Speaker 1: It was the end of the month and I was
Speaker 1: helping a friend paint her home. Her house was about
Speaker 1: thirty five miles away from mine, which is in the
Speaker 1: city of Boston, so in lieu of driving home, she
Speaker 1: opted to get me a room because I was going
Speaker 1: to be helping her the following day. Once I opened
Speaker 1: the hotel door, it was hot and musty, and you
Speaker 1: could tell no one had entered that room for a while.
Speaker 1: I turned on the ac and was hit in the
Speaker 1: face with a musty mist. That smell still lingers with
Speaker 1: me today. Didn't think anything of it, ate food and
Speaker 1: went to sleep. Continued with my weekend as scheduled, basically
Speaker 1: the gym and sleep. That following Monday, I felt out
Speaker 1: of it. I wasn't sick, just exhausted. I thought it
Speaker 1: was simply from going to the gym. I didn't have
Speaker 1: work because it was Memorial Day and wasn't due back
Speaker 1: to work until Wednesday. But I stayed in bed the
Speaker 1: whole holiday and the day after. I just remember being
Speaker 1: at work tired. I thought it was from oversleeping, and
Speaker 1: the best cure for that was more sleep. As the
Speaker 1: weekend rolled around, I was back at my friend's house, painting,
Speaker 1: but I noticed I needed a break every five to
Speaker 1: ten minutes or so. I was a bit sore and
Speaker 1: always out of breath and sweating profusely. Monday rolled around,
Speaker 1: and it had been nine days since I was at
Speaker 1: the hotel. I went to bed, and when I awoke,
Speaker 1: I could no longer walk straight. I was slamming into
Speaker 1: walls and couldn't see straight. When I awoke, it was
Speaker 1: already midnight. I overslept again, but now I lost all
Speaker 1: motor skills, couldn't walk at all, and my speech was
Speaker 1: slurring so Siri didn't recognize my voice. I had to
Speaker 1: crawl to use the restroom and had a hard time
Speaker 1: not knocking things over when I did. I awoke in
Speaker 1: my bed to my mom asking me about the mess
Speaker 1: in the bathroom. She immediately knew I was sick once
Speaker 1: she heard me speak. I woke up in the hospital
Speaker 1: surrounded by nurses and doctors trying to figure out why
Speaker 1: I couldn't talk or walk and why I had a
Speaker 1: fever of one hundred and six degrees. It took about
Speaker 1: four days before they figured out it was Legionnaire's I
Speaker 1: still had a temperature of one hundred and three, still
Speaker 1: couldn't walk, no motor skills at all, and was unable
Speaker 1: to speak. Hallucinating at this point was the most enjoyable
Speaker 1: part of the day. I know I had rooms of
Speaker 1: family and friends, and by the look on their faces,
Speaker 1: I could tell they were told the severity of everything
Speaker 1: which I didn't even know. I was in the hospital
Speaker 1: and rehab for about three and a half weeks. I
Speaker 1: can walk and talk again, and all my motor skills
Speaker 1: have returned. I drop things a lot, and I'm very
Speaker 1: forgetful at the minor tasks. I had to relearn what
Speaker 1: I did for a living and how to drive. I
Speaker 1: used to love working out, but it's so dangerous now
Speaker 1: because I can't balance weights like I should and walking
Speaker 1: hurts after a while. My joints feel like they are
Speaker 1: on fire most of the day. Steps are my new
Speaker 1: arch nemesis. My knees feel like they are about to
Speaker 1: buckle and crumble whilst walking up or down them. I
Speaker 1: have dizzy spells, get tired at the drop of a dime,
Speaker 1: and lose my train of thought halfway through tasks. It
Speaker 1: has been interesting, and I am glad to know I
Speaker 1: am not the only one out there dealing with these
Speaker 1: side effects and that things can get better. Wow. Yeah,
Speaker 1: that sounds very horrible and terrifying. Yeah, so that was
Speaker 1: from a website called legionella dot org, where under a
Speaker 1: section called share your Story.
Speaker 2: I didn't realize until kind of reading through some of
Speaker 2: those first hand accounts and researching this episode how long
Speaker 2: lasting some of the effects of infection with Legionella can be.
Speaker 1: Oh yeah, No, it's like I think there is a
Speaker 1: lot more under the surface than as per usual then
Speaker 1: we think there is at the beginning of these episodes. Hi,
Speaker 1: I'm Aaron Welsh and I'm Aaron Alman. Update and this
Speaker 1: is this podcast will Kill You.
Speaker 2: And today, of course we're talking about Legionella, the causative
Speaker 2: agent of Legionnaire's disease.
Speaker 1: Yeah, and pontiac fever and pontiac fever other things. It's
Speaker 1: it's gonna be an interesting I have lots of biology
Speaker 1: questions already, so cool.
Speaker 2: I knew that was coming, and I like hope that
Speaker 2: I know the answers to them. But you're probably not
Speaker 2: gonna like a lot of them as usual.
Speaker 1: You mean, like it's I'm not gonna like them because
Speaker 1: it's well, we don't quite know. Yep. Yeah, great, great, great, great,
Speaker 1: they're not satisfying answers. Dang it. That's okay. Well we'll
Speaker 1: get there, but first we do some podcast stuff.
Speaker 2: We should yeah, because it's let me check quarantin any time.
Speaker 1: It is quarantin any time. What are we drinking this week?
Speaker 2: We're drinking losing your Cool?
Speaker 1: Yeah, for reasons I think we always say this, but
Speaker 1: that will become more clear as the episode goes on. Basically,
Speaker 1: we're talking about air conditioning, we're talking about fevers. You're
Speaker 1: just gonna lose your cool.
Speaker 2: You're gonna lose your cool, and what's in losing your cool?
Speaker 1: Eric It is a I think it's actually a really
Speaker 1: delicious one. So it has normal rum, pineapple rum, lime juice,
Speaker 1: Apricot liquor, and simple syrup. And we will post the
Speaker 1: full recipe for losing your cool on our website This
Speaker 1: podcast will kill You dot Com, as well as on
Speaker 1: all of our social media channels like Twitter, Facebook, Instagram,
Speaker 1: and those are the places where you can also find
Speaker 1: the non alcoholic place seburrita recipe exactly.
Speaker 2: Speaking of our website, this podcast with you dot Com
Speaker 2: check it out if you haven't already. We have so
Speaker 2: many things there like merch and a bookshop dot org
Speaker 2: affiliate account. We've got a good Reads list, we have
Speaker 2: a Patreon, we have links to Bloodmobile, our music. We
Speaker 2: have transcripts for so many of our episodes, soon to
Speaker 2: be all of them.
Speaker 1: So definitely check out our website. Yes, check it out. Uh.
Speaker 1: I guess like, I feel like this was a really
Speaker 1: fast intro, but I'm I'm like I do. I don't
Speaker 1: know what else to do here.
Speaker 2: I'm excited about this episode, so maybe let's take a
Speaker 2: quick break and then just get started.
Speaker 1: Let's do it. So.
Speaker 2: Legionella is a genus of bacteria that has a whole
Speaker 2: bunch of species, way more than I realized. I think
Speaker 2: at least over fifty.
Speaker 1: Yeah. I think that's been a fairly recent development.
Speaker 2: Yeah, and I believe that at least thirty of these
Speaker 2: bacterial species can be pathogenic to humans. And in general,
Speaker 2: these are a much more interesting group of bacteria than
Speaker 2: I realized. I feel bad because I was just like, oh,
Speaker 2: they're another gram negative like waw. They're much more interesting
Speaker 2: than that. They are gram negative little rods. And when
Speaker 2: they're not infecting us humans, they live in freshwater sources,
Speaker 2: but not just free floating in modern No.
Speaker 1: No, I'm so glad you're going to talk about those.
Speaker 1: Oh yeah, it's so cool.
Speaker 2: So they don't just live free floating in the environment.
Speaker 2: They exist as pathogens of amibe uh huh.
Speaker 1: And other protozoa. I was when I was reading that,
Speaker 1: because I was like reading about the evolutionary history and
Speaker 1: I came across that, and I was like, this is
Speaker 1: so well timed with our Nicleeria Fleriye episode exactly. It's wild.
Speaker 1: And also I was like, oh, this is definitely an error,
Speaker 1: Like I'm reading too much about Aaron's biology section. I
Speaker 1: need to stop. Yeah, it's so fascinating.
Speaker 2: So I always thought of them as just a water
Speaker 2: born bacteria, which they are, but in water they can
Speaker 2: live and persist free floating as well as in biofilms,
Speaker 2: which is what makes them very difficult to deal with
Speaker 2: in pipes or water heaters, air conditioning coolers.
Speaker 1: Et cetera.
Speaker 2: But they only multiply inside of another organism like an
Speaker 2: amiba or another protozella.
Speaker 1: It's really cool because that also has implications for like
Speaker 1: why it infects humans or how to affects humans.
Speaker 2: Just gonna say, but I'm going to put a pin
Speaker 2: in that, but keep that in mind, because when we
Speaker 2: talk about the sort of pathophysiology of how it gets
Speaker 2: us sick, Yeah.
Speaker 1: It makes complete sense. M hm. Okay.
Speaker 2: So we have a lot of different species of Legionella,
Speaker 2: but the one that's most famous and probably the most
Speaker 2: common pathogen of humans, at least in the US and
Speaker 2: throughout Europe is Legionella pneumophila, which has a whole number
Speaker 2: of different subgroups and then specific strains within those subgroups,
Speaker 2: so it's a pretty large overall group of bacteria. And
Speaker 2: so this is an environmental pathogen, and the way that
Speaker 2: people get infected with it is through contact, generally aerosol
Speaker 2: contact with water that is contaminated with Legionella and also
Speaker 2: amiba of course, and Legionella in general grows well at
Speaker 2: warm temperatures like twenty five to forty five celsius, just
Speaker 2: like the amibas that we talked about in our Nigeria
Speaker 2: palrite episode. It's happiest around thirty five celsius, which is
Speaker 2: like ninety five fahrenheit. It's pretty warm water. Yeah, And
Speaker 2: what's interesting is that although this is a bacterial species
Speaker 2: that's found naturally in aquatic environments across the globe. It
Speaker 2: generally doesn't reach high enough levels to get you sick
Speaker 2: in those natural environments.
Speaker 1: So what's the infectious dose?
Speaker 2: Then, Aaron, I knew you were going to ask that
Speaker 2: I have it in bold.
Speaker 1: We don't know you have in bold. We don't know, well, no,
Speaker 1: I have in bold. What is infectious dose?
Speaker 2: Because yeah, that was my biggest question too, because all
Speaker 2: these papers say, you know, it's in human altered environments
Speaker 2: where we're artificially heating water. Then you have this disproportionate
Speaker 2: growth of Legionella the bacteria in comparison to the amibe,
Speaker 2: and that's what leads to human infection. But there isn't
Speaker 2: a well established dose response relationship or even a clear
Speaker 2: infectious dose or lethal dose. There are some papers that
Speaker 2: list numbers, but those studies were in guinea pigs, so
Speaker 2: we really don't know how accurate they are.
Speaker 1: Well. And it's really interesting too, because, as I'm sure
Speaker 1: you'll talk about, there's a wide range of like host susceptibility,
Speaker 1: where like your immune system and your age and you're
Speaker 1: whatever risk factors must change a lot of like the
Speaker 1: infectious dose for one person might not be the infectious
Speaker 1: dose for somebody else exactly.
Speaker 2: And we'll talk a little bit more about that when
Speaker 2: we talk about the symptoms of like the kind of
Speaker 2: range of symptoms that you see in these disorders, because
Speaker 2: I think that plays a huge part in it. Okay, Yeah,
Speaker 2: it also makes it difficult in terms of prevention and
Speaker 2: control to like do environmental monitoring because we don't know
Speaker 2: what is a safe level versus an unsafe level of
Speaker 2: Legionella in water sources. Yeah, yeah, great question, Eric, But
Speaker 2: in general, this is not a pathogen that's transmissible person
Speaker 2: to person asterisk. It has happened maybe a handful of
Speaker 2: times at least once that I saw documented, but that's
Speaker 2: very rare, and in general, outbreaks that happen are from
Speaker 2: a shared environmental source.
Speaker 1: What were the circumstances of the person to person transmission?
Speaker 1: It was a.
Speaker 2: Mom who was caring for someone who was very severely
Speaker 2: ill for like over eight hours a day in a
Speaker 2: very small room without any ventilation and so presumably and
Speaker 2: she didn't have contact with that same water source that
Speaker 2: he had.
Speaker 1: Had contact with. Okay, interesting, that was the one that
Speaker 1: I saw. Yeah, So.
Speaker 2: All right, so let's talk about what happens when these
Speaker 2: bacteria get inside of our body because I think it's
Speaker 2: really fascinating. I might go into more detail than I
Speaker 2: sometimes do on this, but I think it's gonna be fun.
Speaker 1: Okay, let's do it.
Speaker 2: So, since these are bacteria that generally live inside of
Speaker 2: ambae when they're in the environment, it's not surprising that
Speaker 2: once they get inside our body via inhalation into our
Speaker 2: respiratory tract. These are also intracellular bacteria like Ricketsia and
Speaker 2: chlamydia and a lot of other bacteria that live and
Speaker 2: multiply inside of our cells rather.
Speaker 1: Than just in our bodies.
Speaker 2: So in us, what they do is these bacteria adhere
Speaker 2: to our cells. I think from what I read they
Speaker 2: can infect other cells like our respiratory cells, our epithelial cells,
Speaker 2: but primarily they infect Macrophagious Macrophasias are white blood cells
Speaker 2: that normally serve the function of gobbling up bacteria and
Speaker 2: then killing them. But Legionella is able to persist inside
Speaker 2: these macrophages. Here's how they do it. Normally, when a
Speaker 2: macrophage gobbles up a bacteria, you can imagine them taking
Speaker 2: their little macrophages kind of almost look like amiba. They
Speaker 2: have like wiggly arms and they take those wiggly arms
Speaker 2: and they wrap it around a bacterium like a giant
Speaker 2: hug and then they bloop it inside of the macrofage cell.
Speaker 2: But once it gets inside the cell, it's wrapped in
Speaker 2: a little bubble of macriphage cell membrane. M hm. It's
Speaker 2: called the phagosome. Yeah, yeah, you know this erin And
Speaker 2: now normally, once that fhagosome is inside the macrophage, all
Speaker 2: of these other mechanisms inside of the macrofage cell would
Speaker 2: see that bubble and be like, ugh, there's another bacterium. Boop,
Speaker 2: and they'd pop that bubble, release the bacterium.
Speaker 1: And kill it mm hmm.
Speaker 2: But lee Janella prevents that bubble from ever popping, So
Speaker 2: they persist inside a bubble inside a macrophage, and they
Speaker 2: replicate and replicate and replicate. The reason I think this
Speaker 2: is fascinating is because it's exactly the same thing that
Speaker 2: they do inside an amoba. Because amibas eat bacteria the
Speaker 2: same way that our macrophages do.
Speaker 1: Right, it's also very virus like behavior.
Speaker 2: It is, it's very viral huh yeah. And then inside
Speaker 2: of us they do the same thing that they do
Speaker 2: to amiba. They kill our cells just like they would
Speaker 2: kill an amiba. So that's how we get infected, how
Speaker 2: we get sick. What does the disease that Legionella causes
Speaker 2: actually look like? Kind of like in our chicken pox episode,
Speaker 2: And we already mentioned this at the top, there are
Speaker 2: two different named diseases that are associated with infection with
Speaker 2: Legionella bacteria. But I as I was reading this, I
Speaker 2: was like, I find it annoying that we have these
Speaker 2: two different named diseases because they're not truly really different.
Speaker 2: They're kind of just a spectrum of symptoms which all
Speaker 2: seem possible after a Legionella infection, including asymptomatic infection. There's
Speaker 2: evidence of people who become infected zero convert, so they
Speaker 2: show evidence of infection and immunity, but never have any
Speaker 2: symptoms of infection with legionella. So some places have started
Speaker 2: just sort of naming this legionellosis as a spectrum of
Speaker 2: disease rather than legionnaire's disease versus pontiac fever.
Speaker 1: Right, I mean? And I also think that probably the
Speaker 1: likelihood of someone being diagnosed with pontiac fever is much
Speaker 1: lower than with legionnaire's disease, and like if the exposure
Speaker 1: is the same, Okay, I guess that leads into the
Speaker 1: question of why are there two diseases? Like why are
Speaker 1: there two name diseases? I mean, historically it makes sense,
Speaker 1: but like why did that differentiation persist for so long?
Speaker 2: Great question? And I knew that you were going to
Speaker 2: ask this question. That's another place I have it in bold.
Speaker 2: We don't know, no, yeah, yeah, I So my big
Speaker 2: question was is it species specific? Is it different species
Speaker 2: of Legionella that are causing pontiac fever versus legionnaire's disease? Maybe,
Speaker 2: but not really as far as I can tell from
Speaker 2: all of my research, because not only do we mostly
Speaker 2: test for Legionella pneumophilla zero group one, and so like
Speaker 2: one specific group of Legionella numophila, that particular bacterial species
Speaker 2: has been found to cause both legionnaires and pontiac fever,
Speaker 2: as well as asymptomatic infections. So it can't be entirely
Speaker 2: based on zero group, and it can't be entirely based
Speaker 2: on species of bacteria, because again, there's a lot of
Speaker 2: different species of Legionella, so there's likely a huge amount
Speaker 2: of host factors that go into it. We know there
Speaker 2: are risk factors that make Legionnaire's disease a lot more likely,
Speaker 2: things like if you smoke or have any kind of
Speaker 2: chronic lung disease, an older age, especially anyone over age
Speaker 2: fifty is at higher risk than people younger, and any
Speaker 2: kind of immunal compromise, especially immuno compromise associated with cancers
Speaker 2: or being on cancer therapy or steroid treatment. So those
Speaker 2: things we know make it more likely that someone exposed
Speaker 2: to Legionella will develop Legionnaire's disease. But like you said, Erin,
Speaker 2: we also just don't know as much about pony because.
Speaker 1: It's pretty mild.
Speaker 2: So pontiac fever is basically just a mild flu like
Speaker 2: illness caused by legionella. It's fever, body aches, maybe some
Speaker 2: respiratory symptoms, but it lasts for a few days and
Speaker 2: then you get better. No pneumonia, no death, No pneumonia,
Speaker 2: no death exactly.
Speaker 1: Yeah.
Speaker 2: Legionnaire's disease, on the other hand, is a pneumonia, and
Speaker 2: we've talked about pneumonia a lot, actually, even this season
Speaker 2: in our coxsidioidomcosis episode.
Speaker 1: That's what kept popping into my head when I was
Speaker 1: reading about this, Yeah, definitely. So.
Speaker 2: The symptoms of Legionnaire's pneumonia generally start anywhere from two
Speaker 2: to fourteen days after infection, so that's the incubation period.
Speaker 2: It can be quite long. It starts very often with
Speaker 2: a fever, and like you heard in the first hand account,
Speaker 2: this fever can get quite high. Often you'll have chills
Speaker 2: which are osociated with such high fevers, a cough. Unlike
Speaker 2: some of the more quote typical pneumonias, this cough is
Speaker 2: not often very productive, so you don't have a ton
Speaker 2: of phlegm that you're bringing up, but you still likely
Speaker 2: have a cough. You'll probably have some difficulty breathing and
Speaker 2: some chest pain because there's intense inflammation happening in the lungs.
Speaker 2: And if you read the kind of classic descriptions of
Speaker 2: Legionnaire's disease, it's often described as having GI involvement, so
Speaker 2: like diarrhea, nausea, vomiting, But in reality, this can happen
Speaker 2: with other atypical pneumonias as well. Atypical pneumonia just means
Speaker 2: a pneumonia that doesn't fit the old school, very classic
Speaker 2: definition of pneumonia that's generally caused by streptococcus pneumonia or
Speaker 2: clebcila or something like that. So there's a whole group
Speaker 2: of atypical pneumonias of which Legionnaire's disease is.
Speaker 1: One, right, Yeah, I was I kept wondering what a
Speaker 1: typical Like, what distinguishes atypical pneumonia from typical pneumonia.
Speaker 2: Yeah, there's there are things like maybe the X rays
Speaker 2: will look a little bit different than pneumonia with strep pneumo,
Speaker 2: But there isn't any one specific X ray finding that
Speaker 2: tells you this is Legionnaire's disease versus something else. So
Speaker 2: it's kind of it's a very non specific way of
Speaker 2: grouping pneumonia's.
Speaker 1: So like if somebody came in with symptoms of pneumonia,
Speaker 1: some kind of pneumonia, like, what would make you go, oh,
Speaker 1: that's typical pneumonia versus atypical Would it be like you, you know,
Speaker 1: screen them for strap or you look at the X ray?
Speaker 1: Is it a combination? Like yeah, it's a really good question.
Speaker 2: There's not a good answer to that because what we
Speaker 2: end up doing is just treating for all of it
Speaker 2: very often. Okay, Yeah, so there are X ray findings
Speaker 2: that are maybe more specific for a strip pneumo pneumonia
Speaker 2: versus more atypical pneumonias, like maybe the X ray will
Speaker 2: be a little bit more diffuse and patchy versus like, Oh,
Speaker 2: here's a pneumonia in one lobe of your lung. Very
Speaker 2: clearly defined, but that's not specific, right, None of the
Speaker 2: kind of ways that we used to diagnose, like oh,
Speaker 2: is your cough productive versus not productive? Are you very
Speaker 2: very very sick versus your X ray looks terrible, but you.
Speaker 1: Don't look that sick.
Speaker 2: That's something that's usually associated with an quote atypical pneumonia
Speaker 2: is the X ray might look really bad, but the
Speaker 2: person doesn't seem that sick.
Speaker 1: Clinically, gotcha. Also, like I said, GI.
Speaker 2: Involvement, right, classically you would think, well GI involvement, Maybe
Speaker 2: I'm thinking legionella is more likely, but that can happen
Speaker 2: in other pneumonias as well. So there's no like one
Speaker 2: specific thing that if someone walked in you would say, oh, well,
Speaker 2: this is most definitely this one cause.
Speaker 1: Et cetera, et cetera. M hm.
Speaker 2: And that's what makes pneumonia in general difficult because it's
Speaker 2: often difficult to test for direct causative agents, especially if
Speaker 2: someone doesn't have a lot of phlegm that they can
Speaker 2: cough up that you can use as something to culture.
Speaker 2: Right for legionella, there is another test that you can
Speaker 2: use on urine. It's a urine antigen test that can
Speaker 2: test directly for the presence of the bacteria.
Speaker 1: Which is very cool.
Speaker 2: It is very cool, and so that is something that
Speaker 2: you can do to test directly for it.
Speaker 1: It's of course not a perfect.
Speaker 2: Test, just like any diagnostic test, but it is effective,
Speaker 2: So that's pretty awesome. And it's a lot faster than
Speaker 2: something like culture, which takes many days. Yeah, so that's
Speaker 2: kind of what it would look like if somebody was
Speaker 2: infected in general Legionari's disease, legionellosis with pneumo has about
Speaker 2: a five to ten percent fatality rate that's with treatment.
Speaker 1: Is that just because of just how fast the bacteria
Speaker 1: is like already cause damage before it's caught, or is
Speaker 1: it like the efficacy of treatment isn't as great as
Speaker 1: for other pneumonias, Like why is that?
Speaker 2: So it's actually pretty similar to the fatality rate for
Speaker 2: pneumonia's in general.
Speaker 1: Okay, that's just a bad it's just a bad pneumonia.
Speaker 2: And I think that historically Legionnaire's disease was considered a
Speaker 2: more severe form of pneumonia, and if untreated, the mortality
Speaker 2: rate can be a lot higher than for other forms
Speaker 2: of pneumonia. It can be as high as forty to
Speaker 2: eighty percent, whereas for other pneumonias it might be less
Speaker 2: like thirty percent or so. But as we've gotten better
Speaker 2: at recognizing Legionaire's disease, I think people get diagnosed earlier,
Speaker 2: and so we've seen that it's not always necessarily the
Speaker 2: most severe form of pneumonia. It's just that previously we
Speaker 2: were only seen the sickest of sick people. If that
Speaker 2: makes such yeah, yeah, yeah, okay. And the other thing
Speaker 2: that you would say would make this a more atypical
Speaker 2: pneumonia is that if you treat it like we would
Speaker 2: treat a typical pneumonia with something like a penicillin or
Speaker 2: a cephalosporin, it wouldn't respond because those type of antibiotics
Speaker 2: that we use for more quote typical. And when we
Speaker 2: say typical and atypical that doesn't mean common versus uncommon.
Speaker 2: Atypical pneumonias are still quite common.
Speaker 1: It's very confusing.
Speaker 2: I don't like real at all, but it's if you
Speaker 2: read about pneumonia's they use that terminology all the time.
Speaker 2: I'm not a fan, but yeah, so it doesn't respond
Speaker 2: to those You have to use different antibiotics, which is
Speaker 2: why in the US and a lot of other places,
Speaker 2: if somebody comes in with pneumonia, they'll often get an
Speaker 2: antibiotic that will cover both the atypicals.
Speaker 1: And the typicals. If that makes sense. Yeah, yeah, because.
Speaker 2: Because if we aren't able to test for the exact
Speaker 2: bacteria that causes it, you just want to cover everything
Speaker 2: that makes sense. Yeah, well that's the biology pretty much.
Speaker 1: Oh my goodness, that was so fast it was. Do
Speaker 1: you have any more questions? I guess I have more
Speaker 1: questions about like exposure, I think, and so maybe that's
Speaker 1: for the current status situation.
Speaker 2: Yeah, we'll probably talk about that a bit.
Speaker 1: Yeah, yeah, I think that's I think I don't have
Speaker 1: any more for the biology.
Speaker 2: Even though all my answers were I don't know.
Speaker 1: We made it through.
Speaker 2: So Aaron, do you know more than I do? Like
Speaker 2: where did this pathogen come from? And what's up with it?
Speaker 1: I will try to answer those right after this break.
Speaker 1: I like the story of Legionnaire's disease, because on the surface,
Speaker 1: it seems like a fairly straightforward example of a classic
Speaker 1: outbreak investigation and unraveling the mystery of a new infectious agent,
Speaker 1: which is basically what I thought it was when I
Speaker 1: first started researching for this episode, and that investigation, that
Speaker 1: whole outbreak epidemiology part of it is super duper interesting.
Speaker 1: But what I find makes it even more interesting is,
Speaker 1: of course, the context always the context. Why did this
Speaker 1: outbreak happen when it did, and what about it? Stances
Speaker 1: led to the way it played out, both in terms
Speaker 1: of the epidemiological investigation as well as how it was
Speaker 1: portrayed by the media. So let's get into it by
Speaker 1: going back to nineteen seventy six Philadelphia, Pennsylvania aka the
Speaker 1: City of Brotherly Love. This entire year, everyone around the
Speaker 1: US was celebrating the bi centennial of the country, including
Speaker 1: more than four thousand members of the American Legion, which,
Speaker 1: if you didn't know because I had to google it,
Speaker 1: is an organization of US War veterans. They do a
Speaker 1: lot of lobbying on behalf of veterans, and they also
Speaker 1: hold meetings or commemorative events, and one of these such
Speaker 1: events took place from July twenty first to July twenty
Speaker 1: fourth at the Bellevue Stratford Hotel in Philadelphia. This was
Speaker 1: specifically the fifty eighth annual convention of the American Legion
Speaker 1: Department wow YE. Over the course of that convention and
Speaker 1: in the weeks that followed, two hundred and twenty one
Speaker 1: people became ill with a mysterious disease and thirty four died,
Speaker 1: which is a rate of about fifteen percent. Most, but
Speaker 1: not all, of those affected were members of the American Legion,
Speaker 1: hence the name Legionnaire's disease. So what went down at
Speaker 1: this hotel? Yeah, The outbreak was first brought to the
Speaker 1: attention of the CDC when a local physician at the
Speaker 1: VIA diagnosed several of his patients with pneumonia. But this
Speaker 1: pneumonia wasn't typical pneumonia whatever it what means was it?
Speaker 1: And this one didn't seem to respond well to the
Speaker 1: normal antibiotics that he generally prescribed, and alarm bell started
Speaker 1: going off when four of his pneumonia patients died. Oh gosh.
Speaker 1: On the morning of August two, David Fraser, a former
Speaker 1: EIS officer, who worked as an epidemiologist at the CDC,
Speaker 1: got the call that something was going down in Philadelphia
Speaker 1: and he was put in charge of a field team
Speaker 1: to find out what. Fraser and his team arrived on
Speaker 1: the scene fairly early on in the epidemic curve, and
Speaker 1: while they had a lot to go on epidemiologically, that
Speaker 1: knowledge didn't help them too much in their top priority
Speaker 1: stopping or at the very least, slowing the epidemic. They
Speaker 1: knew that the linking factor among all of the people
Speaker 1: getting sick was this convention at the Bellevue Stratford Hotel.
Speaker 1: And as it turned out, these first few patients that
Speaker 1: the doctor at the VA sort of sounded the alarm
Speaker 1: on that was just the tip of the iceberg. More
Speaker 1: and more cases of pneumonia began to appear in doctor's
Speaker 1: offices around the city, and the death toll was mounting.
Speaker 2: Can you remind me how long after the convention this
Speaker 2: doctor told the CDC, like what the timeframe was?
Speaker 1: So I think the doctor told the CDC in like
Speaker 1: the very like August first, or like the very end
Speaker 1: of July. And I think the first cases were a
Speaker 1: few days in the middle of that convention. Oka and
Speaker 1: so which was July twenty first to July twenty fourth,
Speaker 1: And so the CDC got there like the first week
Speaker 1: of August, so like pretty soon, and it's like the
Speaker 1: epidemic curve maybe hadn't quite peaked, it was close to peaking, yeah,
Speaker 1: but yeah, but more and more cases started to like
Speaker 1: roll in. But it is likely that given the incubation
Speaker 1: period of two to fourteen days, those that were going
Speaker 1: to get sick had already been exposed, right, and there
Speaker 1: may not have been a whole lot more exposures happening.
Speaker 2: And that that convention was over and they presumably had
Speaker 2: left the city.
Speaker 1: A lot of people, I think a lot of them
Speaker 1: were in were in Pennsylvania at least. Okay, okay, So yeah,
Speaker 1: So even though probably a lot of the exposures had
Speaker 1: already happened, the disease was still showing up. And so
Speaker 1: more and more of these cases of pneumonia began to
Speaker 1: appear in doctors' offices. The death toll was mounting. And
Speaker 1: immediately the first thing that they suspected, the CDC suspected
Speaker 1: was influenza, but not just any influenza, swine flu or
Speaker 1: H one N one and so here comes some of
Speaker 1: the historical context. So earlier that year, there had been
Speaker 1: some cases of H one N one swine flu at
Speaker 1: Fort Dix, New Jersey, which got a lot of public
Speaker 1: health officials a bit concerned that this could be the
Speaker 1: start of another influenza pandemic similar to the one that
Speaker 1: happened in nineteen eighteen. And these cases of influenza were
Speaker 1: worrisome for a couple of reals. One was that although
Speaker 1: in nineteen seventy six people didn't know exactly what strain
Speaker 1: the nineteen eighteen influenza one was, studies had suggested that
Speaker 1: it was a similar isolate to the H one N
Speaker 1: one swine flu that had popped up at Fort Dix,
Speaker 1: and as we know now, it is like very similar.
Speaker 1: And another thing that was, you know, concerning, was in
Speaker 1: the timing. So these Fort Dix cases had happened very
Speaker 1: early in the year, like in January, which is much
Speaker 1: earlier than seasonal flu tends to increase in incidents, and
Speaker 1: that was another characteristic that it shared with the nineteen
Speaker 1: eighteen influenza. Okay, and so even though the nineteen seventy
Speaker 1: six swine flu outbreak at Fort Dix had caused only
Speaker 1: thirteen hospitalizations and one death. These similarities between the nineteen
Speaker 1: eighteen influenza were striking enough to lead to Gerald Ford,
Speaker 1: who was president at the time, to call for a
Speaker 1: mass immunization program. Over the next six months after first
Speaker 1: appearing at Fort Dix, swine flu had caused no additional cases,
Speaker 1: no hospitalizations, no deaths, and its spread seemed unlikely, and
Speaker 1: so the momentum for its vaccination or control seemed to
Speaker 1: be slowing somewhat. That is until these mysterious pneumonia deaths
Speaker 1: began to happen in Philadelphia, and these deaths led people
Speaker 1: to urge Congress to pass legislation indemnifying vaccine manufacturers for
Speaker 1: a swine flu vaccine, which is a decision that Ford
Speaker 1: later received a lot of criticism for, and in general,
Speaker 1: this like rapid response and some of the subsequent decisions
Speaker 1: regarding the potential you know, nineteen seventy six swine flu
Speaker 1: epidemic that never was. They were really controversial at the
Speaker 1: time and have in retrospect been called too strong of
Speaker 1: a response for this outbreak that never was, sort of
Speaker 1: like this miscalculation of risk and like being overly cautious,
Speaker 1: and I mean, I think It just serves as an
Speaker 1: example of, like, it's really hard to know what the
Speaker 1: right move is, but I bring it up because it's
Speaker 1: really important in understanding, at least in part, why there
Speaker 1: was such media frenzy around this mysterious illness in Philadelphia.
Speaker 1: You know, you have you have newspaper headlines calling it
Speaker 1: like the you know, Philly killer or killer fever, you know,
Speaker 1: ill in Philly. And actually I think I made that
Speaker 1: last one up.
Speaker 2: Everyone was just sort of primed to be paying attention
Speaker 2: to something like this. Yes, exactly, Okay, that makes sense.
Speaker 1: I mean it's sort of like I was thinking about
Speaker 1: it in the context of today and COVID and how
Speaker 1: like if there was a convention let's say, like this
Speaker 1: summer and next summer, and it was like, oh these
Speaker 1: cases of atypical pneumonia and fever, people would be very
Speaker 1: concerned for a good reason.
Speaker 2: Uh huh, yeah, remember that for later. Yeah, O great, okay,
Speaker 2: oh yeah.
Speaker 1: And the other thing is that swine flew this H
Speaker 1: one N one. This wasn't the only potentially deadly epidemic
Speaker 1: disease that was featuring in headlines during the nineteen seventies. Ebola,
Speaker 1: lass of fever, marburg virus, camplobacter enteritis, and gastritis lime disease.
Speaker 1: These were all making themselves known and scaring the world
Speaker 1: along the way throughout the nineteen seventies. And there's a
Speaker 1: quote that's often used to characterize the attitude of Western
Speaker 1: medicine in the middle of the twentieth century regarding infectious disease. Quote,
Speaker 1: it's time to close the books on infectious diseases, declare
Speaker 1: the war against pestilence I and shift national resoarch to
Speaker 1: such chronic problems as cancer and heart disease. So it
Speaker 1: turns out, and I found this out while trying to
Speaker 1: find this exact quote, that this is an urban legend.
Speaker 1: I knew it.
Speaker 2: I feel like I remember looking up that quote like
Speaker 2: when we first started this podcast and being like, it's
Speaker 2: not a real it's not real.
Speaker 1: It's not real. Yeah, No, like this no one like
Speaker 1: this quote was never said. It's it's just yeah, no
Speaker 1: one can find the origin. I know, I know, And
Speaker 1: so yes, it may be a misquote. And while the
Speaker 1: war on infectious disease was never declared over, it is
Speaker 1: true that advancements in antibiotics and vaccines may have made
Speaker 1: many clinicians a bit say, over confident, maybe regarding their
Speaker 1: ability to handle like whatever came their way totally. And
Speaker 1: even if we lacked the tools to take care of
Speaker 1: a pathogen, the number of newly diagnosed human pathogens, especially
Speaker 1: those that could cause epidemics, was kind of slowing to
Speaker 1: a near crawl, like since the heyday of you know,
Speaker 1: early germ theory and et cetera. If the first half
Speaker 1: of the twentieth century was basically like stick some sputum
Speaker 1: onto a slide, pop that slide under the scope, and
Speaker 1: then describe a global pathogen that had been infecting humans
Speaker 1: for millennia, then the second and half of the twentieth
Speaker 1: century felt to like many people, that there's like nothing
Speaker 1: new under the sun. We've gone it all, or just
Speaker 1: like a few things, like it's it's more of an
Speaker 1: anomaly to find a new pathogen than it is to
Speaker 1: just see your typicals right then, just your typical pneumonias,
Speaker 1: right and obviously that's not our feeling now right like
Speaker 1: not in the age of COVID nineteen of Zeka of
Speaker 1: bird flow of sin nombree virus, like we are keenly
Speaker 1: away the globe right now is keenly aware that emerging
Speaker 1: infectious diseases are very much a part of life, but
Speaker 1: this was not necessarily the case. In nineteen seventy six,
Speaker 1: Legionnaire's disease would really become one of the first or
Speaker 1: at the very least like part of the first cohort
Speaker 1: of emerging infectious diseases, which was this concept, a new
Speaker 1: concept at that time that would eventually force humans to
Speaker 1: evaluate the ways that they interact with their environment that
Speaker 1: may increase the risk of a spillover event or at
Speaker 1: the very least alter the ecology of the pathogen that
Speaker 1: could lead to an increase in human disease. And this
Speaker 1: trend of emerging infectious disease isn't solely one due to
Speaker 1: environmental disturbance, of course, it's also due to the constant
Speaker 1: development of technology and the growth of our own knowledge
Speaker 1: base that allows us to see more detail where previously
Speaker 1: it was all sort of a blur, like we're going
Speaker 1: to describe new species because we described one genus in
Speaker 1: the first place, or a new genus, right, so it
Speaker 1: just kind of like it builds and builds and builds.
Speaker 1: But let's head back to the hotel. Let's check it
Speaker 1: on what's going on there? Yeah, the CDC had shown
Speaker 1: up in full force and were quickly at work surveying
Speaker 1: those with the mysterious pneumonia as well as other attendees
Speaker 1: of the convention that hadn't gotten sick. These surveys revealed
Speaker 1: that older, age and smoking were pretty big risk factors,
Speaker 1: and that men were three times as likely to get
Speaker 1: the disease as women. They checked hospital logs they determine
Speaker 1: whether it was just the legionnaires or if other hotel
Speaker 1: guests or if anyone local had gotten sick too, and
Speaker 1: they certainly had. There were several cases of what was
Speaker 1: referred to as Broad Street pneumonia, which is the street
Speaker 1: where the hotel was on, that had popped up. Basically,
Speaker 1: these were people who weren't legionnaires or had not even
Speaker 1: necessarily gone into the hotel. Some had just been on
Speaker 1: the sidewalk next to the hotel. So what the heck
Speaker 1: was causing this disease? And even more pressing, how was
Speaker 1: it transmitted? And it would take some time for the
Speaker 1: second question to be answered, and I'll get to it,
Speaker 1: But what all of this shoe leather epidemiology did was
Speaker 1: help with the second question. At least in the form
Speaker 1: of ruling out, so food born and transmission was ruled out,
Speaker 1: Arthur pod vector borne transmission was ruled out. Person to
Speaker 1: person transmission was ruled out, which also kicked influenza to
Speaker 1: the curb at the same time. And it seemed most
Speaker 1: likely to Fraser and the others on this field team
Speaker 1: who were investigating the outbreak that either airborne or water
Speaker 1: contamination might be the culprit oh, but extensive sampling of
Speaker 1: the sources of water and all of the air ducks
Speaker 1: in the hotel it turned up nothing. Like they were baffled.
Speaker 1: Not long after the CDC had arrived on the scene,
Speaker 1: cases began to decline, and eventually there was nothing left
Speaker 1: to do but go back to Atlanta and begin preparing
Speaker 1: the reports, which they did on August twentieth, usually just
Speaker 1: like two and a half weeks of like hardcore investigation,
Speaker 1: like so many people on the ground right, and even
Speaker 1: though the field workers had covered a tremendous amount of
Speaker 1: ground in their investigation of the outbreak, the fact that
Speaker 1: they had come back without a causative agent, and that
Speaker 1: they seemed no closer to being able to prevent a
Speaker 1: subsequent outbreak of whatever this was. It made the CDC
Speaker 1: a big target in the media reporting at the time,
Speaker 1: which was already super critical of their handling of the
Speaker 1: whole swine flu situation. Right and also like this was
Speaker 1: in the headlines for ages, it became like part of
Speaker 1: popular culture. Almost like Bob Dylan wrote a song called
Speaker 1: Legionnaire's Disease.
Speaker 2: I okay, I know who Bob Dylan is, so that's
Speaker 2: like almost a.
Speaker 1: First for the two US. Good first step.
Speaker 2: But I feel like even today, most people will have
Speaker 2: heard of Legionnaire's disease.
Speaker 1: Like it's a thing.
Speaker 2: People have heard of it, it's a headline, et cetera. Yeah, yeah, yeah, Do.
Speaker 1: You want to hear the Bob Dylan like a couple
Speaker 1: of lines? I would love to. Okay, Okay. Some say
Speaker 1: it was radiation, some say there was acid on the microphone.
Speaker 1: Some say a combination that turned their hearts to stone.
Speaker 1: But whatever it was, it drove them to their knees. Oh,
Speaker 1: Legionnaire's disease. I love it. Yeah, and it goes on.
Speaker 1: There's more. I haven't listened to the actual song, so
Speaker 1: I don't know how the melody goes, but it exists.
Speaker 1: But anyway, I think that the song. I think that
Speaker 1: the you know, the little lyrics that I shared really
Speaker 1: speaks to the fact that no one knew what was
Speaker 1: going on, and that was part of the reason that
Speaker 1: it was like so persistent in you know, headlines and
Speaker 1: like the news stories at.
Speaker 2: The time, right, people love a mystery exactly.
Speaker 1: And all that the CDC and the affiliated institutions could
Speaker 1: could do, all they could say was what Legionaire's disease
Speaker 1: was not. And this was such an enormous investigation, even
Speaker 1: in just a short time period, Like, for instance, the
Speaker 1: Franklin Institute looked into the air conditioning system, The Academy
Speaker 1: of Natural Sciences examined the water supply. Drexel University used
Speaker 1: mass spectrometry to look at whether there was anything in
Speaker 1: the water. Harvard and MIT were involved in testing hair
Speaker 1: of survivors to look for an environmental toxin. University of
Speaker 1: Connecticut examined nickel poisoning, which was actually a pretty popular
Speaker 1: hypothesis for a minute until it was revealed that autopsy
Speaker 1: not which were nickel coated was leading to the like
Speaker 1: inflated appearance of contamination. Yeah, huh, like, but this was
Speaker 1: a huge undertaking.
Speaker 2: Yeah, and nobody even when they tested like the air
Speaker 2: conditionings and things, they didn't they couldn't find it.
Speaker 1: The why, But yeah, there was At the end of this,
Speaker 1: like after some of the reports had been produced, committees
Speaker 1: of infectious disease specialists and committees of pathologists came to
Speaker 1: one conclusion regarding the legionnaire's disease outbreak. Whatever had caused it,
Speaker 1: it definitely wasn't a bacterium. Yeah.
Speaker 2: Gosh, yeah, I love it when those kind of conclusions happened.
Speaker 1: I know. I mean it's so easy in retrospect to
Speaker 1: be like, well come on, but it is like yeah,
Speaker 1: so like why why were they so sure? Well, I
Speaker 1: mean it wasn't showing up on any of their routine
Speaker 1: or even in their non routine screens. Yeah, microbiologists had
Speaker 1: swabbed and smeared and cultured and stained every sample they
Speaker 1: could think of on all different types of culture media,
Speaker 1: but to no avail, Like nothing was there. Antigen tests
Speaker 1: revealed nothing. The pneumonia itself more closely resembled that of
Speaker 1: a viral pneumonia than a bacterial pneumonia, and so they
Speaker 1: were like, well, it must be either some sort of
Speaker 1: virus or some strange environmental contaminant. And I should note
Speaker 1: that there were some groups that did believe it was
Speaker 1: some sort of like undescribed bacterium, but like by and large,
Speaker 1: there were committees that were like, no, this is not bacterial.
Speaker 1: And now that the outbreak appeared to be over, the
Speaker 1: window of opportunity for uncovering what caused it seemed to
Speaker 1: be narrowing. Right. Of course, the failure to identify the
Speaker 1: causative agent led to constant criticism of CDC researchers assigned
Speaker 1: to the task. And there were still so many people
Speaker 1: assigned to the task. One of them was doctor Joseph McDade,
Speaker 1: who was a microbiologist at the CDC, and he had
Speaker 1: started working there in nineteen seventy five, I think, just
Speaker 1: like eight months or so before this nineteen seventy six
Speaker 1: Philadelphia outbreak, and he worked in the department for Rickettsial Diseases.
Speaker 2: Ooh.
Speaker 1: He had spent the previous decade studying various ricketsier both
Speaker 1: in the lab and in the field, including outbreaks of
Speaker 1: typhus in Egypt and Ethiopia. And if you think back
Speaker 1: to our Rocky Mountain spotted fever episode, which is a
Speaker 1: ricketzial disease. You may remember that ricketsie are notoriously difficult
Speaker 1: to cultivate to culture since they're these intracellular pathogens, right,
Speaker 1: And so mcdaide's background working on Rickettsia would prove to
Speaker 1: be key in finding the missing piece of the puzzle
Speaker 1: of Legionnaire's disease.
Speaker 2: And that's just fortuitous. Like well, I mean, it's lucky
Speaker 2: that McDade was there, or was.
Speaker 1: It because there were so many people working on so
Speaker 1: many different angles of this, Like was it fortuitous? Was
Speaker 1: it serendipitous or was it inevitable? Yeah? Yeah, So, like
Speaker 1: I mentioned, all kinds of these different hypotheses were being
Speaker 1: put forth to explain the outbreak, all at the same time.
Speaker 1: So you had a million different moving parts all looking
Speaker 1: at this angle and that angle, and this virus and
Speaker 1: that virus, and this fungus and that fungus whatever. And
Speaker 1: one of these hypotheses was q fever, which is a
Speaker 1: mild infection caused by Coxiella burnettii, which is a Ricketzia
Speaker 1: like pathogen. So it's really small and intracellular that can
Speaker 1: cause a typical pneumonia in people and it doesn't generally
Speaker 1: do that, but it and mcday didn't really think that
Speaker 1: this deadly outbreak, like I said, fifteen percent mortality rate
Speaker 1: was q fever, especially since people get Q fever through
Speaker 1: exposure to contaminated animals and like inhaling dust from them.
Speaker 1: But he was like, well, no, no, of course I'm gonna,
Speaker 1: you know, rule it out. And so he set to work.
Speaker 1: And so, like other ricketzial pathogens, Coxiella burnettii is a
Speaker 1: bit tricky to culture and isolate. So first you need
Speaker 1: to take the blood or tissue sample, grind it up
Speaker 1: and like put it in solution and then inject that
Speaker 1: into guinea pigs. And then you call the guinea pigs
Speaker 1: and take tissue from them to put in embryonated eggs.
Speaker 1: And when mcday did this with lung tissue from people
Speaker 1: who had died of Legionnaire's disease, the guinea pigs became febrile,
Speaker 1: like right away, like with a severe fever. Okay, nothing
Speaker 1: grew in the eggs when he tried to do that
Speaker 1: part of it. But when he looked at smears of
Speaker 1: guinea pigs spleen that had been stained by a technique
Speaker 1: common for like staining raquetzial species, he saw rod shaped bacteria,
Speaker 1: and he showed other researchers who kind of shrugged it off,
Speaker 1: saying it was a contaminant and not in high enough
Speaker 1: numbers to be the causative agent. Oh my gracious. Well,
Speaker 1: and around the same time, the nickel hypothesis had gathered
Speaker 1: steam because it was kind of being consistently found in
Speaker 1: all of the people who had died from Legionnaire's disease,
Speaker 1: which makes sense because it was on the autopsy knives anyway,
Speaker 1: and so, but so he didn't pursue this like rod
Speaker 1: shaped bacterium too much, Oh my gosh. But a few
Speaker 1: months later the nickel theory had been debunked and McDade
Speaker 1: found himself like wondering about it, just kind of like why.
Speaker 1: He was like, why can't I drop this idea about
Speaker 1: this rod shape bacterium? He was like, why is it there?
Speaker 1: Why why was nick culture in the eggs? Blah blah blah.
Speaker 1: And so he went in over like the Christmas break
Speaker 1: and was like, there's no one here. So I'm going
Speaker 1: to have the lab all to myself and I'm going
Speaker 1: to be able to do this work without being disturbed.
Speaker 1: Oh my gosh. And so he went back and he
Speaker 1: started to look at all of the slides again that
Speaker 1: he had prepared, and on one of them he saw
Speaker 1: not just a single, you know, rod shape bacterium, but
Speaker 1: a cluster of bacteria, which made him realize that this
Speaker 1: probably wasn't just a random contaminant, but likely the culprit.
Speaker 1: And additional testing revealed that he was right. More than
Speaker 1: ninety percent of the Philadelphia patients had antibodies to this bacterium,
Speaker 1: and they were also able to isolate it from additional
Speaker 1: autopsy specimens. Oh, but they still didn't know exactly what
Speaker 1: it was like. Was it a Ricketsia. No, it certainly
Speaker 1: didn't look like or behave like a Ricketzio species, so
Speaker 1: maybe it was something else. Eventually, through lots of trial
Speaker 1: and error, researchers were able to put together a recipe
Speaker 1: for a culture medium that met the very specific needs
Speaker 1: of this super festidious new bacterium. It's very picky. I yeah,
Speaker 1: I love the word festidious for bacteria. It's a good one.
Speaker 1: It's a good one. And through this they were also
Speaker 1: able to solve the mystery of its outbreak because it
Speaker 1: turned out that this bacterium loves warm water and the
Speaker 1: warm weather in July proved a perfect time for this
Speaker 1: bacterium to be misted out by the air conditioning system
Speaker 1: into the lobby of the hotel and into the sidewalk
Speaker 1: next to it. Just this like killer missed. Oh, by
Speaker 1: the time that the CDC had examined the AC system,
Speaker 1: it had been cleaned, so no traces of the bacterium
Speaker 1: had been found. Huh yeah, interesting. And this new bacterium
Speaker 1: was given the name Legionella numophila as a nod to
Speaker 1: this outbreak who was affected by it, and then the
Speaker 1: tendency of it to cause disease in the lungs like
Speaker 1: lung loving. And this turned out to be like a
Speaker 1: whole new genus of bacteria. But new doesn't necessarily mean
Speaker 1: new to humans. It may just mean newly described. So
Speaker 1: had the world seen Legionella numophilla before, absolutely always aways.
Speaker 1: All you needed to do, it seemed, was just to look.
Speaker 1: Once Legionella numophila was pinpointed as the causative agent, researchers
Speaker 1: immediately began combing through past unsolved outbreaks that resembled the
Speaker 1: one in nineteen seventy six to see if it had
Speaker 1: emerged before. And it apps lutely had in nineteen sixty eight,
Speaker 1: for example, when ninety five out of one hundred people
Speaker 1: who worked in a health department in Pontiac, Michigan, became
Speaker 1: ill with a mild illness, no deaths, And at that
Speaker 1: time there had been extensive epidemiological investigation into the outbreak,
Speaker 1: and the air conditioning units had been suspected, but it
Speaker 1: again didn't yield like any solid answers, and so it
Speaker 1: was kind of just like it's a mystery. But then
Speaker 1: once Legionella numophila had been described, people who had pontiac
Speaker 1: fever like were in that outbreak were tested for antibodies,
Speaker 1: and it was shown that they were one and the same.
Speaker 2: Interesting because of just the sort of epidemiological similarities, even
Speaker 2: though the disease itself wasn't nearly as severe.
Speaker 1: M exact fascinating. Yeah, and even at the Bellevue Stratford Hotel,
Speaker 1: so the same place where like this nineteen seventy six
Speaker 1: Legionnaires disease outbreak, first outbreak happened two years before during
Speaker 1: a meeting of the Odd Fellows Society. Yeah, several people
Speaker 1: had become ill with atypical pneumonia. So it was again
Speaker 1: shown that the same bacterium had been hiding out there.
Speaker 1: And then another outbreak of unexplained pneumonia in Saint Elizabeth's
Speaker 1: Hospital in Washington, d C. In August of nineteen sixty
Speaker 1: five that was also linked to the bacterium, And there
Speaker 1: was a specimen from nineteen forty three that revealed a
Speaker 1: strain of Legionella macdadi, and then another sample in nineteen
Speaker 1: forty seven turned up Legionella and so like it had
Speaker 1: definitely been around. I didn't really find anything on like
Speaker 1: the evolutionary origins of it, but it was clear that
Speaker 1: like outbreaks or cases of the disease weren't just a
Speaker 1: thing of the past, and also not just something that
Speaker 1: happened in the US. After the bacterium was discovered and
Speaker 1: described in December January of nineteen seventy six nineteen seventy seven,
Speaker 1: additional outbreaks occurred in Vermont in nineteen seventy seven, in
Speaker 1: England in nineteen eighty five, the Netherlands and nineteen ninety nine,
Speaker 1: a big outbreak in Spain in two thousand and one
Speaker 1: involving like seven hundred people, two thousand and five in
Speaker 1: Canada and Portugal, and twenty fourteen the bronx in twenty fourteen,
Speaker 1: I mean happening all over the world, and those are
Speaker 1: just the outbreaks. Like this disease also happens very sporadically,
Speaker 1: just like individual cases.
Speaker 2: Yeah, I feel like that's important to say because I
Speaker 2: think people think of it as just this outbreak pathogen,
Speaker 2: but really it can cause pneumonia in anyone anywhere, even
Speaker 2: just one case.
Speaker 1: H Yeah, absolutely, and so I am almost ready to
Speaker 1: turn it over to you, Aarin, But first I want
Speaker 1: to talk about the timing of all of this. Why
Speaker 1: did this disease seem to emerge in the mid twentieth century,
Speaker 1: Because you know, I didn't say anything about ancient Rome
Speaker 1: or Hippocrates or the Ebers Papyrus, So was it truly
Speaker 1: new to at least the twentieth century. No, not at all.
Speaker 1: I mean, like you said, this is an environmental bacterium,
Speaker 1: like it doesn't need humans to infect in order to
Speaker 1: live out its life. So it's possible that it caused
Speaker 1: cases here and there before the twentieth century. But there
Speaker 1: were two important developments or trends I guess that happened
Speaker 1: to lead to its emergence. Then. The first is simply
Speaker 1: advancements in microbiological technology and epidemiological techniques that allowed us
Speaker 1: to isolate and describe this pathogen. The second is air
Speaker 1: conditioning and water cooling towers. Like outbreaks with this bacterium
Speaker 1: are often linked to the HVAC systems in various buildings,
Speaker 1: especially hospitals and prisons as the source of exposure, which historically,
Speaker 1: obviously you know, wouldn't have been an issue, Like there
Speaker 1: were passive air conditioning systems, but they weren't the things
Speaker 1: that we have today. The things that we have today,
Speaker 1: those sort of developed for more widespread commercial and at
Speaker 1: home use around the middle of the twentieth century. And
Speaker 1: so that's right when these outbreaks of Legionella first started
Speaker 1: to happen, right, And so it all comes back to
Speaker 1: timing and context. Yet again, why did it happen when
Speaker 1: it happened, Why was it discovered then and not earlier,
Speaker 1: Why was there so much media attention? How did the
Speaker 1: demographics of the victims affect the attention it got. I
Speaker 1: didn't go into it here, but there has been a
Speaker 1: lot of discussion about that and the fact that these
Speaker 1: were members of the American legion who are largely impacted
Speaker 1: and comparing and contrasting that to the early days of
Speaker 1: the AIDS crisis and how little attention that got In comparison,
Speaker 1: all of these things play a huge role in how
Speaker 1: epidemics or outbreaks, including this one, play out. So, Aaron,
Speaker 1: as I sit here sweating because my own air conditioning
Speaker 1: unit is broken in my apartment and it's summer in Chicago,
Speaker 1: so it's kind of funny to just read constantly about
Speaker 1: air conditioning. I'm like, okay, yeah.
Speaker 2: Like dripping breathing in Legionella.
Speaker 1: Will you get me up to speed on where we
Speaker 1: stand with Legionella today?
Speaker 2: I would love to right after this break for a
Speaker 2: cold glass of water. Since the theme of this episode
Speaker 2: is we don't really know, we'll continue that here in
Speaker 2: the Epidemiology portional, Aaron, we know some things. It seems
Speaker 2: as though worldwide and in the US specifically, the overall
Speaker 2: risk for Legionella infections seems to be increasing, or at
Speaker 2: least the overall case numbers are certainly increasing, even though
Speaker 2: we have better guidelines in terms of cleaning of air
Speaker 2: conditioning system, et cetera on how to try to prevent
Speaker 2: Legionella contamination. So in the US from the year two
Speaker 2: thousand to around twenty fourteen, the US, which reports case
Speaker 2: numbers a little bit differently than the.
Speaker 1: Rest of the world.
Speaker 2: Of course, the US case numbers increased from about less
Speaker 2: than one per one hundred thousand people to one and
Speaker 2: a half cases per one hundred thousand people per year.
Speaker 1: This brings to mind that paper from Nygleria Fallerei where
Speaker 1: it was like, is this an emerging parasite.
Speaker 2: There's a very similar paper for legionella.
Speaker 1: Yeah.
Speaker 2: And so these numbers include both outbreaks and those single
Speaker 2: sporadic cases like we talked about, which do happen, and
Speaker 2: it also importantly includes both Legionnaire's disease and pontiac fever.
Speaker 2: But the biggest problem is that in all the surveillance
Speaker 2: systems in the US in Europe, over like ninety nine
Speaker 2: percent of cases that are reported are Legionnaire's disease. Why
Speaker 2: because that's the severe disease. So those are the people
Speaker 2: who are going to the doctor, going to the hospital,
Speaker 2: getting really sick, and then that disease is then reported.
Speaker 1: Question, uh huh. Has the frequency of outbreaks or the
Speaker 1: intensity or the size of outbreaks increased or is it
Speaker 1: the number of sporadic cases that have increased or have
Speaker 1: they increased in parallel. Good question.
Speaker 2: It seems like both have increased.
Speaker 1: Okay.
Speaker 2: Interesting In Europe, the European surveillance system in twenty eleven
Speaker 2: reported a prevalence of nine point seven per one million people,
Speaker 2: so it's a different scale. But and here's the biggest problem.
Speaker 2: We talked about this as well with our coccidioido mycosis episode.
Speaker 2: Even when you have a surveillance system in place, when
Speaker 2: we're dealing with a pneumonia, it's not super common that
Speaker 2: we're able to actually test for or identify a specific
Speaker 2: pathogen that's causing that pneumonia. So we not only don't
Speaker 2: have a good handle on the number of true legionnaire's
Speaker 2: cases every year, we also don't have great stats on
Speaker 2: the overall mortality rates every year because.
Speaker 1: We just don't know.
Speaker 2: In the US, in one paper from CDC, they suggested
Speaker 2: that the overall burden in terms of like if you
Speaker 2: look at all pneumonias, about two to nine percent of
Speaker 2: total community acquired pneumonia. And again that doesn't include hospital
Speaker 2: acquired pneumonia. And like you mentioned, Aaron, the HVAC systems
Speaker 2: in hospitals are a big place where contamination is possible,
Speaker 2: and therefore this could be a hospital acquired infection. But
Speaker 2: if we just look at community infection, two to nine
Speaker 2: percent of all pneumonias might be associated with legionella. Other
Speaker 2: papers that looked more globally suggested even up to fifteen
Speaker 2: percent of pneumonias that required hospitalization were associated with legionella.
Speaker 2: So if we go back in the coxsidioido my kosis episode,
Speaker 2: I did a bunch of like air in math right
Speaker 2: where we tried to calculate, like how many cases might
Speaker 2: there be. So there are in the US at least
Speaker 2: between twenty three and twenty seven cases per ten thousand
Speaker 2: adults of community acquired pneumonia that results in hospitalization every year.
Speaker 2: So if we think that maybe on the high end,
Speaker 2: ten percent of those might be caused by legionella, that
Speaker 2: would be two and a half cases per ten thousand
Speaker 2: adults every year, which is of course a lot more
Speaker 2: than are reported, And that would be about fifty two
Speaker 2: thousand cases per year in the US.
Speaker 1: So the substantial number, it's a substantial number. Yeah.
Speaker 2: So for sure globally, tens of thousands of people are
Speaker 2: becoming infected, potentially even hundreds of thousands, but we don't
Speaker 2: exactly know how many. The good news though, is that,
Speaker 2: unlike with coxcidioidomycosis, in many countries and in many parts
Speaker 2: of the world, the sort of standard treatment for community
Speaker 2: acquired pneumonia does include antibiotics that treat against legionaires, right ammonia,
Speaker 2: So that's at least a small silver lining.
Speaker 1: And have there been any seroprevalence studies that just like,
Speaker 1: look out it out of the blue? Good question.
Speaker 2: I didn't find many, Okay, Yeah, And overwhelmingly that's one
Speaker 2: of the biggest areas that we still need to do
Speaker 2: research on, is just getting a handle on the true
Speaker 2: like epidemiological risk.
Speaker 1: Yeah, so a question about that, like what is it
Speaker 1: about certain air conditioning systems? How are they cleaned? How
Speaker 1: does it get there in the first place, And like
Speaker 1: how do you protect yourself or or know whether you're
Speaker 1: inhaling you know this? Killer? Miss? Yeah? Killer miss. Yeah.
Speaker 2: It's a good questionnaire and not to freak you out, excellent.
Speaker 1: Yeah.
Speaker 2: But the biggest thing I've seen recently is a lot
Speaker 2: of news articles talking about the risk of legionnaires increasing
Speaker 2: as the pandemic of COVID nineteen begins. To wane because
Speaker 2: so you asked, like, what are the like, what kind
Speaker 2: of conditions lead to this growth? Right, unused air conditioning
Speaker 2: units that have a little bit of water in them,
Speaker 2: those kind of stagnant water in pipes. That is beautiful
Speaker 2: biofilm territory. Oh.
Speaker 1: No, all of these office buildings.
Speaker 2: Exactly, all the office buildings, all the hotels, all of
Speaker 2: these things that were closed or vacant during the pandemic.
Speaker 2: All of these months of these systems not being used,
Speaker 2: there's a huge potential again not to freak people out,
Speaker 2: but for legionnaires to increase.
Speaker 1: Wow.
Speaker 2: But the good news is that that people have been
Speaker 2: thinking about this. I read one article. It was just
Speaker 2: from like a news source, but it was about someone
Speaker 2: whose entire job during the pandemic was running the water
Speaker 2: in hotel like bathrooms and flushing all the toilets and
Speaker 2: running water through the pipes every week so that this
Speaker 2: hotel maintains good quality of water.
Speaker 1: How many of these cases are linked to or is
Speaker 1: it really known whether it's like these industrial HVAC systems
Speaker 1: or like personal at home HVAC systems. It's a good question.
Speaker 2: I don't think that we have a good handle on it,
Speaker 2: especially as we really just don't know how many cases
Speaker 2: there are per year, and I would guess, especially if
Speaker 2: you're talking about a personal h VAC system that you
Speaker 2: know maybe only one person ever gets exposed to it
Speaker 2: and gets infected, those cases are going to be even
Speaker 2: harder to pick up and to link to something specific. Okay, right,
Speaker 2: it's the larger outbreaks that you can then trace back
Speaker 2: to specific environmental sources. So yeah, that's Legionnaire's. There's some
Speaker 2: other pretty cool research being done. There's a lot of
Speaker 2: cool research being done, especially on the kind of detailed
Speaker 2: molecular biology. I'll link to a couple of papers on
Speaker 2: that to try and understand how Legionella is able on
Speaker 2: a molecular level to survive and persist in our cells,
Speaker 2: as well as on vaccine development. So we're nowhere near
Speaker 2: having a vaccine, but there are people who are working
Speaker 2: on mouse models to try and develop a vaccine because
Speaker 2: it's at least theoretically possible based on how much of
Speaker 2: an immune response humans mount to it.
Speaker 1: Okay, so well sources. Man, this was like short and
Speaker 1: sweet episode. Not that sweet, I guess.
Speaker 2: But short and moderately horrific.
Speaker 1: Yeah, absolutely, Yeah, I have a bunch, but I want
Speaker 1: to shout out a few that I found super helpful.
Speaker 1: One by Weiss from nineteen ninety two called a Plague
Speaker 1: in Philadelphia, Another by macdade himself from two thousand and
Speaker 1: two Legionnaire's Disease twenty five years later, Lessons Learned, and
Speaker 1: by When from nineteen eighty eight Legionaire's Disease A historical perspective.
Speaker 2: Wow. I love that there was a historical perspective like
Speaker 2: twelve years later.
Speaker 1: Yeah, I know right.
Speaker 2: I had a number of different papers. There's a really
Speaker 2: great comprehensive one from the Lancet twenty sixteen just called
Speaker 2: Legionnaire's Disease. Another from nineteen ninety three in Clinical Infectious
Speaker 2: Diseases called Legionnaire's Disease. We'll post the links to all
Speaker 2: of our sources on our website, This podcast will Kill
Speaker 2: You dot Com, where you can find every single source
Speaker 2: that we use for this episode and all of our episodes.
Speaker 2: Mm hmm.
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 the Exactly Right Network, of whom we're
Speaker 2: very proud to be a part.
Speaker 1: And thank you to you listeners. We hope you enjoyed
Speaker 1: this one. Actually, we just got an email like the
Speaker 1: other day being like can you do one on Legionnaire's disease. Yeah,
Speaker 1: it was like come in your way, you ask me
Speaker 1: answer and a big special thank you also to all
Speaker 1: of our patrons, you are amazing. We love you so much. Okay, well,
Speaker 1: until next time, wash your hands. You filled the animals.
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