Ep 35 Lyme Disease: I'd like to check you for ticks

00:00:01
Speaker 1: My name is Brian Allen. I'm an associate professor in the Department of Entomology at the University of Illinois, and I studied the ecology of ticks and tick born diseases. And I got into this line of work as a result of my first experience with lime disease, which was both my first research experience with lime disease but also my first experience with contracting lime disease. So I was fortunate the summer after my senior year of college to get a research internship at the Kerry Institute of Ecosystem Studies in Upstate New York, and I was funded to study the ecology of lime disease. This was the summer of two thousand, so I had this summer internship and a lot of what it involved was traveling to different lime disease hotspots and collecting ticks in those locations, and so, of course, in the course of that work, I was pretty diligent about protecting myself against tick bites, but the infection rate in ticks in that area is incredibly high, and so that point in the summer, at least one tich got through my defenses and I came down with lime disease, and so that was my first brush with the illness as well as with studying the biology of the disease. I don't believe I ever found the one that got me. So I just came down with the symptoms. I mean I was typically, you know, despite wearing protective clothing, I was typically removing at least one tick per day, and so for the most part, I was probably removing those ticks before I could be exposed to the lime pathogen. But yeah, I just came down with the lime symptoms, and it came on like a freight train. So I first woke up feeling the arthritic pain in my joints and a little bit of a fever. And I, you know, I'd been spending the summer studying lime disease, so I was really quite confident in my self diagnosis, and so I went straight to a physician. And in that part of the US, the second you report symptoms in the summertime that even you know remotely approximate line disease, they treat you with antibiotics. And so I was feeling better within twenty four hours. I mean, I got better quite quickly, and then I eventually got the bulls eye rash, but it was about a week later. I was already well recovered at that point, back out doing fieldwork collecting more ticks. So in that lab I was unfortunately the only person to get lime disease that summer. There were probably about twenty or twenty five students, and you know that this was a research group working on lime disease, and so one of the you know, the mantra of the research group was don't get lime disease, right like, everybody was supposed to take these preventative measures really seriously, and so I felt, well, it was disappointing that I was the one person who got lime disease that summer. And then of course everybody wanted to see the bulls ie rash. And so you know, for that week that that rash was on the back of my knee. I couldn't get down the hall without you know, somebody asking to stop and look at it, which was just this constant reminder that I had failed to prevent myself from getting line disease while collecting ticks. And I haven't had any tick bore disease since, so I've I've been bitten by hundreds, if not thousands of ticks since then, But I'm really it made me all that much more cautious about during the course of doing field work on ticks, I'll check myself multiple times a day, don't just trust in my clothing and repellents to get the job done, because tik checks really are the best strategy for preventing tickborn disease.

00:03:23
Speaker 2: Hi, I'm erin Welsh and I'm erin olman Updyke And this is this podcast will kill You And it's.

00:03:53
Speaker 3: Our final episode of the season.

00:03:58
Speaker 4: It is and you know what, guys, it's gonna be.

00:04:01
Speaker 3: Okay, Well, we'll all get through this time.

00:04:04
Speaker 4: Yeah, we're gonna miss as much as you do. It's true, Actually, yeah, it really is. It really is. So we have to take a break though, because there are a number of really important and cool and exciting things happening. Aaron, what's going on? What's gone on with you? So with me?

00:04:27
Speaker 3: What's going on? Is I Well, by the time this episode comes out, I will have birthed a baby human.

00:04:35
Speaker 4: A baby human, A baby human.

00:04:41
Speaker 3: Yeah, So I'll be doing that during our break until we come back for season three. It trying to keep that baby human alive outside of my body.

00:04:51
Speaker 4: It's a new challenge. Well, you'll be doing Aaron. I will be moving across the Atlantic. Actually, within a couple of weeks after this episode airs, I will be moving all of the stuff that I brought with me over to Europe back to the US, which means will be in the same place recording for once.

00:05:14
Speaker 3: I am so thrilled. I can't even express my emotions.

00:05:18
Speaker 4: Me too. And it's not going to be a long wait until season three starts. It's only the until the end of October. And don't worry. We've got plenty of stuff that we're working on during our break yep, including crossover episodes including we're working on merch. Yeah, we are more merged. I know that you all have requested different T shirts and stuff like that, and guess what we want to bring them to you.

00:05:45
Speaker 3: Yeah, we do, so we're working on that. So make sure if you don't already, to follow us on Twitter at TPWKY and or on Instagram and Facebook at this podcast will kill you so that you stay up to date with what we're doing in the meantime, and make sure you click that subscribe button so that when we come back for season three at the end of October, you won't miss a single episode.

00:06:11
Speaker 4: So this week, as you may have guessed, we are talking about the much requested, much requested lime bereliosis lime disease.

00:06:25
Speaker 3: Everybody, we've gotten more requests for this than I think any other disease.

00:06:31
Speaker 4: Yeah, I think so too. And you just heard from our incredible, wonderful, supportive.

00:06:41
Speaker 3: Kind fantastic tall That was weird.

00:06:45
Speaker 4: Very tall. He is very tall though, Yes, advisor PhD advisor doctor Brian Allen.

00:06:55
Speaker 3: The one and only, folks, the one and only. Hope you give him a round of applause wherever you're listening to this, because we've mentioned him before, we haven't ever had him on the pod. We're thrilled that he is here to give us not only our first stand account, but also some insight into the current research on the ecology of lyme disease later in this episode.

00:07:15
Speaker 4: Yes, Brian, thanks for coming on. And also, so many people during their PhDs one of the sources of stress or complaint or frustration is their advisors and that conflict between student and advisor, and it was that was never the case with Brian, and it's just like, it's amazing how much that paved the way for a as pleasant as could be PhD experience. Brian, you're the best. Anyone who wants to work on disease ecology please yeah, contact me, Brian Allen.

00:07:53
Speaker 3: Mean, he's so the best that he let two of his grad students start a podcast during the last year of their PhDs. That's pretty I mean, I feel like that speaks for itself.

00:08:04
Speaker 4: I mean, to be fair, he called it a blog for like four months.

00:08:09
Speaker 3: Still not sure that he'll ever listen to this.

00:08:11
Speaker 4: I don't know if he knows he will he will.

00:08:17
Speaker 3: Oh anyways, Okay.

00:08:20
Speaker 4: On to more important things, the most important things in fact. Quarantiny time.

00:08:25
Speaker 3: It's quarantiny time. What are we drinking this week?

00:08:28
Speaker 4: Aaron? We are drinking the dilution Effect.

00:08:34
Speaker 3: This is such a good name for this drink. You'll just have to wait until the history section to find out why. Yep, it's a really great name. I'm pretty I'm pretty strict about it. What is in the dilution effect?

00:08:50
Speaker 4: The dilution effect?

00:08:51
Speaker 3: It's essentially a lime Ricky, which was our first name.

00:08:55
Speaker 4: Yeah, for this quarantine.

00:08:57
Speaker 3: Which is also a great name. It's also a great name. This is gin lime juice. Sugar, chunks of lime and club sodas sat forward and of course.

00:09:11
Speaker 4: This beautiful plump cherry pop that sucker in there so that it's like a fully engorged tick full of blare just waiting to be popped.

00:09:22
Speaker 3: Your blood just gooing out of it. Yeah, it's lovely. It's a very delicious drink. And we will post the recipe for that quarantine along with our non alcoholic place burrita on all of our social media channels as well as our website. This podcast will kill you dot com. All right, that's fun.

00:09:40
Speaker 4: All Right, we're there, We're in the mood. We're in the mood. Start this.

00:09:44
Speaker 3: Let's get into the biology of lime disease, shall we?

00:09:50
Speaker 4: I think we shall? Okay, do we need a break? We'll take a quick break.

00:10:24
Speaker 3: So lime disease is a bit of a doozy. Yes, this is the longest pages of notes I've ever.

00:10:32
Speaker 4: Had, so, oh my god. Really yeah, longer than vaccines.

00:10:37
Speaker 3: Maybe not longer than vaccines, but that was two episodes, so it doesn't really count. Okay, okay, So lime disease people have been requesting this for a very long time, and it's probably because this is something that many of our listeners or their friends may have had in the past. If you live in the US, or in Europe, or in Canada, or even in parts of Asia, which I didn't realize that lime disease was quite so widespread.

00:11:07
Speaker 4: It's global, baby, global disease.

00:11:10
Speaker 3: Lime disease is the most common tickborn disease diagnosed in both the US and Europe, and I'm pretty sure in Canada as well, and the most common vector born disease in the United States.

00:11:23
Speaker 4: Yes, so it's a big one.

00:11:26
Speaker 3: I also can't kind of believe that this is the first time that we've ever covered a tickborn disease on this podcast.

00:11:34
Speaker 4: Yeah, I have noticed that, and I think it's surprising and not surprising at the same time. And it also won't be the last one that.

00:11:43
Speaker 3: We cover, definitely not. There's a lot of really really interesting tickborn diseases out there, So get excited. Okay, I'm not going to talk about the life cycle or the ecology of ticks, because you're going to do.

00:11:57
Speaker 4: That, am I right erin, I'm gonna attempt that.

00:12:00
Speaker 3: You're going to do a great job. So we'll just jump right in to when humans get infected essentially, So lime disease is a disease that's caused by bacteria, specifically little spier keet bacteria, which means they're adorable, little corkscrew shaped little creatures, which also makes them very hard to find because they're very thin and spindily, so when you try and stain for them the way that we stain for other bacteria, they're really difficult to find on stains. And I'm saying bacteria plural on purpose because we're not just talking about a single species. This disease is very much more complicated than that. Most commonly, lime disease is caused by the bacterium Burrelia borgdorferi in the US and in Canada as well as in Europe. However, in Europe, lime can also be caused by two others species of Burrellia Burrellia aphizellii and Burrellia gerinii.

00:13:05
Speaker 4: Am I saying those right? I always hear a F.

00:13:08
Speaker 3: Celli, but cell yeah's and also right yeah.

00:13:13
Speaker 4: There are a couple other ones that are newly discovered as well, but it's sort of just let's just call it the Burrellia group in Europe and the Brellia group in North America. The Brellia group in Asia.

00:13:24
Speaker 3: Yes, there's many other species as well. So on top of that, they're transmitted by multiple different tick species across their range.

00:13:34
Speaker 4: So we've got.

00:13:35
Speaker 3: Multiple tick species, multiple bacterial species, one multifaceted disease.

00:13:43
Speaker 4: Oh okay, it's I mean, yeah, yeah, all right, complicated.

00:13:52
Speaker 3: So how do humans get infected? That's the first question we have to answer. So when you encounter an infected and it bites you, it's not like a mosquito. It doesn't just feed on you for like ten seconds and barfet's whole salivary glands into you right away. Ticks take their time, they burrow their face into you, and after some time of being attached, they will then start spitting the contents of their salivary glands into you and transmitting the disease. So that's how you get infected. You get bit by a tick. It stays on for long enough to spit its contents into you, and now these little spier keats are free underneath your skin.

00:14:38
Speaker 4: Did you know though, that lime disease? So like Burrellia, the tick needs to be attached for a lot longer than for something like tick born encephalitis, which is just instantaneous. Yeah, it's like deeper.

00:14:52
Speaker 3: Is it just like it's deeper in their salivary glands or something it takes them longer to get it up and out or what.

00:14:58
Speaker 4: I don't know. I think maybe it's something like that. Maybe it's something about the feeding process itself or where exactly. Yeah, I don't know.

00:15:09
Speaker 3: Yeah, but in general, they have to be attached for at least like twenty four to thirty six hours before you're at risk of getting infected with lime disease, which.

00:15:17
Speaker 4: Is tickchecks are important. Tic checks.

00:15:19
Speaker 3: Check your bod and your friend's bod for tics.

00:15:23
Speaker 4: There are several country songs about this.

00:15:28
Speaker 3: Should we get permission to play one.

00:15:30
Speaker 4: I'd like to check you for ticks, which is played bood. There we go.

00:15:37
Speaker 3: Okay, so now you're infected. You have little spirakeet bacteria underneath your skin, spiraling their way through your skin tissue, maybe making their way into your bloodstream. And here's where we run into our first set of complications when it comes to lime disease. We don't have a really great handle on what burrellia does once it's in your b or exactly where it goes, which can make it difficult if you're trying to find the actual bacterium in someone's bloodstream, for example, which is how we usually test for infections. Right We take your blood and we look for stuff in it, or we take some of the bodily fluid and we look for bacteria in it. Burellia are kind of hard to find, and we don't know exactly where they go. What we do know is that as they're making their way through your body, they stimulate a massive immune response on your part, So your body knows that these spira keets are there and really starts attacking them. So what that means is that most of the symptoms that we'll talk about are not caused by the bacterium directly, but by your immune system's response to the bacterium. Cool, right, right, Well, okay, so that's the easy part. Now we'll move in to the hearder part, lime disease. We can't get that far into this episode without talking about the fact that there's a lot of controversy.

00:17:09
Speaker 4: I guess you'd call it.

00:17:11
Speaker 3: Around lime disease. There's a lot of misconceptions and a lot of miscommunications and a lot of angry yelling when it comes to lime disease. And this has led to a lot of mistrust between the medical community and patient advocacy groups and a lot of people not feeling very heard or seen by physicians. So, while full disclaimer, we don't have all of the answers when it comes to lime disease, there are still some gray areas, there is a lot that we do know. So while this is a complex disease, what we're going to do for you is try and break down the scientific data that we have as it currently stands. So what I want to do is first talk about the symptoms and how we diagnose and treat lime, and then I'll try and address some of the specific conceptions and controversies surrounding lime disease.

00:18:05
Speaker 4: Does that sound good? Yeah, sounds great, Okay.

00:18:09
Speaker 3: So the first thing to know about lime is that there are actually three different stages of lime disease, early localized, early disseminated, and late lime disease. Those are the three main stages. As you can imagine, Early localized lime starts the earliest after exposure, and it's characterized by a very very specific type of rash called erythema. Migrands em em baby em means rithema means redness and migrands like is to migrate.

00:18:48
Speaker 4: So this is a red rash.

00:18:50
Speaker 3: It's not itchy, it's not usually painful at all. It's usually round, or at least round ish, and often it has an area of what they call central clearing, so there's a part towards the middle that's less red than the edges, which are more red. And then sometimes right in the center you'll get some serious inflammation or necrosis, even where the tissue starts to die right in the middle. Yeah, this is what we call the bulls eye rash. It really doesn't look like an actual bullseye all that often, but it is a very distinctive rash, this sort of red margin and then it's more clear in the center. And it while it can be confused for something like cellulitis or something like that, in general this is not painful at all and so and it also slowly grows over time, which is why it's called arithema migrants.

00:19:50
Speaker 4: It's like it migrates.

00:19:53
Speaker 3: This rash doesn't have to happen where you got bit from the tick, so it's not like the tick bite is an the center of the rash or anything like that. It can happen anywhere on the body. Most often it happens in the armpits, the groin, or the back of the knee. Don't really, don't ask me why, well, hold.

00:20:12
Speaker 4: On, but armputs growing in the back of the knee, so at least in the armputs in the groin, there are lymph nodes.

00:20:18
Speaker 3: Back then too, there's tons of lymph nodes in the back.

00:20:21
Speaker 4: Really in the back of the knee. Yeah, I wonder if it has something to do with that.

00:20:24
Speaker 3: Yeah, it absolutely could. That's actually a really great that's actually probably has a lot.

00:20:30
Speaker 4: To do with it. Okay.

00:20:34
Speaker 3: So this early localized form of the disease begins within usually a few days of exposure, although it can take up to a month after exposure for this rash to first appear. And this rash, you could have only this rash, and that could be the only symptom that you have of lime disease, but very often you might have some other very non specific symptoms, things like a mild fever, nothing bonkers high or anything, just a low grade fever. Generalized weakness and muscle aches or thralgias or joint pain are pretty often associated with lime disease, And then things like headache, stiff neck, maybe you have some swelling of lymph nodes all around. What you don't see are things like respiratory symptoms or cough or anything like that. Okay, So two important things about EM, this rash specifically, it's estimated that eighty percent of patients actually have this rash.

00:21:44
Speaker 4: Wo percent higher than I thought.

00:21:47
Speaker 3: That's literally what I wrote. That is way higher than I thought.

00:21:50
Speaker 4: I was sixty percent. Yeah, it's it's.

00:21:53
Speaker 3: A more common And my guess is that this is eighty percent of people who are actually diagnosed with LIME. So it might be lower in people who end up not getting diagnosed or something like that. But it's estimated that that EM rash happens in eighty percent of patients. And EM doesn't happen in basically any other disease except for something called starry, which is Southern tick associated rash illness, the est name for an illness of all time, and I'm not going to talk about it. It's another beast entirely that we don't know a lot about, but it causes this same rash. It's transmitted by a different tick. It's in different geographic areas.

00:22:35
Speaker 4: Okay, which tick? Uh I'm mean amblyhem americandumar and I don't remember. I'm sorry.

00:22:46
Speaker 3: Maybe it's the Lone Star.

00:22:47
Speaker 4: Is that Amblyoma americanum?

00:22:50
Speaker 3: Yeah, yeah, I think it might be that one. It's in the South.

00:22:54
Speaker 4: Okay.

00:22:55
Speaker 3: So what that means is if you have if you come in to a doctor's office with this em rash, you've got lime done especially and hopefully this is true, you have some kind of way that you've potentially been exposed to ticks, even if you never found a tick on your body, right, Like, you've been outside in an area where ticks could potentially exist, right, Okay. But what's important is that at this stage, testing is often negative, and we'll talk more later about why that is. But at this point, if you see that rash, that's lime, and it can be treated as such. M h okay, that's early localized disease. Second stage is early disseminated lime disease, which is similar in that it's an early manifestation, usually again within a week to several months. But someone may or may not have ever had the specific symptoms of early localized disease. It's basically just you can think of it as like a little bit more severe down the scale of lime disease, where now in addition to potentially having multiple of these em rashes, early disseminated disease is characterized by like neurologic symptoms, so that means that the bacteria or the inflammation has reached your nervous system, especially things like meningitis are very common, which we've talked about before. That's inflammation of the lining of your nervous system that shows up with things like headache and stiff neck. You can get nerve palsies, which is nerve what's the word paralysis, especially like one of the kind of classic symptoms is bilateral facial nerve palsy, so bilateral bells palsy. Both of your facial nerves get paralyzed, essentially, but it can happen to any other nerves. It's not only your facial nerves, but it is really common to happen in cranial nerves, where you'll have cranial nerves that get paralyzed. You can also get nerve pain or end up with something even more serious like encephalomyelitis, which is inflammation of the brain and spinal cord both, so those are sort of more serious manifestations, and they're also more rare manifestations of lime.

00:25:34
Speaker 4: Okay.

00:25:35
Speaker 3: The other common presentation at this stage of lime disease, the early disseminated stage, is what's called lime carditis, which card as in cardio like your heart, means that there are heart manifestations. The most common is called heart block, which means that the conduction system of your heart is no longer working properly, so that then your heart can't beat properly, a pretty serious illness that can happen as a part of lime disease. You also can get myo pericarditis, which is inflammation of the muscle tissue itself, so not the conduction system, but the muscle tissue and the lining of your heart, the surrounding of your heart. So there's a lot of different ways that lime disease can affect and all of this is part of early disseminated lime disease.

00:26:29
Speaker 4: Cool. That's okay, super cool, well, super fast, terrible. Yeah. Are you gonna give me some numbers on what percentage of people this happens to that? It's a good question.

00:26:45
Speaker 3: I don't have exact numbers, Okay, yeah, I mean we'll talk about how many people get diagnosed. In general, I don't know what the breakdown generally is between how many people are diagnosed early localized versus early disseminated late, except to say that the vast majority of people are diagnosed at some point in the early stages, So whether it's early localized or early disseminated, And honestly, it's kind of a it's a little wishy washy the window between those, right, Like, it's really just if you have these serious nerve or heart manifestations, then we're going to call that disseminated, whereas if the symptoms are less severe, just like fever and joint pains, they'll probably call that early localized. And if you have multiple versus a single of the bullsye rash.

00:27:33
Speaker 4: And so how does this play into the actual microbiology of the bacterium itself? Like what is it doing inside your body? Where is it going? How is it actually causing these neurological symptoms. You're throwing your hands up there.

00:27:51
Speaker 3: My hands up in the air, because that's it's a great question. It's it's really unclear. And like I said, it's it seems as though many of the manifesting of lime are caused by inflammation, so our body's response to the spira keet. But we don't really know where the spira keet is going. I mean, obviously it's attacking our heart and it's attacking our nerves. How exactly it's doing that isn't entirely clear. There's a lot that we don't know about lime.

00:28:24
Speaker 4: Yeah, there really is. There really is. Yeah, there's a lot that we do know.

00:28:31
Speaker 3: But there's a lot that we do know, and we'll keep talking to tell you all those things. So generally, by the time that somebody presents with some of these more severe symptoms, that generally means that they have been infected long enough that their body has started to make antibodies against the bacterium. So that means that now we can actually test for lime disease. In the early localized stage, when you just have like just the bulls I rend and maybe a fever, you haven't started to make enough antibodies to be able to test for whether or not you're infected with lime. But by this stage you have, so now we can check your blood and find evidence of the fact that you've been exposed. Because, like I said before, since we don't know exactly where the spira keet is going, and it doesn't seem to. If it does hang out in your blood stream, it makes itself really hard to find. We don't have a lot of good tests to look for the bacterium itself. So the way that we tell that someone has been infected with the lime spira keet with Burrellia is that we look for antibodies against Burrellia.

00:29:47
Speaker 4: Okay, so that's the antibid test is the primary like a seropod yes, seropositive seer positive test be the only way pretty much.

00:29:58
Speaker 3: Yeah, there are some others, but they're not as good. And one thing I want to address, even though I said I was going to address misconceptions later, let's start with one right now. There's a lot of I think, misinformation about whether or not these zerological tests are reliable. And obviously, no tests that we have in all of medicine is one hundred percent perfect. I don't think there's a single one that's like one hundred percent sensitive and specific. Maybe there is, and someone's gonna yell at me for saying that, but a test that is has a really high sensitivity will accurately identify everyone with the disease. They won't miss a lot of people, so you end up with a lot less falsely negative people.

00:30:45
Speaker 4: Does that make sense.

00:30:46
Speaker 3: Yes, A highly specific test means that if you got a positive, it's definitely just that disease that you're testing for. So you end up with a lot less false positives with a highly specific test, but you might miss some positives with a highly specific test.

00:31:06
Speaker 4: Does that make sense. Yes, So you want a test to be highly sensitive over highly.

00:31:16
Speaker 3: Specific, potentially depending on this scenario. And in this scenario, yes, you'd probably want to test that's highly sensitive because that means that we're not going to be missing any cases of lime. Yeah, we might accidentally diagnose people with lime that actually don't have it, that are falsely positive, but we won't miss anyone and say, oh, don't worry, you don't have lime when they actually do right, with a highly sensitive test. So early on, in like an early localized stage of the disease, these tests, these serological tests are not very sensitive. They're may be like forty percent forty five percent sensitive. However, as the stages progress, so as time goes on, they are between ninety and ninety nine percent sensitive, and they're also pretty dang specific as well. So these are actually very good zerological tests. So what that means is if someone has been tested, especially after a certain period of time, and tests negative, it's very very very unlikely that they had lime disease.

00:32:33
Speaker 4: Does that make sense? Makes sense? All right?

00:32:37
Speaker 3: So glad we cleared up that first misconception. Okay, we have one more stage of lime disease, and that is late lime disease. So this is something that happens if someone who was exposed to lime disease was never treated, and it generally happens between a few months to even a few years after exposure, again if someone was never treated for lime. The most common feature of late lime disease is arthritis, especially in a few large joints, so not like all of your joints, but not just one, but a few large joints.

00:33:16
Speaker 4: But it also can.

00:33:17
Speaker 3: Present with encephalopathy, which means mental status changes, so something like mild memory loss or feeling fuzzy, not feeling like yourself. And what's scary about this one is it's usually really subtle.

00:33:31
Speaker 4: It's not like it's not like full on, like all of a sudden.

00:33:36
Speaker 3: You can't remember anything. It's just little brain shifts, which sounds just so insidious and yucky. Yeah, and you also could have poly neuropathy, so nerve pain. And then because we're talking about in some cases different species of Burellia in Europe, there's actually a few different manifestations of both the early disseminated and the late descent dominated that are more common in Europe, and a lot of them are sort of skin manifestations, so like weird blue blue colored lesions that slowly enlarge and that's vain, stay distended. Yeah, it's called acrodermatitis chronica atrophicans.

00:34:17
Speaker 4: That's very interesting and strange.

00:34:21
Speaker 3: Okay, so those skin manifestations are mostly due to Burellia Afzelli infection specifically, so late lime disease is actually the type that was first characterized, which is cool.

00:34:36
Speaker 4: I didn't know that.

00:34:38
Speaker 3: But these days it's fairly uncommon because most people have some kind of early symptoms and are able to be diagnosed and treated. But if somebody never was like maybe they just had a rash and very mild symptoms and never notice the rash because it was in a weird spot, then it is possible that they could present for the very first time with simp of late lime disease. But this is diagnosed in exactly the same way as early disseminated, where we look for antibodies in your blood.

00:35:09
Speaker 4: Cool. Okay, okay, So how do we treat it? So question though active infection versus residual Let's talk abouation processes.

00:35:26
Speaker 3: It's a long convos so let's first talk about how we can treat it. Then we can talk about what might happen after we treat it.

00:35:32
Speaker 4: Okay.

00:35:33
Speaker 3: So, most people who present with signs and symptoms of early disease, whether early localized or disseminated, will need between ten and twenty one days of oral antibiotics. It's usually doxycycling, which is a pretty standard antibiotic. There are some others that people use as well, and so current recommendations are between ten and twenty one days for early disease.

00:35:57
Speaker 4: Now, if you have.

00:35:58
Speaker 3: Certain neurologic or cardiac or more complicated manifestations, that may require IVY antibiotics for up to a month or so, and the same is true for some people with arthritis or arthritic manifestations of line they might require longer courses or IVY antibiotics, and about ten percent of people in the US who present with severe joint symptoms don't seem to respond very well to that first round of antibiotics and may require a second round. There is not a ton of evidence so far for antibiotic resistance for burellia, but obviously antibiotic resistance is a huge issue in general, so that's a concern for every bacterial disease.

00:36:43
Speaker 4: Most people, if.

00:36:44
Speaker 3: They present with either early localized or early disseminated symptoms, will recover completely most of the time within twenty days, which is still a very long time. Twenty days to be sick and feeling missy like that's still a really long time, and in some cases it can actually take up to six months. So it's not that you're on antibiotics for six months, but it might take you up to six months or more to be before you're actually feeling all.

00:37:13
Speaker 4: The way better.

00:37:16
Speaker 3: Yeah, yeah, which is miserable, especially with some of these symptoms like joint pain, muscle pain, fatigue like this can make it really difficult to function like a human, you know, in the society.

00:37:26
Speaker 4: That we currently live in. Yeah.

00:37:29
Speaker 3: Now, several studies have shown in addition to this that even though most people recover completely. Between eleven to fifteen percent of people who are treated for lime will report persistent symptoms so lasting longer than six months. Symptoms like fatigue, myalgia, so muscle pain, and difficulties with concentration and memory. So it makes sense. It's a logical jump to think that, Hey, I got sick with lime and I felt like crap, and I got treated with antibiotics, but I'm still miserable. That must mean I need more treatment, right, the antibiotics didn't work.

00:38:10
Speaker 4: But this is where lime.

00:38:12
Speaker 3: Gets a little tricky. For some people. These persistent symptoms after treatment for lime disease have led to a diagnosis of chronic lime disease. This is a really controversial term and it's not one that currently has a definition in the medical community. It's not a recognized disease in the medical community. This is in part because the notion of a chronic lime disease implies a chronic or prolonged infection with Burellia burgdorferi, the spirokeet bacterium that causes lime.

00:38:48
Speaker 4: Right.

00:38:49
Speaker 3: However, there is no good evidence in people with these persistent symptoms of persistent infection with the lime bacterium right. Okay. So while there have been a few animal models that suggest that small amounts of the spirokeet might persist in certain tissues, these studies don't translate well to human disease for a couple of reasons. One, this is, as you'll hear later, a wildlife disease. So it's very reasonable to think when we're studying it in rodents that the spirokeet might behave very differently than it does in.

00:39:25
Speaker 4: Humans, particularly in its reservoir hosts.

00:39:29
Speaker 3: Exactly, which are small rodents that are very commonly used for animal testing. Additionally, a lot of the persistent symptoms, most of the persistent symptoms that we see are subjective. They are things like arthritis and fatigue. Animals can't tell you if they're feeling those feelings the way that humans can, so it's really difficult to even understand how that might translate from an animal model to a human. However, in study of humans with persistent symptoms after treatment for lime disease, there is no good evidence of chronic infection with Burrellia, so they've tested for trying to find the actual bacterium in various tissues blood, skin, tissue, joint aspirits, especially, so like, if you're having joint pain and it's caused by a bacterial infection, you would expect to find bacterial in the joint fluid, and there's no good evidence that after treatment you still find those bacteria.

00:40:34
Speaker 4: So like they've tried to culture it and nothing has happened.

00:40:36
Speaker 3: Yes, yeah, exactly, which means that chronic or long term antibiotic use is not beneficial for people suffering from these symptoms. There have been multiple studies which have shown no benefit of long term antibiotic use compared to a placebo, and in some cases they have shown more harm than good can come from long term antibiotic use because antibiotics are not without their own risks, like what like antibiotic resistance, clearing out your own microbiome right, disrupting your natural gut flora and things which can lead to secondary infections. And then antibiotics also have a number of nonspecific effects, so they can be bad for your liver, they can be bad for other organs. They're not overall drugs that you want to take unless you really have to. But the problem is people are still suffering, and in some cases they might have been through a lot of testing and different drugs and who knows what else to try and get relief for their symptoms. And honestly, there's likely no shortage of doctors who are crappy listeners and just ignore or downplay or don't take seriously these kind of subjective complaints. And I think that's in large part where so much of the frustration between people's suffer from these symptoms and the medical community has come from it's not feeling heard. So the question then, is what is actually causing these symptoms in people who have evidence of having had line disease and were treated but are still miserable. There is some evidence that these symptoms may be caused by autoimmune or inflammatory type reactions, much in the way that rheumatic heart disease can be a manifestation following an infection with a bacteria called Strep piogenes, or the way people can get geon Beret syndrome after an infection with Camplobacter.

00:42:38
Speaker 4: Right, this is like a common theme in exact infections.

00:42:43
Speaker 3: Yeah, this isn't a phenomenon that's unique to Lime. To think that maybe what's happening here is some kind of autoimmune or inflammatory reaction after treatment for lime bacteria, and in fact, some people with these persistent symptoms, especially the joint type symptoms respond well to ensids, non steroidal anti inflammatories like eboprofin, or to joint injections with steroids, or in some cases to anti rheumatic treatments. These are things that we would normally give to someone with something like rheumatoid arthritis or lupus. This is evidence suggesting in favor of the idea that these post treatment line symptoms are indeed related to autoimmune or inflammatory disease, not persistent infection.

00:43:35
Speaker 4: And the issue too, is.

00:43:36
Speaker 3: That we don't have a good handle on what burellia is doing precisely inside of our bodies in the first place, and we definitely don't have a good handle on what anigens it might be that we potentially could be making antibodies against that then lead to this sort of autoimmune type flare up. So because we don't have a good handle on what's going on, that can be really frustrating because it means that we don't have very directed therapies.

00:44:06
Speaker 1: Right.

00:44:06
Speaker 3: It's just like try ibuprofency if that helps, kind of a thing, which.

00:44:10
Speaker 4: Is very unsatisfying.

00:44:12
Speaker 3: Yeah, There's also there's a few other issues at play here, and that is that so, for one thing, there are actually pretty high rates of co infection both in the ticks and then it can be passed on to humans. So there's co infection between burellia and other tickborn illnesses, many of which don't respond to the same antibiotics as lime. So anaplasma, which is one tickborn disease that can be co that a tick could be co infected with and could therefore co infect you with, that's treated with doxycycling. But babizia and tick born viruses, these things don't respond to the antibiotics that we use to treat lime. So it's also possible that somebody could be adequately treated for lime but have another underlying infection that is untreated.

00:45:01
Speaker 4: M Yeah.

00:45:03
Speaker 3: But the thing I do want to stress, in addition to what you said, Aaron, that it's not like these symptoms aren't real, and we know that post treatment symptoms can occur for a number of people. The thing that I do want to point out is that there also have been people treated for a lime with these lime type symptoms who don't have any evidence of a lime infection, and I think that those people sometimes get grouped into this chronic lime or.

00:45:37
Speaker 4: Post treatment lime.

00:45:39
Speaker 3: And like we talked about earlier in terms of diagnosing lime, while the tests that we have to diagnose lime are not perfect, they're actually pretty good as long as you're testing late in the course of disease.

00:45:51
Speaker 4: Hypothetically speaking, let's say that somebody was infected with Burrellia. Yes, they're going to test negative up unto a certain point.

00:46:04
Speaker 3: Yeah, until their body starts making antibodies against burelia. Right, then they will test negative on that zerological test. But after a week or two, if you test them again, they would be positive.

00:46:17
Speaker 4: And then for the rest of their lives would they test positive pretty much?

00:46:21
Speaker 3: Yeah, And so that is something that like you can't tell if the infection is necessarily an active infection versus you had it ten years ago or something like that. So if someone tested positive with symptoms and had never been treated for lime, they should be treated for lime, right. But if they test positive but they've been treated for lime, that's just residual antibodies. It doesn't mean they have an active infection, gotcha. Although there's some nuance to that because there are early antibodies, and then there are late antibodies. But you can tell if you got reinfected, for example. But that's a difference story.

00:47:01
Speaker 4: Because that's also possible that happened to Brian. Yeah it did.

00:47:07
Speaker 3: That's basically lime in a nutshell, A tickshell in a tickshell.

00:47:13
Speaker 4: Oh do you need a break? I think I need a break. I need a break. For many people, a walk in the park is no longer just a walk in the park. It feels like taking a gamble with your or your family's health on the line. Multi day treks, short hikes, picnics, gardening. All of these formerly unocuious activities are now or at least they should be accompanied by a full body screen for a tiny hitchhiking arthropod, a tick check, and if such a critter is found, panic mode might set in as you frantically search for tweezers to rip this invader from your flesh. At this point, if Google fails to give you satisfactory answers about the odds of you coming down with an infection, or if you are simply spurred into action by the horror inducing headlines that flash across your screen, you may schedule a doctor's appointment to confirm or assuage your fears. And that's if you spot the tick in the first place. For many people, if not most, the horror only comes afterwards, when your body starts to tell you something is wrong, and the source of this wrongness the even tinier hitchhiker hidden inside the tiny tick hitchhiker, burrelier brigdora forry.

00:48:54
Speaker 3: That makes it sound so cute.

00:48:56
Speaker 4: Well, I mean it is kind of cute. Ticks are cute. That's my opinion. That's your opinion. If you don't believe me, look up ambliomagema. It's a genuinely beautiful tick.

00:49:05
Speaker 3: Yes, it's beautiful in its coloration and stuff, but it doesn't It's not any less creepy and awful.

00:49:12
Speaker 4: No, And I will be the first to admit that as a person who has studied ticks for the last six or seven years. Okay, they are creepy and I don't like finding them on my body. This fear of lime, that, this paranoia that surrounds tick bite. These aren't deeply rooted things going back millennia. More of a like ew, get this thing off of me, maybe, but not sort of the instant panic and fear that I think now is a lot more prevalent. And that's because lime bureliosis is a recent emerging infectious disease, and it's now one of the most common vector born diseases worldwide, and it's one that has surged in prevalence in the decades since it was given its name. And so I'll go into some of the ideas as to how and why it seems to have spread so rapidly. But first, let's trace the lime back to its roots, as I usually do, our favorite thing always. While the fear of line berrelliosis only goes back a few decades, the disease itself and certainly the pathogen goes back a lot farther, goes back a lot further. Sorry, that was so dorky. Farther and further are.

00:50:27
Speaker 3: Very different things, I know, But I wouldn't I wouldn't have done it correctly.

00:50:35
Speaker 4: Oh God. The history of Burrellia burdor fray and lime burelliosis are separate chapters of the same story. So I'll start at the beginning, Okay, the first chapter. Pathogen. As you mentioned, lime burelliosis can be caused by a number of different species of Burrellia, and that depends on where in the world you are. It could be borgdor for I, Sensus stricto, Brelli afceelli, Brellia garinii, Burrellias spielmenii, and many others, with more being described all the time. And this diversity of Berrellia species causing infection in humans and the existence of multiple strains within a species point towards this being a very old group of bacteria, and that's supported by genomic research. So by comparing the Berrellia is found in infected people and infected ticks from all over the world and then overlaying that with the geographic location of the infection, researchers could point out not just how long the bacteria have been around, but also when they went from point A to point B, and just what those points A and B are. Awesome. So here's a general disclaimer that this is an area of active research, so conclusions aren't necessarily firm, and that's probably something I should just say for as a blanket statement for this entire section, but for sure, Yeah, but a few things do stand out in this research. So okay, so we have a bunch of Burrellia species that cause disease in humans, some of which are only found in North America and some of which are only found in Europe or Asia, and some that are found in both places. Those that are just found in Europe are likely of European origin, pretty simple, and those that are found in North America likely in North American origin. But what about Burrellia Burgdorfries census tricto, which is found in both places. There's not a super clear story here, but it seems moderately more likely that this species originated in Europe and then was introduced to North America several times. And how that happened is still a bit of a mystery, since humans are considered a dead end host for the disease, which means that it's extremely unlikely that an uninfected larvae will feed on a human infected with Burelia and then become infected itself and then able to reduce the disease into the ecosystem. So I don't think that I knew that. Yeah, they don't contribute to the disease cycle.

00:53:06
Speaker 3: Wow, Yeah, I mean that makes a lot of sense, But I never really thought about like it was something like West Nile. It's like, obviously humans are dead end. But with line, I never really thought about it. Great job disease ecologists.

00:53:21
Speaker 4: Yeah so, I mean, but that makes it more confusing because if you imagine the human migrations to North America, it's unlikely that that would be the source of infection there, right, So then maybe what about something like birds? But apparently there aren't very many bird species that migrate east to west, so it's more north to south generally speaking. And then maybe so maybe some seabirds could do the trick, but that really hasn't been fully investigated. Okay, so still some questions there. But that does seem to be multiple introductions from Europe to North America. But what's the timescale that talking about here? When is all of this taking place over thousands and thousands of years?

00:54:08
Speaker 1: What?

00:54:09
Speaker 2: Oh?

00:54:09
Speaker 4: Yeah? One study I read puts the most recent common ancestor of Berrellia Brigdworfry, at sixty thousand years ago. Whoa yeah, and other studies agree that the bacterium existed in North America in pre Columbian times. Wow. Okay, so it's gonna get really cool because I was very thrilled to read this what about any physical evidence of Berrellia Burgdworfry's ancientness?

00:54:36
Speaker 2: Yeah?

00:54:37
Speaker 4: Is that the word ancientness? For sure? That's the word. Okay, good, Well, here there are a couple of cool findings. Have you ever heard of the Tyrolean Iceman? No? Okay, yeah, I didn't either. He was found in nineteen ninety one in the Italian Alps and was estimated to be about fifty three hundred years old. Okay. He had brown eyes, type O, blood lactose intolerance, and an increased risk for coronary hype disease, and probably died a violent death judging from the arrowhead that was lodged into his shoulder. Okay. Oh, and also he probably had lime burellioses. Oh and also and also the researchers who analyzed his genome for all of those traits that I just listed also looked for bacteria and they found evidence for infection with brelli Or Burgdorfry fifty three hundred years before the cluster of juvenile rheumatoid arthritis cases in Lime, Connecticut.

00:55:41
Speaker 3: Wow.

00:55:42
Speaker 4: Okay, that's very cool. That's very cool.

00:55:45
Speaker 3: We haven't had a like a ice mummy or anything in a while on this show.

00:55:50
Speaker 4: Oh yeah, okay, what else? Researchers have also tested museum specimens of mice and ticks for evidence of Brellia infection, and in Germany, an Exodi's recinnas tick from eighteen eighty four tested positive for Burrellia, and several Exodias scapularis ticks from Long Island, New York, collected in the nineteen forties were also found to carry the bacterium cool. A couple of whitefooted mice from Massachusetts that died or were collected in eighteen ninety four also tested positive for Burrellia in Massachusetts. Okay, uh huh okay. So my goal for this chapter of the story, the pathogen chapter, was to show you that these bacterial species have been around and widespread multiple continents for millennia and so are likely to have cause disease in humans throughout that time. But, like I said, the story of Burrellia and the story of line burelliosis are two separate chapters in the same story. So when did humans first recognize burelliosis as a disease? Yeah, spoiler alert, it wasn't in Lime, Connecticut in the nineteen seventies. Ooh, it wasn't in the nineteen hundreds at all. Oh or in North America. What okay this is going? Yeah, okay, chapter two. The disease. The story of lime starts in Lime, Connecticut in the US in the nineteen seventies. Right, No, you just said it doesn't correct. That was my leading question. Glad you're paying attention. But that's the story that I'm guessing most people in North America are most familiar with. But it's really only part of the story, and it's definitely not the beginning. The disease that we know as lime disease was actually first described ninety two years before it was given that name.

00:57:44
Speaker 3: Whoa, So that's the eighteen hundreds, yes, way to go math.

00:57:48
Speaker 4: In the late eighteen hundreds, a German physician noticed that several people were presenting with a chronic skin disorder, and he named it, let's see acrodermatitis chronica trophecans. Yeah, we talked about that, we did, and his description didn't fade into obscurity. Throughout Europe, physicians were finding people that had this rash, and by the early nineteen tens, it was proposed that this rash was caused by a tick bite. Wow, this just goes way back. Yeah, that's amazing. Yeah. Okay, so the rash might be a pretty easy one to spot and then associate with a tick bite. But what about the neurological or arthritic symptoms? Those were also described long before lime disease had been coined as a name.

00:58:35
Speaker 3: Wow.

00:58:36
Speaker 4: In nineteen twenty two, two French neurologists published a case study of someone with berrellial infection of the central nervous system, and the link between the rash and the neurological symptoms was made in nineteen thirty, again by a German doctor. Right after World War Two, when antibiotics started to be widely used, a Swedish doctor named Arvid Afzelius, which sounds like a name from Harry Potter, right it does. Yeah, it also is as yeah as I could see your little light bulb turn on. Is where the posative agent of lime burelliosis in northern Europe got its name, Barellia afcelli. So Afcelius treated dozens of his patients that had the characteristic rash and followed up with them for two years and found that seventy percent had fully recovered once he treated them with antibiotics, yeah, with penicillin fabulous. Over the next few decades leading up to the discovery of the cluster of cases in Lime, Connecticut, researchers and physicians, most of them European, continued to work on getting the full picture of this disease. They had described its chronic rash and linked it to persistent neurological symptoms. They had concluded it was infectious, most likely bacterial because of how it responded to antibiotics, and they thought it was most likely tickborn. So the only thing missing was the best bacterial agent itself. So this is all had been done almost one hundred years before. Amazing. Yeah, yeah, okay, So let's head to Lime, Connecticut. In the nineteen seventies. In the small, affluent town of about two thousand people, neighbors began to talk. Something strange was happening to the kids of Lime. Several had been diagnosed with something called juvenile rheumatoire. I cannot say that quickly, juvenile juvenile rheumatoid arthritis. It's a tongue twister.

01:00:33
Speaker 3: It feels like me trying to say g aread yet just saying.

01:00:37
Speaker 4: Yeah, there we go. Oh, how the turntables. Yes. So, Juvenile rheumatoid arthritis is an autoimmune condition where your joints become damaged and inflamed when your white blood cells attack the healthy tissues there. And so, as with a lot of other autoimmune diseases, it's not super clear on what causes this self attack. It's a full condition, but it had been well described for quite a while. So what was strange about these particular cases in Lime then, simply was the number of them. Only About one in fifty thousand or one in seventy five thousand children are diagnosed with JRA, so when there were several in a town of two thousand, it threw up some red flags. Researchers at Yale were notified of these cases, and they concluded that there was a statistical cluster in Lime and that there was probably something going on in the town to have caused this sudden rise in juvenile rheumatoid arthritis. Could it be an environmental contaminant, outbreak of some food borne illness, or a new infectious disease? Ooh, The first two were pretty quickly ruled out, and so that left infectious agent. It was time to talk to the patients to see if there was anything else linking them. It turned out that these kids had all had a skin rash just a couple of weeks before developing the joint pain and arthritis, so they suspected the two were linked. The researchers began tracking new people who came in with similar skin rashes and found that several later also developed joint pain. At the same time, other researchers were doing some deep dives into old literature, where they found some articles from the late eighteen hundreds describing the same thing.

01:02:26
Speaker 1: Oo.

01:02:27
Speaker 4: The link between this disease that had been previously described in Europe and this new disease wasn't solid by their eyes, and so researchers gave this new one a new name, Lime disease to indicate where it was found. Even though shortly after that first lime cluster was investigated, a bunch more kids all over New England were found to have this condition. By the late nineteen seventies, the Yale researchers had put together a pretty compelling case that this disease was caused by bacterium transmitted by a tick bite. Wow. The only thing missing were the two smoking guns, which were the bacterium and the tick. But they didn't have long to wait because at the same time, this is a lot of things happening all at the same time that at the same time that these researchers were tracking their cases, other researchers were looking at ticks around that same area, but for different reasons. They had been looking for the tick species that transmits Ricketzia ricketsiai, the causative agent of Rocky Mountain spotted fever, but they had much more success finding a different tick, exodioscapularis, in this in the New England area. They thought maybe this also carries the Racketsia responsible for Rocky Mountain spotted fever, and so they sent them to Willi Bergdorffer's lab for testing. Willie for there we go. Willy didn't find Rikkeetzia ricketsii, but he did find another type of bacterium told a spy, and this wasn't like one or two ticks with the bacterium. This was an infection prevalence of about sixty percent.

01:04:08
Speaker 3: Wow, very high.

01:04:10
Speaker 4: So maybe he thought this could be the lime bacterium. So his lab cultured it. They tested it on lab animals and they found that it caused a lime like disease, and they named it Berelli er Burgdorfry to honor the key discoverer. Really really so, now that the causative agent and arthropod vector had been identified, work could start on the medical side of things, using antibiotics to treat the disease, and also on the ecological side of things, understanding what animals and habitats led to the transmission of the disease so that people could actually try to start controlling or preventing its spread. This also meant that researchers could test for it in tick and human and animal samples, which is when they finally concluded that what they had on their hands was not a new disease at all, not even a newly described one strictly speaking, because there was a match between the North American and European cases. The Berelias were found all over. So what was happening. Were we witnessing the emergence of a brand new disease on two continents simultaneously. The answer is yes and no. Oh lyme disease definitely fits the definition of an emerging disease because it's something that is increasing rapidly in a period of time in new geographic areas and increasing in prevalence. But as we know, this certainly was not a new pathogen or a new disease. So what led to the sudden uptick in cases? Uptick I didn't even realize. But a good one and would it ever stop? So to answer these questions, let's talk ecology. Yes, here we go.

01:05:58
Speaker 3: That was really a beautiful intro to just to be able to get to talk about the ecology of line.

01:06:06
Speaker 4: Oh, thank you, thank you so much. It's very nicely done. Okay, Chapter three ecology. I might be biased, but I feel that as a field disease ecology owes a lot to Lime disease because in many ways, the ecological complexity of that disease system made researchers look at it not just from the perspective of an entomologist studying tich biology, or an epidemiologist studying exposure patterns, or a microbiologist studying Burlierbergdorfrice strain diversity. Yeah, they had to look at it from all of those perspectives, tossing in species interactions and the impact of environmental variables and many other things. Just to get a glimpse into how infection happened.

01:06:51
Speaker 3: Yeah, I agree.

01:06:52
Speaker 4: But even though the lime disease system is complicated and a lot of different factors are at work, that doesn't mean that it's impossible to under stand. So let's work our way upward. I want to start with the system itself, introducing the pathogen, tick and hosts, and then talk about the timing of lime disease emergence. So why it started popping up when it did? Awesome? Okay, So for lime disease, we have three players to consider, the tick, the pathogen, and the host. Let's start with a tick. Ticks are obligate ectoparasites, which basically just means that they need hosts to survive, and they live on the outside of their hosts, spending most of their lives in the environment. A tick starts its life as a little egg, waiting patiently in the environment until conditions are just right for it to hatch into a larvae and start looking for an animal to feed on. Burrellia isn't transmitted from a mother tick to her offspring, so all of these larval ticks are free from Burellia infection. Yeah, if you are bitten by a larval tick, it is extraordinarily unlikely that you will get line burrelliosis from it. That's important. There are other things you can get, of course, like Rocky Mountain spat of fever, but we won't go into that on this episode. It's a different, different episode. Yes, So anyway, this larva is an innocent, well most likely an innocent, uninfected little parasite. It's still sucking your blood, but it's still sucking your blood. But you know it needs it needs you to survive. Yeah, okay, well, yeah, to this little larva, all it's looking for is a host. Let's say that that host that it finds is a white footed mouse if we're in the US, or a bank full if we're in Finland, for instance. Both of these animals are notoriously good at being infected with Burrellia. So if that larva has a nice juicy meal on one of those guys, it's going to fall off completely sated and utterly infected with Burrellia. Ticks only feed one time during each of their life stages, so that little engorged larva is going to just chill out in the environment until it molts into the next stage, which is called a nymph. Now this nymph is the one you're gonna want to watch out for. Lime disease researchers often use the density of infected nymphs, so like, how many nymphs on average are infected in a certain area like one hundred square meters as a measure of disease risk. And that's because nymphs can be infected. Unlike, larvae are more numerous in the environment compared to adults and are more likely to bite humans nymphs, So you should all, like, we'll post a picture, but also do yourself a favor and look up the size differences of larva nymph an adult. Yeah, just to you know, inform yourself. Larvae have six legs nymphs that adults have eight legs. Yeah.

01:09:47
Speaker 3: The larvae of exodes scapulars are so tiny. I feel like you won't even see them.

01:09:52
Speaker 4: Period. You're super tiny. It's just very difficult when you're drag sampling. Yeah, like my eyes. Okay, okay, so anyway I knew. So it's usually one of these nymphs, then one of these little creeps that's responsible for making you sick. If that infected nymph bites say another mouse or a bank full rather than a human. It will pass on the berellia while it's feeding, leading to another infected rodent or host and another full and happy tick which is still infected. It doesn't lose the infection over its life. That nymph again chills in the environment, eventually molting into a male or adult female tick. These adult ticks tend to be a bit pickier in their tastes, choosing larger hosts like deer over rodents or humans, although that still does occasionally happen. Once on this larger host, a love story ensues. The male and female lock eyes over their shared blood meal, gazing at each other through the strands of tawny deer fur until they're both full and they can have their moment dear, Yeah, oh, dear, I can't. Oh no, I'm sorry, I'm sorry, Okay. After their moment, they drop off the host. The female lays eggs and then dies, and the cycle starts anew. Pretty simple eggs hatch into larvae. Larvae feed on a host and turn into nymphs. Nips feed on a host and turn into adults. Adults feed on a host mate, lay eggs and ie boom rapid fire. Yeah, there you go. There is nothing new about the way that ticks carry out this life cycle. They have been doing it for millennia. Nor is there anything new about the bacteria themselves, as we've learned their ancient So that begs the question why now, What has been happening in the past fifty years to lead to the emergence of what is now the most common tick born disease in the northern hemisphere. The answer does not lie in conspiracy theories about bioweapons, surprise, surprise. It's simply in the ecology of the system. And to me it's much more interesting not to mention actually based on facts than a wild America centric story created to sell books in headlines. In the interest of not overgeneralizing, I am going to concentrate on the North American emergence of the pathogen, which does have some parallels to what happened in Europe. Okay, so before Columbus came over and started the devastation of the people in land of North America, the line Bacterium probably existed in the same cycle that it does today. The many large forests allowed for higher populations of hosts like deer and mice that could support the ticks and the pathogens. Then, after colonization, the woods turned into a resource which was used almost to the point of exhaustion. Deer and other large mammals, the hosts that are great for producer more ticks, were hunted until their numbers dwindled, and tick populations probably also dropped a bit. Patches of forests with deer and ticks remained in places such as Long Island and some islands off Massachusetts, where Berellia probably also hit out. The mid twentieth century saw a big reversal of fortune for deer and forests. Large areas were reforested and deer populations were being reintroduced everywhere. At the same time, the human population was growing and they had to have somewhere to live. This led to the suburbs neighborhoods being built right next to or in place of forests. The barrier between humans and deer or just humans and other wildlife species shrank. As this suburban spread continued. With all of these deer, ticks now had ample hosts to feed on, which meant that the chances of a human and encountering a tick was much more likely. These things set the stage for the seemingly sudden reappearance of lime disease, even though we know it's been around a lot longer. But it's not a simple equation of more deer equals more lime disease. So don't go blaming the deer. It's probably more of a threshold thing. An area might need just a few deer to keep tick populations plentiful. And notice that I'm also just talking about deer in ticks, not deer in burrellia. And that's because there's a key element to the lime disease system that makes it a whole lot more complex than just more hosts equals more disease, because not all hosts hashtag not all hosts are I won't do that, now, please do that, hashtag not alos are equally good at being infected with burrellia. In disease ecology terms, we would say that hosts vary in their reservoir competence. Deer not so good, whitefooted mice and bank vols fantastic excellent, Western fence lizards terrible, worst, opossums terrible horrible, Eastern chipmunks great beautiful. So there's a lot of variation depending on the host species, and it's a spectrum.

01:15:25
Speaker 3: Yeah, those those terms, by the way, were beautiful at being a host for burrellia aka horrible for humans.

01:15:34
Speaker 4: Right, so western fence lizards being terrible at being reservoirs. Yes, So remember that a larval tick turns into an infected nymph by feeding on an infected host. If the host that that larva feeds on is a good reservoir like a white footed mouse, meaning that that mouse is probably chalk full of burrellia, the tick will probably become infected because chances are that host is infected. But if the host of choice is a poor reservoir like a western fence lizard, that lizard is probably uninfected and so the tick probably won't become infected. So it's not just about the number of hosts that are present in an area, it's about which hosts are present and in what proportions. Yeah, it's excitful.

01:16:28
Speaker 3: I haven't done such like a deep ecology episode before, and this is just really exciting.

01:16:34
Speaker 4: It's really exciting. And also it's like it's I think so crucial to under in understanding the patterns of lyme disease and how it works. And there's just such a big like there's so many pieces to this puzzle. It's fascinating. Yeah. So, as a general rule, the newly forested regions and the forest fragments created by suburbs and development, in general, they tend to be species poor and the species that are there are predictable. Guess what. They're often great reservoirs, meaning highly infected like the white footed mice, or important for tick populations like white tailed deer. White tailed deer are great at living in urban or suburban areas.

01:17:18
Speaker 3: Yeah, they're very well adapted to the destruction that we've caused.

01:17:22
Speaker 4: Yeah. Yeah. And in these areas, the ticks are much more likely to feed on a host that is a good reservoir, and the prevalence of Barelia will likely climb and climb, and the density of infected nymphs will be high. These areas are often the closest to humans, where people live or picnic or garden or simply go for a walk. In larger, more undisturbed areas with higher biodiversity, there are more species there, and a larval tick has many different hosts to choose from, and some of these hosts are going to be less likely to be infected in these more intact biodiverse forests, the density of infected nymphs is likely lower than in those forest fragments. So this idea, the idea that higher biodiversity reduces disease spread, is called the dilution effect. The dilution effect is definitely a controversial or at least contentious issue in disease ecology. Oh my god. Yeah, yeah, there's this ongoing debate about whether biodiversity leads to lower disease. So the dilution effect or increased disease in humans called the amplification effect. And the unexciting answer I would say to what is actually happening is that both can happen. It just depends it's ecology, It depends on the disease system, the location, the scale, the time frame, so many things. But in the case of lyme disease, there are many studies that show that the dilution effect is likely what's happening in eastern North America. Yeah, so in those forests when you have low biodiversity, the hosts that tend to be there, the hosts that the ticks are feeding on, are likely infected and great at being infected, and that causes a higher disease risk for humans, right, one more reason for people to care about biodiversity and stopping habitat loss. Yeah. Okay, So now that you know what a beautifully complex ecology that lyme disease has, let's talk about the bioweapon conspiracy theory that's been in the news lately. Oh, I just love it. Well, hopefully, now that I've talked about the history and the ecology, you'll agree that this conspiracy has makes no sense and has no basis. In fact, I've heard different and read different variations of this conspiracy, but the basic story is that in an attempt to make bioweapons, the US government either cooked up Barellia birgdor fry and purposefully infected ticks with it and released those ticks, or just infected and release ticks with Brellia bergdorfry. The seemingly sudden emergence and spread of lime disease over the past fifty years in North America is because of this bioweapon experiment gone wrong, according to the conspiracy theory. Okay, so this idea doesn't make sense for a number of reasons. Here are just a few number one ticks would make terrible bioweapons. Yeah, they're high maintenance.

01:20:27
Speaker 3: That's the thing that really really grinds my gears. It's like, if you're going to make a bioweapon.

01:20:33
Speaker 4: You would you wouldn't want it to be a vector.

01:20:36
Speaker 3: Absolutely not, No, absolutely not, especially not Burrellia in ticks, which have to be attached for at least twenty four to thirty six hours to even cause infection.

01:20:47
Speaker 4: Yeah, they also ticks are high maintenance. They need a lot of things like the right environmental conditions, the appropriate hosts, and high enough densities, and then they would still have to to bite someone. Like, yeah, it doesn't make any sense, Okay, Moving on number two, Lime disease isn't fatal. Bioweapons programs tend to focus on the diseases that will actually kill you and are not curable. So what would the purpose be of releasing a disease that is fully treatable with antibiotics.

01:21:20
Speaker 3: And has a very very very very low fatality rate even when untreated, though it has chronic symptoms for sure, if it's untreated, it's very low fatality rate.

01:21:32
Speaker 4: That's often not causing chronic symptoms in a population who are unlucky enough to get bitten. By a tick is not often the goal of bioweapons programs. Number three. Lime disease certainly wasn't cooked up in a lab. It's been around for a millennia, as we know. A lot of the bioweapon conspiracy theories lean heavily on the sudden emergence of the cluster of cases in Lime, Connecticut. But how many of them talk about the person in nineteen seventy in central Wisconsin that was described as having arithma migrants after a tick bite he got while grouse hunting.

01:22:10
Speaker 1: Ooh.

01:22:11
Speaker 4: The doctor who treated him guessed that it was caused by a spiro keep bacterium, so he treated it with penicillin.

01:22:18
Speaker 3: Okay, wait, that's awesome, right, yeah, right, that guy doesn't get enough cred I know.

01:22:24
Speaker 4: And how many of these conspiracy books are articles mentioned the presence of lime disease in Europe, where it was described and treated long before the Lime cluster. Our hands are up in the air, you guys, they're up in the air.

01:22:39
Speaker 2: Just yeah.

01:22:41
Speaker 4: Even if ticks were purposely infected and released, it wouldn't be enough to explain the sudden global increase in the disease. This is a very American centric conspiracy theory that has no support from lime bureliosis researchers, no support whatsoever. Conspiracy theory about this conspiracy theory is that the people who are promoting it are not willing to accept the role that humans have played in the wide scale environmental change, including climate change, that has set the stage for lime bureliosis emergence, which.

01:23:14
Speaker 3: Is so funny, like, let's blame just this small group of people instead of all of humanity.

01:23:21
Speaker 4: Yeah, it's kind of classic. Yeah, totally okay. So anyway, the answer to any ecological question about lime disease could start with it depends how will climate change impact the spread of lime disease. It depends. It depends on the scale of your question, neighborhood, county, state, country, It depends on what climate change projections you're looking at, depends on the animals in a region. What we do know is that it will change as the climate changes, And there are so many different aspects of the lime disease system that need to be examined before where we can understand enough about what's going on in a region to make any predictions. The biology of the pathogen and the tick, the environmental conditions affecting tick survival, the types of host species that are there, the human behavior leading to exposure. All of these things interact and this complexity I think has contributed a lot to the controversies surrounding the disease, as well as the frustrations of people who feel as if they're being lied to or at the very least ignored. I talked in this section about the history of the pathogen and the history of lime disease, but I didn't really touch on how lime disease has been perceived in the medical community since being discovered, which is a big part of its history, and I think it's something that's really important to talk about because lime disease is a very controversial issue and it's important to examine why that controversy exists. When a new disease shows up, it can take a while before anyone recognizes it as something new, and then even longer before there's a treatment for it. And if you've listened to this podcast before, that probably sounds really familiar. Yeah. In Lime, that journey towards pathoge and discovery was relatively quick. After the cluster of juvenile rheumatory arthritis cases in Lime Connecticut was identified, but then figuring out how to describe lime disease as an infection took a little bit longer because of the wide variety of symptoms it can cause, and then figuring out what might be happening long after the Burrellia are gone and no longer causing an active infection was even trickier. And people are still trying to puzzle that out. Yeah, definitely, in the beginning, even recognizing that there could be autoimmune symptoms triggered by burrellia took time. Back in the mid nineteen nineties, the Infectious Disease Society of America did not do a great job of acknowledging people who were suffering and seeking help, and some people on the receiving end of that didn't respond well, either making death threats or verbally attacking researchers. It really happened.

01:26:04
Speaker 3: Yeah, it sounds like it was madness.

01:26:07
Speaker 4: Yeah, chaos, and this clash, this chaos kind of set the tone for what is unfortunately still a big part of the lime disease conversation today. Since then, we have come a long way and what we know about how the disease works. And Aaron, I think you did a really good job talking about long term antibiotic use and how it won't actually help someone who does not have an active barellia infection, and how it can actually hurt them. And I feel like a lot of this controversy is because the terminology that we use and the science that we have based it on is still being developed. We know so much more now than we did twenty or even ten years ago, but it takes time for that information and in particular that terminology and the science behind it, to trickle down to physicians and also to people who aren't in any medical field whatever. Yeah, and in a way, it's not that surprising then that lyme disease would have led to such controversy, because you really need a huge foundation of knowledge to understand the ecology of the system as well as the biology of the pathogen, which is something we're still grappling with. It's an incredibly complex disease, and even though we know a lot, there's still a lot that we don't know. And this lack of knowledge is a really common theme, and a lot of chronic or autoimmune diseases that don't have a very clear pathology or a treatment that we've figured out yet, especially those with subjective symptoms that we can't quantify well. The more mysterious a diseases, the more we don't understand it, the more gray areas that end up surrounding it. And that's especially the case when we're dealing with as I mentioned these non specific subjective symptoms of disease. In our last episode on cystic fibrosis, I talked a bit about language and disease and how it's so hard to know what someone means when they say they're tired, or when they're in pain, or when their brain is foggy, because those are things that might feel different to each person, and so I think that can make them be more easily dismissed. Definitely. But at the same time, you know yourself and you are baseline in a way that no one else can, which means you would probably know when things are beyond normal. And so then being told no, this is normal, this is just normal wear and tear, that must be incredibly frustrating. Yeah, when you go to a physician because you have something wrong with you, but you don't know what that is, I feel like you have two basic expectations. One the doctor will be able to tell you what's wrong with you, and two they will be able to help you get better or at least try. And I think these are reasonable expectations because over our lives, we go to the doctor and we get treated. This is sort of the situation that we have experienced all of our lives, and so that norm yeah, that's what we expect, and that has made us have trust and confidence in our physicians and the medical establishment as a whole. So then when you're told we don't know what's wrong with you, or you've been treated so your symptoms should have gone away, or we can't find anything wrong with you, it's no wonder that it feels like you're being dismissed or outright ignored. Not having a diagnosis sucks because that feels hopeless. Yeah, it really does.

01:29:39
Speaker 3: And I can only imagine how frustrating that must be for physicians as well, because there is so little you can do for your patients if you can't figure out what's wrong, right, And that's often what happens in a lot of these chronic illnesses, not only in lyme disease. And I think that part of the problem has become that in some cases, a diagnosis of lime disease has been made based on exclusion, and lime disease is not and should not be a diagnosis of exclusion. It shouldn't be that just because we can't figure out what else is going on to cause your symptoms, that we then call it lime disease. That's what a diagnosis of exclusion is. Well, we've tested for everything that we can think of, and we can't find what's going on, so you have lime disease. That's not accurate for lime because contrary to some of the information on the internet, we actually can diagnose lime. So by diagnosing somebody with lime disease based on these exclusion criteria alone without laboratory confirmation, it can actually make it a lot harder for people who have had confirmed diagnoses of lime and who are still suffering from these post treatments victoms, because I think it conflates these groups and makes it really hard for us to even study from a scientific perspective what's going on so that we can develop better treatments.

01:31:09
Speaker 4: Yeah, that's a that's a really good point. Yeah, it's a it's a really the whole thing is a very I mean, it's a complex disease and as such, it has led to really complex issues, but big time. What we need to talk about next, Aaron, I think, is the scope of this. Okay, what is actually going on in the world of line, both in terms of eptymiology and also some maybe medical advancements. Maybe what's some cool cutting edge ecological research.

01:31:41
Speaker 3: Oh, let's let's find out. But maybe we'll take a We need a breather first, I think, so let's take a breather too. So let's talk about the epidemiology of lime lime barilliosis.

01:32:20
Speaker 4: In the US.

01:32:21
Speaker 3: In twenty seventeen, there were forty two thousand cases reported. Wow, that's a lot more than I expected, and it's estimated that the actual number is probably closer to three hundred thousand.

01:32:38
Speaker 4: Yeah, I've seen that number widely. Quote. Yeah, it's a big number.

01:32:42
Speaker 3: It's a huge number. And lime is a reportable disease. So those forty two thousand cases that were reported, like, those are all the people who were basically treated for lime disease essentially, right, So it's estimated that there's a lot more people who never get seen and therefore never get reported or treated.

01:33:02
Speaker 4: Okay, do we know what proportion of people can clear the infection? Good question, be no idea, treated no clue.

01:33:11
Speaker 3: But I mean, based on if we're estimating that three hundred thousand cases are happening every year and only forty two thousand people are getting treatment, I would say it's probably pretty high, right right. I would guess that for a large proportion of people, it's a relatively self limiting disease.

01:33:28
Speaker 4: Okay, But that's a guess. Don't quote me on it, please. In Europe.

01:33:36
Speaker 3: There's not great aggregate data in general, so you can go country by country, but that's a lot to do. So in a paper from twenty sixteen, they estimated that there was probably around two hundred and thirty five thousand cases annually across Western Europe.

01:33:55
Speaker 2: Wow.

01:33:56
Speaker 3: Yeah, that seems low compared to the s emits for the numbers in the US, but I don't know, huh. In the UK there's an estimated three thousand cases annually, okay, and then in places like Germany, Austria and Sweden the numbers are quite a bit higher.

01:34:13
Speaker 4: Than three thousand, though I don't have the exact numbers. I noticed you left out Finland. I did.

01:34:19
Speaker 3: I didn't find good numbers on Finland.

01:34:21
Speaker 4: What plenty of good numbers.

01:34:23
Speaker 3: Google it, Aaron, this is my favorite because, okay, listen, in Canada, Lime is the most prevalent tickborn disease, most prevalent vector born disease right in Canada.

01:34:39
Speaker 4: Uh huh.

01:34:40
Speaker 3: Guess how many cases there were in twenty fifteen in Canada, that huge amount of country.

01:34:47
Speaker 4: Let's okay, if there were three hundred thousand in the US, let's say fifty thousand.

01:34:53
Speaker 3: Nine hundred and seventeen. What there were nine hundred and seventeen cases reported in Canada in twenty fifteen. However, that is a crap ton more than in two thousand and nine, when only one hundred and forty four cases were reported in all of Canada.

01:35:13
Speaker 4: Wow, isn't that fascinating? That increase is a factor of both the tick vector spreading northwards because of climate change and also diagnostic and people reading articles and saying I'm going to go get treated or go talk to a doctor. Yeah.

01:35:28
Speaker 3: So first, let me say that the disease has been reported in other places as well. It's in Japan and Korea, and it's well established in China, but we don't have numbers for those areas. But overall, there's across the globe, hundreds of thousands of cases and the vast majority go undiagnosed. Okay, but like you said, the geographic distribution and the overall case numbers are going up. So what is it that's driving these increases in prevalence. Probably diagnostics is a huge part of it. Where getting better at recognizing and diagnosing lime disease than we were twenty years ago, especially in realizing that it is spreading geographically. That means that people are looking for it in wider areas than they would have been before. So somewhere in the Midwest twenty years ago, people might have been like, no, no, there is no lime disease here. It's only on the East coast. But now we know it's actually much more widespread than that.

01:36:25
Speaker 4: I remember seeing at a conference a few years ago a map of state by state prevalence of lime and Kentucky was zero, and I was like, Oh, that's weird. It's surrounded by Tennessee, which has a bunch. It's surrounded by Island, or by Indiana, by Ohio, by Virginia or West Virginia, all these places that were prevalent with lime disease. And I asked the presenter I was like, why is Kentucky like a hole there? Like, why is there no lime in Kentucky? And he's like, oh, no, one's looked there. Yeah, it's probably all over there.

01:36:57
Speaker 3: And I'm like, oh, okay, just no one has looked yet.

01:36:59
Speaker 4: Yeah he has looked in the tics for Burilla. Yeah, yeah, I'm sure they have.

01:37:02
Speaker 3: Now there's also the issue of if somebody is diagnosed with lime, let's say in Florida, did they get did they actually get infected with lime in Florida or did they get infected when they were on vacation somewhere else, And so then where do you report that as being a case in Florida or where they got it? So it does get really complicated when we're looking at, you know, especially geographic reports of the disease. But that's one reason that we're probably seeing increases is just getting better at recognizing it. But the tic is spreading, and the disease is also spreading. So the real question is why is it that we're seeing this increase in spread not only in the US but across the globe. And I'm not going to answer that question for you because we have with us today so on with a lot more knowledge on the subject.

01:37:57
Speaker 4: Who can tell us about the.

01:37:59
Speaker 3: Ways that we interact with our environment and the effect that ecology, climate change, et cetera, forest fragmentation, urbanization, all of these awesome big picture questions, What do they have to do with the increase in lime disease? So let's ask our favorite.

01:38:18
Speaker 4: Our favorite advisor in the whole world, doctor Brian Alan. Take it away.

01:38:27
Speaker 1: Lime disease is amazing because it's received a huge amount of attention from ecologists and epidemiologists. It's arguably the most prevalent factor born disease in North America. The economic and health impacts are enormous, and so despite the amount of attention it's received, we're still making new discoveries in the ecology of lime disease, and so it's been really a productive system From a biological standpoint. What it has told us about the role of infectious agents and ecological communities and the way humans can disrupt ecological communities and influence their risk of exposure to a tick born disease lime disease has been just really illuminating. There is this intersection between the applied and basic research when it comes to lime disease. Because it's this human health problem, and so I think one of the big areas going forward is going to be just understand why does lime disease continue to grow both in incident so the number of people who are reported getting lime disease every year, but also the spatial distribution is expanding as well, and so the tick is spreading, the pathogen is spreading. That is biologically an interesting problem because we don't fully understand mechanistically how that's happening. So we don't think that these ticks are capable of any kind of significant dispersal on their own, nor is the pathogen right. The pathogens either residing in the tick or it's residing in one of the animal hosts, one of the vertebrate hosts. So it must be some movements of wildlife facilitated by humans or influenced by humans that's allowing the tick and the pathogen to spread to new areas. And so the frontiers I think will include how does climate change influence the spread of tiken pathogen, but also how do humans modify their landscapes in ways that can affect the distribution of the lime disease system as well. Another really interesting aspect of this is that lime disease was really the big tick born disease on our radar initially because it was causing so many cases. But through the study of the biology or ecology and lime disease, we've discovered that there are a number of other pathogens that are transmitted by this particular species of tick, the black leged tick. It's also shine spotlight that there are other ticks in North America and other diseases associated with them as well. And so there's probably at least fifteen tick born diseases that occur in North America that are associated with several different tick species, and they're all biologically somewhat different from each other. And so how much does what we know about the biology of lime disease, which we understand really well at this point, how much of that applies to these other tickborn agents versus how much are these all idiosyncratic and similar levels of effort need to be put into studying each of these tickborn diseases to unders and their biology and their control.

01:41:02
Speaker 4: So what do you think is going on in terms of the spread of the ticks and the pathogens, Like, how are these ticks and pathogens getting from point A to point B. And how is that different depending on where you're looking. I mean, if you look in North America in the northeast, that might be different than if you look in the west, or if you look in Europe and other places, like what do you think are there any general rules here?

01:41:29
Speaker 1: So there's been a lot of research looking at what wildlife hosts might be involved in the dispersal of both the ticks and the pathogens, and it creates a really interesting landscape that probably suggests there will be major differences among the tick born diseases in terms of how they spread through the landscape. So, for example, there's been an impressive research on the role of migratory songbirds in the dispersal of ticks and pathogens. And it's not, I think something people typically think about when they think about songbird migrations. You have these birds flying overhead. The typical tick burden per bird, by which I mean how many ticks are on each individual animals not that many. We've captured birds here in Illinois, and one or two or maybe three ticks is a typical number of ticks per bird. But when you have millions of birds flying overhead, you actually have millions of ticks flying overhead as well, and so you have the timing of the spring and the fall migrations and to what extent that aligns with the timing of the different stages and the tics life cycle can determine which tick life stages are being dispersed in which direction. And then some of those birds are also capable of transmitting the line pathogen too, ticks and others are not. And so under some scenarios you can have a tick being dispersed without the pathogen, which that tick is then annoying or a nuisance, but it's not much of a health risk versus a TIS being dispersed with the pathogen. And then you can even have a scenario where you have infected animals dispersing the pathogen without the tick, and then if they arrive someplace where the ticks are established, then they can be bitten and start the cycle there. And so you actually have a number of different pathways by which you can have this spread of either the tick or the pathogen, or the tick and the pathogen. So that's pretty cool. Some of the work from the Northeast indicates that lime disease is spreading faster than another tickborn agent, the one that causes baby ziosis in humans, and that's because of the wildlife hosts that are what we refer to as the reservoirs for those the pathogens that cause those illnesses, and the case of babyziosis, it's mostly small mammals that don't disperse long distances, and so baby's ciosis is spreading slowly, whereas lime disease can be carried by wildlife that travel much further distances, and so lime disease is spreading faster. The extent which climate change, as one form of human environmental change, will impact these processes in part depends on the timing of when wildlife migrate, the timing of the tick life cycle, and so that's an area where there's a lot of active research going on trying to project into the future what can we expect for the distribution of tickborn disease under environmental change.

01:43:57
Speaker 4: So, with all this information and research about invasion and how ticks and the pathogens spread into new areas, is there any ecological research being done on how to use this information to actually control the disease itself? Like, are there any interesting bits of research in that arena?

01:44:19
Speaker 1: There are, but I would argue both are important, and so just knowing where these diseases are occurring is actually one of the most useful pieces of information we can provide because a surprising extent of the public health effort against tick more diseases like lime disease still depends on good biological information on where risk is high and where risk is low, and that helps physicians understand when a patient comes in describing symptoms that could potentially apply to a number of different illnesses, what are the chances that they might be looking at lime disease versus something else. And we still are really lacking for good distribution information, and so that's actually been a big focus these last few years with a push from the CDC, is to try to get better distribution maps for the ticks and the pathogen so that we can really keep the public health community updated on where these occur. But there are interventions and control measures that have been proposed. Their efficacy is also an ongoing area of study. So a technology that was developed several decades ago but hasn't seen that widespread deployment is different types of traps is not quite the right word, but something that brings wildlife in to get a reward like a feeding station, and then they get a pesticide applied to them when they come in for the bait, and so there are versions of these for deer which treat deer against tics. There are also versions that can be used for mice and some of the other small mammals that are these critical hosts for the line pathogen, and so there are challenges in the deployment of those over large spatial scales, but it's possible that in areas that are particularly high risk or where we're seeing a lot of human cases, those could be adequately deployed. Another controversy in the ecology of lime disease is how critical is deer population size, and that has been a focus of lime disease research for a long time. But it's a surprisingly tough question to answer. And so, if you have high deer population density, will that always equate high line disease risk. The data suggests not always, and so in the context of deer management this often comes up, and so some communities engage in deer management not necessarily just because of lime disease. It can be also because of vehicle collisions and other concerns. But lime disease particularly in areas where endemic is often proposed as a reason. And so another area where there's ongoing research is to address to what extent of these deer management programs also manage lime disease risk. So there are things communities can do I think educating the public about the level of risk. And then from what I've seen from the public health literature is that getting people to engage in preventive measures is still one of the most effective things the scientific community can do. And so if we can get people to take precautions at an individual level, that probably will do more to reduce winds these cases than just about any other strategy.

01:47:16
Speaker 4: I have a question that I think you probably get asked all the time, because I have been asked it frequently. Why do ticks matter? Why can't we just kill them all? What would happen? So I want to hear your take on this.

01:47:31
Speaker 1: Yeah, Yeah, this is also probably the most frequent question I receive, and not just from the public, I mean sometimes from other scientists as well, and so you know, I usually have a couple of responses I given to that question. First is that you know, from nature's perspective, there isn't good or bad. These are organisms that are occupying an open ecological niche, and parasitism is one of the most common strategies in nature. There's many species on Earth that have adopted a parasitic strategy because it works. And so, you know, nature doesn't think in terms of good or bad. We find ticks a nuisance and they make us six. So we have a very negative perception of ticks, understandably so, and you know, from the perspective of ecosystems, I've seen the argument made, and I've seen some data that supports this that in the absence of predators, one can expect an increase in the abundance of parasites. And so it's actually a really interesting paper that came out a few years ago showing that the extirpation of the gray wolf from North America probably released lime disease, caused it increase in deer populations and also indirectly an increase in populations of small mammals, and as a result, that might have set the stage for the emergence of lime disease. And so in the absence of top predators, top carnivores, and ecosystems, what you may see emerge in their place are an abundance of parasites, and so this all in some ways may be consequences of the way humans have modified the ecosystems than.

01:48:58
Speaker 2: Which we live.

01:48:59
Speaker 3: I have a question, So you have been directly impacted by lyme disease and yet still study ticks constantly. What are your favorite and least favorite parts of studying tics and tick ecology.

01:49:14
Speaker 1: I love that question. I'll start with my favorite part. So to me, the most interesting thing about studying ticks is that most tick species are many tick species. Anyway, we'll feed on a wide diversity of different wildlife hosts, and so by studying ticks, I get to study many different organisms, not just ticks, and so I build myself as a tch biologist and that's served me well. But I really do find it interesting the way ticks connect many of the organisms within the ecosystem in which they occur, and so I am able to study a much greater diversity of wildlife as a result of working on tics. Least favorite part, you know, I hear from a lot of people who are suffering from serious illness, including people who haven't been able to get the treatment they need to feel better, And I feel bad for people who are suffering from long term illness from tickborn disease. And I'm not a physician. I'm not really able to offer them anything other than my sympathy. And I hope through the research I do, I can make things better for people who haven't yet been exposed to tickboorn disease. But it is heartbreaking sometimes to hear people's stories. Some people are very sick, very debilitated from things like lime disease.

01:50:49
Speaker 4: That was fantastic. It was so much fun it was to take Brian. I can't believe it took us two full seasons to get him on the show. I think we were just waiting for the right moment. This was the right moment. This was the right moment.

01:51:02
Speaker 3: Thanks Brian, Thanks for everything for literally the last six years of our life.

01:51:07
Speaker 4: Yes, so, Aaron, there's more like medical things though, right, Like, can you tell me any updates about them on the medical side of lime? Is there a vaccine in the works? Why do dogs get vaccines?

01:51:20
Speaker 3: Great questions. Yeah, so there is a vaccine for dogs. You can get it for your dogs. I think for your cats as well. I got it for my dog because she runs around and gets bit by ticks. Even though she's on tick prevention and things like that, why not might as well. There used to be a vaccine for humans used to be used to be it was relatively effective. From what I can tell, what is relatively effective. I'm not sure exactly what the effectiveness was, but it was like more than fifty percent effective, okay, meaning that like more than fifty percent of people if you gave them this vaccine would mount and response and then not get infected with the lime pathogen.

01:52:02
Speaker 4: Okay.

01:52:03
Speaker 3: But there was a theoretical fear raised that giving this vaccine would increase the risk of lime arthritis. Because it's very likely that lime arthritis is an autoimmune response and not directly caused by the pathogen, So this is not an unreasonable idea that maybe giving a killed version of this bacteria in some way would activate that same sort of immune response. There wasn't any actual evidence in any clinical trials that this happened. But after that idea was raised, there was like no market for the vaccine and the manufacturers weren't making any money, so they stopped making it.

01:52:49
Speaker 4: That's it. So it's that did it become unlicensed or anything like that.

01:52:53
Speaker 3: I think it's been so much time, so much time has passed that it's no longer a licensed vax it's no longer available for humans. So there is no human lime vaccine. I think that's hilarious.

01:53:07
Speaker 4: So then are there any research groups that are working on a vaccine or anything like that?

01:53:14
Speaker 3: There probably are, I've had a hard time finding them. So there's like things that you can find on like different lime vaccine patents and things like that. Let me check Clinical Trials dot gov really quickly. Actually, So there was a paper that came out in twenty seventeen that was analyzing the past line vaccines that have existed and kind of trying to guide the way for further vaccine development. But yeah, it's really interesting. Huh, line vaccine used to exist, maybe it will again.

01:53:51
Speaker 4: Do you know why it was not highly effective? Is it have something to do with strained diversity of lime? And was it only brilliant?

01:54:00
Speaker 3: I think it was only brellly Aboordworfry. I think it was pretty effective though, reduce new infections and vaccinated adults by nearly eighty percent eighty percent, so yeah, it was almost eighty percent effective. But then they withdrew sales Ooh, this is a great paper.

01:54:18
Speaker 4: I will post this.

01:54:22
Speaker 3: Line vaccine at Cautionary Tale.

01:54:25
Speaker 4: I'm curious. I'd like to read that.

01:54:27
Speaker 3: Yeah, we didn't touch at all in the episode. Really about the Pacific Coast side of lime disease and the tics that transmit there and the hosts that are there are entirely different than on the Northeast coast. And if you want to hear more about that, I would recommend an episode of Ologies that features none other than doctor Andrea Sway, who's fantastic and she talks a lot about her research on lime disease on the Pacific coast. So if people are interested, they should definitely check out that episode of Ologies.

01:55:03
Speaker 5: Yeah, that's a good recommendation. So that's it on the medical side of things. That's it on the medical side of things. I had a fun with this episode.

01:55:14
Speaker 4: I did too. I tickborn diseases and vector borne diseases are fascinating because of how complex they are, and it's a little bit daunting to try to learn each new system and all the different terminology, reservoir competence and tick hosts and blah blah blah. But I think it's just such an amazing thing to try to weave like tease apart all of these strands. And that's I mean, that's ecology, Like this is disease ecology at its most beautiful.

01:55:43
Speaker 3: Yeah, I agree, So sources, sources, Okay, So.

01:55:50
Speaker 4: I read a few different books and a bunch of articles for this. One book that I definitely want to shout out is called Lime Disease The Ecology of a Complex System and it's this is by Rick Osfeld, and he is the most knowledgeable lime disease person. I think he has been doing lime disease research and has teased apart so much of the ecology. So this is a really well written, understandable and fact based book. In David Kwaman's Spillover, there's a great chapter on lime disease called The Deer, the Parrot, and the Kid next Door. Super fun. And then a bunch of papers. I'll post them all. I do want to point out that there are some books out there that are not reliable and that present a lot of non scientific information that's not based on fact or on the research that has wide consensus among lime researchers. And this is a real problem because what they do, what some of these books do is use scientific language, and they use interviews with scientists to bolster whatever argument they're trying to portray or whatever story they're trying to sell. And this makes finding reliable information very difficult. And I read a few of these books because I wanted to explore this realm, and I am going to list them here as a way of saying, hey, these are some that are not reliable. Yeah. One is called Lime the First Epidemic of Climate Change by Mary Beth Pfeiffer, and the other is called Lab two five seven, and that's by Michael C. Carroll. And I found in both of these books what seemed to be a lack of understanding of the lime disease system, which made me doubt the credibility of the rest of the books.

01:57:42
Speaker 3: I think that's really important, because it's hard enough to find good information out there. You expect that if it's a book, it's fugit, right, Yeah.

01:57:54
Speaker 4: I mean, And that we need to remember is that there is no peer review process for publishing non scientific books the way there is for these journals, which have to go through pretty rigorous screening of this of the study, design, of the interpretation of the analysis, all of these things.

01:58:13
Speaker 3: Even then there's sometimes wrong and so then with books there's not even a screening.

01:58:19
Speaker 4: No, this is a realm that can be very tricky to then know where to find the right information or correct information. Yeah, absolutely cool.

01:58:30
Speaker 3: I have several really great articles a few one really really great one by that I really enjoyed by John Halpern. That's addressing a lot of the common misconceptions about lime disease. That's the title, Common Misconceptions about Lime Disease wonderful. It was published in twenty thirteen. And then there are several other reviews that I found that are super comprehensive and really easy to read if you want some just really good info about lime disease in general. So we will post the links to these sources as always on our website, This podcast will Kill You dot com. You can find every source that we cite from every single one of our episodes.

01:59:13
Speaker 4: And yeah, yeah, we would like to thank Brian once again for coming onto the podcast. We really appreciate it. It was so much fun. It was so fun to have you.

01:59:24
Speaker 3: We'd like to thank Bloodmobile for the music for this episode and all of our episodes. You can find a link to his music on our website.

01:59:32
Speaker 4: And also we'd like to thank you for listening to us and for so many of you who suggested lyme disease, and also for being patient as this is our final episode of this season, but we will be back in just a few short.

01:59:50
Speaker 3: Weeks, So thank you so much for allowing us to make two whole seasons of this podcast and listening to it, and then.

01:59:58
Speaker 4: A third one and then a third one one.

02:00:00
Speaker 3: Don't worry, it's coming.

02:00:02
Speaker 4: It's coming.

02:00:03
Speaker 3: We just have some things to take care of in the meantime. Yeah, okay, with that, wash your hands, you filthy, beautiful animals, and check yourself for ticks.

02:00:15
Speaker 2: Do a tick check, am