This Podcast Will Kill You - Ep 49 Eastern Equine Encephalitis: Triple EEEk!

Episode Date: April 28, 2020

In 2019, eastern equine encephalitis (EEE), a viral disease transmitted by mosquitoes, made headlines in much of the US as cases skyrocketed compared to previous years. But why is this disease so feared and even more importantly, why is it on the rise? Those are just a couple of the questions we seek to answer on this week’s episode. From the nitty gritty on what this virus does to your body to centuries-long forest dynamics in Massachusetts, we connect the disease ecology dots of EEE. We promise, the biology and history of eastern equine encephalitis is much more exciting than its etymology. See omnystudio.com/listener for privacy information.

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Terms and conditions apply. Visit blueapron.com slash terms for more information. I'm Amanda Knox, and in the new podcast, Doubt, the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story? Evidence has been made to fit. The moment you look at the whole picture, the case collapsed. What if the truth was disguised by a story we chose to book?

Oh, my God, I think she might be innocent. Listen to Doubt, the case of Lucy Lettby, on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. I'm Clayton Eckerd. In 2022, I was the lead of ABC's The Bachelor. But here's the thing. Bachelor fans hated him. If I could press a button and rewind it all I would. That's when his life took a disturbing turn.

A one-night stand would end in a courtroom. The media is here. this case has gone viral. The dating contract. Agree to date me, but I'm also suing you. This is unlike anything I've ever seen before. I'm Stephanie Young. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts.

On the 7th of September, my boy took her from the pasture a little before sunset and harnessed her. While standing at the door, I observed she slavoured freely and was stupid and downcast in her appearance. I observed that she was loath to go faster than the walk, and although repeatedly urged forward by the whip, would shortly resume the walk. Once or twice on ascending a hill, she stopped for a second as if fatigued, or in pain, and several times in descending small pitches, she appeared in great danger of falling from the very bungling manner of using her forefeet. I continued my ride without discovering anything farther till the latter part of the evening,

except that whenever the whip was applied, a distinct interval was obvious between the time I struck her and the time she perceived the blow. When she did perceive it, the effect was greater than expected, for she started off as if surprise had been added to the usual effects of the lash. On my return home in the latter part of the evening, I experienced great difficulty in keeping her in the road, on account of an obstinate and constant tendency to the left, that required strong effort to counteract. She could scarcely be urged out of a walk, and it was perfectly evident that she was laboring under some alarming disease. I now made a careful examination and found the whole surface of the body cold and tremulous, countenance dull and listless, a leaning and stepping to the left, with so much appearance of general weakness as to induce the fear that she would fall in the harness. With much ado, I got her home, which was then but a short distance.

She, however, grew worse very fast, and when she arrived home, did not recognize her own stable. She was now well rubbed and a gallon of blood taken from the neck. While this was doing, and afterwards, she often kicked violently with her left foot. About 11 p.m. I was called from home and did not return until the next day about 2 p.m. when she was down and incapable of rising. She was left in care of a ferrier who had her blood again and given her several cathartic medicines without effect. She lay stretched out upon the floor, with her head drawn back, and the muscles of the neck, abdomen, and limbs frequently convulsed. At short intervals, she would revive or attempt to get

up, but could only get upon her hind feet, for her four legs appeared to be completely paralyzed. She would, however, make a powerful exertion to rise forwards and throw herself several feet ahead without regard to anything that might be in her way. No material alteration took place till next morning except gradual diminution of strength and exertion. In the morning, she commenced moving her legs backwards and forwards, was generally convulsed, and apparently in greatest distress. This state of things continued till 9 a.m. when she expired. I know.

That's really sad. Also, that was about a horse. That was, yeah. It wasn't obviously clear in the first hand, but that was. about a horse. Like taking her from the pasture, yeah, we should guess. We should hope. Four feet. So that was an account of the 1831 Eastern equine encephalitis outbreak in Massachusetts, written by Gardner M. Peck. And it was from a 1957 article titled an epizuadic of equine encephalomyelitis by R. P. Hansen. Hi, I'm Aaron Welsh. And I'm

I'm Aaron Oman Updike. And this is, this podcast will kill you. And today we're talking about AAA. Triple E, Eastern equine, encephalitis. Yes. That's very exciting. It is. So we actually, this is similar to our Dengue episode.

We have done this already in person at the University of Michigan. Whoop, whoop. Yeah. But just like Dengue, I've forgotten. I don't remember. I didn't even remember Aaron, like my own part of this. So when I went back to my notes, I was like, oh, this is depressing. Oh, yeah. It is. And I, yeah, I didn't remember any part of mine, which definitely means I remember zero part of yours. Oh, no. I don't know the history of this, like in the slightest. So I feel like it's kind of alarming how little. How quickly we forget. Yes. But that

But it was super fun to be in Michigan. And we really loved hanging out with Laura. So we wanted to give Laura and that group a huge shout out to having us and inviting us. That was so fun. That was when we did like actual chemistry. Remember that? Oh my gosh. It was like such an action-packed fun day. It really was. We enjoyed meeting everyone and talking to everyone. And yes. It was super fun. It was great. Ann Arbor is so cute. Yeah. I know. I wish we got more. more time there. Yeah. Maybe someday in the future we can go back.

Yeah. Someday. Someday. All right. Do we have any business to attend to, Erin? I mean, we could just do the usual suspects one more time. So we've got alcohol-free episodes. You can find them on this podcast, We'll Kill You.com under the episodes tab.

And we also have two things related to books. One is a Goodreads list. So we have a link to that on our website under the Books tab. And we also have an affiliate page on bookshop.org. That is an online bookseller that works with independent bookstores. All right. Now for the most important business of all. It's quarantine time.

It's quarantini time. What are we drinking today, Aaron? We are drinking the Triple E shot. That's a straightforward name. Yeah. I know. I feel like I think at the time we were like, oh, we'll come up with a better one when the episode comes out. And then here we are today.

Our creative juices have just been dried up, I think. Or used up. I don't know. Both, maybe. Well, what's in the Tripoli shot? The Tripoli shot has three things. Mm-hmm. Of course.

A half an ounce of coffee tequila. Okay. Delicious, even on its own. A half an ounce of hazelnut liqueur and a half an ounce of half and half. Fab. It's delicious. It's simple. It's easy.

There you go. All right. Fabulous. Anything else that we should cover or should we just jump straight into this depressing episode? I mean, I think it's just, let's just do it, Aaron. Let's just dive right in. It's actually, it's going to be very interesting. Okay.

Well, I'm excited to relearn everything that I've forgotten. Yeah, me too. Right. Well, we will start doing that right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients, so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep.

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Podcast 50. Terms and conditions apply. Visit blueapron.com slash terms for more information. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's Working Hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments.

It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters. when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit o'Keef's company.com slash this podcast and code this podcast at checkout. China's Ministry of State Security is one of the most mysterious and powerful spy agencies in the world. But in 2017, the FBI got inside.

This is Special Agent Regal. Special Agent Bradley Hall. This MSS officer has no idea the U.S. government is on to him. But the FBI has his chats, texts, emails, even his personal diary. Hear how they got it on the Sixth Bureau podcast. I now have several terabytes of an MSS officer, no doubt, no question, of his life. And that's a unicorn. No one had ever seen anything like that.

It was unbelievable. This is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Eastern equine encephalitis, aka Tripoli, aka also sometimes called sleeping sickness,

but not to be confused with African sleeping sickness or tropanosomiasis. Okay. Or encephalitis lethargica, because I think at the time it was also confused with that disease for at least the early years. Fascinating. Huh. Yeah. All right.

Well, this is not that. Eastern equine encephalitis is a viral infection. It is an alpha virus, which I don't believe that we've covered any alpha viruses thus far in this series. Triple E virus. It's an RNA virus. It is round in shape. So it's really kind of adorable when you look at it under scanning electron microscopes. There are four major lineages of this virus, so four major strains. But group one, which is the one that's most common in North America, is also the most virulent and the most common cause of disease in humans. So that's the one that will focus on just because that's the one that makes people sick. Okay? Uh-huh. All right. So I'm not going to talk a lot about the evolutionary history or the ecological cycle of this virus because you're going to do that, right, Aaron? Uh, I hope so. Excellent. But I will say, because we have to understand how this virus is transmitted, uh, Trips E, that's what I wrote down is the name for it. That's not going to

be confusing at all. Tripoli virus. It's mostly a bird virus. Okay. So it circulates enzootically among a number of different bird species. But it can cause both epizzootics. So that is an epidemic in animals when it jumps from bird populations into, for example, horse populations, equine populations, hence the name. And it can also cause zoonotic outbreaks. in humans if it jumps from birds into humans. Okay? Mm-hmm. All right. So among birds, it's primarily transmitted by mosquitoes in the genus Culeceta, but it can be transmitted by a number of different genera of mosquitoes, including 80s, mosquitoes, and others. There's an asterisk to that statement that I'll go into.

Oh, I can't wait to hear about it. I want to know. Okay. Do you want to know right now? Yeah, kind of. So basically they call these other mosquito species the bridge vectors. Uh-huh. Okay.

So jumping a little bit into the ecology side of things. Kuloceta, which is the genus, well, Kulocetta melanura, which is the main species that seems to perpetuate this infection cycle in like, you know, birds. Right. They are not mammal biters or human biters, like very, very little. And so researchers are like, well, it might be that there's either they occasionally bite them. humans and that's how these things happen or it's bridge vectors. But in one study that looked at the like viral load of other species of mosquito, some of the proposed bridge vector species, none of them had viral loads that were high enough to actually cause infection. Fascinating. So it might

be that you can detect the virus because that mosquito fed on an infected bird. but the virus might not be able to replicate within that mosquito. Oh. But there's still a lot of like question mark, question mark, question mark, and this sort of thing. So it's like that aspect of the ecology is pretty not very well clarified yet in terms of like the contributions of this mosquito species versus this mosquito species and also geographically because that can play a huge role.

So then it's like unclear exactly which mosquitoes might be infecting humans. Right. So basically I think the takeaway that. that I got from that article was that even if you detect this virus in a mosquito, it doesn't necessarily mean that it's going to be infected and able to transmit. Right, because these viruses have to be able to replicate within the mosquito and then leave the mosquito's gut and travel to their salivary glands and then be there in high enough concentration that when the mosquito bites its next host, it's injecting enough virus to

actually get that host sick. So these are very complicated cycles within the mosquito. So it makes sense that not every mosquito is going to be able to transmit every virus. Right. So even if you can detect it just when you smush that mosquito, like, yeah, you found some virus, but where was that virus within the mosquito? And how much of it was there. Cool. How interesting. All right. So we've covered now that this is a disease transmitted by mosquitoes will ignore the detail. of which mosquito it is for now. So let's talk about how this virus makes you sick once it gets inside you, okay? Mm-hmm.

So like many arbiviral diseases, so viruses transmitted by arthropods like mosquitoes, when a mosquito bites you, the first place that it spits that virus is kind of towards your lymphatic system, right? So it's kind of right under your skin. They don't spit it necessarily directly into your bloodstream. but they spit it under your skin and that virus goes into your lymphatic system. From there, it travels to your lymph nodes. And in the case of Eastern equine encephalitis virus, it infects our white blood cells.

Okay. So those are the cells that it goes into and that's where it replicates. Remember that viruses have to replicate inside of our cells. They don't replicate on their own. So it turns out that Triple E replicate. replicates inside of our white blood cells. White blood cells can travel pretty much anywhere in our body, including crossing the blood brain barrier and making it into our nervous system.

All right. So let's go through kind of how this makes you sick. This is a bit of a spoiler, but this is a horrible, horrible disease. Okay. So that much I do remember. Yes. from Michigan. If you had like a magic eight ball and you shook it, it would say outlook, not so good. Yeah. Okay. One of the questions that I like to try and answer when we look at a disease that causes such

terrible outcomes is how does it do that? We are usually very good at fighting off infections. So how can this virus kind of beat our own immune system, right? Like how can it make us so very sick? Okay. So the other reason that it's important to understand how this virus makes us so sick is because in theory, if we can understand how it makes us so sick, we could maybe try and do something about it, right? We can try and counteract that. Okay. So I found a few different studies that tried to shed some light on exactly how this virus makes us so sick. One of the important things is that this virus is very good at evading our immune system. Specifically, it seems to do a very good job of inhibiting one of our major responses to viral infections. And that is something called interferon, which I think we've talked about in like the hepatitis episode, probably. I don't remember. But anyways, interferon is a protein that we make that helps to stimulate our immune response specifically to target and kill viruses and virally infected cells. Gotcha.

So, AAA, like many other viruses and a lot of arbiviruses specifically, targets and shuts down the production of interferon, it seems like, in us. And what's really interesting is that there have been some other studies I found that compared the effectiveness of interferon on actually killing virus-infected cells. So like, even if you gave someone a bunch of interferon, Like if that's the problem, the virus is blocking this production, give them interferon. This virus actually, like, inhibits the action of interferon. That's wild.

I know. And here's where it gets even cooler. This is why I get excited about this. Remember I said there are many different strains of this virus, like at least four. And it's only the North American strain that tends to be the most virulent and cause infection in humans. So this one study compared North American strains to South American strains. And what they found was that across the board, all cells infected with AAA viruses, North American or South American, had very low levels of interferon.

So they blocked the production of interferon. But on top of that, the North American strains were the ones that were also resistant to the effects of interferon. Huh. So, like, no matter how much interferon you had in your body, it was going to be lower with a triple E infection than with other viral infections. Right. But the interferon that you do have works to kill that South American virus, but not the North American strains. Wow, that's very interesting. I know.

Okay. So that's how it causes disease and why, at least part of the reason why it probably causes such severe. disease, okay? Now let's start to talk about the really depressing part, which is the actual symptoms, okay? The one good news I have, this is it. It's estimated that only about four to five percent of human infections actually result in symptomatic disease. So like... I was just about to ask that. Oh, good. I preempted you. Ninety-six percent of people who get infected with triple E virus will never have symptomatic disease. They're going to be just fine. Okay. That's the estimates. But that's, I feel like that's a trend that we see a lot in arboviral diseases,

that there's a huge rate of asymptomatic individuals. Yeah. Do these people have immunity? Do they develop immunity to AAA virus? Great question. I did see in several review papers, just sort of talking about the symptoms in general, that it is thought that yes, when you are exposed to this, this virus, you develop long-lasting immunity. Remember that point because it will become very interesting when we talk about the vaccine. Yes. Okay. But yes, it is thought that if you get infected with this virus, whether you're symptomatic or not,

you do generate long-lasting immunity. Okay. Yes. That's the thought. That's good news. It is good news. That's the end of the good news. Okay.

So let's talk about the symptoms of this virus. It's called Eastern equine encephalitis. Encephalitis. We've talked about this before, right? This is inflammation in your actual brain. It's not good news. So this causes a viral encephalitis. In theory, almost any virus could potentially cause an encephalitis if it gets into your brain and causes infection there.

For most viruses, that's a very uncommon manifestation. But for some reason, a lot of arboviruses, so musk, Ghetto-borne viruses do cause viral encephalitis. And we've also talked on this podcast about one of the most famous causes of viral encephalitis, that is, rabies. Oh. I saw your face just be completely blank, and I was like, don't worry. So rabies is like the most probably famous viral encephalitis, I think.

So let's talk about the characteristic symptoms of viral encephalitis. there's three. Number one, fever. This fever tends to be quite high and it tends to come on very rapidly. Number two, headache, because your brain is inflamed. Number three, altered level of consciousness. Now, that doesn't necessarily mean that you will go unconscious, although, as you'll see, it often leads to that. But it does mean that like overall you can have fluctuating levels of consciousness. Okay. Okay. And kind of awareness.

And then because viral encephalitis is a viral infection of your brain, you will often have specific neurological symptoms that can be very varied. And they tend to depend, the specific symptoms you see, tend to depend on what part of your brain is the most infected. Okay. So let's talk about triple E specifically. If you have symptomatic infection with triple E, which again, it's only 4 to 5% of people, so that's the good news. The symptoms begin with a prodrome, which essentially means nonspecific symptoms before the real bad symptoms. This is like that fever, maybe headache, maybe even some abdominal pain, just very non-specific symptoms.

And then about five days later is when the neurologic symptoms begin. And in the case of Tripoli, this can be anything from a mild confusion to maybe some focal weakness, like your arm feels weak or your leg feels weak. Okay. You might have seizures. Seizures are actually very common in Tripoli. Okay. You might have paresthesias. So like weird tingling feelings or just like sort of sensory things that aren't normal.

Is this just because your brain is inflamed? Yes, absolutely. Okay. Yep. But in the case of Tripoli, once any of these neurologic symptoms tend to start, even just sort of confusion and maybe like coming in and out of being very aware, you know, like not being able to focus, that kind of thing. very rapidly, in the case of AAA, people progress to coma. Okay, what's the timeline of this? Like hours to a couple of days.

Oh, wow. Yeah. So once people develop these neurologic symptoms, after this like five-day prodrome of kind of feeling crudy, having a fever, having a headache, people deteriorate very, very rapidly. And then, once they're in a coma, the mortality rate is between 30, and 40%. Okay. So what proportion of people go into a coma? Like develop these severe neurological symptoms? So almost everyone. So if you become symptomatic, almost certainly you're going to go into a coma. Of those that survive, about a third of them will have significant neurologic

impairment permanently as a result of this infection. Oh, yeah. I have a question. I have a question. Okay. These unlucky 4%. Why? Such a good question, Aaron. I have no idea. And I think part of the reason that... So, okay, some of the literature says children under age 15 and adults over age 50,

they are more likely to actually get the encephalitis form of Tripoli. That's the most that I've seen in terms of, like, who is it that ends up getting triple E versus just getting infected and not showing symptoms? I think we have to remember that this is a very, very rare infection. So it's really hard to understand exactly who is the most at risk and why. Like what is it about the characteristics of these people that make them more likely to have this neurologic manifestation versus never having symptoms? Right, exactly.

Yeah. So of all the arbiviral encephalitis viruses in the United States, this is by far the worst one. Like mortality rate is so much higher. It's possibly even worse than Japanese encephalitis, although that's more common. That's not in the United States. It's in like China and Japan. But there's a vaccine for Japanese encephalitis. So why isn't there a vaccine then for AAA virus?

Oh, Erin. I was going to talk about all of this in more detail in the future in the current event section. Well, let's just wait for the future then. Yeah. Do you want me to talk about it now or do you want me to talk about it in the future? Up to you, girl. Let's talk about it later because we'll talk in more detail about the research that is being done. Okay. But one thing that I think is really interesting is although there are small case numbers,

they have been a few good studies like grouping all of these. cases and trying to understand like what is affected in the brain when you get infected with Eastern equine encephalitis. And it tends to actually be the basal ganglia, which is part of the brain we talked about that's affected in Parkinson's. It's also infected in encephalitis, lethargica, if you remember? Yeah. Okay. And it also infects like your midbrain and that's part of your brain stem. And so it's really interesting because, you know, when I am looking at this, I want to think, like, why do we see the symptoms that we see? So if you have a virus like rabies that infects your brain, it affects a part of your brain that

changes the way that you behave, right, and your mood. And then we see that in the symptoms, right, where you get angry, et cetera. If you get a herpes encephalitis, which is actually the most common cause of encephalitis, viral encephalitis in the U.S., it infects the temporal lobe, which is where your language centers are. So your symptoms are like having trouble finding words, which is called aphasia. Okay. So for me, I'm like, okay, so we know that it infects this part of the brain, but how come we don't see these symptoms like maybe shakiness like in Parkinson's or these certain types of symptoms? Yeah. My guess is because it causes lesions in these areas like your brain

stem that are so important for generally being alive, then you progress so rapidly and deteriorate so quickly that there's no time to have those specific isolated neurologic findings. Right. Right. So it makes sense. Depressing. Yeah. Yeah.

Makes sense. We can talk quickly about treatment, if you'd like. Okay. There isn't any. I was going to say, is it just supportive care? Yeah, it is. There are no antivirals, even in screening studies that have been shown to be effective against Tripoli virus. So that's a bummer.

I did find a few case reports where they've been using IVIG, which is intravenous pooled, concentrated human immunoglobulin, which is used a lot in autoimmune disorders. It's used in the treatment of neurologic disorders. whether or not it works, who knows? Because I found two case reports that were like, we used this and they survived and did great. And then I found one that said, we used this and they died. But that person also had lymphoma, so like, who knows? But we have such little data on any of this. And it's so difficult to study because we have so few cases that we really have no idea if IVIG would be

actually an effective treatment or not at this point. Gotcha. What about with other of the encephalitis viruses? Whether we have antivirals? Yeah. Good question. I don't know. Yeah.

Yeah. I don't believe we have any for dengue, which can cause encephalitis. The more common ones like St. Louis encephalitis, West Nile virus. I honestly don't know. I haven't done the research on those yet. Okay. Yeah. Interesting. But we will talk in more detail about the vaccine in a bit.

But first, Erin. First. What the heck? Where did this thing come from? And why does it invade our brains and kill us so rapidly? Oh, I don't know if I can answer the why to that. I think we're just sort of a bystander. I mean, once again, this is, we did not plan this. But coincidentally, we're talking about two things for which humans seem to be a bystander.

and for which birds are heavily involved. Birds. Killing us. I will answer those. No, I will attempt to answer those right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something.

That's why O'Keeffe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters

when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. In 2023, a story gripped the UK, evoking horror and disbelief. who should have been in charge of caring for tiny babies is now the most prolific child killer in modern British history. Everyone thought they knew how it ended. A verdict? A villain? A nurse named Lucy Lettby.

Lucy Lettby has been found guilty. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses. I'm Amanda Knox, and in the new podcast, doubt the case of Lucy Lettby, we follow the evidence and hear from the people that lived it, to ask what really happened when the world decided who Lucy Lettby was. No voicing of any skepticism or doubt. It'll cause so much harm at every single level of the

British establishment of this is wrong. Listen to Doubt, the case of Lucy Letby on the Iheart radio app, Apple Podcasts, or wherever you get your podcasts. China's Ministry of State Security is one of the most mysterious and powerful spy agencies in the world. But in the In 2017, the FBI got inside. This is Special Agent Regal, Special Agent Bradley Hall. This MSS officer has no idea the U.S. government is on to him. But the FBI has his chats, texts, emails, even his personal diary. Hear how they got it on the Sixth Bureau podcast.

I now have several terabytes of an MSS officer, no doubt, no question, of his life. And that's the unicorn. No one had ever seen anything like that. It was unbelievable. This is a story of the inner workings of the MSS and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Okay. Ready?

Yes. The year was 1933. I love it when your sections start like this. Aaron. I'll do it each time. I also love the little cherry-picked things that I have here. I'm like, why? Okay, well, whatever.

Anyway, lots of bad things were happening in 1933. In the U.S., the Depression was in its worst year. Hitler became German Chancellor. The Dust Bowl was still raging in the Midwest in the U.S. An earthquake in California caused massive damage in Long Beach. There were forest fires in Oregon, and horses were dying by the dozens. In pockets of the northeast, particularly along coastal or swampy areas of New Jersey, Delaware, and Maryland, horses started acting strange. They started to walk clumsily, their heads were only able to look in one direction, and that led to them walking in circles and gradually losing mobility before.

Dying. Hmm. About 90% of the 1,000 horses, roughly, that were affected by this illness, died during this epizuotic. Wow. Yeah. That's a lot. That's bad.

It's really bad. And because this was 1933, germ theory and microbiology had advanced enough to the point where researchers were kind of like, you know, quickly mobilized on the case, taking brain samples from these horses that had died and seeing if they could isolate whatever pathogen was causing this damage. And they figured out pretty quickly that it was a transmissible, filterable agent, which is essentially code for a virus most of the time. Or a preon, not in this case. Not a preon. And they discover that it was. this transmissible filterable agent because they were able to successfully inject it, whatever

it was, into guinea pigs who also died as a result of the same sort of symptoms. Acting like guinea pigs. And the researchers gave this virus a name. Eastern equine encephalitis virus. Eastern, of course. The etymology is not very exciting for this one. Yeah. Eastern because it was in the eastern U.S. equine to indicate that it was found in horses, as you've mentioned, and encephalitis for all the reasons that you've mentioned.

Boom. Like the least exciting of all of it so far, I think. It's the most boring, yeah. Yep. So at the time when this virus was isolated and named, and many researchers were treating it as a new infection that had never been seen before, but it didn't take long for people to realize that AAA virus had shown up in the northeastern U.S. previously, and it only took a few more years to realize that this

episodic wasn't an isolated one-off, that there would actually be another outbreak even within the same decade. In 1938, which is five years after this massive outbreak in horses took place, another outbreak of Tripoli began, but this time it wasn't just in horses, although horses were affected. Humans, especially children, were showing signs of infection and also dying at extremely high rates. So in late summer and early fall in Massachusetts, particularly the southeastern part of the state, there were 34 cases in humans and 25 deaths. Oh, man. Pretty high case fatality rate. And that's a lot of cases for just a couple of months in one state. Like that's a lot. Yeah. Yeah. And like you said, the handful of people that did survive had these long-term effects.

And so because of the severity of the disease and the really, like, horrible side effects in the people who did survive, this kind of gained really widespread national attention. I imagine, too, because it was primarily affecting children that that would attract. Yeah, it was when it kind of really became apparent that, like, children were a very high-risk group for this. Yeah. And so because of the severity of this illness, people started to put in the hours to do research. They started to look in the past for old epidemics. And they also started looking around them to see whether they could determine what the source of this current disease outbreak was. And people started noticing some unusual deaths among pigeons and ringed-necked pheasants in the same places that people were getting sick.

and then researchers were able to isolate the virus from some of these birds. And researchers were suspicious that mosquitoes were responsible for transmitting the virus or the transmissible filterable agent, but it would take a little bit of time before they could pin down the exact species that seemed to be the culprit. And part of the reason is because a hurricane washed away all of these mosquito collection sites in 1938 when they were... Oh dear. at the height of their research.

Just on things on top of things, huh? Things on top of things. Okay, so as I mentioned, researchers also realized, hey, this is not a brand new disease to humans or to horses. So let's go back to 1831. Yes. The year was 1831. Just kidding.

But just like in 1933, in 1831, lots of horses were dying in the northeast, particularly Massachusetts. Not as many as in the 1933 episodic, but about 75 horses died in total, which, you know, thinking about in 1831 and how people, you know, used to use horses so much more than they did in 1933, it would have been devastating to the horses' owners and also devastating emotionally. But yeah, in terms of economics and losing a horse would have been hugely, hugely devastating. Right. And like in the 1933 epizelotic, the one in 1831 in horses also occurred in late summer and had a very high mortality rate as well, again, close to 90%.

Why is it higher in horses than in humans, Aaron? It's a good question. I've been thinking a lot about that ever since you mentioned that. And also you were mentioning the, like, symptoms that you see in horses where they have a lot more motor symptoms and, like, trouble walking and leaning. Yeah, it's a really good question. I don't know enough about veterinary medicine to know, like, what the differences are in their immune response maybe or what. But I wonder if they, like, have a longer period before they deteriorate, and that's why you see those motor symptoms as it affects their basal ganglia and things like that. But yeah, I don't know. Maybe they have less interferon or something to begin with.

Maybe they just have a different, I don't know anything about horse immunology. So I have no idea. But it's a really interesting question. Interesting. Interesting. So it's also interesting to contrast the 1831 epizootic and the 1933 epizootic and the 1933 epizzoatic in terms of the response, like the scientific response. because if you think about 1831, germ theory wasn't really a thing yet. And so people were like, we have no idea what's causing this.

And so some of the guesses were like, well, the horses that fed on grass were the ones who got sick. So there was maybe something in the grass. What? I have another thought. Okay. Because it sounded like from what you were saying, like 25 out of 30 kids died in Massachusetts, that's a lot higher than today. So I wonder if it could too have to do with supportive care.

Like today, the mortality rate is 30% maybe in humans because we have some supportive care in the hospital, whereas you're not going to probably intubate a horse and try and keep them alive if they've got Tripoli. I don't know. Just a thought. Yeah, I mean, that seems definitely possible. Possible. I don't know. Yeah. Yeah, so like the 1938 outbreak was around 74% of people.

Okay, yeah. Yeah, so maybe it's just the difference in supportive care or something. Yeah. I don't know. Yeah. We're guessing here. Yeah. We should stand on not so shaky ground.

Yeah. And so part of the reason that one of the guesses was, oh, well, the horses that fed on grass were the ones who got sick, as opposed to like hay in the stables. Okay. It's because what they were seeing was that horses that were kept on the pasture seemed to be more likely to be sick than the ones who stayed in the stable. And so the miasma explanation almost kind of worked in this case. But, you know, let's go to the treatments.

So treatments were not helpful for horses. Mostly, as you heard in the first-hand account, it was to drain the horse of a couple of gallons of blood. The one and only thing I remember from our Michigan Day, Erin, was that we had someone in the middle of our presentation Google how many gallons of blood does a horse have. Yeah, I loved that. I think that they also Googled like several other things for us in the midst. An auto fact checker. But do you remember how many gallons of blood a horse has?

No, now I'm going to have to Google it for myself. Okay. 12.3. Did you get that from thehorse.com? I got it. Yeah, thehorse.com. It's got to be a legit website, right? Oh, see, now I'm seeing different responses here. Okay, so it seems like, I mean, horses aren't come in all different shapes and sizes.

So if you have a massive horse, it could be 15 gallons. 15 gallons. Let's say like 10 to 15 gallons. Sure, that sounds reasonable. So a fifth of your blood. That's a lot of blood. It's a lot of blood. And it's not going to do you any good. Mm-mm. Mm-mm.

Okay. But after this relatively short-lived epizootic ran its course, it kind of just faded from memory because it showed up again in 1847, in horses again, and people were like, oh my gosh, there's this new disease, it's horrible, it's killing our horses. We don't know where it came from. So interesting that it fades from memory so quickly. I mean, but it's so, I think it was so localized in 1831. It didn't happen to the same individual people that second time maybe. Right. And I don't think, I mean, maybe it did happen in the same region, but I also don't think that's like, you know, you can't Google. If you're in 1847, you can't Google horse disease.

Yes. It's so true. So there were probably many other things on their minds as well. Mm-hmm. Okay. So all of this had happened before. meaning AAA outbreaks in humans and in horses. But what had taken so long for it to return?

And since the 1933 outbreak in horses and the 1938 outbreak in humans, AAA virus has continued an upward climb in human cases, or at least in the frequency of outbreaks, which is a pretty big concern for the people who live in these high-risk areas. Right. Okay. So, but in order to answer, answer why it seemingly disappeared for about 100 years. Because from 1847 to 1933, there's not,

there doesn't seem to be any outbreaks, or at least notable outbreaks that I could find. And so to answer why it disappeared and then also why it's on the rise now, we have to look back at history, but we have to do that through the lens of ecology, which is our favorite. Our favorite. All right. So we already talked a little bit about the of Tripoli virus. But let's kind of go into it again in a little more detail. Yeah. All right. So first of all, we know about the Tripoli virus itself. We don't need to cover that again. The mosquito. The mosquito species that's most closely associated with triple E virus again is cul-a-seta melanura. And we have not talked about this mosquito on any other

episodes of the podcast before, even though we've done like a fair number of mosquito-borne diseases at this point. And the reason for that is kind of what I've already said. This is not a human biter. And so it's not really associated with many human diseases like dengue, yellow fever, Zika, et cetera, some of the ones that we've covered. And so we haven't really had much of a reason to talk about it before. But this mosquito isn't really even a mammal biter at all, like I said. It feeds on birds. And so this mosquito species can be found over a pretty wide range geographically. So from like the southeastern provinces of Canada, throughout the eastern U.S. and some southern states along the Gulf, they require freshwater wooded swamps or sphagnum bogs with little water-filled hollows in fallen trees in order to lay eggs for the larvae to develop.

So you need trees and water. typically standing water, or at least water at like the soil level. And after the larvae developed these little nooks and crannies, adult mosquitoes then happily emerge to feed on whatever birds are around. And those birds tend to be water-dwelling birds, although not 100% of the time. There was a study in Massachusetts that examined the bloodmills of these mosquitoes, both inside and outside of a swamp. And in both times, nearly 99% of the blood meals were from a bird host. Okay. So it's like a very specific feeding pattern. Very, very specific. Yeah. So then the

virus basically continues in this natural cycle. So in birds, in mosquitoes, and birds and mosquitoes. So from year to year, it's not really entirely clear how it overwinteres. It either overwinteres in birds, although that seems less likely because birds do recover from infection or they die. Okay. There are like some birds, some birds don't seem to be affected at all. And some birds die with it a few days of being infected, at least experimentally. So it's a lot like West Nile, I feel like. Mm-hmm.

Right. There's varying susceptibility among avian hosts. Okay. Yeah. And some birds contribute more than to the viral prevalence. Yeah. But yeah, humans, horses, pigs. So I don't think you mentioned pigs, but pigs have also been shown to be infected with

Tripoli virus. These are all dead-end hosts, as we talked about. So they don't contribute to the circulation of the virus in the environment. So like basically what that means is that if a mosquito, let's say that a horse got infected with the virus and then a mosquito that was uninfected bit that horse, it probably wouldn't get enough virus to be able to replicate in that mosquito. And then it would also take the appropriate mosquito species to bite that horse, which tends to be unlikely, given the low biting frequency outside of birds. Right.

Okay. So how on earth do humans or horses or pigs ever get infected? And it turns out the answer is not that straightforward, as I mentioned earlier, because the disagreement on whether these bridge vector species actually contribute to infection. Okay, but first let's talk about sort of this year-to-year variation in outbreaks because some years we see a big increase in cases, some years we see none at all. And because this is so rare, it's kind of we don't have good enough data to kind of make clear-cut answers on this. But what it seems to be is that it comes down to, you know, mosquito ecology. So mosquitoes, because they live outside, are super dependent on environmental conditions. the weather. So let's say that there was like a super rainy season last year and a hot and humid and

early summer this year. And that could mean, you know, higher warm water for these mosquitoes to lay their eggs in the little nooks and crannies of the trees and then develop more quickly. And then the viral replication itself also depends on external temperature. And so that could mean, you know, so let's say last year, 2019 was rainy. and hot in some of these more, you know, swampy or boggy areas, then maybe this year we would have higher cases of AAA virus. And then geographically, the variation has a lot to do with these larger weather or climate patterns and also just how much mosquito habitat there is for this particular mosquito.

All right, but let's look at some of these larger overall trends in the frequency of outbreaks. So like more on this larger time scale. Okay. Okay. So remember, people get infected by the bite of mosquito, whether it's cula ceta melanura or this bridge vector species. But in either case, those mosquitoes have to be infected by a bird. And these birds tend to live in these boggy, swampy areas. And so you think as a human you'd have to be pretty close to those in order to get infected.

Right. All right. So let's talk about the history of swamps and bogs in the northeast. particularly Massachusetts. And I'm using Massachusetts as a case study because that's where AAA cases have been the highest and the outbreaks have seemed to impact the most. All right, so during the 200-year period from around 1650 to 1850, European settlers essentially stripped the land of forest and wetlands.

They used pines for masks on ships. The cedar swamps were destroyed to make shingles, posts, barrels. Other forests were used for lumber, firewood, and charcoal, or they were cleared entirely to make room for agricultural fields. And by the mid-1800s, deforestation was at its peak in Massachusetts, and the countryside was like naked. It was nothing left. Henry David Thoreau, who wrote Walden, said about Concord Massachusetts around this time, of the primitive wood, woodland which was woodland when the town was settled, I know none. Whoa.

And so as you can guess, this massive deforestation caused enormous cascading ecological effects. And especially relevant to AAA, bird numbers and species richness declined, and culocetamalinaura also lost the swampy habitat that it needed to survive. And starting in the second half of the 1800s, reforestation picked back up because people were like, we can't continue to over-exploit the land because there's nothing left. Like we have really, you know, put ourselves in a very bad situation by doing this already. And also people started to abandon these unproductive farms to move to cities. So sort of both a conscious decision of we need to reforest and also just sort of it happened naturally as people stopped using the wood for farms and whatnot. And so this meant that forest cover increased greatly throughout the early 20th century,

with wetland restoration lagging a bit behind deciduous forests. But ultimately, what this meant was more habitat for birds and mosquitoes and thus Tripoli virus. And several researchers point towards this large-scale landscape change as being a cause of the reappearance of the virus in 1930s and why it has stuck around ever since then. But before you take up your chainsaws to reclearcut the forest of New England and drain the swamps and bogs, consider, please, that it's not the mere existence of these habitats that leads to these Tripoli outbreaks. But really, it's sort of the way that we develop suburban communities, especially the residential ones. With those areas. And so a lot of these suburban neighborhoods tend to create.

into and on the borders of these wetlands. And so that's where you have this, like, once you do that, once you get closer to that, that means that you're just more likely to come into contact with these infected mosquito species. And also, wetland conservation is hugely important for flood protection and healthy water supply. And they provide these amazing habitats for diverse and unique communities of plants and animals. And so by the time this episode comes out, it will have been roughly a week after Earth Day. Oh, cool. Earth Day is April 22nd.

Tomorrow, a couple days from now? A couple days from now. And Earth Day, it'll be the 50th anniversary of Earth Day. How exciting. Wow. Happy late Earth Day, everyone. So let's just keep that spirit going. Yes.

We are certainly not anti-wetland. No, no, no. You're pro-forest, pro-wetland over here. I think it's just a really interesting example of how large-scale landscape change can influence disease transmission, particularly zoonotic diseases. Yeah, definitely. So from these outbreaks on 1930s to the last decade or so, we've seen sporadic human cases here and there, largely restricted to the northeastern U.S. But we have seen more hoarse outbreaks. But since that time, we've seen both an increase in the frequency of cases and in their geographic distribution.

And because this is a vector-borne disease, teasing apart the cause of this reemergence is tricky, because it depends on so many factors. So like I talked about, increased rainfall one year, reestablishment of wetlands or development of human dwellings in close proximity to these wetland areas or any sort of habitat where aculocetamelanora likes to lay its eggs, so many things can play a role in this. And although this is a rare disease, it can be extremely deadly, and that can lead to a fear-respective. sometimes out of proportion to the actual risk. A lot of controversy surrounds the control measures that are often used to try to prevent infections. And there are these questions like, should there be widespread aerial spraying with insecticides? Or is that just asking for another ecological disaster?

Is public education effective? Or is it even enough? Are we in for a bad year of Tripoli virus? Aaron? What do you think? where do we stand with AAA today? Let's talk about it right after this break. So, AAA is unsurprisingly a nationally notifiable disease, right?

Because it's pretty devastating. So let's talk about how many cases we tend to see in the U.S. per year. From 2009 to 2018, so about the last 10 years, on average, there were seven cases per year. And that ranged from three in 2009 to 15 in 2012. Okay. Okay. So like pretty rare and like not a huge amount of variation year to year from 2009 to 2018.

Mm-hmm. Now. In total, I will say that entire period, there was only 72 cases in total. Could you extrapolate upwards and say if that that, that's 4%, then there were X number of people who were likely exposed to the virus? Sure, let's do that. Like, is that a reasonable extrapolation? That's a good question.

Theoretically, why not? If we think that 96% of people are asymptomatic, then yeah. If there were 72 known cases that were reported, then how many cases is that total over that time period? I actually have no idea how you do that. Math. 76 over X equals 4 over 100 and then find the X. 72 times 100 divided by 4? Mm-hmm.

1,800 cases over about 10 years. Still pretty low prevalence. Pretty low, yeah, absolutely. Now, that was 2009 to 2018. What about 2019? There's a reason that we did this as a live episode in Michigan, and that is that 2019 was far and away the worst year of Tripoli in a very long time. As of December 17, 2019, there were a total of 38 confirmed cases of Tripoli in the United States, including 15 deaths.

Wow. Yep. That is more than twice the maximum. of the last 10 years. That's very, okay, why? Great question. I don't know. I mean, it likely was a lot of what you said, right?

Like a bad year for rainfall the year before or something like that. But what's interesting is that these cases happened in number of different areas. It wasn't just all in one spot. The two states' most hardest hit last year were Massachusetts and Michigan. So in Massachusetts there were 12 confirmed human cases and 10 confirmed deaths. Now there was also a large increase in the number of animal cases last year as well. There were in Michigan 48 cases of AAA in animals last year. So yeah, it's a good question.

I don't think that we have a full handle on exactly how to predict which years are going to be the worst. like Fauci said in that article, right? He wasn't the first author. Yeah, it was Morin's at all. Morin's at all said in that article, we need to do better research to be able to answer those types of questions, right? We need to have a better handle on what are the factors that contribute to whether or not we're going to have a bad year. Right.

Now, the only good news about this is that, so you kind of mentioned where this tends to be a disease that's common, right? It's on the east coast, a lot of it in the northeast, but also along the east coast and the Gulf Coast, as well as the Great Lakes region. Right. So the other states that had reported cases last year include Alabama, Connecticut, Georgia, Indiana, New Jersey, North Carolina, Rhode Island, and Tennessee. What's the good news in this? Most of those areas have like a mosquito season. Gotcha. Okay.

So at least it's over for now effectively, right? Although now it's springtime, so welcome back. Yep, yep, yep, yep. Yeah, so that's the only good news is like at least it's over for now. We can hope that this year's going to be better. And that's the other thing too is that it seems to be, based on when these cases happen, it does seem to be like in a very narrow time window throughout the year, particularly in the more northern places where the eskido season is so concentrated.

Yep. Which makes sense. You can sort of heighten your vigilance during that time, I guess. So that's where we stand in terms of the number of cases of Tripoli. You asked about a vaccine. Because there's one for horses. There is one for horses. It is a whole killed virus vaccine.

It's not great even for horses. So from what I have gathered, for some reason, and this is very interesting considering that we believe that if you are infected with Tripoli virus, you do mount a good immune response and are then prevented from getting infected again. But for some reason, the vaccine that we've tried to develop for humans and that we even have for horses and other animals, it doesn't generate a very good immune response. And the immunity that it provides is not very long lasting. Huh. Even in horses. Yeah. So I'm not sure, like, the schedule for if you have a horse, how often you have to give that horse boosters. It might

be something like, I have to give my dog the rabies shot like every year or something like that. So it might be the same for horses. Yeah, they do do boosters. Yeah. But so that's, it's really interesting, Right? Like, why is it that we can't develop a vaccine that is more immunogenic that provides us with a longer lasting immune response? Is part of it in the funding and that this is a rare disease? You put the nail on the head there, Aaron. Is that how that goes? That's how that goes. Yeah.

There is no market for a AAA vaccine. Right. Right. We still don't even have a West Nile vaccine. and that causes a lot more infection in humans every year than this does. So if you want proof that there's really not a market for it, I have found papers of people doing research on this. So in 2007, there was a really interesting paper that made a hybrid attenuated vaccine.

So instead of doing a killed virus, they made a hybrid virus out of Tripoli virus and some other virus. I don't remember which one. And they tested it in mice. and they found that it was highly immunogenic. That was in 2007. Nothing else. Okay, so in theory, it could. In theory, it's possible.

I did check clinical trial.gov, which, again, is where you can find all the clinical trials that are happening. And there are studies listed for AAA. Two of them were U.S.A.M.R.D. U.S. Samrid. I don't know how you say it. The U.S. Army Medical Research Institute of Infectious Diseases. they had two vaccine trials that are now concluded.

One of them had results posted, which are actually very difficult to sort through on clinical trials, by the way. Overall, it's hard to get an estimate on exactly how long-lasting the immunity was from this virus that they tested, but it was somewhere between like 28 to 70% of people, depending on the time frame that you looked at it. So like 70% of people that they tested had an immune response, like, right after their second booster. But then of the people they were able to test out a one-year follow-up, only 28% of them still had high titers of antibodies. So they mounted an immune response, but it wasn't very long-lasting.

Right. Just like the horse vaccine. Yeah. And so that makes it even harder to try and get funding for a vaccine like this. If you think, like, this is a very, very, very rare infection. And you'd have to get a vaccine for it, what, like every year? Like, that's very difficult to try and sort of convince funders or people to get a vaccine like that, right? Right. So then a lot more, so it comes down a lot more to the prevention and surveillance aspect. Absolutely.

Yeah. Yeah, definitely. So, yeah, that's where we stand. With Tripoli virus. Well, do you know what the predictions are for this year? Was it rainy in places? Was it hot? Let's see. Is there an early summer? It snowed in Chicago like two days ago, so.

You know, I've been thinking about that. It snows every April in Illinois. Every April I go, I can't believe that it's snowing, but it does it every April. I remember my prom in Kentucky, it snowed. That's wonderful. Yeah, I got out of prom and there was snow on my car. I was like, I'm in a hot pink sleeveless dress. Oh, I can't believe I've never seen pictures of your prom dress. Because now I'm really...

It's about what you'd expect. Oh, I really want to see it now. Hot pink sleeveless. I love it. Let's see. According to this news article I just found, health experts believe Tripoli will rise again next year. I guess normally these cycles tend to last for two to three years. Well, you have two to three years in a row of bad year. And it was very wet and rainy in 2019.

Great. Great. You know how with Lyme disease and ticks, there's like that distinct, like the mast and the mice and then the deer and then the ticks. Right. The sequence of events that lead to these high outbreaks or these like outbreaky. they're just not well known. And I think it's because the outbreaks themselves are so small. So small.

And so it's sort of now we're playing like, you know, retrospective detective trying to pick apart the pieces. And that's challenging because ecology is ecology. Things don't happen according to some, I don't know, plan or. It's so hard. Yeah. Yeah. There's so much like random noise in the system. And so trying to say, is this noise or is this a component is really challenging, particularly

when you have such a low incidence of disease. Yeah. Well, and if you have so many different hosts, you have so many different bird species that can be affected and they're affected so differentially that it also, you know, that plays a big part of it too. That's really difficult to get a handle on. Disease ecology, Erin. Yeah.

I mean, part of it's why I love it and also why it can be so frustrating. Yep. Okay. Well, that was fun. Hopefully it wasn't too depressing. Oh. I don't know. We'll see.

I don't think I can judge it anymore. Okay. Sources? Sources. All right. So I want to shout out a few. I have a bunch of papers that I liked, but a few that I leaned more heavily on. One is titled, or one is by Armstrong at all from 2013.

called Eastern Equine Encephalitis Virus, Old Enemy, New Threat. And then there was that Arrigo et al paper titled Evolutionary Patterns of Eastern Equine Encephalitis Virus in North versus South America. There's more to that title, but it's very long, so I'm not going to keep going. Oh, and then another one where I got a lot of the ecological sort of timeline of reemergence in Massachusetts is from a paper by Comar and Spielman from 1994 titled Emergence of Eastern Encephalitis in Massachusetts. Massachusetts. Excellent.

There are a bunch of different papers that I used for different parts. We'll post all of these online. If you'd like kind of the most cited source of the clinical aspects of Eastern equine encephalitis, there's a paper from 1997 called Clinical and Neuro-Radographic manifestations of Eastern equineencephalitis. But again, we'll post all of our sources from this episode and all of our episodes online under the episodes tab. You can find all of our sources listed there, as well as links to bookshop.org if you'd

like to purchase the books. Yep. And also, we neglected to say it earlier, but you can find the recipe for our quarantini and our non-acoholic placebo rita on our website, this podcast, will kill you.com under the quarantini's tab. And we also post those on social media. So if we'd like to see them, follow us. Yep.

Thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to you for listening. Hope you enjoyed this episode. Yeah. And I hope. Anyone who was at the show in Michigan, first of all, thanks so much for coming. We had so much fun there. And second of all, hope you still learn something new from this episode.

Yeah. Thanks again to everyone at Michigan who helped us make that trip one of just the most amazing days ever. Awesome. All right. Well, until next time, wash your hands. You filthy animals. I'm Amanda Knox, and in the new podcast, Doubt, the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story? I mean, this has been made to fit. The moment you look at the whole picture, the case collapsed.

What if the truth was disguised by a story we chose to believe? Oh, my God. I think she might be innocent. Listen to Doubt the case of Lucy Lettby on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. I'm Clayton Eckerd. In 2022, I was the lead of ABC's The Bachelor. But here's the thing. Bachelor fans hated him. If I could press a button and rewind it all I would. That's when his life took a disturbing turn. A one-night stand would end in a courtroom. The media is here. This case has gone viral.

The dating contract. Agree to date me, but I'm also suing you. This is unlike anything I've ever seen before. I'm Stephanie Young. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. This is Special Agent Regal, Special Agent Bradley Hall. In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world.

The Sixth Bureau podcast is a story of... the inner workings of the MSS, and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts.