Speaker 1: A pathologist RS, aged thirty years, had been working with
Speaker 1: rift Valley fever virus for several weeks before the onset
Speaker 1: of his illness. On the evening of December twenty second,
Speaker 1: nineteen thirty two, he felt chilly while walking home and
Speaker 1: complained that his eyes and the calves of his legs
Speaker 1: ached during the night. His rest was disturbed by general
Speaker 1: malaise and pains, especially around the knees and hips. On
Speaker 1: awakening the second day of illness, his temperature was one
Speaker 1: oh one fahrenheit. He attempted to continue his work, but
Speaker 1: had several chills during the day and felt so miserable
Speaker 1: that he took to bed. He complained at this time
Speaker 1: of a vague soreness over his abdmen, constant dull headache,
Speaker 1: and pain behind the eyes associated with slight photophobia. There
Speaker 1: was no sore throat, rhinitis, nausea, or vomiting. He was
Speaker 1: admitted to the hospital of the Rockefeller Institute twenty four
Speaker 1: hours after the onset of symptoms. On admission, the temperature
Speaker 1: was one o two point six fahrenheit pulse respirations twenty four.
Speaker 1: The patient was definitely prostrated by his illness, but rational
Speaker 1: and cooperative. The throat culture was negative for hemolytics streptococcie
Speaker 1: and influenza bacille, and blood cultures in infusion broth remained sterile.
Speaker 1: A tentative diagnosis of riffelly fever or influenza was made.
Speaker 1: In an attempt to confirm the tentative diagnosis of riffelly fever,
Speaker 1: six ce seeds of the patient's blood was injected into
Speaker 1: six mice. All of the mice died within forty eight hours.
Speaker 1: Almost immediately after admission, the patient began to improve. The temperature,
Speaker 1: which reached a peak of one oh three point eight
Speaker 1: fahrenheit on the night of admission, fell promptly to normal
Speaker 1: within twenty four hours. The symptoms, however, abated somewhat less rapidly.
Speaker 1: By the twelfth day of illness, the patient had improved
Speaker 1: to such an extent that he was allowed to sit
Speaker 1: in a chair for a short time, and on the
Speaker 1: following day was permitted to walk a short distance. On
Speaker 1: the evening of the sixteenth day, however, he complained of
Speaker 1: pain in the life left leg. The patient was returned
Speaker 1: to bed and the leg was immobilized in an elevated position.
Speaker 1: Four days later, twentieth day of illness, the patient awakened
Speaker 1: with pain in the right chest, which was more pronounced
Speaker 1: during deep inspiration or exhalation. In the X ray photograph
Speaker 1: made at this time, there was a distinct shadow at
Speaker 1: the base of the right lung. On several occasions, blood
Speaker 1: was expectorated in small amounts. On the thirty eighth day
Speaker 1: of illness, recovery seemed to be proceeding uneventfully. On the
Speaker 1: morning of the forty fifth day of illness, however, the
Speaker 1: patient suddenly collapsed and died within a few minutes. Death
Speaker 1: was apparently due to a large embelis in the pulmonary vessels.
Speaker 1: That's a tough, tough story, yeah, and what a rollercoaster too,
Speaker 1: really is like you have no idea where it's going
Speaker 1: to go until you're there.
Speaker 2: Yeah. I don't know anything about the path of physiology
Speaker 2: of rift valley fever, so I'm very curious to know
Speaker 2: how well this fits in with like the clinical picture
Speaker 2: that has been seen, you know, not super well but interesting.
Speaker 1: But I can see how these things ended up happening,
Speaker 1: So we can when we talk at the pathology, we
Speaker 1: can kind of tie back into it.
Speaker 2: Okay, So that first hand account was from a paper
Speaker 2: by Schwenker and Rivers from nineteen thirty four titled Rift
Speaker 2: Valley Fever in Man Report of a fatal laboratory infection
Speaker 2: complicated by thrombo phlebitis. And this actually is the first
Speaker 2: recorded death due to Rift Valley fever. Oh interesting, I
Speaker 2: mean likely not the first death right humans, but the
Speaker 2: first recorded human death detailed recorded. Huh. Yeah. Hi. I'm
Speaker 2: Aaron Welsh and I'm Erin Alman Updike, and this is
Speaker 2: this podcast Will Kill You, And today we're talking about
Speaker 2: Rift Valley fever. We've had a lot of.
Speaker 1: Requests for this one, which I feel like is surprising
Speaker 1: because I knew almost nothing about it except I had
Speaker 1: heard there is Rift Valley fever, like I knew that
Speaker 1: it existed. I knew it was mosquito born. That's all
Speaker 1: I knew.
Speaker 2: Yeah, I say, I was like, oh, this is a
Speaker 2: dangerous virus. But I didn't really know much more than that.
Speaker 2: And I was kind of shocked when I got into
Speaker 2: the history of outbreaks.
Speaker 1: I am shocked at how little I knew, considering like
Speaker 1: that we were deep in disease ecology for so long.
Speaker 2: Oh yeah, I mean I still I would like flip
Speaker 2: through parasite books for fun. Yeah. Yeah, somehow just goes
Speaker 2: to show that there is no limit to the number
Speaker 2: of diseases and viruses and pathogens and parasites and fungi
Speaker 2: out there.
Speaker 1: Yeah, it's true. So with Valley fever is the one
Speaker 1: we're talking about today, but before we can tell you
Speaker 1: all about it and all the things that we learned,
Speaker 1: it's quarantine anytime.
Speaker 2: It is aaron. What are we drinking this week?
Speaker 1: We're drinking wolf in sheep's clothing.
Speaker 2: It'll make sense, it'll make sense. Sheep are involved. Wolf
Speaker 2: is the virus. I love to over explain a joke.
Speaker 2: It's well, we went back and forth by text. The
Speaker 2: wolf is the virus. The virus is the wolf. Yes, okay,
Speaker 2: that's a great name. What's in a wolf in sheep's clothing?
Speaker 2: A wolf in sheep's clothing is your basic concoction of mescal,
Speaker 2: grapefruit juice, a lemon lime soda of your choice, and
Speaker 2: you know, maybe a squirt of lime or something.
Speaker 1: And some halpinios write a little spicy mescal paloma.
Speaker 2: Yes, situationial the crucial muddled jalapenios, and we'll.
Speaker 1: Post the full recipe for that quarantini as well as
Speaker 1: the non alcoholic equally delicious plusy burrita on our website
Speaker 1: This Podcast will kill You dot Com and all of
Speaker 1: our socials, So if you're not already following us, you
Speaker 1: should because the picks are delicious.
Speaker 2: On our website This Podcast will Kill You dot Com,
Speaker 2: you can find all manner of things you know. There's
Speaker 2: transcripts for all of our episodes. You can find links
Speaker 2: to our bookshop dot org, affiliate account, our Goodreads list,
Speaker 2: music by Bloodmobile merch. We've got great merch we do.
Speaker 2: Links to Patreon, links to a submit your first hand
Speaker 2: account form, links to a contact us form. There's more
Speaker 2: there too.
Speaker 1: There's so much this podcast. Okay, dot com check it out. Yeah,
Speaker 1: if you haven't already, please check your podcast and make
Speaker 1: sure you're subscribed. If you haven't left us a review
Speaker 1: or a rating and you'd like to, now's your opportunity.
Speaker 2: You can do that right.
Speaker 1: Now, And we would so appreciate it. We would really
Speaker 1: love it. It really helps the show, So thank you.
Speaker 2: She's not lying, she's totally right. We appreciate it and
Speaker 2: it helps us. Well, then shall we get into this virus.
Speaker 2: Let's do it. Let's take a quick break and begin.
Speaker 1: I think part of what surprised me about how little
Speaker 1: I knew about Rift Valley fever is how much of
Speaker 1: a classic TPWKY story it really is. Yeah, I know
Speaker 1: that we are getting back to the roots of this
Speaker 1: podcast when I can go on the World Health Organization's
Speaker 1: website and find so much of the information that I'm
Speaker 1: looking for, and even more so when there's a page
Speaker 1: on the World Organization for Animal Health website.
Speaker 2: So buckle up.
Speaker 1: This is a really classic piece of TPWKY content. So
Speaker 1: Rift Valley fever is a disease that's caused by a
Speaker 1: virus called Rift Valley fever virus.
Speaker 2: It's not very creative.
Speaker 1: And this is an RNA virus in the genus flebovirus.
Speaker 2: I think that's how you say it.
Speaker 1: And I think that the phylogeny of this group viruses
Speaker 1: has changed relatively recently, But in any case, it's in
Speaker 1: the order Bunia viralus, which is the same group that
Speaker 1: includes hantaviruses and loss of fever virus and some others
Speaker 1: that we haven't yet covered.
Speaker 2: Have we done loss of fever.
Speaker 1: Er No, we haven't done loss of fever. But maybe
Speaker 1: people have heard of los of fever. I know, we
Speaker 1: haven't done it. Wow, Okay, there's aaron. There's so many
Speaker 1: that we haven't done yet. Yeah, but hantaviruses we have.
Speaker 1: And with the exception really of the hantaviruses and loss
Speaker 1: of fever and other arenaviruses, most all of the other
Speaker 1: viruses in this order Bunia viralis are transmitted primarily by
Speaker 1: arthropod vectors like ticks and mosquitoes, and rift Vali fever
Speaker 1: virus is no exception asterisk, but let's talk about it.
Speaker 1: So rift valley fever in humans is really considered a
Speaker 1: zoonotic disease, which means that primarily it's not affecting humans,
Speaker 1: it's infecting animals, and it's generally considered to be only
Speaker 1: these spillover events that end up causing disease in humans.
Speaker 1: So there has to generally be some kind of animal outbreak,
Speaker 1: which we call an epizootic before there is then a
Speaker 1: human outbreak. And this virus infects a pretty wide variety
Speaker 1: of animals, and the ones that end up being most
Speaker 1: important for us as humans are our livestock. So this
Speaker 1: virus infects cattle, sheep, goats, and other small ruminants and
Speaker 1: camels and sheep and goats tend to be the most
Speaker 1: severely affected. And it's transmitted to these livestock primarily by mosquitoes,
Speaker 1: but not just any one mosquito, no, no, no, whole
Speaker 1: bunches of mosquitoes in multiple different genera, mostly transmitted by
Speaker 1: eighties mosquitoes of dengey fever, yellow fever chickengunyet like all
Speaker 1: the viruses eighties mosquitoes as well as a qlex mosquitoes
Speaker 1: of like West Nile virus and Japanese encephalitis virus fame.
Speaker 2: It's so strange because usually viruses are so hyper adapted
Speaker 2: to their mosquito vector hosts, like that specific species. But
Speaker 2: this isn't. So What's how.
Speaker 1: I have so many questions, Aaron, about the path of
Speaker 1: physiology or the like the life cycle of this virus
Speaker 1: in mosquitoes because it it doesn't We don't have as
Speaker 1: much information as I expect, Okay, and it's really interesting.
Speaker 1: So there's at least like fifty different species of mosquito
Speaker 1: that have been found to harbor this virus, and the
Speaker 1: transmission is like usually when we picture like a transmission
Speaker 1: cycle among let's say you know vector host, maybe there's
Speaker 1: a secondary host. It's like a circ goal, right, the
Speaker 1: transmission of this virus. When you look at this cycle,
Speaker 1: it's not a circle. It's like a circle with a
Speaker 1: line and another line and like two other branches.
Speaker 2: It's get the mess create a peometry.
Speaker 1: Yeah, so how does it go?
Speaker 2: Really?
Speaker 1: Usually when we're covering a vector borne disease on this podcast,
Speaker 1: I can start like this, and I'll start like this
Speaker 1: for this episode. Ready, a female mosquito, it's always a
Speaker 1: female mosquito takes a blood meal from a host, let's
Speaker 1: call it a sheep for accuracy. It drinks up some
Speaker 1: of the virus in that blood meal because the sheep
Speaker 1: is infected. And after some amount of time in the
Speaker 1: mosquito and varying amounts of this virus moving through the mosquito,
Speaker 1: it maybe makes it to the salivary glands or something
Speaker 1: like that, and then that mosquito takes another blood meal,
Speaker 1: spits the virus into the host, and boom, Now you've
Speaker 1: completed the transmission cycle. And cycle can happen in Withfalley fever.
Speaker 1: But how long does it have to exist in the mosquito?
Speaker 1: How long does this virus have to be there?
Speaker 2: I don't know.
Speaker 1: What does it do inside this mosquito?
Speaker 2: I don't know.
Speaker 1: Where does it go? Does it travel to the salivary
Speaker 1: glands or does it not?
Speaker 2: I don't know. I don't know, Aaron, Okay, and I
Speaker 2: anticipate that the answer to this question is I don't know,
Speaker 2: but huh. Our different mosquito species differently capable of harboring
Speaker 2: transmitting the.
Speaker 1: Virus almost certainly yes, which one's more likely than less?
Speaker 2: I don't know. Here's where we.
Speaker 1: Can add another layer of complication. In addition to that
Speaker 1: transmission cycle, this virus can also be and is known
Speaker 1: to be, transmitted from female mosquitos into their eggs. This
Speaker 1: is called vertical transmission, and we know this happens at
Speaker 1: least in some way species of eighties mosquitoes, but maybe
Speaker 1: not in all species.
Speaker 2: We're not sure, which has huge implications for the distribution
Speaker 2: of this virus in the landscape and the potential for
Speaker 2: outbreaks to happen in subsequent years, even outside of like
Speaker 2: big outbreaks like the inter epidemic years or whatever. It
Speaker 2: sure does, Aaron.
Speaker 1: You're one hundred percent right, because it means that Mosquito
Speaker 1: babies are essentially born infected, so they can inject virus
Speaker 1: into their host with the very first blood meal that
Speaker 1: they take. So not only can this virus potentially persist
Speaker 1: like among different seasons without necessarily needing to have reservoir
Speaker 1: hosts that are infected, you also can then have viral
Speaker 1: transmission even if mosquitoes aren't living long enough to transmit
Speaker 1: from animal to animal to animal, because the very first
Speaker 1: blood meal that they take, they can potentially transmit this virus.
Speaker 2: Okay, so here's another question. Though it's not just the mosquito.
Speaker 2: It's not just the mosquitoes. It's not a question.
Speaker 1: But you know where I'm going with that. There's let's
Speaker 1: keep going, shall we. I said that this was a web,
Speaker 1: so we shall continue along this transmission web. Once an
Speaker 1: animal host is infected, and again mostly in this case
Speaker 1: we're talking about livestock, ruminants, sheep, cattle, goats, camels, all
Speaker 1: of these animals also have vertical transmission themselves. So if
Speaker 1: a pregnant animal gets infected from a mosquito, it will
Speaker 1: almost inevitably pass that virus through the placenta to their offspring,
Speaker 1: and this almost always causes spontaneous abortion or pregnancy loss.
Speaker 1: This virus can also be transmitted from mosquitoes to other wildlife,
Speaker 1: and we don't fully understand the whole wildlife cycle.
Speaker 2: That's just like a black box.
Speaker 1: We know that it happens, but we don't know what
Speaker 1: hosts are important. Are they amplifying hosts or are they not,
Speaker 1: et cetera.
Speaker 2: Are they maintenance hosts?
Speaker 1: Yeah, But then we get to humans. How do we
Speaker 1: get infected in this tangled web. Well, it could be
Speaker 1: the same way that our animal friends are getting infected
Speaker 1: via these mosquitoes, But what's far more common is that
Speaker 1: humans are infected from our infected animal friends themselves, either
Speaker 1: from direct contact with something like their blood, their raw milk,
Speaker 1: or other bodily fluids, directly getting into our eyes, mouth
Speaker 1: or other mucous membranes, or through breaks in our skin
Speaker 1: in the process of caring for or slaughtering these animals,
Speaker 1: or from inhaling aerosolized bodily fluids. So it's usually a
Speaker 1: kind of more direct transmission from animal to humans that
Speaker 1: ends up causing disease in humans. And then we as
Speaker 1: humans can also pass this virus through the placenta and
Speaker 1: potentially cause infection in a fetus. The only good thing
Speaker 1: thus far is that horizontal meaning human to human transmission
Speaker 1: has yet to be documented, and the same is true
Speaker 1: for direct transmission from animals to animals like among a herd.
Speaker 1: So then why is it that humans can get infected
Speaker 1: from animals?
Speaker 2: We don't know.
Speaker 1: Is it just because of the ways that we happen
Speaker 1: to be interacting with and handling their tissues and bodily fluids?
Speaker 2: I don't know.
Speaker 1: But that is the like good news that I can
Speaker 1: say about the transmission of this virus.
Speaker 2: Okay, I mean that makes sense because it's not like
Speaker 2: the animals are doing the slaughtering and inhaling the blood.
Speaker 2: It's it's yeah, humans are doing that. Okay. How many
Speaker 2: viral particles ooh? No? Idea great question though, okay, okay?
Speaker 2: And it is through the aerosolization, like, is it also
Speaker 2: contaminated surfaces? Is there? What's the durability of this virus
Speaker 2: in the environment.
Speaker 1: There's so many other questions. I could have tried to
Speaker 1: go down rabbit holes to answer that. I don't have
Speaker 1: the answers for aaron. Yes, so there's differential virulence and
Speaker 1: that's likely due to like like you asked how many
Speaker 1: viral articles does it take and things like that. People
Speaker 1: get more or less sick depending on what route they
Speaker 1: were more likely exposed to, and aerosol transmission seems to
Speaker 1: be the most virulent, so most likely to cause really
Speaker 1: severe disease is when it's you're inhaling it and it's
Speaker 1: going into your mucous membranes that way. The other common
Speaker 1: way that people get infected, and this could be from
Speaker 1: contaminated surfaces, but it's through contact with like broken skin,
Speaker 1: so like you have an injury and blood or something
Speaker 1: like that gets into your bloodstream from that. So those
Speaker 1: are kind of the two most common ways. There have
Speaker 1: been some cases of things like raw milk, which means
Speaker 1: that could be potentially an oral or a GI exposure,
Speaker 1: but we have just less data on that overall.
Speaker 2: Interesting. Okay, yes, this is maybe jumping ahead a little bit,
Speaker 2: but jen in an outbreak where it's not just livestock
Speaker 2: impacted but also humans, is there a any known breakdown
Speaker 2: between how people have gotten exposed, Like what proportion is
Speaker 2: mosquito versus direct contact that kind of thing.
Speaker 1: Of all the outbreaks that we have good data on
Speaker 1: primarily are happening from direct contact with animal fluids. It
Speaker 1: is very likely that mosquito born transmission absolutely plays a
Speaker 1: role in some outbreaks, but it seems that overall across
Speaker 1: the board, it is animal to human transmission that causes
Speaker 1: the vast majority of human cases. Okay, which means that
Speaker 1: the people at highest risk are people who work in
Speaker 1: industries where they are coming into contact with animals. Okay,
Speaker 1: But as I'm sure you know, and we'll probably talk about,
Speaker 1: some of the historic outbreaks have been very large, which
Speaker 1: means that certainly there's other things that are going on,
Speaker 1: and why in those cases did the outbreaks get so big.
Speaker 1: They're presum probably must have been also mosquito borne transmission happening.
Speaker 1: So yes, it definitely can happen. But does it also
Speaker 1: just depend on, like our mosquitos more likely to bite
Speaker 1: humans or to bite animals, and what mosquito species are
Speaker 1: circulating in those regions, because again, this is so many
Speaker 1: different mosquito species. So yeah, there's a lot, there's a
Speaker 1: lot of layers, and we don't have great data on
Speaker 1: a lot of details.
Speaker 2: On a lot of these outbreaks. Yish that we had
Speaker 2: more data. I wish that we had more data. I mean,
Speaker 2: don't we all don't we?
Speaker 1: Yes, we do know some more about like what does
Speaker 1: this disease do, Like what does it look like if
Speaker 1: an animal or if a person gets rifally fever. Unsurprisingly,
Speaker 1: given that this is a virus that infects so many
Speaker 1: different species, it presents very differently across different animals, but
Speaker 1: even within humans it can present very differently across the board. Though,
Speaker 1: we know that there's two main cell types in mammalian
Speaker 1: bodies that this virus is predominantly infecting, and everyone who
Speaker 1: listens to this show is well aware at this point
Speaker 1: that a virus has to infect a host cell in
Speaker 1: order to use our machinery to replicate. So which cells
Speaker 1: it's infecting tend to be really important in what kind
Speaker 1: of symptoms and what kind of disease we see. So
Speaker 1: in the case of rift Valley fever, the two main
Speaker 1: cell types that this virus is infecting are liver cells,
Speaker 1: so we'll talk about what that ends up doing, and
Speaker 1: then monocytes, which are a type of white blood cell.
Speaker 1: And so especially in severe cases, the liver is one
Speaker 1: of the main sites of damage. So what does that
Speaker 1: end up actually looking like If we look at animals Again,
Speaker 1: the symptoms will vary depending on the type of animal
Speaker 1: that's infected, as well as how old that animal is,
Speaker 1: because universally, young animals so fetuses as well as newborn animals,
Speaker 1: are much more severely affected than older animals. But in general,
Speaker 1: in almost all animals that are infected, all of these
Speaker 1: livestock animals, we see things like fever. We'll see the
Speaker 1: animal stop eating, they stop like moving about, They don't
Speaker 1: really like walk around or get up and go around.
Speaker 1: They become really like listless and lethargic. Especially in sheep,
Speaker 1: you might start to see evidence of gi inflammation, abdominal pain,
Speaker 1: bloody diarrhea, and these animals are like visibly in pain
Speaker 1: and uncomfortable. But the way that this virus ends up
Speaker 1: wiping out entire populations of livestock is because it passes
Speaker 1: through the placenta and then causes spontaneous abortions in pregnant
Speaker 1: animals and then has massive mortality rates in newborn and
Speaker 1: young animals. So in these livestock herds, especially in lambs
Speaker 1: and kids which are baby goats, the more mentality rate
Speaker 1: can be as high as seventy to one hundred percent.
Speaker 1: It's devastating it's devastating, and even in adult sheep and
Speaker 1: things like baby cows or calves and adult cattle, the
Speaker 1: mortality rates can be as high as twenty to seventy percent.
Speaker 1: So this is a very lethal infection for livestock animals.
Speaker 1: When it comes to humans, there is a really wide
Speaker 1: range of how this disease can present. Most papers across
Speaker 1: the board estimate that about fifty percent of people who
Speaker 1: are infected are essentially asymptomatic, like don't really show any
Speaker 1: symptoms whatsoever. And most people who do have symptoms will
Speaker 1: have a relatively mild disease and only a small percentage
Speaker 1: And most papers say maybe one to two percent develop
Speaker 1: severe symptoms, and we'll talk about what those severe symptoms
Speaker 1: look like. But I want to caveat early on those numbers,
Speaker 1: because a it seems like maybe that one to two
Speaker 1: percent is an underestimate for recent outbreaks or more modern outbreaks,
Speaker 1: And some papers cite this number instead of saying one
Speaker 1: to two percent of all cases, they'll say it's like
Speaker 1: eight to ten percent of symptomatic cases, Okay, And I
Speaker 1: feel like looking at it that way really changes your
Speaker 1: perspective on this disease, because as we'll go through some
Speaker 1: of these symptoms. This can be incredibly terrifying and really severe,
Speaker 1: and so I think trying to understand how big are
Speaker 1: these outbreaks that we're talking about and how many people
Speaker 1: are affected are really really important. So let's talk about
Speaker 1: what it ends up looking like. If somebody is going
Speaker 1: to show symptoms of refali fever.
Speaker 2: Symptoms usually start between.
Speaker 1: Two to six days after exposure, and it usually starts
Speaker 1: as the name suggests, with a fever along with a headache.
Speaker 1: You'll have muscle or joint pain. Very often we see
Speaker 1: some like neurologic symptoms like vertigo or like in the
Speaker 1: first hand account that photophobia.
Speaker 2: Like it hurts to look at light.
Speaker 1: Yeah, you might have nausea or vomiting, and then if
Speaker 1: it remains a mild case, then this might last anywhere
Speaker 1: from like a few days, like four days to a
Speaker 1: week or so, and then often that person will get better.
Speaker 1: Sometimes it's not uncommon that people will have like a
Speaker 1: bi phasic illness, which means they'll get better, and then
Speaker 1: a couple of days later, their fever will spike again
Speaker 1: and they'll get sick for another few days before they
Speaker 1: improve for good. But there are several ways, three different
Speaker 1: ways really that this can cause a much more severe illness.
Speaker 2: Here's the three ways.
Speaker 1: It can infect your eye, it can infect your brain
Speaker 1: and spinal cord, or it can destroy your liver, and
Speaker 1: then you have a hemorrhagic illness.
Speaker 2: So let's go through those. And these are not mutually exclusive.
Speaker 1: They're not mutually exclusive, but they're very different, and so
Speaker 1: I don't know how often they happen altogether. Okay, So
Speaker 1: in some people, this virus seems to infect the eye,
Speaker 1: the back of the eye, and it can infect like
Speaker 1: a whole variety of parts of that. It could be
Speaker 1: the retina itself, it could be your nerve in your eye,
Speaker 1: it could be the macula, a whole bunch of different parts.
Speaker 1: And in those cases that person might have had the
Speaker 1: same mild illness that I already described, get better, and
Speaker 1: then a week or several weeks later, they'll start to
Speaker 1: have blurry vision or decreased vision. And then this can
Speaker 1: last a few months or it can end up causing
Speaker 1: permanent damage, depending on which part of the eye ends
Speaker 1: up being infected with this virus. Why the eye, Why
Speaker 1: the eye, I don't know. Is it just an easy
Speaker 1: target there's good blood supply there is it just that
Speaker 1: that's where the virus was close to. I have no idea. Also,
Speaker 1: why is it so long after the initial infection. I
Speaker 1: don't know the specific path of physiology of.
Speaker 2: What's going on.
Speaker 1: But that's not the only way that you can see
Speaker 1: this delayed response. Another way that it could go is
Speaker 1: that again, a few weeks or even months after an
Speaker 1: initial infection, somebody might come down with a severe headache
Speaker 1: and signs of brain inflammation that might look like confusion, disorientation, vertigo,
Speaker 1: even things like hallucinations or loss of memory. And this
Speaker 1: can progress to seizures, coma, and potentially death. And this
Speaker 1: is all a me ninjo encephalitis, So inflammation that's happening
Speaker 1: in the brain and the spinal cord as a result
Speaker 1: of ri Valley fever.
Speaker 2: Okay, And so this is like a consequence. This isn't
Speaker 2: the virus attacking those things necessarily. It's like a consequence
Speaker 2: of our immune responses reaction to the virus.
Speaker 1: I don't know, Aaron, okay, because we know a lot,
Speaker 1: and I'll link to a bunch of specific papers that
Speaker 1: look at like the gross anatomic pathology that's happening in
Speaker 1: these cases. We know that it's a lot of inflammation.
Speaker 1: Is it that virus is laying latent and then reactivating
Speaker 1: and causing this or is it that you're having delayed
Speaker 1: immune reaction to the virus. I am not one hundred
Speaker 1: percent sure from all of my reading, and it could
Speaker 1: be that I'm not interpreting the reading correctly. Given the delay,
Speaker 1: it seems more likely that it's an inflammatory reaction, like
Speaker 1: an immune response, But it's a little bit unclear to
Speaker 1: me from all of the reading that I did.
Speaker 2: Well, and I will say too in that first hand account,
Speaker 2: they talked about how as this person you know, seemed
Speaker 2: to get better and then got worse and worse, and
Speaker 2: then got better again and then worse later on, they retested,
Speaker 2: they retook blood and re injected it into mice to
Speaker 2: see is this still rift valley fever and the mice refine.
Speaker 1: Okay, interesting, So that suggests that it's more immune mediated.
Speaker 2: I mean pay Pers nineteen thirty four, like yeah, but
Speaker 2: still but still.
Speaker 1: And just timing wise, that's sort of what it seems
Speaker 1: like right right. This kind of neurologic disease, when it happens,
Speaker 1: can cause long term neurologic complications, and some sources suggest
Speaker 1: that it doesn't tend to cause death, But there was
Speaker 1: an outbreak in Saudi Arabia in the early two thousands
Speaker 1: which like fifty percent of people that ended up having
Speaker 1: neurologic complications died from that. So I don't think it's
Speaker 1: entirely accurate to say that you would never have death
Speaker 1: as a result of this type of neurologic manifestation of
Speaker 1: Rift Valley fever. Yeah, but it's less common than the
Speaker 1: final manifestation, which is the most severe, and that is
Speaker 1: when this virus causes a hemorrhagic disease, and it does
Speaker 1: this because of damage to the liver. So the way
Speaker 1: that this might present is that during that acute illness,
Speaker 1: So during that time when someone is sick with a fever, etc.
Speaker 1: Someone might then start to appear jaundiced, so their skin
Speaker 1: or their nails or their eyes are starting to turn yellow,
Speaker 1: and that's a sign of liver damage because that yellowness
Speaker 1: is caused by something called bilirubin building up in your
Speaker 1: skin or your eyes because your liver can't break it
Speaker 1: down into the form that you can excrete. And as
Speaker 1: your liver gets damaged because your liver is also in
Speaker 1: charge of making most all of our clotting factors. Now,
Speaker 1: all of a sudden, your blood can't clot the way
Speaker 1: that it should, so you start to have signs of bleeding.
Speaker 1: And this could be things like large bruises or purpura,
Speaker 1: which are these big, dark purple splotches on the skin
Speaker 1: that are essentially just signs of bleeding. Underneath the skin,
Speaker 1: you might see bleeding from mucus membranes like your nose
Speaker 1: or your gums. You'll see bloody vomiting or diarrhea, really
Speaker 1: heavy menstrual bleeding. If this person is already hospitalized and
Speaker 1: getting poked for things like blood draws or ivs, they'll
Speaker 1: start to have bleeding from these sites of napuncture. And
Speaker 1: this form of hemorrhagic disease is the most severe form.
Speaker 1: About fifty percent of people who develop hemorrhagic disease from
Speaker 1: refelly fever will usually die within three to six days
Speaker 1: of the first sign of these hemorrhagic symptoms.
Speaker 2: Do we know what factors make someone more likely to
Speaker 2: develop the hemorrhagic form, or the ocular form, or the
Speaker 2: neurological form, or be completely asymptomatic. Yeah, it's such a
Speaker 2: good question.
Speaker 1: It's probably similar to different species of animals that we see.
Speaker 1: It likely depends on host factors, right, so like who
Speaker 1: you are and what your immune system does in response
Speaker 1: to this virus, but also things like the root of transmission.
Speaker 1: So overall, like I said, the intr nasal or airborne
Speaker 1: transmission seems to be more likely to cause severe disease
Speaker 1: than in animal models where we've like injected this virus
Speaker 1: into animals. But beyond that, there's like a lot that
Speaker 1: we don't know and don't understand. And again I have
Speaker 1: several papers that go really deep into detail on what
Speaker 1: we do know, which is a lot about like viral
Speaker 1: receptors and the histopathology of like what's happening in your
Speaker 1: liver and what's happening in where in your brain? Is
Speaker 1: there inflammation? But like, how does this actually happen? Why
Speaker 1: are some people so severely affected in others are not?
Speaker 1: I don't have a good answer to that question.
Speaker 2: Okay, Yeah, and you mentioned that the virus can also
Speaker 2: be transmitted from pregnant person to fetus. What does the
Speaker 2: infection look like in that situation?
Speaker 1: Yeah, it depends and we don't have a lot of
Speaker 1: data on this because there haven't been that many well
Speaker 1: documented cases. There's been enough to show that it is
Speaker 1: very likely that this virus can cross the placenta and
Speaker 1: infect a fetus. It can cause, potentially, like it does
Speaker 1: in animals, spontaneous abortion, but again, we haven't seen significant
Speaker 1: increased rates of spontaneous abortion in areas where there have
Speaker 1: been outbreaks, which is good news. But certainly it can
Speaker 1: also then cause infection in a newborn, and because newborns
Speaker 1: have very little immune system, that infection is likely more
Speaker 1: likely to be severe. So there have been cases of
Speaker 1: neonatal deaths from this virus.
Speaker 2: And where do we stand on treatment?
Speaker 1: Yeah, we don't stand Okay, there are no treatments that
Speaker 1: are specific for this virus, which means that there's a
Speaker 1: lot of things that we have to do to try
Speaker 1: and prevent it. So mosquito control is an important part
Speaker 1: of that. Vaccines and there are a couple of different
Speaker 1: vaccines for live stock, no vaccines for humans, but there
Speaker 1: are both like live attenuated vaccines, and there are inactivated
Speaker 1: or killed virus vaccine. Pros and cons to both of those,
Speaker 1: but they both exist and they both can be used both,
Speaker 1: like on a regular basis in endemic areas in livestock
Speaker 1: as well as in the case of outbreaks, at least
Speaker 1: the inactivated form. But yeah, that's rip valley fever.
Speaker 2: It is. It can be a really severe infection.
Speaker 1: And we'll talk more in detail about recent outbreaks that
Speaker 1: have happened, Like why is it so severe sometimes or
Speaker 1: is it getting more severe?
Speaker 2: I don't know, Aaron, that is a great question. It is.
Speaker 1: I still have a question, so, Aarin, when did we
Speaker 1: first find out about this virus? When did it spill
Speaker 1: over from animals to humans?
Speaker 2: What do we know about it? Let me see what
Speaker 2: I can answer right after this break on the surface,
Speaker 2: history and disease ecology seem like two entirely different fields. History,
Speaker 2: of course, deals with past events, especially from a human perspective,
Speaker 2: while disease ecology examines the relationship between a pathogen or pathogens,
Speaker 2: its host or hosts, and the environment. Like what would
Speaker 2: you learn in a history class that would be repeated
Speaker 2: in a class on disease ecology besides the discovery of
Speaker 2: one disease or another. Not a lot, Aaron. That's why
Speaker 2: I love our podcast. We do it. But as I
Speaker 2: was reading about rift valley fever, the first described outbreaks,
Speaker 2: the potential impact of climate change and land you change
Speaker 2: on future outbreaks. I realized how similar the approach that
Speaker 2: these two fields take really is, because it all comes
Speaker 2: down to understanding the context, why did this happen when
Speaker 2: it did? And what can the past tell us about
Speaker 2: the future. Oh love that? Yeah, I know, this is
Speaker 2: my hyper nerd. I was like, whoa dies? Easy? College
Speaker 2: in history the same thing. I finally get why I
Speaker 2: love this. It finally all makes sense. It all makes sense.
Speaker 2: But let's start with the first part of that, the
Speaker 2: why did this happen when it did? Getting at the
Speaker 2: earliest known emergence of rift valley fever. In August of
Speaker 2: nineteen thirteen, the Department of Agriculture of quote unquote British
Speaker 2: East Africa published its annual report on the whole. It's
Speaker 2: some pretty dry reading, crop counts, detailed descriptions of personnel vacations,
Speaker 2: the number of ingoing and outgoing letters for each sub department. Like,
Speaker 2: do you want to know how many letters the Veterinary
Speaker 2: department received and wrote in nineteen thirteen? I actually do.
Speaker 2: It's sixty eight hundred. Wow, it's more than I thought, yeah,
Speaker 2: that seems like a lot.
Speaker 1: I know, they didn't have email, thinking about how many
Speaker 1: emails they probably send now.
Speaker 2: But I know it's kind of I was like, wow,
Speaker 2: that's that's that's a lot. It's a lot. I mean,
Speaker 2: that's a lot of letters. And these reports also included
Speaker 2: casual mentions of land theft and forceful removal under the
Speaker 2: guise of manifest destiny. Ah yeah, right, so quote in
Speaker 2: June nineteen twelve, the removal of the Massai and their
Speaker 2: stock from Lykipia was commenced and was brought to a
Speaker 2: successful conclusion on the twenty seventh of March nineteen thirteen. Wow.
Speaker 1: Imagine just talking about like decimating human populations and forcibly
Speaker 1: removing human beings from their home that way cool.
Speaker 2: Yeah, yeah, I mean, success definitely in the eye of
Speaker 2: the beholder in that successful conclusion, because just for a
Speaker 2: little bit of extra context, this removal broke the nineteen
Speaker 2: oh four promise that the British had made to the
Speaker 2: Massai to stop taking their land, which they ultimately stole
Speaker 2: about seventy percent of to make space for the incoming settlers.
Speaker 2: And they were like, oh, the Lykipia Plateau being at
Speaker 2: higher elevation, it's going to be more hospitable to the
Speaker 2: Europeans that are coming. Like it's it's just all part
Speaker 2: of it.
Speaker 1: Yeah.
Speaker 2: Yeah. But if you keep scrolling past this detached reporting
Speaker 2: of you know, land theft and so on, you'll eventually
Speaker 2: come to a mention of a devastating disease impacting sheep. Quote.
Speaker 2: A mortality of ninety percent was recorded among the lambs
Speaker 2: at government Farm Naivasha. Other farms in the Rift Valley
Speaker 2: also suffered considerable loss. In some cases, the symptoms were
Speaker 2: very acute and death occurred within a few hours. In others,
Speaker 2: the disease ran a more or subacute or chronic course.
Speaker 2: In the acute form, the only symptoms shown were dullness,
Speaker 2: rapid respirations, collapse, and death within four hours. In post mortem,
Speaker 2: the liver was found to be soft and friable and
Speaker 2: the kidneys congested. In the subacute or chronic form, the
Speaker 2: umbilicus was incompletely closed and swelling of the joints occurred.
Speaker 2: Investigation pointed to the disease resulting from infection gaining entrance
Speaker 2: through the umbilicus end quote. Yeah. The sheep that were
Speaker 2: primarily impacted by this disease were marino, which were introduced
Speaker 2: for their wool, but there didn't seem to be much
Speaker 2: follow up or concern about this particular disease, perhaps because
Speaker 2: quote the setback was only a temporary one end quote.
Speaker 2: So this brief mention from nineteen twelve, buried in pages
Speaker 2: upon pages of bureaucratic minutia, stands out as the first
Speaker 2: description of what was likely riffed vlley fever. Yeah, why
Speaker 2: then why nineteen twelve?
Speaker 1: Right? Just because you brought all them sheeps there.
Speaker 2: I mean, that's part of it. But it also does
Speaker 2: seem to impact the native species there as well. So
Speaker 2: maybe it's just visibility, like these marino sheep were more susceptible.
Speaker 2: That's part of it. But I think there are some
Speaker 2: other things going on too. So later genetic analyzes would
Speaker 2: place the origin of the Rift valley fever virus as
Speaker 2: recently as the eighteen eighties to eighteen nineties. What Yeah,
Speaker 2: So it could have just been that this was one
Speaker 2: of the earliest outbreaks that this virus caused. Interesting, So
Speaker 2: where did this virus come from? Great question? I don't know,
Speaker 2: because also viruses do this thing where one strain tends
Speaker 2: to dominate in an outbreak, and it replaces all the
Speaker 2: other strains and kind of makes it look like it's
Speaker 2: the only one. And so this could underestimate how old
Speaker 2: the virus truly is. It is a lot older, but
Speaker 2: it's just sort of doing this whole strain replacement type
Speaker 2: of thing. But regardless of when the virus evolved, it
Speaker 2: likely had caused infections prior to nineteen twelve. And the
Speaker 2: reason though that it was first described then is probably
Speaker 2: because of colonization, right, importing merino sheep, which might be
Speaker 2: more susceptible to the virus as we talked about, But
Speaker 2: also there's the looking for it in these agricultural reports.
Speaker 2: The British were monitoring their investments, seeing how well the
Speaker 2: introduced crops and livestock like marino sheep did on the
Speaker 2: lands that they stole, and noting what diseases posed a
Speaker 2: threat to their income, like rift valley fever. This is
Speaker 2: the reason that tropical medicine was founded as a field
Speaker 2: of study right to better understand, prevent and treat the
Speaker 2: diseases that were prevalent in an area undergoing colonization. The
Speaker 2: chief veteran officer who made the initial report R. J.
Speaker 2: Storty wasn't noting this sheep disease out of academic curiosity,
Speaker 2: but out of a oh, this might be something we
Speaker 2: have to look out for as suttlers set up their
Speaker 2: farms here type of a thing, right, Our E. Montgomery,
Speaker 2: the veterinary pathologists at the time, even signed off his
Speaker 2: report with quote in conclusion, I may add that only
Speaker 2: such diseases as appeared to me to possess considerable interest
Speaker 2: to the stock owner have been dealt with in this report.
Speaker 2: There have been a considerable number of others, which are
Speaker 2: as yet fortunately of minor importance. I consider it our duty,
Speaker 2: so far as possible, to undertake the preliminary investigation of
Speaker 2: all diseases which come within our knowledge, and by doing so,
Speaker 2: to be in some measure prepared for eventualities end quote.
Speaker 2: Science and the questions that we ask in science have
Speaker 2: always been guided by certain values or principles or interests. Yeah,
Speaker 2: and I just I feel like it's that part doesn't
Speaker 2: really get highlighted a whole lot inside. Oh, no, this type.
Speaker 1: Because it is right, Yeah, stories of like discovery for
Speaker 1: discovery's sake, or like this is so cool and interesting,
Speaker 1: And then was used.
Speaker 2: But yeah, no, I mean.
Speaker 1: Much of the time specific things were being studied at
Speaker 1: the bottom line for money.
Speaker 2: Yeah, I mean, then the Chief Veterinary Officer for the
Speaker 2: Department of Agriculture wasn't just like screening sheep left and right.
Speaker 2: The more interested in diseases affecting sheep, then the disease
Speaker 2: is affecting wildlife because sheep was where the money was.
Speaker 2: Not wildlife. Okay, but what happens next? Right, like what
Speaker 2: happens after nineteen twelve, Well, nearly twenty years would pass
Speaker 2: before the disease appeared in another scientific publication, one that
Speaker 2: would give it its name and identify the causative agent.
Speaker 2: In nineteen thirty one, Dabney and Hudson from the Division
Speaker 2: of Veterinary Research, Kenya Colony described a devastating outbreak of
Speaker 2: unknown cause in sheep Merino sheep on a farm in
Speaker 2: the Rift Valley. The disease primarily impacted newborn lambs or
Speaker 2: pregnant sheep. At the start of the outbreak, sixty of
Speaker 2: the eighty lambs born died within a matter of weeks.
Speaker 2: The authors noted that the farm manager chose July and
Speaker 2: August as the lambing season. That year, which was somewhat unusual.
Speaker 2: Normally it was May or October to November. Right, So
Speaker 2: you choose like when the lambs are born. Sorry, how
Speaker 2: do you choose that you put the sheep together at
Speaker 2: a certain time? Oh wow, yeah, I know you well,
Speaker 2: And you do this so that you can time it
Speaker 2: with like when rainfall, when grass is available, grazing lands,
Speaker 2: et cetera. Interesting, Okay, so why July and August of
Speaker 2: that year. Well, it turns out that in that same year,
Speaker 2: the area had received an unusually large amount of rainfall,
Speaker 2: over forty five inches compared to the annual average of
Speaker 2: twenty five which is a ton. So this meant more
Speaker 2: grazing habitat during the dry season, and so the manager
Speaker 2: figured it would be safe to lamb in July and August,
Speaker 2: especially if the heavy rains in the beginning of the
Speaker 2: year were repeated in November, which would make it harder
Speaker 2: on the lambs that were born then. So you kind
Speaker 2: of just like hedging your bets, like, well, things are
Speaker 2: looking good right now, let's lamb right now, or like
Speaker 2: you know, however, many months from now and the rainfall
Speaker 2: and mosquitoes the excess to rainfall. Ye, have also meant
Speaker 2: more habitat for other critters like midges, which can transmit
Speaker 2: a virus that causes the livestock disease blue tongue, which
Speaker 2: I also saw peek in that year, and mosquitoes, which
Speaker 2: of course carry the riffed felly fever virus. Those sixty
Speaker 2: lamb deaths in early July turned out to be only
Speaker 2: the tip of the iceberg, as the disease tore through
Speaker 2: the flock, killing lambs and use within hours of the
Speaker 2: first symptoms appearing. By August tenth, nineteen thirty, about a
Speaker 2: month after the outbreak began, quote, the total mortality in
Speaker 2: lambs had reached approximately thirty five hundred and upwards of
Speaker 2: twelve hundred us had died. Wow. I think it was
Speaker 2: a mortality of ninety five percent. Oh my god. Yeah.
Speaker 2: The farm manager was desperate to save the surviving sheep,
Speaker 2: and so he transported them to another farm higher up
Speaker 2: around seven thousand to eighty five hundred feet in altitude,
Speaker 2: which is twenty one hundred and twenty six hundred meters
Speaker 2: other farm. The original farm was about fifty five hundred
Speaker 2: to six thousand feet seventeen hundred to eighteen hundred meters
Speaker 2: after arriving there. At higher up the deaths continued for
Speaker 2: a few days but eventually stopped. Okay, but the disease
Speaker 2: continued on on the original farm for months after. And
Speaker 2: so this could be because there aren't as many mosquitoes
Speaker 2: at higher elevations, maybe like the temperatures keep it down,
Speaker 2: or the humidity or whatever it is, or the mosquitoes
Speaker 2: that carry the virus don't live at higher elevations even
Speaker 2: if there are other mosquitoes there, or the mosquitoes at
Speaker 2: those higher altitudes just weren't infected. And so to try
Speaker 2: to answer this, I did a little bit of digging
Speaker 2: and found a twenty sixteen paper that noted that the
Speaker 2: risk of Rift Valley fever tended to go down as
Speaker 2: altitude went up. But it doesn't seem like there's been
Speaker 2: extensive research about the altitudinal range of the vector mosquitoes
Speaker 2: or you know, like all of these questions that are
Speaker 2: like are mosquitoes capable of transmitting the virus existing or
Speaker 2: living at higher altitudes?
Speaker 1: Right? Well, and it's hard because there's so many species
Speaker 1: erin like which one do you pay?
Speaker 2: Many species? Right? Yeah? And then like if higher altitude
Speaker 2: means less likely infection. Will that change is the climate changes, probably,
Speaker 2: but I'm getting ahead of myself. Dobney and Hudson, the
Speaker 2: authors of this nineteen thirty one paper, got to the
Speaker 2: farm and began their susceptibility tests, their post mortems, their analyzes.
Speaker 2: They isolated a virus that they named the Rift Valley
Speaker 2: fever virus, found that it caused the highest mortality in sheep,
Speaker 2: but that goats and cattle could also be infected, as
Speaker 2: could humans. Quote. During the course of the investigation, all
Speaker 2: the four Europeans engaged developed a dangae like fever, which
Speaker 2: we now know to have been due to infection with
Speaker 2: the virus. The first person to be attacked was mister F. Lyons,
Speaker 2: the laboratory assistant in charge of the exposure experiment on
Speaker 2: the farm where the disease first appeared. Mister E. J. Hall,
Speaker 2: who assisted in the laboratory investigation, was next attacked a
Speaker 2: few days later. Both writers developed symptoms within a few
Speaker 2: hours of each other. In every case, the onset of
Speaker 2: the attack was characterized by a very brief period of
Speaker 2: general malaise, followed rapidly by sharp riggers and headache. The
Speaker 2: temperature rose to about one hundred and three degrees fahrenheit,
Speaker 2: and the face was brightly flushed in From three to
Speaker 2: six hours after the riggers had passed off, pains developed
Speaker 2: in or near the joints, extending from the base of
Speaker 2: the skull to the extremities. Fever persisted for a period
Speaker 2: of from twelve to thirty six hours, and the pains
Speaker 2: gradually disappeared within about four days. And then they would
Speaker 2: go on to say that every quote unquote native that
Speaker 2: was hurting sheep during the attack also got sick with
Speaker 2: fever and aches and pains, and that the manager just
Speaker 2: chalked it up to eating quote the somewhat decomposed carcasses
Speaker 2: of dead sheep end quote great great, yeah, okay, yeah,
Speaker 2: just just some casual racism thrown into that paper. Not
Speaker 2: surprising at all. Nope, Nope. This nineteen thirty one paper
Speaker 2: clearly described this newly recognized disease, the responsible virus, the
Speaker 2: symptoms it caused, and its association with wet years, even
Speaker 2: noting that quote the DNGE like fever in man would
Speaker 2: in all probability fail to attract serious attention in view
Speaker 2: of the fact that in such years the incidents of
Speaker 2: malaria would be unusually high, and quote, yeah, they're like obscured.
Speaker 1: Right, it's here, but it's not as big of a
Speaker 1: deal as the other stuff, so no one's looking at.
Speaker 2: It, right, And it's also like everyone's getting sick from
Speaker 2: these other things, and so it kind of flies under.
Speaker 1: The radar, right right right now, Okay, makes sense.
Speaker 2: And so but with that similarity to malaria pointed out,
Speaker 2: they made an educated guess that the Rift Velly fever
Speaker 2: virus was transmitted like malaria, by mosquitos. Love that, yeah,
Speaker 2: but it was also clear that mosquitoes were not the
Speaker 2: only way you could get exposed to the virus. First,
Speaker 2: you had the four who worked on the virus, including
Speaker 2: Dobney and Hudson, get sick, along with so many people
Speaker 2: who worked with sheep in the field, presumably from handling
Speaker 2: samples or directly interacting with the sheep themselves. But then
Speaker 2: the disease started to crop up in laboratory researchers a
Speaker 2: long way from Kenya, especially those who performed in a
Speaker 2: cropsies on the lambs, and the first known death from
Speaker 2: Rift Valley fever in humans was recorded in nineteen thirty
Speaker 2: three or nineteen thirty two from our first hand account. Okay.
Speaker 2: This death, though, would stand out as somewhat of an anomaly.
Speaker 2: For the four or so decades that followed the publication
Speaker 2: of Dobni and Hudson's paper, from the nineteen thirties to
Speaker 2: the nineteen seventies, Rift Valley Fever caused nearly two dozen
Speaker 2: epizootics throughout Africa, first spreading from East Africa to South Africa,
Speaker 2: and infections seemed limited to livestock. Only few human cases
Speaker 2: were noted and no deaths, and these weren't necessarily small outbreaks.
Speaker 2: One epizootic in Kenya from nineteen fifty to nineteen fifty
Speaker 2: one led to five hundred thousand sheep infections and one
Speaker 2: hundred thousand deaths. Wow.
Speaker 1: Yeah, that's like when I feel like when you hear
Speaker 1: numbers like that, like it's just so hard to imagine
Speaker 1: that much death and devastation.
Speaker 2: Honestly it is, and like livelihoods ruined, absolutely ruined. Yeah.
Speaker 2: Was it possible that in an epizolotic like this just
Speaker 2: no one was looking for human cases and they were
Speaker 2: just mild or asymptomatic, I mean, potentially likely, But researchers
Speaker 2: screened some of the people that were handling animals during
Speaker 2: the outbreaks and found really low levels of antibodies to
Speaker 2: the Rift Valley fever virus, suggesting that they weren't getting
Speaker 2: infected at all. I have so many questions, erin, I know,
Speaker 2: because this isn't the way things stayed. Yeah, right, Like
Speaker 2: this epizootic happening every few years, causing a few mild
Speaker 2: human infections if any, but lots and lots of animal
Speaker 2: infections and death. That was going to be a thing
Speaker 2: of the past. The first signal that something changed came
Speaker 2: in nineteen seventy four and nineteen seventy six, when South
Speaker 2: Africa saw half a million animal infections and the first
Speaker 2: human deaths due to Rift Valley fever virus in South Africa,
Speaker 2: this time not from laboratory workers, and more human infections
Speaker 2: than had ever been reported one hundred and ten lab
Speaker 2: diagnosed cases and seven deaths. Wow. But this outbreak would
Speaker 2: quickly be overshadowed by another, resulting in a total paradigm
Speaker 2: shift for this disease that would shape our understanding of
Speaker 2: the virus and its relevance in public health. Between nineteen
Speaker 2: seventy seven and nineteen seventy nine, riffed vellley fever ripped
Speaker 2: through Egypt, which had never seen a case before. In fact,
Speaker 2: no cases outside of Sub Saharan Africa had been seen
Speaker 2: before this. Officials estimated that half of all susceptible animals
Speaker 2: in the country were infected. Whoa, Yeah, which absolutely devastated
Speaker 2: the Egyptian economy. As if that wasn't bad enough, the
Speaker 2: disease also caused extensive morbidity and mortality in humans, with
Speaker 2: an estimated two hundred thousand human infections and six hundred deaths.
Speaker 1: I mean, so different than these early outbreaks that you're
Speaker 1: just holding.
Speaker 2: So different And even in the past outbreaks when there
Speaker 2: had been some human infection, they were mild, right, and small, small,
Speaker 2: small numbers. Yeah, But this outbreak in Egypt, there was
Speaker 2: heemorrhagic disease, there was encephalitis, there was ocular disease, all
Speaker 2: of these extreme manifestations of the virus that you described.
Speaker 2: And with this outbreak came the realization that this was
Speaker 2: more than a potentially devastating disease for livestock, Rift valley
Speaker 2: fever also posed a serious threat to humans. This became
Speaker 2: more and more apparent over the following decades. First in
Speaker 2: nineteen ninety seven to nineteen ninety eight, with a devastating
Speaker 2: epizootic and epidemic in Kenya after rainfall exceeded sixty to
Speaker 2: one hundred times a normal amount WOW, resulting in livestock
Speaker 2: losses up to seventy percent on some farms and an
Speaker 2: estimated eighty nine thousand infections and four hundred and seventy
Speaker 2: eight deaths in huge Then rift velly fever continued to
Speaker 2: expand its geographic range, with the first cases of rift
Speaker 2: valley fever outside of Africa happening in Saudi Arabia and
Speaker 2: Yemen in two thousand, where it caused eight hundred and
Speaker 2: eighty lab confirmed cases the real number is likely much
Speaker 2: much higher and one hundred and twenty three deaths. Since then,
Speaker 2: rift valley fever has settled into this new pattern, causing
Speaker 2: occasional episolotics and epidemics after periods of unusually heavy rainfall,
Speaker 2: often resulting in hundreds, if not thousands or tens of
Speaker 2: thousands of human cases and deaths, as well as severe
Speaker 2: economic losses due to livestock mortality and so circling back
Speaker 2: to those two questions that I asked at the start
Speaker 2: of this why did rift valley fever become deadlier and
Speaker 2: cause larger outbreaks over the past fifty years or so,
Speaker 2: And what can that tell us about future outbreaks. The
Speaker 2: answer to those questions is complicated because we've got so
Speaker 2: many interconnected factors at play. We've got the virus itself,
Speaker 2: how likely it is to mutate or reassort or recombine.
Speaker 2: How often it gets an opportunity to become more virulent.
Speaker 2: We've got the vectors, how abundant they are, Which species
Speaker 2: are in which areas, Whether different species are equally good
Speaker 2: at transmitting the virus, whether different species tend to bite
Speaker 2: humans or livestock more readily, how often they feed, how
Speaker 2: long their eggs, which could potentially contain the virus last
Speaker 2: between epizootics in the environment. We've got the hosts. How
Speaker 2: many sheep are in a certain area, how controlled their
Speaker 2: movements are, how susceptible they are. Whether the animals have
Speaker 2: been vaccinated when lamming happens, importation of animals from affected
Speaker 2: regions to ones where the virus has never appeared. How
Speaker 2: many humans live or work near outbreak areas, whether they
Speaker 2: have access to protective equipment when handling infected animals, whether
Speaker 2: this region has the resources to monitor outbreaks and take
Speaker 2: steps to prevent or control the disease if it appears.
Speaker 2: I'm not done. Oh there's more I know. Then there's
Speaker 2: the environment, right, rainfall amount, humidity, temperature, soil type. Some
Speaker 2: soils retain water better than others, which in turn has
Speaker 2: an effect on mosquito habitat, the propensity of certain areas
Speaker 2: to flood, vegetation density and type, which also affects mosquito
Speaker 2: breeding habitats and grazing, deforestation, irrigation, dams, al Nino events, wind,
Speaker 2: and so many other factors. Well, wildlife, wildlife, Yes, what
Speaker 2: potential hosts, What other hohosts.
Speaker 1: Are around besides your livestock? And what kind of density,
Speaker 1: and what kind of environments, what kind of mixing? What
Speaker 1: species of mosquito biting them versus you versus your livestock?
Speaker 2: There, it is.
Speaker 1: An unbelievably complicated This is why we don't have predictive models.
Speaker 2: That's the well we do. That's the kind of cool thing.
Speaker 2: I mean, no, like we do, and we don't write
Speaker 2: do we have perfect models. There's no such We're never
Speaker 2: going to have the amount of data. Ecology is just
Speaker 2: too noisy there's too much going on, it's too difficult
Speaker 2: to collect. Things are changing too much. Drawing a straight
Speaker 2: line from cause to effect is impossible, doesn't exist. I mean, yeah, yeah,
Speaker 2: just not really feasibility. But even with all of these
Speaker 2: moving parts, there are some ways that we are able
Speaker 2: to see what the future might look like. And it
Speaker 2: also might help us to answer some questions about the past.
Speaker 2: Why Rift Valley fever became more deadly and more likely
Speaker 2: to cause human deaths about fifty years ago. I mean,
Speaker 2: it's probably a mix of those moving parts, maybe mutations
Speaker 2: or reassortments of the virus, increased rainfall events because of
Speaker 2: climate instability, increasing herd sizes, and crucially, movement of infected
Speaker 2: animals across large geographic areas, especially from endemic to naive areas.
Speaker 2: More virus equals more infections equals more opportunities to become deadlier.
Speaker 2: We don't have a perfect roadmap for how this happened,
Speaker 2: but putting together the drivers of these past outbreaks or
Speaker 2: some factors associated with these past outbreaks can give us
Speaker 2: clues about the future. So there's a cool paper from
Speaker 2: twenty twenty four by Chemisen at All that talks about
Speaker 2: how they created a model using climate data to see
Speaker 2: if they could accurately predict past riftfelly fever outbreaks across Africa.
Speaker 2: And it is just like primarily climate data, but their
Speaker 2: model did a pretty good job, which is exciting in itself.
Speaker 2: But what this also means is that you could tell
Speaker 2: this model, Okay, this is what the climate is projected
Speaker 2: to look like in the next ten years for this
Speaker 2: region or that region, or even the next year or
Speaker 2: the next five years, whatever you want, and you could
Speaker 2: see how those different climate scenarios or climate change scenarios
Speaker 2: could impact the risk of rift felly fever out breaks
Speaker 2: broad strokes. Right now seems to be that things will
Speaker 2: get wetter in affected regions, which means more outbreaks potentially,
Speaker 2: And so you could say, okay, next year, what is
Speaker 2: it going to look like potentially for rainfall, and you
Speaker 2: could place higher alert and so then if an outbreak
Speaker 2: does start to happen, are there things that you can
Speaker 2: do to cut that outbreak short? Right?
Speaker 1: What are the plans that you put in place knowing
Speaker 1: that this is going to be a wetter year, knowing
Speaker 1: that that's going to increase the risk of transmission? How
Speaker 1: do you then deal with it right right, And.
Speaker 2: So these models are not perfect, but they can help
Speaker 2: to create early warnings to focus resources during certain areas
Speaker 2: at certain times, in places where resources typically are often
Speaker 2: very limited, to see where rift valley fever might spread
Speaker 2: as the climate changes. You'll see some papers that are
Speaker 2: like rift valley fever in Europe, is this where it's
Speaker 2: going to be now? And these models can be updated
Speaker 2: as we learn more about this virus, about the climate,
Speaker 2: about the host, about all about the mosquitoes, about everything.
Speaker 2: They are a really important part of our toolkit, but
Speaker 2: they're not the only thing. So speaking of which Aaron,
Speaker 2: I was hoping that you could tell me where we
Speaker 2: are with rift valley fever today and whether there's maybe
Speaker 2: a human vaccine in the works.
Speaker 1: We'll talk about it right after this break. So, like
Speaker 1: you mentioned, Aaron, when you were talking about where we
Speaker 1: first saw this virus and how it has spread, this
Speaker 1: is a virus that's endemic at this point in animals
Speaker 1: and or mosquitoes across eastern Africa, all the way into
Speaker 1: southern Africa, honestly across the entire continent into western Africa,
Speaker 1: and has gone north into Egypt and caused a few
Speaker 1: outbreaks on the Arabian Peninsula. Looking at the World Health
Speaker 1: Organization's outbreak reports, because they have disease outbreak news reports,
Speaker 1: and this is absolutely one of the viruses that gets
Speaker 1: reported on if there are any human cases. The most
Speaker 1: recent outbreaks that they reported were actually a couple of
Speaker 1: years ago, which I was a little bit surprised about.
Speaker 1: There haven't been any that they reported thus far as
Speaker 1: of the time of recording in twenty twenty three or
Speaker 1: twenty twenty four. The most recent outbreak that the World
Speaker 1: Health Organization reported on was in Mauritania in twenty twenty two,
Speaker 1: and in this outbreak there were forty seven cases confirmed
Speaker 1: in humans. Almost all of them were people who worked
Speaker 1: with animals of some kind, many animal breeders. But of
Speaker 1: those forty seven cases, twenty three people died wow, which
Speaker 1: is a case fatality rate of forty nine percent. In
Speaker 1: this outbreak. Of the animals that they tested, there were
Speaker 1: nearly three hundred animals that were positive for refali fever virus.
Speaker 1: Twenty four percent of those animals died, and these were
Speaker 1: a mix of cattle, camels, and small ruminants. If we
Speaker 1: look back at past outbreaks, in twenty twenty one, there
Speaker 1: was an outbreak in Kenya that had thirty two confirmed
Speaker 1: human cases and eleven deaths, which is a case fatality
Speaker 1: rate of thirty four percent. There was an even larger
Speaker 1: outbreak in Mauritania in twenty twenty with at least seventy
Speaker 1: five people confirmed positive, over two hundred people were suspected
Speaker 1: to be infected, and at least twenty five deaths. And
Speaker 1: what I was thinking in looking through all of these
Speaker 1: individual outbreaks, and again you can link to all of
Speaker 1: these on the World Health Organization website. There's a number
Speaker 1: more dating back to like the twenty tens, that these
Speaker 1: are very high case fatality rates, very high compared to
Speaker 1: what we have seen in the past, and very high
Speaker 1: compared to what all of the sources that I read
Speaker 1: would lead you to expect when we talk about one
Speaker 1: to two percent of cases or even eight to ten
Speaker 1: percent of symptomatic cases being severe and fifty percent of
Speaker 1: hemorrhagic cases ending in death. Right, that's the numbers that
Speaker 1: I cited earlier.
Speaker 2: Yeah, so what is going on here?
Speaker 1: Does this mean that in these outbreaks, the cases that
Speaker 1: we are able to report that the World Health Organization
Speaker 1: is reporting, are those cases only the tip of the
Speaker 1: iceberg in a case.
Speaker 2: Yeah, that's possible.
Speaker 1: I did some air in math to try and get
Speaker 1: a handle on what that would mean. So if we
Speaker 1: look at the outbreak in Mauritania in twenty twenty two,
Speaker 1: we had forty seven people that were confirmed to be
Speaker 1: infected and twenty three.
Speaker 2: People who died.
Speaker 1: If we think that that means that those cases were
Speaker 1: only the people who had severe infection. If we tried
Speaker 1: to air in math that outbreak, then we would estimate
Speaker 1: that outbreak could have been as large as like four thousand,
Speaker 1: seven hundred people who were infected. If we were expecting
Speaker 1: that only one to two percent of all people who
Speaker 1: were infected had severe symptoms, and fifty percent of people
Speaker 1: with severe symptoms that would be those forty seven people.
Speaker 1: Fifty percent of those people would end up dying. That's
Speaker 1: that's my air and math of the situation. Does that
Speaker 1: make sense.
Speaker 2: Yes, we don't have.
Speaker 1: Any data to suggest that that is what happened, at
Speaker 1: least that has been reported that I have seen. So
Speaker 1: I'm not trying to say that these cases are actually
Speaker 1: these outbreaks are actually thousands more than we think, but
Speaker 1: that is one possibility. The other possibility is that case
Speaker 1: fatality rates are indicative of much more severe illness than
Speaker 1: we have seen in the past. And if so, why
Speaker 1: is that because the virus is changing? Is that because
Speaker 1: something was happening with hosts who were infected at the time.
Speaker 1: I don't know, But there was a paper from PLUS
Speaker 1: Neglected Tropical Disease that was the systematic review and meta
Speaker 1: analysis of all the case reports from the last few decades.
Speaker 1: They looked at like thirty two different studies and they
Speaker 1: found an overall twenty one percent fatality rate among those
Speaker 1: who had symptoms of disease. So it seems like the
Speaker 1: mortality rate may be on the rise from with Valley fever,
Speaker 1: and we don't as far as I read, understand what
Speaker 1: exactly might be driving.
Speaker 2: That, which is very interesting because, as we talked about,
Speaker 2: the virus is not directly transmitted human to human exactly.
Speaker 1: It is not, and there still has been no evidence
Speaker 1: that that has started.
Speaker 2: And so what is going on in the environment, Like
Speaker 2: it must be something that is happening to increase the virulence.
Speaker 2: Is there a corresponding increase in virulence in the affected
Speaker 2: animal species?
Speaker 1: And it's hard because it's already so virulent. So right,
Speaker 1: how could you go up from ninety percent?
Speaker 2: Right?
Speaker 1: Yeah, so no, and I haven't seen data that suggests
Speaker 1: that it's killing more animals. It's certainly still killing hundreds
Speaker 1: tens of thousands, if not hundreds of thousands in many outbreaks.
Speaker 1: But yeah, so it's it's very interesting. It's going to
Speaker 1: be important, I think, to watch what is actually happening.
Speaker 1: And I think too, I'm sure that especially for these
Speaker 1: last few years of outbreaks, there will be more papers
Speaker 1: coming out that maybe look at a larger swath of
Speaker 1: the population where these outbreaks occurred to try and get
Speaker 1: a sense of like, what is the zero prevalence in
Speaker 1: that population? How big were these outbreaks really? In some
Speaker 1: studies that have looked across like endemic areas, there have
Speaker 1: been zero prevalence studies that have estimated anywhere from like
Speaker 1: six to eight percent of humans and eight to twelve
Speaker 1: percent of livestock show evidence of prior infection. So this
Speaker 1: virus is out there circulating even when we're not necessarily
Speaker 1: seeing it cause episootics or outbreaks in humans.
Speaker 2: So what do we do about it all? Yeah, I
Speaker 2: was just about to say, is there a vaccine in
Speaker 2: the works.
Speaker 1: There are many so there are two already at least two,
Speaker 1: and there might be multiple versions, but there are two
Speaker 1: that exist for animals for livestock. Neither of them are perfect.
Speaker 1: The live vaccine is very effective. A single dose of
Speaker 1: the live vaccine is very effective, but it has a
Speaker 1: lot of drawbacks. It tends to cause spontaneous abortion in
Speaker 1: animals if they are pregnant because it is a live vaccine,
Speaker 1: even though it's less virulent. You also can't give that
Speaker 1: vaccine during an outbreak because it can actually end up
Speaker 1: amplifying the outbreak. And there's always a risk because it's
Speaker 1: a live vaccine that it would then kind of mutate
Speaker 1: back closer to the wild type and then cause disease
Speaker 1: outbreaks amongst animals or humans. So those are the big
Speaker 1: drawbacks of the live vaccine. There is also an inactivated vaccine.
Speaker 1: They require multiple doses, I think at least three doses,
Speaker 1: which makes them more difficult to implement in a lot
Speaker 1: of areas, and they just don't provide quite as long
Speaker 1: lasting of protection. But they also don't have the drawbacks
Speaker 1: that the live vaccine has, so unsurprisingly, this is one
Speaker 1: of the main areas of research is developing a vaccine,
Speaker 1: especially one that could be used for both livestock and humans.
Speaker 1: There's at least one that's being studied right now in
Speaker 1: both the UK and in Uganda, or at least when
Speaker 1: this paper was published in twenty twenty two, it was
Speaker 1: being studied in these areas in both livestock and humans
Speaker 1: that was using a viral vector, very similar to some
Speaker 1: of the COVID vaccines that we saw that use like
Speaker 1: a viral vector as a vaccine. But there's also like
Speaker 1: a whole bunch of different vaccine candidates that people are studying.
Speaker 2: We don't have.
Speaker 1: Any that I saw that are super close to being
Speaker 1: ready or use in humans.
Speaker 2: Okay, that's disappointing.
Speaker 1: Yeah, but maybe by the time this episode comes out
Speaker 1: there will be a new paper that changes that, because
Speaker 1: I mean, as of a couple years ago, they were
Speaker 1: definitely studying it. And I think that with all of
Speaker 1: the advancements that we've seen in vaccine platforms since COVID,
Speaker 1: I think that we are very likely to see the
Speaker 1: development of vaccines for viruses like rift valley fever because
Speaker 1: of what a huge impact it has on livestock, on economics,
Speaker 1: and on human health and public health. So there is
Speaker 1: a vaccine that some veterinarian laboratory personnel have gotten. Oh,
Speaker 1: there is a vaccine that people have gotten when they're
Speaker 1: at very high risk for infection. But it's an animal
Speaker 1: vaccine that has never been licensed or approved for use
Speaker 1: in any country.
Speaker 2: Interesting, Okay, yeah, someone's like, I've been vaccinated. That's very cool.
Speaker 2: It's not approved, so.
Speaker 1: Yeah, that's real. I feel like it is one that
Speaker 1: should get more pressed than it has gotten perhaps, well,
Speaker 1: I mean more nervous.
Speaker 2: Absolutely, I feel like, yes, it is a scary and
Speaker 2: potentially very impactful disease in a public health context, but
Speaker 2: also just as a livestock disease. It's so economically devastating
Speaker 2: and traumatizing, yes, because, like I just again, from one
Speaker 2: day to the next, or like one week to the next,
Speaker 2: you could lose your entire herd, your entire livelihood.
Speaker 1: It's I mean absolutely dosting the size of some of
Speaker 1: these outbreaks. And we'll link to some papers that have
Speaker 1: kind of details on all of the dozens of outbreaks
Speaker 1: that have happened over even just the past twenty years.
Speaker 1: I mean, some of them have been hundreds of thousands
Speaker 1: of livestock it's just I mean.
Speaker 2: Horrific, unfathomable. Yeah. Yeah, Well, speaking of sources, shall we
Speaker 2: share some sources? Let's share so you can read some more. Okay,
Speaker 2: I'm going to shout out three in particular by Baba
Speaker 2: at All from twenty sixteen. Has rift valley fever virus
Speaker 2: evolved with increasing severity in human populations in East Africa
Speaker 2: by mc millan and Hartman from twenty eighteen, Rift Valley
Speaker 2: Fever in Animals and Humans Current Perspectives. And that modeling
Speaker 2: paper that I mentioned in the last bit of the
Speaker 2: history by Chemisen at All from twenty twenty four Ability
Speaker 2: of a dynamical climate sensitive model to reproduce historical rift
Speaker 2: valley fever outbreaks over Africa.
Speaker 1: I have a number of papers, a couple that I
Speaker 1: wanted to give a shout out to. When was that
Speaker 1: plus neglected Tropical disease paper? It was from twenty twenty two.
Speaker 1: It was titled Clinical Manifestations of riftflly Fever in Human
Speaker 1: Systematic Review and Meta Analysis. Another was from the Journal
Speaker 1: of Veterinary Research from twenty twenty one called riftfallly fever
Speaker 1: a growing threat to humans and animals, And there was
Speaker 1: a number of other ones, so we will post the
Speaker 1: list of all of our sources from this episode and
Speaker 1: every single one of our episodes. You can get so
Speaker 1: deep on the neuropathophysiology on our website This podcast will
Speaker 1: Kill You dot com under the episode STAB.
Speaker 2: Thank you to Bloodmobile for providing the music for this
Speaker 2: episode and all of our episodes.
Speaker 1: Thank you to Tom Bryfogal and Leona Scilaci for the
Speaker 1: audio mixing.
Speaker 2: Thank you to everyone at Exactly Right.
Speaker 1: And thank you to you listeners. I hope that you
Speaker 1: enjoyed this episode.
Speaker 2: Yeah, I hope you learned something new. That's always my hope.
Speaker 2: I certainly did.
Speaker 1: It's our favorite thing is to learn new things.
Speaker 2: It truly, truly is. Yeah. And a special thank you
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