Ep 164 Rift Valley Fever: Ruminating on ruminants

Hemorrhagic virus? Check. Deadly disease? Check. Mosquito-borne? Check. Affected by animal movement, human activity, and environmental change? Check. Rift Valley Fever has all the markings of a classic TPWKY episode. This week, we’re doing a deep dive on this deadly virus, taking a One Health approach to explore the intricate relationships between animals, humans, and the environment to understand how this virus moves across the landscape. We trace the various paths this virus takes: through the organisms it infects, across the globe as it spreads, and over time as it appears to be evolving to be deadlier. Tune in to learn more about Rift Valley fever and what we might see with this pathogen in the years to come.

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Episode Transcript

Speaker 1 (00:00):
A pathologist RS, aged thirty years, had been working with
rift Valley fever virus for several weeks before the onset
of his illness. On the evening of December twenty second,
nineteen thirty two, he felt chilly while walking home and
complained that his eyes and the calves of his legs
ached during the night. His rest was disturbed by general
malaise and pains, especially around the knees and hips. On

(00:24):
awakening the second day of illness, his temperature was one
oh one fahrenheit. He attempted to continue his work, but
had several chills during the day and felt so miserable
that he took to bed. He complained at this time
of a vague soreness over his abdmen, constant dull headache,
and pain behind the eyes associated with slight photophobia. There

(00:45):
was no sore throat, rhinitis, nausea, or vomiting. He was
admitted to the hospital of the Rockefeller Institute twenty four
hours after the onset of symptoms. On admission, the temperature
was one o two point six fahrenheit pulse respirations twenty four.
The patient was definitely prostrated by his illness, but rational

(01:06):
and cooperative. The throat culture was negative for hemolytics streptococcie
and influenza bacille, and blood cultures in infusion broth remained sterile.
A tentative diagnosis of riffelly fever or influenza was made.
In an attempt to confirm the tentative diagnosis of riffelly fever,
six ce seeds of the patient's blood was injected into

(01:27):
six mice. All of the mice died within forty eight hours.
Almost immediately after admission, the patient began to improve. The temperature,
which reached a peak of one oh three point eight
fahrenheit on the night of admission, fell promptly to normal
within twenty four hours. The symptoms, however, abated somewhat less rapidly.
By the twelfth day of illness, the patient had improved

(01:48):
to such an extent that he was allowed to sit
in a chair for a short time, and on the
following day was permitted to walk a short distance. On
the evening of the sixteenth day, however, he complained of
pain in the life left leg. The patient was returned
to bed and the leg was immobilized in an elevated position.
Four days later, twentieth day of illness, the patient awakened

(02:09):
with pain in the right chest, which was more pronounced
during deep inspiration or exhalation. In the X ray photograph
made at this time, there was a distinct shadow at
the base of the right lung. On several occasions, blood
was expectorated in small amounts. On the thirty eighth day
of illness, recovery seemed to be proceeding uneventfully. On the

(02:30):
morning of the forty fifth day of illness, however, the
patient suddenly collapsed and died within a few minutes. Death
was apparently due to a large embelis in the pulmonary vessels.

(03:28):
That's a tough, tough story, yeah, and what a rollercoaster too,
really is like you have no idea where it's going
to go until you're there.

Speaker 2 (03:37):
Yeah. I don't know anything about the path of physiology
of rift valley fever, so I'm very curious to know
how well this fits in with like the clinical picture
that has been seen, you know, not super well but interesting.

Speaker 1 (03:53):
But I can see how these things ended up happening,
So we can when we talk at the pathology, we
can kind of tie back into it.

Speaker 2 (04:03):
Okay, So that first hand account was from a paper
by Schwenker and Rivers from nineteen thirty four titled Rift
Valley Fever in Man Report of a fatal laboratory infection
complicated by thrombo phlebitis. And this actually is the first
recorded death due to Rift Valley fever. Oh interesting, I

(04:26):
mean likely not the first death right humans, but the
first recorded human death detailed recorded. Huh. Yeah. Hi. I'm
Aaron Welsh and I'm Erin Alman Updike, and this is
this podcast Will Kill You, And today we're talking about
Rift Valley fever. We've had a lot of.

Speaker 1 (04:43):
Requests for this one, which I feel like is surprising
because I knew almost nothing about it except I had
heard there is Rift Valley fever, like I knew that
it existed. I knew it was mosquito born. That's all
I knew.

Speaker 2 (04:55):
Yeah, I say, I was like, oh, this is a
dangerous virus. But I didn't really know much more than that.
And I was kind of shocked when I got into
the history of outbreaks.

Speaker 1 (05:08):
I am shocked at how little I knew, considering like
that we were deep in disease ecology for so long.

Speaker 2 (05:17):
Oh yeah, I mean I still I would like flip
through parasite books for fun. Yeah. Yeah, somehow just goes
to show that there is no limit to the number
of diseases and viruses and pathogens and parasites and fungi
out there.

Speaker 1 (05:33):
Yeah, it's true. So with Valley fever is the one
we're talking about today, but before we can tell you
all about it and all the things that we learned,
it's quarantine anytime.

Speaker 2 (05:44):
It is aaron. What are we drinking this week?

Speaker 1 (05:47):
We're drinking wolf in sheep's clothing.

Speaker 2 (05:50):
It'll make sense, it'll make sense. Sheep are involved. Wolf
is the virus. I love to over explain a joke.
It's well, we went back and forth by text. The
wolf is the virus. The virus is the wolf. Yes, okay,
that's a great name. What's in a wolf in sheep's clothing?
A wolf in sheep's clothing is your basic concoction of mescal,

(06:15):
grapefruit juice, a lemon lime soda of your choice, and
you know, maybe a squirt of lime or something.

Speaker 1 (06:23):
And some halpinios write a little spicy mescal paloma.

Speaker 2 (06:27):
Yes, situationial the crucial muddled jalapenios, and we'll.

Speaker 1 (06:32):
Post the full recipe for that quarantini as well as
the non alcoholic equally delicious plusy burrita on our website
This Podcast will kill You dot Com and all of
our socials, So if you're not already following us, you
should because the picks are delicious.

Speaker 2 (06:45):
On our website This Podcast will Kill You dot Com,
you can find all manner of things you know. There's
transcripts for all of our episodes. You can find links
to our bookshop dot org, affiliate account, our Goodreads list,
music by Bloodmobile merch. We've got great merch we do.
Links to Patreon, links to a submit your first hand

(07:06):
account form, links to a contact us form. There's more
there too.

Speaker 1 (07:10):
There's so much this podcast. Okay, dot com check it out. Yeah,
if you haven't already, please check your podcast and make
sure you're subscribed. If you haven't left us a review
or a rating and you'd like to, now's your opportunity.

Speaker 2 (07:24):
You can do that right.

Speaker 1 (07:25):
Now, And we would so appreciate it. We would really
love it. It really helps the show, So thank you.

Speaker 2 (07:30):
She's not lying, she's totally right. We appreciate it and
it helps us. Well, then shall we get into this virus.
Let's do it. Let's take a quick break and begin.

Speaker 1 (08:08):
I think part of what surprised me about how little
I knew about Rift Valley fever is how much of
a classic TPWKY story it really is. Yeah, I know
that we are getting back to the roots of this
podcast when I can go on the World Health Organization's
website and find so much of the information that I'm
looking for, and even more so when there's a page

(08:31):
on the World Organization for Animal Health website.

Speaker 2 (08:35):
So buckle up.

Speaker 1 (08:37):
This is a really classic piece of TPWKY content. So
Rift Valley fever is a disease that's caused by a
virus called Rift Valley fever virus.

Speaker 2 (08:47):
It's not very creative.

Speaker 1 (08:49):
And this is an RNA virus in the genus flebovirus.

Speaker 2 (08:54):
I think that's how you say it.

Speaker 1 (08:55):
And I think that the phylogeny of this group viruses
has changed relatively recently, But in any case, it's in
the order Bunia viralus, which is the same group that
includes hantaviruses and loss of fever virus and some others
that we haven't yet covered.

Speaker 2 (09:14):
Have we done loss of fever.

Speaker 1 (09:16):
Er No, we haven't done loss of fever. But maybe
people have heard of los of fever. I know, we
haven't done it. Wow, Okay, there's aaron. There's so many
that we haven't done yet. Yeah, but hantaviruses we have.
And with the exception really of the hantaviruses and loss
of fever and other arenaviruses, most all of the other
viruses in this order Bunia viralis are transmitted primarily by

(09:41):
arthropod vectors like ticks and mosquitoes, and rift Vali fever
virus is no exception asterisk, but let's talk about it.
So rift valley fever in humans is really considered a
zoonotic disease, which means that primarily it's not affecting humans,
it's infecting animals, and it's generally considered to be only

(10:02):
these spillover events that end up causing disease in humans.
So there has to generally be some kind of animal outbreak,
which we call an epizootic before there is then a
human outbreak. And this virus infects a pretty wide variety
of animals, and the ones that end up being most
important for us as humans are our livestock. So this

(10:25):
virus infects cattle, sheep, goats, and other small ruminants and
camels and sheep and goats tend to be the most
severely affected. And it's transmitted to these livestock primarily by mosquitoes,
but not just any one mosquito, no, no, no, whole
bunches of mosquitoes in multiple different genera, mostly transmitted by

(10:51):
eighties mosquitoes of dengey fever, yellow fever chickengunyet like all
the viruses eighties mosquitoes as well as a qlex mosquitoes
of like West Nile virus and Japanese encephalitis virus fame.

Speaker 2 (11:04):
It's so strange because usually viruses are so hyper adapted
to their mosquito vector hosts, like that specific species. But
this isn't. So What's how.

Speaker 1 (11:19):
I have so many questions, Aaron, about the path of
physiology or the like the life cycle of this virus
in mosquitoes because it it doesn't We don't have as
much information as I expect, Okay, and it's really interesting.
So there's at least like fifty different species of mosquito

(11:43):
that have been found to harbor this virus, and the
transmission is like usually when we picture like a transmission
cycle among let's say you know vector host, maybe there's
a secondary host. It's like a circ goal, right, the
transmission of this virus. When you look at this cycle,

(12:04):
it's not a circle. It's like a circle with a
line and another line and like two other branches.

Speaker 2 (12:09):
It's get the mess create a peometry.

Speaker 1 (12:13):
Yeah, so how does it go?

Speaker 2 (12:18):
Really?

Speaker 1 (12:18):
Usually when we're covering a vector borne disease on this podcast,
I can start like this, and I'll start like this
for this episode. Ready, a female mosquito, it's always a
female mosquito takes a blood meal from a host, let's
call it a sheep for accuracy. It drinks up some
of the virus in that blood meal because the sheep
is infected. And after some amount of time in the

(12:41):
mosquito and varying amounts of this virus moving through the mosquito,
it maybe makes it to the salivary glands or something
like that, and then that mosquito takes another blood meal,
spits the virus into the host, and boom, Now you've
completed the transmission cycle. And cycle can happen in Withfalley fever.

(13:05):
But how long does it have to exist in the mosquito?
How long does this virus have to be there?

Speaker 2 (13:12):
I don't know.

Speaker 1 (13:13):
What does it do inside this mosquito?

Speaker 2 (13:15):
I don't know.

Speaker 1 (13:16):
Where does it go? Does it travel to the salivary
glands or does it not?

Speaker 2 (13:20):
I don't know. I don't know, Aaron, Okay, and I
anticipate that the answer to this question is I don't know,
but huh. Our different mosquito species differently capable of harboring
transmitting the.

Speaker 1 (13:35):
Virus almost certainly yes, which one's more likely than less?

Speaker 2 (13:41):
I don't know. Here's where we.

Speaker 1 (13:44):
Can add another layer of complication. In addition to that
transmission cycle, this virus can also be and is known
to be, transmitted from female mosquitos into their eggs. This
is called vertical transmission, and we know this happens at
least in some way species of eighties mosquitoes, but maybe
not in all species.

Speaker 2 (14:04):
We're not sure, which has huge implications for the distribution
of this virus in the landscape and the potential for
outbreaks to happen in subsequent years, even outside of like
big outbreaks like the inter epidemic years or whatever. It
sure does, Aaron.

Speaker 1 (14:19):
You're one hundred percent right, because it means that Mosquito
babies are essentially born infected, so they can inject virus
into their host with the very first blood meal that
they take. So not only can this virus potentially persist
like among different seasons without necessarily needing to have reservoir
hosts that are infected, you also can then have viral

(14:41):
transmission even if mosquitoes aren't living long enough to transmit
from animal to animal to animal, because the very first
blood meal that they take, they can potentially transmit this virus.

Speaker 2 (14:52):
Okay, so here's another question. Though it's not just the mosquito.
It's not just the mosquitoes. It's not a question.

Speaker 1 (14:59):
But you know where I'm going with that. There's let's
keep going, shall we. I said that this was a web,
so we shall continue along this transmission web. Once an
animal host is infected, and again mostly in this case
we're talking about livestock, ruminants, sheep, cattle, goats, camels, all
of these animals also have vertical transmission themselves. So if

(15:23):
a pregnant animal gets infected from a mosquito, it will
almost inevitably pass that virus through the placenta to their offspring,
and this almost always causes spontaneous abortion or pregnancy loss.
This virus can also be transmitted from mosquitoes to other wildlife,
and we don't fully understand the whole wildlife cycle.

Speaker 2 (15:44):
That's just like a black box.

Speaker 1 (15:46):
We know that it happens, but we don't know what
hosts are important. Are they amplifying hosts or are they not,
et cetera.

Speaker 2 (15:53):
Are they maintenance hosts?

Speaker 1 (15:54):
Yeah, But then we get to humans. How do we
get infected in this tangled web. Well, it could be
the same way that our animal friends are getting infected
via these mosquitoes, But what's far more common is that
humans are infected from our infected animal friends themselves, either

(16:16):
from direct contact with something like their blood, their raw milk,
or other bodily fluids, directly getting into our eyes, mouth
or other mucous membranes, or through breaks in our skin
in the process of caring for or slaughtering these animals,
or from inhaling aerosolized bodily fluids. So it's usually a

(16:36):
kind of more direct transmission from animal to humans that
ends up causing disease in humans. And then we as
humans can also pass this virus through the placenta and
potentially cause infection in a fetus. The only good thing
thus far is that horizontal meaning human to human transmission

(16:58):
has yet to be documented, and the same is true
for direct transmission from animals to animals like among a herd.
So then why is it that humans can get infected
from animals?

Speaker 2 (17:10):
We don't know.

Speaker 1 (17:10):
Is it just because of the ways that we happen
to be interacting with and handling their tissues and bodily fluids?

Speaker 2 (17:15):
I don't know.

Speaker 1 (17:17):
But that is the like good news that I can
say about the transmission of this virus.

Speaker 2 (17:22):
Okay, I mean that makes sense because it's not like
the animals are doing the slaughtering and inhaling the blood.
It's it's yeah, humans are doing that. Okay. How many
viral particles ooh? No? Idea great question though, okay, okay?
And it is through the aerosolization, like, is it also
contaminated surfaces? Is there? What's the durability of this virus

(17:45):
in the environment.

Speaker 1 (17:46):
There's so many other questions. I could have tried to
go down rabbit holes to answer that. I don't have
the answers for aaron. Yes, so there's differential virulence and
that's likely due to like like you asked how many
viral articles does it take and things like that. People
get more or less sick depending on what route they
were more likely exposed to, and aerosol transmission seems to

(18:08):
be the most virulent, so most likely to cause really
severe disease is when it's you're inhaling it and it's
going into your mucous membranes that way. The other common
way that people get infected, and this could be from
contaminated surfaces, but it's through contact with like broken skin,
so like you have an injury and blood or something

(18:28):
like that gets into your bloodstream from that. So those
are kind of the two most common ways. There have
been some cases of things like raw milk, which means
that could be potentially an oral or a GI exposure,
but we have just less data on that overall.

Speaker 2 (18:42):
Interesting. Okay, yes, this is maybe jumping ahead a little bit,
but jen in an outbreak where it's not just livestock

(19:03):
impacted but also humans, is there a any known breakdown
between how people have gotten exposed, Like what proportion is
mosquito versus direct contact that kind of thing.

Speaker 1 (19:16):
Of all the outbreaks that we have good data on
primarily are happening from direct contact with animal fluids. It
is very likely that mosquito born transmission absolutely plays a
role in some outbreaks, but it seems that overall across
the board, it is animal to human transmission that causes
the vast majority of human cases. Okay, which means that

(19:39):
the people at highest risk are people who work in
industries where they are coming into contact with animals. Okay,
But as I'm sure you know, and we'll probably talk about,
some of the historic outbreaks have been very large, which
means that certainly there's other things that are going on,
and why in those cases did the outbreaks get so big.
They're presum probably must have been also mosquito borne transmission happening.

(20:03):
So yes, it definitely can happen. But does it also
just depend on, like our mosquitos more likely to bite
humans or to bite animals, and what mosquito species are
circulating in those regions, because again, this is so many
different mosquito species. So yeah, there's a lot, there's a
lot of layers, and we don't have great data on
a lot of details.

Speaker 2 (20:25):
On a lot of these outbreaks. Yish that we had
more data. I wish that we had more data. I mean,
don't we all don't we?

Speaker 1 (20:34):
Yes, we do know some more about like what does
this disease do, Like what does it look like if
an animal or if a person gets rifally fever. Unsurprisingly,
given that this is a virus that infects so many
different species, it presents very differently across different animals, but
even within humans it can present very differently across the board. Though,

(20:57):
we know that there's two main cell types in mammalian
bodies that this virus is predominantly infecting, and everyone who
listens to this show is well aware at this point
that a virus has to infect a host cell in
order to use our machinery to replicate. So which cells
it's infecting tend to be really important in what kind

(21:19):
of symptoms and what kind of disease we see. So
in the case of rift Valley fever, the two main
cell types that this virus is infecting are liver cells,
so we'll talk about what that ends up doing, and
then monocytes, which are a type of white blood cell.
And so especially in severe cases, the liver is one

(21:41):
of the main sites of damage. So what does that
end up actually looking like If we look at animals Again,
the symptoms will vary depending on the type of animal
that's infected, as well as how old that animal is,
because universally, young animals so fetuses as well as newborn animals,

(22:01):
are much more severely affected than older animals. But in general,
in almost all animals that are infected, all of these
livestock animals, we see things like fever. We'll see the
animal stop eating, they stop like moving about, They don't
really like walk around or get up and go around.
They become really like listless and lethargic. Especially in sheep,

(22:25):
you might start to see evidence of gi inflammation, abdominal pain,
bloody diarrhea, and these animals are like visibly in pain
and uncomfortable. But the way that this virus ends up
wiping out entire populations of livestock is because it passes
through the placenta and then causes spontaneous abortions in pregnant

(22:48):
animals and then has massive mortality rates in newborn and
young animals. So in these livestock herds, especially in lambs
and kids which are baby goats, the more mentality rate
can be as high as seventy to one hundred percent.
It's devastating it's devastating, and even in adult sheep and

(23:09):
things like baby cows or calves and adult cattle, the
mortality rates can be as high as twenty to seventy percent.
So this is a very lethal infection for livestock animals.
When it comes to humans, there is a really wide
range of how this disease can present. Most papers across

(23:32):
the board estimate that about fifty percent of people who
are infected are essentially asymptomatic, like don't really show any
symptoms whatsoever. And most people who do have symptoms will
have a relatively mild disease and only a small percentage
And most papers say maybe one to two percent develop

(23:54):
severe symptoms, and we'll talk about what those severe symptoms
look like. But I want to caveat early on those numbers,
because a it seems like maybe that one to two
percent is an underestimate for recent outbreaks or more modern outbreaks,
And some papers cite this number instead of saying one

(24:16):
to two percent of all cases, they'll say it's like
eight to ten percent of symptomatic cases, Okay, And I
feel like looking at it that way really changes your
perspective on this disease, because as we'll go through some
of these symptoms. This can be incredibly terrifying and really severe,
and so I think trying to understand how big are

(24:36):
these outbreaks that we're talking about and how many people
are affected are really really important. So let's talk about
what it ends up looking like. If somebody is going
to show symptoms of refali fever.

Speaker 2 (24:48):
Symptoms usually start between.

Speaker 1 (24:49):
Two to six days after exposure, and it usually starts
as the name suggests, with a fever along with a headache.
You'll have muscle or joint pain. Very often we see
some like neurologic symptoms like vertigo or like in the
first hand account that photophobia.

Speaker 2 (25:08):
Like it hurts to look at light.

Speaker 1 (25:10):
Yeah, you might have nausea or vomiting, and then if
it remains a mild case, then this might last anywhere
from like a few days, like four days to a
week or so, and then often that person will get better.
Sometimes it's not uncommon that people will have like a
bi phasic illness, which means they'll get better, and then

(25:30):
a couple of days later, their fever will spike again
and they'll get sick for another few days before they
improve for good. But there are several ways, three different
ways really that this can cause a much more severe illness.

Speaker 2 (25:45):
Here's the three ways.

Speaker 1 (25:46):
It can infect your eye, it can infect your brain
and spinal cord, or it can destroy your liver, and
then you have a hemorrhagic illness.

Speaker 2 (25:56):
So let's go through those. And these are not mutually exclusive.

Speaker 1 (26:00):
They're not mutually exclusive, but they're very different, and so
I don't know how often they happen altogether. Okay, So
in some people, this virus seems to infect the eye,
the back of the eye, and it can infect like
a whole variety of parts of that. It could be
the retina itself, it could be your nerve in your eye,

(26:21):
it could be the macula, a whole bunch of different parts.
And in those cases that person might have had the
same mild illness that I already described, get better, and
then a week or several weeks later, they'll start to
have blurry vision or decreased vision. And then this can
last a few months or it can end up causing

(26:45):
permanent damage, depending on which part of the eye ends
up being infected with this virus. Why the eye, Why
the eye, I don't know. Is it just an easy
target there's good blood supply there is it just that
that's where the virus was close to. I have no idea. Also,
why is it so long after the initial infection. I

(27:06):
don't know the specific path of physiology of.

Speaker 2 (27:09):
What's going on.

Speaker 1 (27:11):
But that's not the only way that you can see
this delayed response. Another way that it could go is
that again, a few weeks or even months after an
initial infection, somebody might come down with a severe headache
and signs of brain inflammation that might look like confusion, disorientation, vertigo,

(27:33):
even things like hallucinations or loss of memory. And this
can progress to seizures, coma, and potentially death. And this
is all a me ninjo encephalitis, So inflammation that's happening
in the brain and the spinal cord as a result
of ri Valley fever.

Speaker 2 (27:50):
Okay, And so this is like a consequence. This isn't
the virus attacking those things necessarily. It's like a consequence
of our immune responses reaction to the virus.

Speaker 1 (28:02):
I don't know, Aaron, okay, because we know a lot,
and I'll link to a bunch of specific papers that
look at like the gross anatomic pathology that's happening in
these cases. We know that it's a lot of inflammation.
Is it that virus is laying latent and then reactivating
and causing this or is it that you're having delayed

(28:26):
immune reaction to the virus. I am not one hundred
percent sure from all of my reading, and it could
be that I'm not interpreting the reading correctly. Given the delay,
it seems more likely that it's an inflammatory reaction, like
an immune response, But it's a little bit unclear to
me from all of the reading that I did.

Speaker 2 (28:44):
Well, and I will say too in that first hand account,
they talked about how as this person you know, seemed
to get better and then got worse and worse, and
then got better again and then worse later on, they retested,
they retook blood and re injected it into mice to
see is this still rift valley fever and the mice refine.

Speaker 1 (29:03):
Okay, interesting, So that suggests that it's more immune mediated.

Speaker 2 (29:07):
I mean pay Pers nineteen thirty four, like yeah, but
still but still.

Speaker 1 (29:11):
And just timing wise, that's sort of what it seems
like right right. This kind of neurologic disease, when it happens,
can cause long term neurologic complications, and some sources suggest
that it doesn't tend to cause death, But there was
an outbreak in Saudi Arabia in the early two thousands

(29:32):
which like fifty percent of people that ended up having
neurologic complications died from that. So I don't think it's
entirely accurate to say that you would never have death
as a result of this type of neurologic manifestation of
Rift Valley fever. Yeah, but it's less common than the
final manifestation, which is the most severe, and that is
when this virus causes a hemorrhagic disease, and it does

(29:56):
this because of damage to the liver. So the way
that this might present is that during that acute illness,
So during that time when someone is sick with a fever, etc.
Someone might then start to appear jaundiced, so their skin
or their nails or their eyes are starting to turn yellow,
and that's a sign of liver damage because that yellowness

(30:17):
is caused by something called bilirubin building up in your
skin or your eyes because your liver can't break it
down into the form that you can excrete. And as
your liver gets damaged because your liver is also in
charge of making most all of our clotting factors. Now,
all of a sudden, your blood can't clot the way
that it should, so you start to have signs of bleeding.

(30:40):
And this could be things like large bruises or purpura,
which are these big, dark purple splotches on the skin
that are essentially just signs of bleeding. Underneath the skin,
you might see bleeding from mucus membranes like your nose
or your gums. You'll see bloody vomiting or diarrhea, really
heavy menstrual bleeding. If this person is already hospitalized and

(31:03):
getting poked for things like blood draws or ivs, they'll
start to have bleeding from these sites of napuncture. And
this form of hemorrhagic disease is the most severe form.
About fifty percent of people who develop hemorrhagic disease from
refelly fever will usually die within three to six days
of the first sign of these hemorrhagic symptoms.

Speaker 2 (31:24):
Do we know what factors make someone more likely to
develop the hemorrhagic form, or the ocular form, or the
neurological form, or be completely asymptomatic. Yeah, it's such a
good question.

Speaker 1 (31:38):
It's probably similar to different species of animals that we see.
It likely depends on host factors, right, so like who
you are and what your immune system does in response
to this virus, but also things like the root of transmission.
So overall, like I said, the intr nasal or airborne
transmission seems to be more likely to cause severe disease

(31:59):
than in animal models where we've like injected this virus
into animals. But beyond that, there's like a lot that
we don't know and don't understand. And again I have
several papers that go really deep into detail on what
we do know, which is a lot about like viral

(32:19):
receptors and the histopathology of like what's happening in your
liver and what's happening in where in your brain? Is
there inflammation? But like, how does this actually happen? Why
are some people so severely affected in others are not?
I don't have a good answer to that question.

Speaker 2 (32:37):
Okay, Yeah, and you mentioned that the virus can also
be transmitted from pregnant person to fetus. What does the
infection look like in that situation?

Speaker 1 (32:49):
Yeah, it depends and we don't have a lot of
data on this because there haven't been that many well
documented cases. There's been enough to show that it is
very likely that this virus can cross the placenta and
infect a fetus. It can cause, potentially, like it does
in animals, spontaneous abortion, but again, we haven't seen significant
increased rates of spontaneous abortion in areas where there have

(33:12):
been outbreaks, which is good news. But certainly it can
also then cause infection in a newborn, and because newborns
have very little immune system, that infection is likely more
likely to be severe. So there have been cases of
neonatal deaths from this virus.

Speaker 2 (33:28):
And where do we stand on treatment?

Speaker 1 (33:31):
Yeah, we don't stand Okay, there are no treatments that
are specific for this virus, which means that there's a
lot of things that we have to do to try
and prevent it. So mosquito control is an important part
of that. Vaccines and there are a couple of different
vaccines for live stock, no vaccines for humans, but there

(33:54):
are both like live attenuated vaccines, and there are inactivated
or killed virus vaccine. Pros and cons to both of those,
but they both exist and they both can be used both,
like on a regular basis in endemic areas in livestock
as well as in the case of outbreaks, at least
the inactivated form. But yeah, that's rip valley fever.

Speaker 2 (34:16):
It is. It can be a really severe infection.

Speaker 1 (34:21):
And we'll talk more in detail about recent outbreaks that
have happened, Like why is it so severe sometimes or
is it getting more severe?

Speaker 2 (34:30):
I don't know, Aaron, that is a great question. It is.

Speaker 1 (34:34):
I still have a question, so, Aarin, when did we
first find out about this virus? When did it spill
over from animals to humans?

Speaker 2 (34:43):
What do we know about it? Let me see what
I can answer right after this break on the surface,

(35:19):
history and disease ecology seem like two entirely different fields. History,
of course, deals with past events, especially from a human perspective,
while disease ecology examines the relationship between a pathogen or pathogens,
its host or hosts, and the environment. Like what would

(35:40):
you learn in a history class that would be repeated
in a class on disease ecology besides the discovery of
one disease or another. Not a lot, Aaron. That's why
I love our podcast. We do it. But as I
was reading about rift valley fever, the first described outbreaks,
the potential impact of climate change and land you change

(36:00):
on future outbreaks. I realized how similar the approach that
these two fields take really is, because it all comes
down to understanding the context, why did this happen when
it did? And what can the past tell us about
the future. Oh love that? Yeah, I know, this is
my hyper nerd. I was like, whoa dies? Easy? College

(36:22):
in history the same thing. I finally get why I
love this. It finally all makes sense. It all makes sense.
But let's start with the first part of that, the
why did this happen when it did? Getting at the
earliest known emergence of rift valley fever. In August of

(36:43):
nineteen thirteen, the Department of Agriculture of quote unquote British
East Africa published its annual report on the whole. It's
some pretty dry reading, crop counts, detailed descriptions of personnel vacations,
the number of ingoing and outgoing letters for each sub department. Like,

(37:04):
do you want to know how many letters the Veterinary
department received and wrote in nineteen thirteen? I actually do.
It's sixty eight hundred. Wow, it's more than I thought, yeah,
that seems like a lot.

Speaker 1 (37:16):
I know, they didn't have email, thinking about how many
emails they probably send now.

Speaker 2 (37:20):
But I know it's kind of I was like, wow,
that's that's that's a lot. It's a lot. I mean,
that's a lot of letters. And these reports also included
casual mentions of land theft and forceful removal under the
guise of manifest destiny. Ah yeah, right, so quote in
June nineteen twelve, the removal of the Massai and their

(37:41):
stock from Lykipia was commenced and was brought to a
successful conclusion on the twenty seventh of March nineteen thirteen. Wow.

Speaker 1 (37:49):
Imagine just talking about like decimating human populations and forcibly
removing human beings from their home that way cool.

Speaker 2 (37:57):
Yeah, yeah, I mean, success definitely in the eye of
the beholder in that successful conclusion, because just for a
little bit of extra context, this removal broke the nineteen
oh four promise that the British had made to the
Massai to stop taking their land, which they ultimately stole
about seventy percent of to make space for the incoming settlers.

(38:18):
And they were like, oh, the Lykipia Plateau being at
higher elevation, it's going to be more hospitable to the
Europeans that are coming. Like it's it's just all part
of it.

Speaker 1 (38:28):
Yeah.

Speaker 2 (38:29):
Yeah. But if you keep scrolling past this detached reporting
of you know, land theft and so on, you'll eventually
come to a mention of a devastating disease impacting sheep. Quote.
A mortality of ninety percent was recorded among the lambs
at government Farm Naivasha. Other farms in the Rift Valley

(38:50):
also suffered considerable loss. In some cases, the symptoms were
very acute and death occurred within a few hours. In others,
the disease ran a more or subacute or chronic course.
In the acute form, the only symptoms shown were dullness,
rapid respirations, collapse, and death within four hours. In post mortem,
the liver was found to be soft and friable and

(39:13):
the kidneys congested. In the subacute or chronic form, the
umbilicus was incompletely closed and swelling of the joints occurred.
Investigation pointed to the disease resulting from infection gaining entrance
through the umbilicus end quote. Yeah. The sheep that were
primarily impacted by this disease were marino, which were introduced

(39:35):
for their wool, but there didn't seem to be much
follow up or concern about this particular disease, perhaps because
quote the setback was only a temporary one end quote.
So this brief mention from nineteen twelve, buried in pages
upon pages of bureaucratic minutia, stands out as the first

(39:57):
description of what was likely riffed vlley fever. Yeah, why
then why nineteen twelve?

Speaker 1 (40:05):
Right? Just because you brought all them sheeps there.

Speaker 2 (40:08):
I mean, that's part of it. But it also does
seem to impact the native species there as well. So
maybe it's just visibility, like these marino sheep were more susceptible.
That's part of it. But I think there are some
other things going on too. So later genetic analyzes would
place the origin of the Rift valley fever virus as

(40:28):
recently as the eighteen eighties to eighteen nineties. What Yeah,
So it could have just been that this was one
of the earliest outbreaks that this virus caused. Interesting, So
where did this virus come from? Great question? I don't know,
because also viruses do this thing where one strain tends

(40:49):
to dominate in an outbreak, and it replaces all the
other strains and kind of makes it look like it's
the only one. And so this could underestimate how old
the virus truly is. It is a lot older, but
it's just sort of doing this whole strain replacement type
of thing. But regardless of when the virus evolved, it
likely had caused infections prior to nineteen twelve. And the

(41:13):
reason though that it was first described then is probably
because of colonization, right, importing merino sheep, which might be
more susceptible to the virus as we talked about, But
also there's the looking for it in these agricultural reports.
The British were monitoring their investments, seeing how well the

(41:34):
introduced crops and livestock like marino sheep did on the
lands that they stole, and noting what diseases posed a
threat to their income, like rift valley fever. This is
the reason that tropical medicine was founded as a field
of study right to better understand, prevent and treat the
diseases that were prevalent in an area undergoing colonization. The

(41:59):
chief veteran officer who made the initial report R. J.
Storty wasn't noting this sheep disease out of academic curiosity,
but out of a oh, this might be something we
have to look out for as suttlers set up their
farms here type of a thing, right, Our E. Montgomery,
the veterinary pathologists at the time, even signed off his

(42:20):
report with quote in conclusion, I may add that only
such diseases as appeared to me to possess considerable interest
to the stock owner have been dealt with in this report.
There have been a considerable number of others, which are
as yet fortunately of minor importance. I consider it our duty,
so far as possible, to undertake the preliminary investigation of

(42:41):
all diseases which come within our knowledge, and by doing so,
to be in some measure prepared for eventualities end quote.
Science and the questions that we ask in science have
always been guided by certain values or principles or interests. Yeah,
and I just I feel like it's that part doesn't

(43:01):
really get highlighted a whole lot inside. Oh, no, this type.

Speaker 1 (43:04):
Because it is right, Yeah, stories of like discovery for
discovery's sake, or like this is so cool and interesting,
And then was used.

Speaker 2 (43:12):
But yeah, no, I mean.

Speaker 1 (43:15):
Much of the time specific things were being studied at
the bottom line for money.

Speaker 2 (43:21):
Yeah, I mean, then the Chief Veterinary Officer for the
Department of Agriculture wasn't just like screening sheep left and right.
The more interested in diseases affecting sheep, then the disease
is affecting wildlife because sheep was where the money was.
Not wildlife. Okay, but what happens next? Right, like what
happens after nineteen twelve, Well, nearly twenty years would pass

(43:44):
before the disease appeared in another scientific publication, one that
would give it its name and identify the causative agent.
In nineteen thirty one, Dabney and Hudson from the Division
of Veterinary Research, Kenya Colony described a devastating outbreak of
unknown cause in sheep Merino sheep on a farm in
the Rift Valley. The disease primarily impacted newborn lambs or

(44:07):
pregnant sheep. At the start of the outbreak, sixty of
the eighty lambs born died within a matter of weeks.
The authors noted that the farm manager chose July and
August as the lambing season. That year, which was somewhat unusual.
Normally it was May or October to November. Right, So
you choose like when the lambs are born. Sorry, how

(44:29):
do you choose that you put the sheep together at
a certain time? Oh wow, yeah, I know you well,
And you do this so that you can time it
with like when rainfall, when grass is available, grazing lands,
et cetera. Interesting, Okay, so why July and August of
that year. Well, it turns out that in that same year,

(44:50):
the area had received an unusually large amount of rainfall,
over forty five inches compared to the annual average of
twenty five which is a ton. So this meant more
grazing habitat during the dry season, and so the manager
figured it would be safe to lamb in July and August,
especially if the heavy rains in the beginning of the

(45:11):
year were repeated in November, which would make it harder
on the lambs that were born then. So you kind
of just like hedging your bets, like, well, things are
looking good right now, let's lamb right now, or like
you know, however, many months from now and the rainfall
and mosquitoes the excess to rainfall. Ye, have also meant
more habitat for other critters like midges, which can transmit

(45:35):
a virus that causes the livestock disease blue tongue, which
I also saw peek in that year, and mosquitoes, which
of course carry the riffed felly fever virus. Those sixty
lamb deaths in early July turned out to be only
the tip of the iceberg, as the disease tore through
the flock, killing lambs and use within hours of the

(45:59):
first symptoms appearing. By August tenth, nineteen thirty, about a
month after the outbreak began, quote, the total mortality in
lambs had reached approximately thirty five hundred and upwards of
twelve hundred us had died. Wow. I think it was
a mortality of ninety five percent. Oh my god. Yeah.

(46:20):
The farm manager was desperate to save the surviving sheep,
and so he transported them to another farm higher up
around seven thousand to eighty five hundred feet in altitude,
which is twenty one hundred and twenty six hundred meters
other farm. The original farm was about fifty five hundred
to six thousand feet seventeen hundred to eighteen hundred meters

(46:41):
after arriving there. At higher up the deaths continued for
a few days but eventually stopped. Okay, but the disease
continued on on the original farm for months after. And
so this could be because there aren't as many mosquitoes
at higher elevations, maybe like the temperatures keep it down,
or the humidity or whatever it is, or the mosquitoes

(47:01):
that carry the virus don't live at higher elevations even
if there are other mosquitoes there, or the mosquitoes at
those higher altitudes just weren't infected. And so to try
to answer this, I did a little bit of digging
and found a twenty sixteen paper that noted that the
risk of Rift Valley fever tended to go down as
altitude went up. But it doesn't seem like there's been

(47:22):
extensive research about the altitudinal range of the vector mosquitoes
or you know, like all of these questions that are
like are mosquitoes capable of transmitting the virus existing or
living at higher altitudes?

Speaker 1 (47:35):
Right? Well, and it's hard because there's so many species
erin like which one do you pay?

Speaker 2 (47:38):
Many species? Right? Yeah? And then like if higher altitude
means less likely infection. Will that change is the climate changes, probably,
but I'm getting ahead of myself. Dobney and Hudson, the
authors of this nineteen thirty one paper, got to the
farm and began their susceptibility tests, their post mortems, their analyzes.

(47:59):
They isolated a virus that they named the Rift Valley
fever virus, found that it caused the highest mortality in sheep,
but that goats and cattle could also be infected, as
could humans. Quote. During the course of the investigation, all
the four Europeans engaged developed a dangae like fever, which
we now know to have been due to infection with

(48:20):
the virus. The first person to be attacked was mister F. Lyons,
the laboratory assistant in charge of the exposure experiment on
the farm where the disease first appeared. Mister E. J. Hall,
who assisted in the laboratory investigation, was next attacked a
few days later. Both writers developed symptoms within a few
hours of each other. In every case, the onset of

(48:41):
the attack was characterized by a very brief period of
general malaise, followed rapidly by sharp riggers and headache. The
temperature rose to about one hundred and three degrees fahrenheit,
and the face was brightly flushed in From three to
six hours after the riggers had passed off, pains developed
in or near the joints, extending from the base of
the skull to the extremities. Fever persisted for a period

(49:03):
of from twelve to thirty six hours, and the pains
gradually disappeared within about four days. And then they would
go on to say that every quote unquote native that
was hurting sheep during the attack also got sick with
fever and aches and pains, and that the manager just
chalked it up to eating quote the somewhat decomposed carcasses
of dead sheep end quote great great, yeah, okay, yeah,

(49:28):
just just some casual racism thrown into that paper. Not
surprising at all. Nope, Nope. This nineteen thirty one paper
clearly described this newly recognized disease, the responsible virus, the
symptoms it caused, and its association with wet years, even
noting that quote the DNGE like fever in man would

(49:49):
in all probability fail to attract serious attention in view
of the fact that in such years the incidents of
malaria would be unusually high, and quote, yeah, they're like obscured.

Speaker 1 (50:01):
Right, it's here, but it's not as big of a
deal as the other stuff, so no one's looking at.

Speaker 2 (50:05):
It, right, And it's also like everyone's getting sick from
these other things, and so it kind of flies under.

Speaker 1 (50:09):
The radar, right right right now, Okay, makes sense.

Speaker 2 (50:12):
And so but with that similarity to malaria pointed out,
they made an educated guess that the Rift Velly fever
virus was transmitted like malaria, by mosquitos. Love that, yeah,
but it was also clear that mosquitoes were not the
only way you could get exposed to the virus. First,
you had the four who worked on the virus, including
Dobney and Hudson, get sick, along with so many people

(50:33):
who worked with sheep in the field, presumably from handling
samples or directly interacting with the sheep themselves. But then
the disease started to crop up in laboratory researchers a
long way from Kenya, especially those who performed in a
cropsies on the lambs, and the first known death from
Rift Valley fever in humans was recorded in nineteen thirty

(50:55):
three or nineteen thirty two from our first hand account. Okay.
This death, though, would stand out as somewhat of an anomaly.
For the four or so decades that followed the publication
of Dobni and Hudson's paper, from the nineteen thirties to
the nineteen seventies, Rift Valley Fever caused nearly two dozen

(51:16):
epizootics throughout Africa, first spreading from East Africa to South Africa,
and infections seemed limited to livestock. Only few human cases
were noted and no deaths, and these weren't necessarily small outbreaks.
One epizootic in Kenya from nineteen fifty to nineteen fifty
one led to five hundred thousand sheep infections and one

(51:39):
hundred thousand deaths. Wow.

Speaker 1 (51:42):
Yeah, that's like when I feel like when you hear
numbers like that, like it's just so hard to imagine
that much death and devastation.

Speaker 2 (51:52):
Honestly it is, and like livelihoods ruined, absolutely ruined. Yeah.
Was it possible that in an epizolotic like this just
no one was looking for human cases and they were
just mild or asymptomatic, I mean, potentially likely, But researchers

(52:12):
screened some of the people that were handling animals during
the outbreaks and found really low levels of antibodies to
the Rift Valley fever virus, suggesting that they weren't getting
infected at all. I have so many questions, erin, I know,
because this isn't the way things stayed. Yeah, right, Like
this epizootic happening every few years, causing a few mild

(52:35):
human infections if any, but lots and lots of animal
infections and death. That was going to be a thing
of the past. The first signal that something changed came
in nineteen seventy four and nineteen seventy six, when South
Africa saw half a million animal infections and the first
human deaths due to Rift Valley fever virus in South Africa,

(52:59):
this time not from laboratory workers, and more human infections
than had ever been reported one hundred and ten lab
diagnosed cases and seven deaths. Wow. But this outbreak would
quickly be overshadowed by another, resulting in a total paradigm
shift for this disease that would shape our understanding of
the virus and its relevance in public health. Between nineteen

(53:22):
seventy seven and nineteen seventy nine, riffed vellley fever ripped
through Egypt, which had never seen a case before. In fact,
no cases outside of Sub Saharan Africa had been seen
before this. Officials estimated that half of all susceptible animals
in the country were infected. Whoa, Yeah, which absolutely devastated

(53:44):
the Egyptian economy. As if that wasn't bad enough, the
disease also caused extensive morbidity and mortality in humans, with
an estimated two hundred thousand human infections and six hundred deaths.

Speaker 1 (54:01):
I mean, so different than these early outbreaks that you're
just holding.

Speaker 2 (54:04):
So different And even in the past outbreaks when there
had been some human infection, they were mild, right, and small, small,
small numbers. Yeah, But this outbreak in Egypt, there was
heemorrhagic disease, there was encephalitis, there was ocular disease, all
of these extreme manifestations of the virus that you described.

(54:25):
And with this outbreak came the realization that this was
more than a potentially devastating disease for livestock, Rift valley
fever also posed a serious threat to humans. This became
more and more apparent over the following decades. First in
nineteen ninety seven to nineteen ninety eight, with a devastating
epizootic and epidemic in Kenya after rainfall exceeded sixty to

(54:47):
one hundred times a normal amount WOW, resulting in livestock
losses up to seventy percent on some farms and an
estimated eighty nine thousand infections and four hundred and seventy
eight deaths in huge Then rift velly fever continued to
expand its geographic range, with the first cases of rift

(55:07):
valley fever outside of Africa happening in Saudi Arabia and
Yemen in two thousand, where it caused eight hundred and
eighty lab confirmed cases the real number is likely much
much higher and one hundred and twenty three deaths. Since then,
rift valley fever has settled into this new pattern, causing
occasional episolotics and epidemics after periods of unusually heavy rainfall,

(55:31):
often resulting in hundreds, if not thousands or tens of
thousands of human cases and deaths, as well as severe
economic losses due to livestock mortality and so circling back
to those two questions that I asked at the start
of this why did rift valley fever become deadlier and
cause larger outbreaks over the past fifty years or so,

(55:52):
And what can that tell us about future outbreaks. The
answer to those questions is complicated because we've got so
many interconnected factors at play. We've got the virus itself,
how likely it is to mutate or reassort or recombine.
How often it gets an opportunity to become more virulent.

(56:14):
We've got the vectors, how abundant they are, Which species
are in which areas, Whether different species are equally good
at transmitting the virus, whether different species tend to bite
humans or livestock more readily, how often they feed, how
long their eggs, which could potentially contain the virus last
between epizootics in the environment. We've got the hosts. How

(56:35):
many sheep are in a certain area, how controlled their
movements are, how susceptible they are. Whether the animals have
been vaccinated when lamming happens, importation of animals from affected
regions to ones where the virus has never appeared. How
many humans live or work near outbreak areas, whether they
have access to protective equipment when handling infected animals, whether
this region has the resources to monitor outbreaks and take

(56:56):
steps to prevent or control the disease if it appears.
I'm not done. Oh there's more I know. Then there's
the environment, right, rainfall amount, humidity, temperature, soil type. Some
soils retain water better than others, which in turn has
an effect on mosquito habitat, the propensity of certain areas
to flood, vegetation density and type, which also affects mosquito

(57:20):
breeding habitats and grazing, deforestation, irrigation, dams, al Nino events, wind,
and so many other factors. Well, wildlife, wildlife, Yes, what
potential hosts, What other hohosts.

Speaker 1 (57:34):
Are around besides your livestock? And what kind of density,
and what kind of environments, what kind of mixing? What
species of mosquito biting them versus you versus your livestock?

Speaker 2 (57:44):
There, it is.

Speaker 1 (57:45):
An unbelievably complicated This is why we don't have predictive models.

Speaker 2 (57:50):
That's the well we do. That's the kind of cool thing.
I mean, no, like we do, and we don't write
do we have perfect models. There's no such We're never
going to have the amount of data. Ecology is just
too noisy there's too much going on, it's too difficult
to collect. Things are changing too much. Drawing a straight
line from cause to effect is impossible, doesn't exist. I mean, yeah, yeah,

(58:17):
just not really feasibility. But even with all of these
moving parts, there are some ways that we are able
to see what the future might look like. And it
also might help us to answer some questions about the past.
Why Rift Valley fever became more deadly and more likely
to cause human deaths about fifty years ago. I mean,

(58:40):
it's probably a mix of those moving parts, maybe mutations
or reassortments of the virus, increased rainfall events because of
climate instability, increasing herd sizes, and crucially, movement of infected
animals across large geographic areas, especially from endemic to naive areas.
More virus equals more infections equals more opportunities to become deadlier.

(59:06):
We don't have a perfect roadmap for how this happened,
but putting together the drivers of these past outbreaks or
some factors associated with these past outbreaks can give us
clues about the future. So there's a cool paper from
twenty twenty four by Chemisen at All that talks about
how they created a model using climate data to see

(59:27):
if they could accurately predict past riftfelly fever outbreaks across Africa.
And it is just like primarily climate data, but their
model did a pretty good job, which is exciting in itself.
But what this also means is that you could tell
this model, Okay, this is what the climate is projected
to look like in the next ten years for this
region or that region, or even the next year or

(59:50):
the next five years, whatever you want, and you could
see how those different climate scenarios or climate change scenarios
could impact the risk of rift felly fever out breaks
broad strokes. Right now seems to be that things will
get wetter in affected regions, which means more outbreaks potentially,
And so you could say, okay, next year, what is

(01:00:11):
it going to look like potentially for rainfall, and you
could place higher alert and so then if an outbreak
does start to happen, are there things that you can
do to cut that outbreak short? Right?

Speaker 1 (01:00:21):
What are the plans that you put in place knowing
that this is going to be a wetter year, knowing
that that's going to increase the risk of transmission? How
do you then deal with it right right, And.

Speaker 2 (01:00:30):
So these models are not perfect, but they can help
to create early warnings to focus resources during certain areas
at certain times, in places where resources typically are often
very limited, to see where rift valley fever might spread
as the climate changes. You'll see some papers that are
like rift valley fever in Europe, is this where it's

(01:00:51):
going to be now? And these models can be updated
as we learn more about this virus, about the climate,
about the host, about all about the mosquitoes, about everything.
They are a really important part of our toolkit, but
they're not the only thing. So speaking of which Aaron,

(01:01:11):
I was hoping that you could tell me where we
are with rift valley fever today and whether there's maybe
a human vaccine in the works.

Speaker 1 (01:01:20):
We'll talk about it right after this break. So, like

(01:01:57):
you mentioned, Aaron, when you were talking about where we
first saw this virus and how it has spread, this
is a virus that's endemic at this point in animals
and or mosquitoes across eastern Africa, all the way into
southern Africa, honestly across the entire continent into western Africa,

(01:02:19):
and has gone north into Egypt and caused a few
outbreaks on the Arabian Peninsula. Looking at the World Health
Organization's outbreak reports, because they have disease outbreak news reports,
and this is absolutely one of the viruses that gets
reported on if there are any human cases. The most

(01:02:39):
recent outbreaks that they reported were actually a couple of
years ago, which I was a little bit surprised about.
There haven't been any that they reported thus far as
of the time of recording in twenty twenty three or
twenty twenty four. The most recent outbreak that the World
Health Organization reported on was in Mauritania in twenty twenty two,
and in this outbreak there were forty seven cases confirmed

(01:03:03):
in humans. Almost all of them were people who worked
with animals of some kind, many animal breeders. But of
those forty seven cases, twenty three people died wow, which
is a case fatality rate of forty nine percent. In
this outbreak. Of the animals that they tested, there were

(01:03:26):
nearly three hundred animals that were positive for refali fever virus.
Twenty four percent of those animals died, and these were
a mix of cattle, camels, and small ruminants. If we
look back at past outbreaks, in twenty twenty one, there
was an outbreak in Kenya that had thirty two confirmed
human cases and eleven deaths, which is a case fatality

(01:03:49):
rate of thirty four percent. There was an even larger
outbreak in Mauritania in twenty twenty with at least seventy
five people confirmed positive, over two hundred people were suspected
to be infected, and at least twenty five deaths. And
what I was thinking in looking through all of these

(01:04:09):
individual outbreaks, and again you can link to all of
these on the World Health Organization website. There's a number
more dating back to like the twenty tens, that these
are very high case fatality rates, very high compared to
what we have seen in the past, and very high

(01:04:30):
compared to what all of the sources that I read
would lead you to expect when we talk about one
to two percent of cases or even eight to ten
percent of symptomatic cases being severe and fifty percent of
hemorrhagic cases ending in death. Right, that's the numbers that

(01:04:52):
I cited earlier.

Speaker 2 (01:04:53):
Yeah, so what is going on here?

Speaker 1 (01:05:00):
Does this mean that in these outbreaks, the cases that
we are able to report that the World Health Organization
is reporting, are those cases only the tip of the
iceberg in a case.

Speaker 2 (01:05:14):
Yeah, that's possible.

Speaker 1 (01:05:16):
I did some air in math to try and get
a handle on what that would mean. So if we
look at the outbreak in Mauritania in twenty twenty two,
we had forty seven people that were confirmed to be
infected and twenty three.

Speaker 2 (01:05:29):
People who died.

Speaker 1 (01:05:32):
If we think that that means that those cases were
only the people who had severe infection. If we tried
to air in math that outbreak, then we would estimate
that outbreak could have been as large as like four thousand,
seven hundred people who were infected. If we were expecting

(01:05:54):
that only one to two percent of all people who
were infected had severe symptoms, and fifty percent of people
with severe symptoms that would be those forty seven people.
Fifty percent of those people would end up dying. That's
that's my air and math of the situation. Does that
make sense.

Speaker 2 (01:06:12):
Yes, we don't have.

Speaker 1 (01:06:14):
Any data to suggest that that is what happened, at
least that has been reported that I have seen. So
I'm not trying to say that these cases are actually
these outbreaks are actually thousands more than we think, but
that is one possibility. The other possibility is that case
fatality rates are indicative of much more severe illness than

(01:06:36):
we have seen in the past. And if so, why
is that because the virus is changing? Is that because
something was happening with hosts who were infected at the time.
I don't know, But there was a paper from PLUS
Neglected Tropical Disease that was the systematic review and meta
analysis of all the case reports from the last few decades.

(01:06:57):
They looked at like thirty two different studies and they
found an overall twenty one percent fatality rate among those
who had symptoms of disease. So it seems like the
mortality rate may be on the rise from with Valley fever,
and we don't as far as I read, understand what

(01:07:17):
exactly might be driving.

Speaker 2 (01:07:19):
That, which is very interesting because, as we talked about,
the virus is not directly transmitted human to human exactly.

Speaker 1 (01:07:29):
It is not, and there still has been no evidence
that that has started.

Speaker 2 (01:07:32):
And so what is going on in the environment, Like
it must be something that is happening to increase the virulence.
Is there a corresponding increase in virulence in the affected
animal species?

Speaker 1 (01:07:47):
And it's hard because it's already so virulent. So right,
how could you go up from ninety percent?

Speaker 2 (01:07:53):
Right?

Speaker 1 (01:07:53):
Yeah, so no, and I haven't seen data that suggests
that it's killing more animals. It's certainly still killing hundreds
tens of thousands, if not hundreds of thousands in many outbreaks.
But yeah, so it's it's very interesting. It's going to
be important, I think, to watch what is actually happening.

(01:08:15):
And I think too, I'm sure that especially for these
last few years of outbreaks, there will be more papers
coming out that maybe look at a larger swath of
the population where these outbreaks occurred to try and get
a sense of like, what is the zero prevalence in
that population? How big were these outbreaks really? In some

(01:08:36):
studies that have looked across like endemic areas, there have
been zero prevalence studies that have estimated anywhere from like
six to eight percent of humans and eight to twelve
percent of livestock show evidence of prior infection. So this
virus is out there circulating even when we're not necessarily
seeing it cause episootics or outbreaks in humans.

Speaker 2 (01:08:59):
So what do we do about it all? Yeah, I
was just about to say, is there a vaccine in
the works.

Speaker 1 (01:09:05):
There are many so there are two already at least two,
and there might be multiple versions, but there are two
that exist for animals for livestock. Neither of them are perfect.
The live vaccine is very effective. A single dose of
the live vaccine is very effective, but it has a

(01:09:25):
lot of drawbacks. It tends to cause spontaneous abortion in
animals if they are pregnant because it is a live vaccine,
even though it's less virulent. You also can't give that
vaccine during an outbreak because it can actually end up
amplifying the outbreak. And there's always a risk because it's
a live vaccine that it would then kind of mutate

(01:09:47):
back closer to the wild type and then cause disease
outbreaks amongst animals or humans. So those are the big
drawbacks of the live vaccine. There is also an inactivated vaccine.
They require multiple doses, I think at least three doses,
which makes them more difficult to implement in a lot
of areas, and they just don't provide quite as long

(01:10:08):
lasting of protection. But they also don't have the drawbacks
that the live vaccine has, so unsurprisingly, this is one
of the main areas of research is developing a vaccine,
especially one that could be used for both livestock and humans.
There's at least one that's being studied right now in

(01:10:29):
both the UK and in Uganda, or at least when
this paper was published in twenty twenty two, it was
being studied in these areas in both livestock and humans
that was using a viral vector, very similar to some
of the COVID vaccines that we saw that use like
a viral vector as a vaccine. But there's also like

(01:10:50):
a whole bunch of different vaccine candidates that people are studying.

Speaker 2 (01:10:54):
We don't have.

Speaker 1 (01:10:55):
Any that I saw that are super close to being
ready or use in humans.

Speaker 2 (01:11:02):
Okay, that's disappointing.

Speaker 1 (01:11:06):
Yeah, but maybe by the time this episode comes out
there will be a new paper that changes that, because
I mean, as of a couple years ago, they were
definitely studying it. And I think that with all of
the advancements that we've seen in vaccine platforms since COVID,
I think that we are very likely to see the
development of vaccines for viruses like rift valley fever because

(01:11:28):
of what a huge impact it has on livestock, on economics,
and on human health and public health. So there is
a vaccine that some veterinarian laboratory personnel have gotten. Oh,
there is a vaccine that people have gotten when they're
at very high risk for infection. But it's an animal
vaccine that has never been licensed or approved for use
in any country.

Speaker 2 (01:11:48):
Interesting, Okay, yeah, someone's like, I've been vaccinated. That's very cool.
It's not approved, so.

Speaker 1 (01:11:59):
Yeah, that's real. I feel like it is one that
should get more pressed than it has gotten perhaps, well,
I mean more nervous.

Speaker 2 (01:12:10):
Absolutely, I feel like, yes, it is a scary and
potentially very impactful disease in a public health context, but
also just as a livestock disease. It's so economically devastating
and traumatizing, yes, because, like I just again, from one

(01:12:32):
day to the next, or like one week to the next,
you could lose your entire herd, your entire livelihood.

Speaker 1 (01:12:38):
It's I mean absolutely dosting the size of some of
these outbreaks. And we'll link to some papers that have
kind of details on all of the dozens of outbreaks
that have happened over even just the past twenty years.
I mean, some of them have been hundreds of thousands
of livestock it's just I mean.

Speaker 2 (01:12:55):
Horrific, unfathomable. Yeah. Yeah, Well, speaking of sources, shall we
share some sources? Let's share so you can read some more. Okay,
I'm going to shout out three in particular by Baba
at All from twenty sixteen. Has rift valley fever virus
evolved with increasing severity in human populations in East Africa

(01:13:17):
by mc millan and Hartman from twenty eighteen, Rift Valley
Fever in Animals and Humans Current Perspectives. And that modeling
paper that I mentioned in the last bit of the
history by Chemisen at All from twenty twenty four Ability
of a dynamical climate sensitive model to reproduce historical rift
valley fever outbreaks over Africa.

Speaker 1 (01:13:38):
I have a number of papers, a couple that I
wanted to give a shout out to. When was that
plus neglected Tropical disease paper? It was from twenty twenty two.
It was titled Clinical Manifestations of riftflly Fever in Human
Systematic Review and Meta Analysis. Another was from the Journal
of Veterinary Research from twenty twenty one called riftfallly fever
a growing threat to humans and animals, And there was

(01:14:00):
a number of other ones, so we will post the
list of all of our sources from this episode and
every single one of our episodes. You can get so
deep on the neuropathophysiology on our website This podcast will
Kill You dot com under the episode STAB.

Speaker 2 (01:14:16):
Thank you to Bloodmobile for providing the music for this
episode and all of our episodes.

Speaker 1 (01:14:21):
Thank you to Tom Bryfogal and Leona Scilaci for the
audio mixing.

Speaker 2 (01:14:26):
Thank you to everyone at Exactly Right.

Speaker 1 (01:14:28):
And thank you to you listeners. I hope that you
enjoyed this episode.

Speaker 2 (01:14:33):
Yeah, I hope you learned something new. That's always my hope.
I certainly did.

Speaker 1 (01:14:39):
It's our favorite thing is to learn new things.

Speaker 2 (01:14:42):
It truly, truly is. Yeah. And a special thank you
to our wonderful patrons. We appreciate your support so so
very much. It really means a lot to us, it
really does. Thank you. Well. Until next time, wash your
hands you feelthy animals.

Speaker 1 (01:15:04):
Bumba buba, bumba

Speaker 2 (01:15:15):
Bumbo ba