On the seventh of September, my boy took her from the pasture a little before sunset and harnessed her. While standing at the door, I observed she slavered 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 fore feet. 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 eleven p m. I was called from home and did not return until the next day, about two pm. When she was down and incapable of rising. She was left in care of a farrier, 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 fore 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 nine am when she expired. Oh, I know, it's really sad. Also, that was about a.
Horse, that was Yeah, it wasn't.
It wasn't obviously clear right the firsthand.
But that was about a horse like taking her from the pasture. Yeah, we four feet four feet.
So that was an account of the eighteen thirty one Eastern equine encephalitis outbreak in Massachusetts, written by Gardner M. Peck, and it was from a nineteen fifty seven article titled in an Epizootic of Equine and Cephalomyelitis by RP.
Hanson.
Hi, I'm Aaron.
Welsh and I'm Erin omen Updyke.
And this is this podcast will kill you.
And they were talking about triple.
A triple A Eastern equine encephalitis.
Yes, that's very exciting.
It is so we actually this is similar to our Dangay episode. We have done this already in person at the University of Michigan.
Whoop whoop.
Yeah.
Uh.
But just like Dangay, I've forgotten everything.
I don't remember. I didn't even remember Erin 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 a mind, 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 hotly we forget. Yes, but that was but it was super fun to be in Michigan and we really liked 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.
Is so cute?
Yeah, I know, I wish we got more time there. Yeah, maybe someday in the future we can go back. Yeah, someday someday. All right, to be business to attend to, Aaron.
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 will Kill You dot 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 dot org that is an online bookseller that works with independent bookstores.
All right, now for the most important business of all, it's quarantiny time.
It's quarantiney time.
What are we drinking today, Aaron?
We are drinking the Triple E Shot.
That's it'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 our creative juicies have just been dried up. I think we're used up.
I don't know both maybe, Well, what's in the triple E shot?
The triple E shot has three things, of course, a half an ounce of coffee tequila okay, delicious even on its own, A half an ounce of hazel nut liqueur, and a half an ounce of half and half fab It's 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 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.
Eastern equine encephalitis aka triple E aka also sometimes called sleeping sickness, but not to be confused with African sleeping sickness or trepanasamiasis 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 very 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 we'll 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 erin, I hope, so excellent.
But I will say, because we have to understand how this virus is transmitted. Trips E. That's what I wrote down is the name for it.
That's not going to be confusing at all.
Triply virus, it's mostly a bird virus, okay, So it circulates enzootically among a number of different bird species, but it can cause both epizootics, 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, all right, So among birds, it's primarily transmitted by mosquitos in the genus Cula seta, but it can be transmitted by a number of different genera of mosquitoes, including eighties mosquitoes and others.
Okay, 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 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, Quelo seta, which is the genus well, Kulo seta melanera, which is the main species that seems to perpetuate this infection cycle in like, you know, birds, they are not mammal biers or human biers, like very very little, and so researchers are like, well, it might be that there's either they occasionally bite 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 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. But there's still a lot of like question mark, question mark, question mark, right, 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 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 I got from that article was that if 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 there, 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, right, 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 details of which mosquito it is for now, So let's talk about how this virus makes you sick once it gets inside you. Okay, So, like many arboviral diseases,
so virus is 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 you lymph nodes, and in the case of eastern equine and stephalitis 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 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 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? M 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 evating 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. 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 virallly infected cells.
Gotcha.
So Triple E, like many other viruses and a lot of arboviruses, 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 interfer on. This virus actually like inhibits the action of interferon.
That's wild.
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 Triple E 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. Ah, So, like, no matter how much interferre on you had in your body, it was going to be lower within triple E infection than with other viral infections. But the interfere on 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'm 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 rble viral diseases, that there's a huge rate of asymptomatic individuals. Yeah, do these people have immunity? Do they develop immunity to treat 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 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. Okayes, 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 causes infection there. For most viruses, that's a very uncommon manifestation, but for some reason, a lot of arboviruses, so mosquito born 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 being 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, 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 is only four to five percent 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
abdom o pain, just very non specific symptoms. And then about five days later is when the neurologic symptoms begin. And in the case of triple E, 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 triply Okay. You might have peristigias, 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 triple E, 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 Tripoli, 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 cruddy, having a fever, having a headache, people deteriorate very, very rapidly, and then once they're in a coma. The mortality rate is between thirty and forty percent.
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. Okay, these unlucky four percent.
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 fifteen and adults over age fifty they are more likely to actually get the encephalitis form of triple E. 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 ARBA viral encephalitis viruses in the United States, this is by far the worst one, Like, yeah, 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 triple A virus?
Oh, Aaron, I was going to talk about all of this in more detail in the future, in the current events.
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 your 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, uh, although there are small case numbers, there 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 neck wine 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 mid brain 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 US. 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 me pressing. Yeah, yeah, it makes sense. We can talk quickly about treatment if you'd like.
There isn't any I was gonna say, is it just supportive care?
Yeah, it is. There are no anti virals, even in screening studies that have been shown to be effective against Tripoli virus. Okay, that's a bummer. I did find a few case reports where they've been using iv ig, 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 iv ig would be actually an effective treatment or not at this point.
But gotcha. But 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 dengay, which can cause encephalitis. The more common ones like Saint Louis and cephalitis West Nile virus, I honestly don't know. I haven't done the research on those yet. Yeah.
Interesting, But we.
Will talk in more detail about the vaccine in a bit. But first, Aaron, 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. I will attempt to answer those right after this break. Okay, ready, Yes, the year was nineteen thirty three.
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 nineteen thirty three in the US. The Depression was in its worst year. Hitler became German Chancellor. The dust Bowl was still raging in the Midwest. In the US, an earthquake in California caused massive damage in Long Beach. There were four 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. About ninety percent of the one thousand horses roughly that were affected by this illness died during this epizootic.
Wow, yeah, that's a lot. That's bad.
It's really bad. And because this was nineteen thirty three, 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 case, not a preon. And they discovered 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, like the etymology is not very exciting for this one Eastern because it was in the Eastern US equine to indicate that it was found in horses. As you've mentioned, encephalitis for all the reasons that you've mentioned, like the least exciting.
Of all of the most are I think 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 triple E virus had shown up in the northeastern US previously, and it only took a few more years to realize that this epizootic wasn't an isolated one off, that there would actually be another outbreak, even within the same decade.
In nineteen thirty eight, which is five years after this massive outbreak in horses took place, another outbreak of TRIPLEY 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 rate. So in late summer and early fall in Massachusetts, particularly the southeastern part of the state, there were thirty four cases in humans
and twenty five deaths. Oh so, 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, 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 way, m hm, 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 were started to put in the hours to do research. They started to look in the past, asked 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 neck 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 transmitsible 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 nineteen thirty eight when they were fear 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 and brand new disease to humans or to horses. So let's go back to eighteen thirty one. Yes, the year was eighteen thirty one, just kidding, but just like in nineteen thirty three and eighteen thirty one, lots of horses were dying in the Northeast,
particularly Massachusetts. Not as many as in the nineteen thirty three epizootic, but about seventy five horses died in total, which you know, thinking about in eighteen thirty one and how people you know, used to use horses so much more than they did in nineteen thirty three. It would have been devastating to the horse's owners and also devastating emotionally.
But yeah, in terms of like economics and losing a horse would have been hugely, hugely devastating, right, And like in the nineteen thirty three episolotic the one in eighteen thirty one, and horses also occurred in late and had a very high mortality rate as well, again close to ninety percent. Why is it higher in horses than in humans, Sarin, Uh.
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 huh 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 this interfere on 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 eighteen thirty one epizootic and the nineteen thirty three epizootic in terms of the response, like the scientific response, because if you think about eighteen thirty one, 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 have another thought? Okay, because it sounded like from what you were saying, like twenty five out of thirty 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 thirty percent, 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 TRIPI I don't know, just a thought.
Yeah, I mean that seems definitely possible. Possible, I don't know. Yeah, yeah, so like the nineteen thirty eight outbreak was around seventy four percent 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, is 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, Aaron, was that we had someone in the middle of our presentation, Google how money gallons of blood does a horse have?
Yeah? I loved that. I think that they also googled, like several other things for us. Yeah, an auto fact checker. But do you remember how many gallons of blood a horse has?
No? Now I'm gonna have to google it for myself.
Okay, twelve point three. Did you get that from the horse dot com?
I got it, Yeah, the horse dot com. It's gotta be a legit website. Right.
Oh see, now I'm seeing different responses here. Okay, so it seems like, I mean, horses aren't coming all different shapes and sizes. So if you have a massive horse, it could be fifteen gallons fifteen gallons, let's say like ten to fifteen 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. Okay. But after this relatively short lived epizootic ran its course, it kind of just faded from memory because it showed up again in eighteen forty seven 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 eighteen thirty one.
It didn't happen to the same individual people that second time.
Maybe right, And I don't think I mean it 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 eighteen forty seven, you can't google horse disease. Yes, it's true, So there were probably many other things on their minds as well. Okay, so all of this had happened before, meaning Triple E outbreaks in humans and in horses, But what had taken so long for it to return?
And since the nineteen thirty three outbreak in horses in the nineteen thirty eight outbreak in humans, Triple E virus has continued an upward climb in human cases, or at least in the frequency of outbreaks, which is, you know, a pretty big concern for the people who live in these high risk areas, right, Okay, So, but in order to answer why it seemingly disappeared for about one hundred years,
because from eighteen forty seven to nineteen thirty three. 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 ecology of triple E 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 triple virus itself. We don't need to cover that again. The mosquito. The mosquito species that's most closely associated with triple virus again is Cula 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 born 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 Danngey, yellow fever, Zeka, etcetera. Some of the ones that we've covered and so we haven't really had much of a reason to talk about it before. Yeah, 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 US and some southern states along the Gulf. They require fresh water, wooded swamps or Sphagnum bogs with little water filled hollows in fallen trees in order to lay eggs for the larvae to develop. Interesting trees and water right typically standing water or at
least water at like the soil level. And after the larva develop 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 one hundred percent of the time. There was a study in Massachusetts that examined the blood meals of mosquitoes. Of these mosquitoes both inside and outside of a swamp, and in both times, nearly ninety nine percent of blood meals
were from a bird host. Okay, so it's like a very specific feeding patterns, 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 overwinters. It either overwinters in birds, although that seems less likely because birds do recover from infection or they die. There are like some birds, some birds don't seem to be affected at all, and some birds die within a few days of being infected, at least experimentally, So.
It's a lot like West Nile.
I feel like, right, there's very varying susceptibility among abi and host birds. Okay, yeah, and some birds contribute more than to the viral prevalence. Yeah, but yeah, humans, horses, pigs, so I don't think I don't think you mentioned pigs, but pigs have also been shown to be infected with triple A virus. These are all dead and 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 case 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 and 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 twenty nineteen was rainy and hot in some of these more you know, swampy or boggy areas, then maybe this year we would have a higher cases of triple A 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 time scale. Okay, okay, So remember people get infected by the bite of mosquito, whether it's Keela seta melenura 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 triple E cases have been the highest
and the outbreaks that seemed to impact the most. All right, So during the two hundred year pero from around sixteen fifty to eighteen fifty, European settlers essentially stripped the land of forest and wetlands. They used pines for masts on ships. These 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 eighteen hundreds, deforestation was at its peak in Massachusetts and the countryside was like naked It
was nothing left. Henry David Threaux, who wrote Walden, said about conquered Massachusetts around this time, of the primitive wood woodland, which was woodland when the town was settled, I know none, and so as you can guess, this massive deforestation caused enormous cascading ecological effects and especially relevant to triple E bird numbers and species richness declined, and Kulasata melanura also lost the swampy habitat that it needed to survive, and
starting in the second half of the eighteen hundreds, reforestation picked back up because people were like, uh, 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 were started to abandon these unproductive farms to move to cities.
So it sort of both the 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 twentieth century, with wetland restoration lagging a bit
behind deciduous forests. But ultimately what this meant was more habitat for birds and mosquitoes and thus triple A virus, and several researchers point towards this large scale landscape change as being a cause of the reappearance of the virus in the nineteen thirties 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 triple the outbreaks. But really it's sort of the way that we develop
suburban communities, especially the residential ones with these areas. And so these a lot of these suburban neighborhoods tend to creep 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 pre 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 is April twenty second, tomorrow, a couple days from now, a couple days from now and Earth Day, it'll be the fiftieth 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 pro forest pro wetland over here.
I think it's 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 nineteen thirties to the last decade or so, we've seen sporadic human cases here and there, largely restricted to the northeastern US, but we have seen more horse 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 born disease, teasing apart, the cause of this re emergency is tricky
because it depends on so many factors. So, like I talked about increased rainfall one year, re establishment of wetlands, or development of human dwellings in close proximity to these wetland areas, or any sort of habitat where a quela seta melinura 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 response, 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 triple A virus? Aaron, what do you think? Where do we stand with tripoli today?
Oh, let's talk about it right after this break. So TRIPLEI 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 US per year. From two thousand and nine to twenty eighteen, so about the last ten y, on average, there were seven cases per year, and that ranged from three in two thousand and nine to fifteen in twenty twelve. Okay, okay, So like pretty rare and like not a huge amount of variation year
to year from two thousand and nine to twenty eighteen. Now, in total. I will say that entire period there was only seventy two cases in total.
Could you extrapolate upwards and say, if that's four percent, then there were X number of people who were likely exposed to the virus?
Sure, let's do that.
Is that Is that a reasonable extrapolation?
That's a good question theoretically? Why not? If we think that ninety six percent of people are asymptomatic, then yeah, if there were seventy two 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?
Seventy six over ax equals four over one hundred and then find the.
X seventy two terms one hundred divided by four eighteen hundred cases over about ten years.
Still pretty low prevalence.
Pretty low? Yeah, absolutely, Now that was two thousand and nine to twenty eighteen. What about twenty nineteen. There's a reason that we did this as a live episode in Michigan, and that is that twenty nineteen was far and away the worst year of Triple E in a very long time. As of December seventeenth, twenty nineteen, there were a total of thirty eight confirmed cases of triple e in the United States, including fifteen deaths. Wow, yep, that is more than twice the maximum of the last ten 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 twelve confirmed human cases and ten confirmed deaths. Now, there was also a large increase in
the number of animal cases last year as well. There were in Michigan forty eight cases of tripoli and 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, but it was Moran's at all. Come on, Born 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 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.
Yeah, So that's that's the only good news is like, at least it's over for now, we can hope that this year is 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 northern in the more northern places where mosquito 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 tripolei 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.
Is that.
How that goes, How that goes?
Yeah, there is no market for a triple E vaccine, 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 two thousand and seven, 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 triple E virus and some other virus, don't remember which one, and they tested it in mice and they found that it was highly immunogenic. That was in two thousand and seven. Nothing else, okay,
So in theory, in theory, it's possible. I did check clinicaltrial dot gov, which again is where you can find all the clinical trials that are happening, and there are studies for triple E. Two of them were USA mrid Us zamord I don't know how you say it. The US 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 twenty eight to seventy percent of people depending on the timeframe that you looked at it. So like seventy percent 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 twenty eight percent of
them still had high tiders of antibodies. So they mounted an immune response, but it wasn't very long lasting, right, just like the horse that 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 tripoly virus.
Well, do you know what the predictions are for this year? It was identy in places? Was it hot? Let's see, they're in early summer. It's snowed in Chicago like two days ago, so.
You know, I've been thinking about that. And 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 wonderable.
Yeah.
I got out of the prom and there was snow in 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.
Now I'm not 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 TRIPLEI will rise again next year. Uh. I guess normally these cycles tend to last for two to three years. So you have two to three years in a row of bad year and it was very wet and rainy in twenty nineteen, so great, great.
You know, like how with with lime disease and ticks, there's like that distinct like the mast and the mice and then the deer and then the ticks.
Right now, there's sequence of events that lead to these high outbreaks or these like outbreak years. 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 right challenging because ecology is ecology. Things don't happen according to some I don't
know plan or 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 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. Is easy college here.
In Yeah, it's, I mean part of it's. It's why I love it and also why it can be so frustrating.
Yeah, okay, well that was fun. Hopefully it wasn't too depressing. Oh I don't know.
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 my Armstrong at All from twenty thirteen called Eastern equineencephalitis virus Old Enemy, New Threat. And then there was that a rego at All paper titled Evolutionary patterns of Eastern Equine andcephalitis virus and 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 re emergence in Massachusetts is from a paper by Comar and Spielman from nineteen ninety four titled Emergence of Eastern Encephalitis in 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 equin encephalitis, there's a paper from nineteen ninety seven called Clinical and neuro Radiographic Manifestations of Eastern equin Encephalitis. But again, we'll post all of our sources from this episode in all of our episodes online
under the episode's tab. You can find all of our sources listed there, as well as links to bookshop dot org if you like to purchase the books yep.
And also, we neglected to say it earlier, but you can find the recipe for our quarantiny and our non alcoholic La Siberta on our website this podcast will Kill You dot com under the quarantinis tab, and we also posts on social media, so if you'd like to see them, follow us.
Yep.
Thank you to Bloodmobile for providing the music for this episode in all of our episodes.
And thank you to you for listening. Hope you enjoyed this episode. Yeah, and I hope you always 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 learned something new from this episode.
Yeah. Thanks again to everyone at Michigan who, yeah, 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.
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