This Podcast Will Kill You - Ep 84 West Nile virus: The Crow in the Coal Mine

Episode Date: October 19, 2021

It’s the summer of 1999 in New York City, and everyone's looking towards the future, towards millennium parties and potential Y2K catastrophes. But if they turned their eyes to the streets around and skies above, they might have seen something else on the horizon, something much more real and alarming than a Y2K glitch: the arrival of West Nile virus. In this episode, we take a close look at the virus whose recent emergence in the Western Hemisphere serves as a crucial reminder of how pathogens know no political boundaries and how working across disciplines is the only way to effectively control and prevent disease outbreaks. We are also so excited to be joined by Dr. Sarah Wheeler, Biologist at Sacramento-Yolo Mosquito and Vector Control District, who talks us through the ecology of this mosquito-borne disease and shares the birds-eye view of the situation in North America. Last but certainly not least, we round out this episode with a delightful and informative song about West Nile virus: West Nile Story by MC Bugg-Z and the Fairfax County Health Department. Check out this action-packed episode wherever you get your podcasts! See omnystudio.com/listener for privacy information.

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There was a guy who bought a 2021 Porsche Cayman that was well loved. I mean, there are plenty of Caymans in great condition on eBay. But this one needed some more. work. This guy buys it and rebuilds the whole thing, all with parts he found on eBay. And now, that nearly scrapped Kamen is out tearing up the track. From Toyotas to Aston Martins, eBay has thousands of cars and the largest online selection of vehicle parts and accessories. eBay, things people love. My name is Reagan, and I grew up in a very small town. I had exactly 17 people in my high school graduation. So I just wanted to set the stage of what I was dealing with in the medical

community. When I was 16, my school was getting ready for homecoming. And we were the last class. They got to have a bonfire at ours. We really wanted to go all out for everyone, not just for us. And I really wasn't big on outdoors. I wasn't an outside fan. I didn't like wearing the long sleeves, the pants, the mosquito spray. But I really, I worked hard for this. And it was. an amazing bonfire. It was actually only a few days later that I was spinning the weekend with my grandmother, and right after school, I came down with a headache. And I wasn't interested in watching TV. I wasn't interested in eating dinner. I even went to bed before the sunset. And my grandmother was really increasingly worried over this behavior. She was checking on me every half hour.

She wanted to take me to the ER, but she knew, especially in a town like ours, that they were just going to send me home with Tylenol. So then the fever hit. And when it hit, it came on hard and fast. And my grandmother called the hospital who said that all they would do was put me in an ice bath and send me home. That was their fever protocol. So she called my mom, who was a five-hour drive away. And all I remember her saying is, something isn't right. I think you need to come home. She'd been gone for school. She'd been with a friend. She didn't even have her. own car, but something in my grandmother's voice convinced her. So she rented at something, she came home. And by the time that the fever got so bad that she was having to lay on me to

keep the chills from shaking the bed, she decided she was done. We were going to the ER. I don't really remember much from then out. It gets really hazy. I remember being super uncomfortable. I remember begging my mom to go home. I just wanted my bed. I wanted to sleep. The doctors were asking me to do all these things that I couldn't do. I couldn't stand up. I couldn't stay conscious. And they were asking me to touch my chin to my chest. And I couldn't do it. It hurts so bad. And that's when things started to get scary. I didn't know until later that they told my family that I was going to die. And I was like in the room, like laying on the bed. And my mother demanded that I'd be moved to the hospital that was in the bigger city. It was an hour away.

And they said that I wouldn't make it. And then there was one doctor who came into the room, said he was getting me an ambulance and that he would have a friend waiting for my arrival because he was very scared that this was something very serious. Everything after that kind of comes and flashes. I remember the night's sky, becoming the roof of an ambulance. I remember my mother's face while she stroked my hair. I remember being pulled away from her so they could do a spinal tap, which was the scariest thing that has ever happened to me in my entire life. I remember too many hands on me while they moved me to a stretcher. I remember my father arriving, which was like a big deal if my dad actually came to a hospital. And I remembered my pediatrician because I had been so healthy

up into my teen is that I hadn't actually acquired a GP yet. I remember hazard suits because I didn't actually know if what I had was bacterial or viral. I was so dehydrated that they blew my veins, trying to give me IVs. I was so mad-nourished that I lost 15 pounds in the hospital. I was so weak that I had to relearn how to walk, and I remember thinking that I was going to die and I was okay with that. And it was actually well before the results came in, West Nile meningitis. I didn't. I I missed two weeks of school between treatment and recovery. It took even longer to return to normal. And my classmates had to help me carry things between classes

because the locks were too long and my body was too exhausted. And I remember my teachers giving me gift baskets and extensions on my homework and my family members made me homemade cinnamon rolls to gain my weight back. And it didn't occur to me and so much later that everyone was doing this because I wasn't supposed to make it. Everyone had said that I was going to die. Preparations have been made at the school for me to not come back.

And because I did, nobody wanted to let me research what had almost killed me. They waited patiently for my obsession with it to disappear. And it did until I started listening to your podcast. That's all. Thank you so much, Reagan, for taking the time to tell your story. Wow. I mean, what a story. Yeah.

Wow. Thank you. Absolutely terrifying. Yeah. Seriously. Yeah. Well, hi, I'm Erin Welsh. And I'm Aaron Uphdike. And this is, this podcast will kill you. Welcome to West Nile Virus. Welcome to West Nile Virus. And what is our second to last episode of this season? I really truly can't believe that we've made it this far, Aaron. I'm going to be completely honest. I mean, same. Yeah.

And yeah, so we are after the end of this season. So not this episode, but the one after will be the last of the season. We're going to be taking a short break. Don't worry, we won't be gone forever. We'll be back. We'll be back. So, you know, make sure that you're subscribed to the podcast, to all of our social media, so you know what we're doing in the break.

And also when we're coming out with a new episode. Yeah. Or any other fun surprises that could happen. Who knows? We don't know. Anything could happen. Anything could happen. But yeah, West Nile. Erin, this is our first mosquito-born one of this season. Is that right? Is it? I guess it is. I'm going to be totally honest. This season, I don't even remember what things we've done. I know we did shog us. So I know that was a vector-born disease. I'm just also surprised that we hadn't done West Nile yet. Like this is a, this is kind of a big deal. Oh, Erin. You could just play a broken record of us in our intros saying the exact same thing for every single episode.

It is. It is. It is true. Oh, man. It's going to be a good episode, though. It is for a number of reasons. So you just heard that incredible first-hand account. And we have another fantastic guest lined up for this episode to help shed some light on the ecology of West Nott. virus and one of the most exciting things you have to stay tuned for the very very end of the episode and that's because there is a West Nile rap a West Nile rap it is called West Nile Story and it is by friend of the podcast MC Bugsie who made it in collaboration with the Fairfax County Health Department working in the disease-carrying insects program. Fairfax County, Virginia. I had to look that up.

I am so excited for everyone to hear it. Oh, my gosh. So it is absolutely a fantastic song, and not only that, like this is not MC Bugsie's only song. So make sure you go to YouTube. We'll provide a link. Don't worry. And you can check out all of the wraps. There's even one about COVID vaccines.

It is incredible. Awesome. Well, and speaking of classic TPWKY, it's about time for quarantini. It is. What are we drinking this week? We're drinking for the birds. Which, like, we want to make sure that, you know, it's for the opposite of the reason that people usually say for the birds. We wanted to name it this to honor the birds.

It's for the birds. It is for the birds. This is For the Birds. How many times can we say it? What is in For the Birds, Aaron? So For the Birds is actually based on an existing cocktail, also named after a bird, called the Yellow Bird Cocktail. Very apt, very apt. It is, and that is made with white rum, orange lique, galliano, and lime juice. Delish.

It is tart and delish. We'll post the full recipe for that quarantini, as well as our non-alcoholic placebo-a-a-brieta on our website, this podcast will kill you.com, and all of our social media channels. Absolutely. Other business, website stuff. Yeah. Always. Check out our website. This podcast will kill you. com. Should we even go through like what's on the website? I mean, everything is there. Anything that you could want, it's there. Yeah, it is. Should we just get started on this episode? Can we? Let's take a quick break and then dive straight in. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again.

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West Nile virus is a flava virus, which listeners of this show should be very familiar with by now because we've covered so many other flava viruses, right? Have. Dengue virus, yellow fever. hepatitis C even, so many viruses. We're running out of flabavaviruses to cover. Just kidding. There's always more.

But anyways, flavaviruses, for anyone who hasn't listened to every one of our episodes, is a large family of RNA viruses, many of which are transmitted by arthropod vectors to animals and humans. West Nile virus causes a disease that, primarily is what's called enzootic. That is, it has a cycle that is completely independent of humans. It's essentially a vector-borne disease of wildlife. This cycle is maintained in nature, specifically through an avian mosquito cycle, so birds and mosquitoes, where mostly mosquitoes in the genus Culex feed on avian or bird hosts. They pick up the virus in their blood meal, and then it

passes through their gut, makes it to the salivary glands, they spit it back out, and then transmit it to other birds. And that's the primary cycle. Simple enough. Yeah, simple enough, especially compared to a lot of things that we cover. We'll make it more complicated, don't worry. Oh, yeah. It's thought that the virus is able to persist and perpetuate even in temperate regions of the world where adult mosquitoes aren't present all year round, both via adult mosquitoes that undergo diapause. So the virus persists in overwintering adults that are just not active. I have also seen that it's also possible that adult mosquitoes transmit it transovarially. I don't know how common that is. But it's also possible that migratory birds play a large role,

bringing in virus from areas of higher transmission or places where you have year-round transmission, or even just harboring low levels of virus, and then during their migration cycles, bringing that virus back to temperate areas. But in any case, this avian mosquito cycle is the main enzyotic cycle of West Nile virus. And birds are the predominant reservoir host for West Nile virus. In North America alone, hundreds of species of birds have been shown to be competent reservoir hosts, so harboring the virus, whether or not they get sick and show symptoms. And the majority of bird species do seem to survive infection relatively unscathed. Don't worry, someone else is going to talk a lot more about this virus in birds.

I'm going to focus on this virus in people. But other than birds and people, people. people, other animals can get infected as well. Importantly, horses also get infected relatively frequently. But humans and horses are what are called dead end hosts. That means that while we can become infected when a mosquito bites us and we can get sick, we can get clinical disease, humans and horses don't actually contribute to the cycle of infection. So mosquitoes that then feed on us don't tend to become infected from feeding on infected people. Right. And so I am going to focus on this disease as it manifests in humans. But like we kind of said up front, it's also very important to

understand the ecology and persistence of this disease is a lot more complex than just the human side of it. So we'll get to that and I'm really excited to get to that later. All right. Just focusing then on humans. Let's talk about what it looks like when a person gets West Nile disease. First off, it's unclear exactly how infectious West Nile virus is. That is how many people who get bitten by mosquitoes harboring West Nile virus actually go on to become infected? We don't really know. Well, and I would also imagine that the amount of virus varies mosquito to mosquito. Definitely. Absolutely. I would, yes. So we really don't know what the like overall infectiousness of West Nile virus is. But we do know that of those people who get infected, about 25 percent, some estimates say 20 to 40 percent, but most that I've seen are

around 20 or 25% of people will develop symptomatic disease, aka West Nile Fever. And about one in 150 to 250 or less than 1% of those people will develop what's called neuroinvasive disease. Or sometimes it's called WN-N-D, West Nile neuroinvasive disease. And this includes one of three possible, neurological manifestations that are common and then there's also honestly any range of neurologic complications that can happen but the three big ones are west nile encephalitis west nile meningitis and west nile acute flaccid paralysis and because i know you're going to ask me

aaron we don't fully know why exactly it is that some people get invasive disease and others don't but I know I can see your downtrodden face it's true we have some ideas okay it's likely a combination of that viral load like you already mentioned so how much virus do you get injected with from this mosquito to begin with and then a lot of other individual risk factors like older age especially over age 65 or 70 is very strongly associated with increased risk of neuroinvasive disease

and then other things like hypertension, kidney disease, things that affect your overall immune status. Also, West Nile virus being a disease transmitted by mosquitoes into your bloodstream, is a disease that can also then potentially be transmitted from things like organ transplants. And people who have gotten West Nile infection from things like organ transplants are also far more likely to develop neuroinvasive disease compared to those that get infected from mosquitoes. Interesting. Okay. But that is very rare. Just saying.

So generally, the incubation period for West Nile fever is anywhere from 2 to 14 days most of the time. And symptoms can really range from a pretty mild, almost flu-like illness to, like I mentioned, a very debilitating neuroinvasive disease. But in most people, it often starts like this. A sudden onset of headache, very sudden onset of a pretty bad headache, generalized malaise just feeling really crappy, a fever, muscle aches, and then fatigue. And very often, as this fever starts to subside, a rash will develop, usually along the torso and then extending out to the arms and legs.

And this rash actually looks kind of like the rash from measles. So it's like what we call maculopopular. It's a little red, flat little spots with raised little bumps inside. Yeah. It's the kind of rash that really like a lot of different viruses cause similar rashes. Unlike measles, this doesn't tend to go head down. Interesting. This is just like a torso to extremities type rash.

Why? Why? Great question. I have the slightest idea. Honestly, a lot of viruses cause similar rashes like this. So whether it's a combination of the damage that that virus is doing to your cells versus just that kind of generalized immune response causing that rash, I don't know the answer. Yeah. Rashes. Rashes. Let's ask a dermatologist. I don't know. I have a question about the complications, the neuroinvasive disease. Oh, don't worry. We're going to get there, Aaron. Okay, but I just, the breakdown among them.

So you mentioned the three different kinds. Yeah. What is the breakdown of those? That's a good question. I actually don't have a good handle on the breakdown. Everything just sort of said less than 1% will develop these complications. Okay. And part of it, I think, is probably because there's a bit of a spectrum.

Like, it doesn't mean that you maybe only have one of the three. You might have some acute flaccid paralysis with a little meningitis. You might have a meningioencephalitis. Yeah, but that's a good question. Also, I think because it is so rare, we probably don't have really good numbers to be able to break it down when it's less than 1%. Okay. Okay, but the rash. Back to that.

That, those type of kind of mild symptoms can last anywhere from a hand. handful of days to up to a few weeks. So this can be a pretty prolonged course of illness, even if it's not severe. Now, if it progresses to that neuroinvasive disease, the symptoms then just kind of look like whatever part of your nervous system is being invaded by this virus. So in the case of West Nile menendritis, the symptoms look like meningitis, which is a sudden onset of fever, a very, very massive headache, stiff neck, photophobia, which is difficulty looking at light, and it becomes very painful to look at light. If it progresses to encephalitis, then you often have those same meningial symptoms, but then you also will have things like. like altered level of consciousness, which means you can slip into a coma, essentially, or just personality changes because of swelling and inflammation in different areas of your actual brain.

And West Nile encephalitis tends to be the most severe with the worst outcomes. Okay. And so this might be a very basic question, but does it always progress meningitis and then encephalitis? No, not necessarily. And we'll get to that in just a minute. Kind of, maybe. Well, let me just keep going. So West Nile virus also then can cause acute flaccid paralysis.

Erin, do you remember what other disease we've covered that does this exact same thing? Oh, you remembered so quickly. Well, okay, but I have to confess, I've watched like a bunch of YouTube videos on West Nile virus, and there was one where like a physician came on and talked about it. And it was like, I haven't seen a polio case, but this is apparently exactly like polio. Yeah, they actually call it poliomyelitis, even though it's caused by a completely different virus, which I think is really interesting. It confused me, too. I was like, but wait.

Yeah. But basically what can happen is that if West Nile virus specifically infects the anterior horn cells of the spinal cord, this is the part of our spinal cord, where our motor neurons, exit the spinal cord. That is the exact same area that polio virus infects and causes swelling and then damage. And so this looks just like polio did. Your muscles and your limbs go weak. In the case of West Nile virus, it's often asymmetric, so it can look a lot like a stroke. Interesting. It is interesting. Why is it asymmetric? I don't know. And it's not always. It's just that oftentimes it can be. Okay. Presumably it's just that this is where the virus ended up.

So if somebody goes to the hospital and presents with acute flaccid paralysis, are there other things, like, or is West Nile sort of top of the list? I mean, depending, of course, on geography and their history, etc. Depending, it would depend on all those things. And West Nile virus, of course, polio can also cause it, but that's generally not around most of the world these days. I don't know. I don't know. know if there are other viruses. I imagine there are a handful of other viruses that can do that. One way that might differentiate this from stroke could be age range, especially if it's someone who has no other risk factors coming in. Importantly, West Nile virus tends to not affect your

cranial nerves and strokes often do. So if you think of stroke, they have like those, you know, public information campaigns about looking for a drooping face. That's when your cranial nerves are affected, which tends to not be affected with West Nile. In fact, in many cases, West Nile, acute flaccid paralysis can mimic Gionne-Barray disease. But Gionne Bray usually has sensory symptoms as well. And West Nile tends to not, although it can. Huh. Okay. I know. It's complicated. It's complicated. And with any of these neuroinvasive versions of West Nio virus, you may also have some other signs. things like nausea, vomiting, you might have a rash, you might have vision changes. So it's the constellation of all these symptoms.

It tends to not just be one symptom isolated. And some people have like a viral prodrome. So some kind of mild viral type symptoms, fever, chills, feeling cruddy prior to the onset of these invasive symptoms. Others don't, or at least don't remember having one. So the good news is that for most cases of West Nile virus, even the neuroinvasive cases, people tend to make a full recovery. However, the worst outcomes do tend to be in people who progress to encephalitis. And when we look at all of the neuroinvasive disease lumped together, so this is meningitis, encephalitis, AFP, but really the fatality, tends to come from encephalitis or meningitis. In those neuroinvasive disease cases, the case fatality

rate can be as high as 10% overall, or even higher for those that are older than 70. And for many, many people, especially with this neurologic symptoms, the recovery process can be very, very slow, taking up to a year or more. And in some cases, especially with this acute flaccid paralysis, or in some cases with encephalitis, people may lose function that they never are able to regain because nerves are damaged, things are damaged that just are not able to recover. And the damage is caused by just inflammation by the viruses being there. Yeah, so that's the question, right? Right, right.

What is the pathophysiology of this disease? I haven't even started to talk about it. So here, let's try. Shall we? Let's do it. Okay. So being a virus, we all know by now that viruses have to invade our cells in order to cause disease. It's thought that initially, primarily when we get infected, one of the major cells that West Nile

virus tends to infect are our dendritic cells, which are one of our immune cells that usually help to present antigens to our immune system, like a flag, so that we can make antibodies. So it's a pretty good cell for a virus to hide within. And West Nile virus, like many other flava viruses, is very good at suppressing our overall immune response to infection. So as it invades these dendritic cells, those cells travel to our lymph nodes, because that's where they like to go to present their antigens. But West Nile virus is then able to escape from those dendritic cells from our lymph nodes, enter our bloodstream, and travel wherever. it wants. And as we've just gone over, one of the big hallmarks of West Nile virus is that it somehow can make it from our bloodstream into our central nervous system, our spinal cord, our meninges,

or our actual brain. So how is it actually able to do this? Like how can it be so neuroinvasive? We're supposed to have a blood-brain barrier that's supposed to literally stop this. And the answer is that we don't know exactly how it's able to do this. How is it so good at evading our immune response and making its way into our central nervous system? There are four, at least, different hypotheses. One is that it just releases or causes us to release a lot of cytokines. We've, probably a lot of people have heard of cytokines by now because of COVID and our influenza episode way back when. But these basically just increase the permeability of our vascular membranes, allowing more things to pass through. It's so that inflammation can get in there to do its job.

But it also allows for viruses to make it across that blood brain barrier. That's one hypothesis. The second is that it actually just can warm its way by entering through our endothelial cells, those cells that line the blood brain barrier. It can invade those cells and then make it through. Another possible hypothesis is that it invades via macrophages. Ah. Right? So macrophages are another one of our white blood cells that sometimes move across the blood

brain barrier for our protection. But this virus can potentially be harbored within those macrophages. And finally, my favorite hypothesis is maybe it does a little bit of rabies. and it actually travels on our neurons and does retrograde axonal transport all the way to our central nervous system. That is scary. Yeah. And we don't know. We don't know which of those tends to be the biggest driver and why.

Huh. Yeah. It's especially interesting because, again, neuroinvasive disease can be very serious, but it's very rare in West Nile. And yet, it's also one of the most. common causes of viral, certainly a vector-borne viral encephalitis in North America. Right. Interesting. It's very interesting. So I don't have a good answer for you, Erin, in terms of how much of this damage is caused by viral damage directly versus our immune response and inflammation

therein, because we don't even fully understand how this virus even makes it into our central nervous system to begin with. So there are other flavvy viruses that invade the central nervous system? Certainly. And do we know the mechanisms for those? I don't. I don't. But I imagine that these hypotheses that have been proposed, which I didn't come up with,

have been proposed based on both mouse models of West Nile virus infection as well as other similar flavoviruses like Japanese encephalitis, etc. That makes sense. Yeah. So that's kind of the overall biology. It is, I will say, relatively easy to diagnose, but also, of course, difficult to diagnose in other ways. Mainly we tend to diagnose by looking for antibodies to the virus, which tend to be apparent after about eight days after the onset of symptoms. Most of the time you can find them after that amount of time, but you have to be able to test like between 8 and 21 days after symptoms start for that test to be accurate.

You can test for the virus itself, but then those tests are sometimes hard to come by depending on where you live, etc. I've also read that it's not easily detectable because humans tend to like circulate less virus in their blood. Right, very low levels of virus. And then it also depends on are you testing blood? or are you testing cerebral spinal fluid? Is it for meningitis or is it just for like a general infection? In general, at least as far as I could tell, we don't have any specific antiviral treatment for West Nile virus.

So treatment is just supportive the way that you would treat anybody with a meningitis or an encephalitis that's not bacterial. So just sort of supportive care. And that is the biology of West Nile. Erin. I know you have a lot to tell me about where this. virus came from. I do.

Okay, good. Shall we? Yeah, I'll dive in as soon as we take a quick break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands

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or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. Why have we asked our contractor we found on Angie.com to be our kids' legal guardian? Because he took such good care when redoing our basement that we knew we could trust him to care for our kids.

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Hey, I'm Jesse Palmer, host of The Bachelor with some exciting news. After more than 20 years of drama, the Bachelor Mansion is getting... Is getting... Is getting... My bad. A makeover. Your favorite former contestants move back into the mansion to spill their secrets, refresh rooms, and win the hearts of the judges.

Bachelor Mansion Takeover, Special Series Monday at 8 on HGTV. Well, actually, Aaron, this history section is going to be kind of like a total break from the last few episodes we've done. Okay. In what way? Well, okay. Diabetes, absolutely enormous history. Anthrax, huge. Oh, my gosh, so big.

Yeah. Shagas disease, super extensive history. All of it. But the history of West Nile, although it does date back, you know, probably further than you might think, it's fairly what I would say that's straightforward. Okay. Which isn't to say. Like, that's not to say that it's uninteresting or that I can't tell us. anything about big picture science or big picture society or big picture public health issues

because it definitely can. Oh, I have no doubt, Erin. But before we get to that, we have to start back a bit, of course. Where did this virus come from? And how did we get to where we are today with it? And what did they say in the Ebers Papyrus? Well, sadly, or not sadly, I don't know. It doesn't seem to be mentioned at least that I could gather.

I tried. I tried. So like you mentioned, Aaron, West Nile virus is a flavvy virus, and it's related to other flavvy viruses, like, you know, the ones you named. Yellow fever virus, which I honestly, it's been so long that I don't remember if I covered this in that episode, but the name Flavvy virus actually comes from the Latin word flavis for yellow, which I also think then kind of adds a fun little layer to the base quarantine to the recipe for our drink yeah yeah i agree also i can't remember if you said that in

yellow fever either so i'm glad that you told us again yeah but yeah danky virus sycca virus japanese encephalitis virus st louis encephalitis virus and so on so many so many and of all of these flaviviruses west nile virus is one of the earliest described and one of the most widely distributed. Huh. Yeah. I know. It was a little surprising.

Yeah, I knew it was widely distributed. I didn't know it was one of the earliest ones. Get in and get into it. Oh, I am. I am. So we can use things like serological studies and genomic analyses to tell us how it came to have what is basically this global distribution. And what it looks like is that West Nile virus evolved in Africa.

I don't have an exact or even a rough date estimate for that. or an exact location or even a rough location. But that's where serological studies show that the virus is circulating continuously and has been that way for quite some time. And this year-round transmission is in contrast with the patterns in other places, such as Europe, where West Nile virus was introduced from Africa via migratory birds and where it tends to pop up in this more, you know, seasonal, transient form. and West Nile virus was brought to India via trade, probably around like the early 1800s, 1820s or so,

when there was extensive trade between Africa and India, and then to Australia or the Australasia region in the mid-1800s. And this last one, like how it got to Australia, is a bit of a mystery because there are apparently no bird migrations that connect Australia and Africa, although any bird friends, Nick, Fred, Cole, Maria, Nate. Nick, we have a lot of bird friends. We do have a lot of bird friends. We do have a lot of bird friends. We weigh in if you know something else. But yeah, so it, because of that, it's been suggested that West Nile virus was actually introduced to Australia from Africa in a similar way that yellow fever virus was brought to North America from infected mosquitoes on ships carrying enslaved people as Europeans traveled to Australia from Africa.

Oh, okay. And it seems that really the only place where West Nile virus is not present besides, like, the Arctic and Antarctica, is in a lot of parts of Eastern Asia. And the reasons for that are not quite clear. Maybe it's like a competition thing with other encephalitis viruses. I don't know, a mosquito incompatibility, hosting compatibility, I don't know. And I'm not going to get too much into the details of like the different lineages and the clades that the virus can be broken down into because there's a lot.

But just to say that they do exist and that they can help us in new outbreaks to see where the virus is coming from and identify possible ways that it got there. For instance, like was it a single introduction event or multiple? It's thought that West Nile virus was introduced to Europe and North America in several independent introduction events while it was brought to Australia in just one. And then how much has the virus evolved since arriving in a new area? Are there pathophysiological differences among the different clades that could have clinical implications or ecological differences that could change the way we control it, etc?

So it's a useful area. It's just like a lot of minute detail that sort of. of open-ended questions in some ways. Yeah. Yeah. So I mentioned that West Nile virus was one of the earliest described flabby viruses, but the way that it happened was kind of a fluke. Oh, yeah?

Oh, yeah. In 1937, researchers were conducting a wide-scale epidemiological study on yellow fever in Uganda, and a person from the West Nile District of Northern Uganda was brought into the study presenting with a fever. But when they tested this person's serum against yellow fever virus, it didn't match. Instead, it looked to be more similar to other flavvy viruses that caused encephalitis, St. Louis encephalitis and Japanese B-encephalitis viruses. And even though the person only had a fever, they noted that it seemed to have neurotropic tendencies.

The researchers described this new virus in a paper in 1940, which is like older than I expected for Westmorel virus. It really is. Yeah. Also, I just have to complain here for a second because that paper published in 1940, so 81 years ago, is still behind a paywall. Are you serious? I am serious. That's ridiculous.

Yeah. I mean, like, can we just make everything open access? It would make the world a better place. Okay. 81 years old. I know. I know. Wow.

frustrating yeah anyway so why did i call the discovery of west nile virus a fluke well for one it was discovered kind of accidentally like those researchers weren't out looking for the cause of an outbreak of unexplained febrile illness and for two over the next 60 years or so after its discovery west now virus was not really considered that much like it didn't rank that highly on the list of pathogens of public health importance yeah No, there were a lot of other, and there still are, a lot of other mosquito-borne viruses that cause a lot more widespread morbidity and mortality. And so West Nile virus was kind of just like, oh, that's just another one of those flavy viruses. Right.

And the third reason is that, you know, like we talked about in the biology, the virus isn't often easily isolated and infected humans, like in blood. So the fact that they were able to isolate it at all, I think is kind of interesting. So it wasn't until the 1950s that the first outbreaks of West Nile virus were observed. Like the first time that people recognize that West Nile virus could be capable of causing widespread outbreaks. Right. Like an outbreak, not just like an incidental disease here and there. Exactly. And that started with the first recognized epidemic in Israel in 1951.

123 cases occurred in a small town the size of 303 people. I'm sorry, you said 160 cases in a town of 300? 123 out of 300 people. Oh, my goodness. I know. That's a pretty high attack rate. Really, really high. No fatalities occurred.

And in fact, most of the people affected were children. Hmm. But this was the first time. really that the various disease symptoms that this virus could cause were recognized. Things like you already mentioned, you know, fever, headache, abdominal pain, vomiting, etc. And around the same time as this epidemic in Israel, or not long after, a series of outbreaks of West Nile virus popped up in Egypt. And during these outbreaks, a lot more ground was covered in terms of understanding the disease ecology, clinical characteristics, and epidemiological patterns. For instance, this is

when researchers realized that a large proportion of people infected never showed any symptoms, that children in these areas tended to have more symptomatic illness, but adolescents and adults tended to have higher seroprevalence. So suggesting that, like, in these places where the virus was endemic and, like, continuously circulating, people were likely exposed to the virus at a young age. Interesting. Interesting. Yeah. And researchers also in these early outbreaks in the 1950s found the virus in many species of birds and also in some species of mammals. And this is when they made the link between mosquitoes and the virus. Okay, cool.

Wow. Wow. Yeah, a lot of ground. Yeah. And finally, some of the neurological complications of infection were observed during these early outbreaks in Israel and Egypt, things like these rare instances of meningitis or encephalitis. But overall, these outbreaks really kind of served.

to reinforce the idea in many ways that West Nile virus was mostly asymptomatic or, if anything, generally like a mild mosquito-borne illness. And this prevailing perception can be seen in the experimental infection studies that took place in Egypt during this time, where people with terminal cancer were intentionally infected with the virus to see if the resulting fever would help suppress the cancer's growth. Oh, gosh. Well, this was actually apparently like a fairly common or at least occasional type of experimental treatment during this time that people were like exploring or looking into. Interesting. Was it effective? So I don't know because, again, I don't have access to this old paper either from the 1950s, which is kind of annoying. Which also means that I couldn't read between the lines to see whether this fall. under, you know, actual experiment or medicalized torture.

Right. You know, does volunteer have quotes around it? Yeah. Et cetera. Okay. Yeah. But these studies were terminated when several of the people who were infected developed encephalitis.

Makes sense. Yep. Reasonable stopping point. But during these studies, the researchers also did make some important observations in terms of things like viremia, like how much virus was circulating and when. and how long it could be detected, and how the amount of virus circulating correlated with the severity of disease. Okay. So following these outbreaks in Egypt and Israel, West Nile virus continued to make sporadic appearances across parts of Africa, the Mediterranean, and Europe, popping up in France, South Africa, Russia, Spain, and India, some other places.

And in the course of these epidemics, it became more apparent that this virus can absolutely cause neuroliferation. disease in some people, which might have brought it more research attention at the time. So like in the 50s and 60s, if not for the fact that large outbreaks of the virus all but stopped throughout the 1970s and 1980s. Like they just, I don't know whether it was just like observation plummeted or the ecology made it to just like really put it in a lull period. I don't know. But in 19th, In 1996, a new era of West Nile virus began, first with a large epidemic in southern Romania. And not only was this one of the biggest recognized outbreaks of West Nile virus with at least 393 hospitalizations and 17 deaths, and who knows how many actual infections, but it also involved a lot of neurological cases. And it was the first to happen in what was basically a mostly urban area.

Whereas previous outbreaks had been more rural. And over the next couple of years, it became clear that this wasn't, like, this wasn't a one-off. West Nile virus seemed to be undergoing a change in its epidemiology. After the epidemic in Romania, the virus popped up in Morocco in 1996, in Tunisia in 1997, in Italy and Israel in 1998, and in Russia in 1999. And like the 1996 Romanian outbreak, these were also. in urban areas, seemed to have higher rates of neurological involvement with a higher fatality rate, and had a tendency to impact mostly people in older age groups. So by the time August 1999 rolled around, the pattern had already been set. But West Nile virus still held one more

big surprise for everyone. And that was that it had made the leap across the ocean and into North America. Big splash. Big splash. So far, West Isle virus, I think, has taught us a couple of really important lessons, or at least like reemphasize them. And since Erin, you're like, we've talked about this many times and listeners, if you've tuned in before, these are going to sound familiar, but I'm going to say them anyway. The first is to not underestimate a virus. Never underestimate a virus. Yeah. Many viruses that appeared mild at first can go on to have serious complications or long-term effects. Not all, of course, but the potential is there. Like remember chicken pox, for instance? Remember it? And the second lesson is that human movement and human modification of the environment can alter the dynamics of infection in a very major way.

Yeah. This isn't new stuff, but it's definitely important stuff. And so these two lessons were also learned during what would be the first epidemic of West Nile virus in North America, beginning in August of 1999. But that outbreak also carried with it another hugely important warning. Human health is wildlife health, is domestic animal health, is environmental health. It's all connected. What's that?

It's all connected? What's that? A one health approach? A one health approach. So let's get into it. Do you remember the 1999 West Nile virus outbreak at all? You know, I remember when West Nile virus became a thing because my dad had a pond in the backyard and it was like, oh no, we can't have a pond anymore because West Nile virus made it to California. Hmm. Huh. Yeah. Yeah, I don't remember specifically like the 1999 one, but I remember suddenly it was like

West Nile mosquitoes, you know, put on that off, whatever, all the time. All I knew was that it appeared and then that was it. Yeah. So let me fill in some of the details. Some of our gaps in memory. Yeah, yeah. So beginning in the summer of 1999, all over New York City, crows started dropping dead. It was like dropping out of the sky just dead.

Everywhere you went, you could find the carcasses of dead crows. And maybe if you lived in New York City at the time, you might have seen some of these dead crows and thought, oh, gross, these poor crows, probably rat poison, who knows? Bad pizza. Yeah. I don't know. And then went on with your day. Yeah.

But the sight of these crows brought a lot more alarm to one person in particular, Dr. Tracy McNamara, who is the lead pathologist at the Bronx Zoo. If these crows were dying of some kind of infectious disease, the birds at the zoo, some of which were rare or endangered, were at serious risk. And that risk soon became a reality when some of the zoo birds began to die, starting with a snowy owl. Oh, no. And this definitely pointed towards an infectious agent, but like what was it? Dr. McNamara examined some brain tissue from the dead birds under the scope to try to answer that question. And what she saw, in her own words, took her breath away.

Wow. Quote, it was the worst encephalitis I'd seen in 18 years as a comparative pathologist. Oh, no. Yeah, staggering. Yeah. Not far away at Flushing Hospital in Queens, an unusual number of encephalitis cases began coming in, some with paralysis and some leading to death. But these were inhumans rather than birds, just to...

clarify. And these encephalitis cases were clustered enough in time and space to make an infectious disease specialist at the hospital, Dr. Debbie Asnes, wonder whether there might be a link among them. So she brought in the Department of Health to ask the patient's question after question about where they ate, what they ate, where they worked, where they lived, what train they rode, what shampoo they used, and so on. The only commonality among them seemed to be that, they enjoyed spending a lot of time outside, especially in the evenings. And household surveys of where they lived show that there had been a lot of mosquito breeding habitats around. Could it be a mosquito-borne outbreak? It had been a long time since something like that had

happened in New York. Remember, this was before Zika. This was like, way before. Way before. for chicken guinea before, yeah, this is like. But it was still a possibility, like enough so that Dr. Asna sent off samples to the CDC to have them test for any known infectious agents, which, side note, deserve some major props.

Because there are plenty of doctors who would have chalked up the cases to coincidence. Like, there isn't always an answer in medicine, and there are plenty of unexplained fevers or illnesses that resolve themselves without revealing what they really are. And so for Dr. Asanus to send out those samples is, like, in many ways, I think, going above and beyond and likely helped enact control measures earlier than they would have otherwise. And so off those samples went to the CDC, and before long, they came back with a

match, with an answer. St. Louis encephalitis virus. And this seemed like a reasonable explanation. St. Louis encephalitis virus is a rare mosquito-borne virus that can, as its name suggests, caused encephalitis, and it's a flabby virus. But that answer, which was now by this time reported in the news like outbreak of St. Louis encephalitis, that didn't sit right with Dr. Tracy and McNamara. After hearing about the human encephalitis cases, she felt very strongly that there was a link between those cases and the sick and dying birds at the zoo. But if she was right and there was such a link, it couldn't be St. Louis encephalitis virus because birds can't get that virus. And so she reached out to the CDC with her concerns and urged them to test some of her samples to see if there was

a match to the human samples. But the CDC turned her down. Really? Really. Okay, partly Because it was a bureaucracy thing. Yeah. Like the testing of animal samples, all animal health stuff, that fell under the jurisdiction of like the USDA, I think. Interesting. And it was a totally different, like the CDC in some ways they were like, well, we don't have the capabilities to do this.

This isn't like we're not allowed to do this in the, you know, the job description. It's so interesting because as you were saying, like she reached out to the CDC, I was like, Wow. How does one just reach out to the CDC? That's a good question. I mean, I guess if you're like the lead pathologist at a zoo, you might have some. I would think you'd have an end somehow. Yeah. But it's a bummer that she couldn't get around whatever bureaucracy existed.

It was bureaucracy, but I think the other part was that she kind of ran into a lot of resistance wherever she faced. And that's like that's how she described it. Yeah. Because at that time, like, there was this prevailing attitude that, you know, human health and wildlife health weren't necessarily connected. And so the death of a few birds at a zoo, like, that doesn't have anything to do with the people sick with encephalitis at the hospital. Plus, we already have an answer. I just, it's a lot of times, Aaron, on this podcast, we have stories like that from like the 1800s where you look back and you're like, it was so obvious. How did you not see it?

And like this was 1999, so it feels painful. It does. And yeah, and it's also just kind of like, I think the aspect of the bureaucracy is frustrating. Oh, my gosh, yeah. So, yeah. But Dr. McNamara didn't let that stand in her way, her rejection by the CDC. So she sought out some colleagues in the Army and asked them to test her. samples. Awesome. And they did. And what they found was not St. Louis encephalitis virus, but rather a

virus that hadn't ever been detected in North America before. Of course, West Nile virus. West Nile virus. Suddenly, the CDC became interested and stopped screening Dr. McNamara's calls. Just kidding. They re-examined the samples from Dr. Asnus's patients, and sure enough, West Nile virus. Yeah. It's not surprising that it cross-reacted. Oh, yeah, not at all. That's like, I think that's a very reasonable thing for to happen, I guess. And so I'm not 100% clear on the timeline, but I did watch an interview with Dr. McNamara where she estimated that there was about a two or two-and-a-half-month delay resulting from the CDC not testing her samples. And so it's a couple of months where public health departments and wildlife health researchers could have gotten ahead of this virus

and like to try to begin awareness campaigns and control efforts. And I think that, you know, one of the biggest lessons is that this 1999 West Nile virus outbreak revealed how siloed we were and in many ways still are in terms of monitoring the links between human, wildlife, and environmental health. I feel like that's something we just touched upon in our anthrax episode. It absolutely is. Like, what good is a canary or crow in the coal mine if you ignore it when it signals danger? Or if you can't figure out what that danger is because you lack the diagnostic tools. This initial outbreak of West Nile virus in New York involved an estimated 8,200 human infections, 80% of which were asymptomatic, and the remaining 20% were mostly those with mild fibrile illness and then less than 1% of it.

develop this neuroinvasive disease. But in terms of confirmed cases, those numbers were a lot lower. 62 cases, I think, in seven deaths, something around there, like very low. Wow. Yeah. The 1999 outbreak in New York City was not an isolated event. It continued on to New Jersey and then to Connecticut. And it seemed likely that it was here to stay. The National Surveillance Program, Arbonnet, was created by the CDC and state health

departments to monitor bird and human disease to be on the lookout for potential outbreaks of arbiviral disease like West Nile. And one good indicator of an upcoming outbreak is the die-off of birds preceding the emergence of West Nile virus in an area. And that's exactly what happened in 2002 in the huge epidemic of West Nile in North America, reaching all the way to Montana and Texas and as far north as Quebec and Ontario. And this dwarfed the 1999 outbreak in New York with over 4,100 confirmed cases of the disease and 284 deaths. And I don't know how many estimated infections. But with a lot of the cases of severe disease and just general illness happening in the Midwest, U.S.

So like it had kind of shifted its distribution. In the period of just a couple of. years, this virus had traveled incredible distances, but we still don't know exactly how it got to the U.S. It's possible that it was introduced from Israel, but the mechanism is unclear that we may never know for sure. But in the time since these epidemics, we have learned a lot about the virus and its ecology. We've learned that horses can become sick with the virus. We've learned that it can be transmitted through blood transfusions and organ transplantation through the placenta and breast milk. Environmental conditions are hugely important, like warmer temperatures mean a shorter time

from infection to infectiousness in the mosquito, and they can also increase viral replication within those mosquitoes. So in cool weather, the mosquito has to like live a longer time in order to pass on the virus to humans. So it like has to live longer to become infectious after feeding on the infected bird. Average rainfall years seem to provide suitable conditions or the best conditions for mosquito proliferation. Warm winters mean more mosquitoes survive over winter. All of these bits of information are like pieces of the West Nile virus puzzle.

The more we gather, the more we can fit them together to get a better picture of why outbreaks happen where and when they happen. the role that different bird species play in transmission, and how things like climate change and land use change may alter the landscape of disease risk for this virus. And we are so excited to bring on a special guest to help us with a huge chunk of this West Nile virus puzzle. Yes, we told you it was coming. Uh-huh.

And that is the bird part of the puzzle. We'll let her introduce herself right after this break, and then, After that, Erin, I want to hear more about like West Nile virus in the world today. And I want to tell you about it. My name is Sarah Wheeler and I'm currently the biologist at Sacramento Yellow Mosquito and Vector Control District. And at the district, I am now focused on applied research into mosquito control. But I started my journey on this path as an ornithologist. And I've spent a lot of time investigating the role.

of wild birds and the spread of West Nile virus, the spread amplification and maintenance of West Nile, really. And so I'm happy to talk some more about that today. Awesome. Thank you so much for taking the time to chat. I just kind of want to start off by, you know, talking about the effects of West Nile virus on birds. So in this episode so far, we have talked about the range of effects that West Nile virus has had on humans, things like asymptomatic, or mild disease, all the way to these severe neurological complications or even death. So can you talk a bit about what infection looks like in birds? And is there a similar wide clinical range of symptoms?

Yeah, there's absolutely a wide range of symptoms. And it can go from completely asymptomatic in some species or individuals to debilitating to the point where the animal can't survive on its own to completely fatal infections. And a lot of this can be somewhat generalized by the species. So we know that some species are more susceptible to West Nile virus. So generally we think of passerines or songbirds being more susceptible to West Nile virus, but that is a huge range of bird species. And even within the range of songbirds, some are more refractory than others.

And so for a bird that is going to deal with an infection fine, you will never even know that they're infected. They might have a couple of days of viremia or no viremia that's virus circulating in the blood of the bird to the point where they could infect mosquitoes. They might not infect mosquitoes at all and not really become sick to a bird that produces so much virus in its blood that it could infect any mosquito that feeds on it. it succumbs within, you know, four or five days. So, yeah, it's a really wide range. Okay. So in the ones that are, like, severely impacted, what are some of the symptoms that they show? Yeah, so outward symptoms. If you see a bird with West Nile, it might be kind of hunched and puppy-looking. So we were doing some work with House Finches and West Nile virus. And it turned out that they were sitting there just looking very puffed up, and that's a common symptom in a bird that's sick.

And those birds actually had really low body temperature, so I think that it was having a hard time dealing with the infection and having trouble thermoregulating. Some birds develop acute neurological symptoms, so they get tremors or head pilt. So I think that sometimes birds that are in the transition period of just becoming very sick can actually just start acting weird. So we were studying the fatality events of crows in Davis, California. And it turned out that many of the crows that died of trauma actually were infected with West Nile. So, I mean, a crow doesn't usually just get hit by a car, but if it's not feeling well, it might not, you know, get out of that gutter.

Birds like raptors can actually develop ocular lesions, which means that they can clear the infection. but then they turn up at wildlife care centers for a body condition because they can't hunt for themselves. Right. So it's not necessarily that a lot of birds are dying outright or maybe some birds are dying outright from infection, but others are dying as a consequence of infection simply because they can't, like you said, exist on their own or survive on their own anymore. It's affected their fitness. Wow. Okay. Very interesting. And so, you know, as you mentioned, there are some birds that seem to be more susceptible to West Nile virus infection than others. Do we know anything about the reasons for

these differences in susceptibility? You know what? I really wish I knew this because it's, it is a wide range. And like I said before, we think of it as being, you know, taxa-based. So crows, birds in the crow family, so crows, jays, magpies are for the most part exclusively sensitive to West Nile virus. They're very common in dead bird programs. they, you know, have higher mortality when exposed. They don't all die. We don't have a lot of evidence of crows surviving West Nile, but we definitely have antibody positive jays and magpies.

This does happen. So they survive the infection. They produce antibodies, and that's something that we can detect in different zero surveys. But birds like pigeons, chickens, chickens are actually really common sentinel birds for West Nile virus surveillance. So we put them out in flocks and we bleed them every two weeks and see if they develop antibodies to West Nile virus. And this was a really classic way for doing Arbavirus surveillance, especially before you had PCR.

You could put your chickens out and serology techniques have developed before PCR technique. So this is a really handy way of doing surveillance. And chickens show no sign of infection. They don't infect mosquitoes. It's a total dead end host. So what is different between a chicken and a crow? I don't think we understand this, but there is something different, whether or not it's some sort of pathogen effect where the virus is just not replicating as efficiently or if it's that the bird is fighting it off more effectively. I don't think we know that.

Yeah. Interesting. So a follow-up question about susceptibility in birds with West Nile. is about geography. So are there any patterns geographically in terms of susceptibility? Like, are there, do there tend to be more resistant birds in places where the virus has been circulating for, you know, a really long time, like I'm talking on the scale of hundreds or thousands of years, versus places where the virus has been introduced more recently, such as in North America? I think that that is plausible. I mean, we don't see the mortality event. And,

where, you know, West Nile virus first evolved that we see in North America. So our birds in North America are living with West Nile currently, like multiple generations have now been living with West Nile. And I don't know if we'll ever get to completely asymptomatic. But it's plausible to think that. But what that might look like in North America is an open question because it's not a static system. So how a bird deals with an infection, if it's able to fight that infection off and not develop as strong of viremia, then that would push the virus to being more virulent. So there's always that host pathogen interaction. And so West Nile, compared to other arboviruses in North America, has tended to be more virulent. And we thought that this, you know,

help to drive it into more refractory mosquito species. So it took a higher viremia in order to get our native mosquitoes infected. And so that's kind of helped drive the system. And just over 20 years of West Nile virus, I think that we've seen some species that felt like they were getting more refractory. And it might be happening, but I don't know that we know that for sure. But West Nile virus transmission is not constant. It's not constant pressure.

So, you know, a population that's under constant pressure might get a lot of West Nile exposure for multiple years. And then we have two years of not a lot of West Nile pressure, which allows that population to build back up. Perhaps you have more open niches and more, you know, nesting success. And so it allows populations to recover somewhat. Yeah, that's really fascinating. You do have to consider all the different components of the system.

and the cycle that it's not just about the bird and the virus. It's also about the mosquito and the bird and the virus and all of these moving parts that are difficult to sometimes get a handle on. Yeah, I mean, the mosquito is a huge part of this whole situation. Yeah. The mosquito is in a way like the driving force of the whole transmission cycle because the mosquitoes that transmit West Nile would almost like nine times out of 10 prefer to feed on a bird. So Qylex, they really like to feed on birds.

They prefer birds. So if you look at blood meal ID studies where people collect blood fed QLex and you look at the DNA and the blood meal and identify what they fed on, you'll generally see a bird species there. Even though nine times out of 10 that Kulix mosquito is going to feed on a bird, if a human is sitting out there, you know, barbecuing or making it easy for the mosquito, the mosquito might just take advantage of that. So that's why it's predominantly a bird mosquito cycle because the mosquitoes are predominantly feeding on the birds. The birds are the amplifying posts. And that's kind of how it cycles with it, you know, occasionally spilling over into humans or horses.

And I get the question a lot like, well, what about my dog or my cat, you know? And I think I'm sure that they're bitten by infected mosquitoes, but we don't see any kind of reports of infection in dogs and cats. So probably just another get-in-post. I'm, like, now brimming with a bunch of questions about mosquitoes and mosquito ecology. And so is it really just sort of availability and opportunity of, you know, whatever hosts are there for the mosquitoes? Do these tend to be more silvatic species? Like, do they hang out mostly in wooded areas or are they also urban species?

You know, what are some of those differences among competent mosquito species? So in our area, the two main vectors of West Nilever, are Kilex Pippians and Kulex Tarsalis. Kulex Tarsalis tends to breed more in rural areas. So in our area, they breed really heavily in the rice fields that surround our urban centers. But Kulex Pivians is totally an urban breeder. They love catch basins. So in your gutter, there's that little grate and there's like a little cement compartment down there

that is supposed to catch the debris before it flows out to the creek or whatever. Well, those almost always hold watch. And so Qylex Pivians can really take advantage of that, a bucket of water in your backyard, or, you know, a green swimming pool or any source that they can take advantage of. And those happen quite regularly in urban areas. So you can definitely have both urban and rural transmission of West Nalveris. So sometimes in urban areas, you have a concentration of very competent. amplifying hosts. So in the city, you see a lot of crows, you see a lot of jays, you see house finches, house sparrows, and all these species are competent amplifying hosts. And then you also have the mosquitoes, so you have a concentration of players that can contribute to an amplification cycle. When you get out into rural areas, you also have competent amplifying hosts out there, and great vectors, the tarcellus is out there. Sometimes you can have pippians and rural species. But you

might have an introduction of more species, and sometimes the addition of greater species variety can have a diluting effect on effective transmission. So if you have a range of possible hosts, and 50% of them are great amplifying hosts, that's going to lead to a different transmission cycle than a scenario where 25% of them are great amplifying hosts. So that's why a lot of times we've seen West Nile be a little bit more urban in nature. I mean, it does happen rurally, absolutely. Yeah. So before I shift to talking about sort of more of the role that birds play in the transmission cycle of West Nile virus,

I want to just ask this, you know, overall question about the impact that West Nile virus has had on bird populations in North America since it's been introduced. And I'm sure that it's not consistent across the board, but have we seen substantial declines in some species and no impact on others. Yeah, so especially when West Mal was tearing across the U.S. and there was huge bird die-offs across the U.S. A lot of people were very concerned about different bird species, like zoo collections were even getting hit and, you know, precious animals that, you know, might be sensitive or in decline. Like, there was a lot of concern about what West Nile would do to those fur communities. And so my sense.

and other researchers have spent some time trying to figure out what the impact of West Nile has been on these bird communities. And the kind of data that you usually use for these kinds of analysis are some of these big bird census databases. So the Christmas bird count or the breeding bird survey can kind of help you understand impacts on bird communities because they've been in place for a long time before West Nile even got here. And so you can look at the the impact on those bird communities after West Nile and see if there's been any kind of changes in their population dynamics. It's not perfect, right? There's other things that affect birds than West Nile. And I would say especially like within the first five years, there are species

that absolutely saw declines. Like there are, there were declines. So a bird in our area of the yellow bill magpie. It's a bird that's only only found in the Central Valley of California. Like a huge part of its population was under West Nile virus pressure. Like you could see clear declines in that bird. They're kind of noisy birds. They're like a big black and white bird with a yellow bill. Like you notice them, right? Anecdotally, people were saying, yeah, all of a sudden the magpies were just gone. Well, you know, they by their own nature probably help preserve themselves a bit because not only can Yellow Bill magpies themselves be somewhat nomadic in nature, like West Nile does not exert even pressure every year.

And I think that that was what really allowed them to kind of level out and, you know, get back on a better track with their population. So that, you know, when West Nile first came in, like we had multiple heavy years of pretty steady transmission. And now it's like from year to year. year, it's like, oh, it's a big year for Sacramento and it's not a big year for San Joaquin. And so it moves around so it's not exerting that constant pressure on that bird population. Crows definitely have had some impact. Like, they're the most sensitive. They're just exquisitely sensitive. But the odd thing

about crows, and this isn't somewhat of the sidebar, they're always underrepresented in mosquito blood meal ID study. So you're like, well, why do we have all these dead crows if mosquitoes aren't feeding on them? And so that, I mean, that may be a function of just how a crow lives its life or how those blood-fed mosquitoes are collected. But yeah, I mean, I think that West Nile has a huge impact on those species. Yeah, I had heard that about crows, but I think that's really curious about the lack of representation in the mosquito blood samples. Yeah, that's a big story right there. And so it's been a source of debate about why we don't see them represented in

blood meal ID studies. And is it that they're not really an important amplifying host, despite the fact that they're like exquisitely sensitive to West Nile virus? And of the birds that you have been investigated for their response to West Nile infection, their viremias are like some of the highest, right? So they produce like the most virus in their blood, makes them extremely competent amplifying hosts. So it's like, are they not important amplifying hosts with all this virus?

And a crow especially, they'll sit there moribund for like two or three days before they actually succumb to infection. so they could just infect any mosquito that comes by to feed on them. And so, but when you do these blood meal ID studies, you find a lot of pigeons, you find doves, you find robins, you find a lot of other species like house winches. And you're like, well, that leads me to believe that they're more important because that's what mosquitoes are feeding on. That is so interesting.

Yeah. And so it's not as cut and dry as the birds that are the most susceptible and most abundant in a community or in an area are the ones that are going to play the biggest role in transmission or risk of exposure to humans. So are there these other ecological characteristics or certain species that do play a larger role as these reservoir hosts? So I feel like I used to see this more clearly than I see it now. So I think that before we had a lot more information. We had some good baseline data on what types of viremia, different species of birds kind of produced. So basically, the higher the viremia,

the more likely that a greater number of mosquitoes will be infected to the point where they will then be able to transmit. So that is on itself a spectrum. So a mosquito needs to be able to take enough virus, from the bird in order for it to become infected the point where then it can transmit. So birds that produce higher vireneas ultimately infect more mosquitoes that can then themselves transmit. I used to think, okay, like pigeons and doves, they're not great amplifying hosts,

crows, jays, magpies, house finches, house sparrows. these tend to be, you know, pretty good amplifying hosts, especially the corvids. But it's like once you get out of the box of looking at a figure on a paper of what's known about different viremia profiles for different birds, like it is a whole assemblage. It's a community of birds. And you know that even like though there are certain patterns that are followed for a given species, individual to individual are going to vary. At this point, I mean, we never even used to test morning dubs as a part of our dead bird surveillance program because it was like, well, they're not great amplifiers. So we don't even really need to look at them because chances are that they've died of something else. Well, on a whim, we decided to, well, let's just test this.

And it turns out that no, this species that's pretty much refractory to West Nile virus infection can actually still die of West Nile or it can die with a high amount of virus in its blood and tissues. Which you would think then is that it actually succumbed to infection. Maybe it didn't, but it had a high amount of virus in its tissues. So it's created like less steady ground for assertions that I would have made in the past. Like, oh, they're not really playing a role. If you have a bunch of doves, maybe that would not be like a community that would produce as much virus as you would think if there were more crows and jays and things like that around. So when you look at an area, there could be 200 species in that area. Some of them will maybe never amplify West Nile.

But once you take that scale of birds and run it all the way up to say a crow is the most susceptible in a community, it's going to be a spectrum, right? It's a spectrum. And so as far as do certain assemblages of birds, create a more risky West Nile virus scenario. I think that from a very high-level view, urban areas tend to create assemblages of birds that can lead to amplifying events. But it's not ever the bird that is dangerous to people.

It's the mosquito, right? So people don't have to worry about protecting themselves from the birds. They have to protect themselves from the mosquito. And so that's why we really, when we think about risk, we think about mosquitoes. And so we think about, well, how many mosquitoes are in this area? Like what proportion of them are infected with less now virus? Like what can we do to interrupt that transmission cycle? Because it's easier to deal with it and focus on the mosquito.

And it's the more direct link to exposure. Yes, bird community matters. It matters. but it's variable and it's hard to absolutely state what's the best amplifying community, you know? Right. Ultimately, it comes down to the mosquito and how many mosquitoes there are in a certain environment and how often humans are out and so on. Yeah, absolutely. So let's talk a bit about bird migration. So we know that bird migration has an impact on potentially the geographic spread of West Nile virus and potentially other, you know,

bird-associated pathogens. But how do things like the stress of migration impact bird communities or, you know, the immune systems of birds and making them more susceptible potentially to West Nile virus? Yeah. So migration has been definitely a thing that we've spent a lot of time thinking about. So there is a somewhat of a mystery with what. West Nile, and that's where does it go in the winter? So overwintering mechanisms for West Nile virus are not well understood. It was always a possibility that West Nile was overwintering, you know, down somewhere where

it's warmer, where you could have year-round transmission, and then reintroduction of events were kind of by migrating birds, bringing it into new areas every year, and maybe that could a tribute to why we see it flare up in different places from year to year. Looking at the genetics of the virus, this is not really supported, but we did spend a lot of time looking at migratory birds to kind of figure out if they were spreading the virus around. At some point, I was down at the Coachella Valley, like along the Salton Sea, and every year we would go down there to collect as many migratory birds as we possibly can. and collect a small blood sample and test that blood sample for both antibodies and viral particles,

basically. Has this bird been exposed to West Nile and is it currently infected? So it's a long shot looking for a viremia, especially in a migrating bird, because migration is a very costly event for those birds. So for them to be able to be fit enough to migrate while acutely environment. infected is, I don't, I don't know if that's possible. It may be. I mean, birds are amazing. It could, they could do it, especially for short hops. Maybe, like, from one stop to the next, they might get infected and then be able to carry it to the next hop. And then if it's a species that's so

refractory to West Nile that it's able to migrate in an infected state, like how is that going to play a role in a transmission events. So there have been other researchers that have found some kind of indication of birds migrating while infected. So I'm sure it happens. But when we looked at the data for the birds coming in and the birds that were here, it just really seemed like the majority of the infection was happening here. So when we did find migrants that were infected, with West Nile virus, they were heading back down south. They weren't heading north. They had been here all summer and were heading back down to their Central American overwintering grounds, and they had already been exposed. And so it really seemed like it wasn't migratory birds that

were constantly reseeding infection, just by what we're observing with, you know, West Nile virus activity in the birds. That it seemed to be. like there was something that it was overwintering locally and flaring up. And then as migrants were coming through, there was always the potential that they could be exposed and then hop it to the next location. That is very interesting. It kind of turns a bit like on the narrative that is so like, oh, well, you know, birds that move from one place to another. And it makes it so easy for it to spread, it might not necessarily be why we see, you know, these events happening. And so on that note, about how long, or is there any sort of window during which in an infection there is circulating virus in the birds that are susceptible and do seem to have like this viremia?

Is there a length of time during which you can collect virus? So if you're looking at a bird who's just been infected by about two days, you can detect virus in the blood. and then by about seven days, if it's not cleared, it's most likely not going to survive. Okay. And then is there, you know, lasting immunity following or can a bird get reinfected? It seems to be lasting immunity. Okay. So as someone who works in the applied, you know, side of things and has this, like, research background as well, what do you see as the biggest challenges to West Nile virus control? Honestly, for West Nile virus, we have to be able to have good effective surveillance

methods. We have to have effective mosquito control tools. And so thankfully, we've gotten a very efficient system for how mosquitoes are trapped and how they're tested. These are kind of pretty well worked out. But at this point, in mosquito control, there are two active ingredients that are used for controlling mosquitoes. So you have pyrethrines and pyrethroids and you have organophosphates. So these are the insecticide classes. And they're used in many, many other fields. So they're common in agriculture. They're common like if that pest control guy comes by your house. It's like, oh, you know, you have spiders all over. I could spray for that. Well, they're spraying, but we're spraying. And so insecticide resistance is a growing problem. And so as

we move forward, we're going to have, we're going to have to find creative solutions or how to break that transmission cycle through effective mosquito control. And this will continue to be a problem moving forward because, I mean, mosquito control is a small slice of the, you know, insecticide usage pie, especially public health mosquito control, like applications. So there aren't generally products designed, especially for mosquito control, because it's like not, it's not the largest market, you know. There are innovations that are coming out. So for a species 80s, Egypti, which is a terrible vector around the world,

all the spreads dangi and Zika and chingunya. It's been invasive in a lot of areas of California. So we're now dealing with the jifty in California and throughout California. And so there's a lot of talk now about, well, can we, you know, use sterile insect programs to control these mosquitoes? And I think that that's being used more and more. Like it's still an emerging option. And it might not be like what we can use for Culex control.

But it's an example of thinking of new solutions to old problems. And I think that that's what we're going to have to continue to do moving forward is think outside the box and, you know, push the envelope. Thank you so much. That was awesome. We knew that we were missing such a big part. I mean, I learned a lot. So much. So tell me more. Let's hear even more.

So we'll just now focus on West Nile virus mostly in humans and look at the big picture, shall we? Mm-hmm. Focusing first on North America, since that's where we ended your section, Aaron. Since West Nile virus made its debut in New York in 1999, the virus has resulted in over 48,000 reported cases in the U.S., 24,000 of those have been neuroinvasive, and it has resulted in over 2,300 deaths. Wow. Yeah, in about 20 years. Now, it's estimated that the true number of infections is over 7 million human infections in the continental United States.

Wow. Wow. Yeah. I just am going to keep saying, wow. That's all we can say. It's by far one of the most important zoonotic diseases and one of the most important causes of viral, especially vector-borne encephalitis in the U.S. since its introduction. And like you said, Erin, it has spread throughout the entire United States. It's present throughout all of North America. It's likely present in Central and South America as well, but we don't have great data on Central and South America. whether that's because it's overshadowed by other infections that look similar, like maybe dengue fever, or whether it's there but at very low levels, or it's just not being reported. We don't really know, but we don't have good data on it. But even within the U.S., while, like, over 50% of counties in the U.S.

have reported at least one case, like, over the course of time, they're not evenly distributed like cases are not evenly distributed and outbreaks tend to happen in like discrete areas that vary a lot year to year. Right. So overall, the actual number of reported cases in the U.S. since its introduction has been, it varies a lot year to year, but it hasn't necessarily been steadily growing or anything like that. But you do see a lot of year to year variation.

a lot of geographic variation. Like one year you'll have a whole bunch in Montana and another year, a whole bunch somewhere else, etc. And it's not just humans, of course. West Nile virus is a substantial animal pathogen. In the U.S., it's caused over 28,000 cases in horses and mortality that we know of in over 300 bird species, like we heard a lot about already. In Canada, over 5,000 human infections have been reported. And across Europe, outbreaks happen almost every year. But the biggest outbreak, especially in Europe by far, was in 2018, when there were over 1,500 cases that were reported across Europe. That was over seven times as many cases as had been reported in the previous seven years. Dang. Right? In one single year.

And so whenever we see outbreaks like this that happen, like really big outbreaks all of a sudden, especially of a vector-borne disease, we have to think about, like, what are the factors environmentally that are impacting this? And Erin, you kind of touched on this a little bit, but we're going to get into it a little bit more. Oh, yeah. And then, of course, we're going to talk about climate change. So like many, if not all, of the vector-borne diseases that we've covered on this show, it's not entirely clear how climate change either is going to affect or has already begun to affect West Nile virus, incidents, prevalence, and also distribution. But we can gather at least a little bit of information based on especially that 2018 Europe outbreak, as well as just what we know about the mosquito and the virus.

So given that West Nile virus is mostly transmitted by mosquitoes in the genus Culex, their natural ecology is such that in an increasingly warm climate, it's very likely that that type of climate will increase both the abundance of these mosquitoes as well as increase their overall distribution. And like you mentioned, Aaron, if they're better at harboring virus, in warmer climates compared to colder climates where they're maybe not as good of vectors, that's important

as well. Oh yeah, that's not good news. No, it's really not. And that outbreak in Europe in 2018 it turns out that year was not only one of the hottest years ever recorded

it was also a very, very wet spring that was followed by a summer drought, which likely led to a very early expansion of the Culex mosquitoes, which led to an increase in viral transmission. So what we saw that year was cases being reported earlier in the year than ever before, and then an outbreak that was the largest ever recorded, more cases, like I said, in the previous seven years.

And over a larger geographic distribution than had been previously recorded, That year alone cases were reported in Austria, Bulgaria, Croatia, Cyprus, Czech Republic, France, Greece, Hungary, Italy, Portugal, Romania, Serbia, Slovenia, Spain, Turkey. Everywhere. Yeah. So despite its global prevalence, despite it being such a common cause of mosquito-borne infection in the U.S. for over 20 years, we still don't have any specific treatments, and we still don't have any licensed human vaccines. And with every year, I feel like becoming the hottest year on record. Right. Yeah.

Every year it feels like that this one. There are at least four different animal vaccines, I think primarily for horses. And there have been phase one and two studies of human vaccines, but there haven't been any phase three or like the larger efficacy studies. And it seems mostly because there's not a market for it, financial. which is so frustrating. And what's even more frustrating is that we have vaccines for a lot of other flava viruses, like yellow fever virus, we have a vaccine. Japanese encephalitis virus, we have a vaccine.

Now we even have a vaccine for dengue virus. Apparently, from a paper from 2019, there have been at least six different candidates of vaccines that have gone through these phase one and two trials. at least two of them seem to produce good immunity after a single dose, which is what would be needed for it to be a cost-effective vaccine. None of the animal or the horse vaccines are single dose. They all require multiple doses as well as annual boosters. Oh, okay.

But there is at least promise, I think both in terms of the immunology of West Nile virus and of flava viruses in general, and then the fact that at least we have vaccines in phase one, phase two trials, it seems to be kind of like a funding issue, etc. But in general, because of this lack of vaccine, control efforts really rely on prevention of infected mosquitoes. So things like integrative pest management, mosquito infection, like you mentioned, Erin, sentinel bird surveillance, and all of that, to try and reduce the prevalence of infected adult mosquitoes. And that, my friends, That's West Nile virus.

That's West Nile virus. That was a fun one, Erin. I learned a lot. Yeah. It was a really interesting one. I can't believe we hadn't done this yet. Hey, we did it now. We did it now.

And, yeah. Sources? Sources. I have a lot of papers. I'm going to shout out just two. And one is by Savor from 2000, titled West Nile Virus and Historical Ours. overview. And the other that I wanted to shout out for fun is by our PhD advisor, Dr. Brian Allen. Yay. Yay. And that is Alan at all from 2009 titled ecological correlates of risk and incidents

of West Nile virus in the United States. And I also watched, as I mentioned, several videos on West Nile virus. And I will post links to these. There were a couple ones that were especially helpful West Nile virus the first decade by Richard Ailer, one on PBS, West Nile Outbreak in New York City, and then also a great interview with Tracy McNamara and this video titled One Health and the Lessons Learned from the 1999 West Nile Outbreak, and that is by Microbbe World. I also had a good number of papers. A couple of my favorites for the general overview of West Nile virus were both titled West Nile virus, one from the Lancet Neurology, 2007 and one from the Lancet infectious disease in 2002, so kind of older papers, but still really good.

If you want more info on the development of vaccines, there was a paper called 20 years of progress towards West Nile virus vaccine development in viruses from 2019. And we'll post all of our sources from this episode and every one of our episodes on our website, this podcast will kill you.com. We will. Thanks again so much to the amazing guests for this episode. We so appreciate you coming on to chat with us. Yeah, thank you.

Thank you also to Bloodmobile, who provides the music for this episode and all of our episodes. And thank you to exactly right, of whom we are a very proud member. And thank you to you, listeners. We really love making this podcast, so thanks for listening to it. Yeah, and a special shout-up. out also to our amazing, incredible supporters on Patreon. We love you. You're amazing.

And everyone, you only have a few more seconds to wait until your ears get to be blessed with the joyous sounds of MC Bugsy and West Nile Story. West Nile Story. Bring us out, Aaron. Wash your hands. You filthy animals. virus. It may not realize it, but it's inside of mosquitoes and they can spread it to people. So cover up, rock repellent, get rid of standing water. Mosquito bites can be more than just a

bottle. No vaccine to protect. No medication to treat it. That means attention to prevention is the challenge. So meet it. Empty, scrub, turn over cover, tip and toss out containers. Clean up the yard once a week and you live your best life later. Long loose, light colored clothes, so no skin's exposed to biting mosquitoes attempting undercover probes. Use repellents to protect yourself and those that you love from the potential health threats are being bitten by a bug who's heard a west now virus you may not realize it but it's inside of mosquitoes and they can spread into people so cover up rock repelling get rid of standing water mosquito bites can be more than just a bother yo who's heard a west now virus you may not realize it but it's inside of mosquitoes and they can

spread it to people so cover up rock repelling get rid of standing water mosquito bites can be more than just a spread the public health in the summertime. Been here for 20 years. Shout out to Queens 99. Rapid spread from east to west. Now it's throughout the continental U.S. Qlex, mosquito vector with a bird preference. In nature, West Nile cycles between mosquitoes and birds,

when those mosquitoes feed on people infections occur. Steady sipping dust till dawn because they're nighttime biteers. Attack at twilight like microvampire. Who's heard a West Nile virus? He may not realize it, but it's inside of mosquitoes, and they can spread it to people. So cover up rock repelling get rid of standing water Mosquito bites can be more than just a bother.

Hoos are to ask now, virus you may not realize it, but it's inside of mosquitoes and they can spread into people. So cover up rock repelling, get rid of standing water. Mosquito bites can be poor than just the bother. Now luckily most folks infected will never feel sick but some will suffer from fever, rash, aches and weakness. Though most recover completely, the fatigue can persist.

For weeks or months you could be living, lethargic and listless. Unfortunately, any age can get severe illness But people older than 60 and the sick have the highest risk Of neuroinvasive cases with lifelong effects, Encephalitis, meningitis from a virus that wrecks Protect from West Nile virus, here's hoping you realize that it's inside of mosquitoes And they can spread it to people So cover up rock repelling, get rid of standing water

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