Speaker 1: Hi, I'm umat And when I was a graduate student,
Speaker 1: I was doing field work in Panama. It was just
Speaker 1: this amazing place with tropical birds, and I loved the
Speaker 1: field work I did. I had to like hike up
Speaker 1: these rivers in the forest and find these insects, and
Speaker 1: it was so diverse and amazing. But you know, it
Speaker 1: was also tropical, so we had we were getting bit
Speaker 1: by insects, we were getting water and boots. You know,
Speaker 1: We're dealing with a lot of animals and things. And
Speaker 1: there was five of us living in this house. It
Speaker 1: was pretty crowded, five of us and a cat. And
Speaker 1: then one morning I woke up exhausted. I had had
Speaker 1: fever the night before and these awful dreams and a headache,
Speaker 1: and I knew that something was up, and so I
Speaker 1: I just rested that day and I tried to kind
Speaker 1: of you know, nourish myself, have a lot of water,
Speaker 1: have a lot of food, and I got I felt better,
Speaker 1: you know, by the afternoon, I was even able to
Speaker 1: a walk and everything. I said, Okay, maybe this was
Speaker 1: just a short term thing. Everything will be fine. And
Speaker 1: then that night it was worse. I had this awful fever,
Speaker 1: really really bad headaches, and in the morning, I was,
Speaker 1: I was just feeling awful, and so, you know, I
Speaker 1: didn't have a car at the time, and luckily I
Speaker 1: got a friend of mine to drive drive me to
Speaker 1: a clinic. And so I got to the clinic and
Speaker 1: I explained my symptoms, and you know, they're like, well,
Speaker 1: this is this sounds like dangay, and we're going to
Speaker 1: test your blood. And so they took a blood test
Speaker 1: and they didn't find dan kay. So they sent me
Speaker 1: home and told me that you know, this is probably
Speaker 1: some virus or something, and you should probably just recover
Speaker 1: on your own. Just you know, take lots of water
Speaker 1: if I demand, just take care of yourself. And so
Speaker 1: I said, okay, but but these is just progressed, and
Speaker 1: so I started getting more fevers and the next day
Speaker 1: I was, I was really awful, but it would be
Speaker 1: also kind of cyclical. So I would feel better and
Speaker 1: you know, I think it's improving, and then suddenly it
Speaker 1: would hit me again and I would get these fevers
Speaker 1: and headaches and be sensitive to light. So two days
Speaker 1: after I went to the clinic, I woke up and
Speaker 1: my sister just happened to be visiting, and I was
Speaker 1: showing her the tropics. I was showing her my field site,
Speaker 1: and so we woke up in the morning. I was
Speaker 1: not feeling great, but I was feeling okay, and so
Speaker 1: we drove up to the kind of be tower, saw
Speaker 1: some beautiful tropical birds, and I remember driving back and
Speaker 1: just suddenly being extremely sensitive to light, slowly feeling this
Speaker 1: weakness coming over my body, this fever coming. And by
Speaker 1: the time I got back, I was I was in
Speaker 1: bed shape. I kind of hobbled to bed and my
Speaker 1: head was killing me. And luckily I had a friend
Speaker 1: who said, you know, I think, you know, we should
Speaker 1: we should go right to the hospital right now. This
Speaker 1: is really bad. And we got to the hospital and
Speaker 1: I remember just having a hard time kind of even
Speaker 1: walking to hospital reception in the emergency room and stuff,
Speaker 1: and remember somebody bringing me a wheelchair and I thought,
Speaker 1: you know, I was like, I don't need that wheelchair,
Speaker 1: but as soon as you know, they brought it to me,
Speaker 1: I did sit down in it, and I just I
Speaker 1: was like, whow Okay, I definitely did need that wheelchair.
Speaker 1: And I remember my friends talking to the doctors and stuff,
Speaker 1: and they immediately took a blood test that was a
Speaker 1: moment when I knew things were way more serious than
Speaker 1: I had initially thought. I saw the doctor's expression and
Speaker 1: he came up with his paper and he said, this
Speaker 1: is a critical situation. Some of my liver enzymes were
Speaker 1: off the charts. We need to get to the IC immediately.
Speaker 1: So I got immediately admitted to a bed in the
Speaker 1: intensive care unit. They had me monitored my heart rate
Speaker 1: and my blood pressure and everything, and then I was
Speaker 1: under twenty four hour surveillance. Every twenty minute, somebody would
Speaker 1: come and check on me, because apparently that's how critical
Speaker 1: this isuuational so it progrets so quickly, at least from
Speaker 1: my perspective, and I remember just being extremely uncomfortable and confused,
Speaker 1: and so I did. I did improve slightly when I
Speaker 1: was in intensive care, but it still wasn't good and
Speaker 1: they still couldn't figure out what it was, and so
Speaker 1: I stayed in the hospital, and I just remember there
Speaker 1: was this routine somebody would come and take a lot
Speaker 1: of blood from me, and then you know, I would
Speaker 1: spend my time in my room and I'd be very comfortable.
Speaker 1: I was still getting these headaches this fever, but I'd
Speaker 1: also started getting pain in my stomach. I'd never experienced
Speaker 1: this before, but apparently my liver was extremely swollen, and
Speaker 1: so my stomach had become tight and tender, and i'd
Speaker 1: you know, just kind of terrifying thinking that like a
Speaker 1: single organ has flen to a level where it's like
Speaker 1: distending your body a little bit. And I spent almost
Speaker 1: two weeks in that hospital and they still couldn't figure
Speaker 1: out what it was. I was not getting any positive tests.
Speaker 1: They were prescribing me kind of general antibiotics. But eventually
Speaker 1: I started to feel a little better. I'd lost a
Speaker 1: lot of weight. I was weak, but after about two
Speaker 1: weeks I was released from the hospital, but I was
Speaker 1: still very weak, and it really bothered me that we
Speaker 1: didn't know what it was. I mean, is this something
Speaker 1: that was dormant that could come back again? And research
Speaker 1: something this serious? I really wanted to know. Could it be?
Speaker 1: You know, It's just not knowing was really really stressful,
Speaker 1: and so I ended up going to Canada. I'm a
Speaker 1: Canadian citizen, and I went to Canada and I called
Speaker 1: the hospital beforehand, and it turns out they had a
Speaker 1: tropical medicine program going on there with the med students.
Speaker 1: When I called them and told them my situation. They
Speaker 1: put me in touch with this doctor who's teaching this course,
Speaker 1: and it turns out they don't get a lot of
Speaker 1: tropical these patients in Canada. So I was talking to
Speaker 1: him about all the stuff I'd read and trying to
Speaker 1: try to figure out what, you know, what I had,
Speaker 1: and he asked me if it was okay if I
Speaker 1: could participate in trying to help figure out what was
Speaker 1: going on. And so he had a bunch of these
Speaker 1: med students around the bed and it was like an
Speaker 1: episode of House or something, one of those medical dramas
Speaker 1: where they try to figure out what you have, and
Speaker 1: different medical students gave their hypotheses. The experienced doctors said, well,
Speaker 1: maybe that's something you should pursue. Oh maybe that that's
Speaker 1: not right because you know of these chart readings or something,
Speaker 1: and they were trying to figure out what it might
Speaker 1: be to try to look for antibodies or some indication
Speaker 1: of what I had. And so then I left the
Speaker 1: hospital and I was recovering slowly, and then it wasn't
Speaker 1: until three months later I got a call and one
Speaker 1: of the medical students found figured it out. It was leptospirosis.
Speaker 1: And so when I found out that it was leptospurosis,
Speaker 1: now I had, you know, a diagnosis. I could start
Speaker 1: thinking about what the mode of transmission was. And I
Speaker 1: remembered when I was living in that house with those
Speaker 1: five people and that cat. That cat didn't like me
Speaker 1: very much, and I would go on these runs on
Speaker 1: pipeline on this road, this muddy road, and I would
Speaker 1: leave my shoes outside because this one time this cat
Speaker 1: keyed in my shoes and I didn't realize until I
Speaker 1: was walking around and I could smell something weird. And
Speaker 1: it was an outdoor cat too, so it was probably
Speaker 1: grabbing all sorts of rats and rodents outside and also,
Speaker 1: you know, a potential vector for leptosporrosis. So that time
Speaker 1: I also happened to have this cut in my foot,
Speaker 1: and so there's this possibility that it was this direct
Speaker 1: blood transmission that got me infected. But yeah, so that's
Speaker 1: that's the story of me getting leptosporrosis. It is.
Speaker 2: I remember that so vividly, and it was terrifying.
Speaker 3: It sounds awful, I remember hearing about it after the fact.
Speaker 2: Yeah, well, Uma, I'm so glad that you are better
Speaker 2: and that everything you know eventually turned out okay. And
Speaker 2: also thank you so much again for sharing your story,
Speaker 2: because for those of you who are longtime listeners, you
Speaker 2: may have recognized Umat's voice from season one when he
Speaker 2: provided the first hand account for malaria.
Speaker 3: Let's hope Uman, that there's no more diseases that we
Speaker 3: need to have you provide a first hand account.
Speaker 2: For Let's let's hope. Hi, I'm erin.
Speaker 3: Welsh and I'm erin Allman Updike and this.
Speaker 2: Is this podcast will kill you.
Speaker 3: And today we're talking about leptosporrosis.
Speaker 2: Leptosporosis.
Speaker 3: Yeah, can I make Can I make a quick confession?
Speaker 3: I just want to say this off the bat. Of
Speaker 3: course I don't know why, but leptosporosis, lee jonella, and
Speaker 3: leshmaniasis constantly confused in my brain. Interesting those three, and
Speaker 3: now we've covered all of them.
Speaker 2: That's like me and Gerard Butler and Clive Owen, they're
Speaker 2: the same person.
Speaker 3: They actually are the same person. So that's very valid.
Speaker 2: Well, and so now you don't have to worry about
Speaker 2: getting them confused anymore because this is just we're done right.
Speaker 2: I'm really excited for this episode because when I was
Speaker 2: going through emails to be like, Okay, what do people
Speaker 2: want to hear? I was so surprised at the number
Speaker 2: of requests for leptosporosis. Yeah, And one of the reasons,
Speaker 2: it seems like, is because this is a disease that
Speaker 2: affects not just humans but also many animal species. And
Speaker 2: it's just it's so much more prevalent and important than
Speaker 2: I think I realized, even after, you know, watching Uma
Speaker 2: go through this horrible ordeal.
Speaker 3: Yeah. I think it's it's easy to think of this
Speaker 3: as a disease of the tropics or as a disease
Speaker 3: of you know, other places, but it's a worldwide pathogen,
Speaker 3: as we'll talk about, and I think a lot of
Speaker 3: pet owners and veterinarians are probably a lot more familiar
Speaker 3: with it than maybe the general public. Yes, totally, Yeah,
Speaker 3: I'm excited it's going to be good.
Speaker 2: First things first, it's quarantiny time, It's quarantine any time.
Speaker 2: What are we drinking this week?
Speaker 3: We're drinking I smell a rat?
Speaker 2: And why are we drinking? I smell a rat?
Speaker 3: It turns out, Aaron, that rats are a very important
Speaker 3: part of the overall distribution and prevalence and life cycle
Speaker 3: of leptospira.
Speaker 2: And I also want to say just right here that
Speaker 2: we are not trying to intentionally further the stigma against rats.
Speaker 3: Don't blame the rat.
Speaker 2: Don't blame the rat. Rats are just one piece of
Speaker 2: the puzzle. Many other animals do this. But the title
Speaker 2: was too good to pass up.
Speaker 3: Yeah, because who doesn't want to drink? Who doesn't want
Speaker 3: to drink I Smell a Rat?
Speaker 2: And really, I mean, once you hear the recipe, though,
Speaker 2: you're definitely going to want to drink it.
Speaker 3: Please tell me what isn't it?
Speaker 2: It is a shrub. It's a mango habanero mint shrub.
Speaker 2: So this is like a drinking vinegar. You muddle all
Speaker 2: of these you know, fruits and ingredients together with sugar,
Speaker 2: let it sit, and then you can use that as
Speaker 2: a great base for a cocktail like this one with
Speaker 2: tequila for instance, or you can use it as a
Speaker 2: plusy burita as well with no alcohol. Delicious either way.
Speaker 2: And we will post the full recipe for I Smell
Speaker 2: a Rat the quarantini as well as the plasy Burrita
Speaker 2: on our website this podcast will Kill You dot com,
Speaker 2: as well as on all of our social media channels
Speaker 2: and on.
Speaker 3: Our website, this podcast will kill you dot com. You
Speaker 3: can find all of the best website type things you
Speaker 3: can find.
Speaker 2: Do you think people even need to hear this at
Speaker 2: this point?
Speaker 3: I don't know really, Just check out our website. Yeah,
Speaker 3: there like that.
Speaker 2: I like that, Arin, I am so ready to learn.
Speaker 2: So can we take a quick break and get started.
Speaker 3: Let's do it. Leptosporosis is a disease caused by a
Speaker 3: bacterium in the genus Leptospira or leptospira. These are spirokeets,
Speaker 3: which means those little tirly quirkscrew dudes. Like a few
Speaker 3: other pathogens we've covered, like treponema, the causative agent of syphilis, burelia,
Speaker 3: which causes lime disease, have we done any others?
Speaker 2: I was trying to think of that and I can't
Speaker 2: come up with anymore me neither those.
Speaker 3: Are the two I remember. Yeah, So, this spira keet,
Speaker 3: it turns out, is not just one bug, it's not
Speaker 3: just one species. And it seems like from what I
Speaker 3: could read, the classification and species definition seems to be
Speaker 3: in flux currently, so different papers have a lot of
Speaker 3: different numbers cited, but it seems like there's over sixty
Speaker 3: different species. I think that's the consensus in the genus Leptospira,
Speaker 3: and importantly, this includes more than three hundred sero VARs
Speaker 3: asterisk a note Aaron, I would like to talk about
Speaker 3: this a little bit more, okay, because in our episode
Speaker 3: on Salemonilla, we talked about the idea of like species
Speaker 3: and subspecies in seravars, and in that episode, I feel
Speaker 3: like I did a very bad job of trying to
Speaker 3: define what seravars actually are, and when it comes to
Speaker 3: leptosporosis and salmonella and a lot of other back TOI,
Speaker 3: serr VARs are really important epidemiologically a lot of times
Speaker 3: in distinguishing like was this outbreak all from this source
Speaker 3: or from that source, et cetera. So I wanted to
Speaker 3: give a little bit of a better definition of what
Speaker 3: a cero var actually is in this case. Basically, ser
Speaker 3: of vrs are determined based on the surface antigens, so
Speaker 3: differences in those surface proteins and things, which of course
Speaker 3: are some of the main things that our bodies use
Speaker 3: to recognize various pathogens, right right, And so serrvars are
Speaker 3: like strains or isolates that differ in their surface antigens.
Speaker 3: In the case of leptosporosis, there are over sixty different species,
Speaker 3: not all of which are pathogenic, but which include over
Speaker 3: three hundred ser of VARs at least two hundred or
Speaker 3: over two hundred of which are pathogenic.
Speaker 2: It seems like more are being discovered all the time.
Speaker 3: I am not surprised. So anyways, I hope that was
Speaker 3: at least a little more helpful than my description in
Speaker 3: the salmonella episode.
Speaker 1: It was.
Speaker 2: It's really interesting. Yeah, before we move back to leptosporosis,
Speaker 2: I just want to take a moment to share something
Speaker 2: about salmonella.
Speaker 3: Oh love it.
Speaker 2: A listener reached out to us, and you know how,
Speaker 2: in the salmonella episode, we were like, oh, is it
Speaker 2: pronounced Daniel Salmon or Daniel Salmon the person who salmonella
Speaker 2: is named after.
Speaker 1: Uh huh.
Speaker 2: So someone tweeted at us and said it's pronounced Salmon
Speaker 2: because he is one of her ancestors, which is so thrilling.
Speaker 3: Oh. I love that. I feel like we've had a
Speaker 3: couple times where people have emailed us saying like, I'm
Speaker 3: related to one of the people you talked about, and
Speaker 3: I don't know why. It thrills me.
Speaker 2: Oh on every single time.
Speaker 3: It's so cool. My heart is beating quickly. I love it.
Speaker 3: Back to letos back to leptosporosis, all right, if you're
Speaker 3: related to anyone, no, okay, So anyways, that's the pathogen.
Speaker 3: A lot of different species, a lot of different serivars.
Speaker 3: Like I said up top, this is a pathogen that
Speaker 3: is found worldwide, and while it is more prevalent or
Speaker 3: at least more common, in the tropics, this is mostly
Speaker 3: just because it can be an environmentally transmitted pathogen. This
Speaker 3: is something that can persist in the environment for weeks
Speaker 3: to months, in the water and in the soil, and
Speaker 3: the climate in the tropics is just a little better
Speaker 3: suited for Leptospira growth and survival. But this is a
Speaker 3: bacterium that can infect almost any mammal, pretty much all mammals,
Speaker 3: some of them. Some mammal species are very good reservoirs,
Speaker 3: which means that they can harbor this bacterium mostly in
Speaker 3: their kidneys at really high levels for months at a
Speaker 3: time and pee it out all over the place, often
Speaker 3: without showing any symptoms or getting sick at all. Other
Speaker 3: species are less great reservoirs, and they may get sick
Speaker 3: to varying degrees. But what's really important is that this
Speaker 3: can infect literally almost any mammal, including marine mammals, which
Speaker 3: I always find fascinating.
Speaker 2: Yeah. Question, you are saying this bacterium, do you mean
Speaker 2: like the genus overall or are there species differences in
Speaker 2: terms of like which animals are best reservoirs for which
Speaker 2: species or seravars? Great?
Speaker 3: Great, great, great question. Yes, there are differences where some
Speaker 3: species or some serivars are maybe more common in certain
Speaker 3: animal species and others are more common in other species.
Speaker 3: But of the pathogenic species of Leptospira, they can have
Speaker 3: been shown in the lab to infect nearly any mammal
Speaker 3: if you expose them to.
Speaker 2: It, any given leptosperra pathogenic species, right.
Speaker 3: Exactly, So it probably shouldn't be saying this bacterium like
Speaker 3: this genus. Okay, these pathogenic spirokeets. Yeah, but excellent question.
Speaker 3: So when it comes to humans, we generally get exposed
Speaker 3: either through direct contact with infected domestic animals like cattle
Speaker 3: or dogs, or more commonly, through exposure to infected water
Speaker 3: sources or infected soil, and exposure happens in a variety
Speaker 3: of ways. These spirokeets can corkscrew their way in through
Speaker 3: any little cuts or abrasions on our skin. They can
Speaker 3: enter directly. If you get infected water in your eyes
Speaker 3: or your mouth, they can enter through your mucous membranes.
Speaker 3: Even if you swallow a bunch of contaminated water or
Speaker 3: drinking water sources become contaminated, you can get infected that
Speaker 3: way as well. And that is true for animals as well.
Speaker 3: So that's the way that all other animals are also
Speaker 3: being infected through abrasions on their skin or through their
Speaker 3: mucous membranes.
Speaker 2: Which makes sense about high infection rate in some animals
Speaker 2: because if you just imagine dogs, a lot of dogs
Speaker 2: love drinking out of puddles.
Speaker 3: As I will. My veterinarian when my dog was a
Speaker 3: puppy was like, oh, we could vaccinate for a leptospira,
Speaker 3: Like is your dog a puddle liquor? And I was like,
Speaker 3: are not all dogs lickers? So yes, if you have
Speaker 3: a puddle liquor that they will be.
Speaker 2: Exposed total liquor. Unbelievable.
Speaker 3: So, these highly mobile little spirokeets, once they get into
Speaker 3: our bodies, corkscrew their way directly into our bloodstream and
Speaker 3: begin to replicate. They cause a bacteryemia, which is bacteria
Speaker 3: in our blood. That's all that means over the course
Speaker 3: of usually about a week or so. Oh and then
Speaker 3: once those bacteria reach high enough numbers. And what's fascinating
Speaker 3: about leptosporosis is that the amount of bacterymia can be
Speaker 3: incredibly high. Like we're talking millions of bacteria per milli
Speaker 3: liter of blood, which is very high even before you
Speaker 3: show any symptoms. And this is way higher than what
Speaker 3: we would see from a bacterymia in like an E.
Speaker 3: Coli or something without our bodies freaking out about it.
Speaker 2: Why is that? Why does it produce such a high bacterymia, Well.
Speaker 3: It seems like our bodies are very good at detecting
Speaker 3: and mounting a response to very low levels of antigen
Speaker 3: from something like ecoli, but essentially just don't even recognize
Speaker 3: leptosperosis antigen until it's at very very high levels.
Speaker 2: What interesting, I know, huh.
Speaker 3: Right, Then, after they get to these very very high
Speaker 3: levels in our blood, these bacteria start burrowing their way
Speaker 3: through our endothelials that line our blood vessels and into
Speaker 3: various organs. And that is usually the point at which
Speaker 3: symptoms will tend to start to appear. So the total
Speaker 3: incubation period is anywhere from seven to fourteen days, could
Speaker 3: be as long as a month, and rarely is shorter
Speaker 3: than that.
Speaker 2: Okay. And once these bacteria leave the blood and start
Speaker 2: burrowing and finding their way to organs and whatnot, does
Speaker 2: that mean that they straight up leave the blood? Would
Speaker 2: you be able to detect them in the blood?
Speaker 3: Excellent question. They don't leave the blood entirely, but these
Speaker 3: are still difficult bacteria to detect because like other spira
Speaker 3: keets that we've talked about on this podcast, they don't
Speaker 3: gram stain very well, and so they're just not as
Speaker 3: easy to pick up. And I do think that the
Speaker 3: amount of bacteremia tends to go down once they enter
Speaker 3: our organs.
Speaker 2: Okay, yeah, okay, that plays a relevant role in the
Speaker 2: history section.
Speaker 3: Oh I bet I can't wait bacteremia okyeah? Okay, all right?
Speaker 3: Boilers or just foreshadowing foreshadowing? Yeah, yeah. When it comes
Speaker 3: to animals, various animal species that get infected, they can
Speaker 3: remain infected and primarily in the proximal tubules of the kidney,
Speaker 3: which is just so interesting. That this pathogen loves that
Speaker 3: particular part of a kidney for literally months, in some
Speaker 3: cases up to a year, and then because they're in
Speaker 3: the tubules of the kidney where your kidney is making urine,
Speaker 3: this pathogen is just being shed beautifully at very high
Speaker 3: levels in the urine. So for some animals this process
Speaker 3: can be completely asymptomatic, and for other animals, including dogs
Speaker 3: and in some cases including cattle, they can also get
Speaker 3: sick from leptosporosis. And what's interesting is that, especially in
Speaker 3: the case of dogs, which there's maybe more detailed clinical
Speaker 3: information at least that I could find on dogs compared
Speaker 3: to some other animals, the disease actually can look a
Speaker 3: lot like the disease in humans. So let's talk about
Speaker 3: what those symptoms actually look like. First of all, this
Speaker 3: is something that even in humans can be entirely asymptomatic.
Speaker 2: You could just be shedding shatteria in your urine, okay.
Speaker 3: And importantly, for humans, some papers call humans dead end hosts.
Speaker 3: We're not truly dead end hosts, but transmission from humans
Speaker 3: to humans is very very very very rare. We can
Speaker 3: potentially shed leptospera in our urine, but it tends to
Speaker 3: be at much lower levels than something like a rat.
Speaker 2: Okay, so the general root of infection and course of
Speaker 2: infection where the bacteria go from point A to point
Speaker 2: B and so on, is the same across these mammalian hosts,
Speaker 2: but the symptoms that they show is different, and the
Speaker 2: amount that they excrete is different.
Speaker 3: Absolutely interesting. Yeah mm hmm, I know. But even in
Speaker 3: humans it can be asymptomatic. And I tried to get
Speaker 3: a handle on how often, and that was very difficult
Speaker 3: to do. A couple of studies that I read suggested
Speaker 3: that up to seventy percent of the time people tested
Speaker 3: serial positive for leptosperosis but couldn't call any febrile disease
Speaker 3: in the months prior. So it's kind of hard to say.
Speaker 3: Could it be that someone just is still seral positive
Speaker 3: but they had an infection, you know, a couple of
Speaker 3: years ago that they just don't remember. I don't really know,
Speaker 3: but we do know that in animals and in humans
Speaker 3: it can be asymptomatic, and that's really important when we're
Speaker 3: trying to control or reduce the prevalence of a disease
Speaker 3: and right then, but when there are symptoms, here's how
Speaker 3: it usually starts. It starts with a fever, Yeah, it
Speaker 3: sure does. Usually it's a sudden onset of fever along
Speaker 3: with chill. Yes, Usually there's a pretty severe headache that develops,
Speaker 3: and body aches, generalized muscle aches. And the number of
Speaker 3: pathogens that we've covered, even in this season alone that
Speaker 3: start out that exact same way is a lot. So
Speaker 3: this is something that, especially in the early stages, is
Speaker 3: a very non specific disease that can easily be mistaken
Speaker 3: for a number of other viral or bacterial infections. Yeah. Interestingly,
Speaker 3: with leptosporosis, in contrast to the other spiral keats we've seen,
Speaker 3: you tend to not have any rashes or skin findings
Speaker 3: early on, and that's because of the way that lepto
Speaker 3: goes kind of straight into the bloodstream rather than having
Speaker 3: any skin manifestations. Usually you'll also then start to see
Speaker 3: gi symptoms like nausea, vomiting, maybe some diarrhea, and in
Speaker 3: a lot of cases that might be where this disease ends.
Speaker 3: So you might get pretty sick, but it'll be self
Speaker 3: limited and then you'll recover. But when this progresses to
Speaker 3: a severe illness, and this can happen over the course
Speaker 3: of a few days, and sometimes people get a little
Speaker 3: better and then have a bi phasic illness where then
Speaker 3: they get better and then start to get worse again.
Speaker 3: And at that point, whether you just progress immediately or
Speaker 3: have this biphasic illness, this progression to severe leptosporosis is
Speaker 3: when we start to see signs of real organ dysfunction.
Speaker 3: So what does that mean. It means we see signs
Speaker 3: of liver damage like jaundice, yellowing of the skin, and
Speaker 3: ictorus yellowing of the eyes. This happens from build up
Speaker 3: of bilirubin because of the damage to your liver as
Speaker 3: well as hemolytic anemia. So this bacteria can cause breakdown
Speaker 3: of your red blood cells that also contributes to the jaundice.
Speaker 3: A lot of times you'll have dysfunction in various they're
Speaker 3: blood cells as well, so you can have a lot
Speaker 3: of signs of bleeding because of a decrease in your platelets.
Speaker 3: So it might be mild like little purple spots on
Speaker 3: your skin called petikia, or can be very severe and
Speaker 3: have massive gastriintestinal bleeding or pulmonary hemorrhage, so bleeding into
Speaker 3: your lungs that can be fatal. In fact, if you
Speaker 3: do see that pulmonary hemorrhage, it's an up to fifty
Speaker 3: percent mortality rate at that point. So this is something
Speaker 3: that can progress to a very very severe illness. Okay,
Speaker 3: question give it to me.
Speaker 2: How is it causing all of these different symptoms?
Speaker 3: Great question, We'll get there, Okay.
Speaker 2: And my other question then is about who has these symptoms? Like, yeah,
Speaker 2: are there characteristics that determine or play or seem to
Speaker 2: play a role in whether someone has an asymptomatic or
Speaker 2: a mild or a or a severe case of this?
Speaker 3: Yeah, that's another great question. The older people are the
Speaker 3: more likely that they are to progress to severe disease.
Speaker 3: I didn't see a ton of data on if the
Speaker 3: same is true in people who are very young. But
Speaker 3: I'll talk more in just a little bit about how
Speaker 3: much specific host factors likely play a role in the
Speaker 3: severity of infection. And we truly don't know what those
Speaker 3: specific host factors are at this point.
Speaker 2: And do the different serovars and species play a.
Speaker 3: Role too potentially, yes, But again we don't have like
Speaker 3: great great data on like this erra of r. There's
Speaker 3: a couple of serr of rs icdohemorrhaga. I think that's
Speaker 3: it is one that is known to be of like
Speaker 3: very important human significance because it can cause pretty severe infection.
Speaker 3: But there's so many serra vrs and we just don't
Speaker 3: have a ton of data, so we'll get into a
Speaker 3: little bit more detail on how it's causing these specific findings.
Speaker 3: When it comes to the pulmonary hemorrhage, it really is
Speaker 3: that this bacteria ends up causing damage directly in your
Speaker 3: lungs that then causes that bleeding to the point where
Speaker 3: you essentially can drown in your own blood.
Speaker 2: How is it causing that damage?
Speaker 3: So, it's damaging the endothelial cells, it's damaging the lining
Speaker 3: of our blood vessels. It's damaging our reducing our platelets,
Speaker 3: so it's not allowing for our blood to clot it,
Speaker 3: et cetera.
Speaker 1: Gotcha.
Speaker 3: Yeah, So that's the liver and the lungs and blood
Speaker 3: and blood vessels. But one of the other main target
Speaker 3: organs of leptosporosis, of course, is the kidneys, and so
Speaker 3: when this progresses to severe disease, it often results in
Speaker 3: what's called Wheels disease, which essentially can cause progressive kidney
Speaker 3: damage to the point of kidney failure. Kidney failure, of course,
Speaker 3: can be extremely fatal unless you have access to dialysis,
Speaker 3: and access to dialysis can drastically reduce the mortality rate
Speaker 3: in the case of severe kidney failure. When it comes
Speaker 3: to leptosporosis, so it's a lot. It really can affect
Speaker 3: all of our organs. It can infect the heart and
Speaker 3: cause cardiac involvement, It can cause myocarditis, It can cause
Speaker 3: an aseptic meningitis, so it can get into the CSF
Speaker 3: or at least cause enough inflammation in our brain and
Speaker 3: spinal cord that headache that presented at the beginning can
Speaker 3: become incredibly severe. But overall, a lot of these symptoms
Speaker 3: can be really difficult to distinguish from viral hemorrhagic fevers
Speaker 3: like dange fever, for example, or from things like scrub typhus,
Speaker 3: which we technically haven't covered yet.
Speaker 2: No we have not, but I remember, yeah it comes
Speaker 2: up again.
Speaker 3: Oh good. Symptoms can last a pretty varied amount of time.
Speaker 3: When they get severe, they can persist for potentially weeks,
Speaker 3: and even in the case when symptoms are not that severe,
Speaker 3: there is some suggestion of like post leptosporosis type syndrome
Speaker 3: with things like fatigue, persistent headache, myyalgia that can potentially
Speaker 3: last for months.
Speaker 2: If you get leptosporosis and recover, do you have immunity
Speaker 2: towards it in the future and is there cross protection
Speaker 2: with different seravars or different species?
Speaker 3: What a great question, Aaron. That is such an important
Speaker 3: question because what it basically like, if you circle on
Speaker 3: that question long enough, you ask, can we make a vaccine,
Speaker 3: do we have a vaccine, et cetera. You get at
Speaker 3: least some immunity. How much cross protection there is on
Speaker 3: different seri VARs unclear? How long that immunity might last
Speaker 3: again unclear. There is some data that suggests that like
Speaker 3: waning immunity over time in people who maybe lived in
Speaker 3: an endemic area and were exposed as young people and
Speaker 3: then get exposed again as they're older, are susceptible again.
Speaker 3: So it doesn't seem to be something where you're immune
Speaker 3: for the rest of your life forever. We do mount
Speaker 3: immunity to it in a way that offers at least
Speaker 3: some protection against severe infection. Okay, but obviously this is
Speaker 3: a huge range in disease severity, and you kind of
Speaker 3: already asked the question of, like, what is the underlying
Speaker 3: pathology of this? Why do some people get so sick
Speaker 3: other people don't get so sick? And it boils down
Speaker 3: to three major things, which we've already touched on, but
Speaker 3: I'll go in a little bit more detail. One is
Speaker 3: those virulence factors of the particular Leptospra species or serravr
Speaker 3: that you get exposed to. So some that are more
Speaker 3: or less host specific might cause disease in certain animals
Speaker 3: and not in others, and some with particular virulence factors
Speaker 3: on them might be more or less virulent than others.
Speaker 3: The second factor is the inoculum, so like how much
Speaker 3: PA contaminated water did you guzzle down? Or like how
Speaker 3: many spira keets did you end up with initially? Right?
Speaker 3: And the third is my favorite, the most difficult, the
Speaker 3: host factors. It's a very nebulous category. In the case
Speaker 3: of leptosporosis. What it seems to boil down to is
Speaker 3: our cytokine related immune response. So cytokines are pro inflammatory agents, right,
Speaker 3: These are proteins and like stuff in our body that
Speaker 3: we make and secrete in response to an infection in
Speaker 3: order to get the rest of our immune system on
Speaker 3: high alert to go look for and eliminate this problematic
Speaker 3: spiro keet. But, as we've talked about time and again
Speaker 3: on this podcast, if our body goes on too high
Speaker 3: of an alert, if we get too intense about this inflammation,
Speaker 3: then we can end up with tissue damage that's not
Speaker 3: even directly due to the pathogen, but due to these
Speaker 3: inflammatory cytokines and all of the other immune response that
Speaker 3: they stir up. So while we don't know a lot
Speaker 3: of the details on this, we think that that's a
Speaker 3: huge part of the pathogenesis, especially of severe leptosperosis, is
Speaker 3: this intense inflammatory and cytokine response that is generated, and
Speaker 3: that's what's causing a lot of these severe manifestations. That's
Speaker 3: what's causing the damage to our lungs, that's what's causing
Speaker 3: the damage to our liver, that's what's destroying our red
Speaker 3: blood cells and our platelets and causing us to bleed
Speaker 3: to death.
Speaker 2: Okay, interesting, Yeah, it seems like there's a lot more
Speaker 2: work to be done in that field.
Speaker 3: Absolutely, we don't have enough data just yet to say
Speaker 3: for sure what specific side kinds are being upregulated or
Speaker 3: causing the most damage when it comes to this very
Speaker 3: severe versus not so very severe infection. But I will
Speaker 3: link to a couple of papers that have more detail
Speaker 3: on what we do know about particular cytokines.
Speaker 2: Question about diagnosis, Oh great, So, like you mentioned, this
Speaker 2: disease can be confused with many other diseases. Has kind
Speaker 2: of these non specific symptoms And what would make someone
Speaker 2: suspect leptosporosis number one and number two? You said it's
Speaker 2: difficult to test for because it doesn't show up very
Speaker 2: well on Graham stains. How do you then test for it?
Speaker 2: What are the samples you would take?
Speaker 3: Beautiful questions arin so, how you would suspect it would be,
Speaker 3: of course, if someone is having these symptoms that I described,
Speaker 3: like these laboratory abnormalities that we see jaundice, signs of
Speaker 3: kidney failure, but also if they have a history of
Speaker 3: something that would make us think they've had an exposure
Speaker 3: to potentially contaminate in environmental sources, if they've been one
Speaker 3: water rafting, if they've been jumping off of cliffs into
Speaker 3: freshwater sources, or if they work in a field like
Speaker 3: a race paddy or something like that. So occupational exposures
Speaker 3: or recreational exposures that might make us think maybe this
Speaker 3: is leptosporosis. It might be higher on your list to
Speaker 3: think about in areas where leptosporosis is more common and
Speaker 3: less likely that you'll think about it in places where
Speaker 3: it's less common, but it's important that it exists everywhere,
Speaker 3: so probably overlooked in some places. How you diagnose it
Speaker 3: can be really tricky, so it's hard to diagnose on
Speaker 3: culture alone, but that is like the gold standard. It
Speaker 3: is possible to do. It's just more tricky. So there's
Speaker 3: PCR tests that you can use, but those, of course
Speaker 3: aren't accessible everywhere across the globe because they're difficult and expensive.
Speaker 3: So it's mostly based on sero logic testing, so looking
Speaker 3: for antigens or looking for antibodies againstleptosporosis. Okay, yeah, and
Speaker 3: there is treatment, which is the best news. A number
Speaker 3: of different antibiotics work, but especially in severe cases, it's
Speaker 3: also really important to have access to supportive care like
Speaker 3: potentially emergent dialysis if someone progresses all the way to
Speaker 3: kidney failure and things like that.
Speaker 2: In terms of antibiotics, you said that the first stage
Speaker 2: was this extreme replication in the bloodstream, just tons and
Speaker 2: tons of bacteria, and then that's a symptomatic yeah. And
Speaker 2: then when they move into the organs is when people
Speaker 2: would tend to probably go seek treatment. Does the massive
Speaker 2: die off of bacteria at that point like hurt anything
Speaker 2: about you and your organs?
Speaker 1: Oh?
Speaker 3: What a good question. That's like a thing that can
Speaker 3: happen with a lot of other spirakeat diseases, not that
Speaker 3: I read. Okay, yeah, but that's a really interesting question,
Speaker 3: especially for spira keats. Okay, they are still replicating the
Speaker 3: whole time. They don't just like stop replicating once they
Speaker 3: make it into our organs. Okay, keep on going, just
Speaker 3: chugging away, keep on checking on. So that's kind of
Speaker 3: the disease in humans. Because this is a pathogen, like
Speaker 3: I said, that can infect essentially any mammal. It does
Speaker 3: cause slightly different disease in different animal species, but the spectrum,
Speaker 3: especially in things like dogs, can tend to be pretty similar.
Speaker 3: So there can be asymptomatic infection, and then there can
Speaker 3: be this severe disease that often still has fevers, jaundice, nausea, vomiting,
Speaker 3: liver failure, kidney failure. So it's very interesting to me
Speaker 3: how it tends to affect a lot of the same
Speaker 3: organs and then a lot of what you see might
Speaker 3: be very similar. Yeah, that's leptos borosis. Alrighty, So tell
Speaker 3: me Arin, where did this thing come from? We figure
Speaker 3: it out?
Speaker 2: Yeah, I will do my best. Right after this break.
Speaker 2: I found it really interesting to read about the history
Speaker 2: of leptosporosis because I feel like, although this is not
Speaker 2: the flashiest of diseases that we've covered, you know, it
Speaker 2: hasn't caused these widespread epidemics and left destruction in its wake.
Speaker 2: It's like something like smallpox or plague, for instance. But
Speaker 2: the story of leptosporosis is a classic tale of observation
Speaker 2: and discovery. It's really sort of highlights the golden age
Speaker 2: of germ theory. And I think that what surprised me
Speaker 2: most about the history of leptosporosis was not how we
Speaker 2: learned about the transmission cycle or the causative agent of leptosporosis,
Speaker 2: but how much things haven't really changed. But I guess
Speaker 2: I'm getting ahead of things. So let's start at the beginning.
Speaker 3: Okay.
Speaker 2: Leptosporosis has existed for millennia, and it seems to have
Speaker 2: been globally distributed for quite some time. So that's about
Speaker 2: as precise an answer as you're going to get for
Speaker 2: where did this thing come from? That's about as precise
Speaker 2: as I could find. Okay, then, Yeah, And part of
Speaker 2: that is because of how many different Leptosporis species and
Speaker 2: serivars there are that can cause infection in humans and
Speaker 2: other animals. And so it's hard to say when Leptospira
Speaker 2: emerged or when it.
Speaker 3: Evolved and where it evolved, Okay.
Speaker 2: And it's also hard to say when humans were first
Speaker 2: exposed in which particular species or seravars were responsible, because
Speaker 2: those are also things that would have likely varied geographically,
Speaker 2: and maybe those seravars aren't even around anymore. And in
Speaker 2: the scientific literature discussing the history of leptosporosis, generally speaking,
Speaker 2: researchers refer more to the disease leptosporosis rather than a
Speaker 2: particular pathogen.
Speaker 3: Yeah, I found that really interesting.
Speaker 2: I found that interesting too, And I think that just
Speaker 2: speaks to the importance well, I think it speaks to
Speaker 2: two things. Really. One is the importance of the group
Speaker 2: of pathogenic species rather than any one individually. At least historically.
Speaker 2: And I think the other thing is that maybe it's
Speaker 2: just kind of speaks to the fact that we don't
Speaker 2: maybe know.
Speaker 3: That much about the different seravars than they're Yeah, and
Speaker 3: they're just so hard to culture. I think they're a
Speaker 3: difficult bud to work with.
Speaker 2: It seems like it. Yeah. And that's, of course not
Speaker 2: to say that the differences among Leptospiros species or seravars
Speaker 2: isn't important medically or in terms of public health. Of course,
Speaker 2: like I'm always saying on the podcast, tracing the evolutionary
Speaker 2: relationships among these bacteria can greatly help in understanding things
Speaker 2: like transmission routs or reservoir species, or disease causing abilities.
Speaker 2: Information that, like you talked about aaron, for some or
Speaker 2: even many Leptosperra species isn't that well known.
Speaker 1: Yeah.
Speaker 2: In general, the pathogenic Leptospira are thought to have evolved
Speaker 2: from non pathogenic species that just live in the environment,
Speaker 2: which some Leptospiras species still do.
Speaker 3: I sure do.
Speaker 2: And historically that's how this group of bacteria was divided
Speaker 2: along lines of is it pathogenic or is it not pathogenic?
Speaker 2: And that is in like the classific case, I think
Speaker 2: that that division is still really important in terms of
Speaker 2: public health and medicine, but I'm talking about like classification systems.
Speaker 2: But more recently that division into those two groups turned
Speaker 2: into three groups, essentially saprophytic meaning living on decaying material,
Speaker 2: and nonpathogenic, intermediate in terms of pathogenicity and pathogenic, and
Speaker 2: some researchers are now arguing that this isn't the best
Speaker 2: way to classify Leptospira because it just takes into account
Speaker 2: one characteristic of these bacteria rather than looking at I
Speaker 2: don't know their entire genomes for instance. Yeah, but as
Speaker 2: far as I can tell, that's still under discussion and
Speaker 2: probably won't be resolved in the time by the time
Speaker 2: this episode comes out. Yeah, certainly not.
Speaker 3: Yeah, it was really interesting how much it seemed to
Speaker 3: still be in flux. Yeah, the whole classification of Leptospira.
Speaker 2: Oh absolutely, And not just the classification, but just learning
Speaker 2: more about the ecology and which species are playing a role.
Speaker 2: There are new seravars that are constantly being discovered. Which
Speaker 2: species can cause disease that's still kind of being learned.
Speaker 2: Oh that one, No, that one's just an environmental bacteria.
Speaker 2: Oh wait a second, actually, actually Yeah. The bottom line
Speaker 2: of all of this seems to be that Leptospira is diverse,
Speaker 2: many different species and seravars can cause disease, and there
Speaker 2: are so many research opportunities for understanding more about these
Speaker 2: pathogens from a public health perspective. So if anyone needs
Speaker 2: a master's or phdu project, go for it.
Speaker 3: No, yeah, do it, I love it, We support you.
Speaker 2: But that's just the bottom line for like the ecology
Speaker 2: evolution of these bacteria. What about the human history part
Speaker 2: of it? Yeah, Given how widespread leptosphira are and how
Speaker 2: many of them can cause disease in humans and other animals,
Speaker 2: it's likely, of course that leptosporosis has affected humans for
Speaker 2: millennia as long as humans have been humans, although there's
Speaker 2: an asterisk there. I didn't read anything specifically about the
Speaker 2: historical distributions of these pathogens. I'm not sure if it's known,
Speaker 2: but one paper I read suggested that an epidemic that
Speaker 2: occurred around sixteen sixteen to sixteen nineteen in the area
Speaker 2: that's now eastern Massachusetts could have been leptosporosis. It hit
Speaker 2: the Native American populations living in the area particularly hard,
Speaker 2: with the death toll estimated to be as low as
Speaker 2: one third of the local population to as high as
Speaker 2: ninety percent.
Speaker 3: Oh whoa.
Speaker 2: And since the Europeans living in the area weren't as
Speaker 2: badly affected, some researchers have suggested that rats on the
Speaker 2: ships introduced lepto to the region.
Speaker 3: Got it.
Speaker 2: But also, there's like a huge laundry list of other
Speaker 2: diseases that it could have been, and we may never
Speaker 2: know what it actually was, so lepto is one of
Speaker 2: the suggested options, as with many other diseases that we've
Speaker 2: covered on the podcast, changing patterns in human settlement or
Speaker 2: any other practices that would have increased contact with rodents,
Speaker 2: especially rats, sorry, rats, would have made catching the disease
Speaker 2: more likely. And if you look through historical medical literature,
Speaker 2: there are many many mentions of things that could be
Speaker 2: leptosporosis or have retrospectively been decided to be leptosporosis. Like
Speaker 2: you said, Aaron, jaundice is of course one of the
Speaker 2: primary symptoms of leptosporosis, and references to jaundice go back
Speaker 2: thousands of years. Whether or not that jaundice was caused
Speaker 2: as a result of leptosporosis is anyone's guess.
Speaker 3: Yeah, there's so many there's so many things damage your liver.
Speaker 1: Uh huh.
Speaker 2: There is this passage though, in the Hippocratic text that
Speaker 2: some people believe may be about lepto. Quote, when jaundice
Speaker 2: supervenes in fevers before the seventh day, it is a
Speaker 2: bad symptom unless there be watery discharges from the bowels.
Speaker 3: Interesting.
Speaker 2: Yeah, huh, I don't know. I mean, I'm sure that
Speaker 2: lepto was around.
Speaker 3: So yeah, how interesting.
Speaker 2: Yeah, And medical texts from ancient China discussed diseases referred
Speaker 2: to as rice field jaundice or rice harvest jaundice, and
Speaker 2: the descriptions of those diseases seem very similar to leptospurosis,
Speaker 2: and also old Japanese medical texts describe lepto like diseases
Speaker 2: called autumn fever or seven day fever. In Europe and Australia,
Speaker 2: there were diseases known as cane cutter's disease or swineherd's
Speaker 2: disease and schlam fever mud fever. I hope I doubt
Speaker 2: I pronounced that remotely correctly. And all of these terms
Speaker 2: were used before anyone figured out what caused these diseases
Speaker 2: or whether they were even related. We should have some
Speaker 2: sort of jingle for when I mentioned Napoleon's name, because
Speaker 2: here he is again.
Speaker 3: Oh, I can't wait, d do he he comes?
Speaker 1: Not?
Speaker 3: Of course there we go.
Speaker 2: Oh Napoleon his infamous troops in Cairo, Egypt during the
Speaker 2: early eighteen hundreds may have experienced an outbreak of leptis borosis,
Speaker 2: which they called jaundice fever. Also, I have to shout
Speaker 2: out our chlamydia episode where I talked about trachoma and
Speaker 2: Napoleon's troops in Egypt, and I just at this point
Speaker 2: need to make a list of diseases that these poor
Speaker 2: troops were subjected to during their time under Napoleon. We
Speaker 2: should have just done a series on diseases of Napoleon.
Speaker 3: Yeah, just where all we do is list them because
Speaker 3: it would take two hours.
Speaker 2: But even before germ theory was a thing, what would
Speaker 2: be later known as leptosporosis had recognizable patterns, and you
Speaker 2: can tell that from some of these early nicknames. So
Speaker 2: one was that it was commonly associated with certain occupations,
Speaker 2: and that these occupations and hence the occurrence of this
Speaker 2: disease were often associated with wet marshy areas. They were
Speaker 2: kind of geographically restricted, and this tight link, especially between
Speaker 2: certain areas or certain times of year, and this disease
Speaker 2: made it like a shoe in for miasma theory, which
Speaker 2: was this pre germ theory idea that proposed that diseases
Speaker 2: and disease outbreaks.
Speaker 3: For the result of bad air.
Speaker 2: And it's easy to see how that would have been
Speaker 2: a reasonable explanation for leptosporosis because it did occur in
Speaker 2: certain areas, and it did occur in certain professions, and
Speaker 2: it didn't really occur in large epidemics the way something
Speaker 2: like influenza or smallpox did. And importantly, avoiding those areas
Speaker 2: or removing the source of the bad air like draining
Speaker 2: water around mines, it decreased the incidence of the disease.
Speaker 2: So even before people knew that cane cutter's disease or
Speaker 2: swineherd's disease or rice harvest disease were the same things,
Speaker 2: people were able to limit their exposure to it. That's amazing,
Speaker 2: so interesting.
Speaker 3: Yeah, yeah, I really I love it when those kinds
Speaker 3: of things happen in these episodes erin me too.
Speaker 2: But leptosporosis wasn't alone in causing jaundice and a fever
Speaker 2: and occurring in certain marshy environments. There's also yellow fever,
Speaker 2: infectious hepatitis, lousborn relapsing fever, and it wasn't until the
Speaker 2: late eighteen eighties that leptosporosis, or at least one manifestation
Speaker 2: of it, was officially distinguished from the rest of these
Speaker 2: possible causes of infectious jaundice. In eighteen eighty six, a
Speaker 2: German physician named Adolph Wheel described a disease that involved
Speaker 2: jaundice alongside spleena, megaly, renal dysfunction, conjunctivitis, and skin rashes.
Speaker 2: He called it infectious jaundice. His characterization of this disease stuck,
Speaker 2: but the name obviously did not. A couple years after
Speaker 2: his paper was published, another researcher named it Wheel's disease, and,
Speaker 2: like happens so often, giving this disease a name, giving
Speaker 2: it a description increased awareness of it substantially, and soon
Speaker 2: papers were being published describing outbreaks of the disease in
Speaker 2: coal miners or sugar cane cutters, association with rainfall or
Speaker 2: swimming in certain areas. But even though people were able
Speaker 2: to recognize patterns in where and when this disease occurred
Speaker 2: and in whom without a causative agent identified, Those were
Speaker 2: just patterns without a mechanistic explanation, and you were also
Speaker 2: a little bit limited in your ability to do anything
Speaker 2: for that satisfying understanding of how all the pieces eventually
Speaker 2: fit together and whether the cases of wheel disease in
Speaker 2: England were caused by the same pathogen as those in Japan,
Speaker 2: for instance, we needed a causative agent, and to get
Speaker 2: that we have to wait almost thirty years after the
Speaker 2: clinical description of wheels disease.
Speaker 1: Wow.
Speaker 2: Yeah, So eighteen eighty six was Wheel's disease, huh? And
Speaker 2: nineteen fifteen, I believe was when leptosporosis was identified. Was
Speaker 2: when leptospiro was identified.
Speaker 3: Oh my goodness.
Speaker 1: Yeah.
Speaker 2: So why was there along a wait? And you know,
Speaker 2: none of the papers I read really went into that
Speaker 2: great detail about why. But I think it could have
Speaker 2: been many different things. So even though this period, the
Speaker 2: last decades of the eighteen hundreds and the first few
Speaker 2: decades of the nineteen hundreds, was this golden age of
Speaker 2: germ theory and pathogen discovery, that doesn't mean that all
Speaker 2: diseases received equal attention. I mean if you think about
Speaker 2: it again, leptosporosis is not a big name marquee disease,
Speaker 2: which isn't to say it doesn't deserve that attention. But
Speaker 2: at the time, there were things like plague or syphilis
Speaker 2: or tuberculosis that people were trying desperately to figure out
Speaker 2: because of the death toll, because the number of people
Speaker 2: that were infected with those diseases. Leptosporosis definitely attracted interest,
Speaker 2: but it maybe didn't get the focused attention that some
Speaker 2: of these flashier diseases did. But one thing was working
Speaker 2: in Lepto's favor, which is that spira keets, the kind
Speaker 2: of spiral shape bacterium that causes lepto. These had already
Speaker 2: been discovered and recognized to cause disease, the most important
Speaker 2: of which at the time was syphilis, and so people
Speaker 2: had spira keats on their radar, and they should have
Speaker 2: maybe been able to pluck these little guys out as
Speaker 2: the cause of leptos borosis, except for this quirk that
Speaker 2: you mentioned. Spira keats don't stain well, so they're really
Speaker 2: difficult to isolate. They can be difficult to culture, and
Speaker 2: what the eventual discoverers of leptospira noticed was that, Well
Speaker 2: they blamed it on this anyway, is that after this
Speaker 2: huge influx of bacteria in the bloodstream, those levels drop.
Speaker 2: And they were like, if you don't catch it, then
Speaker 2: then it's going to be really difficult to isolate leptospears.
Speaker 3: Unlike like malaria or something where you have a lot
Speaker 3: of difference in even just like times of day on
Speaker 3: when you have a high enough burden in the bloodstream
Speaker 3: to be able.
Speaker 2: To pick it up exactly. Yeah, and I think I
Speaker 2: think that's what they said. They were like, yeah, we
Speaker 2: didn't see it in the blood stream, and so if
Speaker 2: you test a blood sample of someone who's super duper sick,
Speaker 2: especially considering the microbiology technology that was around in the
Speaker 2: nineteen tens.
Speaker 3: And I want to say, because like I mentioned, how
Speaker 3: like something like E. Coli might be at low numbers,
Speaker 3: you can grow those other bacteria out in culture from blood,
Speaker 3: so even if you only have a tiny bit of it,
Speaker 3: you can grow it to be more. But that's really
Speaker 3: difficult to do with leptospira. So if you can't see
Speaker 3: it right away, it's a lot harder.
Speaker 1: Yeah.
Speaker 2: Yeah, that's a really important point too. So how did
Speaker 2: people eventually discover what was causing wheel's disease seems super difficult.
Speaker 2: They went looking for it specifically. It wasn't just one
Speaker 2: of those serendipitous discoveries. A couple of researchers in Japan
Speaker 2: named Ryokichi Inada and Utaka Edo had an interest in
Speaker 2: wheels disease for years, and an outbreak of the disease
Speaker 2: among coal miners around nineteen fourteen to nineteen fifteen led
Speaker 2: them to run some experiments to see if they could
Speaker 2: isolate a pathogen from an infected person. And I also
Speaker 2: want to point out that their interest was not purely scientific,
Speaker 2: not like, oh, here's this curious little disease, let's see
Speaker 2: if we can find a new pathogen. At the time,
Speaker 2: mortality rates of wheels disease at their clinic have reached
Speaker 2: thirty two percent, oh my, which is incredibly high, really
Speaker 2: terrifyingly high, exactly. And so they wanted to do whatever
Speaker 2: they could to try to control the outbreaks by finding
Speaker 2: the source. They looked for bacteria and blood, urine, feces,
Speaker 2: you name it, in people who had wheels disease, and
Speaker 2: when they didn't find anything, they took some blood from
Speaker 2: these infected individuals and in rejected it into monkeys, rabbits, rats,
Speaker 2: guinea pigs, and the guinea pig turned out to be
Speaker 2: the unlucky or lucky one, depending on your perspective. It
Speaker 2: developed many of the symptoms that were characteristic of Wheel's disease,
Speaker 2: and when they dissected the animal's liver, they found it
Speaker 2: to be teeming with spira keets, which they named spiro
Speaker 2: Keta ictero Hemorrhagia yep okay yep, later, of course, leptospira.
Speaker 2: Almost immediately after they published their findings in nineteen fifteen,
Speaker 2: researchers in Germany also isolated leptospira from infected individuals. But
Speaker 2: the real first placed finisher, even though he didn't know it,
Speaker 2: may have been A. M. Stimpson who observed spira keats
Speaker 2: in the blood of someone that had been diagnosed with
Speaker 2: yellow fever. He figured that what he saw, these little
Speaker 2: squiggly bacteria that looked like question marks, hence the name
Speaker 2: he gave them, Spirokeeta and terragans, was causing yellow fever.
Speaker 2: For a long time, people were like, it must be
Speaker 2: a spirokeet that's causing yellow fever. It wasn't as we know,
Speaker 2: but in retrospect, he did end up being the first
Speaker 2: to describe a bacterium that later researchers would link to leptosporosis.
Speaker 2: Interesting the similarity in symptoms between leptosporosis and yellow fever,
Speaker 2: and not to mention, their association with wet marshy areas
Speaker 2: also made diagnosis sometimes confusing, and that could have potentially
Speaker 2: contributed to the delay and identifying both the causative agent
Speaker 2: of wheels disease and the yellow fever virus. Anyway, soon
Speaker 2: after Inada and Edo and colleagues identified the causative agent
Speaker 2: of wheels disease, they next set their sites on uncovering
Speaker 2: everything they possibly could about this pathogen, and they did
Speaker 2: a hugely impressive job, from culturing it in the lab,
Speaker 2: to characterizing the timeline of infection early vaccination studies, to
Speaker 2: understanding the transmission route of the pathogen. What they did
Speaker 2: was set a really strong foundation for understanding the disease
Speaker 2: and for growing future research, especially research that was focused
Speaker 2: on prevention, because, as we know, if you want to
Speaker 2: stop a disease from spreading, you at the very minimum
Speaker 2: have to know how it spreads in the first place,
Speaker 2: which for leptosporosis. By the time of the causative agents
Speaker 2: discovery was still under debate. They knew it was in marshy,
Speaker 2: wet marshy areas, and associated with water, so could it
Speaker 2: be mosquito born like yellow fever? Several people seem to
Speaker 2: think so, and it was a reasonable explanation given the
Speaker 2: geographic and climate variables associated with outbreaks, and some researchers
Speaker 2: even successfully carried out experiments with mosquitoes transmitting leptos borosis
Speaker 2: to lab animals, but it was likely that the mosquitoes
Speaker 2: were acting as mechanical vectors, like just depositing infected blood
Speaker 2: clinging to the mouth parts into the animal. Wheel himself
Speaker 2: thought it was something that you ingested, while others thought
Speaker 2: vertebrate animals played a large role. Innata an Edo and
Speaker 2: colleagues demonstrated that the leptosphears could be transmitted through the healthy,
Speaker 2: unbroken skin of a guinea pig. The broken skin was
Speaker 2: more reliable. I had no idea it could be through
Speaker 2: like unbroken skin.
Speaker 3: It can be. Yeah, usually it's broken skin, but especially
Speaker 3: if you're submerged in exposed for a long period of time,
Speaker 3: and especially with wet skin wet skin really reduces your
Speaker 3: skins like increases primeability essentially, so then yeah, yeah it
Speaker 3: can be unbroken skin. Wow, okay, yeah yeah yeah.
Speaker 2: Well they also showed that it could cause infection through
Speaker 2: ingesting it yea, but where did it come from? They
Speaker 2: got the idea to look at rodent kidneys and urine
Speaker 2: after a different team of researchers observed spira keats in
Speaker 2: the kidneys of field mice while working on scrub typhus.
Speaker 2: Oh cool yeah, and so they were like, you know what,
Speaker 2: all right, fine, gather all of the rodents that we
Speaker 2: possibly can house and wild rats and then look in
Speaker 2: their kidneys and boom, they found a bunch of their
Speaker 2: spirakeat Spiraketa at the time ictohemorrhagia, and they noticed that
Speaker 2: the lepto spears seemed restricted to the kidneys and that
Speaker 2: the rats seemed in excellent health until they digart their kidneys, yeah,
Speaker 2: prior to their dissection, and that pointed towards their role
Speaker 2: as reservoirs. M And this didn't actually surprise too many people,
Speaker 2: possibly because a rats have been maligned for centuries, but
Speaker 2: also during trench warfare in World War One, cases of wheels,
Speaker 2: disease shot up, particularly in areas with high rat populations.
Speaker 3: Okay, yeah, so they were like I suspected it, Like, oh, yeah, of.
Speaker 2: Course it's the rat, which is sad for rats. Rats
Speaker 2: are great, by the way. Anyway, all of this clinical
Speaker 2: and epidemiological and ecological knowledge about leptosporosis, which is like
Speaker 2: a lot. I mean, that happened in a very short
Speaker 2: time span, just a few years, and that's pretty remarkable.
Speaker 2: And even though antibiotics weren't yet available to help treat
Speaker 2: the infection, understanding the transmission cycle was enough to enact
Speaker 2: control measures in some places, and throughout the following decades
Speaker 2: into the mid twentieth century and beyond, people continued to
Speaker 2: find out more about this group of pathogens, like how
Speaker 2: long it can survive in water and under what conditions,
Speaker 2: what pH is best, what temperature, which animals play a
Speaker 2: role in the transmission of the disease, and so areas,
Speaker 2: how disease progression or severity could be tied to certain
Speaker 2: species or serovars, and also linking all of these previously
Speaker 2: separate diseases or separate name diseases into one big picture
Speaker 2: name leptosporosis and another big development was understanding that other
Speaker 2: animals may not just be asymptomatic carriers or reservoirs, but
Speaker 2: that many of them suffered severe infection from these bacteria
Speaker 2: as well, like domestic cattle, pigs, and dogs. The early
Speaker 2: history of leptosporosis may not be as flashy as some
Speaker 2: of the diseases or topics that we've covered on this podcast,
Speaker 2: and there don't really seem to be at least that
Speaker 2: I could find any major fireworks discoveries during the rest
Speaker 2: of the twentieth century. But that doesn't mean at all
Speaker 2: that this disease is not hugely important, because despite how
Speaker 2: much we've learned about this scroup of pathogens, and despite
Speaker 2: having effective treatment and knowledge of prevention, it is still
Speaker 2: a huge problem globally. As you're about to talk about aaron,
Speaker 2: and since it has such close ties to things like
Speaker 2: weather and temperature, we can expect to see big shifts
Speaker 2: as a result of climate change and land use change.
Speaker 2: So Erin, can you tell me where we stand with
Speaker 2: these pathogens of one health importance today?
Speaker 3: I would love to. Let's take a quick break and
Speaker 3: I'll get into it. Erin, I know that you know
Speaker 3: and have very recently felt just how difficult it is
Speaker 3: to get numbers on some of these topics that we cover,
Speaker 3: and I'm always still somehow shocked at just how difficult
Speaker 3: it can be. And that was the case for leptosporosis,
Speaker 3: very very hard to get an estimate of what the
Speaker 3: true burden of disease is, as well as looking at
Speaker 3: the distribution of that burden, because of course it's not
Speaker 3: equal across the globe. So this is a pathogen that
Speaker 3: is worldwide everywhere except like the Arctic where everything is frozen,
Speaker 3: but it is most common in the tropics, and it's
Speaker 3: very common both in rural areas associated with things like
Speaker 3: agricultural or like mining exposure like you talked a lot about,
Speaker 3: but also in urban especially poor urban areas, where you
Speaker 3: have lack of access to sanitation and potentially high rat burdens.
Speaker 3: But to look at actual numbers, if you look at
Speaker 3: the World Health Organization website, you won't really find any
Speaker 3: numbers because they don't have any fact sheets on leptos borross.
Speaker 3: All of their information is from like two thousand and three.
Speaker 2: Two that I was almost twenty years ago.
Speaker 3: Yeah, and now there's just not a there's not a
Speaker 3: page the links to like World Health Organization LIPTO like
Speaker 3: it goes to page four or four.
Speaker 2: Not found interesting.
Speaker 3: I know, I was shooketh as they say, PAHO, which
Speaker 3: is the Pan American Health Organization, so for the Americas,
Speaker 3: has some information. The CDC has a page on it.
Speaker 3: There are probably a lot of other country specific public
Speaker 3: health agencies that have data, but it's hard to go
Speaker 3: through every single country. So there are two numbers that
Speaker 3: I found which are wildly different as to global estimates
Speaker 3: of leptosporosis. Some papers and the PAHO website estimate about
Speaker 3: three hundred to five hundred thousand cases of leptosporosis globally every.
Speaker 2: Year, which is a huge number.
Speaker 3: Yeah. Well, a paper from twenty fifteen that was trying
Speaker 3: to estimate the global prevalence as well as mortality from leptosporosis.
Speaker 3: Granted this is from twenty fifteen, so it's a little
Speaker 3: bit outdated, but they estimated a million cases annually and
Speaker 3: just under sixty thousand deaths every year, and that's a lot.
Speaker 3: It's a lot. And this was really just an estimate
Speaker 3: of severe cases, cases that are bad enough that are
Speaker 3: people are getting very sick and ending up in the hospital,
Speaker 3: and again, a lot of times this can be asymptomatic.
Speaker 3: So how many cases are there potentially even more? Yeah wow, Yeah,
Speaker 3: And there is a lot of data to suggest that
Speaker 3: the overall burden of leptosporosis is likely going to continue
Speaker 3: to rise because of shifts and things like climate change
Speaker 3: that might worsen storms and flooding events which are really
Speaker 3: high risk for leptosporosis outbreaks yep, as well as like
Speaker 3: you said, land use changes that might increase urbanization in
Speaker 3: a way that also puts people at increased exposure to
Speaker 3: rats and contaminated water sources, et cetera. So it's not
Speaker 3: like good news looking forward, especially with how little data
Speaker 3: we have to begin with.
Speaker 2: It's it's I think, I'm I'm still surprised at this.
Speaker 3: Same I was actually shocked because a lot of papers say, like,
Speaker 3: this is on the scale of things like schistosimiasis, of
Speaker 3: things like leshmaniasis, of things like cholera, and I I
Speaker 3: feel like we don't think of it in that way.
Speaker 3: I think a lot of people think of leptosporosis as
Speaker 3: a disease of animals.
Speaker 2: Or as like recreational exposure.
Speaker 3: Yeah, exactly, which it is that's surely true, but it's
Speaker 3: also just a global serious disease. When it comes to
Speaker 3: animal infections, by the way, it's even harder to get
Speaker 3: a sense of what the magnitude of the problem is worldwide.
Speaker 3: As you can imagine, there are a lot of really
Speaker 3: interesting papers that look at the overall diversity of animal
Speaker 3: species that have been shown to be infected. I mean,
Speaker 3: it really just boils down to like all of them, like,
Speaker 3: if you try it, they will infect. But it's really
Speaker 3: hard to get a handle on like what percentage of
Speaker 3: domestic dogs would test positive, or like how many cattle
Speaker 3: every year are getting sick from this, how much milk
Speaker 3: production is lost because cattle gets sick. We just don't
Speaker 3: have that kind of information. I did find one paper
Speaker 3: that was looking in the United States at hot spots
Speaker 3: of leptosporosis, like within the US, and one thing that
Speaker 3: stuck out to me from that paper is that, at
Speaker 3: least from data from the early two thousands, it did
Speaker 3: seem like zero prevalence in dogs was increasing, which is
Speaker 3: not great.
Speaker 2: Why is it increasing? I have no idea, And there's
Speaker 2: a vaccine available for dogs as well.
Speaker 3: Great question. Yes, there's a vaccine there's a vaccine for
Speaker 3: humans too, and for animals including dogs. Most of the vaccines,
Speaker 3: as far as I can tell, all of the vaccines
Speaker 3: that are currently available, are whole killed spira keets of
Speaker 3: some of the more common sero VARs, depending on what
Speaker 3: area you're in. So you asked very early on aarin,
Speaker 3: like how much cross protection do you get? Like what
Speaker 3: kind of an immune response are we talking about? And
Speaker 3: because the vaccines that exist are just for particular serr vrs,
Speaker 3: they're not universal, so they don't cover every given Leptospira
Speaker 3: sero far seems like a great candidate for an mRNA vaccine. Huh,
Speaker 3: But I'm on bo. Yeah, there's a lot of research
Speaker 3: mostly on recombinant vaccines actually, but an MRINAI could be interesting.
Speaker 3: But a recomminant vaccines would allow you to put a
Speaker 3: whole bunch of different antigens essentially antigen components on like
Speaker 3: one little vaccine and then give that so you could
Speaker 3: get immunity a bunch a whole bunch of different sera VARs,
Speaker 3: and who.
Speaker 2: Gets vaccinated against leptosporosis.
Speaker 3: Such a great question. I had a really hard time
Speaker 3: figuring that out. In the US definitely, dogs like my
Speaker 3: puddle liquor is vaccinated, So domestic animals, livestock can get vaccinated.
Speaker 3: In terms of humans, I think it's relatively uncommon, except
Speaker 3: perhaps during outbreaks were maybe in occupational settings, in particularly
Speaker 3: high risk environments, it might be that people are vaccinated.
Speaker 3: But in general, I didn't even know that there was
Speaker 3: a human vaccine. I don't think it's very common.
Speaker 2: Hmm.
Speaker 3: Yeah, but that is what I know about the status
Speaker 3: of leptosporosis worldwide.
Speaker 2: It's such an interesting I truly cannot believe how overlooked
Speaker 2: this is.
Speaker 3: I can't get over it. I really felt similarly about this. Yeah,
Speaker 3: it's I want to do. I want there to be
Speaker 3: so much more information. Yeah, yeah, Well.
Speaker 2: Sources sources, Okay, I have several. I'm going to shout
Speaker 2: out two in particular. One is a twenty fifteen book
Speaker 2: called Leptospira and Leptosporosis, which the editor of that book
Speaker 2: is Ben Adler. Then there was a paper from two
Speaker 2: thousand and one by Kobayashi and that is titled Discovery
Speaker 2: of the positive Organism of Wheel's disease Historical view.
Speaker 3: I had a lot of different papers, a couple of
Speaker 3: actually book chapters that I wanted to shout out two
Speaker 3: different chapters, one on leptosporosis in humans and one on
Speaker 3: animal leptosporosis, both from the book Leptospira and Leptosporosis from
Speaker 3: twenty fifteen, So those were great chapters. And then I
Speaker 3: had a lot on the genetic diversity and seer of
Speaker 3: r diversity of leptospira and at least some data on
Speaker 3: the epidemiology so you can read for yourself. We post
Speaker 3: all of our sources from this episode and all of
Speaker 3: our episodes on our website, this podcast kill you dot com.
Speaker 3: We sure do.
Speaker 2: Thank you so much again to Umat for sharing your story.
Speaker 3: Again again, thank you also to Bloodmobile for providing the
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Speaker 2: Thank you to the Exactly Right Now Network, and.
Speaker 3: Thank you to you listeners. We liked doing this episode.
Speaker 3: I hope that you really enjoyed it. Thanks for listening.
Speaker 2: Yeah, and a special thank you as always to our wonderful,
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Speaker 2: until next time, wash your hands
Speaker 3: You filthy animals.