
Speaker 3: along those migration routes.
Speaker 2: Okay, okay, yeah.
Speaker 3: But their estimate of when Coxidioides pasodisey arrived in South
Speaker 3: America is like a little bit broad, so anywhere between
Speaker 3: nine and one hundred and forty thousand years ago.
Speaker 2: No big deal, No big deal.
Speaker 3: I mean those are pretty big range. They so they
Speaker 3: also say, Okay, yeah, it could have been like a
Speaker 3: species of rodent, or it could have been before. But
Speaker 3: that does seem to be like the direction that how
Speaker 3: it happened, okay, okay. And I will say that a
Speaker 3: lot of this genomic analyzes of like the evolutionary history
Speaker 3: and stuff are kind of plagued by these problems of
Speaker 3: low of like sampling bias. So like, because Arizona has
Speaker 3: been so extensively sampled, is it just that we think
Speaker 3: it originated there because we see the most diversity. If
Speaker 3: we sampled more in Guatemala, for instance, might there be
Speaker 3: might that point to a Guatemalan origin?
Speaker 2: Totally that totally makes sense.
Speaker 3: Yeah, So in any case, ancient humans in North and
Speaker 3: South America were no stranger to this fungus. And to
Speaker 3: further show this, there's a skeleton from Arizona from around
Speaker 3: one thousand to fourteen hundred CE that has signs of
Speaker 3: destructive lesions and also microscopic examination show that there were
Speaker 3: spherules and endospores that resembled Coxidio imatus or pasodyssy. It's
Speaker 3: an older paper, so everything was called imetus. What, Yeah,
Speaker 3: that's so cool.
Speaker 2: We haven't had bones in a while, air, I know.
Speaker 3: Well, and they were like, well, you know, it's not
Speaker 3: like this may not necessarily cause like actual lesions on
Speaker 3: the skeleton necessarily, but they were like, we weird. They
Speaker 3: were pretty confident it wasn't just contamination from the soil,
Speaker 3: because that you could imagine being a big problem. Yeah.
Speaker 3: And then in prehistoric middens, so like old trash heaps,
Speaker 3: essentially in California, Coxidioides imtis was found at higher rates
Speaker 3: than in surrounding soil, which could suggest that the people
Speaker 3: who use the middens had the disease. That one's a
Speaker 3: little bit more hand wavy to me.
Speaker 2: Yeah, definitely, all right.
Speaker 3: So coxidioido micosis has probably been around and infecting people
Speaker 3: and animals for hundreds of thousands of years before it
Speaker 3: was first described, and Domingo and jo just happened to
Speaker 3: be the first two people whose unfortunate encounter with this
Speaker 3: fungus was documented, but they definitely weren't the last. And
Speaker 3: these two reports, instead of being lost and forgotten, somehow
Speaker 3: ended up kicking off this era of cuxidioido mycosis research
Speaker 3: that picked up steam significantly throughout the twentieth century and
Speaker 3: so after. And part of it is because after those
Speaker 3: first two cases happened, more steamed to kind of like
Speaker 3: steadily trickle in, and the geographic patterns of this disease,
Speaker 3: like you know how they kept popping up in the
Speaker 3: same areas that helped physicians kind of make the link
Speaker 3: between them all got it in nineteen hundred, So just
Speaker 3: a few years after Rixford and Gilchrist named their new microbe,
Speaker 3: a physician also working in San Francisco named William o'fools ophuls, who,
Speaker 3: by the way, had a scar on his cheek from
Speaker 3: a duel back in Germany.
Speaker 2: Love it.
Speaker 3: He later became the dean of the Stanford School of Medicine. Wow,
Speaker 3: with a dueling scar, his cheek are so cool in
Speaker 3: nineteen hundred, Okay, in nineteen hundred and so Ofals was like,
Speaker 3: wait a sec, this is not a protozoin. It's definitely
Speaker 3: a fungus, you guys, what's going on? And so he
Speaker 3: did a bunch more research on it, describing its life cycle,
Speaker 3: it's various morphologies, it's root of transmission and proposing a
Speaker 3: name for the disease, which he called coxidioidal granuloma. But
Speaker 3: this disease, coxidioidal granuloma, was often was like the more
Speaker 3: severe of the ones that you described, right, So it
Speaker 3: was like super painful, disfiguring, debilitating, sometimes fatal. And that
Speaker 3: makes sense that that would be the one described first, right.
Speaker 2: And that was So that's a disseminated infection. So that's
Speaker 2: an infection that has gone to the skin and presumably
Speaker 2: also to other organs, which would be why it would
Speaker 2: be fatal.
Speaker 3: Right exactly. But that's not the only form of disease
Speaker 3: that coxidioids causes.
Speaker 2: And it's certainly not the most common.
Speaker 3: Right so. So east of San Francisco, residents of the
Speaker 3: San Joaquin Valley were plagued by a mild illness which
Speaker 3: usually consisted of respiratory symptoms, a high white blood cell count,
Speaker 3: and sometimes those painful lumps or those red lumps erythema nodosum.
Speaker 3: People called it San Joaquin Valley fever, and no one
Speaker 3: could figure out what was causing it. A physician named
Speaker 3: Mernie Ada Gifford had been working on the problem as
Speaker 3: part of her job as the chief Assistant Health officer
Speaker 3: of Kerrn County in California, and she spent months trying
Speaker 3: to link it to Escaris roundworms. Uh. And then but
Speaker 3: then she finally found coxidioides from a guinea pig that
Speaker 3: had been experimentally infected from like someone's spued him, which
Speaker 3: is poor guinea pig.
Speaker 2: I know.
Speaker 3: And she knew that coxidioides was the pathogen responsible for
Speaker 3: coxidioidl granuloma, But the people she was seeing, like her patients,
Speaker 3: were nowhere near that sick like at all. So could
Speaker 3: there still be a connection or was this just you know, contamination.
Speaker 3: She showed her research to her former teacher mentor Ernest Dixon,
Speaker 3: and asked him whether he thought the two diseases could
Speaker 3: be caused by the same thing. And then she added
Speaker 3: that several of the patients she had treated had also
Speaker 3: presented with Arithema nodosum and for Dixon this was the clincher.
Speaker 2: Huh.
Speaker 3: A few years back, Dixon had a young med student
Speaker 3: working in his lab named Harold Chop who, on day
Speaker 3: one of the job, poor guy opened an old Petrie
Speaker 3: dish like full of an old coxstidioides culture and then
Speaker 3: breathed in a bunch of the old spores. He like,
Speaker 3: he brought it up to look at it closely, breathed
Speaker 3: on it, and it just like all of the spores
Speaker 3: went airborne and then.
Speaker 2: Right into his and breathed it. Oh poor guy.
Speaker 3: Oh yeah. Within nine days, Chope was in the hospital
Speaker 3: with severe chest pain, bad cough, yellowish spudem streaked with blood,
Speaker 3: and there didn't seem to be much of a chance
Speaker 3: that he would recover. And like a bunch of newspapers
Speaker 3: picked up the story and he was presented as this
Speaker 3: like heroic young researcher. You know, martyred for the cause
Speaker 3: of disease. I don't know, but he hung in there.
Speaker 2: Okay, good.
Speaker 3: Eventually he would be discharged from the hospital and sent
Speaker 3: somewhat ironically to Arizona to recuperate. Oh gosh. But before
Speaker 3: that happened, he developed arithema nodosum, which is the same
Speaker 3: symptom that Gifford had observed in some of her patients
Speaker 3: with San Joaquin Valley fever, and to Dixon, this was
Speaker 3: strong evidence that the two diseases, so san Joaquin Valley
Speaker 3: fever and coccidioidal granuloma were caused by the same pathogen, yeah,
Speaker 3: and that the Valley fever was just a mild form
Speaker 3: of yeah.
Speaker 2: Right. I mean it's almost like all of the times
Speaker 2: that we've had people who were reckless enough to intentionally
Speaker 2: infect themselves with whatever thing that they were studying to
Speaker 2: try and improve. But this poor kid just did it.
Speaker 3: Right, I mean in some ways. You know how in
Speaker 3: a Rocky Mountain Spotted Fever episode we talked about how
Speaker 3: like everyone got Rocky Mountain spotted fever or one of
Speaker 3: the other tickborn yeah pathogens. Yeah, it's kind of the
Speaker 3: same thing, right, Like every bunch of people got infected
Speaker 3: who were researchers who worked on this. It was sort
Speaker 3: of like a write of passage.
Speaker 2: I mean, it is very infectious, like one single spore
Speaker 2: and you can get infected. So it's not that surprising.
Speaker 3: It's not that surprising. And so Dixon was like, I've
Speaker 3: solved the puzzle, and he presented this hypothesis at a
Speaker 3: meeting of the California Medical Association, and he never once
Speaker 3: acknowledged that it was actually Gifford who had come up
Speaker 3: with the idea. Yeah, which is really frustrating.
Speaker 2: It is infuriating.
Speaker 3: Eventually, in the nineteen fifties her contribution would be recognized,
Speaker 3: but like, still really annoying.
Speaker 2: Yeah.
Speaker 3: So, now that researchers had a better picture of the
Speaker 3: disease caused by coxidioides, they could start digging into questions
Speaker 3: like where does this happen, what animals does this happen to?
Speaker 3: How often does it happen? And so on, and these
Speaker 3: massive questions would almost all be taken up by another
Speaker 3: of Dixon's students. So Gifford was one of Dixon's students,
Speaker 3: a guy named Charles Smith, also Harold Chope's frat brother.
Speaker 3: Just like, this is just perfectly illustrates how it It's
Speaker 3: not either incestuous or connected the world is.
Speaker 2: It's a small world.
Speaker 3: If you have a very specific study organism, everyone knows everyone.
Speaker 3: And Smith spent the late nineteen thirties wandering all over
Speaker 3: Kern and Tulare Counties in a truck named the Flying Climittispor.
Speaker 2: Nope, yep, don't call it that.
Speaker 3: A clmitispor is a thick walled hiphel cell that functions
Speaker 3: as a spore. It's what I have in parentheses. I
Speaker 3: love it. And he was just like looking for people
Speaker 3: who had developed arathema nodosum. Okay, he was like, okay,
Speaker 3: like I want to know, and so what he and
Speaker 3: he found what he was looking for because over eighteen
Speaker 3: months he saw over four hundred people who reacted to
Speaker 3: a skin test with coxadiyden and this is in two
Speaker 3: counties in California. Like, I feel like that's kind of substantial, Aaron.
Speaker 2: I can't wait to tell you about the current events.
Speaker 3: It's oh, I have a little bit of a taste
Speaker 3: of it. It's yeah, I'm sure fine, yep. And he
Speaker 3: found that a good chunk of the people who seemed
Speaker 3: to have been infected at one point were just asymptomatically infected,
Speaker 3: and that the disease was much more prevalent than previously thought,
Speaker 3: and that people who were new to the area or
Speaker 3: and I saw this in a lot of the early
Speaker 3: studies weren't white seemed to be more likely to develop
Speaker 3: severe disease. And I know that, like these studies were
Speaker 3: back from the nineteen early nineteen hundreds, and so I
Speaker 3: don't know what their reasons were, but that is like
Speaker 3: a very common thing that you see even in literature
Speaker 3: from today.
Speaker 2: Yeah, all of the literature from today still says the
Speaker 2: same thing, and I agree, I don't know exactly what
Speaker 2: they're basing that on, right, right.
Speaker 3: Yeah, So Charles Smith was also infamous for hating to
Speaker 3: wash glassware, like in the lab. He was like, I
Speaker 3: hate he hated doing it. And so that is how,
Speaker 3: through a series of serendipitous accidents, I don't know, involving
Speaker 3: dirty Wasserman tubes, he developed a compliment fixation test for
Speaker 3: the disease, like accidentally figured out accidentally he like left
Speaker 3: him on the counter, and he was like, A wash
Speaker 3: them later, A wash them later, and then they formed
Speaker 3: these little like buttons that he was like, oh, that
Speaker 3: can be anyway. This was a huge step forward, though,
Speaker 3: this compliment fixation test, because it became the standardized way
Speaker 3: to test for exposure to the disease and it allowed
Speaker 3: for these large scale prevalent studies without the need for
Speaker 3: growing the fungus in lab animals. Why was so much
Speaker 3: focus placed on Coxidioida mycosis because it kind of seems
Speaker 3: like it was I mean, like, yes, it could absolutely
Speaker 3: be deadly and debilitating, but there were also so many
Speaker 3: other diseases that were in constant circulation. Yeah, this is
Speaker 3: still pre antibiotic in pre most vaccines. But coxidioida mycosis
Speaker 3: did pose a big threat to California's rapidly growing population.
Speaker 3: Why was it growing the dust bowl? The dust Bowl
Speaker 3: throughout the nineteen thirties, tens of thousands of families picked
Speaker 3: up from their eroded and parched farms in the prairies
Speaker 3: and headed to California. And this enormous influx of people
Speaker 3: meant a whole new bunch of susceptibles for coxdioides, and
Speaker 3: so the disease became much more visible.
Speaker 2: That makes sense.
Speaker 3: And so Aaron I really like side note, really still
Speaker 3: want to do an episode on the dustbel I know it.
Speaker 3: And if you listeners can't wait until that episode comes out,
Speaker 3: go read The Worst Hard Time because that's an amazing book. Okay. So,
Speaker 3: if the dust Bowl was indirectly responsible for cocidioido mycosis
Speaker 3: becoming more visible and fueling more research in the nineteen
Speaker 3: thirties than in the nineteen forties, that role would go
Speaker 3: to World War Two. As the US got ready to
Speaker 3: enter the war, a bunch of airfields were established for
Speaker 3: training purposes, and what better place than the Southwestern US Smith, so,
Speaker 3: like Charles Smith from before, took this opportunity to set
Speaker 3: up a prospective epidemiological study where he began skin testing
Speaker 3: all of the newly arrived personnel to these airfields. He
Speaker 3: made notes of how living conditions impacted disease risk like
Speaker 3: tense and even though on Smith's recommendation, the airfields implemented
Speaker 3: dust control strategies, there was still plenty of cocidioido micosis
Speaker 3: cases for Smith to make detailed study on all the
Speaker 3: ways the disease could manifest, the incubation period, the timeline
Speaker 3: of disease, and so on. And with this and other
Speaker 3: research conducted during this time, ended up showing was that
Speaker 3: this disease was essentially endemic in a good chunk of
Speaker 3: the southwestern United States. And the other thing that the
Speaker 3: nineteen forties would do was to firmly establish coxidioides as
Speaker 3: a pathogen of incarcerated populations. Oh yeah, oh yeah. During
Speaker 3: World War Two, specifically between the years of nineteen forty
Speaker 3: two and nineteen forty five, the United States set up
Speaker 3: concentration camps previously known as internment camps in the Western
Speaker 3: States and other places as well for the forceful relocation
Speaker 3: and incarceration of around one hundred and twenty thousand people
Speaker 3: of Japanese ancestry, two percent of whom were US citizens. Actually,
Speaker 3: at least one of these camps, which had a population
Speaker 3: of thirteen thousand, was located on the Hila River in
Speaker 3: southern Arizona, which was a hot spot for coccidioidomycosis, and
Speaker 3: the high prevalence of this disease was known before the
Speaker 3: camp was established, of course, and so no one was
Speaker 3: too surprised when cases began popping up at the camp
Speaker 3: or nearby at the prisoner of War camp where German
Speaker 3: prisoners were being held. And I didn't see any solid
Speaker 3: numbers for infection rates or like total number of cases
Speaker 3: at these concentration camps, but I did see that at
Speaker 3: the prisoner of War camp where Charles Smith visited, I
Speaker 3: think at least once, he estimated that between two thirds
Speaker 3: to three quarters of new arrivals would become infected within
Speaker 3: one year of arriving. Oh my god, based on living
Speaker 3: conditions and just the super high and dimnicity of the pathogen.
Speaker 3: And there do seem to have been some deaths at
Speaker 3: that camp and erin I'm sure You're going to talk
Speaker 3: a whole lot more about how cocidioidomycosis is still super
Speaker 3: prevalent at prisons, and maybe about some of the ethics
Speaker 3: of intentionally building or maintaining prison facilities where infection is
Speaker 3: a certainty.
Speaker 2: There's so much there, boy.
Speaker 3: But yeah, but at the time that these concentration camps
Speaker 3: and other prisons were first being built, there weren't any
Speaker 3: effective treatments for the disease and no vaccines. And I
Speaker 3: know that treatment is still more art than science even today.
Speaker 3: But the big increase in cases during World War two
Speaker 3: and endemic areas allowed Smith and other researchers to notice
Speaker 3: that infection with the fungus did seem to protect you
Speaker 3: from getting it again, which then spurred on some vaccine work.
Speaker 3: And alongside this vaccine research, which ultimately did seemed to
Speaker 3: produce a vaccine. I read a paperword that was like, oh,
Speaker 3: and then they all injected themselves with this vaccine and
Speaker 3: it seemed to work. Oh, I don't know, nineteen fifties
Speaker 3: and that. Yeah, but it seems like it seems like
Speaker 3: this vaccine research was being done at the same time
Speaker 3: that the US was looking into this as a potential
Speaker 3: bio weapon, not to weaponize it, but to see how
Speaker 3: feasible it was for other people to weaponize, and also
Speaker 3: like how worried should we be about this? Should we
Speaker 3: make a vaccine it's just in case, et cetera. And
Speaker 3: then finally treatment emerged in the nineteen sixties in the
Speaker 3: form of amphiterisen b like we talked about in art
Speaker 3: organ transplant episode and since that one can be a
Speaker 3: bit toxic, later development of anti fungal azoles was kind
Speaker 3: of a relief, and I say kind of because yeah,
Speaker 3: all the problems you talked about. And then the next
Speaker 3: time we really saw like a huge increase an interest
Speaker 3: in coxitioidomycosis was of course, during the AIDS pandemic in
Speaker 3: the nineteen eighties, where that seemed to be suddenly this
Speaker 3: fungus that was like, oh, generally it causes mild infection
Speaker 3: became like an absolute killer disease.
Speaker 2: Yep.
Speaker 3: So it's been about one hundred and thirty years since
Speaker 3: this pathogen and the disease that it causes was first described,
Speaker 3: and we've learned quite a lot since that time about
Speaker 3: its ecology, it's epidemiology, disease course, treatments, et cetera, et cetera.
Speaker 3: But there's still quite a bit that we're trying to
Speaker 3: figure out, and it's becoming more and more of a
Speaker 3: pressing issue with like the steadily growing number of cases,
Speaker 3: climate change, expansion into new areas, disproportionately high rates, and
Speaker 3: incarcerated populations. So Aarin, Oh, here we go. Tell me
Speaker 3: where do we stand with coxcitioid domcosis today and what
Speaker 3: are we doing about it?
Speaker 2: Oh, I can't wait to tell you about it. Let's
Speaker 2: take a quick break first. Excellent, all right, I should
Speaker 2: say really quick in case I didn't say it clearly
Speaker 2: in the biology section, since you mentioned how we still
Speaker 2: don't really have perfect treatment. It's especially true for people
Speaker 2: who don't have a lot of risk factors for a
Speaker 2: disseminated or severe disease. People who we know are high risk,
Speaker 2: who have certain chronic diseases, etc. Like, are probably going
Speaker 2: to need our definitely going to need to be on treatment,
Speaker 2: possibly for their entire rest of their life.
Speaker 3: So and that we do know.
Speaker 2: But yeah, it's the kind of lower risk people that
Speaker 2: it's a little bit tricky. So I'm really excited to
Speaker 2: get into some of these details. Erin unsurprisingly, and as
Speaker 2: always on this podcast, the number of reported cases greatly
Speaker 2: underestimates the actual number of cases. But let's talk at
Speaker 2: least briefly about what those reported cases are. And then
Speaker 2: I want to do something that I haven't done in
Speaker 2: a long time, which is a math, oh, to kind
Speaker 2: of just kind of emphasize why it is that we
Speaker 2: know how underreported this disease is.
Speaker 3: Okay, sounds great, I'm excited me too.
Speaker 2: It was really fun and it took me way too
Speaker 2: long to do this math. So, like you said, the
Speaker 2: number of cases has been steadily increasing, and while there's
Speaker 2: a thought that maybe this is just better recognition, the
Speaker 2: data actually doesn't support that. So this is definitely increases
Speaker 2: in cases, not just increasing in reporting. So in twenty
Speaker 2: eleven was actually the greatest number of reported cases in
Speaker 2: the US. And I'll just say upfront, I really only
Speaker 2: have data for the US that's where this is like
Speaker 2: more well reported and where cases seem to be the
Speaker 2: highest in the world. So in twenty eleven, there were
Speaker 2: twenty two thousand, six hundred and forty one cases reported.
Speaker 2: The vast majority of those are in California and Arizona,
Speaker 2: but several other states as well. And then in twenty eighteen,
Speaker 2: so the most recent year that I could find data for,
Speaker 2: there were fifteen thousand, six hundred eleven cases reported.
Speaker 3: That's a lot of it's a lot, but you're.
Speaker 2: Like fifteen thousand, it's not. The real number is probably
Speaker 2: one hundred and fifty thousand or more.
Speaker 3: So it's like literally an order of magnitude, an order
Speaker 3: of magnitude.
Speaker 2: And let's talk about why, because it gets fun.
Speaker 3: Ooh.
Speaker 2: There have been a number of studies that have tried
Speaker 2: to estimate how much of the share of community acquired
Speaker 2: pneumonia is accounted for by coxidiodo mycosis, and they've done
Speaker 2: this in a number of different ways, and what they
Speaker 2: have found is that in endemic areas, especially in Arizona
Speaker 2: and parts of the Central Valley of California, coxidioto mycosis
Speaker 2: accounts for up to thirty percent of all community acquired pneumonia.
Speaker 3: Thirty percent.
Speaker 2: Okay, so sidebar pneumonia. Huh, pneumonia is very very common. Yeah,
Speaker 2: There's a lot of different types of pneumonia, and we
Speaker 2: often differentiate them by saying, is this a community acquired pneumonia?
Speaker 2: Like did you get this in your normal everyday life
Speaker 2: in the quote community or is this a hospital acquired
Speaker 2: pneumonia like you were in a health care facility and
Speaker 2: that's how you got it. The reason that we do
Speaker 2: that is partly because hospitals don't like it when you
Speaker 2: get sick inside of them, but also because it tends
Speaker 2: to be different organisms that are more likely to cause
Speaker 2: a community acquired versus a hospital acquired pneumonia, So it
Speaker 2: can help clinicians to decide how to treat this pneumonia.
Speaker 3: Uh huh huh.
Speaker 2: But there are a lot of different potential causes. There's
Speaker 2: viral pneumonias that don't need any antibiotics. There are bacterial pneumonias,
Speaker 2: a lot of different types of bacteria, and then there
Speaker 2: are these fungal pneumonias. I'm getting excited. But overall, pneumonia
Speaker 2: as a blanket diagnosis is one of the leading infectious
Speaker 2: causes of hospitalization and death for adults in the United States.
Speaker 2: It's the second leading cause of hospitalization's period adults in
Speaker 2: the US, and there are like four and a half
Speaker 2: million doctors visits annually for community acquired pneumonia.
Speaker 3: This is what's so interesting because coxidioido mycosis is not contagious, right,
Speaker 3: and so like these are all individual exposures, not like
Speaker 3: someone standing next to someone on a bus and yeah
Speaker 3: coughing and.
Speaker 2: Whatever, right, exactly, wow, and thirty percent, that's why thirty percent.
Speaker 2: And community acquired pneumonia is estimated to cause between like
Speaker 2: twenty three to twenty seven. So let's put the difference
Speaker 2: and call it twenty five cases per ten thousand adults
Speaker 2: every year that require hospitalization. So that's just the ones
Speaker 2: that are bad enough that someone ends up in the hospital.
Speaker 3: Yeah, that's a lot.
Speaker 2: That's a lot. So if we back up to knowing
Speaker 2: that coxidioto micosis, thirty percent of all of these community
Speaker 2: acquired pneumonia cases are going to be caused potentially by coxidiodamcosis,
Speaker 2: and estimates range across its geographic range from like seventeen
Speaker 2: to thirty percent. So if we again like split the difference,
Speaker 2: we can do some math here and we can say, okay,
Speaker 2: if there's twenty five cases per ten thousand adults per
Speaker 2: year that require hospitalization, and there's thirty nine million people
Speaker 2: in California, not all of them maybe in super endemic regions,
Speaker 2: but whatever, it's Aaron's math. And let's say only twenty
Speaker 2: percent of those cases are actually caused by coxidiodo mycosis.
Speaker 2: That's almost one hundred thousand cases of pneumonia requiring hospitalization
Speaker 2: every year in California caused by coxidionamcosis.
Speaker 3: That's requiring hospitalization. That's a lot.
Speaker 2: That's a lot. Yeah, So that is how we can
Speaker 2: get to these estimates of what is the true burden likely.
Speaker 2: And so now the question is if we know that
Speaker 2: thirty percent of these cases or you know, seventeen to
Speaker 2: thirty percent of these cases are caused by coxidioits, but
Speaker 2: only fifteen thousand are reported, Like, why do we still
Speaker 2: have such a big discrepancy? And it turns out because
Speaker 2: in the cases where they've looked into this, we find
Speaker 2: that oftentimes anywhere from fifteen to thirty percent, often less
Speaker 2: than fifteen percent of the time do we actually test
Speaker 2: someone with a with a community acquired pneumonia for the pathogen?
Speaker 3: Is that just because like in general, if you're looking
Speaker 3: at the US, it's most likely to be these other pathogens,
Speaker 3: and so you just either give someone like some sort
Speaker 3: of antibiotics or be like, oh, it's viral or whatever,
Speaker 3: and it's just like faster, Like does it cost a
Speaker 3: lot of money to test? Is a lot of resources?
Speaker 3: Like what's the argument against testing? I guess is what
Speaker 3: I'm trying to figure out.
Speaker 2: So you're asking a lot of good questions and the
Speaker 2: answer is it's all of those things and then some.
Speaker 2: So part of it is, certainly, if you live in
Speaker 2: New York State, are you going to test everyone with
Speaker 2: pneumonia for cuxy doomycosis. No, that would be completely not indicated.
Speaker 2: But even in places like they've done studies in California
Speaker 2: and Arizona where this is highly endemic, and they've found
Speaker 2: that less than fifteen percent of all community acquired anemonia
Speaker 2: cases are have an identified pathogen detected. Part of it
Speaker 2: is that it is very difficult to be able to
Speaker 2: get the proper samples that you need to be able
Speaker 2: to do this test. Isn't always easy. But also if
Speaker 2: someone is coming in and isn't all that sick, you
Speaker 2: take a look at their X ray and you know
Speaker 2: they're not going to be hospitalized, they're just going to
Speaker 2: be treated kind of as an outpatient, then a lot
Speaker 2: of times you won't do a ton of testing because
Speaker 2: you'll say this is most likely what it is. If
Speaker 2: you don't get better, then come back right right, that
Speaker 2: makes sense. It's a lot and that's why you know,
Speaker 2: we do distinguish at least between is this hospital acquired
Speaker 2: or community acquired, Like we're trying to narrow down what
Speaker 2: is the most likely pathogen that's causing this and how
Speaker 2: are we going to treat it. Yeah, so it's very
Speaker 2: interesting when you think about that, and then you think
Speaker 2: of how many people might have had this infection, went
Speaker 2: to the doctor, got antibiotics, took them, got better. The
Speaker 2: antibiotics didn't make them better, But most of these cases
Speaker 2: resolve on their own without any treatment.
Speaker 1: But I.
Speaker 2: So that's kind of how we get to those numbers.
Speaker 2: But like you already touched on Aaron, and since this
Speaker 2: is TPWKY, you'll also be unsurprised listeners to know just
Speaker 2: how huge their disparities are in who gets infected probably
Speaker 2: and who gets diagnosed and who gets treated. So we've
Speaker 2: already mentioned a number of different groups that are at risk,
Speaker 2: like people who are immunal compromised in some way or another.
Speaker 2: People who are pregnant have a much higher risk of
Speaker 2: having disseminated disease, and like you mentioned Aarin, it's been
Speaker 2: shown and a lot of the literature states that African
Speaker 2: Americans and people of Filipino descent tend to be more
Speaker 2: at risk for disseminated disease, so that severe manifestation of disease.
Speaker 2: But a lot of the studies that showed this that
Speaker 2: are cited in more recent literature were done in like
Speaker 2: the nineteen forties. And I'm not sure what the kind
Speaker 2: of explanation would be if we think about people during
Speaker 2: the dust bowl time coming in because one thing that
Speaker 2: we have seen in places like Arizona today, where Arizona
Speaker 2: has a large elderly population of people who came from
Speaker 2: somewhere else in the country and moved to Arizona when
Speaker 2: they were older, so they never had any exposures, those
Speaker 2: people seem to be at higher risk for infection. So
Speaker 2: is that what was driving these studies early on? I
Speaker 2: really don't know, but I do think that we really
Speaker 2: need to ask ourselves as a community of people researching
Speaker 2: and writing papers about cacidioidomycosis, is how much of this
Speaker 2: disparity is true today and how much of it is
Speaker 2: due to differences in health care access among vulnerable or
Speaker 2: marginalized populations or among health care providers, and adequate diagnosis
Speaker 2: and treatment and all of that. So I don't know
Speaker 2: the full answer to that. So definitely exposure, and certainly
Speaker 2: people who work in certain situations that put them in
Speaker 2: close contact with soil are at much higher risk for
Speaker 2: contracting disease, like agricultural workers, construction workers, people who work
Speaker 2: in the soil or have contact with the soil. But
Speaker 2: the other place this is a massive issue aarin that
Speaker 2: you mentioned is for incarcerated individuals. California Central Valley, which
Speaker 2: is Cocidoit's territory, is home to a lot of prisons.
Speaker 2: The incarcerated population of California from nineteen eighty to two
Speaker 2: thousand increased eightfold. And so what you're saying Erin is like,
Speaker 2: we already knew this was a problem, I mean back forty.
Speaker 3: Decades, for almost one hundred years.
Speaker 2: But then they were like, let's build a bunch of prisons.
Speaker 2: Right on top of all this, eighty nine percent of
Speaker 2: people who are incarcerated in these prisons in the Central
Speaker 2: Valley are brought from non endemic areas of California. Yeah,
Speaker 2: which means that they have not previously been exposed potentially. Ah. Yeah,
Speaker 2: In the last several decades, there have been quite a
Speaker 2: number of outbreaks in prisons that have resulted in a
Speaker 2: large number of deaths, and in fact continue to result
Speaker 2: in deaths annually. And there's a few papers that say,
Speaker 2: you know, we've tried this type of medical restriction where
Speaker 2: if you have these certain diseases, then you can't be
Speaker 2: put in prisons in this particular area. But it turns
Speaker 2: out there's also been studies from the CDC that show
Speaker 2: that that really doesn't actually work to reduce exposure or cases.
Speaker 2: So there's another program to try and risk stratify people
Speaker 2: using skin testing, where if they've never been exposed to
Speaker 2: coxidioides and don't have a positive skin test, then they
Speaker 2: can't go to certain prisons. But that was a small
Speaker 2: study and I'm not sure that any of that has
Speaker 2: actually been implemented yet today.
Speaker 3: It's an interesting approach because it seems like another solution
Speaker 3: would be to not have prisons, I mean the whole
Speaker 3: prison system. That's a whole other I was.
Speaker 2: Going to say, it's like, yeah, the problems with the
Speaker 2: prison system are not something we're going to get.
Speaker 3: Into scales and scales and scales of different levels of this.
Speaker 2: Exactly, honestly, erin that's still a thing.
Speaker 3: So and it doesn't yeah, yeah, oh my gosh.
Speaker 1: Yeah.
Speaker 2: And so we've kind of covered a lot of sort
Speaker 2: of frontiers on things that we need to do a
Speaker 2: better job of right diagnosing, deciding who and when and
Speaker 2: how to treat the problem of all of the prisons
Speaker 2: in the Central Valley. But also, let us not forget
Speaker 2: that this is an environmental pathagen So what about climate change.
Speaker 2: It's not good, it's not great. There have been a
Speaker 2: number of recent studies that have model what the environmental
Speaker 2: risk factors are for infection, which is awesome, and unsurprisingly
Speaker 2: it seems very related to rainfalls. So larger rainfalls, heavier
Speaker 2: rainfalls in the winter followed by drier summers results in
Speaker 2: what they called in these papers a grow and blow phenomenon. Okay,
Speaker 2: where a lot of the funch i can grow and
Speaker 2: exist in the environment during that wet winter and then
Speaker 2: they get dried out in this dry summer, and then
Speaker 2: you get increases in infection because of the dry soil
Speaker 2: blowing in the air.
Speaker 3: You're basically recreating Harold CHOP's old dried up peachy dish, yeah.
Speaker 2: Or exactly. And so this sort of climate modeling has
Speaker 2: been shown to be like in line with retrospective data
Speaker 2: on where we see cases, and so these match up
Speaker 2: really well, both in Arizona and in California. So now
Speaker 2: the kind of question going forward will be, can we
Speaker 2: use this knowledge to try and predict out to the
Speaker 2: future when we might have like a bad year for
Speaker 2: coxiduods infection something like that. Yeah, but that still doesn't
Speaker 2: answer the question of like climate change specifically. And so
Speaker 2: one thing that I wanted to mention that I think
Speaker 2: is really important in thinking about this is that we've
Speaker 2: seen in the last decade or so a number of
Speaker 2: cases pop up in areas that aren't generally considered endemic,
Speaker 2: like Washington State, which has had also a steady increase
Speaker 2: in the number of confirmed endemic cases of coxcidioido micosis.
Speaker 2: Where in Washington State, Oh, good question, I don't actually
Speaker 2: know what county it was in Washington State, but even
Speaker 2: in twenty seventeen it was still only twelve cases. But
Speaker 2: they have identified that those cases were endemic, they weren't
Speaker 2: from travel, So we don't have a truly great handle
Speaker 2: on what the distribution of this fungus is worldwide to
Speaker 2: begin with. But we know that climate change is very
Speaker 2: likely to have some effect, but since we don't exactly
Speaker 2: know where it is, it's hard to say exactly what
Speaker 2: that's going to do. If that makes sense. Yeah, no,
Speaker 2: that's totally but yeah, so there's a lot of room
Speaker 2: for research here.
Speaker 3: Oh yes, it's an open petri dish.
Speaker 2: Just don't breathe it in.
Speaker 3: Just don't breathe it in.
Speaker 2: So yeah, that's coxsidioido micosis.
Speaker 3: Uh sources sources, Okay, I want to shout out a
Speaker 3: paper by Darrazinski and Murals, coxidioido micosis. What a long,
Speaker 3: strange trip it's been. Definitely wins my favorite title. I
Speaker 3: think that was a very useful paper, as was a
Speaker 3: book from nineteen eighty by David Stevens called coxidioido Micosis
Speaker 3: a text and I have a bunch more that I
Speaker 3: will put on the website.
Speaker 2: I also have quite a number of papers, many of
Speaker 2: which are just titled cocsidioido micosis, which I found hilarious,
Speaker 2: straight to the point, straight to the point, let's no
Speaker 2: messing around. You can find our list of sources from
Speaker 2: this episode and every single one of our episodes on
Speaker 2: our website This podcast will Kill You dot Com under
Speaker 2: the episodes tab.
Speaker 3: Thank you to Bloodmobile for providing the music for this
Speaker 3: episode and all of our episodes.
Speaker 2: And thank you to the Exactly Right Network, of whom
Speaker 2: we're very proud to be a part.
Speaker 3: And thanks again, Tory so much for sharing your story
Speaker 3: with us. We really appreciate it.
Speaker 2: Yeah, and thank you to you listeners for listening to
Speaker 2: this podcast. We hope you enjoyed this one. I feel
Speaker 2: like maybe some people might not have ever heard of it,
Speaker 2: so hopefully this was a fun new one for me.
Speaker 3: Yeah, it's kind of niche, but that it's like also
Speaker 3: really interesting. I don't know, I had a lot more
Speaker 3: fun than I thought I was going to have in
Speaker 3: the research to be ho, feel like.
Speaker 2: We put this one off for a while and I'm
Speaker 2: glad that we did it.
Speaker 3: Yeah, it was a good one. Yeah, Okay, Well until
Speaker 3: next time, wash your hands
Speaker 2: You feel the animals