My name is Alex Trio and I am an assistant professor at Gettysburg College. I'm an professor of animal behavior and tropical biology. I got diagnosed with denge in the
summer of twenty and sixty. I do a lot of field work and I work in Panama Dismissed On and Tropical Research Institute, and our work is to set up speakers and playbacks that have frog calls to attract predators and parasites of these frog 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 Pana. I was doing this work with some of my students in twenty sixty.
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 recalled 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 them, or I had something else than a cold. I was in an actual moment where I was really stressed out because not only that they had to finish old or they 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 still went on on the plane, and I remember arriving to the US 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 my lace like super super tired, and what I had was like really strong joint pain. I remember very
little about the conference. My talk was second or the third day of the conference, so I just worked really hard and 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 twenty four hours. I was fine, but I was in like a lot of pain. When I came back, I got this horrible headaches. It just feels that you have pressure on top of your nose and on the sides of your head like like but the
pressure is from the inside. It 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, we just I just said, we have to go. I 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 sineside as infection, and I was like, I have signed as infections before and this is not it there's something else that's beaker. And it was actually my husband who was like, we're not leaving this place until you test for the like you have to test for. 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 the doctor being there and said like, yes, you know, you were tested positive for denge 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 laise for like at least two months after that. A lot of people thought that I probably had it from working in Gamboa in the forest, but I do remember about ten days a week to ten days before I started feeling sick. I was actually with a friend of mine, you guys know here we were sitting at a at a restaurant outside in the city of Panama. So I honest I think that I got
it in the city. And so from then on, I told my student and I we all like whenever we never were, like nobody were skirts or shorts or or shorts leaves. We all like get lungs leaves 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 doctor Alex Trio, who was nice enough to share her experiences with dangay with us, and if you want to learn more about the awesome research that she does, you can check out her website at www dot Alextrio dot com. That's a l e X t r I l l O and you can also follow her on Twitter at t R I l l O underscore PA. Thanks again, Alex. Hi.
I'm erin Welsh and I'm erin omen Updake and.
This is this podcast will kill you.
Yeah. Today we're talking about do you say dangy or dangay?
I think I say both.
I think we've done this before, right, we have discussed this. We have discussed this and we didn't come to a conclusion.
Yeah, well I'll say dangy, you say dangay perfect.
That sounds excellent. Okay, great, cover all our faces.
We can irritate everyone that.
Way, exactly our favorite thing to do.
Yes, So, as you might have guessed, we are talking about or Dan Gay today, which is a very fascinating mosquito born virus. Yes, and it is actually an episode or a topic that we have covered once 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 Dan Gay, so we technically have heard each other talk about Dan Gay 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, so but 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 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. Ooh, stay tuned. Well is it Quarantini?
Da?
I think it is.
I think it is too.
What are we drinking this week?
We're drinking the bone Breaker?
M what's in the bone Breaker?
It is mes call. Preferably you could use tequila if it's all you've got, passion fruit simple syrup. Oh yeah, pin juice, pineapple juice, and you rim it with taheen, 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 plusy Berta on our website and also so on our social media which you can follow us at This podcast will 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.
Dangay 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 Zeka, a bunch of different encephalitis viruses, etc. Okay, there are five zero types, so that means five different strains of this virus. It used to only be four, but in twenty thirteen they announced a new one. Ooh, and so this means that if you get infected with one strain of dngay, you're not protected against the other strains of dngay. Right,
and as we'll talk about later, it's actually a lot worse. Yeah, spoilers.
I already have a question about that. I'm going to write it down instead of okay.
A 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, ask it later. Okay, Okay. So let's talk about how you get infected with danay. You already mentioned aaron. This is a mosquito born virus. So dangay is transmitted by eighties mosquitos, which we've talked about before. Because these little buggers transmit a whole number of different diseases, including yellow fever, Zeca et cetera, chicken gunyah,
which we haven't talked about yet. One thing that's different though about dangay than some of these other viruses, although not all of them, is that dan gay 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 eighties mosquitoes that
transmit dangay 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, eighties can breed in those small bodies of water. And dangay is a human specific disease, so unlike something like yellow fever that can spill over from animal populations into human populations, dangay
is human spita. So where you have large populations of humans, you're more likely to get spread of dang gay 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 dangay be so specific to humans and so interesting?
Yeah, well, I was hoping you would tell me, like where dangay came from.
I mean, I'll tell you that I don't. I won't be able to answer this question. Huh.
Yeah.
But yeah, there's no like sylvatic 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 dangay fever. We don't fully understand dangay, 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 dangay, there are some like modified mice that you can infect
with dan gay and use. You can do it in monkeys in some cases, but we don't have really good animal models for studying dan gay.
Okay.
The other way that it is possible to get dan gay, 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 zeca 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 dangay or 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 dangay or it might just have antibodies, like it might be born having antibodies against dangae virus.
Okay, like having already been infected and then.
And survived the infection. Yeah, yes, Oh, put a pin in that. Okay, that oh is the perfect Oh 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 born diseases on this podcast by now, so what's important to remember about all mosquito born 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 mm hm. And so the mosquitoes get infected if they bite a person who's actively febrile. For the most part, it's all it's possible like a couple days before you show symptoms and a couple days after you recover. If a mosquito bites a person infected with dungay during that time period, then the mosquito sucks up a bunch of viral particles. Those will travel through 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 dengay, right right, So that's really important. We'll talk even more about that in the current events section, because.
That's a lot of people are 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 pervictage.
I'm so sorry. I think we must have been like nervous blackout when we were presenting.
For sure, I remember nothing of that whole trip there.
Okay. So then when 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 Dane virus, it'll enter your white blood 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 dangay. If you get infected with dangay for the first time, most people will never have any symptoms. What's most eighty percent?
Wow?
Yeah, so, like eighty percent of people who are infected for the first time with dangay 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. Yeah, 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 dange for the second time. Aha, okay,
so here are the three main phases. Febrile, critical but oh not good, and recovery oh asterisk or death 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 one hundred and four fahrenheit, yes, forty celsius sting. Yeah,
wait is that right? Yeah, I'm pretty sure it'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.
Does it does it respond to like anti piretics?
Good question, probably, But it's also often bi phasic. 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, uh, 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 bi phasic, Like, is that part of it?
There?
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 biphasic fevers. 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 dengee are your immune system responding to the virus. Okay, great questions, Aaron as. 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 this 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, like 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 with the rash and the palms?
Oh uh so ricketsia causes that, and syphilis causes that, and then hand foot in mouth disease.
Yeah, okay, cool, Yeah, see I'm remembering thing.
Good. So this one starts on the torsos, writes to 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 the secondary infection, dengay can become more severe.
This is when we get into two different syndromes called dengay hemorrhagic fever and dengay shock syndrome. Overall across like all dengay infections, these two syndromes happen in less than five percent 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 dengay 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 Dangay hemorrhagic fever or dan gay shock syndrome.
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 dengay shock form kind of just deppends 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, ok exactly, 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 tekipnia. 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, et cetera, et cetera. This phase, the critical phase, usually only lasts a couple of days, like one to two days.
Only there's only a couple of days of you bleeding out your gun and your.
Gut and yeah, or you going into shock because all of the plasma has left your 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 dengae, if you get treatment, the overall mortality rate is like one to five percent, But once a person goes into shock, if they don't have treatment, it's like a twenty five to thirty percent 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 ivy 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 twenty five percent to one to five percent. So okay, that's pretty dang good. Yeah, yeah, okay. So there's a couple of things that we need to talk about when we
talk about these severe forms of dan gay. 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 dingay whether or
not it's your first or second infection. Also, overall vy riemia, so how much virus you get exposed to overall is also going to help define whether or not you have severe dangay 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 so I think it's number two in at least in the Americas, is associated with hemorrhagic.
That makes sense, sindra or fever. It's gonna guess two or three.
But I have a question that's related to this. This is the one I wrote down, Oh, excellent. So dangae 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 that being more severe or more likely to occur?
Maybe that's that's a really 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 EPI studies 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 zeka or other flabby viruses.
I don't think so. I don't think so.
Yeah.
I don't think that they're even though they're all flaviviruses, 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 Aaron, Okay. And then the other people who are more likely to have severe dengey 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, older adults and things than in children. Okay, but we talked briefly about how infants
can be born with antibodies to dengay. So a group that's at very very high risk of severe dan gay deng gay hemorrhagic fever or dung gay shock syndrome is infants that have maternal antibodies to dengay 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 dingay, they're at very very high risk of going on to develop severe symptoms.
But how would like if only twenty percent of people show signs or know that they've been infected with dangay, then how do you know.
That's the thing.
How do you know.
That's scary too, It's really scary. Yeah.
And there's no screening protocol in any places.
That are like during pregnancy. Yeah, not that I know of, that I know of. Yeah. So then the question becomes, why is it that a secondary infection with dengay 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 nineteen eighteen flu where it's like the immune system just goes like super ham good question.
That's that is one of the hypotheses that was out there for a long time, that it's kind of like a cytokine response. That was what happened in the nineteen eighteen That's what.
I was looking excited a kind 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 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 dean Gay strain number one, these antibodies are similar to the antibodies that you would make to dan Gay number two, but they're not exactly the same. And so for some reason, these antibodies bind to dangay 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 dan Gay one flag dan Gay two, 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 Danay wants to be. That's where Dangay 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 viromium, right, because the more virus you have circulating, 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 or more support for this hypothesis. So that is dang gay, 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 dungi virus, all of its types probably originated 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.
Two thousand to four thousand years ago, the Dungy 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 dengey would retreat and wouldn't be seen again until the number of sceptible 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 in the distance between these settlements or groups shrink, 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 Dengi start to evolve, and they would also make the leap from the silvatic cycle. So I think originally dengay did circulate in primates and non human primates.
It makes sense that it came from non human primates. Yeah, just like specified onto humans or whatever.
Right, And so more and more strains made the leap from just the that cycle of monkeys and mosquitoes to then this urban cycle or more urban cycle of mosquitos 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 strain 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 sixteenth and seventeenth centuries, the slave trade began, and for Dengey 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 slave trade also spread the key vector
mosquito species eighties Agypti. Yeah, because as you mentioned, eighties Egypti lives really well, like literally well in urban like next to humans, and it doesn't need a whole lot to continue its life cycle. Yeah, it's just basically small bits of water.
They're very hardy. M h.
And I think this is fascinating because eighties Agypti is it's of African origin, So eighties Agypti is now the primary mosquito.
Yeah, but it wasn't the first if no.
Eighties Albapicctus was probably.
Interesting what was originated with eighties Egypti and eighties Albapictus are both the like two main vectors, but they talk about eighties agypti as the like primary just because of I think 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, And so this is this is kind of what caused this debate as to the geographical origin of dengay, 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 that would be the origin that they would have evolved together as well. But it seems that actually albu Pictus is where it came from.
So fascinating.
I don't know anyway, So eighties a jip dye being the super cosmopolitan mosquito species, really helped the distribution of dengay, and so probably by the eighteenth century the Dengae 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 eighties a jip dye, and even in those more northern or more southern places like a little bit outside of the Mosquitos. Year long
environmental requirements it would just be reintroduced. Yeah, it'd be like, oh, it's warm enough in the summer, I'll die off in the winter and then be reintroduced. Knowing the evolutionary origins of danngae is one thing, But when did humans actually first recognize the disease. Yeah, so it's around the late eighteenth century, seventeen seventy nine to be exact, that we see what is considered to be the first dange pandemic.
In seventeen seventy nine, there are descriptions of a dnge like illness in Java in 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 one thousand people he treated them for DENGI.
Two months, one thousand people in Philadelia, 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 dangay in Florida. Benjamin Rush is one of the founding fathers. Yeah, I learn that from you, So glad.
That's see, that's the one bit of trivia next time you go to trivia at the Blind Pig.
Mm hmm. Benjamin Rush, Ben Rush the only one founding fathers. Oh God.
Moving on anyway, So this the epidemic in Philadelphia, from Benjamin Rush's description was pretty likely. Dangy okay Egypt and Java may have been chicken gunya. There's been a lot of recent debate over whether these early descriptions are actually chicken gunya virus as opposed to dangae virus, But in any case, it seems that Philadelphia was pretty likely and that's the earliest more like convinced or most convincing instance.
There are descriptions of a dangye like disease and a Chinese encyclopedia dating back to the year nine nine two. 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 into the water.
So fascinating mosquitoes, and the symptoms of this disease sound a lot like dangy. 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 like much of the world during the eighteenth and nineteenth centuries, with an estimated eight pandemics each lasting three to seven years from seventeen seventy nine to nineteen sixteen.
Wow.
Yeah, With a disease that is as old and in particularly as wide ranging as dengay, 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. Okay, okay. So the word dang gay first seems to pop up in Spain around eighteen oh one, and researchers think that the most likely origin of that was actually from the Swahili name for the disease, key dinga 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 nineteenth century on, but it had a lot of other names. We already heard water poison, I've already heard breakbone fever, break heart fever.
Oh yeah, do.
You remember that one? I do remember that 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 broken hearted. 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 slew thing, which basically means that I went to the Wikipedia article for dandy, which is pretty lengthy. Actually cool. All right, So, according to Wikipedia quote, 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.
Yankee doodle dandy. Yeah, a feather pick it. 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 this means in terms of dandy fever.
It doesn't make any sense.
Any hypotheses, send them our way.
Yep.
Okay, So that's dangay etymology. And also hopefully a little bit more about dandy fever, yeah than we need.
Still not an answer, still.
Unanswered, Okay. So anyway, the disease dangay was known by at least the late seventeen hundreds, but it would take a bit before some of its biological characteristics were discovered. So once scientists made the link between mosquitos and yellow fever, which was in the late eighteen hundreds. They kind of got the feeling that danga 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 dangy was caused by a filterable transmissible agent, which back then before microscopy and microbiology advanced, was pretty much going met It was a virus. The viruses wouldn't be isolated until nineteen forty three. This was during or right after the Nagasaki dangaye epidemic of nineteen forty two,
which had over twenty three thousand 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 dang 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 dungay viruses, but not specifically dung gay hamorrhagic fever. And that's because that's really its own part of the story. So let's go to the nineteen forties for that. So I've talked before many times every episode probably about how important war is in terms of disease transmission. Oh yeah, deung gay and dungay hamorrhagic fever are no exceptions to that.
During World War Two, 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 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, wow, 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 nineteen forties, both during the war and after, you have massive movement of people, not just like from the rural centers to urban centers, you 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 dangay virus strains mixing in the same location, and that, as we know, is how you get dung gae hamorrhagic fever. Of course, this had been described before, but it was really sporadic and like the exception. But in the years after World War Two there were epidemics of dungae hamorrhagic 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, so we see the first epidemics of dangae hamorrhagic fever in Southeast Asia in the nineteen fifties and sixties, starting in nineteen fifty three in Manila in the Philippines, and then these epidemics At first were sporadic every few years, but then they grew in size as trade and urbanization
and populations increase. Epidemics of donge hamorrhagic fever in the Americas lagged a bit behind these epidemics in Southeast Asia, popping up only in the late nineteen seventies early nineteen eighties, 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 twentieth century. I want to talk a little bit about these campaigns because I think they're important not only in understanding like the current landscape of mosquito born disease risk across the Americas, but also I think it's a really good example of why it's so important to work interdisciplinarily and how quickly things can be undone.
Oh yeah, yeah.
The anti mosquito campaigns in the Americas were initially spurred on by a desire to get rid of pest mosquitos like it was before the true extent of the disease causing capabilities of the mosquitoes 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 mosquito's angle, it soon took on public health you know motivations as well, once the links between yellow fever and mosquitos and dangae and mosquitos and malaria mosquitos, once those were all uncovered, and also once 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 the 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 larvacide and whatever. But it's really bad for you know,
the environment treatment dump oil in. So a bunch of fish dyed, a bunch of other animals use like any aquatic animals. Plants also dyed.
They use castor oil.
Just kidding crow 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. The fishermen were like, this can't. We are not standing for this. So they were like, let's drain these marshes and swamps and wetlands.
Great, great plans, 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 a 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 nineteen twenties, anti mosquito campaigns were pretty much set up across the US with one exception being Florida. Like Florida seemed to be strangely resistant.
They love their mosquitos 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 mosquito campaigns came to Florida in nineteen twenty one in the form of a dangae outbreak about five hundred diagnosed cases and hundreds more that one unreported. And then the following year, as there's a massive dangae epidemic across the southeast in like Texas, Georgia, Florida, two hundred thousand people infected. Whoa yeah, wow in nineteen twenty two.
Wow.
So then people were 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 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 nineteen thirties saw even a larger expansion in mosquito control efforts at the US scale, and then the following decade PAHO of Pan American Health Organization got involved and their campaign was to eliminate eighties Egypti across the Americas.
So 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 problem. 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 nineteen forties, a new pesticide called die chlorod phenal trichloroethane DDT, you got it, and that was found to be an extremely 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.
No potential downside to this whatsoever.
Nope. And so the nineteen forties, fifties, sixties all saw a widespread use of DDT. It also saw the emergence of DDT resistance, shocking, and it also saw the widespread destruction and population declines in a host of other animals, and so in nineteen sixty two 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 nineteen seventy and by nineteen seventy two DDT was banned in the US. And around this time also is when PAHO 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 dengay was no longer
an issue in so many of the places. Eighties of JYPDI was successfully eliminated in Mexico, Guatemala, Belize, Honduras, El Salvador, Nicaragua, Costa Rica, Panama, Columbia, Ecuador, Peru, Chile, Bolivia, Paraguay, Argentina, Uruguay, Brazil, the Cayman Islands, and Bermuda. Wow, it was eliminated. That's not 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, this is when and this is when you see the first cases of denge hamorrhagic fever in the late nineteen seventies. Within a couple decades after that, the levels of mosquitos that we have in all of those places are at pre eradication levels, like before any of these campaigns ever got started.
Wow, man, mosquito are hardy little bugs, tell you what.
Yeah, so we're back to where we started essentially, Yeah, and or actually in worse situation.
Right because now it's everywhere.
Now it's everywhere. The first decade of the twenty first century saw huge increases in dang gae 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 dengaye's 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 treatments. So we're in waste management, infrastructure, et cetera. 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 p
demic response rather than prevention. Mm So, Aarin, now that Dengey 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, Aaron.
It's not good news cool.
Worldwide denay is I don't know if you would say endemic, but certainly circulates in over one 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. A modeling study in twenty thirteen 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, et cetera. It's a
pretty I mean, a good modeling study. They estimated three hundred and ninety million dan gay virus infections per year. What of which that's three hundred and ninety million infections. Remember, the vast majority are asymptomatic, so it's estimated that ninety six 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 three point nine billion people are at risk of infection with dengey.
That's that's half of the world, yep, exactly, But how how does that like?
Mathematically?
Every year we need 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 dot com, they say they are, on average about two hundred and fifty.
Babies born every minute, more than one hundred and thirty million in a year.
To find out more, look.
For the link in your Google Home or Google Assistant.
Apt There you go, one hundred and thirty million babies born every year.
Okay, so then at over at a certain point, everyone is going to be infected with danay 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 dangay 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 dengay is growing in its number of cases.
It's not just because we're reporting it more often. But for example, between twenty ten and twenty sixteen, the number of cases reported to WHO increased from less than half a million to three point three 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 dengay? Like is the test expensive or is it like fast?
So that's one of the limitations in dengay research is that we don't have perfect screening methods it. You can screen for it, you use zero prevalence tests, so you'll look for antibodies to dengay 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 dengay. So in twenty seventeen and eighteen, cases were actually down. It was looking good for dengay, like there were fewer cases than the past few years. Twenty nineteen not so much, especially in the Americas. So PAHO reported over two point seven million cases and over twelve hundred deaths between January and October of twenty nineteen. Oh yeah, right, that's a lot. That's just so PAHO 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 twenty nineteen across Australia, Cambodia, China, Malaysia, Philippines, Singapore, Vietnam, Brazil, Colombia, Tanzania, Congo, French Polynesia, everywhere. So overall it's estimated that at least five hundred thousand people every year are hospitalized with severe dengay, and across the globe this has on average about a
two and a half percent case fatality rate. So that's a lot of people dying every year from dengay.
That is so many people. What's our what are is our hope?
Well, there are a few, there are kind of a numbers. 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 like that are undergoing phase three trials, and there's one called denga Vaccia that was licensed in twenty fifteen, So this is currently you can get this vaccine in a number of different countries. It was actually approved by the FDA for the US in May of
twenty nineteen. 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 it's protective against all four zero types 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 dange heemorrhagic fever or danngey shock. Syndrome. So any vaccine has to protect against all of the stereotypes of dangay.
Aren't there five?
There are, but the newest one. I don't know if it's 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 sixty percent for dengay infection overall, but
eighty percent protective against severe dengay. So that's really good. However, when they went back and like 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 dengay, so who are zero negative when they get the vaccine, over time, they're actually more likely to get severe dngay 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 dengay vaccine, they should green 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 dangay.
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 dang gay. 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 they still can't believe that I 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 some the deng gay vaccine after they've been exposed to dengay, why doesn't the vaccine cause dan gay hemorrhagic fever or dungay 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, which means they are live virus of the four different erotypes, 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 dung gay hemorrhagic fever and dan gay 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 dang gay too, 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 Danay, there's a lot of research going on in genetically modifying mosquitoes to no longer be able to transmit dang gay 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 like tons of different species of mosquitoes are naturally infected with a species of bacteria called Wolbachia, and in eighties mosquitoes, it turns out that infection with Wolbachia reduces the ability of the mosquito to transmit danngae and other arboviruses like yellow fever, chicken
gun yazica, et cetera. So what they've been doing, and I'm I don't 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 Wolbachia to be able to be transmitted between mosquitoes so that a whole population of mosquitoes could end up infected with this Wolbachia bacteria and that can then make it so that that population of mosquitoes can't transmit the danngae 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 dangay. That's it.
That's all, dear okay.
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 Dwyane. Was a book by Dwayne Gobbler called Dan Dangay Hamorrhagic Fever, and a paper by Dick at All the History of dange outbreaks in the Americas. And uh yeah, a few more that I'll post on the website.
That paper from Nature twenty thirteen that estimated the global distribution and burden of dangay that was the title was by Semir bat at All. And there was a also very great paper on titled the Pathogenesis of Dangae adwn of a New Era in f one thousand research in twenty fifteen, and then a number of textbooks and other papers that we will post on our website. This podcast will kill you dot 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 show, thank you so much for coming to see us.
Oh my gosh, thank you. It was so most fun. And thanks again, of course to doctor Alex Trio for providing the first hand account for this episode. We'll post her website and her Twitter information in our show notes. Okay, well, with that, wash your hands.
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