This Podcast Will Kill You - Ep 42 Dandy Dengue Fever

Episode Date: January 21, 2020

Our first vector-borne disease episode of season 3 and our first mosquito-borne pathogen in quite some time, dengue virus proves itself to be more than a worthy topic (and quite a formidable adversary in terms of public health). This week we are joined by Dr. Alex Trillo who drops some firsthand knowledge on the excruciating symptoms that give dengue its colloquial name “breakbone fever”, and then we trace the virus’s path from its evolutionary origins in ancient forests to the inevitable emergence of dengue hemorrhagic fever following modern war. We round it all out with some truly horrifying stats on the prevalence of dengue today as well as some promising research on reducing the prevalence of dengue tomorrow.To find out more about Alex’s incredibly cool research, check out her website at www.alextrillo.com and follow her on Twitter at @Trillo_PA. See omnystudio.com/listener for privacy information.

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Need to hire? This is a job for Indeed Sponsored Jobs. My name is Alex Trillo, and I am an assistant professor at Gettysburg College. I'm a professor of animal behavior and tropical biology. I got diagnosed with dengue in the summer of 2016. I do a lot of field work and I work in Panama at the Smithsonian Tropical Research Institute and our work is to set up speakers and playbacks that have frog holes to attract predators

and parasites of these frogs. So we attract bats and we attract these very small midges. And so most of our work during the summer at least is in the field all across different field sites in Panama. I was doing this work with some of my students in 2016. I first started feeling very tired, but I thought that it was just because I wasn't sleeping well because, you know, I had a young baby and I was working at me. And one of the days I was so tired that my husband recalls me just like kind of collapsing on the, on the trail going to one of the sites where we had our speakers. And he noticed that. I just felt, well, you know, one of those days where I just am tired.

And we kind of let that go. And then a couple of days later, I started feeling much more sick. I got a very small fever. I don't really get fevers, and I think that that was one of the reasons why it took me so long to realize I had something else than a cold.

I was in an actual moment where I was really stressed out because not only did I have to finish all, or did I need to do all the field work, I had to leave a lot of things set up during the field work for my students because I was traveling to a conference. And so I wasn't really hoping and or expecting and or wanting to be sick. I was just, you know, trying really hard to power through my cold. I still went on the plane and I remember arriving to the U.S. And I had to walk to my next gate.

And I just remember, like, sitting, you know, on the floor next to the chairs and just being, like, calling my husband and saying, I just don't know if I can make it to the gate, to the connection. Like, I'm that tired. So at this point, what I was feeling mostly was extreme malaise, like super, super tired. And what I had was, like, really strong joint pain. I remember very little about the conference. My talk was the second or the third day of the conference, so I just worked really hard on the day I gave my talk. That day, I started with the fevers. After I finished the talk, I came back to my room and I passed out for like almost 24 hours. I was fine, but I was in like a lot of pain. When I came back, I got these horrible headaches. It just feels that you have pressure on top of your nose and on the sides of your head.

But the pressures from the inside is like if someone's like put a hand inside your brain and trying to pull it from the inside, that's kind of what it feels like. But on the second day of this really terrible headaches, which is, I just said we have to go. Something has to stop. I don't know what it is, but we're going to the emergency room because like I want to literally like pull my brain out. the doctor saw me and he at first said oh it must be a really bad sinusitis infection and I was like I have sinus infections before and this is not it there's something else it's bigger and it was actually my husband who was like we're not leaving this place until you test for dengue like you have to test for dengue and so they went ahead and they tested and then we were waiting at the waiting room so I just remember being asleep and then wake up and then wake up and And then the doctor being there and said, like, yes, you know, you tested positive for dengue. And I just remember both Michael and I actually being happy about it because we finally figured out there was, like, a reason why I was like, I was like, okay, now we know what to do, right?

Like, we have a diagnosis and we know what to do about it. But, I mean, there's not much you can do, right? I slowly started, like, getting a little bit better. I was weak and tired and feeling my lace for like at least two months after that. A lot of people thought that I probably had it from working in Gamboy in the forest. But I do remember about 10 days, a week to 10 days, before I started feeling sick. I was actually with a friend of mine, you guys know him, Sergio, we were sitting at a restaurant outside in the city of Panama.

So I think that I got it in the city. And so from then on, I told my students and I, we all, like whenever we never were, like, nobody wore skirts or shorts or short sleeves. We all like get long sleeves and pants and shoes every time we go to town because we're like a little bit nervous about that. So yeah, so no more skirts in the city. You just heard from Dr. Alex Trio, who was nice enough to share her experiences with Dengay with us. And if you want to learn more about the awesome research that she does, you can check out her website at www.

alextrio.com. That's A-L-E-X-T-R-I-L-O. And you can also follow her on Twitter at T-R-I-L-O-U-U-U-S-P-A. Thanks again, Alex. Hi, I'm Erin Welsh. And I'm Erin Alman Updike.

And this is, this podcast will kill you. Yeah, today we're talking about, do you say dengue or dengue? I think I say both. I think we've done this before, right? We have discussed this. We have discussed this. we didn't come to a conclusion.

Yeah. Well, then. I'll say dengue, you say dengue. Perfect. That sounds excellent. Okay, great. Cover all our bases. We can irritate everyone that way.

Exactly. Our favorite thing to do. Yes. So as you might have guessed, we are talking about dengue or dengue today, which is a very fascinating mosquito-borne virus. Yes. And it is actually an episode or a topic that we have covered one. before. We have. Although only a few of you may have heard it. Yeah. So in October, we got invited

shout out Nick Kaiser to University of Florida to give a little talk, and we talked about dengue. So we technically have heard each other talk about dengue before. However, I don't remember anything you said, Erin, because I was really nervous during this talk, so I was like not actually paying attention. Well, thank you. And same. Also, my memory is terrible. Yeah, there you go. It'll be great. I'll still learn new things.

Apologies to anyone who was in the audience in Florida, because if you remember anything, then some of this or all of this will be a repeat. But we did add a little bit more to kind of fill in the edges. We definitely have some new things and some answers to some questions that people asked during that event. So stay tuned. Well. Is it quarantine time? I think it is.

I think it is too. What are we drinking this week? We're drinking the bone breaker. Mm-hmm. What's in the bone breaker? It is. Mescal, preferably. You could use tequila if it's all you've got.

Passion fruit simple syrup. Oh, yeah. So good. Slime juice. Pineapple juice. And you rim it with tahin, which is one of our little favorite things. It is. And it's really refreshing.

and delicious. So tasty. And hopefully won't make your bones feel like they're breaking. Let's hope not. Just your head the next day if you have too many. Don't do that. Just have one. We will post the recipe for the alcoholic quarantini and the non-alcoholic placebo-rita on our website and also on our social media, which you can follow us at this podcast, We'll Kill You, on Instagram, and TPWKY on Twitter. And you can also find us on Facebook. Yeah. Any other business that we should discuss, Erin?

I don't think so. I don't think so either. Should we jump right into this episode? Let's do it. 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.

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podcast to get free shipping and 365-day returns. Quince.com slash this podcast. Dengue virus. You already know a lot about it. It's a virus. This is a flava virus. So that's in the same group of viruses as yellow fever, West Nile, Zika, a bunch of different encephalitis viruses, etc. Okay. There are five serotypes. So that means five different strains of this virus. It used to only be four, but in 2013, they announced a new one. Ooh. And so this means that if you get infected with one strain of dengue, you're not protected against the other strains of dengue. Right. And as we'll talk about later, it's actually a lot worse.

Yeah. Spoilers. I already have a question about that. Oh, excellent. I'm going to write it down instead of... How about that? Okay. This is so nervous.

Write your question down and then ask me later? Yeah. Okay. You don't want to ask it now? I mean, because it's kind of jumping ahead to... Okay. All right. Yeah.

Okay. Okay. So, let's talk about. about how you get infected with dengue. You already mentioned, Aaron, this is a mosquito-borne virus. So dengue is transmitted by 80s mosquitoes, which we've talked about before because these little buggers transmit a whole number of different diseases, including yellow fever, Zika, etc. Chicken gunia, which we haven't talked about yet. One thing that's different, though, about dengue than some of these other viruses, although not all of them, is that

Dengue is pretty specifically often a disease of more urban areas where a lot of other viral hemorrhagic fevers tend to be diseases of more rural areas. And this is for a couple of different reasons. One is that these 80s mosquitoes that transmit Dengue are very well adapted to urban environments. They breed in little tiny containers of water. And so anytime you have like, let's say, pots or tires or whatever in your yard that could collect water, they breed. water, 80s can breed in those small bodies of water. And dengue is a human-specific disease. So unlike something like yellow fever that can spill over from animal populations into human populations, dengue is human-specific. So where you have large populations of humans, you're more likely to get

spread of dengue in those areas. I forgot about that aspect of yellow fever. Yeah. Like, why do you think evolutionarily there would be a difference between the two, you know? Like, why would dengue be so specific to humans and yellow fever? Oh, it's so interesting. Yeah. Well, I was hoping you would tell me, like, where dengue came from. I mean, I'll tell you that, but I won't be able to answer this question. Huh.

Yeah, but yeah, there's no, like, Silvatic Wild Cycle like there is for yellow fever. It's really interesting. Interesting. So that also, I will say, contributes to some of the lack of understanding that we have about dengue fever. We don't fully understand dengue. And it's because when we have human-specific diseases, it's often really difficult to find good animal models to study these diseases in. So in the case of dengue, there are some modified mice that you can infect with dengue and use. You can do it in monkeys in some cases. But we don't have really good animal models for studying dengue.

Okay. The other way that it is possible to get dengue, although this is much more rare, than mosquito transmission is vertical transmission, so across the placenta. So it's possible for this virus to cross the placenta. So during pregnancy, if someone is infected, especially late in the pregnancy, then the fetus can potentially get infected as well. And this can have pretty bad outcomes once the baby is born that we'll talk about a little bit more later. Okay.

But it doesn't seem to cause birth defects the way that something like Zika virus does, which I think is very interesting. Yeah. Huh. Yeah. It's not entirely clear if someone gets infected very early in their pregnancy, if they might have poor outcomes, like maybe a miscarriage or something like that. It's not entirely clear if that happens if you get infected with dengue early in your pregnancy. Okay. But definitely if you get infected late, then the fetus can get infected. And then basically when it's born, it can either have symptoms of dengue or it might just have antibodies. Like it might be born having antibodies against. stengue virus. Okay. Like having already been infected and then... Oh.

And survived the infection. Yeah. Yes. Put a pin in that. Okay. That O is the perfect O. Okay. Okay. So that's how you get transmitted or how you get infected, rather. That's the transmission cycle. What basically happens, we've talked about a number of mosquito-borne diseases on this podcast by now. So what's important to remember about all mosquito-borne diseases is that there's the cycle of the virus in the human, and then there's also the cycle of the virus in the mosquito. And so the mosquitoes get infected if they bite a person who's actively febrile, for the most part. It's also possible like a couple days before you show symptoms and a couple

days after you recover. If a mosquito bites a person infected with dengue during that time period, then the mosquito sucks up a bunch of viral particles. Those will travel through the the gut of the mosquito, and then they have to make it out of the gut and back to the salivary glands of the mosquito. Importantly, that whole process in the mosquito takes like eight to ten days. Wow. Yeah. It's kind of a long time.

Okay. And that means that if you can somehow stop that process in that eight to ten day window, then you could block the transmission of dengue. Right? Right. So that's really important. We'll talk even more about that in the current event section because that's what a lot of people are doing. You're dropping all these little hints? It's all I do. This whole bio section is just going to be hints for later.

Oh my God. Also, I just need to have a little point out right now that I remember nothing. Excellent. Like I'm like, okay, yeah, I know that it's a flavivirus. I know that this and that. But like, that was all pre-knowledge. I'm so glad. This is great. I think we must have been like nervous blackout when we were presenting. For sure. I remember nothing of that. that whole trip. Okay. So then when you, if that does work properly in the mosquito, then you have a bunch of virus

in the mosquito salivary glands, then they're going to bite another human and spit all of that virus into you, essentially. And then that virus will go into your, usually your lymph system. And in the case of dengue virus, it'll enter your white blood system. cells. And that is where the virus replicates in human bodies. So then after about four to seven days, usually, after you get infected with this virus, that's when you'll start to show symptoms. Okay. Cool. Okay. So now we know the transmission. We know that it's infecting your white blood cells, which, if you don't recall, are part of your immune system. So that's really important because it's

directly sort of targeting your immune cells. Okay. So what kind of symptoms do we have if you get infected with dengue? If you get infected with dengue for the first time, most people will never have any symptoms. What's most? 80%. Wow. Yeah. So like 80% of people who are infected for the first time with dengue have either very, very mild symptoms or are entirely asymptomatic, which you can imagine makes it even more difficult to understand how many people really do get infected every year and how to actually control this virus. If you do get symptoms from a primary infection, it generally starts, as all of our favorite diseases do, with a fever. You'll often get a headache.

And very classically, you get severe muscle and joint pain. So that's how it got the name breakbone fever. Right. And the symptoms can actually be broken down into three main phases, but the last two phases tend to only happen if you're getting infected with dengue for the second time. Aha. Okay. So here are the three main phases. Fibrile, critical. Uh-oh. Not good. And recovery. Oh, great. Asterisk or death. Oh. Okay. Yeah. Okay. So the febrile phase that we kind of already started talking about, if you get infected for the second time, it's much more likely to be symptomatic. And this phase will probably start out worse than the first infection. So it starts out with a super high fever.

We're talking over 104 Fahrenheit. Yes. 40 Celsius. Dang. Yeah. Wait, is that right? Yeah, I'm pretty sure that's right. That's high.

It's very high. And this fever lasts usually between two and seven days. Oh my gosh. I know. It's a long time. You're very, very sick with dengue. Does it respond to like anti-piratics? Good question.

Probably. But it's also often biphasic. So often you'll get a really high fever and then you'll start to get better and then a couple days later it'll come back again. Does the fever intensity correspond to like circulating virus? Anything like that? That's a really good question that I don't fully know the answer to. We'll talk a little bit more about like viremia, how much virus you have in your body when we talk

about some of the more severe symptoms of it. But definitely the higher the viral load, the more sick you'll probably get. Right. And the more likely you are to like have symptoms and things like that. But is that why the biphasic, like is that part of it? It definitely could be. I mean, that's usually when we think of things like malaria and stuff like that, that's usually when you have those bifasic fever. So it could be that like you get an initial infection and maybe

your immune system kicks in, is able to knock it down a bit. But then the viruses just start replicating like crazy. And then you get a secondary, second wave. Interesting. Yeah. And do we know whether the fever is a defense mechanism by your bucket, like an immunological response or is it induced by the virus? Excellent question. Most of the symptoms of dengue are your immune system responding to the virus. Okay. Great questions. Aaron, as always. Other symptoms that you'll see are severe headache. And for some reason, don't ask me why on this one, because I won't have an answer. It's often behind, like right behind your eyes, where you get the severe headache. And then like I mentioned already, muscle and joint pain,

nausea and vomiting are really common. And then a rash can often happen after a few days. And the rash, unlike other viral illnesses that are really common, or that used to be really common, something like measles where you also get a rash. This rash starts on the torso and then spreads to the limbs. Okay. So a lot of other rashes will start like on the head and go down. So where rashes start can kind of help you figure out what disease it might be. Isn't that weird? Why?

I don't know. Viruses are just so cool. What did we talk about? about with the rash and the palms. Oh, so rickettsia causes that and syphilis causes that. Got it. And then hand, foot, and mouth disease. Yeah. Okay. Cool. Yeah. See, I'm remembering things. Good. So this one starts on the torso spreads the limbs. But what's really important is that it's often really, really hard to see this rash. So it's not like, you know, this really huge, you know, scary looking rash or anything. It's a very light red, pink, kind of splotchy rash. So it's

not very descriptive. So after those few days, a couple days, you know, two to seven days of fever, as the fever starts to fade out, especially with a secondary infection, dengue can become more severe. This is when we get into two different syndromes called dengue hemorrhagic fever and dengue shock syndrome. Overall, across like all dengue infections, these two syndromes happen in less than 5% of cases, but the vast majority of those are when someone's been infected the second time. You mean the second time with a different strain? With a different strain, exactly. Okay. And so you cannot get sick again from the same strain. Do you have lifetime immunity, or what's the deal? Pretty much, yeah, from that particular strain. Like maybe, unless

you got infected with a really, really low viral load and you didn't mount a great immune response, then maybe you could be reinfected with the same strain. But for the most part, in areas where dengue circulates, multiple strains circulate at the same time. So you're much more likely to get infected with a different strain. And that's when you see dengue hemorrhagic fever or dengue shock syndrome. Right. So what's happening in these two syndromes? Both of them are related to capillary leakage. So your capillaries are the tiny ends where your arteries and veins come together, right, where like gas exchange is happening. And so what happens is the virus and your immune response to the virus both cause damage to these tiny blood vessels and it causes them to leak. And that is going

to cause you to not have enough blood essentially in your blood vessels. And then you're going to go into shock and potentially die. So whether you have the hemorrhagic form or just the dengue shock form kind of just depends on whether it's damage that's somewhere like in your GI tract and then causing massive bleeding or whether it's damage in other areas that just cause plasma leakage. So you're not losing blood volume, you're losing plasma volume. Okay. So the mechanism is the same. It's just the end result. That's different. Okay. Exactly. And, and And both of these, you can end up with massive organ dysfunction, eventual death. And symptoms, while they're different, across the board, you can get severe abdominal pain,

especially if you have GI tract involvement. Persistent vomiting. If this happens in your lungs, then you can have leakage in your lungs, which can make it really hard to breathe. So someone might have really rapid breathing, which we call tachypnea. You can have bleeding from your gums because your mucous membranes, if those are starting to leak, that's going to be blood coming out of your gums, etc, etc. This phase, the critical phase, usually only lasts a couple of days, like one to two days. Only, it's only a couple of days of you bleeding out your gums and your gut and your...

Or you going into shock because all of the plasma has left your bloodstream and you have no blood for your heart to pump, essentially. So if you survive... then you'll enter the recovery phase, which in theory in itself actually happens relatively quickly. Like your blood vessels kind of heal themselves and stop leaking relatively quickly within two or three days. But you can imagine that this has caused a lot of damage to your body overall. So actual recovery like you feeling better can take weeks at a time. Okay. How many people do survive? So overall, for severe dengue, if you get treatment, the overall mortality rate is like 1 to 5%.

But once a person goes into shock, if they don't have treatment, it's like a 25 to 30% mortality rate. But if you do receive treatment, it's mostly supportive care. It is. Entirely supportive care. Yeah. So it's a lot of like fluid resuscitation to try and combat that fluid leakage. So a lot of IV fluids and things like that to keep your blood, to keep your blood vessels full of fluid. Okay.

Yeah. And that's pretty successful. Yeah, I mean, it reduces the mortality rate from 25% to 1 to 5%. Okay. That's pretty dang good. Yeah. Yeah. Okay, so there's a couple things that we need to talk about when we talk about these severe forms of dengue.

First is that there's a lot of differences in the severity, not just based on whether or not it was your first or second infection. So comorbidities, like if you already have a number of comorbidities, say like diabetes, hypertension, maybe immune compromise. These things are obviously going to make it more likely that you might have a more severe denge whether or not it's your first or second infection. Also, overall viremia, so how much virus you get exposed to overall is also going to help define whether or not you have severe denge or not. The strain of the virus can also play a part, so some strains are more likely than others.

and for some reason I didn't write down which ones those were. I think it's number two, at least in the Americas, is associated with hemorrhagic syndrome or fever. I was going to guess two or three. But I have a question that's related to this. This is the one I wrote down. Oh, excellent. So dengue hemorrhagic fever happens when you get infected with a second strain or a different

strain than you first were infected with. Are there different combinations of strains that, like, will lead to, you? that being more severe or more likely to occur. Maybe that's not a note. It's a good question. Like, if you get infected with one first and then two versus two first and then one. Right. Yeah, good question. I don't know based on what I've read about, but I'm sure there's some epistudies out there that are looking into that or that have looked into it. It's a really good question. And is there any partial immunity conferred based on like yellow fever, if you've been exposed to yellow fever or Zika or Are there flabiviruses, you know?

I don't think so. I don't think so. Yeah, I don't think that they're, even though they're all flabaviviruses, I don't think they're similar enough to provide any sort of cross immunity or anything like that. Yeah. Good questions, though. So fun, Erin. Okay.

And then the other people who are more likely to have severe dengue, regardless of number of infection, are children and the elderly. And this is for a couple of reasons. Both children and the elderly have kind of a lower threshold. for capillary leakage to begin with. So they're at increased risk for bleeding in general. They're like in older people, their capillaries are just kind of weak. And in children, they're not fully formed.

So they're more likely to have leakage from that. Bleeding especially is more common in older adults and things than in children. Okay. But we talked briefly about how infants can be born with antibodies. to dengue. So a group that's at very, very high risk of severe dengue, dengue hemorrhagic fever or dengue shock syndrome is infants that have maternal antibodies to dengue still circulating. So if a mom was infected and then the baby is born with those antibodies, if that baby gets infected with another strain of dengue, they're at very, very high risk of going on to develop severe symptoms.

But how would, like, if only 20% of people show signs or know that they've been infected with dengue, then how do you know? That's the thing. How do you know? That's scary. It's really scary. Yeah. And there's no screening protocol in any places that it adds like endemic. Like during pregnancy?

Yeah. Not that I know of. Okay. Not that I know of. Yeah. So then the question becomes, why is it that a secondary infection with dengue is worse than a first infection? Yeah. That's very bizarre, right?

So I can't tell if this is a true guess or recovered memory. But is it something like the way, you know, in the 1918 flu where it's like the immune system just goes like super ham? Good question. That is one of the hypotheses that was. out there for a long time, that it's kind of like a cytokine response. Yeah. That was what happened in the 1918. That's what I was looking for. Cytokine stories. Maybe not a recovered memory then. Yeah, that's one of the hypotheses that are out there. There's a number of different hypotheses out there as to what exactly is the cause of this secondary, severe infection. The exact mechanism isn't

entirely clear, but the most parsimonious and the most well-supported hypothesis is called antibody-dependent enhancement. And I will say the fact that infants who are born with antibodies only, like to me, that provides really good support to this hypothesis, because the idea is basically this. If you have antibodies against, let's say, Dengue strain number one, these antibodies are similar to the antibodies that you would make to dengue number two, but they're not exactly the same. And so for some reason, these antibodies bind to dengue number two virus, right? And when antibodies bind, what they do is they encourage your white blood cells to engulf

that virus in order to kill it, right? That's the point of an antibody. It's like a flag that our immune system puts on viruses. So these antibodies that you've made to Dengue 1 flag Dengay 2, but they don't do it perfectly. And for some reason, what that does is it causes the virus when it gets into the white blood cells, which remember is where Dengay wants to be. That's where Dengue replicates. It causes a massive amount of replication.

So something about the antibodies that are a little bit mismatched binding to that virus enhances their ability to replicate. and then increases viremia. Ooh. Right? Also, what's really interesting about this is that these strains evolved in isolation, because that's how strains evolve. And so this is like a recent thing. So it just so happens that it turned out to be really, really, really bad for humans.

Yeah. And really good for the virus if it's increasing viremia, right? Because the more virus you have circulars, then the more likely a mosquito is going to be able to pick up that virus and transmit it to the next host. That's really fascinating, though. It is. And there's a number of really cool papers out there looking into, like, you know, getting more detail on, on, or more support for this hypothesis. So that is Dengue. That's the biology. That's how it gets you sick. That's how it kills you. It's a horrible illness.

And we'll talk later about how many people it kills every year. Aaron, where did this thing come from? Why is it here and why is it so bad? Great questions. Let's take a quick break and then we'll begin. Excellent. 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.

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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'Keef's. Just visit O'Keef's Company.com slash 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, 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.

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Just go to Indeed.com slash podcast right now. Indeed.com slash podcast. Terms and conditions apply. Need to hire? This is a job for Indeed sponsored jobs. Dengi virus, all of its types, probably originating. in Asia and then kind of exploded out from there. And there has been some debate about like whether it really originated or diversified in Asia or Africa, but most things that I read

suggested Asia as the origin. Okay. So about 2,000 to 4,000 years ago, the dengue virus, which had been hiding out in the jungle, hitched a ride in a type of mosquito species that likes to hang around human settlements. And these mosquitoes probably transmitted the infection to these small human settlements, but then these outbreaks were like little bursts, so they would happen infrequently, everyone would get exposed, and then everyone would gain immunity, and then Dengi would retreat and wouldn't be seen again until the number of susceptible people in that settlement would increase to a point where an outbreak could happen again. So then that kind of like that cycle continued on and on, until humans started to live in bigger and bigger groups, and then the

distance between these settlements or groups shrank and then things like commerce and migrations led to the groups being like more and more connected. And so over the course of that time, it was kind of a one location, one strain situation. But evolution happens. And different strains of dengue start to evolve. And they would also make the leap from the sylvatic cycle. So I think originally Dengay did circulate in primates. Right. It makes sense. It makes sense that it came from non-human primates and then just like specified onto humans

or whatever. Right. And so more and more strains made this leap from just the sylantic cycle of monkeys and mosquitoes to then this urban cycle or more urban cycle of mosquitoes and humans. But still, even though more strains evolved, there was still this geographical isolation among the strains. So, you know, one strain would be in this location, one string would be in that location, and there wasn't a whole lot of opportunities for overlap. It did, of course, happen occasionally, but not that often. But it's kind of, in a way, having these different strains

is really interesting because researchers can compare the DNA sequences of these strains and then put a timeline on their emergence and where they emerged as well. Okay, so this general pattern that I just described, one strain per outbreak, small outbreaks, very sporadic. This continued for hundreds of years, probably thousands of years. And then around the 16th and 17th centuries, the slave trade began. And for Dengue in particular, this meant that A, the world became flat, so the virus could be transmitted or carried all over the world by these ships and introduced to new populations that were full of susceptible humans. And the other thing is that the that the slave trade also spread the key vector mosquito species, 80s Egypti. Yeah. Because as you

mentioned, 80s Egypti lives really well, like it lives really well in urban, like next to humans, and it doesn't need a whole lot to continue its life cycle. Yeah. It's basically small bits of water. They're very hardy. Mm-hmm. And I think this is fascinating because 80s Egypti is, it's of African origin. So 80's egypti is now the primary mosquito. Yeah, but it wasn't the first. No, 80s albiptis was probably what it originated with. 80s Egypti and 80s albipetis are both the two main vectors, but they talk about 80s Egypti as the primary just because of, I think,

it's distribution and it's a more voracious biter as well. Apparently it's, yeah, it's more efficient at transmitting the virus as well. Wow. Interesting. This is kind of what caused this debate as to the geographical origin of dengue, because it would make more sense that, like, this virus and this mosquito species fit so well together and work so well together. Yeah. That would be the origin, that they would have evolved together as well. But it seems that actually Alpictus is where it came from.

Fascinating. I don't know. Anyway. So 80s-Agypti being the super cosmopolitan mosquito species really helped the distribution of, you know, of dengue. And so probably by the 18th century, the dengue virus was all over the global tropics, and also its distribution could creep northwards during the warmer months, especially in port cities, thanks to the widespread distribution of 80s-Agypti. And even in those more northern or more southern places, like a little bit outside of the mosquito's year-long environmental requirements,

it would just be reintroduced. Yeah. It would be like, oh, it's warm enough in the summer. I'll die off in the winter and then be reintroduced. Yep. Knowing the evolutionary origins of dengue is one thing, but when did humans actually first recognize the disease? Yeah.

So it's around the late 18th century, 1779, to be exact, that we see what is considered to be the first dengue pandemic. Ooh. In 1779, there are descriptions of a dengue-like illness in Java and Egypt, and in the following year, we see, it pop up in Philadelphia. And this is actually when it gets its colloquial name, Breakbone Fever, which was coined by Benjamin Rush.

And he was also a physician. And so to give you an idea of the scale of this epidemic in Philadelphia, he saw over the course of like two months around a thousand people, he treated them for dengue. Two months, one thousand people in Philadelphia. He alone. Yeah. Wow. And so, yeah, I couldn't find an exact estimate of the total number of people likely infected, but probably it was pretty high.

Wait a second. This is the one recovered memory I have from the time that we talked about Dengay in Florida. Benjamin Rush is one of the founding fathers? Yeah, he is. Oh, I learned that from you. So glad that's the one bit of trivia. Next time you go to trivia at the Blind Pig. Benjamin Rush. Benjamin Rush.

The only one I know now. The only one I know now. Oh, gosh. Moving on. Anyway. So the epidemic in Philadelphia from Benjamin Rush's description was pretty likely dengue. Okay. Egypt and Java may have been chicken guinea.

There's been a lot of recent debate over whether these early descriptions are actually chicken gunia virus as opposed to dengue virus. Okay. Cool. In any case, it seems that. that Philadelphia was pretty likely. And that's the earliest more like convinced or most convincing instance. There are descriptions of a dengue-like disease in a Chinese encyclopedia dating back to

the year 992. Whoa. Yeah. And in this encyclopedia, this disease is referred to as water poison and was known to be associated with flying insects that live near the water. Fascinating. So mosquitoes. And the symptoms of this disease.

you sound a lot like dengue. So you've got the fever, rash, eye pain, bleeding, sometimes high mortality. And this also lends further support to the hypothesis that the virus originated in Asia. But anyway, the virus was circulating throughout much of the world during the 18th and 19th centuries with an estimated eight pandemics, each lasting three to seven years from 1779 to 1916. Wow. Yeah. With a disease that is as old and particularly as wide-ranging as dengue, it makes sense that it would accumulate a few names over its lifetime. Yes, I love the name.

Yes. I hope that there's another one that you remember because I did a little more digging. Oh, okay. So the word dengue first seems to pop up in Spain around 1801. And researchers think that the most likely origin of that was actually from the Swahili name for the disease. Key Dingo PEPO, meaning a disease characterized by a sudden cramp-like seizure caused by an evil spirit. That sounds familiar. Okay.

Yeah. So it was called Dinga or Denga from the early 19th century on. But it had a lot of other names. We already heard water poison, already heard break bone fever, break heart fever. Oh, yeah. You remember that one? I do remember that one. Because all the women that Benjamin Rush treated were crying.

They were crying women. Yeah. Yeah. And old Ben was like, well, These poor ladies and their heartbreak. No, one of the supposed patients was like, you should call it break heart fever because I'm just brokenhearted. Oh, gracious. Scarlatina rheumatic, polka fever, ephemeral fever, and our, the most baffling one at the time, dandy fever.

Dandy fever, yes. You remember this? We were like, what the heck is a dandy? and I was thinking of that character in American Horror Story, that's who I think of. And I still haven't seen that, so I don't know. Well, everyone else, you know, the circus season. It's the guy who's a really horrible person, but he's like a dandy. I think he's a dandy.

Tell me what's a dandy. Okay. So I did a little sleuthing, which basically means that I went to the Wikipedia article for dandy, which is pretty lengthy, actually. Cool. All right. So according to Wikipedia, A dandy historically is a man who places particular importance on physical appearance, refined

language, and leisurely hobbies pursued with the appearance of nonchalance in a cult of self. Like Yankee doodle dandy. Yeah. He puts a feather in his cap because he's concerned about his appearance. He called it macaroni. He wanted to stand out. Exactly. Yeah.

Yeah. Okay. So that's a dandy. That's a dandy. I still don't understand what this means in terms of dandy fever. In terms of dandy fever. It doesn't make any sense. Any hypotheses?

Send them our way. Yep. Okay. So that's Dengue etymology and also hopefully a little bit more about dandy fever. Yeah. But of those, still not an answer. Still unanswered. Okay.

So anyway, the disease Dengue was known by at least the late 1700s, but it would take a bit before some of its biological characteristics were discovered. So once scientists made the link between mosquitoes and yellow fever, which was in the late 1800s, they kind of got the feeling that dengue was also transmitted by mosquitoes. And that took a little bit longer to show, but they did show it. Let's have these infected mosquitoes bite humans, human volunteers, quote unquote. And then right after that, researchers discovered that dengue was caused by a filterable transmissible agent, which back then, before microscopy and microbiology advanced, was pretty much going, meant that it was a virus. The viruses wouldn't be isolated until 1943.

This was during or right after the Nagasaki Dengue epidemic of 1942, which had over 23,000 reported cases. Wow. And so at this time, researchers isolated some serum from someone who was infected, and then they injected it into the brains of suckling mice. Oh. And it gave them dengue. Okay. Weird. But the important thing about this was that this isolation of this virus allowed researchers to also look at the different strains and which strains were causing which outbreaks.

So that was pretty important. So speaking of strains, up to this point, this history is mostly about the history of dengue viruses, but not specifically dengue hemorrhagic fever. Right. And that's because that's really its own part of the story. So let's go to the 1940s for that. So I've talked before many times, every episode probably, about how important war is in terms of disease transmission. Oh, yeah. Dengue and dengue hemorrhagic fever are no exceptions to that.

During World War II, especially in the Pacific and Asian theaters of war, there was massive destruction of like everything. The landscape, both natural and urban, was just destroyed. And so in urban areas in particular, the infrastructure for water supplies or draining and plumbing essentially collapsed. And people had to store water in large containers. And a lot of water pools would form rather than drain. Mosquito populations grew enormously. And they found plenty of hosts as people were also on the move, both during and following the war, with a huge influx into urban centers. And the urban centers couldn't keep up with the growth.

in terms of infrastructure. And so you just have like all of a sudden these mosquitoes are like, well, we have plenty of hosts here to be able to do our thing. And collapsing infrastructure with plenty of places for water to collect and. Exactly. Yep. It's sort of like perfect storm of, yeah, bad things happening. So the other thing is that during the 1940s, both during the war and after, you have massive

movement of people not just like from the rural centers to urban centers. have like movement across the entire world. What this turned into was no longer a one strain, one city situation. Suddenly there were two or three or four dengue virus strains mixing in the same location. Right. And that, as we know, is how you get dengue hemorrhagic fever. Of course, this had been described before, but it was really sporadic. Okay. And like the exception, But in the years after World War II, there were epidemics of dengue hemorrhagic fever of very large scales. And since then, they have pretty much only correct me if I'm wrong, but only increased in frequency and geographic spread and size in many cases. Yeah.

Yeah. So we see the first epidemics of dengue hemorrhagic fever in Southeast Asia in the 1950s and 60s, starting in 1953 in Manila in the Philippines. And then these epidemics at first were sporadic. few years, but then they grew in size as trade and urbanization and populations increased. Epidemics of dengue hemorrhagic fever in the Americas lagged a bit behind these epidemics in Southeast Asia, popping up only in the late 1970s, early 1980s. And this delay was possibly due to simple geography, but also probably had something to do with the widespread mosquito eradication campaigns throughout the Americas in the 20th century.

I want to talk a little bit about these campaigns because I think they're important not only in understanding the current landscape of mosquito-borne disease risk across the Americas, but also I think it's a really good example of why it's so important to work interdisciplinarly and how quickly things can be undone. Oh, yeah. Yeah. The anti-mosquito campaigns and the Americas were initially spurred on by a desire to get rid of pest mosquitoes. Like it was before the true extent of the disease causing capabilities that the mosquitoes were known. And so mostly it was just like... These are annoying. These are horribly annoying.

And to read some of these quotes, like, I can't really blame them. Like, it sounds madness. Okay, let me... Here's one. This is from an English settler. Okay. They said, the noise they make in flying cannot be conceived by persons who have only heard Nats in England. That's one.

And a Catholic priest said, The greatest torment in comparison with which all the rest would be but sport is the mosquitoes. The cruel persecution of the mosquitoes. The plague of Egypt, I think, was no more cruel. This little insect has caused more swearing since the French have been in Mississippi than had previously taken place in all the world. So. More swearing in Mississippi than in all the world.

Yeah. What a strange sentence. That is a really weird sentence. But it does seem that mosquitoes were like unheard of... Super annoying. Yeah. And they did drive people out of towns. They slowed tourism and they reduced property values.

And so people, particularly landowners, wanted something to be done. Even though it started out as this like, let's get rid of nuisance mosquitoes angle, It soon took on public health motivations as well once the links between yellow fever and mosquitoes and dengue and mosquitoes and malaria and mosquitoes once those were all uncovered. Right. And also once the, in the yellow fever episode, we talked about the elimination of mosquitoes and reduction in yellow fever in the predominantly white Panama Canal zone. Exactly. So that kind of was like, oh, it can be done. So maybe we should, you know, try it.

And it started in New Jersey, of all places. New Jersey. New Jersey. They were one of the most vocal about their mosquito problem. And so that's where this began. Basically, the first strategy of this campaign was to essentially use oil, as they did in Panama, to dump it in mosquito breeding grounds like standing water. And then this would be like a larvicide and whatever.

But it's really bad for, you know, the environment to just dump oil in. So a bunch of fish died, a bunch of other animals used, like any aquaids. aquatic animals, plants also died. Did they use castor oil? Just kidding. Throw back. Two weeks ago. And also only a subset of mosquitoes were affected by the oil.

And so they were like, we need another solution. Yeah. The fishermen were like, this can't, we're not standing for this. Yeah. So they were like, let's drain these marshes and swamps and wetlands. Great, great plan, guys. Great plan. And they were like, well, no matter that there are hundreds of thousands of acres of this, let's do it anyway. And they did run into some problems. One was just the sheer size of the project that they were trying to undertake. One was funding. And the other was that not everyone wanted to have their land be drained. So then there were laws put in place, starting in New Jersey, then California followed suit, saying that any standing water is a public nuisance. And the person would either be fined or agree to comply to have.

their land be drained. Mosquito engineering is what it was called. By the 1920s, this anti-mosquito campaigns were pretty much set up across the U.S. With one exception being Florida, like Florida seemed to be strangely resistant. They love their mosquitoes down there. It's always mosquito season. As we learned. As we learned when we were there. But mosquito control cost money and it wasn't exactly promising results because it would be like, oh yeah, New Jersey was doing great and then there would be heavy rains one year and all their work would be undone. Shocking.

And everything else died. So, yeah. But then some unexpected and unasked for good PR for the anti-missquito campaigns came to Florida in 1921 in the form of a dengue outbreak. about 500 diagnosed cases and hundreds more that went unreported. And then the following year, there's a massive dange epidemic across the southeast. In like Texas, Georgia, Florida, 200,000 people infected. Whoa.

Yeah. Wow. In 1922. Wow. So then people got behind these anti-mosquito campaigns pretty quickly after that. So I think it's important to point. out that this blanket hatred for mosquitoes and full steam ahead approach wasn't necessarily unanimous among the people in charge. It's easy to look back and assume that's the case because

this is what actually did happen. There was a lot of, you know, let's kill all the mosquitoes. But there were dissenting voices early on. So there are people who worked directly in the mosquito control business were suspicious that these poisonous gases were also toxic to fish and birds. And others saw right through some of the efforts as a money-making scene. scheme for real estate developers. But because there was more money to be made in complete mosquito eradication than in an ecologically balanced approach, these dissenting voices were drowned out. Yeah, in the swamps that they drained.

Exactly. The 1930s saw even a larger expansion in mosquito control efforts at the U.S. scale. And then the following decade, Paho, Pan American Health Organization, got involved. and their campaign was to eliminate 80s Egypti across the Americas. How'd that work out for them? Well, great, actually, for a very short time. Okay, all right. Yeah.

So in general, these projects were developed or carried out by engineers, not ecologists. And so that led to some major problems. In some of these marshy areas, there was diverse habitat, rich with plant and animal life, a few years later was just destruction. Yeah. And this led to a pretty big rift, actually, between mosquito control advocates and conservationists, even though it seems like they should both be on the same side of things.

But this rift would only grow larger because in the 1940s, a new pesticide called dichloroidifinal trichloroethane. DDT. You got it. And that was found to be an extreme. cheap and really effective way to control or kill both adult mosquito populations and larvae. And like everything else, it's great. Just kill everything. Just kill everything. And it was great also because it persisted in the environment. You just needed one treatment.

And then you can kill everything for years to come. And just for decades and decades and decades. There's no potential downside to this whatsoever. Nope. And so the 1940s, 50s, 60s all saw a widespread use of DDT. It also saw the emergence of DDT resistance. Mm-hmm. Shocking. Mm-hmm. And it also saw the widespread destruction and population declines in a host of other animals.

And so in 1962 is sort of when things started to turn against the tide of mosquito campaigns. Rachel Carson's book, Silent Spring, was published. and in effect, that was the birth of the modern environmentalist movement. First Earth Day was celebrated in 1970, and by 1972, DDT was banned in the U.S. And around this time also is when Pahoe kind of stopped or slowed its efforts for mosquito elimination campaigns. And a lot of that was just a loss, like a stop loss of funding. Another was that they no longer felt it was necessary because, Yellow fever and dengue was no longer an issue in so many of the places.

80s Egypti was successfully eliminated in Mexico, Guatemala, Belize, Honduras, El Salvador, Nicaragua, Costa Rica, Panama, Colombia, Ecuador, Peru, Chile, Bolivia, Paraguay, Argentina, Uruguay, Brazil, the Cayman Islands, and Bermuda. Wow. It was eliminated. That's a lot of countries. Not everywhere. It wasn't successful everywhere. Right. But a lot of them.

But when these campaigns stopped, within a few years, all the mosquitoes came back, as you might expect. I would expect. And this is when you see the first cases of dengue hemorrhagic fever in the late 1970s. Within a couple decades after that, the levels of mosquitoes that we have in all of those places are at pre-eradication levels. Like before any of these campaigns ever got started. Wow. Man, mosquitoes are hearty little bugs.

Tell you what. Yeah. So we're back to where we started, essentially. Yeah. Or actually in a worse situation. Right, because now it's everywhere. Now it's everywhere. The first decade of the 21st century saw huge increases in dengue incidents in the Americas,

including two Pan American epidemics with over a million reported cases, as well as local transmission within different places. I found an article that said there are five major reasons. for denguez emergence as a public health problem. Excellent. One, unprecedented global population growth. Okay. Two, uncontrolled urbanization and all that goes with it, including substandard water

treatment, sewer and waste management infrastructure, etc. Three, lack of effective mosquito control in places where the disease is endemic. Four, increased air travel. And five, decay in public health infrastructure, meaning that there was more of a focus on epidemic response rather than prevention. So, Erin, now that Dengay is around us everywhere at all times, well, not here in Chicago in the middle of January, how worried should we be? Tell us about the vaccine. Tell us about the latest epidemics. What's going on? All right. Let's talk all about it. We'll take one quick break first.

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'Keefe's company, dot com slash this podcast and code this podcast at checkout. This is Bethany Frankel from Just Be with Bethany Frankel.

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Erin, it's not good news. Cool. Worldwide, Dengay is, I don't know if you would say endemic, but certainly circulates in over a hundred countries. Okay. We don't, as per usual, have a good handle on how many cases there actually are every year. However, do you want to hear some terrifying estimates? Mm-hmm. A modeling study in 2013 that was published in Nature, which we'll link on our website, estimated. And this is now the estimates that, like, WHO has on their website, etc. It's a pretty, I mean, a good modeling study. They estimated 390 million dengue virus infections per year.

What? Of which, that's 390 million infections. Remember, the vast majority are asymptomatic. So it's estimated that 96 million of those will manifest clinically at some level of severity. So, yeah. Hold on. Okay. This is every year.

Every year. But how are there even that many susceptible people? Another study estimated that 3.9 billion people are at risk of infection. with dengue. That's half of the world. Yep. Exactly. And, but how does that, like, mathematically, every year, we would all be.

How many people are born every year? Hey, Google. How many people are born every year? Here's some information from the web that might possibly help. On the website, the guardian.com, they say, There are on average about 250 babies born every minute more than 130 million in a year. To find out more, look for the link in your Google Home or Google Assistant app. There you go.

130 million babies born every year. Okay, so then over at a certain point, everyone is going to be infected with dengue is what that means. Yeah, it's only a matter of time. It's only a matter of time. Fascinating. Wow. Way to go Google. Okay.

Now, here's where it gets even more interesting. like you kind of mentioned, the number of dengue cases has been increasing. Now, you know, we have to balance the fact that we're getting better at, you know, it's being reported more often, et cetera, et cetera. But there's no doubt that dengue is growing in its number of cases. It's not just because we're reporting it more often. Right. But for example, between 2010 and 2016, the number of cases reported to WHO increased.

from less than half a million to 3.3 million in only six years. What? Right. And that's just what's reported, you know. So that's a lot less than what is actually what it's estimated that people are actually infected. So is it pretty easy to get screened for dengue? Like, is the test expensive or is it like fast? So that's one of the limitations in dengue research is that we don't have perfect screening methods. It, You can screen for it. You use seroprevalence tests.

So you'll look for antibodies to dengue, just like we do for a lot of other diseases. It's usually, I think, a PCR test. So those aren't super cheap, but they're not, you know, super expensive or very cost prohibitive or anything. But it is a limitation that we don't have, you know, screening everywhere. Not every clinic is going to be able to test for dengue. So in 2017 and 18, cases were actually down. It was looking good for dengue. like there were fewer cases than the past few years.

2019, not so much. Especially in the Americas. So Paho reported over 2.7 million cases and over 1,200 deaths between January and October of 2019. Ooh. Yeah, right? That's a lot. Wow. So Pahou is the Pan American Health Organization.

That's just the Americas. Across the globe, there was also increases kind of across the board. So there were outbreaks in 2019 across Australia, Cambodia, China, Malaysia, Philippines, Singapore, Vietnam, Brazil, Colombia, Tanzania, Congo, French Polynesia, everywhere. So overall, it's estimated that at least 500,000 people every year, are hospitalized with severe dengue. And across the globe, this has on average, about a 2.5% case fatality rate. So that's a lot of people dying every year from dengue. That is so many people. What's our hope?

Well, there are a few. There are kind of a number. Let's end this episode on a positive note for once in our lives. So there is a vaccine and there's more than one. There are, I think, four or five vaccines under study that are undergoing phase three trials. And there's one called denguevaxia that was licensed. in 2015. So this is currently, you can get this vaccine in a number of different countries. It was actually approved by the FDA for the U.S. in May of 2019. The only problem, not the only problem,

one of the problems with this vaccine is that, you know, when they first did studies on it, it's protective against all four serotypes, all four strains of virus, which is really important, because remember, if you get infected with a different strain, then you're more likely to have dengue hemorrhagic fever or dengue shock syndrome. So any vaccine has to protect against all of the stereotypes of dengue. Aren't there five? There are, but the newest one, I don't know if it only circulates in really small areas or if we just didn't know enough about it. It's not in any of these vaccines. But the four are the ones that are like really prevalent.

Okay. Yeah. So from initial trials, the overall efficacy of this vaccine was around 60% for dengue infection overall, but 80% protective against severe dengue. So that's really good. However, when they went back and over time did some longer-term studies, what they realized is that if you give this vaccine to people who have never been infected with dengue, So who are zero negative when they get the vaccine, over time, they're actually more likely to get severe dengue infection. Okay.

So what that suggests is that this vaccine isn't providing complete immunity against all four strains. Okay. Okay. So the current recommendation right now is that if countries are going to start introducing the dengue vaccine, they should screen people for previous infection before they give them. the vaccine because in people who have been exposed to at least one strain, the vaccine is very protective and doesn't increase your risk of severe dengue. Gotcha. Okay.

So yeah. So that's kind of the preferred option at this point. It's pre-vaccination screening. And you only give the vaccine to people who have previously been infected with dengue. Here's where I'm going to answer a question. shout out to Kobe from University of South Florida, who first of all drove all the way from Tampa to Gainesville to come and see us talk, which... Oh my gosh. I still can't believe that people drove to see us.

Like, that's... Wow. Yeah. So he asked an amazing question after the talk that I want to make sure I touch on. He asked, why is it that if you give somebody the Dengue vaccine, after they've been exposed to dengue, why doesn't the vaccine cause dengue hemorrhagic fever or dengue shock syndrome in those people? I remember this question. Right.

It's a really good question. And my thought at the time was, well, maybe the vaccines are only component vaccines. Turns out they're not. So the vaccines that are licensed, the vaccine that's licensed and most of the ones that are in trials are live attenuated vaccines. Okay. which means they are live virus of the four different serotypes, but the viral strains have been grown in the lab until they're no longer very virulent.

So they don't make us sick. All they do is stimulate an immune response. But your immune system has a lot to do with the dengue hemorrhagic fever and dengue shock syndrome, like manifestations. So why is it that we don't see this in the vaccine? And the answer, I think, from what I can tell, just turns out to be because these strains are not virulent, they don't induce that response. But theoretically, they could. Huh.

Yeah. Isn't that fascinating? That's really interesting. So, Kobe, that was a really good question. Yeah. Yeah. Huh. And there's a couple of cool papers that I found looking at, like, the current status of vaccine research.

Because, again, this isn't the only vaccine that's out there. There's other vaccines under trials. So we'll post all of those on our website as usual. So that's the good news about the vaccine. What's really cool about Dengay 2, though, is there's a ton of research going on in better mosquito control, but not the way that we've done it in the past. So for Dengue, there's a lot of research going on in genetically modifying mosquitoes to no longer be able to transmit Dengue virus.

Very cool. I absolutely love this. So one of the main strategies that people are using is a bacteria called Wolbachia. Oh, yeah. So mosquitoes in general, like across tons of different species of mosquitoes, are naturally infected with a species of bacteria called Wolbachia. And in 80s mosquitoes, it turns out that infection with Wolbachia reduces the ability of the mosquito to transmit dengue and other arboviruses like yellow fever, chicken guinea, Zika, etc.

So what they've been doing, and we don't have time to really get into the nitty-gritty details of this, but what they're basically doing is, you know, engineering Wobokia to be able to be transmitted between mosquitoes so that a whole population of mosquitoes could end up infected with this Wobachia bacteria, and that can then make it so that that population of mosquitoes can't transmit the dengue virus. Isn't that cool? That's really cool. Yeah. So we'll end this one on a happy note. It's not all doom and gloom and hundreds of thousands of people dying every year. It's just hundreds of millions of people getting infected with dengue. That's it. That's all. Dear. Okay. Sources. Sources? So I have several,

And I want to shout out a few. One is called The Mosquito Crusades, and this is a book by Gordon Patterson. And then another great source was Dwayne. It was a book by Dwayne Gubbler called Dengue and Dengue Hemorrhagic Fever and a paper by Dick et al, the history of Dengue Outbreaks in the Americas. And, yeah, a few more that I'll post on the website. That paper from Nature 2013 that estimated the global distribution and burden of Dengal that was the title, was by Samir Bot at all.

And there was also very great paper on titled The Pathogenesis of Dengay, Adon of a New Era in F-1000 Research in 2015. And then a number of textbooks and other papers that we will post on our website, this podcast will kill you.com. Cool. Well, thank you to Bloodmobile for providing the music for this episode and all of our episodes. And thank you all for listening and allowing us to make this podcast. And if you were at our Florida a show. Thank you so much for coming to see us. Oh my gosh. Thank you. It was the most fun. And thanks again, of course, to Dr. Alex Trio for providing the firsthand account for this episode. We'll post her website and her Twitter information in our show notes. Okay, well, with that, wash your hands. You filthy animals. This is Bethany Frankel from Just Be with Bethany

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