This Podcast Will Kill You - Ep 109 Chikungunya: Not dengue (or is it?)

Episode Date: November 8, 2022

Somehow it’s taken us until the penultimate episode to cover this season’s first mosquito-borne virus. But we assure you, this episode is well-worth the wait. Although Chikungunya virus is often lumped in with dengue or Zika, the unique characteristics that distinguish Chikungunya virus from these other arboviruses are just as important to note as the similarities among them. In this episode, we explore these differences and similarities in the biology of Chikungunya virus before reassessing what we thought we knew about the history of this disease, a history that is presently under revision. Finally, we wrap up the episode as we always do, by taking stock of where we stand with Chikungunya virus today. Tune in for a good deal of dengue compare/contrast, a whodunnit (or whichdiseaseisit) in the history of these two diseases, and a frustrating attempt to gather present-day case numbers. See omnystudio.com/listener for privacy information.

This is exactly right. There are already enough things charging your card every month. Dinner should not be one of them, which is exactly why Blue Apron is now subscription-free. You heard that right, Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another recurring charge. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients, so there's no meal planning and no extra grocery trip. Order now at Blue Apron.com. Get 50% off your first two orders plus free shipping with code this podcast 50.

Terms and Conditions Apply. Visit blueapron.com slash terms for more information. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these quote-unquote fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies. 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious.

These are foods that you would want to eat. Not that the babies would ever share. Just Food for Dogs is the number one bet recommended fresh dog food back by over a decade of research. No marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging, paws tapping, full Broadway performance every single night. So I do care about the food I feed big and smalls. So go to just food for dogs.com for 50% off your first box, no code, no gimmicks, just real fresh food.

HGTV is taking over the iconic Bachelor Mansion. If they thought picking a soulmate was hard, just wait until they have to pick the right shade of egg shop. Bachelor Mansion Takeover, special series Monday at 8 on HGTV. Towards the end of September 1827, a disease of a visual. very singular character suddenly made its appearance in the island of St. Thomas, and attacked almost every individual in the town, which contains a population of about 12,000 souls. The disease appeared so suddenly, and spread with such rapidity, and the suffering attending it was so great that at first it caused universal alarm and was considered a sort of plague that would probably

ravage the whole country. It was soon, however, discovered that although a very painful, it was by no means a dangerous disease, and that if the attack was rapid, the recovery was no less speedy. This, at least, was the general belief, until longer experience showed the troublesome nature of the secondary pains that constitute the third stage of the disorder. The most usual mode of attack was the following. A person in perfect health would suddenly feel a stiffness amounting almost to a pain in one of his fingers, and most frequently his little finger. The stiffness increased and was accompanied by an intense degree of pain, which spread rapidly over the whole hand and up the arm to the shoulder. The fingers of both hands in a few hours became swelled, stiff, and painful, preventing all attempts at bending the joints. This was followed in a short time by restlessness, depression of spirits, and a degree of nausea, ending in some cases in vomiting.

Then came on shivering, succeeded by fever, great heat of sun, skin, intense headache, most acute pain in the back, knees, ankles, and in short, in every joint. But perhaps the most distressing symptom of this stage was the intense pain in the eyeballs. In every case where the first stage was in any degree well marked, patients declared that they had never experienced nor could have conceived pains equal to what they felt in this fever. Not one inch of the body from head to foot was exempt from suffering. An efflorescence was perceived at this time to begin at the palms of the hands and to spread over the whole body. After the eruptive stage, the patient began to recover his spirits and his strength,

but in many cases a complete want of taste remained for some days. Many people did not get rid of the pains in the joints for many weeks. In general, however, the disease gave a degree of respite for three, four, and even in some cases six weeks, and then attacked the joints with more pain and paralysis. than at first. I conclude with the hope that I have done my duty in endeavoring to record a disease attended with so many curious symptoms as justly to challenge the attention of every medical man and particularly of those who are destined to practice in tropical countries. I love this old-timey descriptions, Aaron, so much. I love that. So that was excerpted from this paper published in 1828 by George

Stedman, yeah, titled some account of an anomalous disease which raged in the islands of St. Thomas and Santa Cruz in the West Indies during the months of September, October, November, December, and January 1827 to 1828. I guess they didn't have character limits and titles back then. The most descriptive and specific title. Yeah. So that, like, that whole paper, which is available online, is an interesting read. There's so much more detailed there. but I just pulled little excerpts that I thought were most descriptive of the topic of today's episode, which is chicken gungunya virus. Chicken gungia virus. Hi, I'm Erin Welsh. And I'm Aaron Almann Updike.

And this is, this podcast will kill you. Welcome to, is this our first mosquito-borne virus of our whole season? I think so. Wow. I can't keep track anymore, Erin. I know, same. I feel like we've done, I mean, we've done like some lice and things. Yeah, we've done some vectors.

Yeah. But yeah, mosquito-borne virus, I think so. I'm excited. It's going to be a good one. It is. I didn't really know anything about chicken guinea besides the name before getting into this. And yeah, I'm very curious to hear how the biology works. I know.

I remember in 2013 and 2014 when the big outbreaks were happening in the Americas and being like, what's going to happen with chicken gunya? And then that was it. And I never really learned much more about it. So it was fun to get to research. Yeah. But first, it's quarantini time. It's quarantini time. What are we drinking this week? We're drinking head, shoulders, knees, and toes.

Yeah, so we are drinking head, shoulders, knees and toes because one of the hallmark symptoms of chicken guinea virus, as you heard in our first-hand account, is joint pain and headache. Yep. Pretty, pretty severe, as we'll discuss. Very severe. Yeah. Yeah. So what is in head, shoulders, knees, and toes? Oh, it's a perfect little fall concoction. You've got some apple cider, some orange, and some mescal for smokiness. Yeah. And also as a call back to dengue, our dengue episode and our dengue quarantini, which had mescal in it. And because you're going to hear a lot about dengue. I know. There'll be a lot of compare, contrast, dengue, change. can goa, et cetera. So it makes sense. So we called back to it. We'll post the full recipe for our quarantini as well as our non-alcoholic publicity barita on our website. This podcast will kill you.com and all of our social media channels. Before we dive into the episode, of course, like the routine, check out our website, et cetera, et cetera. There's a lot of stuff there. But also this is our second to last episode of season five. What? Yeah. There's just one

more coming out after this, but don't worry, we will be back. We're just going to take a break and not read about disease stuff for a minute. I mean, we'll probably still read about disease stuff, but like just quietly into ourselves. Actually, that's true. And then we'll just text each other. Exactly. Well, in any case, we will be back. And so make sure you follow us on all of our social media accounts so that you know when we are on our way back. And if you have suggestions that you really want to hear for next season, send them our way. Well, with that, Erin, shall we get into chicken guinea virus? Let's do it.

Right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep. Just spread the pre-chopped ingredients on a sheet pan, put it in the oven, and that's it. And if there's truly no time to cook, dish by Blue Apron meals are fully prepared.

Just heat them in the oven or microwave, and dinner is ready. And here's the exciting news. Blue Apron no longer requires a subscription. You can order meals when you want them and skip when you don't without adding another recurring charge. Order now at blue apron.com. Get 50% off your first two orders plus free shipping with code this podcast 50. Terms and conditions apply. Visit blue apron.com.

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

conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. A timeless wardrobe starts with pieces that are built well from the beginning. From the fabrics to the fit, everything needs to last beyond one season. And that's how Quince approaches design. Quince has all the staples covered, from 100% organic cotton sweaters to premium denim made with stretch for all-day comfort and luxe cotton cashmere blends, perfect for the changing seasons.

The quality shows in every detail, the stitching, the fit, the fabrics. Every piece is thoughtfully designed to be your new wardrobe essential, and each piece is made with premium materials in ethical trusted factories and priced far below what other luxury brands charge. I recently got a pair of Quince's Bella stretch wide-leg jeans, and they are now in constant rotation. They are so comfortable. The fit is amazing.

and they come in a bunch of different washes, so I'm about to go order some more. Refresh your wardrobe with Quince. Go to quince.com slash this podcast to get free shipping on your order and 365-day returns, now available in Canada too. That's Q-U-I-N-C-E.com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. Chicken gunia virus is an Arbovirus, which means a virus transmitted by Arthropodvect. and in this case, like we said, mosquitoes. I'm probably going to end up talking about the two main mosquito vectors more than anyone bargained for. It's going to be fun.

I'm so glad because I did a little bit of diving into the ecology and I was like, I don't know where this goes in the history section. Hopefully, Erin, we'll talk about it. Well, I found myself thinking so much of Allie and Allison in our old lab and being like, I wish I could call and be like, can you tell me about their ecology? Anyways. So let's get into it, shall we? Chicken gunia virus is in the genus Alpha virus in the family Toga Virae. And these viruses, their RNA viruses, the majority of which are arboviruses. They are transmitted by mosquitoes and other vectors. A few that people may have heard of include Ross River virus and Western and equine encephalitis viruses. One thing I thought was interesting about alpha viruses in general is that at least one of the papers that I was reading was talking about how for a lot of alpha viruses, humans and our domestic animals are often considered dead-end hosts. So we aren't necessarily like the evolutionary hosts for these pathogens, which is, I think, very interesting, especially because I'm going to end up comparing and contrasting chicken guinea virus in this episode, because it's compared. a lot in the literature to a few other arbiviruses like dengue, Zika virus, yellow fever virus.

All of those viruses are not in the alpha virus family. Those are all flava viruses. So a completely different family of viruses, some of which are very human-specific, like yellow fever, or can cause disease in animals and humans kind of equally. That's interesting that humans are considered the dead-end host for alpha viruses, is that because of like viremia and mosquitoes not being able to get enough virus? Or is it because mosquitoes aren't biting as much? Yeah, I think both from what I could tell. Okay. Yeah, yeah.

But as we'll see, that's not the case for chicken gunya. Mm-hmm. Mm-hmm. So the two major vector species of chicken guinea virus are mosquitoes that might be familiar to longtime listeners. They are mosquitoes in the genus 80s, particularly 80s albipictus and 80s Egypti. These are the same mosquitoes that are responsible for the transmission of dengue fever, of yellow fever, and of Zika virus, among many others.

There are a lot of other species of 80s mosquitoes that can also transmit chikungunya, as well as perhaps some species of Culex that have been found to be infected, but predominantly, especially for humans, it's albapictus and Egypti, and that's probably how I'll refer to them throughout this episode. And like many of our mosquito-borne viral and other pathogens, this life cycle can be a little bit complicated, but it goes a little something like this. The mosquito takes a bite of an infected blood meal from an animal or a human in the case of chicken guinea. the virus has to travel through the guts of that mosquito, disseminate through the gut wall of the mosquito, travel through the hemolymph and invade the salivary glands where they can replicate. And this process for chikungunya virus within the mosquito takes between two and five days to happen.

Okay. So what that means is that the adult mosquito, after it takes its first blood meal, has to live at least two to five days to then be infectious to another person. I have a question about mosquito longevity. Oh, cute. So glad. Aaron has so many fun facts about these mosquitoes. Yes. Okay. Excellent. How long on average do the different species Alba Pictus and Egypti live? So these mosquitoes take about a week to develop from egg into adult. But once they are adults, they can live for four to six weeks. Okay. Mm-hmm.

Which is a lot of biting potential. It sure is. And it's only female mosquitoes that bite. They have to take a blood meal in order to make eggs in order to lay a brood. And 80s mosquitoes, if they are able to take an entire blood meal, and there are differences between 80s, Egypti and Alba Picdis in terms of, like, how often they lay eggs and things like that. But if they took a whole entire blood meal, they might be able to go. several days between feedings. But what often happens is that they get interrupted really frequently during their feedings. So they don't get a whole blood meal at once. So they might bite and then bite

and then bite and then bite in order to get enough blood to be able to make an egg brood. So it's not like one blood meal or one feeding sesh, one infected person. It could be five feeding sashes to get your, you know, stomach full and you infect. five people. So is there, yeah, like viral load, infectious dose, like, you know, does that play a role in it as well? Great question. I totally don't have answers for you on that, like how many viral particles do as a mosquito have in their salivary glands and how many are they injecting with aged feed? I have no idea. But at least in theory, if this mosquito is biting many different hosts, not only is that many opportunities to become infected, but it's also many opportunities to

transmit that pathogen. Makes sense. And wow. But going back to the timeline of it, so two to five days for that process of dissemination through the guts before a mosquito becomes infectious. Here we start to compare contrast, something like chicken guinea with something like dengue virus. Dengue virus takes eight to ten days before it's transmissible in the adult mosquito. So already you have a mosquito that doesn't have to live nearly as long, before it can start infecting other people. Interesting. So I guess that would probably play a big role in how fast an epidemic or an outbreak happens. Sure could. Mm-hmm. All right.

So continuing on in our life cycle, once that mosquito is infectious, it takes another blood meal, and then those viruses are injected from the salivary glands into our subcutaneous tissues. Those viruses make their way into our bloodstream. They infect a number of different. cells. They infect our fibroblast cells. They can replicate in our skin cells. They make their way into our liver and into our joints where they infect a variety of cells. I'm going to pause in the life cycle here because I want to talk a little bit more about these two species of mosquito, even though we've already kind of dove into some of the fun bits. These two species of mosquito, 80s alpictus and 80s Egypti, we've talked about. We've talked about.

about them a lot because we've done Zika, we've done yellow fever, we've done Dengue. These mosquitoes are particularly good, particularly well adapted to rural, urban, and human-built environments, especially 80s Egypti. This is a mosquito that, like, just loves humans and our urban environments. These two mosquito species are generally both container breeding mosquitoes, So they do really well in things like old tires or that pot you forgot about, that one pothole in your street that absolutely never drains, your neighbor's pool that they drained three years ago, but they never filled it. So there's just like an inch of water in there. Also tree holes in more like suburban or rural environments, etc. Any tiny amount of standing water is enough for 80s, Egypti and Alba Piccdis both to be able to breed and survive.

These two mosquitoes are also very aggressive. They're really aggressive biters, especially for humans, like they really like humans. And especially 80s alpictus tend to be more diurnal than most mosquito species. So they can primarily bite during the daytime in the mornings and in the evenings. So they're really difficult to avoid. And things like bed nets that are often used to protect against other. mosquito species that bite at night don't do anything to prevent the bites of 80s, albapictus, and 80s Egypti.

Right. And like I said, they can complete their entire initial life cycle in as little as a week from egg all the way to adult. So in times of plenty in terms of rainfall, like the rainy season, you have many, many broods of mosquitoes over and overhatching and going out in search of new blood meals. But at the same time, like many mosquito species, these eggs can dry out completely and then survive until the next rainfall season. That's why they can do so well in these small containers of water that might dry out completely.

They can just hang on. It's amazing and I respect it, but I also hate it. I know, I know. I know. So that's just kind of some fun facts about Aedes Aetia's and Alba Picdis. I'll probably talk more about them in the current event section because they're also really important invasive species worldwide, especially 80s alpictus. Yeah. And so, and they spread so many different diseases that they're an incredibly important source of vector-borne disease. But if that isn't enough, chicken gunya virus can also be spread via vertical transmission within the mosquito, meaning it can pass into the eggs and result in larvae.

and therefore adults that are already infected. It's horrible. It's terrible. I don't know the rate at which this happens, but it definitely happens. And just to make it even worse, males who become infected at birth, males do not blood feed, so they can't become infected as adults, but they can be born infected and can infect females during the mating process. So this virus is just really good at spreading through these mosquitoes. And that's just for 80s Egypti, right? The vertical transmission?

I saw it primarily for 80s Egypti. Okay. Yeah. And like I said, chicken gunia virus is more than just a human virus. So these mosquitoes can become infected by biting a huge variety of mammals, including rodents, bats, non-human primates, but also even birds and reptiles. that can become infected and harbor chicken guinea virus. I didn't get a sense, and I think that because this disease has largely been an outbreak disease, the outbreak patterns in humans tend to be from human to vector to human transmission. So like humans being the primary reservoir, largely because these two species of mosquitoes do really like to bite humans. So I didn't get a sense of what the natural reservoirs likely are across the globe, but it probably

varies in different parts of the world. Yeah. It seems like historically they found it in non-human primates. And then the more sampling they did, the more they found in other species, as often happens. Yeah. So all of that is just the virus, the mosquitoes, and the transmission. Let's get into the disease that chikungunya causes, shall we? Let's do it.

So once a person gets bitten and this mosquito injects you full of virus, the incubation period tends to be about two to four days. Different papers report slightly different ranges, but that's about the average. I feel like that's a pretty tight range. It is. I mean, it does range from like one to 12, but I think... Okay. Never mind.

I take it back. I know, I know. But in general, like most... papers, consensus, two to four, some like to say three to seven just to hedge their butts. Okay. But symptom onset tends to be abrupt and severe. The firsthand account that we read was actually a pretty decent description of what I'm about to talk about, especially when you consider those from the 1800s. So love that.

The symptoms tend to start with a fever, of course. headache, back pain, very, very severe joint pain, and in potentially any joint, ankles, wrists, fingers, hips, knees, large joints, small joints. And it does tend to be like so severe that it is difficult to bear and people often will have like rigors and be bent over and just in an excruciating amount of pain. about 50% of people ish will also have some kind of skin involvement the most common rash is a very itchy red splotchy kind of what i think of is just a very generic viral looking rash so like little red splotches with bumps in the middle what we call maculopular and this can be across the chest the stomach the back i know the firsthand account mentioned the palms but i don't think that we tend to see that very commonly. What's interesting is that in children, the rash can often be quite different with more of a blistering appearance, like very large blisters across the whole skin,

or even with patiquiae, which are those tiny little purple spots that mean that you're having little tiny pinpoint bleeds underneath your skin. Why is it different, just immune system stuff? Yeah, great question. No clue. And in general, chicken guinea fever tends to be considered a self-limited condition. Usually, these symptoms are going to resolve in seven to ten days, which is a long time to be this sick. However, this incredibly painful arthritis can, in some cases, persist for months or even years afterwards. Oh my gosh. Yeah, it's horrible. And what's truly awful is that this happens in up to 30 to 40 percent of people who are infected with chicken guinea virus. Whoa. So it's a huge number. We don't know exactly what causes this chronic joint pain, this chronic arthritis. But so far, it's not thought to be due to chronic infection. Okay. Because in general, when we've tried to study it, people have not been able to isolate virus from the virus.

the joint fluid of people with this chronic arthritis as a result of chikungunya. So it's thought to likely be something that's immune mediated, which is something that we see with other arboviral, viral and bacterial infections as well. And one of those things that we still just don't really understand. What causes the acute joint pain? Oh, great question, Erin. To say that we don't really understand the pathophysiology of chikungunya virus, I think, is an understatement. And I always say that we don't understand things. In small animal studies, we see that it's primarily musculoskeletal tissues that are infected by this virus, especially muscles surrounding joints as well as skin fibroblasts.

Fibroblasts are this like generic cell type that are involved in connective tissue formation. And so since this is a virus that has to infect ourselves in order to replicate, these are the cell. types, these fibroblasts and these muscle cells that they tend to infect and replicate in. There is some evidence from these, again, animal studies that mice who lack T cells, especially certain subsets of T cells, have much less severe joint swelling and tissue damage as a result of this viral infection. So it's thought that perhaps it's at least in part a T-cell-mediated response that causes all of this joint pain and inflammation in those spaces because that's where the virus is actually infecting. And that's like the muscle, there's like muscle involvement?

It can infect muscle cells. It doesn't mean that the inflammation will be in the muscles necessarily. But there's also often a lot of muscle pain with chicken bunya as well. So only because we just covered cow. How does this joint pain differ from? gout joint pain. What a fun question. So gout tends to be a very one joint at a time or a few joints at a time. This is every joint in your body. There's similarities in that in both of them, a lot of the pain is going to be driven by the inflammation, which is driven by our immune response to some kind of stressor. In this case, we think that it is the virus, infecting particular cells, fibroblasts, muscle cells, other cells near and around our joints that then cause a lot

of inflammation, that then cause a lot of pain. Okay. The difference in gout, of course, is that we know exactly what those particular drivers are. See our gout episode for that. Okay. Interesting. But I do think it's important to talk about this pain and especially the chronicity that this pain can have. This can last for weeks to months to potentially years after this acute infection. And it can be debilitating. And chicken gunia virus is often portrayed as a much less virulent pathogen compared to other herbiviruses like yellow fever or dengue. And in a lot of ways, it is. In general, the estimated case fatality rates for chicken gunia are less than 1%. It was thought, especially historically to be very, very rare to die from chicken guinea, although with more recent

outbreaks we have seen an increase in mortality, especially in the very old, the very young, or the otherwise immunocompromised. So that less than 1% is probably an underestimate. But it certainly historically has been much less virulent than dengue fever, which if it causes dengue shock syndrome has a mortality rate of 20% or more, or yellow fever, which has a case fatality rate between 10 and 50% or more. So when you compare those, then yes, chicken guinea seems relatively benign. But months or years of debilitating joint pain can cause disability. It can cause inability to work, which might mean inability to feed your family. So it does have really serious consequences. So I want to emphasize that it's not a benign illness by any means.

Yeah. Chikungunya can also infect people during pregnancy. Of course, you can be infected at any point in your life. It doesn't seem to cross the placenta and cause fetal infection the way that something like Zika virus does. But it can cause neonatal infections if someone is highly viremic, like has an acute infection at delivery. and those can actually be very severe and have resulted in neonatal deaths. Okay. When it comes to whether or not you can have an asymptomatic infection, which is something that we talk a lot about, especially in viral diseases or mosquito-borne diseases, I don't know who to believe in terms of how many asymptomatic cases there are.

A lot of papers that I read, I would say the majority estimate that it's actually very rare to have. have an asymptomatic infection, which is quite different than something like dengue or Zika. Yeah, I think I saw like a CDC cheat sheet that was like three and four chicken gunya cases are symptomatic and one in four dengue are symptomatic. Yeah. It's estimated that anywhere from like five to 25 percent, but most of the estimates I saw were about 15 percent of people will be asymptomatic, which is pretty low. Yeah, very low. But then some of the papers, were like lots of asymptomatic. And I'm like, I don't know. But anyways, I think it's low compared to dengue compared to Zika, as far as we can tell. So joint pain is like the hallmark symptom of chikungunya. Are there any

other organs that are involved? Great question. There doesn't tend to be a ton of organ involvement that results in organ damage that we would then see on things like lab results or results. resulting in, like, kidney failure, liver failure, which I think is why it's historically been considered a pretty mild disease. It can and has in more recent outbreaks caused neurologic effects, but again, tends to do that in a much lower rate than something like Zika. Right. It's something that you would commonly see in huge outbreaks, but.

Yeah. Yeah. Yeah. Okay. Yeah. Okay. So let's say that there's an outbreak of what is suspected to be chicken guinea and someone is sick with what is probably chicken guinea, what do they do? What happens? Great question.

So in terms of treatment, it's mostly supportive care. We don't have any particular antivirals. We don't have any specific treatments targeted towards chicken guinea virus. Most of what you'll see online is Tylenol. Huh, that's it. Tylenol. What's interesting about that is that public health agencies do tend to specify Tylenol over any other things like nsides, like ibuprofen. And the reason for that is because clinically during outbreaks, both because the symptoms can be very nonspecific in the acute phase, they can overlap a lot and these two viruses tend to occur in the same areas. Dengue and chicken guinea virus can be difficult to tell apart. And nseds can be very dangerous in dengue because it can lead to bleeding.

Right. Okay. Yeah. And so for that reason, it's like if you're not sure, just Tylenol. Yeah. Okay. Yeah. And like many neglected tropical diseases, we don't have the best of diagnostics for chicken

gunya either. But they exist, you know. Work on it. So that is. is Chickangunya and it's biology or what I know about it. So, Erin, tell me, where did this virus come from? Why does it infect us? Well, tell me about it.

I don't know if I can answer that second one, but I'll certainly try for the first right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture.

It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments. It's been relied on for decades by people who wash their hands constantly or work in harsh conditions because it actually works. O'Keefs is my hand cream of choice in these dry Colorado winters when it feels like my skin is

always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keefscom.com. This Podcast and code this podcast at checkout. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these, quote-unquote, fresh dog foods in your fridge are not even 100% human-grade,

which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies. 100% human-grade, real ingredients, beef, sweet potatoes, green beef, delicious. These are foods that you would want to eat. Not that the babies would ever share. Just Food for Dogs is the number one vet recommended fresh dog food backed by over a decade of research. No marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging, paws tapping, full Broadway performance every single night. So I do care about the food I feed Biggie and Smalls. So go to Just Foodfor Dogs.com for 50% off your first box. No code, no gimmicks.

just real fresh food. Texting privacy policy and terms and conditions posted at textingterms. Texting enrolls you for occurring automated text marketing messages. Message and data rates may apply or apply stop, opt out. Visit ISSA online for details. Excuse me, what do you do for a living? Weight tables. You like it?

Not really. Do you work out? Every day. Best part of my day. Would you like to get paid to work out? Are you kidding me? How? With ISS you could become a certified personal trainer in as little as six weeks.

Once you're certified, you can start your own business. Work at a gym or just do it as a side hustle. Some trainers are making as much as $100 an hour. 100 bucks an hour. Yes, please. But how do I even find a job as a trainer? That's the best part. There's such a huge demand for personal trainers that ISSA guarantees you'll get a job.

I'm in. How do I get started? Just send them a text. Get your free personal training evaluation kit today. Just text, gym to 3232.32 right now. Get certified in as little as six weeks. And ISSA guarantees you'll get a job. Text gym to 323232.

Text, Jim to 32, 32, 3232. Jim to 32 32 32 32. The story of chicken gungia virus, or at least part of the story of this virus, will probably sound a bit familiar to you. Aaron, it definitely will for you because we have recorded dengue and Zika episodes, and you just talked about all the similarities. But for our listeners, too, not just the biology or the transmission or the epidemiology of these viruses will sound similar. but also a bit of the history, I think. Okay. We'll sound a little bit echoes of each other.

All mosquito-borne viruses, all on the rise, all recently attracting more attention and generating more headlines than historically they used to, due to their recent geographic spread into new regions, especially regions like Europe and North America, where the disease has changed from being an over-there disease to a wait, it's here now, one. And with Dengue and Chickangunya especially, the similarities extend beyond epidemiology and disease ecology and down into the clinical side of things, since they can cause a lot of the same symptoms, as well as their histories, which, as I'll talk about, have blended together and are kind of in the process of being rewritten. Oh, I love it.

Yeah. But with as many similarities as these diseases share, they are also distinct in many ways that play a huge role in their transmission, their evolution, and in the way that public health efforts are focused. And I'm not going to do a thorough compare and contrast between chicken guinea and like dengue, although I may call on you to help me, Erin, and some of these, we'll get to the section where I'm like going to be like, all right, let's take a closer look. But I do, in researching for this, it struck me that these herbiviruses are often kind of

lumped together and talked about as a single entity. And I feel like it's just as important to remember what differences among these infections can tell us as it is to ask what their similarities can say about these diseases. Yeah. And I think that throughout this episode, we'll have the opportunity to do both. But first things first, Erin, you asked, as you always do, where this virus came from. And it's a great question that I'm only going to be able to to answer in part. Okay. Most papers I read for this episode, if they mentioned the evolutionary origin of

chicken gunia virus at all, it was just to say that it wasn't clear when or where this virus emerged, right? Love it. Of course. One paper gave a not super narrow estimate that the ancestor of chicken guinea virus emerged fairly recently, maybe as recently as 1850 or as far back as the year 650, C.E. which like in the scheme of things is not a big range but it does seem like a big range that's still a big range it's a big range it's a big range it's a big range but there was a more

recent paper that examined the different lineages of the chicken guinea virus and estimated that the virus emerged somewhere in central or east Africa around 300 to 500 years ago okay And the East Central South African lineage, which I think is the predominant one in a lot of places, that appeared around 1903 and then gave rise to the West African and Asian genotypes or lineages in the decades after. Wow. Yeah. So it's like pretty, pretty recent. And the most recent lineage, the Indian Ocean lineage, only emerged in the very early 2000s. I know.

I can't wait to talk about it. It's so mind-blowing, really is. We'll get into later. But long story short, this seems to be a relatively new virus whose ancestors infected mosquitoes and non-human primates and other vertebrates with occasional spillover into humans from this enzootic cycle. And then at some point, this virus diverged into chicken gunya virus transmitted by 80s mosquitoes and oh-nongyang virus. I don't know if that's how you're going to. you pronounce it, but that's transmitted by Anophilies mosquitoes. As humans began to settle in larger groups and especially began to store water, even you didn't even have to store that much of it, that provided opportunities for the evolution of the

more domestic 80s, Egypti Egypti mosquito subspecies, which hung around these settlements and allowed for human-to-human transmission of chicken guinea. So it's maintained in just humans and mosquitoes. And that's in contrast, of course, to the spillover into

humans from the anzootic cycle when a bridge vector species of mosquito, one that feeds on both humans and non-human primates or other vertebrate reservoirs bites a human and transmit the virus. Very much like dengue, honestly. It is very much like dengue. It's much like a lot of other mosquito-borne viruses or mosquito-borne infections. Like there's this enzyotic cycle that just happens all the time in the background. And then it happens to spill over into humans. And then depending on the circumstances, that can cause this big outbreak. Yep. And so these big outbreaks would happen from time to time and it fed initially by the spillover

and then it would just sweep through the population until most people became immune. And then the virus would go quiet for a while. And this is essentially how the cycle would have continued for hundreds of years until its discovery in 1952. In July of that year, a seemingly new disease began popping up in the Makande Plateau's region in Tanzania. Within two or three weeks of the first case appearing in a village, 60 to 80 percent of the population became infected. Whoa. With some households reporting a 100% infection rate.

That is impressively fast and impressively infectious. Yes. I honestly, I just couldn't get over it. Well, and I think it so does lend credence to this idea that there's not a lot of asymptomatic infections. Yes, totally. The disease seemed to come on suddenly with the rapid development of a high fever in these horrible joint pains, quote, the pain was frightening in its severity, completely immobilizing many patients and preventing sleep in the first few days of the illness. It was intensified by movement and localized in larger joints. In some cases, there was also severe backache. Morphia was the only analgesic which was found to modify the pain. Aye, aye, aye. Yeah.

No one in the region could remember a similar epidemic ever occurring there, and so this disease was given a new name from the McConday dialect, chicken gunia, meaning that which bends up. Or I've also seen it as the disease that bends up the joints. No one who had the disease got it a second time. Wow. And people said you either definitely had it or you definitely did not. There was just no in between.

No in between, yeah. Researchers immediately suspected that it was mosquito-borne or at least transmitted by some blood-sucking arthropod vector, both due to its pattern of transmission, its occurrence in the rainy season, and its similarity to dengue fever. In one of these papers reporting the initial outbreak, quote, clinically indistinguishable from dengue, if a lack, is made for the inherent variability of that disease. Because dengue is, like, clinically quite diverse. Yeah. Studies were carried out where researchers collected blood feeding arthropods from all around the villages where the outbreak occurred.

And sure enough, all signs pointed to 80s Egypti. Because of the clinical similarity to dengue, people figured that when they found the virus, it was just going to be like a new subtype or a new strain of the dengue virus. but analysis of serum samples collected showed that it seemed to be a new kind of virus, not a dange virus. And so it got to keep the name that it got during this first outbreak, chicken guinea. And maybe it's because we've done so many episodes where this story goes something like, the disease was first recognized into ancient times and people wrote about it for hundreds of years, but no one knew what caused it or how it was transmitted until recently.

But I just think it's so amazing that within a few years of its first appearance, we had a name, we had a clinical picture, we had a vector, and a causative agent for this new disease. Yeah. I mean, and it shows how far we come by the 1950s in terms of microbiology. If you cast your mind back to our dengue episode, you may remember that the first epidemics of dengue were described in the late 1700s, and it took another hundred years and then some. before it was linked to mosquitoes and decades after that before the virus was identified and, like, classified. And here we are with Chicken Gunia, learning all that and more about this brand new disease in just a few years. It's amazing. Or is it? No, it is. But maybe things aren't as simple as I presented them. Well, Erin, I'm just, I'm waiting for you to drop the other shoe because I know that our first-hand account was from the 1800s.

So. Yeah, yes. On that. Yeah. So maybe chicken gunya isn't as brand new as we thought it was. Maybe 1952 was not the year of chicken gunya first being discovered. maybe some of those historical outbreaks of dengue weren't caused by the dengi virus after all, but rather the chicken guinea virus.

Of course, that doesn't take away from how, like, incredible it is to have built that knowledge about the seemingly new disease so quickly. Yeah, totally. But I did want to take some time to revisit the early history of dengay and see if maybe what people thought was dengue was actually chicken guilla. And this isn't something. that I came up with on my own. There are lots of papers that have been looking into this possibility for decades. And they've come up with some pretty convincing evidence. All right. So a 1971 paper by Donald Carey titled Chicken Gunia and Dengue, a case of mistaken identity, takes a closer look at many so-called dengue epidemics since the 18th century and uses clinical

descriptions from eyewitnesses to see whether it seems more in line with dengue or chicken guinea. Because although the two diseases do bear many similarities and can be quite varied in terms of symptom presentation, there do seem to be some distinguishing features between the two. Like one of them is this lingering, long lingering joint pain in chicken guinea and also just the fact that dengue has a much higher mortality rate. And so these days, these days are a very long lingering joint pain in chicken guinea. And so these differences would be a lot more easily seen in outbreaks and epidemics when you can look at a whole bunch of people and see patterns emerge rather than looking at two people side by side that like both have kind of a rash, both have headaches and joint pains and fever. Fever, yeah.

Live in an area with 80s Egypti and 80s alpictus. And yeah, I'm really excited for this, Erin, because I do think it's really important. Many of the clinical papers written And recently talk a lot about how difficult it is to distinguish chicken guinea and dengue, say in the moment, during a chicken gunya outbreak or a dengue outbreak when you don't know which one is at play or if both are happening simultaneously, which can absolutely happen. Yeah. So it is really interesting to be able to take a step back and look at things historically because there are patterns that emerge when you're able to look not at an individual person, but at a population. Yep. That just actually made me wonder, though, is there any in places where both the viruses co-occur? Is there a competition between them within mosquitoes? Oh, my gosh, Erin, such a good question. There is some evidence in one of the papers that I read that especially in 80s, I think it's an 80s alpictus that some of the mutations that I know you'll talk about actually might facilitate co-infection with dengue and chicken gunya. It's terrifying. It's terrifying. It's terrifying.

That is really terrifying. Yeah, but anyways, sorry. Anyways, no, no, that's fascinating. Okay. But the other thing about looking historically at dengue and chicken gunya is that 80s Egypti achieved a global distribution since the 1600s or so. And that greatly expanded the range of dengue and yellow fever. So it seems pretty plausible that chicken gunia, which does the same transmission cycle, more or less,

could have been another virus carried by these mosquitoes. Yeah. In 1779, there was an outbreak of something called knuckle courts or knuckle joint fever in present-day Jakarta. And the description written by David Bylon does suggest, who was witness at the time, does suggest chicken gunia. Quote, I noticed a gnawing pain in my right hand and in the joints of the hand and arm, which gradually increased, extending to the shoulder and then over my whole body, so that at nine o'clock that evening I was in bed with a high fever. I had a restless and sleepless night suffering severe pains over the entire body, especially in the legs and arms and in the joints. This is a brief notice

concerning a very well-known disease, which, however, in the memory of man here in Batavia, has never reached an epidemic, and which has, therefore, seemed wondrous to the inhabitants. Around this time, an outbreak of a similar disease was happening in Cairo, this one known as, quote, the knee trouble. It threw all the people into a fever. Its first attack lasted for three days, after which the illness increased or diminished, according to the disposition of the individual. It was accompanied by pain in the joints, knees and extremities, as well as inability to move, and often with swelling of the fingers. The after pains lasted more than a month. The onset was sudden, the body being broken by it, and the head and knees taken hold of. So the descriptions of this

disease painted this excruciatingly painful picture, but not really a deadly one. And that was something that's in sharp contrast to what Benjamin Rush saw during a 1780 epidemic in Philadelphia of a disease that he nicknamed breakbone fever. This is often considered to be the first description of dengue fever. And I actually had this passage in my dengue notes, and I don't think I read it in the episode. So I'm just going to read you a snippet of it here. And also this is like a very full of quotation section, but I feel like it's important because we're, yeah, going through historical outbreaks. Okay.

Quote, the fever generally came on with rigor, but seldom. with a regular chili fit. When the fever did not terminate on the third or fourth day, it frequently ran on to the 11th, 14th, and even 20th days. In some cases, the discharge of a few spoons full of blood from the nose accompanied a solution of the fever, while in others a profuse hemorrhage from the nose, mouth, and bowels on the 10th and 11th days preceded a fatal issue of the disease. The pains which accompanied this fever were exquisitely severe in the head, back, and limbs.

The disease was sometimes believed to be a rheumatism, but its more general name among all classes of people was the breakbone fever. Rush's description, which also mentions a rash and burning in the palms of the hands and souls of the feet, it does have some echoes of chicken guinea. Like there are lots of similarities between these descriptions that I've read so far. But it's also much deadlier. Like he's talking about hemorrhaging. He's talking about people dying and how often it happens. And that didn't seem to happen in the descriptions, at least from the 1779 Jakarta epidemic, as well as the series of outbreaks of a similar disease that occurred in India and the West Indies in the 1820s,

which, like in Jakarta, had a super high attack rate, but a low mortality rate. In 1824 to 1825, an epidemic of Kedinga Pepo began in East Africa and spread to India, where it caused huge outbreaks with one contemporary observer, estimating that 95% of the population of one region was affected. Wow. Yeah. And although this has historically been chalked up to Dengay, more recently it's been suggested to have been chicken gunya. and that's in large part due to the emphasis on the sudden onset, an extremely fast onset, and lingering joint pain. Quote, a protracted debility and long-continued pains in the ankles and dull aching in the joints

of the fingers and toes for many weeks after the cessation of the fever. The outbreak, which also had high prevalence and low mortality, that occurred in the West Indies a few years later, around 1827, 1828. So that was a description from our first-hand account. Okay. And that's what led to the nickname Dandy Fever. So, yeah. What?

I remember talking about that. Uh-huh. Oh my gosh. How interesting. Isn't that fascinating? So he even says, he even writes in that description, like, this is not a deadly disease. This is not known to be deadly. And it's so funny because I definitely like baited you by being like, Aaron, does that

sound like chicken guinea? Is this a good firsthand account? Is this accurate? I love it. Yeah. So, so some researchers, you know, over the past few decades, have started to think like, hey, well, wait a second. Was that actually dengue? Right. Or was that actually caused by dengue virus, I should say. Yeah. Well, it's interesting, too, to think about dengue potentially infecting a new population who has never been exposed versus endemic dengue because if anyone remembers back to our dengue fever episode, initial infections tend to be much more mild. So if you have an entirely immune population, all of that is going to be primary infection. And it's not until the second time that people are exposed that you have dengue shock, dengue hemorrhagic fever, and severe

infections. So especially in an initial infection and in that acute phase, I do think that that chicken guinea and dengue can be very hard to tell apart. For sure. Yeah. But what I think is interesting is that people made a distinction. Doctors who wrote about these diseases during the 1800s made a distinction between dengue and Benjamin Rush's breakbone fever. So Stedman, who wrote the article where we drew the first-hand account from, he brings up

this point in that article. Quote, some of the physicians here seem to consider this fever the same as that described by Dr. Rush under the name of the breakbone fever or the bilious remittant fever. I think that the diseases, though somewhat alike in a few symptoms, are essentially different. Four circumstances chiefly distinguish the fever that I have described. First, the suddenness and peculiarity in its mode of attack. Secondly, the well-marked distinction between different stages. Thirdly, the peculiar eruption. Fourthly, the peculiar nature and duration of the after pains. So dengue and breakbone fever were not always used synonymously. And in fact, for many doctors, for a time, they seem to be written about as similar but distinct diseases, with breakbone

fever being this more deadly and debilitating disease and one that you could become reinfected with or like you could be susceptible to multiple attacks is like how it was talked about. And what they called dengue was milder except for the long period of lingering joint pain and it was a one-time only disease. That's very interesting, Erin. Isn't it interesting? Yeah, and I don't remember it at all from our dengue episode. No.

I don't I think that like there were a few like I think I made a throwaway comment that was something like and some people think this could have been chicken guinea. Who knows? But then yeah, with this it was like there's there's a lot more because I think that's so interesting that like people made this distinction. But in making that distinction what were they calling dengue versus what were they calling something different and what? what was Chikungunya versus what was, you know, new introductions of dengue or first outbreaks of dengue? Totally. Oh, how fun.

Isn't it? Isn't it? It's so interesting to think about. And yeah. So throughout the rest of the 1800s, more and more outbreaks of what was called dengue or what was called breakbone fever. These were described across the tropics and subtropics. And some observant writers would note the clinical differences.

between the two, but sometimes they would use the terms interchangeably. So how did the two become one? How did breakbone fever and dengue become absolutely the same thing? Yeah. How did we forget about these differences? And honestly, it seems to me like it comes down to just a coincidence. So yeah, like I said, a lot of physicians that wrote about these epidemics did distinguish between dengue and breakbone fever, but by the 1800s, because there's such similar diseases, dengue became increasingly used to describe both. After 80s Egypti was identified as the vector for yellow fever, researchers became interested in seeing whether dengue was also transmitted by mosquitoes.

And I feel like I'm not doing a very good job of this, but like when I'm talking about dengue in these historic outbreaks, I'm really should be putting quotes around dengue, so like what they were calling dengue. Right. Yeah. And so when these researchers decided like, hey, okay, let's see if we can link mosquitoes to this, there was an outbreak of, quote, dengue that was going on in Lebanon, in Australia, and in the Philippines.

And these outbreaks provided the perfect opportunity to test this out, this mosquito hypothesis. Using human quote-unquote volunteers, researchers successfully demonstrated that the disease was caused by a virus and transmitted that virus from sick people to healthy people through the bite of an infected 80s-Agypti. But it just so happens that the virus that was endemic in these study sites in this outbreak of, quote, dengue was not the chicken guinea virus, but the dengue virus. And so it was assumed that this and all preceding historical epidemics that went under the name Dengay were caused by this virus alone. And the reason I say coincidence, maybe that's like not really the right word, just a matter of like happenstance, I guess, is because if these researchers had instead been working on an outbreak of, quote, dengue that was actually caused by a chicken gunya virus. Right. Dengue would mean something different than it does today. It would mean the chicken gungia virus or what we call the chicken gungia virus.

And the virus that we called dengue today would probably have a different name. How fascinating, Erin. Isn't that neat? So at the end of it, we still can't actually distinguish a lot of those early descriptions of quote dengue and chicken guinea. I mean, we can try. But no, that's definitely something that I think is a key takeaway. Yeah. Right.

Like this was a very long-winded way of me saying that chicken gunia has probably been around longer than since the 1950s and that it probably caused some historical outbreaks attributed to dengue. But I wanted to kind of dig a little bit deeper because I think it's a fascinating example of how the history of a disease is. is constantly evolving. Yeah. Whether through the discovery of old texts that, you know, put it in a new place or bring it back even farther, or through molecular tools tracing the actual evolution of a pathogen or a vector, or because modern events add to the story.

The history of chicken gunya that somebody tells in 10 years probably isn't going to sound the same as this one, the one that, you know, we're telling now. And the second reason is that I think this highlights both the benefits of using historical descriptions of disease because they allow you to retrace the steps of its spread and how our understanding grew. But it also highlights the drawbacks. It certainly seems likely that chicken gunya has been more widely distributed for longer than we initially thought, given some of these historical descriptions being like pretty on the money about chicken guinea. Yeah. And also the fact that its vector, 80s Egypti, or one of its vectors, was present in a lot of these places, which would have made transmission, you know, feasible, possible. But we can't know for sure. We can't know whether the author of an account was highlighting an unusual case or a typical one, whether they were interested in a certain set of symptoms. So they played those up while ignoring others. whether there was some reason that they were like invested in making a difference between dengue and breakbone fever and really like highlighting those differences.

These are also similar viruses with a substantial overlap in disease symptoms and geographic range. And it's possible that one outbreak of dengue was actually caused by dengue virus, while another was caused by chicken guineo virus. Maybe another was caused by oh-yang-yang virus or a different virus. entirely. But in any case, these historical accounts aren't just useful for historians, but like you talked about, Aaron, also for modern-day researchers looking for clues into a disease's ecology and epidemiology. What do we see on a big scale? What are the things that stand out historically and why? But speaking of modern-day researchers, let's head back to the 20th century to see what happened with Chick and Gunia once it was formally identified in the 1950s.

So, as you might expect, having a name, a vector, and a virus made it easier for people to recognize subsequent outbreaks, which occurred throughout the 1960s and beyond in sub-Saharan Africa. Chicken Gunia was first detected outside of Africa in 1958 in Thailand, and over the next few years, the virus continued its spread throughout Asia into Cambodia and India. Although it was probably not its first rodeo there. Yeah. Antibodies against chicken guinea were found in serum collected from people in India in the early 1950s. And you've already heard this whole spiel that I just gave about mistaken identity between chicken guinea and dengue.

But what was happening in the 1950s, the 1960s, into the 1970s, is that the scale of these epidemics seem to be growing. with one epidemic in Chennai, India in 1964, causing over 400,000 cases. But chicken gunya didn't maintain this huge growth because after the 1970s, things seemed to, like, cool down a bit. Possibly thanks to a high rate of immunity from previous epidemics, it seems like unclear, but researchers have pointed to a possible cyclical nature of chicken guinea outbreaks, which I think is interesting. But then, in 2004, everything changed. Yep. Or rather, an amino acid in the virus changed. So it's been hypothesized, and I think pretty well supported from experimental research,

that this change of this amino acid resulted in this viral lineage of the chicken guinea virus, being able to be more easily transmitted by AD's albopictus, a mosquito's species that previous to this had not really been implicated as a major vector. It was like 80s Egypti for the, you know, urban human to human cycle, and then other 80s species for the anzoatic cycle. But now, suddenly there's this new albipytus species in play. And the result of that was that chicken gunia exploded in 2004 from eastern Kenya into islands in the Indian Ocean, involving hundreds of thousands of people and attack rates as high as 35% or even 63% I saw on one island. Over the next years, Chick and Gunia grew to be a major public health problem,

causing massive outbreaks in South and Southeast Asia involving millions of people where for the first time these neurological and other complications of the infection were observed. And with 80s albopictus now as this major vector, its potential for global spread grew tremendously because albopictus also extends further than 80s Egypti into temperate regions. It's a great urban mosquito that overwinteres really well. Like you talked about, Aaron, loves feeding on humans, has these desiccation resistant eggs. I mean, we're up against quite a lot in terms of chicken guinea control. And I do have a little asterisk there in terms of like genotype by genotype interaction.

between Albuyctus and the virus. So like some combos don't do as well as others, but I mean, it's complicated, but still. And it gets even more complicated when you add urbanization and climate change to the mix, as you have to do when you talk about disease or vector-borne diseases. But yeah, I mean, this is kind of like a rapid wrap-up, but I think that, you know, what I took away from this is that we have a lot to learn about the future of chicken guinea. And it seems quite daunting. But I think looking at the past, and even like the very recent past, chicken guinea can serve as yet another lesson, along with dengue, along with Zika, along with other

arboviruses, on just how easily mosquito-borne viruses or other pathogens can reach global distributions. But also, it's an important reminder that we have to consider their individual ecologies and pathologies in predicting future risk. Like, for instance, Dengue's multiple circulating serotypes or Chicken Gunia's increased transmission via Albuctus. It's all very messy and it's all very complicated, but it's so important. With that, Erin, can you tell me what's going on with Chicken Gunia today? I can't wait to. right after this break. Unsurprisingly, Erin. Let me guess. We don't have good numbers?

Yeah, it's hard to get a sense of global numbers. But what's interesting and different about the reason why for Chikungunya than anything else that we've covered is that Chikungunya really only tends to be reported in outbreaks. Everything about Chikungunya is there was an outbreak this year. There was an outbreak in this area and an outbreak, an outbreak, an outbreak. It's like, when do we just start saying it's everywhere? And these are just the cases that are happening. Well, that's a, that's a question, though. I know. It's a real question. I don't have an answer to it. It's like a genuine. It sounded like a sarcastic question. It's a genuine question. No, I'm, yeah. I'm very curious. And like, because it does seem like chicken gunia could have like more of a propensity to. pop up in outbreaks. Right, because it does, spoiler, provide pretty long-lasting immunity. And so as it races through a population causes a huge outbreak, then everyone has been exposed and now there's no more susceptible people in that particular population. And you have to wait for new people to be born or to move in or for that virus to move to the town next door. So let's talk a little bit about the

numbers that we do have and that we have seen and what Chick-Gunia has been doing globally. shall we? Mm-hmm. Like you mentioned, Aaron, starting in 2004, an outbreak in Kenya spread throughout the Indian Ocean and persisted for several years, this kind of one big outbreak. It spread to La Reunion Island, where more than a third of the entire population became infected. It spread to India, where cases reached more than 1.5 million people by 2006. By 2007, it came to.

continued its spread. And octophanous, one of my favorite words. Oh, me too. Basically, local transmission was reported in Europe for the first time possibly ever, with several hundred cases reported in 2007. Thank you, Alba Pictus. Yeah, that's what I was just going to say, is that much of those outbreaks in the early 2000s were due to spread by Alba Pictus. And so the strain that we saw of this virus was this strain that had these particular mutations that made it more able to be transmitted by 80s alpictus, which is the predominant vector in a lot of these parts of the globe. So that's fascinating and it was terrifying, right? This was millions of people being infected in the early 2000s. By 2013, if we jump ahead, 2013 is when we see Chick and

spread to the Americas for the first time. In 2013, it was across Caribbean islands where cases reached tens of thousands in a matter of months and then rapidly spread to the South American, Central American, North American continent, with 2014 having over one million suspected cases reported to the Pan American Health Organization. Now, these cases, these strains do not. have that albipictus gene and are spread primarily by 80s egypti. Mm-hmm. So we've got them both all over the world. Well, and how difficult would it be for the one that doesn't have the 80s albopictus

ability to gain it? To gain it. Exactly. I mean, it's already done it once. Right. Or the one that does have it to continue its spread. A thousand percent, Aaron. Yes.

And that's kind of the concern. At this point in a lot of parts of South America, Chikungunya is now considered endemic. And yet still, we mostly see reports of outbreaks. I tried to get a sense of scale globally, just like averages. And I did find one paper that was looking at both Chikungunya and Zika virus, but trying to estimate the disability-adjusted life years, which we, we We've talked about on this podcast, these are imperfect measures, but they are one way to get a sense of the impact and burden of disease. And I think in the case of Chickangunya, a really good way to do it because we're not necessarily going to see a lot of death or mortality from Chickengunya, but we are going to see a lot of years of healthy life lost as a result of this disease. And that's what the disability adjusted life years are measuring. So in the case of chicken gunya, these researchers estimated a global annual burden looking at data from 2010 to 2019 of 106,000 disability-adjusted life years. Wow. Which is a lot. And these estimates were based on case estimates, so combined total global case estimates of anywhere from 50 to 350,000 cases per year.

And we know that, again, that varies because some years it might be more than a million and some years it might be less. So it's pretty major. And again, up to 40% of people infected are going to have chronic or in some cases permanent joint pain and potential disability as a result of this disease. That's such a high proportion. I know. It's really terrifying. One theme that I think we end up touching on a lot in this podcast, and you mentioned it, Aaron, especially in our vector-borne disease episodes, are the potential effects of things like land use change, climate change, urbanization, and its effects on disease incidence and disease prevalence. And especially in the case of a vector-borne disease that is spread by urban human-loving mosquitoes like chicken guinea, This is a particularly important thing to be worried about. Both of these mosquito species are very well suited for urban environments. So there are a lot of papers that have looked specifically at the effects of rapid urbanization on mosquito density and distribution.

And the long and short of it is that it's terrifying news in terms of mosquito-borne disease, not just chicken guinea, but including chicken guinea. because these papers tend to conclude that urbanization across the globe, not localized to one particular part of the world, correlates with a higher risk and abundance of these 80s mosquitoes. You have an increase in favorable breeding grounds. You have higher larval development rates in urban areas compared to natural areas. You have potential for greater adult survival time. And all of these things mean that you have a potential. for greater vector competence, that these vectors are living longer and therefore transmitting or at least having the potential to transmit disease more readily.

It's not good news. It's not good news. And then, of course, there's also going to be the effects of climate change. Warming temperatures might mean shifts in vector distribution and vector habitat. They also will mean shifts in rainfall patterns and prevalence, as well as an increase in the strength or severity of natural disasters. And all of these have the potential to, at a minimum shift, thereby moving into new populations, if not also increase mosquito prevalence disease burden across the globe.

I guess I didn't mean for this to be like such a bummer of an ending, but I feel like that's an important part. Like, arboviral diseases like chicken guinea have been popping up throughout, human history, always. They have been here with us. And I think that many of us probably remember when Chick and Gunya was making a ton of headlines in 2013 and 2014 because we had cases in Texas and in Florida. And then it went away and we forgot about it, except that it didn't go away. And these viruses, these diseases are not going away. And it takes a huge effort of like multidisciplinary public health work to be able to understand these risks and potentially reduce them. And it seems like an incredible challenge to do that.

You're working against so many things. I know. I have two questions. Okay. They're unrelated. Okay. The first one is about the impact of infection with chicken guinea virus in mosquitoes. Does it have any sort of negative?

impact. Great question. I didn't see anything on it. So not as far as I know. And I would guess if it's so easily vertically transmitted, then it's not as likely I would think to have detrimental effects on the mosquitoes themselves. Follow up related question before I get into my second question. Wulbacia. Question mark. Yeah. I don't. So Wulbacia. So Wulbacia. for anyone who doesn't remember, I think I talked about it in our dengue episode. Sure. Question mark. I think it was dengue.

Wolbachia is a symbiotic bacteria that live in a lot of insect species, including mosquitoes. And there is a lot of really interesting research on Wolbachia and other like microbiome bugs that live inside of these mosquitoes and their potential effects on either increasing or deep. decreasing the ability of these mosquitoes to spread disease. I don't have a final answer because I just didn't have time to dig into it. But there does seem to be at least some evidence that some Wobakia, if introduced, to AD's mosquitoes might decrease the transmission of chikungunya. So maybe. Okay. Interesting. Asterisk, there's more there. I just didn't read it. There's potential. Got it. Okay. So now my second non-related question is vaccine. Because chicken guinea induces a long immunity. It does. So there's a lot of theoretical potential for a vaccine. There's also a lot of various groups and people that have been working on vaccine development. So there are at least 10 possibly more candidate vaccines that are all at various groups. stages in clinical trials. There's probably one or two in almost every phase, one, two, and three. Most of them are in pretty early clinical trials. But there is a vaccine of almost every flavor. There are MRNA vaccine candidates. There's live attenuated vaccine candidates. There are

measles vector vaccine candidates and viral particle vaccine candidates. But we don't have any that I could tell we're particularly close to licensure at this point. Okay. Whomp, wamp. Womp. Yeah. Yeah. But the potential exists and there's people working on it.

I have a feeling it's largely down to funding. Yeah. As per yuge. As per yuzge. So that's chicken guinea, Aaron. Okay. I don't know. Is that enough?

I think so. I mean, there was a lot there. There's a lot. I mean, there's also like it's very clear that there are limitations and, the knowledge about chicken guinea yeah i can't wait to see what we learn in the coming decades i'm hopefully it'll be a lot well sources sources speaking of learning a lot um i have a ton of sources for this episode i will post them all but i want to shout out two in particular so one by weaver and forester from 2015 was really great about sort of the evolutionary history and the

history of its spread since 1952. And then for the discussion of Dengue versus Chicken Gunia and all of that, there's that paper by Donald Carey from 1971 called Chicken Gunia and Dengay, a case of mistaken identity. That one sounds fun. I also had a lot of papers for this episode. One of my favorites for the biology was a Nature Review's microbiology paper from 2010, so a little old. That was called the biology and pathogenesis of chicken guinea virus. And one of my favorites, just because I love this topic, was from Plas Neglected Tropical Diseases in 2021. And that was the role of urbanization in the spread of 80s mosquitoes and the diseases they transmit a systemic review. I think I have that one too. It's a good one. It's a terrific one. Yeah.

We'll post our sources from this episode and every single one of our episodes. on our website, this podcast will kill you.com under the episodes tab. We certainly will. Thank you so much to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to Exactly Right Network. And thank you to you, listeners. I hope that you enjoyed this first foray into mosquito-borne virus this season. Sounds like a very specific topic now that I say it, but it's not. I feel like we have done our mosquito-borne diseases in very interesting orders. Totally.

Oh, but yeah, thank you, listeners. Hopefully you enjoyed this. A special shout out to our patrons. Thank you so much for your support. Absolutely. We can't thank you enough. And this is our second to last episode as a reminder. As a reminder.

So make sure you are. to our social media and to our podcast wherever you're listening so that you don't miss it when next season drops. Very well done, Erin. Thanks. And until our season finale, wash your hands. You filthy animals. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy.

Sounds great, but a lot of these quote unquote, Fresh dog foods in your fridge are not even 100% human grade, which is why feed your babies, just food for dogs. It's good enough for big and smalls, my precious babies, so it's good enough for your babies, 100% human grade, real ingredients, beef, sweet potatoes, green beans, delicious. These are foods that you would want to eat, not that the babies would ever share. Just food for dogs is the number one bet recommended fresh dog food back by over a decade of research. No marketing fluff. My dogs lose their minds at dinner. They run to the bowl, tags wagging, paws tapping, full Broadway performance every single night.

So I do care about the food I feed big and smalls. So go to just food for dogs.com for 50% off your first box, no code, no gimmicks, just real fresh food. Comcast business helps retailers become seamlessly restocking, frictionless paying favorite shopping destinations. Thank you for shopping. It's how nationwide restaurants become touchscreen ordering, quick serving eateries. and how hospitals become the patient scanning, data managing,

healthcare facilities that we all depend on. With leading networking and connectivity, advanced cybersecurity and expert partnership, Comcast Business is powering the engine of modern business. Powering possibilities. Restrictions apply. 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, all eight of them. Should something happen to us? Are you my dad now? Uh, no, sorry. I do basements. Connecting homeowners with skilled pros for over 30 years. Angie, the one you trust to find the ones you trust.

Find pros for all your home projects at Angie.com.