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Ep 49 Eastern Equine Encephalitis: Triple EEEk!

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this is exactly right. Madison re delivers gorgeous. Professional Ammonia Free hair-color straight to your door starting at just twenty two dollars. Their color is crafted by master colors and with over fifty five shades to choose from. You look like you just came from an expensive salon. Find your perfect shade at Madison. Dash Reed Dot Com and get ten percent off plus free shipping on your first color kit with Promo code this podcast. That's Promo code this podcast at Madison Dash Reed Dot Com 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 slathered 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 the hill. She stopped for a second as 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 four feet 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 time she perceived the blow when she did perceive the effect was greater than expected for. She started off as if surprise have 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 Tremopoulos 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 pm. I was called from home and did not return until the next day about two PM. When she was down 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 forelegs appeared to be completely paralysed. She would however make a powerful exertion to rise forwards and throw herself several feet ahead without regards anything that might be in her way no material alteration took place till next morning except gradual demolition 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 film alone no no no no no no no no no no no no no no no no no no no no no no no no no no no no. Um I know really sad. Also that was about a Horse. That was yeah. It wasn't it wasn't obviously clear rain the first hand but that was about a horse like taking her from the pasture we should. We should feet four feet. So that was an account of the eighteen. Thirty one eastern equine Suffo- lettuce outbreak in Massachusetts written by a gardener impact and it was from a nine fifty seven article titled An epizootic of Equal Status by ARP Hansen. Hi I'm Aaron Welsh and I'm Aaron Omen Updike and this is this podcast will kill you and today we're talking about Tripoli Tripoli eastern equine encephalitis. Yes that's very exciting. It is so we actually. This is similar to ours Deng episode. We have done this already in person at the University of Michigan Bloop. Yeah but just like Dang. I've forgotten everything I don't remember. I didn't even remember Aaron. Like my own part of this. When I went back to my notes I was like. Oh this is depressing so 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 how little aggregate? 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 my gosh. It was like such an action packed. Fun Day it really was enjoyed leading everyone talking to everyone who superfund screen arbor so cute. Yeah I know I wish we got more time there. Yeah maybe someday in the future we can go back someday right to be show 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 will kill you dot com under the episodes tab and we also have two things related to books. One is a good reads 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 time. It's warranty any time. What are we drinking today? Aaron we'RE DRINKING THE TRIPOLI 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 of Gypsies have just been dried up. I think we're you stop. I don't know both. Maybe what's in the Tripoli shot? The Tripoli shot three things 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 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. And let's just let's just dive right in entering. It'd be very interesting okay. Well I'm excited to relearn everything I've forgotten. Yeah me too right well. We will start doing that right after this break. Technology has changed so much the way that we live like. Okay you and I- Aaron we watch a TV show together while we're house partying or facetime ing at the same time so we can follow along and have watched others reactions. It's the best. It's the most fun thing like it's the most fun part about being a part is being able to stay in touch on your phone. You know seriously yeah. Technology one thing. That hasn't changed too much. Is that we color. Our hair using outdated at home colors or spend way too much money and time at salons and do you know. Madison Reed is changing that game. They have gorgeous professional ammonia free hair-color that they deliver right to your door starting at only twenty two books. People who use Madison Reed are always raving about the results beautiful shiny multidimensional and healthy looking hair. Some even say that their new hair-color improves their actual lives. And what makes medicine reads color. So unique is that it's crafted by master Pelorus who blend nuances of light. Dirk cool and warm tones and they have over fifty five shades to choose from. So you look like you just came from expensive salon. Find your perfect shade at Madison. Dash Reed Dot Com. This podcast will kill you. Listeners get ten percent off plus free shipping on their first color kit with Promo code this podcast. That's Promo code this podcast at Madison Dash Reed Dot Com. Hey I'm curt brown older and I'm Scott Landes we're too silly dudes who love the absurd We got a brand new podcast called bananas. You should listen. Every Tuesday we discuss absolutely bonkers news stories from around the world. Things like man. Walking oddly found to have twenty one live pigeons in pants. Missing PARROT TURNS UP MINUS BRITISH ACCENT FOOT SPEAKING SPANISH NASA prepped for Alien Communication with LSD DOLPHIN SEX EXPERIMENT. Who and we've got great guests like Norbert Star Kristin Shaw so for all you. Tv or movies barring actors producers. I'm I'm I can take out my teeth. That's one more. If you WANNA real weird look pretty cheap so give us a listen if you enjoy the nutty shocking and the Downright Bananas Listen To Bananas every Tuesday and exactly right subscribe now on Stitcher Apple Podcast spotify or wherever you like to listen to Eastern at Quine Encephalitis Aka. Tripoli Aka also sometimes called sleeping sickness. But not to be confused with African sleeping sickness Tranessa myositis okay or some light is lethargic because I think I can tell you it was also confused with that disease for at least the early years fascinating. 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 Tripoli virus. It's an Arin a 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 the 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 GonNa talk a lot about the evolutionary history or the ecological cycle of this virus. 'cause YOU'RE GONNA 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 Tripoli virus it's mostly a bird virus okay. So it circulates enzootic -ly 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 echoing ovulations hence the name and it can also cause zone attic outbreaks in humans if it jumps from birds into humans okay All right so among birds it's primarily transmitted by mosquitoes in the genus Kulesza. But it can be transmitted by a number of different Genera- of mosquitoes including eighties. Mosquitoes and others of course an Asterisk to that statement that I'll go into. Oh why can't wait to hear about it? I WANNA know Okay Renault. Right now yet kind of so. Basically they call these. Other mosquito species the bridge vectors. Okay so jumping a little bit into the ecology side of things `cuse at a which is the genus while kilos set a milliner which is the main species. That seems to perpetuate this infection cycle in like birds right. They are not mammal biters wrangler human fighters very very little and so researchers. Well it might be that. There's either occasionally bite humans. And that's how these things happen or it's bridge vectors. But in one study that looked at the 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 in like cause infection fascinate 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 Oh but there's still a lot of question. Mark Question Mark Question Mark in race 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 -squitoes 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 an able to transmit right because these viruses have to be able to replicate within the mosquito and then leave the mosquito's gut and traveled to their salivary glands. And then be there in high enough concentration that win the mosquito bites it's next host. It's injecting enough virus to actually get that host sick so these are. These are very complicated cycles within the mosquito Imax 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 smash that mosquito like found some virus but where was that virus within the mosquito. 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 owe crime so like many Arba Viral Diseases. So virus is transmitted by arthropods like mosquitoes. Win and mosquito bites you the first place that it spits that virus is kind of towards your lymphatic system. Rights was kind of right under your skin. They don't spit it necessarily directly into your bloodstream. That 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 ourselves? They don't replicate on their own so it turns out. That Tripoli 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 have 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 trying to 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. She 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 viral infected cells. Gotcha so triple e. Like many other viruses and a lot of Arba viruses specifically targets and shuts down the production of Interferon. It 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 viruses blocking this production give them interferon. The 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 in these four in. It's only the North American strain. The 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 viruses North American or 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. Oh so like no matter. How much interferon you had in your body. It was going to be lower with an triple e. infection than with other viral infections. Right 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 light was just about to ask. Oh good preempted you. Ninety six percent of people who get infected with triple E. virus will never have dramatic disease. They're going to be just fine. Okay that the ADS. But that's I feel like that's a trend that we see a lot in Arbil viral diseases and there's a huge rate of asymptomatic individuals yet. Do these people have immunity to? They develop immunity to terrific 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'd have a 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 or crass that's the thought goodness 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 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 Arba viruses so mosquito borne viruses do cause viral encephalitis And we've also talked on this podcast about one of most famous causes a viral encephalitis. That is rabies. 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 specifically if you have symptomatic infection with Tripoli which again is only four to five percent of people so that's the good news. The symptoms begin with a pro drome which essentially means nonspecific symptoms before the real bad symptoms. This is like that fever. Maybe headache maybe even some abdominal pain just very nonspecific 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 week okay. You might have seizures. Seizures are actually very common in Tripoli. Okay you might have Paris. Dj's 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 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 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 ours to a couple of days? Oh Wow yeah. So once people develop these neurologic symptoms after this like five day program of kind of feeling cruddy. Having a fever having 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 developed these severe neurological symptoms. So almost everyone. So okay. 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. Yeah who I have a question. Okay these unlucky for percents Why such a good question Erin? I have no idea and I think part of the reason that so some of the literature says children under age. Fifteen and adults over age fifty. They're 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 Arba. Viral encephalitis viruses in the United States. This is by far the worst one like yeah mortality rate 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 China and Japan. But there's a vaccine for Japanese encephalitis. So why isn't there a vaccine then four to believe this? Oh I was GonNa talk about all of this in more detail in the future in the current event. Just wait for the future. Then yeah do you want me to talk about it now or do you want me to talk about in the future up to you girl. Let's talk about it later because we'll talk 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 effected in the brain when you get infected with Eastern Acquaintance. F Lettuce 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 lethargic. If you remember yeah okay. And it also infects 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 etc. If you get a herpes in syphilis 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 a Faiza. Okay so for me. I'm like okay. So we know that it infects this part of the Brain. But how can we don't see these symptoms like maybe shakiness like in Parkinson's or these certain types of symptoms? Yeah Mike Guesses because it causes lesions in these areas like your brain stem that are so important for generally being alive then you progress so rapidly deteriorate so quickly that there's no time to have those specific isolated neurologic findings right raiso pressing. Yeah yeah makes sense We can talk quickly about treatments. If you'd like there isn't any was gonna say just supportive care yet. It is There are no antivirals even in screening studies that have been shown to be effective against Tripoli virus. That's a bummer. I did find a few case reports where they've been using Ivy g which is a intravenous pooled concentrated human immunoglobulin Which is used a lot in auto immune 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 use this and they survived and did great and then I found one that said we used this end. They died. But that person also had informa- select 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 ineffective treatment or not at this point but Gotcha what about with with other of the encephalitis viruses. Whether we have antivirals. Yeah good question. I don't know Yeah Yeah I. I don't believe we have any for Dan. Gay which can cause and several ladies mom the more common ones like Saint. Louis Encephalitis 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 I let 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. 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 human seemed to be a bystander and for which birds are heavily involved birds killers. I will answer those no I will. I will attempt to answer those right after this break Hello there I'm bridgier. Wine Iger Look Chances. Are you've received gifts? You've probably also given gifts. I have a new podcast called. I said no gifts on exactly right every Thursday. I have a conversation with a friend loved one or somebody. I'm secretly trying to ruin. I only have one request. No gifts unfortunately. Every one of them deliberately disobeys maintaining our conversation eventually turns to whatever object lies beneath the wrapping paper. It's an absolute thrill. I've received gifts from all kinds of people. Incredible people incredible gifts subscribe now on Stitcher Apple podcasts. Spotify or wherever you like to listen and no aw. Okay ready yes. The year was nineteen thirty three. I love it when you're section start like this Erin other each time for. I also love the Little Cherry. Pick things that I have here I? I'm like 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 the US an earthquake in California caused massive damage in Long Beach. There forest fires in Oregon and horses were dying by the dozens. In pockets of the northeast particularly along coastal 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 the figuring out pretty quickly that it was a transmissible filter bill agent which is essentially code for a virus. Most of the time or pre-owned Not New York not a fan. And they discover that it was. This transmits will filter real agent because they were able to successfully inject it whatever it was into guinea pigs who also died as a result of the same order systems acting like guinea pigs and the researchers gave this virus a name eastern equine encephalitis virus eastern of course like the. Etymology is very exciting. For this one yeah eastern because it was in the eastern US equine to indicate that it was found in horses as you've mentioned and satellite us for all the reasons that you've mentioned the least exciting of all. I think boring. Yeah Yup so at the time when this virus was isolated and named in many researchers retreating it as a new infection that had never been seen before. But it didn't take long for people to realize that Tripoli virus had shown up in the north eastern 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 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 thirty four cases in humans and twenty five deaths. Oh so man. Pretty high case fatality rate and. That's a lot of cases for just a couple of months in state like dot. 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 gains really widespread national attention. I imagined too because it was primarily affecting children that that Yeah it was kind of really became apparent that like children were a very high risk group for this and so because of the severity of this illness. People were starting 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 ring 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 transmits will filter bubble agent. But it would take a little bit of time before they could pin down the exact species that seem to be the culprit and part of the reason is because a hurricane washed away all of these mosquito collection sites in one thousand nine hundred when they were here at the height of their research. Just on things on top of things Things on top of things. Okay so as I mentioned. Researchers also realized. Hey this is not an brand new disease to humans or two horses so let's go back to eighteen thirty one. The year was eighteen. Thirty one just kidding but just like in nineteen thirty three in 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 used to use horses so much more than they did. Nineteen thirty three. It would have been devastating to the horse's owners and also devastating emotionally. But 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 epizootic. The one in eighteen thirty one horses also occurred late summer and had a very high mortality rate as well again close to ninety percent. 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 in like trouble walking and leaning. Yeah I. 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 may be 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 -nology so I have no idea but it's a really interesting question interesting ingesting a 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 while horses that fed on grass. Were the ones who got sick. So there may be 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. Thanks a lot higher than today so I wonder if it could to 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 gonNA probably intimate a horse and try and keep them alive if they've got Tripoli I don't know just a thought. Yeah I mean it's that seems definitely possible. Possibly I don't know yeah. So like the the nineteen thirty. Eight outbreak was around seventy four percent of people. Okay yes yes or maybe. It's just the difference in supportive care or something. I don't know yet we're guessing here. We should stay on not so shaky ground. Yep and so part of the reason that that one of the guesses was will the horses at Fed on grass for the ones who got sick as opposed to like. Hey and the stables. Okay 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 let's go to the treatment so treatments were not helpful full verses mostly as you heard in the firsthand 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 many gallons of blood is a horse have yet? I loved that ethic that they also googled like several other things for us and auto fact checker. But do you remember how many gallons of blood horses no going to have to Google it for myself. Okay twelve point three. Did you get that from the Horse? Dot Com I got it. Yea Dot COM gotta be a legit website right. Oh see now. I'm seeing different responses here. Okay so it seems like I mean. Horses are coming all different shapes and sizes so if you have a massive Horse Rabi fifteen gallon eighteen gallons of say like ten to fifteen gallons sure. That sounds reasonable. So a fifth of your blood your blood. It's a lot of blood and it's not GonNa do you any good okay. But after this relatively short lived epizootic ran its course it. Kinda 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 as a wasn't it didn't happen to the same individual people that second time maybe right and I don't think it maybe it did happen in the same region but I also don't think that's like Google in nineteen forty seven. You can't Google horse disease. Yes so problem in many other things on their minds as well. Okay so all of this had happened before. Meaning Tripoli outbreaks in humans and 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. Tripoli virus has continued an upward climb and 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 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 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 fame. Britt our favorite all right so we already talked a little bit about the ecology 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. mosquito the mosquito species that's most closely associated with Tripoli virus again is Kua Seta Melania 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 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 Zeka etc. Some of the ones that we've covered and 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 was -squitoes 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. Freshwater wooded swamps or sphagnum bogs with little water filled hollows in fallen trees in order to lay eggs for the larvae to develop interestingly trees and water rate typically standing water or at least water at like the soil level and after the larvae develop these little nooks and crannies adult Miskitos than happily emerged to feed on whatever. Birds are around and those birds tend to be water dwelling birds although not a hundred percent of the time there was a study in Massachusetts that examine the blood meals of mosquitoes of these mosquitoes. Both inside and outside of the swamp and both times nearly ninety nine percent of the blood meals were from a bird host. Okay sounds like a very specific feeding patterns Gary very specific 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 over winters. It either over winters in birds of that seems less likely because birds do recover from infection or they die okay birds. Some birds don't seem to be affected at all and some birds die within a few days of being infected stickler mentally says a lot like West Nile. I feel like Right there's very varying susceptibility among okay. Yeah and and some birds contribute more than two the viral prevalence. Yeah but yeah humans horses pigs so I don't. I don't think you mentioned pigs. But pigs have also been shown to be infected with Tripoli 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 that if a mosquito. Let's say that a horse got infected with the virus and then 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 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 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 it seems to be that it comes down to you know mosquito ecology mosquitoes because they live outside our 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 higher warm water for the 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. 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 Tripoli 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. Let's look at some of these larger overall trends in the frequency of outbreaks. So like more on this larger time. Timescale okay okay so remember people get infected by the bite of mosquito whether it's culas seminar 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 to get infected right all right. So let's talk about the history of swamps and boggs in the northeast particularly Massachusetts and I'm using Massachusetts a case study because that's where AAA cases have been highest and outbreaks that seemed to impact the most All right so during the two hundred year period from around sixteen fifty to eighteen fifty European settlers essentially stripped the land of forest and wetlands. They used pines for masks. On ships. These cedar swamps were destroyed to make shingles posts barrels. Other forest 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 gives. Nothing left Henry David. Thoreau who wrote Walton said about Concord Massachusetts around. This time of the primitive would woodland which was woodland. When town was settled. I know none well. And so as you can guess. This massive deforestation caused enormous cascading ecological effects and especially relevant to Tripoli bird numbers and species richness declined and culas. Melania also lost the swampy hat that it needed to survive and starting in the second half of the eighteen hundreds reforestation picked back up because people were like a we can't continue to over exploit land because there's nothing left like we have really 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 the conscious decision of we need to reforest and also just sort of happened naturally as people stopped using the the wood for farms and whatnot. Yeah 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 Tripoli virus And several researchers point towards this large scale landscape change as being a cause of the reappearance of the virus in Nineteen Thirties. And why it has stuck around ever since then but before you take up your chainsaws us to re clear cut. The forests of New England and drain the swamps in bugs. 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 right especially residential once 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 protection and healthy water supply and they provide these amazing habitats were 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 as April twenty second tomorrow couple of couple of days are now an earth. It'll be the fiftieth anniversary of Earth Day. How exciting wow happy birthday REWA? So let's just keep that spirit going weird certainly not anti wetland no no 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 zone attic diseases yet definitely so from these outbreaks in nineteen thirties 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 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 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 culas. Elenora likes to its eggs. So many things can play a role in this. And although this is a rare disease can be extremely deadly and that can lead to 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 even enough. Are we in for a bad year of Tripoli Virus Aaron what do you think do we stand with AAA Today? Let's talk about it right after this break So Tripoli 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 nine to two thousand eighteen so about the last ten years. On average there were seven cases per year and that ranged from three in two thousand 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 nine two thousand 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 than there were x number of people? Who were likely exposed to the virus? Sure let's do like 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 ASEM dramatic? Then yeah if there were seventy two known cases that were reported then. How many cases is that total over that time period? Actually I have no idea how you do that. Math seventy six over X. equals four over one hundred. And then find the x seventy two times. 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 nine to two thousand eighteen. What about two thousand nineteen? There's 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 Tripoli in a very long time as of December Seventeenth Twenty nineteen. There were a title of thirty eight confirmed cases of Tripoli in the United States including fifteen deaths. Wow Yep that is more than twice the maximum of the last ten years. Pets very okay. Why Green Question? I don't know if it 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 the these cases happened in a 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 in animals last year so yeah. It's 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 she said in that. Article Right. He wasn't the first author at all at all said in that article. We 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 now. It's springtime so welcome back. 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 the more northern places where Schiavo season is so concentrated. Yep So make sense. You can sort of heightened 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 as it is a whole killed virus vaccine. It's not great even for horses so from what I have gathered for some reason. 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 the immunity that it provides is not very long lasting 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 every year. Something like that so it might be the same for horses. Yeah they do boosters. Yeah so that's it's really interesting right like why it that. We can't develop a vaccine. That is more immuno. Genyk that provides us with a longer lasting immune response is is part of it in the funding and that this is a rare disease you put the nail on the head there. Erin how that goes. Yeah there is no market for a triple e vaccines may 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 ahead. Found papers of people doing research on this. So in two thousand 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 Tripoli virus and some other virus. Don't remember which one and they tested it in mice and they found that it was highly immune genyk that was in two thousand seven. Nothing else okay. So in theory in theory it's possible I did check clinical trial Dot Gov. Which again is where you can find all the clinical trials that are happening and there are studies listed for Tripoli. Two of them were. Us A. M. R. I. D. US Amred. 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 time frame that you looked at it so like seventy percent of people 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 tigers of antibodies so they they mounted an immune response. But it wasn't very long lasting right just like a horse. Yeah and so. That makes it even harder to try and get funding for a vaccine like this if you think like this 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 convinced 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. Absolutely yeah yeah definitely. So yeah. That's where we stand with Tripoli. Well do you know what the predictions are for? This year was places. Was IT hot? Let's Caesar early summer. It snowed in Chicago like two days ago. So I've been thinking 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 mom 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. I can't believe I've never seen pictures of your prom. Dress his now. I love what you'd expect. I Really WanNa 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. We have two to three years in a row of bad Year and it was very wet and rainy in two thousand nineteen so great. Great you don't like how with with lime disease and ticks. There's like that distinct like the mast and the mice. And then the deer and the ticks right news events that lead to these high outbreaks or these like outbreak years. They're just not well known. 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. Don't happen according to some. I don't know plan or 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 and if you you have so many different hosts you have so many different bird species that can be affected and their emitted so differentially that it also that plays a big part of it too. That's really difficult to get a handle on disease ecology ear. Yeah I mean part of. It's it's why I love it and also why it can be so frustrating was fun hopefully. It wasn't too depressing I don't know who I don't think I can judge anymore. Okay sources close sources rate. So I WANNA shout out a few. I have a bunch of papers that I liked But a few that I leaned heavily on one is titled or one is by Armstrong at all from twenty thirteen called eastern equine. Satellite is virus old enemy new threat and then there was that a rigo at all paper titled Evolutionary Patterns of Eastern Acquaintance of elitest virus north versus South America There's more to that title but it's very long so I'm not gonNA keep going. Oh and then another one where I got a lot of the ecological sort of time line of Reemergence in Massachusetts from a paper by Komar and Spielman from Nineteen ninety-four titled Emergence of Eastern Satellites in Massachusetts excellent. There are a bunch of different papers that I used for. Different parts will post all of these online. If you'd like kind of the most cited source of the clinical aspects of eastern quantified is. There's a paper from nineteen ninety-seven called clinical and neuro radiographic manifestations of eastern acquaintance lettuce 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. Oliver sources listed there as well as links to bookshop dot org if you like to purchase the books yet and also we neglected to say earlier but you can find the recipe for our quarantine and are Non Alcoholic Placebo Rita on our website. This podcast will kill you. Dot Com under the quarantine tab and we also post those on social made. So if you'd like to see them follow us. Thank you to blood mobile 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 you always anyone who is at the show in Michigan first of all. Thanks so much for coming. We had so much fun there and all hope you still learn something new from this episode. Yes thanks again to everyone at Michigan. Who helped us make that that trip one of just the most amazing games ever also all right well until next time? Wash your hands. You filthy animals

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