Ep 55 Rocky Mountain spotted fever: The tick must be destroyed!

00:00:01
Speaker 1: On July nineteenth, during dinner, announcement was made of the departure of Sister Rogers after an illness of eight days. This was the beginning of a great time of sorrow for Bethabara and for me. A strange kind of fever had broken out amongst us, and most of those living in Bethabara had it in more or less a serious form. My doctor was much worried, for the usual treatment for fever gave little relief. Of those who left us, Sister Rogers was the first, but not the last. Next came Catherine's Sidle, and it seemed almost impossible that only a few short weeks before she had traveled south with us. Her husband missed her sadly, and it was only a few days later that he returned from a visit to Bethania, oppressed by the feeling of utter weariness, which we were learning to recognize as the first symptom of the disease. He did not seem very ill at first, but when hope was expressed for his recovery, he shook his head.

00:00:56
Speaker 2: And so it was.

00:00:58
Speaker 1: And then my Martin, perhaps because of his unremitting efforts for others, he was seriously ill from the first he saw what was coming. His pain was intense, as it always was in the earlier stages of the fever. His request was stay by me and hold my hand, hold it tight. And when the fever mounted, when the terrible red splotches broke out on his body, when delirium came, he still felt my presence and was quieted as I held his hand in mine spoke gently to him or saying some of our best loved hymns. Then he became unconscious of pain or weariness, but we were still hand in hand when the call came that took him back to the eternal home. Others were laid to rest beside him, but I was stunned and rebellious, and nothing seemed to matter much. The fever that took Martin from me persisted until late in the fall, though with decreasing violence, and we heard that it was prevalent in many parts of North Carolina and Virginia.

00:02:37
Speaker 2: WHOA, Yeah, that's a sad story. It's really sad.

00:02:44
Speaker 1: So that is from an account from seventeen fifty nine, and I found it in a paper referenced in a book that I read. The paper is titled a seventeen fifty nine spotted fever epidemic in North Carolina. Before we go any further, it's debated this, Like the whole purpose of this paper is to, you know, say, this might be an instance of spotted fever or Rocky Mountain spotted fever.

00:03:14
Speaker 2: It's not certainty, but I.

00:03:16
Speaker 1: Liked the account so much that I wanted to read it.

00:03:20
Speaker 2: It was a really good account. Right, it's heartbreaking by everything that you that was in that account. It certainly could be Rocky Mountain spotted fever.

00:03:31
Speaker 1: There are a few things that are like, as we'll talk about that seem a little bit off to me. I mean the fact that, like, was it contagious. It seemed to be all at once. It's not contagious anyway. So yeah, okay, maybe we should maybe we should pump the brakes. Yeah, because Aaron, what are we this is this podcast will kill you.

00:03:57
Speaker 2: I'm Aaron Welsh and I'm Aaron Olman Updike. Welcome. Wow, we did that all weird and backwards. Yeah, that was backwards, but we're professionals. Oh totally, We've done this before. We've done this before. Fifty oh my lost count already. This is fifty five or six? No, yeah, I thought it was fifty two. Antibiotics was last week?

00:04:26
Speaker 1: Oh gosh, Well, this week we are covering Rocky Mountain spotted fever or Rickettsia RICKETTSI. I yes, spotted fever group Rickhetsia.

00:04:40
Speaker 2: I am very excited about this episode, Aarin.

00:04:44
Speaker 1: I didn't start out that way, but I've come around and now I'm thrilled.

00:04:51
Speaker 2: I have known that this was going to be a great episode since we literally decided to make a podcast.

00:04:57
Speaker 1: Okay, oh okay, and I guess the two reasons why?

00:05:02
Speaker 2: Uh okay, yeah, please guess them. Are there two reasons why? First to allow, but please guess them? Okay. Number one is because of the Quarantini name. So what's our quarantini name? Aaron, that's segue. Oh my god, we're being so obnoxious. Okay.

00:05:21
Speaker 1: Our quarantini is cold is the Rocky Mountain spotted Fever.

00:05:28
Speaker 2: That's the most clever name that we could come up with. It's so good. We came up with that quarantiny literally the same moment that we came up with a podcast idea.

00:05:38
Speaker 1: Yeah, it was on our list that very first day original at the picnic of like what are we or at the barbecue?

00:05:47
Speaker 2: Yep? Exactly what are the quarantini names? So in this quarantine, of course you have to have Core's light not sponsored.

00:05:57
Speaker 1: Because the logo is called as the Rockies. Just in case anyone has forgotten.

00:06:02
Speaker 2: And well, basically we're making a shandy out of it. Okay, yeah, super simple, delicious. We'll post a full recipe for that quarantine as well as a non alcoholic plus see Burta on our website. This podcast will kill you dot com and all of our social media channels, Yes we will. So, Aaron, what's the second reason that you knew I was going to be excited about this episode because we.

00:06:26
Speaker 1: Get to tell the story of Oh Brett possibly having Rocky Mountain spotted fever.

00:06:35
Speaker 2: Genuinely forgot about that. I mean I didn't forget about that. I just I forgot that aspect of it.

00:06:41
Speaker 1: I can't rememberative moment of our friendship.

00:06:44
Speaker 2: Oh, it absolutely was. I will never forget the moment. Okay, I just meant I forgot that we're going to get the opportunity to talk about it.

00:06:54
Speaker 1: Oh right, right, right, Okay, So why did you think it was going to be such a great episode From the.

00:06:59
Speaker 2: Very Oh mostly the quarantine name. Oh yeah, yeah, yeah, excellent. But as I was researching for this episode, I you know, I also was having a really busy week and I was like, oh gosh, I have to do research. But then the very first paper that I came across to do research for this episode, the first line of the biology section, I was like, Oh, this is this is gonna be a good one. Aaron. I had to google two words in the first sentence. What were they? Fastidious and pleomorphic? Ooh yeah, it's a good sentence. I'll read it to you later.

00:07:44
Speaker 1: Also, I have to say that the book that I read, the very first line, like of the chapter, so you know how like chapters start with like a quote from whatever.

00:07:55
Speaker 2: M hm. It literally it made me go, oh, this is gonna be good, and I put it in my notes. Look at us both we are the same person. Oh man, Oh my gosh, that's really funny.

00:08:11
Speaker 1: So do we get to just like, you know, do the episode now or do we have that business.

00:08:18
Speaker 2: We've got new merch coming out soon. Yeah, keep an eye out for that.

00:08:24
Speaker 1: It's very literally the most exciting thing.

00:08:27
Speaker 2: We love it. Yeah, love love is not a strong enough word. What's a stronger emotion, really love? Okay, I don't think we have any other business to attend to, Aaron, So let's let's take a short break and then get into the biology of this.

00:08:51
Speaker 3: Oh my gosh, let's do it.

00:09:26
Speaker 2: Okay, So here it goes quote ricketsia ricketsi I is a fastidious small pleomorphic gram negative coxo bacillis. Okay, okay, So I feel okay that description. It's why people don't like reading scientific papers, oh for sure. And I the reason that it made me excited for this episode is because I was like, I really like that. This is how if you read that, you'd be like, oh snooze, I don't want to learn anymore. So now I'm going to take that and make it a lot more exciting and tell you why you should be excited about rikkeetsia ricketsia I. Okay, oh yes, please, Okay. So here's what that boring sentience means. We're talking today about a very very tiny, like so tiny that it lives inside of our cells, bacterium that is very difficult to grow in medium. And the reason it's difficult to grow is because it lives inside of cells. Is that the fastidious part. That's what festidious means.

00:10:42
Speaker 3: Yep.

00:10:42
Speaker 2: Okay, when you're talking about fastidious organisms, okay uh. And the pleomorphic part means that not every single coxobacillas, not every single cell looks exactly like every other. So they kind of when you look at them stained inside of another animal's cell, they look like a bunch of little, little and bigger dots, if that makes sense. Okay, why that's a really good question that I don't know, because they divide the same way that anything else divides, right like just by sciently. That's fascinating, all right. So let's get into the disease that Ricketsia ricketsiai causes Rocky Mountain spotted fever. So this is a tickborn disease. OKAYO, we get excited about these. So humans get infected. Humans are essentially dead end hosts, okay, So we're not part of the normal life cycle necessarily of this pathogen. But humans get infected when we are bitten by an infected tick. Specifically, in a number of different species, but most commonly in most of the US, it's derma center very abolises. That's the dog tick, the American dog tick. But there's also the Rocky Mountain wood tick Derma center andersnii. The those live in the Rocky Mountains in Canada, the brown dog tick rifacephalous sanguinosis noeus Rifocephalus sanguineous in Mexico, and of course aarin Ambloma cayanens or Amblioma mixta. I was waiting for you to go correct, correct, correct me as.

00:12:34
Speaker 1: I got corrected at an academic conference. Yes, it is now amblomicayan and say species complex?

00:12:42
Speaker 2: Okay, great, and that's in Is that throughout Central America? That species complex? Yes? Central? Yeah, Central and South America? All right, So now we also know where this disease is found, right, This is a disease of the New World essentially, so North America, Central America and then down into South America. Okay. And like many other tickborn diseases, in order to get infected, the tick does have to be attached for a relatively long period of time, usually a minimum of four to six hours, but sometimes up to twenty four hours. And the reason that the tick has to be attached for a long period of time is because although these bacteria are already in the salivary glands of the tick. When they're in the tick, I get I'm getting excited. When they're in the tick, they're basically not in a virulent state, right, So then they have to bite a host and then something happens within the salivary glands of the tick to reactivate these bacteria and make them virulent, make them able to actually infect our cells. It's so.

00:14:02
Speaker 4: Amazing, and when weird don't know how it happens, and it also like, oh my gosh, yeah, yeah, you're right. This is a thrilling, a thrilling disease.

00:14:12
Speaker 2: Absolutely thrilling. Okay that is I didn't know that either before researching this, and I think that's just super fascinating. Okay, So then you have activation, it gets somehow becomes virulent again, and then it will exit the salivary glands and then enter underneath our skin. Okay. So then, because we know that this is a life cycle, right, how does the tick then get infected? How do we end up with infected ticks? As it turns out, there's two ways that a tick can become infected. One one is the way that we know of ticks getting infected from past tickborn disease episodes, and that is that a tick takes a bite of an infected host and then in that blood meal they suck up some bacteria, okay, and then those bacteria go on to replicate, and like many tick born diseases, once a tick is infected, they remain infected for their entire life. So even if they get infected as a larvae, then when they transition to a nymph, they remain infected. When they transition to an adult, they remain infected. But here's where it gets interesting. I know where you're going. Infected female ticks transmit transoverially and lay infected eggs, so you can have larval tick bombs that burst out already full of Ricketsia just waiting to infect their first blood meal host. Let's put an asterisk on this. I'm great. Well, I actually have a question for you about this, okay, because my understanding from what I read, and you are much more of an expert if you guys didn't know listeners. By the way, Aaron literally did her PhD research on Ricketsias in Central America.

00:16:18
Speaker 1: So on on pathogens in tics in Central America, which happens to.

00:16:23
Speaker 2: Be a lot of Rikkeetzias. Did you hear her trying to ask risk her way out of that. Well, I'm not an expert, okay, So my question is my understanding is that for humans it's really only adult tics that go on to infect humans. Is that just behavioral? Is that just because these ticks species don't tend to bite us unless they're adults, or is that something to do with infectious dose? What is why is that? I don't I mean, honestly, I don't know. Possibly behavioral. I mean, so.

00:17:00
Speaker 1: Different ticks species will have different host preferences overall, So like this tick species might like you know, deer and mammals more, and this tick species might like reptiles more. But even within a tick species, you see a lot of differences in terms of like what they like to feed on at different stages. And so there's a trend. It's not one hundred percent, but there is a trend where as you go to the older life stages, so like from larva to adult, the host range narrows. And part of that is like a mate seeking phenomenon, because if you're trying to find a mate, you want to be like, all right, I want to get on this horse because I know that other you know, ticks, adult ticcks of my species are going to be on this horse, but like you might not be like, oh or maybe that squirrel or maybe that monkey or maybe that sloth. Like you're going to be focused in, right because anyway, So it might be behavioral as far as the bacterial load overall across the life stages, that might be a factor. But another factor might be that as you're in, if you're an adult tick, you've taken two blood meals, and so just the chance that you have acquired the pathogen is greater than if you have taken just one blood meal.

00:18:22
Speaker 2: It's an imful tick, right, that makes sense.

00:18:24
Speaker 1: Yeah, But the asterisk that I want to add to the trans of aerial transmission is that it's fairly rare, oh for Ricketzia ricketsii, Like it doesn't happen all that often. And actually the Racketzi ricketsii I negatively affects the reproductive output of the tick.

00:18:44
Speaker 2: The female six. Yeah, so that's I mean good news in a way.

00:18:48
Speaker 1: So if you look at horizontal transmission, so getting it from an infected animal versus trans of aerial transmission or vertical transmission getting it from mom, it's much less like to get.

00:19:00
Speaker 2: It from mom.

00:19:02
Speaker 1: And then the third way that might be possible is co feeding.

00:19:07
Speaker 2: Oh does cofeeding mean the same thing for ticks as it does for kissing bugs.

00:19:12
Speaker 1: Probably they're like two bugs feeding close to one another and then they oh what does it mean for.

00:19:18
Speaker 2: Kissing Sometimes the adult kissing bugs will come back to the nest and then the nymphs will feed on the adult like from their blood meal. Beautiful and horrifying. Yeah it is.

00:19:33
Speaker 1: That's that's my esthetic, literal lifeblood co feeding.

00:19:38
Speaker 2: So then if you have say an infected adult feeding very close by to another uninfected nymph, then they could that's fascinating.

00:19:49
Speaker 1: Oh yeah, that happens with tick born encephalitis virus as well. I think occasionally you get you do get co feeding events, and this is really important when you have cocurrent stages existing or emerging. So if you have larvae that are emerging at the same time as a.

00:20:07
Speaker 2: Nymphs, yeah, then yeah, very cool. Well that was very fascinating. Okay, so now we understand fully the transmission dynamics of this bacterium. So let's talk about what happens if you get infected. Okay, what are the symptoms. It starts with aaron wait for it, with a fever. Oh okay. So in general, the incubation period after you get infected is about seven days on average, it can range from about two to fourteen, and the first symptom is often a rather sudden onset of fever, pretty substantial malaise and body aches, and very commonly a headache, which very often people will describe as the quote worst headache they've ever had. Is what one paper said. Interesting, I will say in med school, we don't learn Rocky Mountain spotted fever as the worst headache you've ever had. You learn that for a brain bleed. But that's okay. The point is it's a very severe headache. It's not just like I feel a little dehydrated headache. It's like a bad headache. Okay, okay. You can have a lot of other pretty non specific symptoms as well, things like anorexia because your stomach doesn't feel good, anarexia meaning you just don't want to eat, not like an eating disorder, nausea, vomiting, abdominal pain is fairly common. So, especially early on in the course of this disease, it's very potentially easy to mistake it for a kind of viral syndrome. Okay, you feel crappy, but it's very non specific. And then comes the third of what's often called the classic clinical triad of rocky mountain spotted fever. There's actually two different triads, which I think is silly depending on what paper you read. Okay, within two weeks of a tick bite, almost always, in like eighty to ninety percent of cases, you see this third symptom, and that is the spots of rocky mountain spotted fever. There we go. It's a rash. This rash starts out as small what are called macules, which just means flat red spots, little ones, maybe like less than the size of your pinky nail. And these tend to start on your wrists and your ankles. They're a blanching rash. It doesn't itch, usually it doesn't hurt. So if you press on them, then the co would drain from them. Okay, oh that's what a blanching rash. Wow, yeah, cool new word. New word. Then this rash, which starts on your ankles will begin to spread. It will spread up approximately like up your arms and up your legs to your trunk. But It also spreads down down to your palms and your souls, which you may remember from our episode on syphilis is a very uncommon place to have a rash. The palms of your hands and the soles of your feet really don't get rashes except in a few infectious diseases.

00:23:39
Speaker 1: Okay, it was syphilis, syphilis, hand foot mouth Cocksacki virus, and Rocky Mountain spotted fever.

00:23:47
Speaker 2: Rocky Mountain spotted fever. Is that it? That's it? There are you know? You could get fungal infections on your palms or souls. You could get contact dermatitis and things, but in terms of infectious diseases, those are the three big ones, and it would be all like both hands, both feet, both hands, both feet exactly. Yeah. But it's not itchy, not itchy usually, and not painful. Not painful. Well that's that's nice. Yeah, well not really. I spoke too soon. Spoke too soon. Okay, So this rash is now spreading. By the end of about a week of having this rash, the rash becomes raised, so it's now what we call maculo popular. So it has red flat spots with little dots raised bumps in the middle. And then in the center of these lesions you can sometimes get patikia, which are little pinpoint purple spots that usually are a sign that you're having some kind of issues with your blood clotting. And so that is kind of the general course of disease. It doesn't sound that bad, right, Well, that was a leading question. I mean it doesn't though, Right, It's like headache, fever, you're feeling crappy, you get a rash. But then, as it turns out, this disease is about okay without treatment. And before we had treatment for it, it was on average about twenty five percent fatal. But that fatality rate ranged a lot from about twenty percent to maybe up to eighty five percent depending on where geographically you got infected. Yep, so this is a highly fatal illness.

00:25:37
Speaker 1: Right if your average, if your lower level is still over what did you.

00:25:43
Speaker 2: Say, twenty five percent?

00:25:45
Speaker 1: Yeah, If the average is twenty five percent, that's I mean, think about the other ones that we've had that have been twenty five percent, right, it's not that many exactly.

00:25:55
Speaker 2: That that's a huge case fatality rate. Yeah, So the question is what are you dying from? Right, You've got a rash. How is this killing you?

00:26:07
Speaker 1: Well, I feel like the petitia or whatever, the blood clotting issue, that might be an indication.

00:26:13
Speaker 2: Yeah, so that's one sign. So let's talk about kind of the actual pathophysiology of how this makes you sick. What's going on when you have this rash? Okay, So this is a tickborn disease. So, like many other tickborn diseases, when that tick spits the bacteria underneath your skin, those bacteria travel through your lymphatic system to end up in their host cells. And even though this is a bacterium, it acts a little bit more like a virus in that it has to invade our cells. It's an intracellular bacteria in order to replicate. It does not have the machinery to replicate outside of a host cell, much like a virus.

00:27:00
Speaker 1: So isn't there some sort of like isn't it thought that ricketsia are might be closely related to mitochondria?

00:27:10
Speaker 2: Yes? I believe so they think that mitochondria came from something, whether a precursor to a ricketsia or something similar. Because they're like, yep, yes, I just think that's so cool. Oh, it's so cool. It's so cool. Their genomes are tiny. Okay, So in the case of ricketsia ricketsia, the cells that they invade, the cells that they replicate in are our vascular endothelium. So those are the cells that line our blood vessels. Okay, the inside lining of our blood vessels. Okay, you see where we're going with this, I mean, yeah, yeah. Unfortunately, So what happens when they enter our cells and start to replicate, They they do a very good job replicating. They replicate by fission. They also have these ways of mood from cell to cell to sell without necessarily damaging our cells directly as they move from cell to cell, so they can kind of just spread along your blood vessels, just jumping from cell to sell to sell. And because they're in your blood vessels, they are literally anywhere and everywhere in your body because everywhere needs blood, right. And then they start to cause direct damage to the cells that they infect, and they do this in a few different ways. One is free radical induced injury, which I feel like we're experts on now after our radiation episode, Okay, and then they also release a number of different enzymes that cause damage to these cells. So if you are damaging the cells that line your blood vessels. What do you think is going to happen to the fluid that is supposed to be in your blood vessel.

00:29:01
Speaker 1: Well, it's gonna create a little leaky pipeline, A.

00:29:03
Speaker 2: Little leaky pipeline erin exactly. Okay, So this cell damage causes exactly that, not frank hemorrhage. Okay, they're not like, it's not gross enough damage that you're going to be bleeding out necessarily.

00:29:18
Speaker 1: Who's frank hemorrhage?

00:29:25
Speaker 2: I'm sorry?

00:29:31
Speaker 5: Uh oh did.

00:29:33
Speaker 2: You like that? I really did so, not actual hemorrhage. But this damage does cause increase in the permeability of that membrane essentially, so that means you're going to get fluid plasma leaking out. This is going to also cause you to lose protein because as you damage that membrane, proteins are usually kept in your blood vessel in part by a charge differences. So you mess up that membrane, you mess up those charges, so then protein can leak out more easily, which then just draws more liquid out with it.

00:30:10
Speaker 1: Okay, so it's like this cascading horrible exactly, positive feedback.

00:30:15
Speaker 2: Loop exactly, And let's talk about positive feedback loops. Okay, Because, like we talked about in the radiation episode, when you have this free radical damage that happens to these cells, our body mounts a response to that, right, and that's an inflammatory response. And in responding to that, part of what our body does to try and fight off the inflammation and damage that's caused by things like free radicals and these enzymes is that they will vasodilate our blood vessels in order to get more white blood cells to the areas that they need to be to try and fix this damage. That vasodilation means you have more flow, which means you have more vascular permeability, which means you have more leakage. So this will eventually lead to edema, so swelling outside liquid outside of our blood vessels, and eventually hypovolemia where you don't have enough volume in your blood vessels. On top of that, if it happens to be important organs like your brain or your lungs that get involved in this, this is called a vasculitis where you have inflammation of your blood vessels. If it's somewhere like your brain or your lungs, you don't have a lot of good lymphatic drainage to drain that fluid away, so you have pressure that builds up because of that in that interstitial space. So what's interesting about this is that none of the papers that I read really clearly outlined what the exact cause of death tends to be in Rock Mountain spotted fever. But it is essentially organ failure. What organ it is that ends up failing kind of just depends on what organ happens to be the most affected. A very large proportion of people have hippatomegaly on necropsy or on autopsy after they've passed, so your liver is very commonly involved, at least in fatal cases. Many people also have renal failure, so kidneys might fail. Your lungs can certainly be involved, so you could die maybe just from not being able to breathe from respiratory failure because of all the fluid around your lungs. But there's not like a one single thing that tends to be the ultimate cause of death necessarily. But pathophysiologically we know that it's this diffuse vascular damage that leads to hypovolemia, so not enough volume and eventual shock. So yeah, terrible, really terrible. Another thing that I did want to point out that I think is really really important about this disease is that the mortality rates still today, It's non trivial. It usually hovers around five percent even with treatment. And there is very good treatment for this. Doxycycling a few days worth clears infection, but delays in diagnosis are strongly associated with poor outcomes. So not getting to a doctor fast enough, or a doctor failing to make the correct diagnosis or get the treatment initiated quickly, is very strongly associated with a vastly increased risk of death, and especially in the US, this disproportionately affects black individuals. And you know, there was a limited amount of discussion in the papers that I read as to why it's exactly that is, whether it's you know, people not seeking care and things like that. But my guess, and some of the papers also said this, is that we are really bad at diagnosing rashes on black skin. It's yeah, it's a huge issue. When you google pictures of this, I haven't seen a single picture of Rocky Mountain spotted fever on a black skinned person. Yeah, it's yeah.

00:34:28
Speaker 1: I came across that as well in the research and how it's like historically it's been it's been like that as well.

00:34:33
Speaker 2: Yeah, and I mean it's not just for this, but this is a very fatal disease that's also very treatable if you diagnose it properly. And so the thing is, we don't have good tests, like laboratory tests to diagnose this. It's a clinical diagnosis, which means you make that diagnosis based on history and physical findings, including a rash. So if we don't know what a rash is supposed to look like, because no one's taking pictures of it, no one's you know, it's not in our textbooks, et cetera, then people are dying unnecessarily, which is a huge, huge failure of the medical system. So absolutely, So, yeah, that's the biology of Rocky Mountain spotted fever. Well, it's a terrible disease.

00:35:22
Speaker 1: And that is that's a point that I saw made in a lot of different papers in terms of like how important this disease is and how overlooked it tends to be despite the fact that things like landscape change and climate change are going to greatly shift our exposure, our risk, you know.

00:35:42
Speaker 2: Yeah, and I mean it's it's the kind of case where it directly results in like people dying, you know, but it is, it is. It's a difficult thing because it is so rare. And I think that you know, we'll talk later about where you see this geographically, but I think a lot of people well maybe don't know or don't know to think of it, you know, when they're when they're kind of listing their their differentials in their head, it could easily look like a viral illness. It's like, oh, you've got a fever and a headache and you're feeling crappy.

00:36:14
Speaker 3: You know.

00:36:15
Speaker 1: Well, and in the history section, I don't talk much about like the name itself, but if you look at so many different ricketzial diseases they tend to have, particularly the arthropod born ones, they tend to have location specific name. Yeah, And so in one place it's Rocky Mountain spotted fever, in another place it's something else. And so you have like all over the world, you know, different species of pathogetic Rikeetsia called by different names, and that has created a lot of confusion, particularly with Rocky Mountain spotted fever. Since we're talking about it, like, yes, it occurs in the Rockies in the Western States, but the eastern seaboard is like bam, South America bam, right Central America bam.

00:37:02
Speaker 2: Like it's there too.

00:37:05
Speaker 1: And so there was a huge push at one point to just call it spotted fever or spotted fever group of KEETSI but that never really caught on.

00:37:13
Speaker 2: So RMSF is what it is. So well, tell me more, Aerin about this history. How did we get here? Where did this thing come from? Okay, I cannot wait.

00:37:26
Speaker 1: We will take a quick break first, Aaron, you started off biology with a quote, and I laughed because I'm starting off history with a quote.

00:38:00
Speaker 2: I love it.

00:38:02
Speaker 1: You started off with the quote from the first paper you read, and I'm starting off with that quote from the book from the very beginning. Okay, here we go, the unwritten history of the investigational work in connection with Rocky Mountain Spotted Fever, if written would read like a romance.

00:38:26
Speaker 2: I mean you see why. I was like, what what is this? Okay? So yeah, I mean why is that? Yeah? Hopefully I'll tell you.

00:38:41
Speaker 1: Hopefully I'll do a good enough job that you'll understand what that quote means. I'm not sure that I do anyway.

00:38:47
Speaker 5: So.

00:38:48
Speaker 1: I mean, and I before researching this, I didn't know there's quite a bit of like lore or fame or infamy around owned Rocky Mountain Spotted fever research.

00:39:02
Speaker 2: There was a movie.

00:39:03
Speaker 1: Called green Light starring Eryl Flynn from nineteen thirty seven, and one of the subplots it tells the story of the researchers involved on the Rocky Mountain Spotted Fever project. What Yeah, and the disease itself plays a major role in the nineteen forty seven movie Driftwood. I haven't seen either of these, so I can't vouch for their accuracy or how much romance they have in them or whatever. But I have now read about the history of Rocky Mountain Spotted Fever, especially the history of its research, and that does contain a fair amount of drama and romance.

00:39:41
Speaker 2: To start the story, we.

00:39:44
Speaker 1: Don't have to go all that far back, actually, so the first hand account that I read in the beginning of the episode, as I mentioned, is from seventeen fifty nine. But like I said, it's not one hundred percent accepted to be Rocky Mountain Spotted Fever. In any case, there were likely k of our msf Rocky Mountain spotted fevers scattered throughout the Americas for hundreds of years at least, But the real story begins only in the late eighteen hundreds. We don't have written records for anything earlier. Yeah, So around this time, starting in maybe the eighteen sixties or the eighteen seventies, a mysterious illness was seeming to pop up in the bitter Root Valley in Montana. So this if you can picture Montana in your head, go to the far far west, kind of the southwestern part of the state. If you know where Missoula is, it's like the very north end of the valley.

00:40:42
Speaker 2: I don't know where that is, but I can picture Montana, So Okay.

00:40:48
Speaker 1: So this valley, the Bitterroot Valley, runs about ninety five miles long, and it's sandwiched in between the bitter Root Mountains and the Sapphire Range, with the bitter Root River winding its way through the valley. Historically, the Salish tribe of the Flathead Nation lived in Bitterroot Valley, and while the region experienced some settlement throughout the eighteen hundreds, Lewis and Clark passed through in eighteen oh five, it lagged behind other parts of the West, but then the discovery of gold in California and then the increasing number of Mormon settlements in Utah eventually led to people striking out to find a piece of land of their own, and in the second half of the nineteenth century, Montana grew enormously in popularity. The Bitterroot Valley in the second half of the eighteen hundreds in particular, was super popular because it had these ample resources for lumber and fertile farmland for livestock and apple orchards were really popular, and as you can guess, the increasing number of white settlers meant that more land had to be found. So what was the natural solution to this problem genocide? Well, at least forceful removal, So the government removed the Salish, for whom this was their ancestral home, of course, and so in the eighteen seventies, with the Salish driven out, the land of the bitter Rup was ripe for clearcutting and apple farming, and it was also apparently ripe for the emergence of a seemingly new tickborn disease. All this clear cutting to make room for orchards and farms led to proliferation of scrub habitat, which was great for sheep grazing, but also great for mice and other small mammals, which happened to be excellent bloodmeal host for ticks. The first case of what we now know is Rocky Mountain spotted Fever that we can trace back for sure, occurred in eighteen seventy three in Montana.

00:42:50
Speaker 2: Consequences man consequences for our actions, and this case was not a one off.

00:42:58
Speaker 1: So from that first case more followed, and not just in Montana, Colorado, Oregon, Idaho, Wyoming. A lot of other places grew aware and wary of the disease rightfully so, and I have to include another side note here. So for a while it was thought that the Salish Indians had warned the incoming white settlers of Rocky Mountain spotted fever by saying certain canyons in the spring in the bitter Root were full of evil spirits. But this is no longer thought to be in relation to the disease.

00:43:31
Speaker 6: Okay, So rather what, at least in this book, it was thought that the disease probably wasn't super prevalent before the white settlers clear cut the land and allowed for the super proliferation of ticks.

00:43:46
Speaker 1: And so anyway, with this alarming rise of an extremely fatal disease, combined with like the daughter and son in law of the Montana governor dying of the disease, the state feared that they would lose out on prospective land by because of this pesky fatal illness, and so they told the Montana State Board of Health to do something, and that's exactly what they did, starting in nineteen oh two by appointing two young pathologists named Louis Wilson and William Chowning to see what they could figure out about the disease. And that same spring, a bacteriologist named Earl Strain suggested a connection between the disease and a tick bite because he was there touring to kind of see, oh, you know, like what can I figure out about this disease, and he visited someone who had Rocky Mountain spotted fever and noticed a tick embedded in the genitals of the sick person.

00:44:48
Speaker 2: Very interesting that he just happened to see a tick, because almost certainly if that person was suffering from Rocky Mountain spotted fever and they happened to have a tick, that tick was not, in fact the perpetrator of their illness.

00:45:03
Speaker 1: I think it speaks to the high levels of infestation.

00:45:08
Speaker 2: Around the bitter Root at the time. I no, but I mean that's and that would explain why you know, you had such a huge increase in cases if oh, yeah, you know, you were just getting bit left and right and genitals.

00:45:21
Speaker 1: Well, and if you think about like the occupations of people who were settling in the bitter Root at this time, you're outdoors, right, You're outdoors, especially during that time of year, and so it's almost unavoidable.

00:45:35
Speaker 2: Yeah.

00:45:35
Speaker 3: Yeah.

00:45:36
Speaker 1: So so William and Chowning took note of Strain's observation when they were planning their research season, which they had to do basically right away because Rocky Mountain spotted fever season is actually pretty short, which is great news if you're at risk for the disease, but a little bit challenging if you're researching it. Joys of fieldwork and they covered their bases, they performed autopsies, they did epdemiological surveys, lab studies, and what they found was concerning. Between eighteen ninety five and nineteen o two, there were eighty eight cases in the Bitterroot valley with sixty four deaths.

00:46:15
Speaker 2: Wow, it's a seventy two.

00:46:17
Speaker 1: Point seven mortality rate. And they concluded that it was not contagious from person to person and not a result of melted snow water, which was the leading hypothesis at the time.

00:46:30
Speaker 2: Okay, well, a good thing, right, it would.

00:46:34
Speaker 1: Be hard to avoid melting snowwater. Yeah, melted snowwater. And so they suspected instead that it was caused by a protozoman that they had found in some of the tick samples that they had dissected and stuck under a microscope. Interesting, and so by the end of this first season of their research they had a nice little disease ecology cycle all laid out. The woodticks transmitted the protozoan to humans, and ground squirrels aka gophers were the disease reservoirs. This was an untested hypothesis, but that didn't stop reports of it in the news because people were hungry for information about it. They were like, we want to know how to protect ourselves. But just knowing or thinking that ticks were responsible for the disease didn't really do that much because ticks were absolutely everywhere in the spring in the bitter Root, and so the only way to avoid them would be to not live or work there, which was not the solution that the state was looking for. And the only practical step, in their eyes, which wasn't really practical at all, was to eliminate the ticks themselves or the gophers ever.

00:47:43
Speaker 2: Thought to be the hosts. Oh gosh.

00:47:46
Speaker 1: So in the spring of nineteen oh four, the residents of the bitter Root took this to heart.

00:47:50
Speaker 2: They burned, and they burned.

00:47:52
Speaker 1: Vegetation, and they set out poisoned grain to kill the gophers, which actually killed a lot of game animal gamers and other animals.

00:48:02
Speaker 2: And they also got.

00:48:03
Speaker 1: A bunch of sheep to eat the grass that the tall grass that they thought was the ticks habitat. Oh dear, But it's nearly impossible to get rid of ticks. You need possums, Sarin, We need possums to set loose.

00:48:21
Speaker 2: The possums don't do that.

00:48:23
Speaker 1: I feel like maybe we shouldn't gamble through the ecological dye in that way. So the next best thing, though, was just to remove a tick as soon as you saw it attached, right, and people were encouraged to treat it.

00:48:40
Speaker 2: Like a snake.

00:48:40
Speaker 1: Bite like a venomous snake bite, dab some carbolic acid on the side of the bite right away. So then people had a lot of acid burns, accidental spills.

00:48:50
Speaker 2: Infections, et cetera.

00:48:52
Speaker 1: I mean, basically, the bottom line is that, you know, though these efforts had led to some fundamental knowledge being gained, the application to prevention simply wasn't there, right, And so more help was called in in the form of Charles Wardell Styles.

00:49:08
Speaker 2: Does that name sound familiar to you, Yeah, it sounds very familiar. What else did he do? Hookworm? Oh, that's right.

00:49:18
Speaker 1: He discovered or identified the second species of hookworm in the Americas. Yeah, and he I think he played a role in I don't remember, but I think he played a role in determining that it was the cause of the widespread anemia in the South.

00:49:34
Speaker 2: Ah. And he's Harry Styles is great grandpa exactly exactly. I'm so hip just dropping those names.

00:49:47
Speaker 3: My god.

00:49:49
Speaker 1: Okay, So anyway, so Styles set out to basically test the ground squirrel tick protozoan life cycle that Wilson and Chouning had laid out. He was enthusiastic about the hypothesis early on, but he was a little bit close minded when it came to any challenge to the accepted dogma of the time, which was and this is news to me, but apparently for a while it was believed that that arthropods could transmit protozoa, but were not capable of transmitting bacteria other than accidentally, like a fly could accidentally, I don't know, give you an infection because they.

00:50:32
Speaker 2: Stepped in poop or something exactly.

00:50:35
Speaker 1: But mosquitoes and ticks and whatever weren't capable of actually completing the life cycle I bacteria.

00:50:43
Speaker 2: Am that's so interesting.

00:50:47
Speaker 1: Yeah, So when he searched for this, this supposed protozoan in the ticks and the blood of the victims, he came up empty handed again and again. But instead of saying, you know, well the may have something to do with it, but the protozoan probably doesn't, he openly refuted and dismissed the existing hypothesis. And he was started to say, like, oh, you know what, these people or these residents are overreacting. Ticks aren't involved. It's probably snowmelt all along. So and it's in a way, this contemptuous criticism actually was beneficial for the research of Rocky Mountain Spotted Fever because it drew such attention from other researchers, including a pathologist from the University of Chicago named Howard Taylor Ricketts.

00:51:45
Speaker 2: Ricketts RICKETSS.

00:51:49
Speaker 1: Rickets set up a correspondence with Chowning, saying that he believed their hypothesis had gotten unfair treatment by Styles, and Chowning was like, I agree. Also, I've been doing some side experiments in my spare time, including a little bit of medicalized torture.

00:52:07
Speaker 2: Oh great.

00:52:08
Speaker 1: So he had obtained quote consent from two people to attach ticks to them which had been feeding on a man who died of Rocky Mountain spotted fever. Oh, they both got sick with the disease and recovered, And so Chowning was like, must be ticks. So anyway, Ricketts when he told Rickets about this, Rickets just didn't acknowledge it. Apparently okay' denounce them, but he didn't acknowledge it. And he was like, I'm gonna do my own research. And so he went to Montana, okay, But the state had no money to give him, and so he and Wilson and Chowning had to find their own way to pay. So they like cobbled together a bunch of resources, and in nineteen oh six, Ricketts set up a laboratory in a tent on the grounds of the Northern Pacific Hospital in Missoula.

00:53:01
Speaker 2: So he was just like in a tent.

00:53:03
Speaker 1: And that spring and summer proved very productive for Rickets and another researcher named Walter King, who joined in on the research. But it must be said that this wasn't a super collaborative project each one of these men for the most part, maybe you know, Chouning and Wilson worked together, but like Rickets and King were very much like, this is my project, and I want to do it my way, and I want research, and I want publication priority, and I want blah blah blah.

00:53:34
Speaker 2: So anyway, and.

00:53:37
Speaker 1: So first they found Ricketts and King found that they could cause the disease in a guinea pig by injecting serum into the animal, and they could sustain the infection by alternating infecting a guinea pig and then a monkey, and then a guinea pig and then.

00:53:51
Speaker 2: A monkey, which then enabled year round research. Okay, that makes sense.

00:53:58
Speaker 1: Yeah, Then at the very end of this botted fever season, both Ricketts and King demonstrated that ticks can cause infection, and they did this by attaching a tick to a guinea pig and then disease resulted. Ah and this was a super exciting finding, but it came at just the wrong time for them because it was the end of the season and soon there would be no more ticks to be found. Back in Chicago and Washington, Rickets and King tried to keep these tick experiments going by advertising in like Montana papers for anyone who could find a tick, a live tick to send it their way. At one point they offered a financial incentive of ten dollars in gold for anyone who could deliver fifty or more live ticks.

00:54:45
Speaker 2: Oh my gosh, citizen science. But they never got any. They had to wait until the spring.

00:54:53
Speaker 1: Okay, and mid April nineteen oh seven saw the first victim, a twenty six year old lumberman whose family refus used to allow Ricketts to draw any blood. Ricketts was peeved about this, and so he asked the secretary of the State Board of Health to do something about it, And so he drew up an official looking document saying that the family must cooperate with the investigation and then he told Rickets, hey, don't let anyone get too close to look at this because in truth, I have no authority to issue it. So you know, oh my gosh, and people wonder why there's deeply rooted mistrust in.

00:55:37
Speaker 2: The medical establishment and the government research and authority. Yeah, okay, goodness.

00:55:44
Speaker 1: So anyway, in nineteen oh seven, Rickets concentrated on finding out the pathology of the infection in ticks, still without knowing what the causative agent was, and he determined that a small proportion of female tics could transmit the path into their offspring, so larval takes.

00:56:02
Speaker 2: Could be infectious. Awesome, which is a great finding.

00:56:05
Speaker 1: And then in January of nineteen oh nine he seemed to finally hit the jackpot when he published a paper in which he described the teeny tiny basillis cox of bacillis that was the causative agent of Rocky Mountain spotted fever. He had detected ample amounts of the bacteria and eggs of infected females, and while he was unable to culture the bacteria, he was confident in his finding.

00:56:30
Speaker 2: Yeah. Yeah, it's I mean, it's pretty cool.

00:56:35
Speaker 1: His achievements, Like people were psyched about this because he had done I mean, he had done microbiological research, he had done ecological research, he had done some medical research, and so his achievements won him praise and opportunities left and right, and even the state of Montana recognized his work by writing in a bill in nineteen oh nine that would fund a bunch of his research on unspotted fever over the next couple of years. Unfortunately, though, the funds were suspended when the state realized that they had allocated more money than they were going to collect in revenue, and so Ricketts's work was put on hold. Oh Man, and even though his colleagues in Montana encouraged him to stick around get private funds to bridge the gap, Ricketts was like, no, I've got so many opportunities here. I'm going to Mexico to solve the question of another spotted fever like disease, typhus.

00:57:34
Speaker 2: Ah.

00:57:35
Speaker 1: So then he went down to Mexico City. But it was only after he arrived in Mexico City in December of nineteen oh nine when he learned that the big puzzle pieces of Typhus had already been put together. The vector animal model. You know, it was a lot of the stuff that had drawn him to study it was already discovered, identified, done, but he gamely stayed on and tried to figure out the causative agent, which he suspected might be very similar to Rocky Mountain spotted fever.

00:58:12
Speaker 2: So then in early nineteen.

00:58:13
Speaker 1: Eleven, Ricketts got word that it finally looked like the Montana funds were coming through, and he was super happy, but he was not incredibly eager to leave, despite you know that he was working under very dangerous conditions. There was like no protection against Typhus. In his letters to his friends, he wrote, like, my wife is very upset with me. She's very scared for me. Like if she knew what I was doing, she'd be wanting me to come back. But he wanted to see the project through to the end. And so just as tick season was starting in Montana, just as he was like trying to get up there, he came down with Typhus and died May third, nineteen ten, at the age of thirty nine.

00:59:02
Speaker 2: No.

00:59:03
Speaker 1: Yeah, his death was a huge blow to spotted fever research, and it also established a very tragic pattern. If the first decade of the nineteen hundreds was characterized mostly by research on the causative agent and medical treatments for Rocky Mountain spotted fever. The second decade looked towards the tick for answers by the late nineteenth century, when the focus on Rocky Mountain spotted fever was heating up. Entomology and medicine were two totally different fields, particularly in North America. Research combining the two was conducted only rarely, such as with like yellow fever research in Panama, for instance. Largely entomologists played the role of helping combat agricultural pest arthropods or doing like academic foundational biology research, and medical doctors and researchers dealt with human diseases, how it worked in the body, how to control it, and there often wasn't a lot of opportunity for overlap. Rocky Mountain spotted fever, however, required a full understanding of the vector tixie cology, like its life cycle, hosts, behavior, etc. As well as the characteristics of the disease bacteria, pathogenesis, etc.

01:00:29
Speaker 2: And you might.

01:00:30
Speaker 1: Instinctively think that public health researchers or physicians and entomologists working together would be the best way to make progress. But then maybe you forgot about ego. After Ricketts met his untimely end, there was maybe a bit of a vacuum in the Rocky Mountain Spotted Fever research arena in Montana. The head the secretary of the state Public Health Department, whose name was Tuttle, appointed a thing physician named mcclintick to continue work on the project. But then when he arrived, he found an entomologist named Robert Cooley had rudely started on a bunch of control efforts on his own, and neither was willing to seed any ground for publication priority or research area. And apparently neither was willing to work together.

01:01:21
Speaker 2: Oh my gosh, I know, get over yourselves. Get over it.

01:01:26
Speaker 1: So the physician McClintic believed, because it's a human disease, it's a physician or.

01:01:31
Speaker 2: A public health problem.

01:01:32
Speaker 1: And then entomologist was like, no, it's a tick transmitted disease, so that calls for a tick control expert.

01:01:39
Speaker 2: No, it's all of these just were together. Uh good, I know.

01:01:44
Speaker 1: Oh, it's just like goes on and on, this sparring over funds. It's actually spilled over to the federal level and resulted in Cooley the entomologist, losing support for his work. Oh so then mcclintick, who was the physician, was like, a right, I'm gearing up to do some tickwork, setting up giant vats to dip the livestock in to try to prevent tick infestations on livestock. And I'm going to initiate a massive project to identify the reservoir of the bacterium. But that second project was mostly just destroying all small wild mammals like pine squirrels, yellow billy chipmunks, wood rats, woodchucks, weasels, badger, and of course the infamous gopher.

01:02:26
Speaker 2: Cool cool, that's not the way you do it, by the way to control ticks. That doesn't work.

01:02:34
Speaker 1: And so while he was able to rule out several of the species is playing a major role in the infection cycle, such as badgers, he had a hard time finding a single smoking gun species responsible for the disease.

01:02:48
Speaker 2: And he would never.

01:02:49
Speaker 1: Find it because he died of Rocky Mountain spotted fever.

01:02:53
Speaker 2: In nineteen twelve.

01:02:54
Speaker 1: Oh my god, just a year after starting his research in Montana.

01:02:58
Speaker 2: Oh that's sad.

01:03:00
Speaker 1: It's really sad. Once again, spotted fever research in Montana was left without a leader. Maybe this was an opportunity for a fresh start to bring together physician and entomologist.

01:03:13
Speaker 2: I have a feeling it's not going to happen. Erin, No, it didn't happen.

01:03:17
Speaker 1: The budget and the land would be split. The north part of the valley went to the US Bureau of Entomology with COOLi in charge, and the south part of the valley would be designated as US Public Health Service land.

01:03:29
Speaker 2: Kind of an interesting way to do it, Huh, isn't it so fascinating? Who did better? Well? Great question.

01:03:38
Speaker 1: So the entomologists on the north side of the valley were set on just livestock dipping and basically taking a cattle submerging them into a caroside or a pesticide to kill the ticks. And so these entomologists were like, all right, that this is the key killing small rodents. That's wayted effort. And the public health folks on the other hand, were like, no, we're gonna dip and kill small mammals and also not allow cattle to feed in the western on the western side of the river, which was the only side that was infected.

01:04:16
Speaker 2: By the way. Oh yeah.

01:04:19
Speaker 1: And so whether the dipping was actually effective was called into question as well. So from nineteen thirteen to nineteen eighteen, the number of ticks supposedly declined eighty to ninety percent, while the number of cases had been reduced from eleven to three. But these numbers are far from conclusive, like eleven to three is super.

01:04:40
Speaker 2: Could just be seasonal variation or whatever.

01:04:43
Speaker 1: Exactly exactly, And eradication, which was the promised end of these projects, was not on the horizon. The tick must be destroyed. Killing small animals wasn't doing it. Dipping cattle wasn't doing it. Maybe a vaccine could work.

01:05:01
Speaker 2: By the way, that's our title.

01:05:04
Speaker 1: The before Ricketts died, he published his preliminary findings of this bacterium, but the debate continued with still the protozoan leading the pack.

01:05:22
Speaker 2: Gosh, I know.

01:05:24
Speaker 1: The pathologistes Bert Wallbach.

01:05:29
Speaker 2: Like Wallbachia. Oh that's exciting. Yeah.

01:05:33
Speaker 1: He decided to give it a shot, and he also observed teeny tiny bacteria like things in the ticks, their eggs, and the blood of humans and animals that had spotted fever. Okay, but he wasn't sure that they were actually bacteria because he was like, it doesn't make sense, they live entirely within the cells of the animals. So this has got to be some new kind of micro organism somewhere in between protozoa and bacteria.

01:06:00
Speaker 2: I mean yeah, I mean wrong, He's not wrong.

01:06:04
Speaker 1: Like, and even though he was pretty certain he had discovered the causative agent, which he called dermo CenTra zenus rakhetzi, others weren't convinced, chiefly because he was unable to culture the organism in.

01:06:19
Speaker 2: Media in a lab. Of course he was, he.

01:06:22
Speaker 1: Was, like, he was like, listen, like, I understand that these postula its are important, but like we have to evolve, like we're learning new things.

01:06:30
Speaker 2: Maybe we should look at different criteria. Yeah, he was right, He's right.

01:06:39
Speaker 1: But then the discovery of the causative agent of Typhus forced researchers to accept that these intracellular microbes might actually be real and maybe a new type of microbial life, or at least a new version of what we've already seen. And eventually the name that Wollback had given for the spotted fever back Bacterium was changed to Rakkeetzier rakeetzii, giving rise to a whole new genus of pathogenic intracellular bacteria cool. So by the nineteen twenties, the causative agent of Rocky Mountain spotted fever had been discovered and the life cycle had been outlined. But this knowledge didn't translate into live saved yet again. Rather, the incidents of the disease, as well as its mortality, seemed to be on the rise. For instance, in nineteen twenty one, all eleven cases of Rocky Mountain spotted fever died. Land prices reflected this. They were dropping from one hundred and twenty five dollars per acre to fifteen dollars per acre in some places. Oh also, fifteen dollars per acre.

01:07:46
Speaker 2: Can even imagine should have bought erin actually missed out?

01:07:51
Speaker 1: We did, and tourism obviously plummeted. No one wanted to go to a place where you could catch spotted.

01:07:59
Speaker 2: Fever and one hundred percent of you would die.

01:08:02
Speaker 1: Yeah, yeah, And matters were only made worse when the first state bacteriologist, Arthur McCrae, died of Rocky Mountain spotted fever in nineteen nineteen.

01:08:12
Speaker 2: Oh my gosh, eron, how many people are going to die from this? There's more?

01:08:17
Speaker 5: Okay, So panic was at an all time high, so the state finally acquiesced to providing funds to create a laboratory whose main focus was to stop the problem of spotted fever.

01:08:33
Speaker 1: The quote Schoolhouse Lab was established in an abandoned schoolhouse a couple of miles from Hamilton, Montana, in the Bitterroot Valley. There, lab and ecological facilities were built or cobbled together where researchers could actually do the work that they had been doing in their spare time in makeshift tents and distant university labs for years. And to head this new research venture, two people were appointed, physician Roscoe Spencer and entomologist Ralph Parker.

01:09:04
Speaker 2: Parker, I all right, another physician and another entomologist. Are they going to work together this time? Well, this is where the romance comes in.

01:09:15
Speaker 1: Just going at first, the old time rivalry between these two professions seemed like it was going to rear its ugly head yet again, and they were like, oh, you know, before they before they arrived in Montana, I was like, oh, what about publication priority?

01:09:31
Speaker 2: What about this? What about that?

01:09:32
Speaker 1: But then they met in person and they were like, let's work together. All of our research will be published jointly.

01:09:38
Speaker 2: So isn't that nice? Is how you do it? That's how you do it.

01:09:44
Speaker 1: So Parker, the entomologist, he had set his sights on big picture ecological studies like huge, what do we how do we find out the links between ticks and these animals and spotted fever and the behavior and seasonality and all of these like just the most fun questions, right, And Spencer's like.

01:10:04
Speaker 2: I'm gonna do a vaccine. And so there had been.

01:10:08
Speaker 1: Some research by Hideo Nogucci at the Rockefeller Institute that was promising in terms of spotted fever vaccines, and in nineteen twenty three, Nogucci had declared that he had developed an effective vaccine. It just needed to be tested in humans. So who better to volunteer than some of the laboratory staff at the Schoolhouse Lab in Hamilton. For sure, incidents of the disease was disturbingly high.

01:10:35
Speaker 2: The vaccine was not.

01:10:37
Speaker 1: Without side effects, but it seemed to be effective and at least reducing the severity of illness if exposed to the disease. All right, But because the efficacy of Nogucci's vaccine remained doubtful, Spencer, the physician involved in the project continued his own work on a vaccine, work which ended up being delayed because tularimia, another disease, started popping up in the Bitter Root Valley.

01:11:05
Speaker 2: Oh my gosh, this does not make me want to visit this part of Montana. Oh my gosh. What I mean?

01:11:12
Speaker 1: First of all, Okay, that was not the image I was trying to portray with this history, and I feel now very bad about it because it is absolutely beautiful. And yes there are ticks, but we know a lot more about Rocky Mountain spotted fever. We know a lot more about how to protect ourselves and if there's ever an area where the physicians are probably keyed into, Yeah, that makes sense.

01:11:41
Speaker 2: Signs you symptoms, you'd get doxycycling. If you walked in and said I had a fever.

01:11:46
Speaker 1: You're like, I went hiking in the bitter Root. Here's some doxy ceco.

01:11:50
Speaker 2: I'm just kidding. You don't give it prophylactically, but anyhow.

01:11:56
Speaker 1: So okay, tularimia popped up. Both as Ann Parker, the heads of the project, became ill, and they wouldn't be the last to fall during this work.

01:12:07
Speaker 2: No, Aaron, I don't know if my heart can take this. I'm so sorry. This is the whole romance. This is not that.

01:12:14
Speaker 1: I think it was like romance, meant in the way that was like.

01:12:20
Speaker 2: Tragedy. Oh yeah, those are two different categories of film. I don't know, are they? Like a tragic movie could be romantic at the same time and vice versa Romeo and Juliet. Yeah, I don't like that one.

01:12:36
Speaker 1: Well, anyways, regardless, let's learn more about the fallen researchers. Okay, student research assistant William Geddinger died in nineteen twenty two of spotted fever. Field assistant George Henry Cowan, who had worked for over a decade on the disease, died in nineteen twenty four, and another student researcher named Albert Curley died in nineteen twenty eight of spotted fever. In nineteen twenty five alone, six people working at the Schoolhouse Labs became infected with either spotted fever or tularimia.

01:13:13
Speaker 2: Oh my goodness.

01:13:14
Speaker 1: The Schoolhouse Lab was notoriously and deservedly so, an incredibly dangerous place to work because there was no biocontainment facilities and spotted fever ridden ticks were crawling all over the place. Oh no, Like they would have rabbits that they would infect and then the ticks would just be like your tick falls off and then it could go and.

01:13:37
Speaker 2: Oh get up on a lab worker.

01:13:39
Speaker 1: Dogs wandered in and out, bringing ticks with them. I mean they didn't have the best facilities, right. Part of it was funds, Like if there's a lesson here, and it's about funding disease research as usual. There's a famous book called Microbe Hunters by Paul Dacreefe that tells the romantic and swashbuckling tales of like early microbiologists and well micropunters, and it includes the story of the Rocky Mountain spotted fever researchers, which enraged the residence of the Bitter Root because it portrayed them all as like cowering in their cabins hiding from this dreaded disease. But I mean people were rightfully scared of spotted fever, and so when Spencer rolled out testing of his vaccine in nineteen twenty five, people like both workers at the lab as well as residents eagerly volunteered and it seemed effective in at least reducing the duration and severity of the illness. Okay, so overall, retrospective studies showed that vaccinated people had a seventy five percent lower fatality rate than those who were unvaccinated.

01:14:49
Speaker 2: What that's amazing.

01:14:51
Speaker 1: Yeah, yeah, so you know, but the hazardous working conditions remained a concern, and so the state finally put together funds to build new facilities. But where should they go? Should they move to Missoula, where the University of Montana was located, But maybe that was too far from the field, and so we should keep it close to Hamilton, And so it was decided that it was that it would be built on the east side of the river in Hamilton, which had always been spotted fever free.

01:15:23
Speaker 2: Oh no.

01:15:26
Speaker 1: This caused quite a bit of a stir as people became concerned that the disease would become established on the east side, or that infected ticks would escape, or children playing in the yards of the lab would get infected. But tons of special precautions were put in place, including like amoat and heavy duty sterilization procedures WHOA and work began. Ultimately, the residents of Hamilton warmed to the lab and they would occasionally like lead out of town visitors through the building. And then that became problematic because the recent were like, you're putting yourselves at risk. We need to shut this down, like you need to sign in, you need to have somebody supervising this. So but anyway, the availability of a vaccine also alaid some of these fears. But the vaccine was not a permanent solution because in order to make it, researchers had to collect or rear thousands of ticks, get them infected, and then grind them up and then turn that into a vaccine.

01:16:28
Speaker 2: Oh that's what they were using. Okay, mm hmm.

01:16:31
Speaker 1: And there wasn't much work that had been done on streamlining the production process, and nor would there probably be, since the market for the vaccine was relatively like low, only in the Western States.

01:16:44
Speaker 2: Yeah, or was it so?

01:16:49
Speaker 1: Throughout the nineteen thirties, a mysterious typhus like illness was noted along the eastern seaboard of the US as well as in Brazil, and it seemed to be associated with.

01:16:59
Speaker 2: A tick bite.

01:17:00
Speaker 1: And while initially it was thought to be a disease distinct from spotted fever, like doctors would say, oh, I would say this is spotted fever if I were in Montana. But ultimately microbiological research showed it to be one and the same. And this development was pretty crucial since it came around the same time as the Great Depression was sinking its teeth into everything, including scientific research funding. So funding for the Rocky Mountain Laboratory was threatened. And in response to this, one person, one researcher replied quote, and I'm including this quote because I think it's relevant to.

01:17:41
Speaker 2: Today and always.

01:17:44
Speaker 1: If the government should discontinue this activity in the light of our present knowledge, the person's responsible for such action would, in my opinion, be morally responsible for the deaths which will occur as a result of the lack of material. I may add that only a few days ago a request was received from the Army for a large quantity of this material to be used for the protection of its forces in the field.

01:18:11
Speaker 2: So sounds strangely familiar in our affurent climate. And that's all I'm going to say about that.

01:18:22
Speaker 1: It's like the government doesn't want to fund this anymore, but yet they want it so anyway.

01:18:30
Speaker 2: Fortunately, you know.

01:18:31
Speaker 1: Maybe this has cause for optimism. The funds were preserved the lab stayed and placed, and actually some Civilian Conservation Corps CCC camps, which was like part of the whole, you know, Roosevelt's New Deal, were established in the bitter Root to help collect ticks and to do this research for vaccine productions. They had tons of people coming in to work there, which was actually also a problem because there wasn't enough vaccine to vaccinate.

01:19:00
Speaker 2: The newly arrived workers. But anyway, so until the mid nineteen.

01:19:05
Speaker 1: Thirties, research at the Spotted Fever Lab in Hamilton had focused on just that, hence its name, which is the Spotted Fever Lab. Maybe some dips into tularimia, but developments in the mid nineteen thirties would greatly expand its role and give it the name Rocky Mountain Laboratory.

01:19:23
Speaker 2: But that, like Rocky Mountain Labs, is still a thing today.

01:19:27
Speaker 1: Oh yeah, these are its roots.

01:19:30
Speaker 2: Yeah that. I never knew that. And when you said Rocky Mountain Labs earlier, I was like, I never would have. I don't know how I never would have made a connection between Rocky Mountain, Spotted Fever and Rocky Mountain Labs. I never I never made that connection before.

01:19:45
Speaker 1: Oh my gosh, and it's it's so wild because like that's always been like well throughout my PhD. I was like, Oh, that's that's my dream place to work. I want to work on racketzias in Rocky On in RML.

01:19:57
Speaker 2: Yeah, in beautiful ham.

01:20:00
Speaker 1: And But like I didn't know any part of this history, and I also didn't know the incredible significance that this lab has had, like not only on Rocky Mountain spotted fever research, but as we're about to find out even more research.

01:20:15
Speaker 2: Ooh okay.

01:20:19
Speaker 1: So in nineteen thirty six, a researcher at Rocky Mountain Laboratory named Harold Cox had been experimenting with different ways to grow ricketzier outside of ticks, because he was like, I want to put together a better method of vaccine production. One day he ran out of the tissue that he had been using mid experiment, and rather than scrapping the whole thing, he reached for some yolksac that he had put in the fridge. You have that just like I guess well, they were doing like egg yambrane whatever, And the next day he found it teeming with ricketzia.

01:20:59
Speaker 2: He was like, oh my gosh, what he wrote to everyone.

01:21:03
Speaker 1: People were super skeptical and then they saw it in person and they were like you kidding me.

01:21:07
Speaker 2: Good job.

01:21:10
Speaker 1: And this accidental discovery had huge implications but not just for spotted fever research, but other riquettsial diseases. And I know that, like we haven't done a Typhus episode, but like Typhus is really bad. Yeah, I mean you talk about one of the big killers of especially like you know, wartime and any sort of like civil unrest areas, Like Typhus was massive. Yeah, so it's still it's still massive.

01:21:42
Speaker 2: Yeah.

01:21:42
Speaker 1: Yeah, So Typhus was was a huge one, and so so spotted fever. Yeah, across the US and inter Central and South America, incidents of it ran pretty low. Of course, it was very deadly and so that was a huge cause for concern. But of even more interest was this the big killer typhus, Especially as World War two began and as US soldiers began to be stationed in regions where it was endemic. Cox's yolksac method provided a cost efficient way to produce the volume of vaccines that had long been sought after huh. This discovery turned Rocky Mountain Laboratory into a national vaccine factory for typhus and yellow fever and others during World War two. Like it turned into just pumping out vaccines.

01:22:33
Speaker 2: Wow, I did not know that.

01:22:35
Speaker 1: And it played such a hugely important role during World War two that there were armed guards like from you know, armed forces around there around the clock twenty four to seven to make sure that like nothing happened to the lab in old Hamilton, Montana, like tiny town.

01:22:54
Speaker 2: So anyway, super cool.

01:22:57
Speaker 1: And then while at Rocky Mountain Laboratory, Cox also developed the complement fixation test, which allowed for diagnosis of ricketzial diseases.

01:23:08
Speaker 2: Wow, that's a big deal. That's a very big deal. So VACU Mountain Lab, Rocky Mountain Lab.

01:23:17
Speaker 1: The discovery of antibiotics that were effective against ricketzial diseases in the nineteen forties and the nineteen fifties, they took some of the urgency out of the preventative or treatment research programs for spotted fever. Researchers could now focus on understanding the physiology of ricketzier and the microbiology of these bizarre tiny bacteria, and the miracle of antibiotics, as we had discussed a few episodes ago, led to this unfortunate decline in some of the more fundamental medical entomology research that had been the hallmark of the Rocky Mountain Laboratory in its early decades. With the combination of a vaccine and antibiotics, fear of spotted fever declined throughout the fifties and the sixties, despite the fact that it continued to pop up in new locations and with increasing incidents like it. If you look at a chart of the cases over time, it's like increasing, increasing in the late eighteen hundreds, early nineteen hundreds, and then plummets, and then throughout the sixties and seventies it's like on the rise.

01:24:24
Speaker 2: Oh just wait, Aaron, just okay, wait.

01:24:27
Speaker 1: I'm very interested, Okay. And then budget cuts in the nineteen seventies eliminated the medical entomology research program at Rocky Mountain lab And I don't know if it's if it's back up or not. I should have checked that, But and the tick collection was shipped to the Smithsonian.

01:24:47
Speaker 2: Huh.

01:24:48
Speaker 1: Work on Ricketsie continued, and Rocky Mountain.

01:24:51
Speaker 2: Laboratories is still a hugely.

01:24:55
Speaker 1: Important side of research in general, as we mentioned, and a few more pieces of the spotted fever puzzle fell into place during this time. For instance, the recent resurgence in cases in the nineteen seventies was traced to the encroachment of humans into previously wooded areas allah lime disease surprise, surprise, and most interestingly, the long standing mystery of why the east side of the Bitterroot River remained protected from the west side was solved okay by Willie Burgdorfer Burgdorfer.

01:25:35
Speaker 2: Of our lime disease episode. Yet Okay, we don't know.

01:25:42
Speaker 1: So I'm so excited that I get to tell you this.

01:25:45
Speaker 2: Oh I'm so excited too, because I really was expecting this story to go And then they built a lab and then released infected ticks and now they're everywhere, Like that's one hundred percent what I expected.

01:25:55
Speaker 1: So that's not what happened. And here's why. So he discovered that on the east side of the river. He was doing a bunch of, you know, microbiology essays of these ticks, and he discovered that they were infected with Ricketsia, but it was a non pathogenic one, and the Ricketsia in those ticks prevented Racketzia ricketsii, the pathogenic one from colonizing the ticks interference phenomenon.

01:26:27
Speaker 2: Okay, oh my god, I'm getting like chills. I know, I know.

01:26:35
Speaker 1: So researchers had long made the observation that animals freely passed from the east side to the west side of the river. Animals were found on both sides. Like it didn't make sense, right, So if a tick that is infected with this non pathogenic Ricketsia bites an animal that is infected with spotted fever Racketzia Ricketsia I, that spotted fever can't establish in that tick, right because the other bacteria is just already there and so and this bacteria also has better transoviial transmission, so it will not hurt the tick as it's passed from female tick to eggs. This is so interesting, Aaron tick biology is so amazing.

01:27:22
Speaker 2: It really is very so amazing. That is so bizarre.

01:27:26
Speaker 1: So, this this interference phenomenon people have like it's been discussed, this type of thing, We've talked about it with Wolbacchia, and like, yeah, maybe we haven't, but like we've referenced it at least or alluded to it in terms of like finding the certain microbes that can prevent pathogenic ones from establishing in a vector.

01:27:45
Speaker 2: We talked about it with then gay fever.

01:27:48
Speaker 1: Oh yeah, yeah, so anyway, Burgdorf, Yeah, So, even though Rocky Mountain spotted fever has been heavily studied for over one hundred years, there's still a lot that we don't know about it, m M, particularly when it comes to the disease, reservoirs, strain differences, geographic differences, climate change, like the list goes on and on and on, seasonality. Fortunately for researchers now it's a lot safer than it used to be to study.

01:28:19
Speaker 2: And I repeat again, I hope, hope, hope.

01:28:23
Speaker 1: I haven't discouraged anyone from visiting the Bitterroot Valley because you definitely should do so. It's gorgeous, it's amazing and anyway, and you could go see Rocky Mountain Labs and you could go see the infamous, the famous, the amazing Rocky Mountain Labs. Okay, well erin, tell me what's going on with Rocky Mountain spotted fever today.

01:28:50
Speaker 2: Oh oh, I'm really thrilled too. After that history, we'll take one quick break first. I'm going to start off not where I expected to start off. Because I want to ask you questions. Erin, Okay, Okay, I want to start off with vaccine. We don't have one, Erin, No, there is none.

01:29:49
Speaker 1: The one that they had developed, the Parker Spencer vaccine that was used, I don't know how, like it's not been used for several decades now, Yeah, and I I think ultimately it caused some side effects and possibly infection in some.

01:30:06
Speaker 2: People, if that makes sense. If they were just grinding up ticks, then that would that would be Yeah.

01:30:11
Speaker 1: It seems like Riquetsier in general are a tricky bunch to make vaccines for.

01:30:17
Speaker 2: Yeah, I don't I don't know, I don't know, but we don't have a vaccine honestly, from what it sounds like, and I'm I'm sure that this is the case, it's largely just because of a lack of funding and a lack of interest, not just from like a research standpoint, but from a pharmaceutical standpoint. There are not enough cases essentially per year to produce a vaccine. It's not like financially viable, for better or for worse. It is true that patients who survive infection do mount a very good and long lasting immune response and We've also identified a number of the surface protein an egen, so it's certainly theoretically possible to develop a vaccine. But when you you know, I usually use Google scholar that's my preferred search website for finding my papers. And when you search Rocking Mountain spot of Fever vaccine, you the first entire page of results. There is not a single paper from past nineteen ninety on that page. So yep, and some of them are from nineteen twenty five. They're probably some of the ones referenced in your book. Oh my gosh's Parker sponsor, right, But that doesn't mean that no one's doing research on it. I did find a recent paper that was looking at and did develop an effective wholesale vaccine that they tested in dogs. I will link to it, but like, I wouldn't read that paper again. It was very depressing. They killed a lot of dogs. Oh my god. Yeah, but they made a vaccine. So anyways, that's the current research. Let's talk about the epidemiology. Okay, yes, all right, So in the United States, Rocky Mountain spotted fever has been a nationally notifiable disease since the nineteen twenties. Since twenty ten, they've been calling it a different name and therefore reporting it a little bit differently. It's now reported as spotted fever ricketziosis. And the reason is we don't have a good way to differentiate the clinical syndrome that is caused by Ricketzia RICKETSII from the clinical syndromes that are caused by a number of other Ricketzial pathogens, including Ricketzia, Parker eye, which we briefly said those words earlier, ricketzial pox, and a few others. So kind of that's the background I think to keep in mind as I'm going to talk about these numbers, because this gets really interesting, Okay, Okay, so let's talk about you said that cases were increasing, you know, through the late nineteen nineties or through the late nineteen hundreds right after that drop off. Well, if you look at the graphs of cases since the year two thousand, it's terrifying. It is. It's an exponential growth curve, which everyone is now very familiar with. We've all seen a lot of those these days. Okay, The number of cases has increased steadily just about every year. Twenty eighteen was a little better than twenty seventeen, but in twenty seventeen, there were over six thousand cases reported, and that's up from five under five hundred in the year two thousand.

01:33:59
Speaker 1: What okay, that's like And I'm so embarrassed because this is literally what I did my PhD on.

01:34:06
Speaker 2: Yeah, you did it in Panama. Okay, it's fine, Okay, you didn't need to know these numbers. So, but here's the question. We're seeing these huge increases in cases. How many of these are the very deadly Rocky Mountain spotted fever versus other ricketzia and it's really hard to say, And also how much of it is Are we getting better at recognizing it, are we getting better at reporting it? Or are there an increase in infections? I think this is me thinking, but also like based on what I read, uh, it's likely a combination of both as usual. But the increase is so large over such a short period of time, Like we're talking twenty years, right from two thousand you have under five hundred cases to over six thousand in seventeen years. That's massive. And this is a disease that's been notifiable since the nineteen twenties, and our diagnostic tools are not much better today than they were twenty years ago. Okay, the case fatality rate has drastically dramatically decreased since the nineteen forties, since the introduction of tetracyclines for treatment. So in clinical reviews like worldwide, even after tetracyclines were introduced for treatment, case fatality rates still usually are about five to ten percent, usually around five percent. But the current case fatality rate in the US, according to surveillance data, is as low as zero point five percent. What that's excellent. It is excellent, but it bears the question, is this rocky mountain spotted fever or is this something else? So let's look in other parts of the world, what's going on there? Well, turns out that's hard to do. There's not very good surveillance data for much of the rest of the world. But I did find some really good data for Mexico. So in Mexico throughout the two thousands, the incidence of disease has also been increasing, also dramatically. I don't have an exact number. However, unlike in the US, the case fatality rate has also been increasing rather than decreasing. Really, the aggregate case fatality rate has been between fourteen to eighteen percent depending on the region of Mexico, but in some years the case fatality rate has been as high as forty percent. Ooh, so then I think, you know, there's a lot of questions as to what is this. Does this mean that we're looking at different diseases or does it just mean that we're looking at drastic differences in lack of availability of good diagnostic tests, delays in reaching a doctor to get diagnosis or to get treatment. Another issue is that a large proportion of cases, not just in Mexico, but in Mexico and also in the US, are in children, because kids are running around outside getting bitten by ticks, and usually tetracyclines aren't used as treatment for children because it can permanently damage and discolor your teeth. So a lot of physicians might be hesitant to prescribe doxycycling for kids. But it turns out that for Rocky Mountain spotted fever, it's a short enough course that it doesn't actually increase the risk of tooth discoloration. But maybe you don't know that, and so then a kid is delayed in getting the appropriate treatment or receives the wrong kind of treatment, and you have an increase in case fatality rate, but overall it's less than one percent of spotted fever group or keetsioses that are reported in the United States are actually lab confirmed.

01:38:16
Speaker 1: Okay, so it's all based on the trial.

01:38:21
Speaker 2: Yeah, exactly. Oh and the other triad piece is often a tick exposure. So some people say the triad is fever, rash, tick exposure, or history of tick exposures rather than the fever, headache, and rash. But not everyone reports tick exposure, right, and that doesn't mean that they weren't exposed, They just might never have known it. Mm hmm, comforting thought. Yeah, so that's spotted fever group, riquetsiosis, Rocky Mountain, spotted fever. Today. We never told Brett's.

01:39:06
Speaker 1: Story, Okay, okay, now we need to tell Brett's story. Cast your mind back to twenty thirteen, twenty thirteen, twenty.

01:39:16
Speaker 2: Fourteen, twenty fourteen, the summer, the summer of twenty fourteen. Okay, listen, the rainy season in Panama everyone, June. As we mentioned, Aaron Welsh did her research on tickborn disease in Panama. That was what her thesis was on. Our lab is a disease ecology lab. We studied tick and other vector borne diseases.

01:39:46
Speaker 1: Okay, my focus in particular, well, my focus was the general ecology of tics and their pathogens as it related to the climate gradient across the isthmus and seasonality and different animals and blah blah blah. But you know, in all the research proposals I ever wrote during my PhD, I always mentioned rakhetzi RACKETSI I, of course, because it is present there and it is a cause for concern to So you want to understand where they are, what the ticks are, and you want to increase awareness of a tick bite and a rash, a fever and.

01:40:30
Speaker 2: A possible headache. So June of twenty fourteen, Brett, my now husband, and I flew back from Panama after my first field season down there, to California to stay with family for a short time. And on the plane ride back, he started feeling crappy. Okay, he did. He felt unwell. We made it back to my brother's house and I believe he had a fever, but I'm sure we didn't have a thermometer. But he felt he felt sick, like he just really didn't feel good. And I was like, gosh, like I hope you didn't come down with something, you know. But he had no respiratory symptoms. He wasn't coughing, he didn't have you know, like sore throat, any of the normal kind of things I would associate with flu or a cold. He just felt achy, he felt unwell. He had a headache, a fever. And this lasted for a couple of days, and then he went to the bathroom. Is he gonna be? Did you tell him that you were going to tell this? Yes, I told him. He goes, I knew as soon as you said you were doing rocking Mountain spotted fever. He's like, I've been waiting for this for three years. Finally here. So then he came out of the bathroom room and he said, I just I pulled something. I pulled something off of my my the top of my butt crack. And I said what and he was like yeah, it was like there was a bunch of blood and some black stuff. And I said what. And then I grabbed his arms and on his wrists was a rash, a red, blanching, macular rash that did not hurt and did not itch. And oh, he also had one on his legs that he hadn't even fully noticed up to the blood. Okay, And then he said, I pulled this thing off the top of my butt. It was I. I saw it. I squished it. There was blood and then black things, and I went and I threw it in the toilet and I flushed, and I said, you just flush a tick. You have a ricketsia. You need to first of all, go to the doctor. And second of all, I can't believe that you threw the tick in the toilet. I was devastated. Oh, we all were. Our whole lab knows this story. He's also probably going to be like, you told it entirely incorrectly, but I didn't. This is how it happened.

01:43:26
Speaker 1: Yeah, this is the This is the myth as I know it now. At this point, it's legendary status.

01:43:31
Speaker 2: It was classic. I mean, as soon as like and I can't I will say, I can't remember if he if he had the rash before he pulled a tick off, or if if I didn't see the rash until after he told me about pulling the tick off. But as soon as he told me about that, I looked and he had this rash, and I was like, I knew that it was. I was like, this is either racketzia rakhetsi I and you're going to die, or it's a lesser one, but either way, you need to go get treatment. And he wouldn't listen to me until we went to go visit his parents, and I had to tell his mother and she's the one who forced him to go to the doctor and get treatment because he wouldn't listen to me. So thank you, Chris, because otherwise he might be dead. So you went to the doctor and he said that the doctor like he told the doctor that he thought he had rocommend and spot if you've readen, this is why. And then apparently the doctor like went and took his phone and then came back in with his phone and was like, well, we could do a test, but I think I should just give you some antibiotics. And Brett was like yep, and he was better in a couple of days.

01:44:40
Speaker 1: Oh well, I am very glad that Brett was better.

01:44:45
Speaker 2: I'm still I'm still puzzling.

01:44:47
Speaker 1: Over where you picked it up because you had.

01:44:49
Speaker 2: Just been it' scuba diving or something. We had been at Koiba, so it could have been Koiba because we had hiked around that a little bit, but also could have just been in Gamboa because we went up to the ridge or whatever. And well, yeah, we'll never know because he threw the tick in the toilet. Even yesterday when I told him we were gonna tell this story on the podcast, he was like, I should have just thrown it in the trash.

01:45:15
Speaker 1: I know, I know, Brett, like you had killed it dead and good like, oh, it could have been like.

01:45:26
Speaker 2: My entire dissertation right there, right like, at least that's a case report. We could have been co authors, Aarin, we could still be co authors on a paper. Yeah, whip my no, okay, don't jump, Brian. So that's that's our story. That's our story, you know.

01:45:50
Speaker 1: Erin this I feel like it lived up to my expectations, my hype for this episode. I had a great time me too. I feel like it was back to our roots in a way.

01:46:03
Speaker 2: Yes, it really did. It felt good. It felt good.

01:46:06
Speaker 1: I was a little bit afraid to do something that was like very close to my PhD, and then I realized it doesn't have anything to do with my PhD.

01:46:16
Speaker 2: Well sources sources.

01:46:18
Speaker 1: Yes, I mostly used a book called Rocky Mountain Spotted fever History of a twentieth century disease by Victoria Harden, which told the complete story.

01:46:31
Speaker 2: It was great. And then a couple of papers and.

01:46:36
Speaker 1: I will include those on our references page on our website.

01:46:40
Speaker 2: I read through a number of fun papers about the biology and a few good ones on the epidemiology. We'll post all of our sources on our website. This podcast will kill You dot com. Under the episodes tab, you can find all of our sources for this and every single one of our episodes.

01:46:59
Speaker 1: Yeah yeah, thank you to Bloodmobile for providing the music for this episode and all of our episodes.

01:47:07
Speaker 2: And thank you everyone for listening. Yes, thank you.

01:47:11
Speaker 1: We hope that you enjoyed this one as much as we enjoyed talking about it.

01:47:16
Speaker 2: We really enjoyed this one, so we hope that you guys did too, So well with that, until next time, wash your hands. You filled the animals