She began to feel feverish and achy, and believed she had the flu. When the aches and pains grew more severe, she sought medical attention and was hospitalized before the respiratory symptoms appeared. She speaks of drowning, of perceiving a great weight on her chest, and a great exhaustion. She speaks of wanting to see her children one last time, and then of her mixed emotions about being sedated. I wanted to live, she said, of course I did. I didn't want to leave my family. They needed me.
But I was just so tired. I was just so tired.
She did survive, and sometimes she says she still grows so weary that she realized she'll never fully recover from her encounter with the virus. She says, it's the most horrible feeling, the tubes, the liquid in your lungs, the choking. You don't want to die that way, but you know you can't live that way either. Shoot. Yeah, dang bad one.
Yeah.
Every episode, Hello, Hello, I'm Aaron Welsh.
And I'm Aaron Oman Updyke and.
This is this podcast will kill you.
Yeah it's.
And this week we're talking all about hauntaviruses, and so what you just heard was an excerpt from the Book of Mice, Men and Microbes, which goes in to the history of hantaviruses, with particular focus on the Sonombree outbreak, which you'll hear a lot more about in a bit.
Yeah cool, okay, cool. So let's get into our business, and.
Our business is quarantine quarantinies. What are we drinking this week?
This week, we're drinking the mouse Trap. It is so good, unbelievably delicious. It has, which is arguably the best liquor. I'm not even gonna I'm that's I'm immediately cutting that. It could be, it could be argued, but I think I have a different one in mine. Anyway.
It's also got rosemary, simple syrup, blood orange juice, lime juice, and a splash of soda water. So we will post the recipe for this quarantiny the mouse Trap, as well as the Place Barrita on all of our social media.
Which is our non alcoholic version of our quarantine. You'll be able to find the full recipes on our website as well as this podcast Will Kill You on Facebook and Instagram and TPWKY on Twitter.
Okay, so I'm very excited for this episode. And I know that I say that every episode, and I genuinely mean it every episode, because.
Every episode is exciting. It's something new, and we learn stuff while we're researching it, and then we get to learn more stuff as we listen to each other teach us the things that we didn't know.
Let's get started. Tell me about the biology.
Er Okay, I'd love to. Hantavirus is aka ortho hantaviruses. This is a group of viruses. They are single stranded, they're in an envelope, and they're an RNA virus. You just learned so.
Much, okay, and what is the ortho part of all that?
I don't know why they changed the name from hantaviruses to ortho hantaviruses at some point recently. The phylogeny of this is confusing to me. Sometimes they call it the order bunia Viralis. Sometimes they call that the family Bunyaviridae. Who knows. If you see the word bunia virus, that is a larger group of viruses that includes the hauntaviruses.
It also includes a lot of other viruses which cause horrible diseases including crime and congo hemorrhagic fever, rift valley fav several different encephalitis viruses, and so many more.
So this is a pretty.
Gnarly family group.
It's a gnarly group order of viruses. It's a gnarly group of viruses that love to infect humans, which not all virus groups love to do that these ones do. What's interesting about hantaviruses specifically in this family or order or whatever is that they're the only ones, for the
most part, that aren't transmitted by ticks and mosquitoes. So most of the other viruses in this Bunya Veridae or buniavialis group are transmitted by ticks or mosquitoes, not hantaviruses, right, So hantaviruses, in contrast, are transmitted through rodent excrement yummies. So fun. What I love is that so arthropod born viruses that are transmitted by ticks and mosquitoes are often called arboviruses. You could call these roboviruses rodent born. I
love it anyways, very very sci fi. It's very sci fi. So hontaviruses are transmitted by rodent excrement. What does that mean. It means that these viruses live their life cycle inside of rodents, and they're naturally found in rodent populations honestly across the globe. Various different hantaviruses are found in almost every continent, in different rodent species, and they circulate in these rodent populations really without causing a lot of damage.
They don't harm the rodent populations. Really, They kind of do okay.
Overwintering survival.
Okay, so that counts. But they don't cause the kind of damage that they cause in humans in general, in the rodent populations, which suggests that they have sort of a history like these are the groups of animals that they are sort of evolved to infect, if that makes sense. So in humans hantaviruses, of which there are a number, and I'll tell you the names of a bunch of them, they cause two major diseases, sort of two distinct groups of illnesses. The first that you might have heard of
is called hantavirus pulmonary syndrome. You've heard of that aaron, of course, and the other is called hemorrhagic fever with renal syndrome.
That sounds quite bad, right if you had.
To guess like, which one of that sounds the worst?
I mean hemorrhagic fever. I would automatically say, oh my.
Gosh, that sounds terrible.
Right, But knowing hantaviruses and this leading.
Question, so yes, it's actually hantavirus pulmonary syndrome that is the more severe of the disorders. So what I'm gonna do is I'm gonna go through each of these two disorders, hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome, talk about what's different about them, and then talk about what's
similar about them. Sounds good, cool, sounds great. So hauntavirus pulmonary syndrome, We'll start with that because it's my personal favorite, and it's the one that's the one that people are probably more familiar with if you live in the United States, because this is caused primarily by sindombree virus, and this is the hauntavirus that exists in the United States in the Southwest. It's hosted or its its reservoir host is the deer mouse.
I like the term hosted.
Actually it's hosted by the lovely deer mouse, and it causes a disease that has a death rate of thirty eight to fifty percent.
That's enormous.
It's enormous. It's a very very scary illness. So here's how it happens. There's four different phases of HPS hauntavirus pulmonary syndrome. Okay, it starts after an incubation period of between nine and twenty four days, usually about one to five weeks, which is a pretty wide incubation period. And that's again the time from when you're infected to the time when you first show symptoms. And so after that
incubation period, the first phase is the febrile phase. Febrile means fever, so as you can guess, this starts with a fever. You'll also have muscle aches and malaise. You'll probably have a headache, some dizziness kind of like you have the flu. You might even have some nausea or abdominal pain. But what's important is that you don't have upper respiratory symptoms like you would with the cold or the flu, So no stuff, no sore throat things like that. You could end up with a cough at the end
of this phase. Now, this phase, the febrile phase lasts between three and five days, but it could last as long as twelve.
So again, is it because are these wide ranging incubation times and certain phases because there are just a relatively low number of cases that for comparison proper. Is it just that the virus really is host like individual dependent.
I think it's probably a combination of both. So hantavirus pulmonary syndrome. We don't there's not There haven't been a ton of cases of this, so you're definitely gonna have wider variation because of that when you have a small sample size. But it's also very likely that your exposure will determine how much virus you're exposed to, and then that can have a really huge impact on incubation period.
Right. Yeah.
Also, I really like that this is just a total side note, but it started with a fever.
Would have also been a great name for this podcast.
It would have been.
Oh shit, oh god, that's a good name. That's future podcast, Future podcast. And the bummer about this first phase is that it's super hard to diagnose because your symptoms are very nondescript, and you're about to see that after this phase, it gets bad really quick. So phase two is the cardiopulmonary phase. This is the beefy part of the disease, and it happens really fast. Within twenty four to forty eight hours after these symptoms start, up to fifty percent
of infected people will die. Ooh yeah. So basically you present with shock and pulmonary edema. So let's talk about these. We've talked about shock before. Shock is what happens when for some reason, your blood pressure is going to drop and you're not going to get blood profusion to your tissues, so your organs are going to start to die because
they don't have adequate blood flow. In this case, the symptoms that happen are in large part due to what's called vascular permeability, which means your blood vessels become leaky, especially the blood vessels in your lungs. So the fluid that's supposed to be in your blood vessels, aka your blood, starts leaking out into the space between your cells in your lungs, and that results in what's called pulmonary edema, which means fluid on your lungs.
Oh so I knew that that's what that meant, but I didn't know how that happened. Yeah, that's very interesting.
That's how it happens in this case. Pulmonary deal can happen other ways as well. Yeah, oh, I want to know all the ways. I'm sure we'll have so many diseases to talk about. Various forms of pulmonary edema. But it's often from fluid leaking out from your your blood vessels. It's not always straight up blood like in this case. It's often whole blood that's able to get through. Sometimes it's just plasma or just like the fluid and not
like your entire like red blood cells and stuff. It just depends on how big the holes that are allowing the leakage are. If that kind of.
Makes that's so interesting, it's very cool.
You can imagine that all of this edema makes it really hard to breathe. It also because your heart is sort of right in between your lungs, makes it hard for your heart to beat, and so that's why you end up going into cardiogenic shock, which means your heart The reason that you go into shock is because your heart is not pumping enough blood out.
And that's only because it's restricted in space by your lungs filling up with your own fluid slash blood.
Yeah, and because you're bleeding out into your own body, so there's not enough blood getting to your heart, so it's a double.
Your blood pressure is just like exactly totally down.
Yeah, yeah, cool, right, So.
This result is horrifying.
It's very horrifying. There's because of this, because of all the blood that you're leaking out, your blood is then not making it to your other organs, so your kidneys will likely start to fail, so you might end up with what's called aliguria, which means low urine, few urine, it's not good. And yeah, so that basically fifty percent
of people are going to die. However, the other fifty percent or sometimes more, it could be as low as thirty percent of people who die, So fifty to seventy percent of people will then somehow progress to the diuretic phase, which is phase three of this disease, which is when your pulmonary edema clears up, your urine output increases, and the fever and shock resolve. Okay, don't ask me exactly how that happens. Yeah, I would love to have a
great answer on that. It is unclear to me if you're you're an output goes low, that's a very bad sign. If you then all of a sudden start peeing out a lot, that's actually a good sign because it means that something is somehow your body is trying to re equilibrate, and then you're entering the diuretic phase. After that, you're in what's called the convalescent phase, which can last for
several months. So this is a very long recovery period and often often people recover fully, but it is also possible to have long term pulmonary symptoms, like decreased blood flow in your lungs because of just how much damage has been caused.
Okay, that's yeah, yeah, and how like the damage in your lungs is caused by the like in the blood vessels themselves or yeah.
We'll talk about exactly what causes that, what allows for that blood to leak out in just a second, because it's it's a really important part of this disease. So that's HPS hantavirus pulmonary syndrome. Let's talk about hemorrhagic fever with renal syndrome. So this is the other form of hantavirus which many people I guess if you live in Europe or Asia, this might be what's more familiar to you. If you live in the US, you might never have
heard of this. This is caused by a number of different hauntaviruses, including soul virus, which was first discovered in Soul, Korea and is hosted by the Norway rat, and the black rat. Hatan virus also discovered in Korea, which is hosted by the striped field mouse. Uh, pumala is that how you say that? Pumala pumala virus which is from
Finland and hosted by the bank vowl. And do Brava virus, do brava do brava, dobrava virus whatever, which one of those covered in Slovenia and is hosted by the yellow necked field mouse. Oh, that's a lot of viruses. So all of these viruses, which are different haunted viruses, cause various forms of HFRS hemorrhagic fever with renal syndrome.
This is so one of the things, just to pause that I noticed too many acronyms tell me about it. It's ridiculous. It's ridiculous, Okay. So then the hemorrhagic one, So.
The hemorrhagic one. We've got at least four different viruses that we're talking about here, and they cause the same disease, but with varying degrees of severity. So, for example, Pumala virus in Finland has a very low estimated mortality rate between one and three percent, whereas Hatan virus has a mortality rate of between five and fifteen percent, so it's a much more severe illness. What's interesting is that because these viruses cause diseases of varying severity in different countries,
they have different names for them. So for a while, the disease that hunt On virus causes was called KHF or Korean hemorrhagic fever. Pumla virus it's often the disease it causes is often called nephropathia epidemica. It's absurd, they're all the same disease. I'm gonna argue, and hopefully you'll agree with me by the end of this episode, that all of the diseases caused by hauntavirus should be called the same thing. I'm not alone. I have an article
to site for it, so let's get into it. HFRS it has five stages, not just four like we saw with HPS, and it starts similarly first phase febrile fever, muscle aches, headache, nausea. You also might get flushing of your face, and that's because again we know there's going to be vascular involvement, and so anytime your your blood vessels are dilating, you might get flushing of your face
because you've got blood flow there. That makes sense, Yeah, And you'll move more quickly into the second phase, which is the hypotensive phase. So this is again where your blood pressure drops. You'll also likely have what's called thrombocytopenia, which you also do see in HPS, and it just means that you have a low platelet count. A low platelet count is bad because it means you're likely to
bleed out. So platelets are what's responsible for clotting. So without platelets, you are at a higher risk of bleeding. So then because of the thrombocidopenia, you might have certain skin bleeding manifestations little red purple dots, which basically are small hemorrhages happening under your skin. And then you'll move into the oliguric phase, which though we didn't have a phase called oliguria in HPS, we did see that you
also have a drop in your an output. The biggest difference here is that the effects of h FRS tend to happen mostly in the kidneys instead of in the lungs. So we see your kidneys starting to fail first rather than your lungs filling up with fluid. So you're not gonna have a cough, You're not going to have the pulmonary edema. Does that make sense?
Why? Why are they different? Or is that am I jumping the gun?
You're jumping the gun a little bit. Let's finish out this HFRS. Once you see that decrease in you're an output, it's bad news. But again, HFRS overall has a much lower mortality rate. So most people are going to start to recover, and then they'll enter the polyuric phase, which means a lot of p they'll start to diaryse and pee a whole bunch out, uh, and then convalesce.
Cool.
Cool, So the question is not cool, It's terrible. Not cool. But here's the thing what I think is really important and what makes these diseases really really cool, and also why pathophysiology is my favorite subject. Right now is that even though these sound like okay, HPS, you're going to have fluid all over your heart and lungs and you're going to die because you can't breathe and your heart
can't beat HFRS. Your kidneys are going to shut down, and maybe you'll be able to recover, and maybe you won't. These two seem like very different diseases, but they're not. They're so closely related, and if you understand what's happening inside of your cells, it's the exact same thing. So here's what happens. Hantaviruses infect your endothelial cells. These are the cells that line your blood vessels. Okay, they get into those endothelial cells, they replicate, and they cause damage.
They don't necessarily kill the cells themselves, but they cause enough damage that other cells come in and things like histamine are released, which causes vasodilation and increased vascular permeability. This means that your blood vessels are now leaky, so you have fluid loss and blood loss and hypotension. This is the exact same mechanism that happens in HPS and
in HFRS. The only difference is what tissue is the hantavirus primarily infecting the endothelial cells of your lungs or the endothelial cells of your kidneys.
And why is there a difference, Like, why is there a differential preference?
Right that no idea?
Huh yeah? Interesting, right? Is it really sort of this old world new world situation in terms of pulmon versus renal?
Yeah, so the ones in South America do tend to cause more HPS like symptoms, at least from what I read. Okay, so yeah, it's just it's so interesting, hmm. But yeah, they are transmitted in exactly the same way. So they're transmitted in the excrement of rodents. So basically you have to aerosolize pee or poop from a rat or a
mouse or a vole that's infected and inhale it. But what I think is so cool is that you have these two diseases which on their face seem so different, and yet the underlying mechanism that causes the disease is exactly the same.
Yeah, that's super interesting.
Oh, I should say very importantly, for the most part, the disease cannot be transmitted person to person. There's like one case where it possibly a huntavirus. Andy's virus in South America was possibly transmitted person to person, but every other hauntavirus in as many studies as they've tried, has never been shown to be able to be transmitted from person to person. It's exclusively from aerosolized rodent excrement. So, Aaron, tell me about this. How did we get here? How did this all start?
Okay? I think I can answer that. When we picked hantaviruses to cover this season, I don't think either of us realized just how large the world of hantaviruses it is, and also how much the story is still developing. Okay, but before we get to where we are today, let's as always go back to where we started, or at least where the virus started. Hantaviruses have been around for
millions of years. They can be found in rodents on every continent except for Antarctica, and their diversity is astounding. But when did humans start to get involved?
Yeah?
As early humans began to farm and form stationary settlements and store food, which is a key factor, many rodent species settled with them, and the easy access to food
and shelter promoted this close relationship. Because of this, humans have probably been exposed to or infected with hantaviruses for millennia, but it's not until really, like a long time ago, nine hundred and sixty a D. I'm like, oh, but it's not until that time, right, So nine hundred and sixty a D. Thousand years ago that we get our first bit of evidence for this, a Chinese medical account of a disease that sounds a whole lot like heemorrhagic
fever with renal syndrome. But then it more or less disappears from medical textbooks for almost a thousand years. Although side note, some people believe that the mysterious sweating sickness that plagued England and continental Europe during the fifteenth and sixteenth centuries might have been caused by a haunt of virus. Really yeah, so apparently the symptoms were fairly similar. There was this seasonal pattern and in these irregular intervals. Oh, but it's still.
Far from conclusive.
So, for one thing, this sweating sickness seemed to be transmitted person to person, which is rarely or never seen in hantavirus outbreaks. And for another, outbreaks appeared sudden and disappeared suddenly without any mention of previous cases or reports of rodent population increases. But just in case, we should probably do a full episode on sweating sickness, just to you know, cover the basics.
It's only, yeah, it is, it is.
In any case, it's not really until the eighteen sixties that we get a clearer sense of hauntavirus outbreaks in humans. In the US. In the eighteen sixties, the essa's were not very u what in the US, I was so dorky erin.
I liked it.
It's pretty dorky.
It's good, okay, So the s's aren't so you.
The American Civil War was raging, as were cases of
what was being called war nephritis or trench nephritis. The outbreak reached its peak between eighteen sixty two and eighteen sixty three, and an estimated fourteen thousand soldiers came down with this disease, whose symptoms strongly resembled that of the hantavirus caused field nephritis experienced by troops in Flanders during World War I. Hantavirus infections make another appearance again in Wars, this time a little more global, when the Japanese military
invaded Manchuria, and also during World War II in Finnish and German soldiers. These outbreaks prompted modern descriptions of the disease, though the link between the European and Asian infections was yet to be discovered. Scientists investigating these diseases had plenty to keep them occupied and maybe a bit too much license. At this point, you may have noticed the link between
these infections and war conditions. The disease was seen most commonly in soldiers, and not just any soldiers, but ones who were huddled in trenches for long bouts of time. Researchers in the nineteen thirties and forties also picked up on this, and they started looking for the root of transmission. Rodents were immediately implicated, as were arthropods such as mites and ticks, which were also common and crowded conditions like that, right, But how to test?
How to test?
How about human experimentation? Of course, great choice, not really, but it is the choice that some Japanese scientists opted for during World War II, the most notorious of these programs being Unit seven hundred and thirty one, whose official innocuous title was the Epidemic Prevention and Water Purification Department.
Throughout the eight year existence of this program, over three thousand men women in CHLDREN, both prisoners of war as well as civilians, were experimented on, with death being the most common outcome. There was frostbite testing, vivisection with no anesthetic injections with various infectious diseases, including hantavirus material even though they didn't know exactly what that was yet. This is world's weapons, he's testing. Yes, Oh my god, Oh just wait, it gets so much worse.
I know it's just humans, man.
Yeah, weapons testing, starvation and dehydration. Really, the list goes on and on and on. The Results of many of these experiments were published in peer reviewed journals, with any mention of human subjects changed to a non human primate species.
WHOA are you serious? So they fully It's not like they were just like, oh, it's fine. They were like, we know this is not fine. We're just gonna do it anyway and pretend like we did it on a monkey.
Yeah.
Cool, cool, cool cool cool right cool cool.
Okay, but I haven't even gotten to one of the most outrageous parts of this okay, which is that when the US found out about this human experimentation, instead of prosecuting any of the researchers or leaders involved in Unit seven three to one, the US granted them complete immunity as long as they provided all of their results to the US and none of the other allies, namely the Soviet Union.
It is zero percent surprising, quite honestly.
I know, which is also very sad.
It's very sad, not surprising.
Yeah, but you should, really like if you have time, just check out the Wikipedia page, even with just a skims. It is shocking and just something that deserves a lot more attention than I'm giving it right now. So maybe another episode anyway. But yeah, Unit seven three to one was unsuccessful in determining the causative agent of the war associated hemorrhagic fever, and they still didn't have a conclusive answer for how it was transmitted. And they weren't alone
both in their human experimentation and in their failure. The Soviet Union had their own experiments running around at the same time, in which they injected human quote volunteers with various materials to try to bring about infection. By nineteen fifty, various European and Asian countries were familiar with hauntavirus caused infections and their association with rodents, even if they still
didn't know what a hauntavirus was. It's going to take another war to get the interest in funding to solve that problem. In this case the Korean War. Tensions had been running high between North and South Korea for a long time, and it came to a head in June of nineteen fifty when North Korean troops invaded South Korea, seeking complete control of the divided country. UN forces, largely comprised of US military, were sent to South Korea to
stop this offensive. The war lasted three years and resulted in casualties ranging in the tens of thousands to over a million dead. As in all wars, combat is just one of the leading causes of death, often going hand in hand with things like starvation and disease, and with so much of this war fought in the trenches and the frontline barely moving from the thirty eighth Parallel Trench, nephritis or hemorrhagic fever with renal syndrome was one of
those diseases. In general case estimates of hemorrhagic fever aren't very good for this conflict, but we do know that approximately thirty two hundred UN soldiers came down with the illness and a hundred and twenty one died. Obviously, this got people searching for the source of the infection. Ticks and fleas and mites were once again investigated and ruled out, and rodents were found to be the likely culprit, and not just any rodent, Epidemus agrarius the Asian striped field mouse.
Similar disease ecology research was being done in fenaes Gandia to narrow down which rodent might be responsible for disease outbreaks there. In that case, a totally different species was implicated, as you mentioned Myoti's Gleriolus the bank full. But if there was any hope of lessening the suffering caused by this disease, the causative agent still had to be identified, and that's where doctor Ho Wang Lee comes in. A physician, epidemiologist,
and virologists from South Korea. Doctor Lee had set his sights on discovering what was hiding in these rodents that caused illness and humans, and in nineteen seventy six he achieved his goal when he found evidence of viral anti predominantly in lung tissue of an Asian striped field mouse.
So it's in the lungs of these guys. Yeah. He would go on to develop a diagnostic test for hemorrhagic fever with renal syndrome and a vaccine for a strain of hantavirus, as well as a lot of other really important ecological and medical research on hantaviruses and side note, actually, according to Wikipedia, he is the first person in the history of medicine to identify a virus that causes human disease, develop a diagnostic tool for the disease, and develop a vaccine for it as well.
To do all three.
That's cool. Yeah, isn't that amazing?
It's really cool. Okay, we're at.
The point in the story where I tell you the etymology of our pathogen or disease. While in general the trend has been going away from using things like the name of a country or city in naming off and other geographical markers are still used, doctor Lee chose to name the virus after the Hantan River. This river flows near the third eighth parallel, which divides north from South Korea.
This area was a hotspot for hemorrhagic fever with renal syndrome during the Korean War, and continued to be an endemic region for the disease after the war had ended. But in his book, doctor Lee explains that he didn't just name the virus for the river's association with the disease, but also because to him it represented the tragic history of the country and hopes for reunification. The name, as you know, stuck. The virus plagued that part of the world would be known as the Hanton virus and it
would soon gain many relatives. So earlier when you mentioned that, is that hantaviruses are transmitted by through rodent excrement, whereas all the other bunevide are transmitted through arthropods. So some researchers believe that it could indicate that huntaviruses are actually older. They are a more basal subgroup within Bunia verde.
Oh cool, yeah, Okay.
Anyway, with this diagnostic test that doctor Lee had developed, it was now possible to test patients from all over the world, particularly in those regions where a similar hamorrhagic fever or renal syndrome of unknown origin was known to
pop up. This led to the discovery of pumaa virus, soul virus, prospectil virus, etc. You know, all these other viruses, and these viruses were all similar but not identical, and their discovery hinted at the enormous diversity that this group of viruses would later be found to have.
So cool.
On that note, let's travel to the American Southwest, May nineteen ninety three.
Yes, I've been waiting for this.
Bill Clinton as president. Beanie babies have just hit the shelves for the first time. Oh my god, the sandlot is in theaters. Two Princes by the spin Doctors, is on the radio. And in the Four Corners region of the US, which is where Colorado, Utah, Arizona, and New Mexico meet, is in the early stages of a terrifying and tragic outbreak of unknown origin. A twenty one year old Navaja woman named Florena Woody, mother to a five
month old son, started feeling achy and feverish. Within a couple of days, her symptoms progressed into pneumonia, and she began to have difficulty breathing. At the hospital where she was admitted, the doctors tried in vain to keep her oxygen levels high and her lung fluid levels low. Eleven days after the first symptoms appeared, Florina died on Mother's
Day in nineteen ninety three. Her fiance, a nineteen year old Navajo man named Meryl Bahee, a terrific athlete, felt too sick to attend her funeral, and some of his relatives decided to drive him to the hospital. As his condition rapidly deteriorated. On the drive to the hospital, Merrill began gasping for air and collapsed. He was pronounced dead on arrival, five days after the death of Florina. It's five months, so baby, heartbreaking.
Yeah, it's horrible.
It's horrible, and the deaths of these two otherwise healthy young individuals threw up red flags for the attending physician, who alerted the state Medical Examiner's office and the Indian Health Service IHS. Epidemiologist. Autopsies revealed that Florina and Meryl had essentially drowned as their lungs filled up with fluid, and the medical examiner realized she had seen a similar case just a month prior.
Huh.
More calls followed, and as different branches of the IHS learned of the mysterious deaths, A couple other similar cases came to light. In total, five severe illnesses with respiratory symptoms were put in a report which was distributed to hospitals all over the Four Corners area, asking physicians to look for similar cases. Within a few weeks, twenty four suspected cases had been identified, mostly adults or young adults, mostly otherwise healthy. The hunt for the cause had begun
and it was all hands on deck. The CDC showed up in full force with EIS agents decked out in their spacesuits, and every lead was followed. Could it be pneumonic plague? This region is endemic for plague and neumonic plague carries a high mortality rate, but that form was rare there and screening quickly ruled it out. What about a nineteen eighteen like influenza? There were some striking similarities, the health and youth of most of the victims, the drowning,
and the lungs. It seemed plausible another influenza outbreak like the nineteen eighteen one would be well horrible. Yeah, yeah, you know, especially if you've listened to our first episode. Yeah, but again, Tests came back negative. Maybe it wasn't an infectious disease at all. Maybe it was a poison, which is another common cause of acute respiratory distress. But testing of homes revealed no potential poisons. The usual suspects were out.
It was time to widen the search. Tissue samples from those killed by the infection were sent to the CDC in Atlanta, Georgia to screen against their enormous database of pathogens. Several different types of viruses were selected for the first run due to the way they caused disease. Among these were hauntaviruses, fortunately, which matched the tissue samples. There it
was the first piece of this puzzle. Ah, But in some ways this clue raised a lot more questions, like is this a virus we've seen before or is this a brand new species of hantavirus? And if it's a brand new, where did it come from? And why are we only seeing it now?
Yeah nineteen ninety three? Like where did this just pop about? Of nowhere from?
Yeah?
Tell me.
By this time, the press had picked up on this apparent outbreak, and as per usual, began wild speculations as to the cause of the disease. They also gave it a name, initially Navajo flew terrible. Yeah. Yeah when they gave it this name because the first several people who were infected with the virus were a Navajo. But this
name was both stigmatizing and inaccurate. Since this was a hantavirus, close association with rodents was undoubtedly implicated as a risk for infection, and in popular media it was implied that living in poverty or unsanitary conditions greatly increase that risk, which simply wasn't true. Yeah, both rodents and the infection were not limited to any particular ethnicity or income level. Yeah,
but the damage was done. Associating a diagnosis with shame often makes people less willing to come forward to either seek treatment or discuss any aspect of their disease, and with a case fatality rate of seventy five percent, this was not in the best interest of anyone. When it came time to name the virus, which had been confirmed to be a new species of huntavirus, there was an
effort to be more judicious with the naming. The names of nearby geographical features were put forth and ultimately sinnombre, meaning without name, was chosen supposedly after a canyon named Sinnombre, but apparently no one has been able to find it on a map.
I did not know that about the canyon. But I love the name Sinnombre virus. I think it is the most ba it is. It's so fitting for a virus that is this scary.
Yeah, well it was. It was so contentious. The naming was so contentious because like the CDC wanted to name it one thing, and someone else wanted to name it someone else, and it was just like, you know what, it is the perfect name.
It's a really name.
It's a shame that it can only be used once. But still, even though this name existed, the question why now remained. Yeah. The first step to answering that was to determine which animal was responsible for the outbreak. Since it was a haunt of virus, it had to be a rodent, so individuals of twelve different rodent species were rounded up and tested. The culprit Paramiscus maniculatis. The deer mouse A little babe, so cute, You're so cute. But it wasn't like deer mouse had suddenly moved move to
the Four Corners region. The species actually had an enormous distribution, covering most of North America. So why was this the first time we were seeing a disease associated with it. The short answer is that deer mouse population levels in
nineteen ninety three were high. Yeah. In other parts of the world, peaks of hantavirus cases were known to follow peaks and rodent populations, and this pattern has been well established in Fenescandia, for instance, where the carrier of Pumla virus, the bank Fowle, has about this three year population cycle.
You guys, if you don't know, Aaron Welsh is studying voles and disease in Finland right now during the post doc, so she hal cover. She has an extra smile on her face describing the life cycle of a vol to you right now.
I am very thrilled about this. I love it. I'm very thrilled. But trying to fake figure out what is driving those cycles is pretty dang complicated because it often ends up being a mixture of many things, including resource availability, predator abundance, competition within species and among different species.
I mean, the list goes.
On ecology, man ecology.
And this means an ecology also means Long term monitoring of these rodent populations is necessary if you want to understand the cycle, especially if you want to understand the cycle enough to predict it. Unfortunately, in the Four Corners region there wasn't really extensive long term monitoring, so while anecdotal reports of high rodent populations in nineteen ninety three were plentiful, any empirical evidence of population increase was hard to come by.
But there were a few clues, and El.
Nino year in nineteen ninety two meant increased rainfall to the Four Corners region. This increase and rainfall meant a huge harvest year for pinion pines, which produced nuts that act as a favorite food source for our little deer mouse friends. These plentiful food resources and a relatively mild winter allowed the rodents to a survive and b throw in an extra breeding cycle which increased their population quite a bit. So researchers turn their focus to the past.
This may be a newly described virus, but it wasn't new to the deer mice that carried it. In fact, it had probably been around for millions of years, adapting alongside its host, and for their scrutiny of past medical records and examination of preserved tissue showed that sinnombree virus had actually struck in the US decades before, not as extremely as it did in nineteen ninety three, but it
has been around. Why it was only recognized in nineteen ninety three was probably a combination of a lot of things, like the observant eye of healthcare practitioners, rodent population dynamics, el Nino blame it on al Nino, and.
Other factors.
Since the nineteen ninety three outbreak of synombree virus, there has been an explosion of other hauntaviruses coming to light all over the world, some with worrying traits like is that one in South America? Possibly the andes virus? Is that transmitted person to person?
Right?
Who knows?
Terrifying if it is.
But yeah, and if that's the case, how would we even begin to control that? It's very Yeah, it is an alarming thing.
Yeah, because, by the way, there is no treatment for this.
No spoilers.
Sorry, I should have said it in the biology.
I should have asked it in the biology. But yeah, like I said, the history of hantaviruses is still ongoing, and I'm super curious to hear where we stand in terms of treatments, which apparently is nil, vaccines, et cetera. Aaron, tell me about hauntaviruses today.
Please, Okay, so what part of hauntaviruses do you want to talk about the most?
I want to know two things in particular, Okay, One is how many people get sick every year all over the world with these different pulmonary or hemorrhagic syndromes. And then I also want to know how are we actually preventing it?
Yeah, good questions. So in the US, we'll start there. That's where we ended with the history. In the US, there have been a few outbreaks recently. Probably the most famous one that you might have heard about was in twenty twelve, there was a relatively large outbreak of HPS in Yosemite. There were ten confirmed cases and three fatalities. Yeah, yeah,
so that happened. There was also in twenty seventeen an outbreak of soul virus, so not HPS but HFRS caused by soul virus in the US in eleven different states. There were sixteen people infected, and they also found thirty one infected ratteries. Tell me what's a rattery where they bringing rats?
Is that real?
Yeah, that's real.
A rattery is something, it's a.
I mean, I'm assuming that's what I have what is a rattery in my notes? But I'm assuming that's what a rattery is.
It is also a village in Civil Parish in Devon, England.
Well, there you go. But as of January twenty seventeen, in the US, there have been seven hundred and twenty eight cases of hantavirus that have been definitively identified across thirty six states, mostly New Mexico, Colorado, Arizona, and California. Okay, that's in the US, but obviously the US for whatever reason, has very very low case numbers. In China there are thousands of cases annually, likely between twelve and twenty thousand
cases every year. In Finland there have been some years where up to three thousand cases have been reported, and then elsewhere in Europe, in Germany, in Slovenia there can be up to one thousand or so cases a year. In some areas, they've done testing to try and just figure out what serial prevalence is and it's as high as two percent, which means that up to two percent of the total population has been exposed at some point.
And then there's also been clusters of cases throughout South America as well, in Paraguay, Argentina, Panama, Brazil, Uruguay, and most of these are due to Andy's virus.
That's a lot of Hanta.
It's a lot of Hanta. It's way more than I expected in terms of current research. It's really interesting. So there was a vaccine that was developed in the early nineties actually so I think as far as I know, it was actually before Sinombre virus was discovered. This virus was in development in China. It's called Hanta vax. It is licensed, I believe, in both China and Korea, and it's it's a vaccine. They have it, you can get
it there. It's only effective for Hantan and soul viruses and it hasn't been approved for use in Europe or the US, but it's thought that it wouldn't be effective against the viruses that circulate in the US and Europe anyways. Okay, but by using this vaccine they have pretty substantially decreased the number of cases of HFRS in China.
That was like twenty five years ago. Yeah, basically, so are there other vaccines, because it seems like it would be if there's already a vaccine for one hanta, it wouldn't be that difficult to make vaccines for other ones.
Yeah, it's very interesting. It's interesting to me that there there's definitely a lot of research going on about vaccines. So there are various different vaccines that are in development. There aren't any others that are licensed, and from what I can tell, it seems like most of them are
still in rather early phases of development. And I think that in part in the US at least, it's likely because this causes so few cases every year that there's not a lot of incentive, Right, there's not a lot of financial incentive to protect against a disease that's only caused only quote unquote seven hundred cases over the last twenty five years, right, unfortunately, right, Yeah, right, But I mean in other parts of Europe it causes a significant
amount of disease, but it's not that lethal of a disease. So, but there are vaccines that are being developed. What's very cool is that a lot of the research that's being done right now is on DNA vaccines, and I will
admit I don't know that much about DNA vaccines. Yeah, so, okay, most vaccines, what you're injecting is either a whole virus or parts of the outside of the virus, like the proteins of the virus, or the toxin of the bacteria, like inactivated toxoid from bacteria, because that's that's what your body is going to generate an immune response against. Are those outer proteins. DNA vaccines are vaccines that include DNA that codes for those viral proteins rather than the viral proteins themselves.
Why is that an advantage over the proteins.
So one thing is that it's easier to make multi valent vaccines, so you can make one plasmid that has proteins for a whole bunch of different hontaviruses.
Oh m G.
I'm so glad that worked really well the way that you asked that, because it's really good flow, because I had it all right there.
It's good.
Yeah, So it's pretty cool.
I that's so cool. It's very cool.
I don't know a ton about them. I know they're kind of one of these hot things in vaccines right now, and I'm sure I'll do a lot more research on them for our vaccine episode in the future. But it's very cool and it's definitely something that's in the works. In animal models, they do seem to be effective. They've
started to test them on humans. But from what I understand, one of the biggest issues is the mode of delivery, So trying to make sure that the way that you deliver this DNA vaccine is going to be the most effective.
So hmm, okay, yeah, that is fascinating. It's very fascinating. So there's very cool research being done right now with hantaviruses and with vaccine development. It's it's a cool area.
Wow.
Yeah, oh man, my mind is blown open as this DNA vaccine situation.
I'm gonna have to go on a little. It's pretty good.
It's pretty cool stuff. Does infection with one of the hauntaviruses make you immune to subsequent infections or make you immune to other infection to other hantavirus infections?
As far as I know, it definitely does not make you immune to infection with other hantaviruses, which is part of why the haunted vax vaccine doesn't work. For Yeah, I don't know, I would assume that once you've been infected with say sin nombrevirus, if you survive, you probably won't be infected with sin noo brevirus again. Okay, yeah, so probably what everyone wants to know is how to not get haunted virus. Yeah, since we don't have a vaccine in the US.
And we have friends who work on mice and voles.
Yep, including you, so erin, here's how you cannot get anti virus in the future. Basically, if you are in a place like you're cleaning out your grandma's cabin or something, assume that it's invested with rats or mice, because it probably is, and first you air things out before you clean anything out. You try and get rid of any rodent infestation if you can, and don't vacuum up dry mouse poop and.
Stuff or like with a broom or with a broom.
Yeah, so CDC recommends that you wet everything down with ten percent bleach or some other disinfectant and let it sit for a while, and then you make sure that everything is wet essentially when you clean it up, instead of cleaning everything up when it's dry.
I mean, it's if you're inhaling the particle. So just think about how to prevent yourself from inhaling these, you know, poop particles, particle, pea particles.
Pea particles. Yeah, it's like a lot of bleach and spray bottles, is what the CDC recommends. They say, where protective gear and do this in a well ventilated area. Don't just sit in an attic full of ret pee.
I do have a question, mm hm, how scared should we be of haunt of viruses?
You living in Finland or me living in Illinois or everyone who's listening.
Everyone who's listening, everyone.
Who's listening, Eh, not so scared. Okay, it's a scary illness, but it's not super common and you can protect yourself from it. But yeah, I would say, not not super scared. Don't let this one keep you up at night.
Okay, Well, there's plenty else to do exactly to keep us up at night.
There's plenty of things to have anxiety about, versa and preanza. Yeah. So we recorded this episode a few weeks ago, and since then there have actually been some updates on the status of hauntavirus worldwide. Specifically, there have been a couple of outbreaks that have been reported since we last recorded, so I wanted to give you guys an update so
that your is up to date. Possible. Number One, there have been at least one hundred and three confirmed cases that happened in Panama over the course of twenty eighteen, including fifty one of those which were classified as hauntavirus without pulmonary syndrome and forty eight that were classified as HPS, including four deaths. In Argentina, there's actually an outbreak happening
currently as of January fifteenth, twenty nineteen. The most recent numbers that I've found are at least twenty eight people in the hospital currently under observation for hauntavirus infection and eleven people that have died so far. So this is an ongoing outbreak. So we'll try and keep you guys updated on Twitter and our social media as to what's going on. Update over so sources sources.
I used a couple of sources. What is a book called of Mice, Men and Microbes by Andrea S. Meyer and David M. Harper. Another is called Hauntavirus Hunting by Ho Wang Lee, and so that is the man who discovered the virus did the diagnostic test vaccine, et cetera. Cool, and then finally some excerpts from a book titled Hantaviruses which is added by C. Schmall, John and st Nickel. And then also apparently in the X Files movie it's
mentioned that hauntaviruses were brought by aliens. I didn't manage to watch it to verify, but amazing.
Yeah, I have a number of articles. We as always will post all of our sources, books and articles on our website this podcast will kill You dot com, so you can find them all there.
I really enjoyed learning about hantaviruses too.
It was a fun one to research.
It really was.
Thank you to Bloodmobile for providing the music for this episode in all of our episodes.
And thank you to you listeners and to everyone who has ever written a message to us. We really appreciate it, and we if we haven't responded, we're really sorry. We want to and we're going to try to. We're just two people and we're doing this like we each have full time jobs in addition to doing this.
And this is our for funds, and it's super fun to get to hear from you guys, and we really love it, so we apologize if we have ever written you back. We've read your message and loved it, and we're trying.
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