Alpha-Gal Syndrome

SPEAKER_03 0:09

This is a podcast about One Health. The idea that the health of humans, animals, plants, and the environment that we all share are intrinsically linked. Coming to you from a team of scientists, physicians, and veterinarians, this is Infectious Science, where enthusiasm for science is contagious. Alright, hello everyone. Welcome back to this episode of Infectious Science. I'm Camille, one of your hosts, and I am joined tonight by Alex, another co-host. Hello. How are you? I'm doing very well. I'm super excited to talk about our topic. So for those of you listeners who don't know, I recently moved to New England. I live on Cape Cod now. And within a few weeks of relocating, I of course snipped out the interesting infectious diseases available near me. I feel like my ear was to the ground, and I was sitting in a coffee shop, and this topic came up, and I was like, what? I need to know more. So I came across this really fascinating piece that the New York Times ran about how Martha's Vineyard has seen a rise in veganism, and it's all due to cases of AlphaGaw syndrome, which is transmitted by the lone star tick primarily. And what's interesting is that Martha's Vineyard also has like really high cases of Lyme disease, rabiosis, which is another tick-borne disease. And so I, of course, had to dig into this. I thought it was really interesting that lone star ticks have this range. They've been in the Americas, they have a range across the southern and eastern US. It's from Texas all the way over to Florida and then all the way up to Michigan and then parts of New England, including the part that I am in. And I haven't found any yet in my yard, but I have looked because I've been kind of curious. And what's interesting is they're actually considered pretty aggressive ticks. They're more likely to seek a person out than something like a black-legged tick or something, which is just kind of hanging out. If you walk by, it'll take advantage. But other than that, it's not really gonna seek you out. So yeah, but Alex, you also got into this idea of like, what is the range? Why does it look the way that it looks? So tell us a bit about that.

SPEAKER_04 2:17

Absolutely, yeah. I know when I first heard the common name of Lone Star Tick, my first thought was that it had something to do with Texas. But in reality, uh it's all to do with its appearance because there's the female ticks, the adults have a white spot on their back on the shield of the ticks, the male ones have these white streaks that run along the side. And so those sorts of morphological differences, in addition to the legs, as you were mentioning before, in the context of ixides, the genus of ticks responsible for transmitting Lyme disease, that's how you can tell some of these differences along with these behaviors. Because as you alluded to, Camille, these lone star ticks have a habit of actively hunting for their prospective blood mules based off of the odor that those individuals emit. And it's worth noting that all tic life stages at this point, so from the larvae to the nymphs to the adult full form, all of them are capable of and are certainly willing to feed on you and me, which is a delightful prospect. So for some background, yes, they were first characterized by the famed Swedish biologist Carl Linnaeus in 1758, who uh Linnaeus for context was the inventor of the binomial nomenclature system. So kind of the father of modern taxonomy in a way. And so, yes, the lone star ticks are known as Ambiloma Americanum. They're primarily active in the spring and the fall, around April to November, and they feed principally on white-tailed deer, which has a lot of implications then upon its range, as you were alluding to a bit earlier, Camille, because historically the lone star tick was dispersed across the eastern U.S. and parts of Mexico, with its historical range being from about the southern part of New Jersey down to some of the more northern states of Mexico. But as a result of increased deforestation and poorly regulated hunting over the course of the 18th, 19th, and early 20th century, the range of the white-tailed deer significantly decreased as there was a lot of extirpation of the species locally in a lot of places. And so that meant that the TikTok receded from its historical populations in that regard or was present in lower density. But then starting in the 1940s, there were these conservation efforts that really took steam around then, along with these deer relocation programs that were aimed to go and re-establish the white-tailed deer in its historical habitat niche. And that enabled a resurgence of the Lone Star Tick with its historical keystone species.

SPEAKER_03 4:49

Yeah. So I think also something important to note here is we killed off the predators of white-tailed deer. We hunted them out of these areas that we were heavily settled in, a lot of the New England states, and anywhere we were having agriculture and didn't want them attacking livestock. And that also plays a role, right? And if you don't have the white-tailed deer for the ticks to primarily feed on, one, they might be more likely to find a human host, but two, there might just be less of them, right? Because they don't have this kind of big population that's just always there. So I think that's also important to note.

SPEAKER_04 5:21

That's a major issue, yeah, with these sorts of things. And something that, you know, in some ways, when we're thinking about these relocation efforts or you know, re-establishing a species in an area where it's been locally extirpated, it's so important to go and think about the context in which that species historically existed in that space, right? Because yeah, without that sort of presence of a natural predator, then really your deer counts in these areas might be more regulated by hunting season and how many deer end up as the roadkill. They were, you know, there all the time. One hit my father's car, actually. Um I know I I for some reason the deer just decided to run parallel to his car and just ended up ramming into the back of it for some reason. So I don't really know what that deer was thinking, but maybe how to grunt against cars.

SPEAKER_03 6:13

I don't know. Yeah, I don't see a lot of deer being hit by cars here, but certainly they are inhaling my garden and they will eat things to the ground. And so I'm always like, huh, if these are in my yard, in my back garden, then certainly they're able to deposit some of their ticks. They're out and about and that kind of thing. So I think that also matters that as we've talked before in infectious science about how animals become peridomestic, right? They start living closer and closer to us in spaces that we've urbanized. And I think that's an interesting thing to keep in mind when we consider something like ticks, right? So they naturally had this very large range covering the southern and eastern US, and they're certainly expanding back into that.

SPEAKER_04 6:55

It's interesting to think about, yes, how the movement of these deer are responsible for going and enabling like a local deposition of those ticks in areas then that can be closer to us, and and how that wildlife human interface then as we continue our process of urbanization, of suburban sprawl, right? How that line keeps on getting pushed and how that enables these sorts of areas where where these deer and by extension the ticks that are likely to come with them might come into contact with us, right? But it's not just the deer, though, is the is an important aspect to think about though, with that, because it's also these ticks secondarily are more than capable of and have a preference for taking blood meals off of migratory birds as well, for instance. And that has played a significant role in terms of its spread into areas where otherwise it would be incapable of moving over an extended period of time on its own or with the help of the unwitting carrier of the white-tailed deer. And so that migratory bird movement has actually enabled the expansion then of the range into the Midwest, into parts of southern Canada, as well as further north of that southern New Jersey historical range limit to around where you are in that regard. So it's interesting to think about that. And then, of course, climate change plays a key role in that as well, because then as the winters uh get a lot less chilly, then that favors the ticks surviving more through winter. That means that the ticks might be more active for a longer period of time if there's a longer period where it's warmer outside for them and the climatological conditions are favorable. And it also means that those migratory birds can then drop these ticks in areas where they can have a habitat niche that they can latch on to eventually that expands the further movement than northwards of the deer as well, right? And so it's possible that ticks might not just come along with the deer, but that they both might arrive at the same place at roughly similar points in time, enabling the tick population to surge there. Because the movement northwards of the white-tailed deer into Canada is something that's been a bit of an issue ecologically as well, because normally some of those deer species don't exactly do super well in environments that are not supposed to be quite that temperate, right? And they're becoming more temperate as a result of climate change. So just wanted to put that out there as well. And also just as a side note, something that I found really interesting about that northern migration is that there was a study that was done, I think, by the New England Journal of Medicine that showed that tick populations in the northern extremities of that lone star tick range, they were doing some testing in like upstate New York and in other areas beyond, like southern New Jersey, they appear to be genetically distinct from those that are found further south in its historical range, suggesting that there's some adaptive evolutionary process that's going on that enables them to maybe be more hardy and better survive those conditions up there. Although we don't really know what phenotypically the implications of that shift are, but just something to consider as far as why it is that they're adapting so well as well, you know, to new environments further north.

SPEAKER_03 9:59

Yeah, no, that's all very interesting for sure. I just think it's so compelling to talk about this now because I think people act like this is a new problem, right? Like when someone brought this up to me in a coffee shop, they were like, oh, this is a really new thing for the vineyard and the cape, and we hadn't seen these before, but actually these did exist in like the 1750s and things here. So it's more we shifted the problem away. This is something we see constantly in infectious diseases. We shifted the problem away and then it came back to our door, and we're still shocked. Um, but I think what's really particularly compelling, I'm going to the vineyard in two days, actually, for something that's a big event that's gonna actually be held outside on a big yard. So I was like thinking about this, and I'm like I really out as I am having orders. I'll keep my eye out for ticks. But, anyways, I want to talk about what this is doing, right? So we talked about like the historical range was what the the range is now of these ticks, but like why does this matter, right? Like what is imperative to human health? But for these ticks in particular, it really matters where they are because they can cause alpha gal syndrome when they bite a human. So alpha gal is a molecule, a lot of animals produce it, humans do not, so it's foreign to us, but it's found in animal products, things like meat, it's also found in things like dairy products. And what happens is that some tick species, including the lone star tick, produce alpha gal in their saliva, right? And after they bite, there's sort of that mixing of our blood with that saliva, and then there's the potential for that to trigger an immune response, where our body as a human body does not produce alpha gal, does not recognize it. It's a foreign substance, and basically it recognizes it as a threat, and that can trigger something like an allergic reaction, which is what alpha gal syndrome is. It's an allergic reaction to the alpha gal molecule, but because that's found in meats, that can be found in dairy, you can see how like this would drive a rise in what we're seeing right now in Martha's vineyard, where you see this increase in veganism, right? Because people are having to avoid these foods because they're allergic to them after a tick bite, which I think it's something that feels very threatening to a lot of people. It seems very frightening, right? Like you can imagine that there's a lot of social implications for that if you're trying to eat out or anything like that. I also feel like at least people here seem to be comparing what's happening with the threat of Alpha Gow syndrome to basically what happened after Jaws was released when no one wanted to go in the water. Now people are really afraid of getting a lone star tick, right? And so yeah, it's something that made a New York Times news article, right? So it's really hit the public consciousness in a way where this is now recognized as something that that people are leery of, right? And if you think about it, Martha's Vineyard is a place that people really go as a tourist destination. It's something that people go visit, they want to be outside, maybe they want to be out walking or hiking or on the beach, and nobody wants to be worried about ticks.

SPEAKER_04 12:55

And that's a big issue, yeah. No, because when you're out, you're going and enjoying the great outdoors or just living life normally, right? Having that ever-present fear of what if there's a tick on me? And especially considering that these ticks are very good at being unobtrusive when they bite, right? And they can feed on you for up to a week. And because of the nature of the way that they bite and the compounds that are present in their saliva, it's very difficult to sometimes tell when they are going and feeding on you. And if they are, then you have to try to go and manually detach them, right? And that becomes a bit of a problem at that point as well. I can only imagine the way it's kind of taken over and taken root in these sorts of local communities, and especially, I don't know. I think about places like Martha's Vineyard, Chappaquitic, like quintessential small beach towns in New England, and I think about summertime, the 4th of July, burgers, right? Exactly, yeah. It's it's at the heart of a lot of these American summer traditions in some ways, the presence of like Alpha Gal syndrome and the reporting on it, especially as being like a meat allergy. I think it makes sense that it's taken root in the public consciousness because it seems like it's almost an attack on the way that we live in life number birthday. Exactly, yeah.

SPEAKER_03 14:10

Yeah, it's like an attack on vacations, right? I think that's how it's being seen. I think it's so interesting. I had never watched Jaws ever in my life. So, of course, when a local institution is hosting it as like a lawn showing of it, I was like, oh, what a great way to watch it, like right across the water from Martha's Vineyard. And I think it's so interesting that I was more worried about getting a tick from being on the lawn than I was frightened at all by Jaws. Like I wasn't on the ground. Because I was more worried about a tick than I was. I have no concerns about getting in the water here, but I do have concerns about like being even slightly near tall grass.

SPEAKER_04 14:50

So what I'm hearing is that there's a market for a tick horror movie coming soon. Yeah, I'm sure.

SPEAKER_03 15:03

It could still be called Jaws, right? It's still about biting, right? Exactly.

SPEAKER_02 15:12

It's mini jaws. That's when they'll be small but powerful. I can see the post.

SPEAKER_03 15:21

Yeah. I think what's so wild about this is with Alpha Gow syndrome, like we just don't have a great understanding of why it affects people the way it does, right? Like it can cause symptoms that are as mild as food poisoning, which like I'm not saying food poisoning is always mild, but it can be like those kind of symptoms, or it's gonna be all the way up to anaphylaxis, which is life-threatening. And we don't know, and it runs the gamut, and you can see how developing something like an allergy like this, that it just feels like a spinning out of control. And what's also really interesting to me is that Alpha Cal syndrome is actually not a nationally notifiable disease, which really surprised me. It's really odd. So, like, for those that don't know, like nationally notifiable diseases are notifiable because we want to be able to track how many cases we have of this. There are things like tuberculosis or things like that. But I would think that something like you can develop a life-threatening allergy extreme might want to be reclassified as something that is notifiable because when it's not notifiable, your state might keep track of its case numbers, but we don't on a federal level have necessarily a database of that information. Looking at on a national level, like how is this increasing or decreasing or that kind of thing, I just thought that was really wild that we don't actually know how many cases there truly are. And of course, as someone who's in the field of infectious diseases, my gut is always to lean towards there's more cases than you know about, right? Because you only have the number of cases you've tested for and detected, and these are people that are seeking care or can be connected to care. So there's always going to be cases that you didn't know about. What I also think is interesting is that when I was looking into this, I did not come across any like, I'm gonna call it lore or like folklore, like myths or like legends about like if you would think if this was naturally here, you would have some reports historically of this occurring. And so I think it's just really interesting that I didn't find any sort of historical records of it, if that makes sense. And that doesn't mean they don't exist, it just means I didn't find them, but it's compelling to consider though, isn't it?

SPEAKER_04 17:19

Absolutely, yeah, because the initial characterization of it really stemmed as a result of AGS, really as a disease, came as a result of some work that was being done with an anti-cancer treatment, right? So there were these trials with Setuximat, which is a chimeric monoclonal antibody that targets epidermal growth factor and is FDA approved for use in treatment of metastatic colorectal cancer as well as your squama cell carcinoma of the head and the neck. And because it's chimeric in nature and it's derived from these mouse cell lines, that means that that's how the medication contains some alpha gal, because the alpha gal molecule is present in the heavy chain of the antibody, which is one of these components of the antibody. And that means then that when it's administered, if an individual already has developed IgE antibodies from a prior immune exposure to alpha gal in the blood, which would happen as a result of one of these tick bites, for instance, and that's how the allergy then occurs, because it's not as a result of that initial exposure to alpha gal and the tic bite, but it's the response that amnestic that you're exposure to it. Yeah.

SPEAKER_03 18:31

Just to jump in and put that really simply. So if you think about this, in order for your immune system to build a response to something, it has to know what it is. So the first time it's exposed to it, that's when it can essentially recognize something. And then when there's another exposure, that's when you can get this massive inflammation and see these huge sort of upticks into things that's going to make us feel very poorly and like we're having an allergic reaction. I just want to put that in simple terms.

SPEAKER_04 18:57

Exactly. So thank you for that, Camille. So HES was first observed then in 2008, then observing the deaths of some of these individuals who were receiving this antibody treatment as a part of their chemotherapy. I know. And it was ultimately later work that then revealed that there were links between the distribution of cases of this reaction and then the distribution of certain varieties of ticks. And it's worth noting as well that AGS is not solely found in the US and it's not solely spread by Amboloma Americanum, right? So the Lone Star Tick, there are also tic species in Australia and in Europe that are responsible for going and spreading that because similarly, those ticks also carry alpha gal in their saliva. And the origins of it are still something that remain unclear. There has been some research that's been done that seems to show that it might be endogenously produced by the tick in the mid-gut, and then it ends up in the saliva. There's also some theories that it may be just some degraded antigens of alpha gal from previous blood meals of the tick from like other mammalian species might then be taken up by their nuts exactly. And that's how it comes about, but it's still not entirely clear. And I just think it's just fascinating. And it's a really quick AGS in its turnaround time within two to six hours of exposure, is when you can start to develop some of these symptoms, and really there aren't any treatments available. You just have to be mindful of your potential exposures, potentially carry an EpiPen or something like that in case of an emergency anaphylactic response, and maybe take some antihistamines as well in order to reduce some of the milder symptoms if you experience those. But it's just it just seems like a super rough condition. I don't know. I don't know about you, Camille, but I love my cheese way too much to have to worry about this. I've always thought, why is this vineyard? It sounds so nice, but now I'm not I'm not entirely sure if I'm gonna be visiting anytime soon.

SPEAKER_03 20:49

Um but I do think to the island's credit, they have done an incredible job to do all kinds of outreach and education and try to make it accessible to people. They're like, hey, we're mindful of this, we're aware of it, we're doing what we can around it. And I think that it really speaks to some great organization going on at their sort of health department, and I think that's wonderful. I agree with you. I would not want to develop Alpha Gauss syndrome. I'm also very fond of Jesus and charcuterie boards, it would take away my charcuterie, and that would be very sad. But I also just want to drive home like how prevalent this is, right? And it's not necessarily you need to be out hiking in a really densely wooded area where you would expect to have that exposure, right? There was been yard surveys conducted on Martha's Vineyard, and it's really interesting because between 2020 and 2024, in one town, they found that 65% of the yards surveyed had lunch star ticks. That's more than half. That's far more than half. And so, this idea that this is your yard, right? This is I go in my backyard all the time. I'm a gardener, I'm out there hanging in my hammock and reading. I just wanted to consider that we also Want to become people who are just afraid of the outdoors or afraid of nature, and I think that's something to keep in mind. But you know, in some places it's even higher, right? You mentioned what it 85% of yards that they surveyed there have low surface present, which is just unimaginably high. And so I think that this is something that places have to adapt around, right? This isn't something that I keep budgeting anytime soon, and so it's going to look like better education for the public and also just better incentives to protect yourself from ticks, but wearing books for socks, like wearing long pants, which people aren't doing in the summer.

SPEAKER_04 22:40

People want to enjoy the good weather, but at the same time, there are ways to go about doing that, but still ensure that you're protected, right? And uh, you know, long pants some deep and the keratin or some other aceracytes go a long way.

SPEAKER_03 22:56

Let's praise your friends. It keeps coming infectious diseases away. I also just want to throw this totally changing how people are eating, right? Which is such a social thing, and I think cannot be understated how important and wild that is, but it can change what you family gatherings, what you cook for other people if you're willing to go out to eat. That affects the economic of the restaurant industry about whether or not they can offer academic-friendly meals, like all kinds of things. I also think this is going to change health care. Right now, even on Martha's Vineyard, tick my doses are so high that Martha's Vineyard now has a pick center in the Martha's Vineyard Medical Center. It's like that to me just speaks to how much this is being recognized as a problem and it's something that we need specialists for who are looking at the telephone history. What's your history of tick bites? What's your history of maybe reactions to food or things like that? What are your symptoms? And then also things like antibody test to figure out exactly what tech more illness, because there are many all over the world, from the many that we see in New England to those that are commonly found more in the south or in the west and that kind of thing. And so I think that that understanding is changing medicine, so it's changing the economics of food and of healthcare. And those are two really massive industries, and they're all being affected by this one tiny tick, which is just really interesting to look at and to back into, and also definitely something that has negatively impacted a lot of people's lives and caused a lot of suffering.

SPEAKER_04 24:28

That's for sure. Although I think it's important to also look at some of the potential silver linings in some ways out of this, because it has certainly caused quite a bit of suffering, to be sure. But the greater availability of vegetarian and vegan options, certainly at restaurants, potentially, is something that offers more choice for the consumer, and especially for people who may have already had some of those dietary restrictions to begin with. It's possible that restaurants that are adapting to this in some ways may be able to better market to a prouder client health in that regard. And it's also worth noting that certainly I remember when I was still living in Northern Virginia, how the question about Lyme disease in particular was something that I think people were aware of it, but it remained very much underreported and subject to misdiagnosis pretty commonly. And I think that the presence of more public health resources that are centered around these sorts of tick-borne illnesses mean it, AGS, Lyme, lots, and all of these other different diseases that are associated with tick bites, I think would be perhaps a good thing in many ways in these areas where these tick-borne diseases are endemic and are just a part of life of the assuming that we adjust to that reality and we live with it and we allocate the resources necessary to deal with that, the easier that the lives of everybody who would be impacted by it, I think, will ultimately be in the long run, even though the suffering that the individuals who are affected by these illnesses is awful and certainly can't like the way. I really feel for those people who were involved in that study, who thought that they were getting any drug that could potentially save their lives, and maybe could have, but they instead ended up dying of something completely different that they would never have expected to die of.

SPEAKER_03 26:16

Absolutely. There's just so much kind of kind of the fact that we use a massive amount of animal products, right? Whether it's for food, whether it's for other kinds of consumables that we make. And if you can just think of how hard it would be to filter things out, right? And so I think that's something that is worth being really mindful of when discussing this. And this can happen from one small tick bite, right? It's so interesting to me. Our immune systems are these just gorgeously intricate systems that keep us alive, but that can also so massively overreact. And I think it's so compelling to consider that sometimes the very things that are keeping us alive and healthier are also things that can put the risk. And I think there's so much tied up in this sort of case study into Alpha Gauss syndrome on what's the natural range of a species. How much does that change based on people's behavior? How much does people's behavior affect their risk, right? Something that we know might be on your lawn just to find it off the edge of a bike path in the woods. And so I think that is also really compelling, and I think it might change how we see the world. But I think what I do want people to take home is the things we can do to protect ourselves. And I don't want people to miss out on nature or social events like gathering someone charge. I was fear of this because I do think that we have dealt with many things like this in the past, and I'm not trying to minimize its impact or that it can be really exciting to think, but I think that there's still so much to learn and always to untangle with it. And it's nothing that always keeps me coming back to infectious diseases as a whole.

SPEAKER_04 27:57

Absolutely. Uh I couldn't agree more with that. And I do think that'll be interesting to see how we attack this on the long run. Because yeah, absolutely. I'm certainly not going to stop hiking or stop going outside just out of fear of this because yeah, that takes pictures. I kind of looked for so much of the Eastern and Midwestern US at this point. And we all have to keep looking. And so it's just a matter of going and minimizing it. Even if it's really hot outside, or just remembering to put some score when you're out. One way or another. I'm coming out. You better look for those on text when you go, and a couple of things for that event.

SPEAKER_03 28:52

But again, like, I'm still gonna go. That's like pretty much one of the places where it's highest race, right?

SPEAKER_04 29:08

Everything that we do inherently carries a risk of some form. In a way that makes you comfortable. Being aware of what that risk is and minimizing.

SPEAKER_03 29:21

I think you're right. That's totally what it is.

SPEAKER_04 29:28

I think this one leaves us in a place that feels a lot more realistic and trying to form it. And see what informed us of that and try to still live a lot in a way that makes a comfortable enough.

SPEAKER_03 29:46

Yeah, so thanks everyone. Thanks for tuning into this episode of Infectious Science. As always, we'd love to hear from you. If you have an episode topic that you want us to cover, let us know. There's also so many other wild diseases out there that we've never touched on and covered, and they're truly, I don't know, stranger than fiction. They're really, really interesting. So let us know. We always love to hear from you. Thanks again, as always, for listening.

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