This Podcast Will Kill You - Ep 18 Hantavirus: The Real Rat Race

Episode Date: January 22, 2019

What do Korea, Slovenia, Finland, and the southwestern US all have in common? If you guessed Hantaviruses, you’d be quite correct. Today we bring you all the details on hantaviruses, from the deadly and terrifying hantavirus pulmonary syndrome, to the less lethal but still horrifying hemorrhagic fever with renal syndrome. From its long road to discovery, through the infamous 1993 outbreak and up to the present day, you’ll never look at an adorable little deer mouse the same way again.  See omnystudio.com/listener for privacy information.

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and expert partnership, Comcast Business is powering the engine of modern business, powering possibilities. Restrictions apply. 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. This is a bad one. Every episode. Hello. Hello. I'm Aaron Welsh. I'm Aaron Allman Updike. And this is, this podcast will kill you. Yeah, it is. And this week we are talking all about hanta viruses. Yeah.

And so what you just heard was an excerpt from the book of mice men and microbes, which goes into the history of hanta viruses with particular focus on the sinombre 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 time. Quarantinis. What are we drinking this week? This week we're drinking the mouse trap. It is so good.

Unbelievably delicious. It has tequila. Which is arguably the best liquor. I'm not even going to, I'm immediately cutting that. Okay. It could be argued, but I think I have a different one in mind. All right. Anyways. 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 quarantini, the mousetrap, as well as the placebo rita on all of our social medias. Which is our non-alcoholic version of our quarantini. 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. It's 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. Okay.

I'd love to. Haunta virus is, aka ortho-hontoviruses. 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 hauntaviruses to ortho-hontoviruses at some point recently. The phylogeny of this is confusing. to me. Sometimes they call it the order bunia virales. Sometimes they call that the family, bunya viridae. Who knows? If you see the word boonia virus, that is a larger group of viruses that includes the hanta viruses.

It also includes a lot of other viruses which cause horrible diseases, including Crimean Congo haemorrhagic fever, Rift Valley fever, several different encephalitis viruses, and so many more. So this is a pretty gnarly family group. It's a gnarly dinner shows up every night, whether you're prepared for it or not.

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now available in Canada too. That's Q-U-I-N-C-E dot com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. 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 haunted viruses 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 buniaveridae or buniaveralus group

are transmitted by ticks or mosquitoes, not hauntaviruses. Right. So hauntaviruses, in contrast, are transmitted through rodent excrement. Mmm, yummy. It's so fun. What I love is that, so arthropod-borne viruses that are transmitted by ticks and mosquitoes are often called arboviruses. You could call these robo viruses.

Rodent-born? I love it. Anyways. Very, very sci-fi. It's very sci-fi. So honda viruses 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 hanta viruses 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, haunted. 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 hauntavirus 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 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 knowing this leading question. So, yes, it's actually hantavirus pulmonary syndrome that is the more severe of the two disorders. So what I'm going to do is I'm going to go through each of these two disorders, Haunted virus 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 people are probably more familiar with if you live in the United States because this is caused primarily by synombre virus. And this is the hanta virus that exists in the United States, in the southwest.

It's hosted or 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 38 to 50%. 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, Hontavirus Pulmonary Syndrome. Okay. It starts after an incubation period of between nine and 24 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. Fibrile 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 stuffy nose, 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 12. So again, is it, 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? Probably. Or is it just that the virus really is host like individual dependent. I think it's probably a combination of both. So Haunted virus pulmonary syndrome, we don't, there's not, there haven't been a ton of cases of this. So you're definitely going to 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 the, this is just a total side note, but it started with the fever would have also been a great name for the,

this podcast. Oh, it would have been. Oh, shoot. 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, the disease and it happens really fast within 24 to 48 hours after these symptoms start up to 50% of infected people will die oh 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

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 adema can happen other ways as well. Yeah. Ooh, 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 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 sense. 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. So your blood pressure is just like totally down. Yeah. Yeah, cool, right? So this results. 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 oliguria, which means low urine, few urine. It's not good. And yeah, so that basically 50% of people are going to die. However, the other

50%, or sometimes more, it could be as low as 30% of people who die. So 50 to 70% 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, okay. I would love to have a great answer on that. it is unclear to me. If your urine 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? Yeah. We'll talk about exactly what causes that, what allows for that blood to leak out in just a second because it's a really important part of this disease. So that's HPS, Hontovirus pulmonary

syndrome. Let's talk about hemorrhagic fever with renal syndrome. So this is the other form of hauntivirus, 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 U.S., you might never have heard of this. This is caused by a number of different hantiviruses, including Seoul virus, which was first discovered in Seoul, 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. Pumala, is that how you say that? Pumala.

Pumala virus, which is from Finland. And hosted by the bank bowl. And Dobrava virus. Dobrava? Dobrava. Dobrava virus. Whatever. which was discovered in Slovenia and is hosted by the yellow-necked field mass.

That's a lot of viruses. So all of these viruses, which are different hanta viruses, cause various forms of HFRS, hemorrhagic fever with renal syndrome. 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 1 and 3%. Whereas Hatton virus has a mortality rate of between 5 and 15%. So it's a much more severe illness. What's interesting is that because these viruses, causes diseases of varying severity. In different countries, they have different names for them.

So for a while, the disease that Hantan virus causes was called KHF or Korean hemorrhagic fever. Pumala virus, the disease it causes is often called nephropathia epidemica. It's absurd. They're all the same disease. I'm going to argue, and hopefully you'll agree with me by the end of this episode, that all of the diseases caused by hanta virus should be. called the same thing. I'm not alone. I have an article to cite 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 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 thrombocytopinia, 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, which, though we didn't have a phase called oliguria in HPS, we did see that you also have a drop in urine output. The biggest difference here is that the effects of HFRS 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 going to have a cough. You're not going to have the pulmonary edema. Does that make sense? 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 urine 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 polyurec phase, which means a lot of pee. They'll start to diarise and pee a whole bunch out. And then convales. Cool. Cool. So the question is, not cool. It's terrible. It's 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. Haunted viruses 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 hanta virus 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 pulmonary versus renal? Yeah, so the ones in South America do tend to cause more HPS-like symptoms, at least from

I read. Okay. So yeah, it's just, it's so interesting. 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 seems 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, this disease cannot be transmitted person to person. There's like one case where it possibly, a hauntavirus, Andy's virus in South America was possibly transmitted person to person, but every other

Haanta virus 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, Erin, 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 hanta viruses 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 hantoviruses 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. And because of this, humans have probably been exposed to or infected with hanta viruses for millennia. But it's not until really like a long time ago, 960 AD. I'm like, oh, but it's not until. It's a long time. Right.

So 960 AD, 1,000 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 hemorrhagic fever with renal syndrome. But then it more or less disappears from medical textbooks for almost 1,000 years. Although, side note, some people believe that the mysterious. a sweating sickness that plagued England and continental Europe during the 15th and 16th centuries might have been caused by a hantavirus. Really? Yeah.

So apparently the symptoms were fairly similar. There was the seasonal pattern and then these irregular intervals. Oh. But it's still far from conclusive. So for one thing, the sweating sickness seemed to be transmitted person to person, which is rarely or never seen in hantavirus outbreaks. And for another, outbreaks appeared suddenly and disappeared suddenly without any mention of previous cases or reports. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've

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Xfinity. Imagine that. 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 on our list. Yeah, it is. It is. In any case, it's not really until the 1860s that we get a clearer sense of hauntavirus outbreaks in humans.

In the U.S. in the 1860s, the Ss were not very U. What? in the U.S.? That was so dorky, Aaron. 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 1862 and 1863, and an estimated 14,000 soldiers came down with this disease, whose symptoms strongly resembled that of the hanta virus caused field nephritis experienced by troops in Flanders during World War I. Hanta virus 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. just any soldiers, but ones who were huddled in trenches for long bouts of time. Researchers in the 1930s and 40s 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, you know, 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 731, whose official innocuous title was the Epidemic Prevention and Water Purification Department.

Throughout the eight-year existence of this program, over 3,000 men, women, and children, both prisoners of war, as well as civilians, billions 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 War II? Weapons 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? Mm-hmm. So they fully, it's not like they were just like, oh, it's fine. And they were like, we know this is not fine. We're just going to do it anyway and pretend like we did it on a monkey.

Yeah. Cool, cool, cool, cool, cool, cool. Right. Cool. Okay. But I haven't even gotten to one of the most outrageous parts of this. Okay. Which is that when the U.S. found out about this human experimentation,

instead of prosecuting any of the researchers or leaders involved in Unit 731, the U.S. granted them complete immunity as long as they provided all of their results to the U.S. and none of the other allies, namely the Soviet Union. That is zero percent surprising, quite honestly. I know, which is also very sad. It's very sad, but not surprising. But yeah, but you should really like, if you have time, just check out the Wikipedia page. Even with just a skim, it is shocking and does something that deserves a lot of,

lot more attention than what I'm giving it right now. Oh, my goodness. So maybe another episode anyway. But yeah, Unit 731 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 1950, various European and Asian countries were familiar with hantavirus-ca-caused infections and their association with rodents, even if they still didn't know what a hantavirus 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 1950 when North Korean troops invaded South Korea, seeking complete control of the divided country.

UN forces largely comprised of U.S. 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 front line barely moving from the 38th 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 3,200 U.N. soldiers came down with the illness and 121 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 Fenniscandia to narrow down which rodent might be responsible for disease outbreaks there. In that case, a totally different species was implicated, as you mentioned, myodes glariolis, the bankful. 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 Dr. Hoang Lee comes in.

A physician, epidemiologist, and virologist from South Korea, Dr. Lee had to be a doctor, had set his sights on discovering what was hiding in these rodents that caused illness in humans. And in 1976, he achieved his goal when he found evidence of viral antigen predominantly in lung tissue of an Asian striped field mouse. Hmm. 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 hauntivirus as well as a lot of other realtylial. important ecological and medical research on hanta viruses. And side note, actually, according to Wikipedia, he is the first person in the history of medicine to identify our 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?

That'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, often other geographical markers are still used. Dr. Lee chose to name the virus after the Hantan River. This river flows near the 38th parallel, which divides north from South Korea. This area was a hotspot for haemorrhagic 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, Dr. 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 Hantan virus, and it would soon gain many relatives. So earlier, when you mentioned that this is, that hauntaviruses are transmitted by, through rodent excrement, whereas all the other Buna Virde are transmitted through arthropods. Yeah. So some researchers believe that it could indicate that hantaviruses are actually older.

There are more basal subgroup within Bunevirae. Oh, cool. Yeah. Okay. Anyway, with this diagnostic test that Dr. Lee had developed, it was now possible to test patients from all over the world, particularly in those regions where a similar hemorrhagic fever or renal syndrome of unknown origin was known to pop up. This led to the discovery of pulmonary virus, soul virus, prospect hill virus, et cetera, 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 1993. Yes, I've been waiting for this. Bill Clinton is 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 the four corners region of the U.S., 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 21-year-old Navajo woman named Florina 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, 1993. Her fiancé, a 19-year-old Navajo man named Merrill Behi, 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 Florena. It's five months of a little. It's 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 Florena and Merrill 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. 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, 24 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 pneumonic plague carries a high mortality, right? Yeah.

But that form was rare there, and screening quickly ruled it out. What about a 1918-like influenza? There were some striking similarities, the health and youth of most of the victims, the drowning in the lungs. It seemed plausible. another influenza outbreak like the 1918 one would be well horrible yeah you yeah you know if especially if you listen 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 hauntiviruses. Yes. Fortunately, which matched the tissue samples. There it was.

The first piece of this puzzle. Ugh. 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 hanta virus? And if it's brand new, where did it come from? And why are we only seeing it now? Yeah, 1993.

Like, where did this just pop up out 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 that the cause of the disease. They also gave it a name initially. Navajo flu. Terrible. Yeah. Yeah. Way to go. And they gave it this name because the first several people who were infected with the virus were in Navajo. But this name was both stigmatizing and inaccurate.

Since this was a hanta virus, close association with rodents was undoubtedly implicated as a risk for infection. And in popular media, it was implied that living in poverty or in sanitary conditions greatly increased that risk, which simply wasn't true. Both rodents and the infection were not limited to any particular ethnicity or income level. 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 75%, 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 hanta virus, there was an effort to be more judicious with the naming. The names of nearby

geographical features were put forth, and ultimately sin nombre, meaning without name, was chosen. supposedly after a canyon named Sin Nombre, 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 Sin Nombie virus. I know. I think it is the most B.A. It is, it's so fitting for a virus that is this scary. Yeah. Well, 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 someone else and it was just like you know what it is the perfect name it's a really 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 hanta virus it had to be a rodent so individuals of 12 different rodent species were rounded up and tested. The culprit? Paramycous maniculatus, the deer mouse. The little babe. So cute. They're so cute. But it wasn't like deer mouse had suddenly moved 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 1993 were high. Yeah. In other parts of the world, peaks of hantavirus cases were known to follow peaks in rodent populations. And this pattern has been well established in Fenniscandia, for instance, where the carrier of pummelivirus, the bank vault 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-dot. So 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 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 with inspeas, and among different species, I mean, the list goes on. Yeah, ecology, man. Ecology. And this means, and 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 population, in 1993 were plentiful, any empirical evidence of population increase was hard to come by. But there were a few clues. An El Nino year in 1992 meant increased rainfall to the Four Corners region. This increase in 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 allow 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 the scrutiny of past medical records and examination of preserved tissue, tissue showed that Sinombre virus had actually struck in the U.S. decades before. Not as extremely as it did in 1993, but it has been around. Why it was only recognized in 1993 was probably a combination of a lot of things, like the observant eye of health care practitioners, rodent population dynamics,

El Nino, blame it on El Nino, and other factors. Since the 1993 outbreak of Sinombray virus, there has been an explosion of other hanta viruses coming to light all over the world. Some with worrying traits, like, is that one in South America, possibly the Andes virus? Is that transmitting 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, it is an alarming thing. Yeah, because by the way, There is no treatment for this.

Spoilers. Sorry. I should have said it in the biology. Oh, I should have asked it in the biology. But, yeah, like I said, the history of hantoviruses 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 hanta viruses today, please. Okay. So what part of hauntiviruses 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 U.S., We'll start there because that's where we ended with the history. In the U.S., there have been a few outbreaks recently.

Probably the most famous one that you might have heard about was in 2012. There was a relatively large outbreak of HPS in Yosemite. There were 10 confirmed cases and three fatalities. Yeah. Yeah. So that happened. There was also in 2017 an outbreak of soul virus, so not HPS. But HFRS caused by sole virus in the U.S. in 11 different states.

There were 16 people infected. And they also found 31 infected ratteries. Tell me what's a rattery, where they breed rats. Is that real? Yeah, that's real. A rattery is something where you breed rats? I mean, I'm assuming that's what I have what is a rattery. my notes, but I'm assuming that's what a ratarie is. It is also a village and civil parish in

Devon, England. Well, there you go. But as of January 2017, in the U.S., there have been 728 cases of hauntavirus that have been definitively identified across 36 states, mostly New Mexico, Colorado, Arizona, and California. Okay. That's in the U.S. but obviously the U.S., for whatever reason, has very, very low case numbers. In China, there are thousands of cases annually, likely between 12 and 20,000 cases every year. In Finland, there have been some years where up to 3,000 cases have been reported. And then elsewhere in Europe, in Germany, in Slovenia, there can be up to 1,000 or so cases a year. In some areas, they've done testing to try and just figure out what,

zero prevalence is, and it's as high as 2%, which means that up to 2% 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 Andes virus. That's a lot of haunta. It's a lot of haunta. 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 90s, actually. So I think as far as I know, it was actually before Cineombie virus was discovered. Okay.

This virus was in development. In China, it's called hauntivax. It is licensed, I believe, in both China and Korea. And it's a vaccine. They have it. You can get it there. It's only effective for Huntan and Seoul viruses, and it hasn't been approved for use in Europe or the U.S., but it's thought that it wouldn't be effective against the viruses that circulate in the U.S. 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 25 years ago. Yeah. Basically. So are there other vaccines? because it seems like it would be, if there's already a vaccine for one Honda, it wouldn't be that difficult to make vaccines for other ones.

Yeah, it's very interesting. It's interesting to me that 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 U.S. 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, 700 cases over the last 25 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, what does that mean? 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 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 multivalent vaccines. So you can make one plasmid that has proteins for a whole bunch of different hantavirus. Oh, M.G. I'm so glad that worked really well the way that you asked that because this is really good. Because I had it all right there.

That's good. Yeah. So it's pretty cool. 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. out with hontoviruses and with vaccine development. It's a cool area. Wow. Yeah. Oh, man, my mind is blown open at this DNA vaccine situation. I'm going to have to go in a little dive. It's pretty cool. It's pretty cool stuff. Does infection with one of the hontoviruses make you immune to subsequent infections or make you immune to other infection, to other hontovirus infections?

As far as I know, it definitely does not make you immune to infectious. with other hanta viruses, which is part of why the hanta vaccine doesn't work for. Yeah. I don't know. I would assume that once you've been infected with, say, synonbri virus, if you survive, you probably won't be infected with synobre virus again. Okay. Yeah.

So probably what everyone wants to know is how to not get hanta virus. Yeah. Since we don't have a vaccine in the U.S. And we have friends who work on mice and voles. Yep, including you. So, Erin, here's how you cannot get onto 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 infested 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 anything. Or with a broom. Yeah. So CDC recommends that you wet everything down with 10% 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 particles, so just think about how to prevent yourself from inhaling these, you know, poop particles and pee particles. Pea particles. Yeah, it's like a lot of bleach and spray bottles is what the CDC recommends. They say wear protective gear and do this in a well-ventilated area. Don't you sit in an attic full of rat pee. I do have a question.

How scared should we be of hauntaviruses? 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, there's plenty else to keep us up at night. There's plenty of things to have anxiety about Mercer and Priyons. 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 you're as up to date as possible. Number one, there have been at least 103 confirmed cases that happened in Panama over the course of 2018, including 51 of those which were classified as hauntavirus without pulmonary syndrome and 48 that were classified

as HPS, including four deaths. In Argentina, there's actually an outbreak happening current Currently, as of January 15th, 2019, the most recent numbers that I've found are at least 28 people in the hospital currently under observation for hanta virus infection and 11 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 Haanta Virus Hunting by Hoang 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 Haanta viruses, which is edited by C. Schmal John and S.T. 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.

I have a number of articles. We, as always, we'll post all of our sources, books and articles on our website. This podcast will kill you.com. So you can find them all there. I really enjoyed learning about hanta viruses. Me too. It was a fun one to research. It really was.

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