Ep 42 Dandy Dengue Fever

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.

Episode Transcript

Speaker 1 (00:00):
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

(00:23):
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.

(00:45):
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

(01:06):
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

(01:28):
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

(01:53):
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

(02:14):
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

(02:36):
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

(02:58):
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

(03:21):
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

(03:44):
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

(04:08):
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

(04:30):
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

(04:54):
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

(05:16):
more skirts in the city.

Speaker 2 (06:00):
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

(06:21):
follow her on Twitter at t R I l l
O underscore PA. Thanks again, Alex. Hi.

Speaker 3 (06:28):
I'm erin Welsh and I'm erin omen Updake and.

Speaker 2 (06:31):
This is this podcast will kill you.

Speaker 3 (06:33):
Yeah. Today we're talking about do you say dangy or dangay?

Speaker 2 (06:37):
I think I say both.

Speaker 3 (06:38):
I think we've done this before, right, we have discussed this.
We have discussed this and we didn't come to a conclusion.

Speaker 2 (06:45):
Yeah, well I'll say dangy, you say dangay perfect.

Speaker 3 (06:48):
That sounds excellent. Okay, great, cover all our faces.

Speaker 2 (06:50):
We can irritate everyone that.

Speaker 3 (06:52):
Way, exactly our favorite thing to do.

Speaker 2 (06:56):
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.

Speaker 3 (07:18):
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

(07:39):
paying attention.

Speaker 2 (07:40):
Well, thank you and same. Also my memory is terrible,
so but it'll be great.

Speaker 3 (07:48):
I'll still learn new things.

Speaker 2 (07:51):
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.

Speaker 3 (08:03):
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?

Speaker 4 (08:14):
Da?

Speaker 2 (08:15):
I think it is.

Speaker 3 (08:16):
I think it is too.

Speaker 2 (08:18):
What are we drinking this week?

Speaker 3 (08:19):
We're drinking the bone Breaker?

Speaker 2 (08:21):
M what's in the bone Breaker?

Speaker 3 (08:24):
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.

Speaker 2 (08:39):
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

(09:00):
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.

Speaker 3 (09:10):
Yeah, any other business that we should discuss erin?

Speaker 2 (09:15):
I don't think so.

Speaker 3 (09:16):
I don't think so either. Should we jump right into
this episode?

Speaker 2 (09:19):
Let's do it.

Speaker 3 (09:40):
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

(10:03):
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.

Speaker 2 (10:25):
I already have a question about that. I'm going to
write it down instead of okay.

Speaker 3 (10:32):
A question down and then ask me later. Yeah, okay,
you don't want to ask it now.

Speaker 2 (10:37):
I mean, because it's kind of jumping ahead to.

Speaker 3 (10:39):
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

(11:01):
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

(11:24):
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

(11:46):
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.

Speaker 2 (12:05):
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?

Speaker 3 (12:20):
Yeah, well, I was hoping you would tell me, like
where dangay came from.

Speaker 2 (12:23):
I mean, I'll tell you that I don't. I won't
be able to answer this question. Huh.

Speaker 1 (12:30):
Yeah.

Speaker 3 (12:30):
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

(12:53):
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.

Speaker 2 (13:07):
Okay.

Speaker 3 (13:08):
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

(13:29):
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

(13:53):
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.

Speaker 2 (14:14):
Okay, like having already been infected and then.

Speaker 3 (14:18):
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,

(14:41):
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

(15:03):
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

(15:27):
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.

Speaker 2 (15:46):
That's a lot of people are all these little hints.

Speaker 3 (15:48):
It's all I do. This whole bio section is just
going to be hints for later.

Speaker 2 (15:51):
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.

Speaker 3 (16:06):
I'm so sorry. I think we must have been like
nervous blackout when we were presenting.

Speaker 2 (16:11):
For sure, I remember nothing of that whole trip there.

Speaker 3 (16:16):
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

(16:37):
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,

(17:00):
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

(17:23):
for the first time, most people will never have any symptoms.
What's most eighty percent?

Speaker 2 (17:31):
Wow?

Speaker 3 (17:32):
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

(17:54):
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

(18:16):
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,

(18:41):
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,

(19:03):
wait is that right? Yeah, I'm pretty sure it's right.

Speaker 2 (19:05):
That's high.

Speaker 3 (19:07):
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.

Speaker 2 (19:16):
Does it does it respond to like anti piretics?

Speaker 3 (19:21):
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.

Speaker 2 (19:33):
Does the fever intensity correspond to like circulating virus anything
like that.

Speaker 3 (19:39):
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.

Speaker 2 (19:58):
But is that why the bi phasic, Like, is that
part of it?

Speaker 1 (20:02):
There?

Speaker 3 (20:02):
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.

Speaker 2 (20:19):
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?

Speaker 3 (20:29):
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,

(20:52):
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

(21:14):
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?

Speaker 1 (21:26):
Why?

Speaker 3 (21:27):
I don't know? Viruses are just so cool?

Speaker 2 (21:32):
What did we talk about with the rash and the palms?

Speaker 3 (21:35):
Oh uh so ricketsia causes that, and syphilis causes that,
and then hand foot in mouth disease.

Speaker 2 (21:40):
Yeah, okay, cool, Yeah, see I'm remembering thing.

Speaker 3 (21:44):
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

(22:08):
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

(22:29):
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.

Speaker 2 (22:38):
Time, you mean the second time with a different strain.

Speaker 3 (22:41):
With a different strain exactly, okay.

Speaker 2 (22:44):
And so you cannot get sick again from the same strain,
Do you have lifetime immunity or what's the deal?

Speaker 3 (22:51):
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

(23:13):
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

(23:34):
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

(23:57):
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.

Speaker 2 (24:14):
Okay, So the mechanism is the same, it's just the
end result.

Speaker 3 (24:18):
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

(24:40):
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.

Speaker 2 (25:03):
Only there's only a couple of days of you bleeding
out your gun and your.

Speaker 3 (25:07):
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

(25:28):
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.

Speaker 2 (25:44):
Okay, how many people do survive?

Speaker 3 (25:47):
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.

Speaker 2 (26:01):
But if you do receive treatment, it's mostly supportive care.

Speaker 3 (26:04):
It is entirely supportive care.

Speaker 2 (26:06):
Yeah.

Speaker 3 (26:06):
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.

Speaker 2 (26:19):
That's pretty successful.

Speaker 3 (26:21):
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

(26:42):
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,

(27:04):
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.

Speaker 2 (27:22):
I think so I think it's number two in at
least in the Americas, is associated with hemorrhagic.

Speaker 3 (27:27):
That makes sense, sindra or fever. It's gonna guess two
or three.

Speaker 2 (27:30):
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?

Speaker 3 (27:51):
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.

Speaker 2 (28:09):
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.

Speaker 3 (28:19):
I don't think so. I don't think so.

Speaker 1 (28:21):
Yeah.

Speaker 3 (28:22):
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

(28:43):
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

(29:04):
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

(29:27):
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.

Speaker 2 (29:44):
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.

Speaker 3 (29:56):
That's the thing.

Speaker 2 (29:57):
How do you know.

Speaker 3 (30:00):
That's scary too, It's really scary. Yeah.

Speaker 2 (30:04):
And there's no screening protocol in any places.

Speaker 3 (30:07):
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.

Speaker 2 (30:24):
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.

Speaker 3 (30:41):
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.

Speaker 2 (30:49):
I was looking excited a kind stories Maybe not a
recovered memory.

Speaker 3 (30:53):
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.

(31:17):
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

(31:38):
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.

Speaker 1 (31:57):
Right.

Speaker 3 (31:58):
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

(32:21):
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.

Speaker 2 (32:36):
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.

Speaker 3 (32:55):
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.

Speaker 2 (33:08):
That's really fascinating.

Speaker 3 (33:10):
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

(33:34):
is it here? And why is it so bad?

Speaker 2 (33:37):
Great questions. Let's take a quick break and then we'll
begin excellent dungi virus, all of its types probably originated

(34:17):
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.

Speaker 3 (34:29):
Okay, So about.

Speaker 2 (34:32):
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

(34:53):
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

(35:13):
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

(35:37):
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.

Speaker 3 (35:48):
It makes sense that it came from non human primates. Yeah,
just like specified onto humans or whatever.

Speaker 2 (35:54):
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

(36:16):
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,

(36:40):
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,

(37:01):
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

(37:21):
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.

Speaker 3 (37:32):
They're very hardy. M h.

Speaker 2 (37:35):
And I think this is fascinating because eighties Agypti is
it's of African origin, So eighties Agypti is now the
primary mosquito.

Speaker 3 (37:45):
Yeah, but it wasn't the first if no.

Speaker 2 (37:47):
Eighties Albapicctus was probably.

Speaker 3 (37:49):
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.

Speaker 2 (38:04):
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

(38:24):
the origin that they would have evolved together as well.
But it seems that actually albu Pictus is where it
came from.

Speaker 3 (38:31):
So fascinating.

Speaker 2 (38:32):
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

(38:54):
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

(39:17):
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

(39:38):
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

(39:58):
he treated them for DENGI.

Speaker 3 (40:01):
Two months, one thousand people in Philadelia, he alone.

Speaker 2 (40:06):
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.

Speaker 3 (40:15):
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.

Speaker 2 (40:31):
That's see, that's the one bit of trivia next time
you go to trivia at the Blind Pig.

Speaker 3 (40:36):
Mm hmm. Benjamin Rush, Ben Rush the only one founding fathers.
Oh God.

Speaker 2 (40:44):
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

(41:05):
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

(41:28):
to as water poison and was known to be associated
with flying insects that.

Speaker 3 (41:33):
Live into the water.

Speaker 2 (41:34):
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

(41:55):
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.

Speaker 3 (42:07):
Wow.

Speaker 2 (42:08):
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.

Speaker 3 (42:19):
Yes, I love the name.

Speaker 2 (42:21):
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

(42:42):
evil spirit.

Speaker 3 (42:43):
That sounds familiar okay.

Speaker 2 (42:44):
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.

Speaker 3 (42:57):
Oh yeah, do.

Speaker 2 (42:58):
You remember that one? I do remember that all the
women that Benjamin Rush treated were crying.

Speaker 3 (43:03):
They were crying women, yeah, yeah, And old Ben was like, well,
these poor ladies and their heartbreak.

Speaker 2 (43:09):
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,

(43:33):
you remember this.

Speaker 3 (43:34):
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.

Speaker 2 (43:40):
And I still haven't seen that, so I don't.

Speaker 3 (43:42):
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?

Speaker 2 (43:52):
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

(44:13):
hobbies pursued with the appearance of nonchalance in a cult
of self like Yankee doodle dandy.

Speaker 3 (44:19):
Yankee doodle dandy. Yeah, a feather pick it. He puts
a feather in his cap because he's concerned about his appearance.

Speaker 2 (44:25):
He called it macaroni. He wanted to stand out exactly.

Speaker 3 (44:28):
Yeah, yeah, okay, So that's a dandy.

Speaker 2 (44:30):
That's a dandy. I still don't understand this means in
terms of dandy fever.

Speaker 3 (44:35):
It doesn't make any sense.

Speaker 2 (44:36):
Any hypotheses, send them our way.

Speaker 1 (44:39):
Yep.

Speaker 2 (44:40):
Okay, So that's dangay etymology. And also hopefully a little
bit more about dandy fever, yeah than we need.

Speaker 3 (44:49):
Still not an answer, still.

Speaker 2 (44:51):
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

(45:13):
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

(45:34):
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

(45:54):
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

(46:16):
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,

(46:39):
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

(47:01):
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

(47:25):
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.

Speaker 3 (47:35):
To do our thing, and collapsing infrastructure with plenty of
places for water to collect and exactly Yep.

Speaker 2 (47:41):
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,

(48:03):
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

(48:25):
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

(48:46):
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,

(49:07):
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

(49:29):
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.

Speaker 3 (49:43):
Oh yeah, yeah.

Speaker 2 (49:45):
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.

Speaker 3 (50:01):
Just like, these are annoying.

Speaker 2 (50:03):
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

(50:27):
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.

Speaker 3 (50:46):
So more swearing in Mississippi than in all the world.

Speaker 2 (50:50):
Yeah, what a strange sentence.

Speaker 3 (50:55):
That is a really weird sentence.

Speaker 2 (50:57):
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

(51:17):
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.

(51:40):
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

(52:01):
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.

Speaker 3 (52:21):
They use castor oil.

Speaker 2 (52:24):
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.

Speaker 3 (52:45):
Great, great plans, great plan.

Speaker 2 (52:48):
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.

(53:08):
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

(53:28):
US with one exception being Florida. Like Florida seemed to
be strangely resistant.

Speaker 3 (53:33):
They love their mosquitos down there. It's always mosquito season,
as we learned, as we learned when we were there.

Speaker 2 (53:42):
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.

Speaker 3 (53:56):
So yeah.

Speaker 2 (53:57):
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

(54:20):
across the southeast in like Texas, Georgia, Florida, two hundred
thousand people infected. Whoa yeah, wow in nineteen twenty two.

Speaker 4 (54:31):
Wow.

Speaker 2 (54:31):
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

(54:52):
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

(55:14):
there was more money to be made in complete mosquito
eradication than in an ecologically balanced approach, these dissenting voices
were drowned.

Speaker 3 (55:21):
Out, yeah, in the swamps that they drained exactly.

Speaker 2 (55:25):
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.

Speaker 3 (55:44):
So how'd that work out for them?

Speaker 4 (55:46):
Well?

Speaker 2 (55:48):
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.

Speaker 3 (56:08):
Yeah.

Speaker 2 (56:10):
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

(56:35):
extremely cheap and really effective way to control or kill
both adult mosquito populations and larvae.

Speaker 3 (56:43):
And like everything else, it's great.

Speaker 2 (56:46):
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.

Speaker 3 (57:01):
No potential downside to this whatsoever.

Speaker 2 (57:03):
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

(57:25):
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

(57:47):
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

(58:09):
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,

(58:32):
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

(58:56):
of these campaigns ever got started.

Speaker 3 (58:58):
Wow, man, mosquito are hardy little bugs, tell you what.

Speaker 2 (59:04):
Yeah, so we're back to where we started essentially, Yeah,
and or actually in worse situation.

Speaker 3 (59:11):
Right because now it's everywhere.

Speaker 2 (59:13):
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.

Speaker 3 (59:34):
Excellent.

Speaker 2 (59:35):
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,

(59:58):
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

(01:00:18):
should we be? Tell us about the vaccine, tell us
about the latest epidemics. What's going on?

Speaker 3 (01:00:23):
All right, let's talk all about it. We'll take one
quick break first, Aaron.

Speaker 2 (01:00:58):
It's not good news cool.

Speaker 3 (01:01:01):
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

(01:01:22):
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.

(01:01:44):
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.

Speaker 5 (01:01:59):
So yeah, hold on, okay, this is every year, every year.

Speaker 2 (01:02:05):
But how are there even that many susceptible people?

Speaker 3 (01:02:09):
Another study estimated that three point nine billion people are
at risk of infection with dengey.

Speaker 5 (01:02:16):
That's that's half of the world, yep, exactly, But how
how does that like?

Speaker 2 (01:02:27):
Mathematically?

Speaker 3 (01:02:29):
Every year we need all be how many people are
born every year?

Speaker 1 (01:02:33):
Hey?

Speaker 2 (01:02:33):
Google, how many people are born every year?

Speaker 4 (01:02:37):
Here's some information from the web that might possibly help.

Speaker 2 (01:02:40):
On the website the Guardian dot com, they say they are,
on average about two hundred and fifty.

Speaker 3 (01:02:45):
Babies born every minute, more than one hundred and thirty
million in a year.

Speaker 4 (01:02:49):
To find out more, look.

Speaker 5 (01:02:50):
For the link in your Google Home or Google Assistant.

Speaker 2 (01:02:53):
Apt There you go, one hundred and thirty million babies
born every year.

Speaker 3 (01:02:58):
Okay, so then at over at a certain point, everyone
is going to be infected with danay is what that means?

Speaker 2 (01:03:03):
Yeah, it's only a matter of time.

Speaker 3 (01:03:04):
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

(01:03:26):
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.

(01:03:49):
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.

Speaker 2 (01:03:59):
So is it pretty easy to get screened for dengay?
Like is the test expensive or is it like fast?

Speaker 3 (01:04:05):
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

(01:04:26):
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

(01:04:50):
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

(01:05:11):
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,

(01:05:34):
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.

Speaker 2 (01:05:42):
That is so many people. What's our what are is
our hope?

Speaker 3 (01:05:48):
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

(01:06:12):
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

(01:06:34):
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.

Speaker 2 (01:06:52):
Aren't there five?

Speaker 3 (01:06:53):
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.

Speaker 2 (01:07:06):
Okay.

Speaker 3 (01:07:07):
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

(01:07:29):
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.

Speaker 2 (01:07:42):
Okay.

Speaker 3 (01:07:42):
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

(01:08:04):
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.

Speaker 2 (01:08:13):
Gotcha?

Speaker 3 (01:08:14):
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,

(01:08:36):
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.

Speaker 2 (01:08:48):
Yeah.

Speaker 3 (01:08:48):
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

(01:09:09):
syndrome in those people?

Speaker 2 (01:09:11):
I remember this question right.

Speaker 3 (01:09:13):
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

(01:09:34):
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

(01:09:57):
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.

Speaker 2 (01:10:15):
Yeah, yeah, huh.

Speaker 3 (01:10:19):
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

(01:10:39):
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.

Speaker 2 (01:10:54):
Very cool.

Speaker 3 (01:10:54):
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

(01:11:20):
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

(01:11:44):
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?

Speaker 2 (01:12:00):
That's really cool.

Speaker 3 (01:12:01):
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.

Speaker 2 (01:12:08):
It's just hundreds of millions of people getting infected with dangay.
That's it.

Speaker 3 (01:12:12):
That's all, dear okay.

Speaker 2 (01:12:18):
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

(01:12:41):
at All the History of dange outbreaks in the Americas.
And uh yeah, a few more that I'll post on
the website.

Speaker 3 (01:12:48):
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

(01:13:08):
papers that we will post on our website. This podcast
will kill you dot com cool.

Speaker 2 (01:13:13):
Well. Thank you to Bloodmobile for providing the music for
this episode and all of our episodes.

Speaker 3 (01:13:18):
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.

Speaker 2 (01:13:26):
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.

Speaker 4 (01:13:45):
You filed the animals

Speaker 5 (01:14:02):
Mu