Ep 164 Rift Valley Fever: Ruminating on ruminants

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 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 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 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 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 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 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.

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.

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.

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 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 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 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 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.

a secondary host. It's like a circ goal, right, the transmission of this virus. When you look at this cycle, it's not a circle. It's like a circle with a line and another line and like two other branches.

is infected. And after some amount of time in the 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. But how long does it have to exist in the mosquito? How long does this virus have to be there?

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 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.

of these animals also have vertical transmission themselves. So if 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.

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 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 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 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?

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 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.

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.

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.

even within humans it can present very differently across the board. Though, 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

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

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, 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, 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 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 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 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 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 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 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.

improve for good. But there are several ways, three different ways really that this can cause a much more severe illness.

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 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 don't know the specific path of physiology of.

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.

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.

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

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 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. 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 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.

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 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.

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.

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.

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 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 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 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, 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.

Europeans that are coming. Like it's it's just all part of it.

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 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 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

description of what was likely riffed vlley fever. Yeah, why then why nineteen twelve?

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 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 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 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 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 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 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 really get highlighted a whole lot inside. Oh, no, this type.

Not wildlife. Okay, but what happens next? Right, like what happens after nineteen twelve, Well, nearly twenty years would pass 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 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 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, 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 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 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

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.

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 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 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 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?

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 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 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 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, 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 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.

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 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 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 hundred thousand deaths. Wow.

because this isn't the way things stayed. Yeah, right, Like this epizootic happening every few years, causing a few mild 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, 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 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 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.

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 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

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, 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, 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.

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 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 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 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.

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, 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.

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 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 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 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?

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, 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.

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 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 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 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

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 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 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 I cited earlier.

Fifty percent of those people would end up dying. That's that's my air and math of the situation. Does that make sense.

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. 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 exactly might be driving.

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 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.

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 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 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 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 a whole bunch of different vaccine candidates that people are studying.

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.

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.

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 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.