Ep 206 Oropouche Virus: More than a smidge worrisome

Though discovered relatively recently, Oropouche virus has been making headlines as an emerging vector-borne infectious disease on the rise. Not transmitted by the usual suspects (like ticks and mosquitoes), this virus is instead spread through the bites of midges or no-see-ums. Since these arthropods are already widely distributed and their range is growing thanks to climate change, this is a recipe for potential disaster. In this episode, we take you through the story of Oropouche virus, from how it makes us sick to what the construction of a highway has to do with its discovery, from surprising prevalence statistics to the history of One Health. Tune in for the full scoop on this midge and the virus it carries. Support this podcast by shopping our latest sponsor deals and promotions at this link: https://bit.ly/3WwtIAu See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

• 0:01Speaker 00

  This is exactly right.

• 0:06Speaker 01

  Hey, I'm Niall Rogers. This fall, I'll be driving across the country, meeting some of today's coolest and most fascinating artists. We'll explore the stories before the moments that changed everything. Because every musician remembers the moment where it all began. Experience Before the Moment, a Lincoln original series on the iHeartRadio app, YouTube, or wherever you get your podcasts.

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• 1:14Speaker 03

  By US standards, Brazil's highway BR14 is certainly no Indiana turnpike or New York State thruway. Meandering 1,350 miles from Belem to Brasilia through the jungles and scrub of Brazil's wild interior, it is barely two lanes wide. The surface is dust in the dry season, mud in the wet, and some of the ruts could swallow a Volkswagen alive. Yet in the eyes of former President Juscelino Kubitschek, who built the road between 1956 and 1960, BR14 is "the highway of dreams" for underdeveloped Brazil and the means to "a new civilization on the central plateau." So it is.

• 1:56Speaker 03

  Since the road's opening in 1960, some 600,000 settlers have poured into the area to tap Brazil's immense riches. Every day, long lines of trucks rumble north and south, carrying out

• 2:10Speaker 03

  Lumber, rubber, and vegetable oil. New farmlands produce beans, rice, corn, and fruit to feed Brazil's exploding population. What was once useless scrub in the central state of Goiás is now pastureland for four million head of cattle. And prospectors fanning out from the road have found a vast mineral potential with deposits of nickel, tin, lead, zinc, copper, gold, diamonds, and quartz. Towns are sprouting every few miles. If I don't pass a certain stretch of road for two or three weeks, says one road engineer, I almost always find a new cluster of shacks there when I get back. Araguaína, which got its start in 1958 as a road construction camp 500 miles north

• 2:53Speaker 03

  of Brasilia, is now up to 8,000 people, has its own branch of the Bank of Brazil, and will soon have a $1.6 million factory that will refine oil from native barbecue nuts, peanuts, cotton and sunflower seeds, and produce the cans in which to export the oil and cut up local mahogany to make cases for the cans.

• 4:03Speaker 04

  I love your newscaster voice.

• 4:05Speaker 03

  Thank you.

• 4:06Speaker 04

  And I hate everything else about that whole.

• 4:10Speaker 03

  I think it, so that was from excerpted from a Time article published on January 7, 1966, titled Brazil on the Road to Dreams.

• 4:22Speaker 04

  Okay.

• 4:23Speaker 03

  And it's such a fascinating reflection, I think, of how forward progress was viewed at the time, like,

• 4:30Speaker 04

  Yeah.

• 4:30Speaker 03

  we must go forward. And like, it's also understandable.

• 4:34Speaker 04

  Right.

• 4:35Speaker 03

  Right? Like, there's, there's, this is the economy that's driving this.

• 4:38Speaker 04

  Mm-hmm.

• 4:39Speaker 03

  But the reason that we picked this particular article or this excerpt is because that construction on that road is what is thought to have led to the spillover and spread initially of the focus of today's episode, which is?

• 4:58Speaker 04

  Oropooshvirus.

• 4:59Speaker 03

  Oropooshvirus. Hi, I'm Erin Welsh.

• 5:03Speaker 04

  And I'm Erin Allman Updike.

• 5:04Speaker 03

  And this is This Podcast Will Kill You.

• 5:07Speaker 04

  Welcome to Oropooshvirus.

• 5:09Speaker 03

  Oropooshvirus.

• 5:10Speaker 04

  Yeah. Took us a long time to learn how to say that.

• 5:13Speaker 03

  Yeah. Like, this morning. We've gotten some requests over the years for this virus. And it's interesting, I feel like we've been seeing it trickle more and more in the news lately. And so we wanted to just kind of like, get a lay of the land. What's going on? How's it transmitted? Why is it suddenly making headlines?

• 5:32Speaker 04

  It's, it's gonna be a great episode, because I feel like it's really going back to your and my roots, Erin, of like, what got us wanting to make this podcast in the first place? And it's been a really long time since we've done a vector borne disease, since we've done an infectious disease. So.

• 5:46Speaker 03

  I was like, how do we do this?

• 5:48Speaker 04

  I know.

• 5:49Speaker 03

  There aren't many books to read on this.

• 5:51Speaker 04

  Right.

• 5:54Speaker 04

  So, yeah, we've got, we've got a lot for this episode. And I'm excited about it.

• 5:59Speaker 03

  Me too, me too.

• 6:02Speaker 03

  What are we drinking this week, Erin?

• 6:03Speaker 04

  We're drinking a Sloth Spritz.

• 6:07Speaker 03

  Yeah. Oropouche virus is often called sloth fever, or sloth flu, I've even seen it called.

• 6:15Speaker 04

  Oh, God.

• 6:16Speaker 03

  And I don't love it.

• 6:17Speaker 04

  No.

• 6:17Speaker 03

  But we are gonna honor the sloth in this way.

• 6:20Speaker 04

  I love sloths.

• 6:22Speaker 03

  I do, too. I do, too.

• 6:24Speaker 04

  Yeah.

• 6:24Speaker 03

  Tell us what's in sloth spritz.

• 6:27Speaker 04

  You know, it's a delicious little concoction of passion fruit juice, or whatever.

• 6:33Speaker 03

  Nectar.

• 6:34Speaker 04

  Nectar, passion fruit, lime, mint, and, you know, some bubbly of some kind.

• 6:40Speaker 03

  Yeah.

• 6:40Speaker 04

  Your choice.

• 6:41Speaker 03

  Easy peels, delicious, refreshing, et cetera. All of the above. We'll post it.

• 6:46Speaker 04

  On our website. On our socials.

• 6:48Speaker 03

  Yeah.

• 6:48Speaker 04

  On our socials, not our website.

• 6:50Speaker 03

  Yeah.

• 6:50Speaker 04

  But on our website, you can find a lot of other great stuff. Like, for example, transcripts from all of our episodes, sources from this and every single episode, Bloodmobile, who does the music. We've got merch. This is an old one. I don't know if it's still available.

• 7:04Speaker 03

  I love that shirt, though.

• 7:05Speaker 04

  Me, too. We've got Patreon. We've got a contact us form, a firsthand account form. Listen. It's big.

• 7:15Speaker 03

  Listen and look, yeah.

• 7:16Speaker 04

  ThisPodcastWillKillYou.com.

• 7:18Speaker 03

  It's there. It's there. I have a piece of business because this has been bothering me since we listened to the episode for, like, QC purposes. You know what I'm gonna say, Erin.

• 7:29Speaker 04

  I do.

• 7:29Speaker 03

  Elephant poop.

• 7:30Speaker 04

  I didn't at first.

• 7:31Speaker 03

  This has bothered me deeply that I messed this up. Elephants poop, if I had thought about it, I would have, I would have, I would have realized that 15 pounds sounds like a lot to us, but for an elephant, which is gargantuan.

• 7:45Speaker 04

  Right.

• 7:46Speaker 03

  Actually doesn't sound like that much in a day.

• 7:48Speaker 04

  Yeah.

• 7:48Speaker 03

  And it's true. It's not that much for an elephant in a day. 15 pounds is more like in one poop sesh. Throughout the day, it's about 220 pounds that they poop. And they poop like 12 to 15 times a day. So that's how that maths.

• 8:01Speaker 04

  Wow.

• 8:02Speaker 03

  Yeah.

• 8:02Speaker 04

  12 to 15 times a day?

• 8:04Speaker 03

  They're basically, it's just...

• 8:05Speaker 04

  They're just poop pushing.

• 8:07Speaker 03

  Yeah. A constant.

• 8:10Speaker 04

  Wow. I love knowing that fact.

• 8:14Speaker 03

  Subscribe for more poop facts.

• 8:17Speaker 04

  What's really funny, Erin, is in that episode, when you say 15 pounds, I'm like, "Oh, 15 pounds!" Because I also clearly was like, "That sounds like so much." I think numbers are really hard to conceptualize sometimes.

• 8:28Speaker 03

  I mean, when you're talking about pounds of poop, it really does feel... Yeah.

• 8:33Speaker 04

  Yeah, so anyways.

• 8:35Speaker 03

  Anyways, that's my correction. Oh, I just wanted to mention, this is technically the start of season nine.

• 8:41Speaker 04

  I know.

• 8:42Speaker 03

  There's no break.

• 8:44Speaker 04

  Right.

• 8:44Speaker 03

  And so if we, if you hear us say season nine, or new season, or whatever, it's only for, at this point, our file organizational system.

• 8:51Speaker 04

  Our file, but I'm also like, I think our hearts, because I'm really proud that we've made it to season nine. Are you kidding me? We've been doing this for that long?

• 9:00Speaker 03

  Yeah, Halloween 2017.

• 9:02Speaker 04

  Yeah.

• 9:03Speaker 03

  We're still, there's still more things that can kill you, so, speaking of...

• 9:07Speaker 04

  A whole season planned, but first, we begin with, "Or a pooch virus."

• 9:13Speaker 03

  Right after this break.

• 9:17Speaker 01

  Hey, it's Niall Rogers, host of Before the Moment, a Lincoln original series. I'm driving across the country, meeting some of today's most fascinating artists. We're exploring the stories before the moment that changed everything. This week, I'm joined by rising star Sienna Spiro. What is so fascinating to you about impermanence?

• 9:39Speaker 00

  Everything about us, everything we do is, is temporary. And I just got terrified of that, you know, what we do with our time and how I feel like the way the world is today and how fast paced it is and how much we don't even acknowledge anything around us, how I felt temporary to the people around me and how that made me scared and how much I wanted to last and make an impact on people and, I guess, to change the way I looked at things and to change myself and to change how I guess I approached everything in my life. It's important that things are impermanent because nothing would feel special and enjoying, you know, learning to love with knowing it's not going to last.

• 10:13Speaker 01

  Experience Before the Moment, a Lincoln original series on the iHeartRadio app, YouTube, or wherever you get your podcasts.

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• 11:49Speaker 04

  Oropoosh virus is an arbovirus, which means that it's a virus that is transmitted by arthropods, an arthropod-borne virus. Some of our favorites that we've ever covered, I think, are arboviruses, arthropod vector-borne diseases in general.

• 12:06Speaker 03

  I mean, disease ecology really, you know, yeah.

• 12:09Speaker 04

  It's in our heart of hearts.

• 12:10Speaker 03

  True.

• 12:10Speaker 04

  But one of the things that's quite unique about this virus compared to any other that we have covered before is that it's transmitted by a whole new arthropod that we have never talked about on this podcast, and that is a midge.

• 12:24Speaker 03

  A midge.

• 12:24Speaker 04

  So let's talk about what a midge is, shall we?

• 12:27Speaker 03

  Yeah, I am, I can't, I truly can't wait. I mean that sincerely.

• 12:32Speaker 04

  So a midge or a biting midge is a type of biting fly. And the term biting midge is not a very scientific grouping of biting fly whatsoever. Because in some places, these might be called sand flies, even though they might not be what we would have called sand flies. In other places, they might be called noceums. And there's probably even more other terms that people use for these. But in any case, these are teeny tiny, and by teeny tiny, I mean, they're like one to three millimeters long, like the, there's pictures of them online on someone's thumbnail where they barely take up the space that like between your cuticle and your thumb.

• 13:13Speaker 03

  Like barely see them.

• 13:14Speaker 04

  Yeah, no, barely see them. There's other pictures online of them next to a mosquito. And you think of mosquitoes, like, they're not very large compared to many other types of flies.

• 13:28Speaker 03

  Depending on the mosquito, but yeah.

• 13:30Speaker 04

  Yeah, some of them are hefty.

• 13:31Speaker 03

  Some scary ones, yeah.

• 13:32Speaker 04

  Right, but they're, but compared to a mosquito, they're like so teeny, they're like the size of a mosquito's head.

• 13:39Speaker 03

  That is teeny.

• 13:40Speaker 04

  I know, kind of adorable. And in this case, we're talking about these biting midges in the family Serato pogonidae. Specifically, the species, there's one major species that we think is the primary vector for Oropouche virus, and that is Culicoites paraensis.

• 13:58Speaker 03

  Yes.

• 14:00Speaker 04

  And these biting midges in, in this family and in this genus, they share some similarities with mosquitoes, but also quite a lot of differences. First of all, they're quite small. Their proboscis that they use to bite us and do their blood feeding is not nearly as long or robust as mosquitoes, so they can't as easily bite through our clothing.

• 14:21Speaker 03

  Oh, that's good news.

• 14:22Speaker 04

  It is good news. However, they're so small that they can fit through things like most of our screens.

• 14:29Speaker 03

  No.

• 14:30Speaker 04

  Yes, yes, so they're harder to keep out of your house and things like that.

• 14:34Speaker 03

  Okay.

• 14:35Speaker 04

  But similar to mosquitoes, their larvae are aquatic. And similar to mosquitoes, it is only the females who bloodfeed in order to mature their eggs. So in the case of Oropouche virus, this midge, Culecoedes paraensis, will take a blood meal from an infected person or animal, we'll get there. And then upon their next blood meal, will spit that virus back out into another host. And that is kind of all that I can say about the transmission cycle. Sometimes in these virus or arbovirus or vector-borne disease episodes, we can get into a lot more detail about what's going on inside that vector, about how long it takes for this virus to disseminate and then be able to be transmitted.

• 15:19Speaker 04

  It is amazing how relatively little we know about this virus.

• 15:24Speaker 03

  Yes.

• 15:24Speaker 04

  So we think that this one species, Culecoedes paraensis, this one species of biting midge is the primary vector to humans and probably to other animals, too. But much like many other vector-borne diseases that we've covered on this podcast, there are kind of two different cycles of this virus.

• 15:44Speaker 03

  Right.

• 15:44Speaker 04

  There's a wild cycle or a silvatic cycle, and there is an urban cycle. And in the wild or silvatic cycle, it's thought that sloths, especially three-toe sloths, as well as, I know, right?

• 15:59Speaker 03

  They're like, I'm sorry, but they are the cuter sloth.

• 16:02Speaker 04

  But you don't have to apologize. Like by far.

• 16:05Speaker 03

  Yeah, it's quite dramatic.

• 16:08Speaker 04

  It is. They're the ones with the mask. If you haven't, if you don't distinctly know off the top of your head the differences between a two-toe and a three-toe sloth. In addition to the number of toes, the three toes are the ones with the black and white little mask. And the two toes are brown and...

• 16:22Speaker 03

  Have a little pig nose, which is also cute, but in a different way.

• 16:25Speaker 04

  I know. And I do like how fuzzy, like their fur is like longer. And anyways, this is not an episode about sloths.

• 16:32Speaker 03

  It should be. It could be. Another time.

• 16:35Speaker 04

  So it is thought that sloths, as well as non-human primates like capuchins and howler monkeys and some bird species, these are probably the most important vertebrate hosts of this virus.

• 16:48Speaker 04

  But when it comes to the vector species, we don't really know exactly which arthropods, which biting insects are playing the biggest role in transmission in this wild cycle especially. So we know that this biting midge, the Culecoilius paraensis, is definitely present in the Silvatic cycle. It definitely can and does bite freely other animals in addition to humans. But there's some evidence that various mosquito species, including some Culex mosquitoes, which transmit a wide variety of other illnesses, and some Aedes mosquitoes, which are the primary vectors for things like dengue virus, which circulates in the same area as Oropouche

• 17:31Speaker 04

  virus. Some of these mosquitoes have been found to be infected with Oropouche virus, but we don't really know, are they what we call competent vectors? Can they actually transmit this virus to other animals? And like, how big of a role do they play in the environment? We don't know, which is fascinating.

• 17:51Speaker 03

  Okay, so a question about that, like, what is the midge's habitat preferences?

• 17:58Speaker 04

  Great question. We don't really know. We don't really know. Apparently, the larvae, especially of these species, this species in particular, wasn't even like described and identified until the 1990s, which is so recent. And so we really just don't know nearly as much as we should about the natural ecology. And while other biting midge species are known to be important vectors of a variety of animal diseases, like blue tongue virus and other viral infections as well, I don't think that they have historically been considered as important of a vector of human diseases compared to something like mosquitoes. And

• 18:39Speaker 04

  so that's probably part of why their natural ecology and just their understanding as vectors and just in general is not as robust as for some other.

• 18:49Speaker 03

  It's just so interesting because I feel like they occupy, well, do they occupy a similar niche as mosquitoes? They, yeah, but like, there's, there's like, why do midges play less of a role? This is like a bigger question than.

• 19:05Speaker 04

  I don't have answers, but you can ask it.

• 19:06Speaker 03

  In general, you know, mosquitoes are what we think of when we think of like vector borne diseases, like mosquitoes, ticks and. Midges don't feature very heavily.

• 19:17Speaker 04

  Why? Why? Great question. I don't know.

• 19:22Speaker 04

  So, yeah, but so that's, we think, though, that this is the main vector species. There's one other species of culicoides as well that has sometimes been found to be infected that might play a role, especially in the urban cycle as well. And in the urban cycle, meaning in the human cycle of Oropouche virus, it really is us, humans, who play the primary vertebrate host. Our domestic animals do not seem to play a big role in the maintenance of this virus in urban cycles, except maybe chickens.

• 19:51Speaker 03

  Maybe chickens, asterisk, who knows? It's not, not clear.

• 19:54Speaker 04

  Yeah, we don't study it enough. We'll know a lot more in the coming years.

• 19:59Speaker 03

  Yeah.

• 20:00Speaker 04

  But there is still so much that we don't really know about this virus. What we do know is how it tends to present, even though the symptoms of Oropouche virus really overlap with so many other arboviral, so like vector borne viral illnesses, and just other viral illnesses in general.

• 20:22Speaker 03

  Right.

• 20:23Speaker 04

  So they're very nonspecific. The symptoms tend to start with a fever.

• 20:28Speaker 03

  Classically.

• 20:29Speaker 04

  Classically. Headache is a very, very common symptom as well as muscle aches, joint aches, dizziness, you might get chills. Oftentimes, people will have like ocular symptoms, eye symptoms, like photophobia, like your eyes hurt if you're trying to look at the light. Or sometimes people get like redness in their eyes. Not like as full on as like a, you know, red, like pink eye infection, but just a bit of like redness overall in the eyes.

• 20:59Speaker 03

  Isn't, doesn't that happen with Zika or chikungunya?

• 21:03Speaker 04

  It can happen with, it's so nonspecific.

• 21:05Speaker 03

  Okay. I just feel like that was like a feature symptom in one of those mosquito borne ones.

• 21:11Speaker 04

  That is more than I can remember, Erin.

• 21:14Speaker 03

  It could be a false memory. That's possible.

• 21:18Speaker 04

  Sometimes people will have some like GI symptoms like nausea, vomiting, abdominal pain. Sometimes they might have anorexia, like you just feel so sick, you don't really want to eat anything. Sometimes people can get a rash, and I've seen it described as kind of a rubella type of rash. And rubella, if you don't remember, is another viral illness, not vector borne, that causes this red, splotchy, pinpricky type of rash that often is on like the torso and then can spread to the face and spread downward. But it's really like a very kind of nonspecific viral looking rash is the way I would describe it. And rarely, sometimes people can have hemorrhagic symptoms. So that might be things that look like you're

• 22:02Speaker 04

  having a bit of bleeding, but not like bleeding everywhere, but maybe your gums, or maybe a nosebleed, or other kind of mucosal type of bleeding.

• 22:12Speaker 03

  How is the virus causing these symptoms?

• 22:18Speaker 04

  Great question, Erin. No idea.

• 22:20Speaker 03

  Okay.

• 22:21Speaker 04

  We know so little. I have, I have a bit on this later on, but I'll tell you now, Erin. We know so little about the like pathophysiology of what this virus is doing in our bodies. What cells is it even infecting? What cells does it preferentially infect? And where does it replicate? Like, are there specific tropisms? Meaning, are there certain types of cells that it preferentially is going to infect? And how? And why those cells? And what are these symptoms? We, we don't know. We don't know any of that, as far as I can tell.

• 22:49Speaker 03

  Okay, okay.

• 22:50Speaker 04

  So yeah, we don't know why it's causing these very nonspecific viral type symptoms. But it is. Another thing, though, that we see with Oropouche virus, that we see with a lot of other arboviral diseases, is that the course of your symptoms can be what we call biphasic. Meaning that three to 10 days or so after you get infected, that's the usual incubation period. So after you get these bites from this, these midges. And you get infected, you start with these symptoms that I've described. And that first phase usually lasts like two to four days or so.

• 23:26Speaker 03

  Okay.

• 23:27Speaker 04

  And then you will get better. But then a week to 10 days later, you might have a resurgence of very similar symptoms. How often does this happen? We don't really know because again, there's so much that we don't know. But it's suggested that it's like in up to 60% of cases, which is quite high. So quite common that you would have this kind of biphasic illness. And most of the time, I think the best news about Oropouche virus is that the vast majority of the time, this is a self limited disease, meaning

• 23:57Speaker 03

  Right.

• 23:58Speaker 04

  Those symptoms that I described, you feel miserable, you feel sick, maybe it comes back and it lasts for quite a while, but then you get better. When this disease causes more severe symptoms, which it can, it can result in a meningitis or a meningoencephalitis, meaning infection in the brain, brain stem, causing swelling in your central nervous system. Even in those cases, people almost always recover and recover completely as far as we know, and there are asterisks there. But up until 2024, Oropouche virus had not been known to cause any deaths. That's no longer true, but we'll talk more about it later.

• 24:38Speaker 03

  Okay.

• 24:40Speaker 03

  Immunity.

• 24:41Speaker 04

  Immunity, great question. We don't know.

• 24:44Speaker 03

  Okay.

• 24:44Speaker 04

  We don't know how good of immunity we generate. Is our antibody immunity like long lasting? Can you get reinfected with this? We don't know.

• 24:53Speaker 03

  Are there different strains or like subtypes?

• 24:56Speaker 04

  So there definitely are.

• 24:58Speaker 03

  Okay.

• 24:58Speaker 04

  There definitely are. And this is actually a really important part of Oropouche biology that we do know quite a bit about. So similar to flu viruses, Oropouche viruses are an RNA virus that has a segmented genome, which means their genome is not just like one piece of RNA. It's three different chunks. They're named small, medium and large, S, M and L. And similar to flu viruses, if a host, like say a sloth, is infected with two different strains of this virus at the same time, it can lead to a mixing up of different chunks of their genome and result in a completely new version of this virus,

• 25:40Speaker 04

  often one that is drastically different than either of the so-called parent viruses. There's actually a few other viruses that have different names: Iquitos virus, madre de Dios virus, and Perdois virus? I might be pronouncing that one wrong, which that one doesn't infect humans. But these contain parts of the Oropouche virus and then another segment from a related virus in the same, what we call serogroup, the same group of viruses. So yes, the fact that Oropouche can recombine is a really important aspect of the virology of this virus.

• 26:16Speaker 03

  Right.

• 26:17Speaker 04

  And we think it was probably involved in the most recent outbreak that we saw 2024, 2025, and we'll talk a little bit more about that later in this episode.

• 26:24Speaker 03

  Right, changing virulence patterns and transmission patterns and all of those things, yeah.

• 26:30Speaker 04

  And speaking of transmission, so this is a virus that is transmitted via vectors, right? Via these biting midges. There has not been shown so far any direct human-to-human transmission. So even if you're sick and miserable, you're not transmitting it to other people. However, similar to Zika virus, there is now evidence that Oropouche can be transmitted across the placenta. So if someone is infected while they're pregnant, it can infect the fetus, and it's been thought to be associated with a number of stillbirths, fetal losses, so miscarriages, and things like microcephaly, which is when the brain does not fully develop, similar to how we saw with Zika virus. Unlike with Zika virus, we don't know enough about the virology yet

• 27:14Speaker 04

  to understand what's going on, or how common, or any of that. But epidemiologically, this pattern seems to have come out of this most recent outbreak that we've seen. And so we do think that it's crossing the placenta and can cause damage to the fetus, which is pretty serious.

• 27:30Speaker 03

  But no sexually transmitted or maybe?

• 27:34Speaker 04

  Great question. At least one paper that I saw said that they thought that they had detected it in semen. Does that mean that it's able to be transmitted?

• 27:42Speaker 03

  Right.

• 27:42Speaker 04

  We don't know. It's a huge open question.

• 27:45Speaker 03

  Right, okay. Um, question about the habits of these biting midges. When, you know, how like mosquitoes love dawn and dusk, doesn't mean that they don't bite you in other times of day, but like, where do they bite you? When do they bite you?

• 28:01Speaker 04

  Yeah.

• 28:02Speaker 03

  Do, I'm assuming because they are, their larval stage develops in water, that there's like a seasonal or climate component to this? What's going on?

• 28:11Speaker 04

  Yes, you're very right. So there is definitely a seasonal and climate component. So we see that the highest burden of these, of Oropouche virus tends to be during rainy season.

• 28:23Speaker 03

  Okay.

• 28:23Speaker 04

  And that's going to be when you have more water available for larvae to, you know, mature. Um, and for the females to lay their eggs and things like that. So that's definitely the case. In terms of when exactly they bite, they can potentially be kind of throughout the day. They do tend to be dawn and dusk similar to a lot of, some mosquito species, not all mosquitoes are like that. But like I said, because they can't bite through clothing, they're going to tend to go towards areas that are more available. So a lot of times they're biting on legs, they're biting on arms, they're biting on things that they can actually access. And they're really voracious. Their bites hurt. And then beyond that, there's probably more that either I don't know or that we don't know yet about, about these vectors in general, that I didn't Google.

• 29:08Speaker 03

  And maybe you're getting there in the, in the current section, but distribution, geographic distribution of midges.

• 29:14Speaker 04

  Yeah, yeah. So this species of midge is found throughout Central and South America and throughout the southern part of North America, all the way up into like the eastern seaboard. You can even find them sometimes in Michigan and Wisconsin and things like that. And then all throughout the southern United States, which is an important part of the distribution of this virus so far, is that this virus has not been found everywhere, but the vector does exist far beyond the range that we have seen the virus so far.

• 29:46Speaker 03

  Right, which just means potential for spread.

• 29:48Speaker 04

  Potential for spread.

• 29:50Speaker 03

  Yeah.

• 29:50Speaker 04

  Exactly, yeah.

• 29:52Speaker 03

  Which is also, I mean, I know that we'll get there, but like, the fact that this virus can infect so many vertebrates.

• 29:58Speaker 04

  So many vertebrates.

• 29:59Speaker 03

  It seems like.

• 30:01Speaker 04

  And we don't know even.

• 30:02Speaker 03

  We don't know the extent.

• 30:03Speaker 04

  We don't know the extent. We, we, from what we have found so far, we think sloths, capuchins, howlers, and some birds, but like, birds is a huge category alone, right?

• 30:15Speaker 03

  Nah, it's just fun. It's just a few species.

• 30:17Speaker 04

  Just a couple of species of birds in Central and South America?

• 30:20Speaker 03

  I know, some of the most biodiverse areas on this planet.

• 30:23Speaker 04

  Right, exactly. So, yeah, so we don't, we don't know, you know, and who is playing the biggest role, who is involved in the spillover events, and why, like, we don't know any of those things.

• 30:35Speaker 03

  We don't know. We don't know.

• 30:38Speaker 04

  And, as is the case for so many, tropical especially, viral and other infectious diseases, diagnosis remains a really big challenge, and that severely limits our understanding of the true epidemiology and spread of this, because you can't diagnose it without adequate identification, especially because the symptoms are so nonspecific and they overlap so much with other diseases that are in the same geographic areas.

• 31:05Speaker 03

  Yeah.

• 31:05Speaker 04

  So you have to have access to either serology, or like PCR, RT-PCR, which isn't available everywhere, especially in the range of where this virus is found.

• 31:15Speaker 03

  Right.

• 31:16Speaker 04

  And, as with so many other viral illnesses, we have no specific treatment for it. We have no vaccine, and spoiler alert, no vaccines on the horizon that I have seen. Like, as of 2022, there was like, one paper about vaccine development for Oropouche virus, so this is pretty neglected.

• 31:37Speaker 04

  Viral illness.

• 31:38Speaker 03

  Yeah.

• 31:39Speaker 04

  Even though it's not technically considered a neglected tropical disease yet, which is wild.

• 31:44Speaker 03

  I mean, I think it's, it is, it's really interesting to read back through some of these outbreaks and epidemics and it's like so much, it's so much a shot, I don't want to say a shot in the dark, but like the, these estimates are based on the information that was available, which is, can be very often limited based on what you said, how you have to have testing, you have to have, and because the, the virus itself is so, tends to cause these self-limited infections.

• 32:10Speaker 04

  Right.

• 32:11Speaker 03

  Someone's better in a few days, they may never.

• 32:14Speaker 04

  They may never get tested.

• 32:15Speaker 03

  You know, like, right, they may never know that they had Oropouche virus.

• 32:18Speaker 04

  Exactly, yeah. Yeah, and our, so our estimates are very, very limited, so. But that, Erin, is Oropouche. Can you tell me where it came from?

• 32:27Speaker 03

  I can, I can.

• 32:29Speaker 04

  Okay.

• 32:33Speaker 01

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• 32:51Speaker 06

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• 33:27Speaker 01

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• 33:36Speaker 05

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• 35:06Speaker 03

  On September 26th, 1955, a 24-year-old man entered the fever clinic that was run by the Trinidad Regional Virus Laboratory in Sangre Grande, Trinidad.

• 35:17Speaker 04

  I love that there's a fever clinic.

• 35:19Speaker 03

  Oh, those... I'll tell you more about it.

• 35:22Speaker 04

  Okay.

• 35:24Speaker 03

  He hadn't been feeling ill for very long, just like one day. And his symptoms weren't too extreme. He had just like had a backache and a little cough, no sore throat. With the exception of his fever, which was 104 degrees Fahrenheit.

• 35:39Speaker 04

  Ooh, pretty high, pretty high.

• 35:40Speaker 03

  I didn't write that down in Celsius, but it's high.

• 35:44Speaker 04

  High. Maybe over forty.

• 35:47Speaker 03

  Maybe over forty, maybe forty, yeah. He was referred to this clinic, which was kind of standard practice at the time. Uh, but it, his symptoms were so vague that it was like, well, we don't really know what this could be. Let's run some standard tests, which included, you know, looking at blood smears under the microscope. There was one smear that looked like there, maybe there was one single malaria parasite, but it wasn't conclusive. And then people who looked at it later were like, there's nothing here. So it was kind of like, well, this guy got better really quickly. He, the, his illness lasted three days total.

• 36:20Speaker 04

  Okay.

• 36:20Speaker 03

  In normal circumstances, like in many of the time, we would think that like that person would fly under the radar and you're done with that. That's not what happened. And in retrospect, it's, it's kind of amazing that he made it to the clinic in the first place while that illness was still ongoing, which meant that the doctors could, the researchers there could take blood samples while he was acutely ill.

• 36:43Speaker 04

  Right.

• 36:44Speaker 03

  So then they could take that blood and run more tests on it. So they took serum from that blood sample, gave it to mice who died, which suggested that a pathogenic virus was involved. What virus was it? Like, this is not, this is, this is concerning.

• 36:58Speaker 04

  Right.

• 36:59Speaker 03

  It's a great question. It didn't seem to be one of the usual, or even one of the unusual suspects. And so it was given a new name, Oropouche virus.

• 37:08Speaker 04

  Hmm.

• 37:09Speaker 03

  Yeah. Uh, why Oropouche? Well, the man who had visited the clinic that kicked off this pathogen hunt, he lived nearby in a small community called Vega de Oropouche.

• 37:19Speaker 04

  Oh, okay.

• 37:19Speaker 03

  So that's, it's a place name, yeah.

• 37:21Speaker 04

  Where you're from.

• 37:22Speaker 03

  This is, yeah, it was before that became against the, you know, when it was, right. While naming diseases after places was still a conventional thing to do. But, um, subsequent tests with the virus revealed that it could cause disease in a range of animals, like mice, guinea pigs and chicken embryos. So it definitely wasn't nothing to worry about. Whether or not those animals could play a strong role in its spread is not clear, but just the fact that it could cause disease and death in them is.

• 37:52Speaker 04

  You could, you could have symptoms and that. Also, they were just like culturing this virus from this dude's serum this whole time?

• 37:58Speaker 03

  Yeah.

• 37:59Speaker 04

  Wow.

• 38:00Speaker 03

  I know, I know, I know.

• 38:02Speaker 04

  He just went to the best possible clinic, huh?

• 38:04Speaker 03

  Yeah.

• 38:05Speaker 04

  I mean, he got better on his own, so I guess they didn't do much for him, but.

• 38:08Speaker 03

  Right, right.

• 38:10Speaker 03

  They were running all these tests, finding that it was indeed some sort of, previously undescribed, potentially pathogenic or seemingly pathogenic virus. Where did it come from? And this was the question that the Trinidad Regional Virus Laboratory was very motivated and equipped to answer. The first clue came from the patient himself. Although he resided in the village, like, most of the time, Vega de Oropouche, for two weeks before his illness, he had actually been working and sleeping in a forest a few miles away, where he worked as a charcoal burner.

• 38:45Speaker 04

  Okay.

• 38:46Speaker 03

  So, if you didn't know, I certainly did not, a charcoal burner is someone who makes charcoal by burning a bunch of wood. So you, you know, deforest an area, chop down a bunch of trees, you burn those trees and you have to stand by your charcoal pit for weeks, often on end, while the charcoal is being made.

• 39:04Speaker 04

  Okay.

• 39:04Speaker 03

  It's a long, lonely job. There's even like a poem by the creator, I think, of Winnie the Pooh about it, like, how sad it is.

• 39:12Speaker 04

  Oh.

• 39:13Speaker 03

  And because you have to stay by your charcoal pit, in the woods, around where no one else is there. It's not like this is a group activity.

• 39:19Speaker 04

  Oh, okay.

• 39:20Speaker 03

  And so, learning that this guy was a charcoal burner, it immediately set off red flags for the researchers, because they were like, okay, you are spending a lot of time in the forest, this suggests that it's probably vector borne, there's probably a mosquito or something else out there, this is a spillover event.

• 39:34Speaker 04

  Oh, I love that they, that that, oh, I love, I love this story, Erin, keep going.

• 39:41Speaker 03

  And so, they, they went out there. So, in the 1961 paper that first describes this virus, quote, "When it became evident that an agent pathogenic for mice had been isolated from a forest worker, steps were taken to attempt recovery of virus from blood-sucking diurnal insects prevalent about the patient's home and charcoal pit in the forest." Reasonable next steps.

• 40:03Speaker 04

  Very, very.

• 40:04Speaker 03

  Very. And mostly, as far as I could tell, it was mosquito species that were collected, and none of them seemed to be the clear culprit. Although it did suggest that there was like, I think in a later collection, in a later paper, they found one instance of the virus in a mosquito. So they were like, okay, well, that doesn't rule it out, but it's clearly not mosquitoes entirely.

• 40:26Speaker 04

  Right.

• 40:27Speaker 03

  They did also do antibody testing in some animals, like primates, and they found that, yes, some primates seem to have been exposed to this virus previously. And so this suggested that Oropouche virus was not uncommon in wildlife.

• 40:42Speaker 04

  Also, they like developed an antibody test for it already.

• 40:45Speaker 03

  I know.

• 40:46Speaker 04

  I'm amazed.

• 40:49Speaker 03

  I can't wait to tell you more, okay. This was, I will say, like, you're amazed, right? Like, it's really cool to look at this beautiful, like, okay, logical next steps, you have the resources to look at this, you understand what you're looking for, all this stuff.

• 41:03Speaker 04

  Right.

• 41:04Speaker 03

  This was not front-page news, even in the world of viruses.

• 41:07Speaker 04

  Oh, wow.

• 41:08Speaker 03

  Because it was, first of all, viruses are very diverse. There are so many undiscovered viruses out there. And this was one person, who had recovered quickly.

• 41:20Speaker 04

  Who had recovered, right.

• 41:20Speaker 03

  Yeah, this was a handful of howler and capuchin monkeys that showed past infection, maybe an infected mosquito or two. I mean, this was one of an untold number of viruses circulating in wildlife that remain to be named.

• 41:34Speaker 04

  It was like, who cares? Okay, so you found a new virus.

• 41:37Speaker 03

  Right. It was like, thank you for recording that information.

• 41:40Speaker 04

  Right.

• 41:40Speaker 03

  We'll add it to our list of thousands of viruses, just like this, yeah. And also, maybe it was a fluke, maybe this was a one-time event that happened. And the next five years of silence that surrounded this virus seemed to suggest that that was actually the case, until it popped up again in 1960, this time, in an entirely different country over 1,000 miles away.

• 42:03Speaker 04

  Ooh, not good.

• 42:04Speaker 03

  Not good. Well, intriguing.

• 42:07Speaker 04

  Mm-hmm.

• 42:08Speaker 03

  Yeah. And not good. A three-toed sloth in northern Brazil was found to be infected with the virus, in a way, kind of foreshadowing the sizable epidemic that would occur in the region in the following year. So in 1961... An estimated 11,000 people were infected with Oropouche virus in the same region.

• 42:29Speaker 04

  Oh, wow.

• 42:30Speaker 03

  And so as it turned out, no, yeah, that not only was that first 1955 case not a one off, this epidemic would also be just the first in a series that occurred over the next decades as the virus spread to much of Central and South America and especially throughout Brazil.

• 42:48Speaker 04

  So, but they were able to identify it as Oropouche virus because of the work of the people who identified it from the one guy.

• 42:57Speaker 03

  Trinidad in 1955, yeah.

• 42:59Speaker 04

  1955. That's incredible.

• 43:00Speaker 03

  There's, yeah, because of this work, because of this network of information, this was, this virus was able to be named, described, identified.

• 43:10Speaker 04

  Identified.

• 43:10Speaker 03

  And linked to an outbreak.

• 43:12Speaker 04

  That's.

• 43:13Speaker 03

  It's pretty, it's pretty impressive.

• 43:15Speaker 04

  It's very impressive.

• 43:16Speaker 03

  Yeah. And over the next decades, I'm kind of like squeezing a lot in here. The numbers kept climbing. So between 1978 and 1981, an estimated 220,000 cases. 30 outbreaks along the Amazon River between 1961 and 1996 with an estimated half a million cases.

• 43:38Speaker 04

  Yeah.

• 43:38Speaker 03

  And most of these are in Brazil. And it wasn't just the number of cases that kept growing, though. It was also the virus's geographic distribution. First, there was that case, that individual case, as far as we knew, in Trinidad. Then there was the outbreak in Northern Brazil, then all along the Amazon River, then in these non-endemic regions of Brazil, then in Panama, Peru, Ecuador, Bolivia, Venezuela, Haiti, Colombia, French Guiana. You're just like, yeah.

• 44:05Speaker 04

  Yep.

• 44:05Speaker 03

  Guatemala, Cuba, on and on, just to name a few.

• 44:08Speaker 04

  All of these, all of these places, by the way, that don't all touch and are not all that close geographically necessarily.

• 44:15Speaker 03

  Some of these cases are, you know, whether or not this indicates local spread, I'll let you answer that later on. But the increasing number of countries that are reporting this virus at all shows two things. It shows that the potential for increased geographic spread, and it also shows increased awareness. Because better detection and awareness might be driving some of this, because for decades, Oropouche virus cases were probably wrongly ascribed to Dengue, or like outbreaks.

• 44:52Speaker 04

  Right.

• 44:53Speaker 03

  So like, how many of the past Dengue outbreaks were actually Oropouche? Could it have been a mix? This kind of stuff.

• 44:59Speaker 04

  Yeah, or Zika, or Chikungunya, like, they're all so...

• 45:01Speaker 03

  They're all so kind of similar, yeah. But there is no doubt that this disease is on the move, and it might actually be evolving to become more virulent, you know, some recent cases, or it has the potential to become more virulent. Given what you told us, Erin, about the virus's characteristics, you know, its high mutation or recombination rate, multiple insect vector hosts, and multiple vertebrate reservoirs, this is not entirely surprising that we're seeing this kind of spread. But it is concerning, and it begs a few questions. Where did this thing come from, again?

• 45:36Speaker 04

  Yeah.

• 45:37Speaker 03

  And how is it spreading so quickly?

• 45:38Speaker 04

  Yeah.

• 45:39Speaker 03

  And, why was anyone looking for viruses and sloths in the first place?

• 45:43Speaker 04

  Yeah, that's what I want to know.

• 45:45Speaker 03

  Okay, okay.

• 45:46Speaker 04

  Who tested that sloth? And why were they testing that sloth?

• 45:48Speaker 03

  I can't wait. Okay. We're going to answer the first two questions first.

• 45:52Speaker 04

  Okay.

• 45:53Speaker 03

  And we can do this pretty quickly. Oropouche virus probably originated in Brazil anywhere from, prepare yourself for a wide range here.

• 46:00Speaker 04

  Wide range here?

• 46:01Speaker 03

  80 to 360 years ago. Smaller range than we have for a lot of other things.

• 46:05Speaker 04

  Whoa, whoa, whoa, wait, wait, 80 to 360?

• 46:08Speaker 03

  Yeah.

• 46:09Speaker 04

  Wow, so it's super new.

• 46:10Speaker 03

  It's super new.

• 46:12Speaker 04

  Three, it's three, the oldest they think it is is in the hundreds of years?

• 46:15Speaker 03

  Okay, but here's, here's the thing that I, I kind of have questions about because we talked about how it has these different, like the segmented genome.

• 46:24Speaker 04

  Yeah.

• 46:24Speaker 03

  With a lot of reassortment.

• 46:25Speaker 04

  Mm-hmm.

• 46:25Speaker 03

  And so our existing data is, like, the diversity of these viruses is maybe not reflective of the overall history.

• 46:33Speaker 04

  Mm-hmm.

• 46:33Speaker 03

  I'm not sure, but I was thinking about how flu, we have complete extinct viral lineages.

• 46:39Speaker 04

  Right, right, right, right.

• 46:40Speaker 03

  So whether that's-

• 46:41Speaker 04

  Would we have called those different viruses or would we, yeah, it is, because the, the Ciro group that Oropouche belongs to is called the Simbu Ciro group. And I had a really hard time sorting through, like, are these different genotypes? Are these different viruses? Are these different? And, and there are a number that they classify as different viruses, even though they are quite similar. So, yeah, it is, it is a confusing phylogeny of that whole group, including Oropouche virus. So that, I guess, makes sense in that way. So like, the Simbu Ciro group is probably much older, but Oropouche itself, who knows? I don't know.

• 47:20Speaker 03

  I don't know. I mean, I do think that it's like, there are viruses that, that emerge or evolve. And when, when does a new virus become a new virus? I think is a, ooh, that's a question for a virologist.

• 47:31Speaker 04

  A philosophical question, too? No, just kidding.

• 47:32Speaker 03

  Or a philosopher, sure.

• 47:36Speaker 03

  But I think that whenever it originated, it has seemed to expand relatively recently. Like, it's only in the last few decades that it's expanded across the, most of South America and Central America. Why it has done so is because of humans, bottom line. Deforestation and widespread movement of humans created the perfect conditions for Oropouche virus spillover and spread. As forests were cut down, that led to more opportunities for infected mosquitoes to bite the humans living on the forest edges. So like, think about the construction of that highway.

• 48:12Speaker 04

  That highway, mm-hmm.

• 48:13Speaker 03

  Mm-hmm. And then increased movement, uh, hu, for humans, both short scale, like from deforested region to city, and then long scale, from one city to another region or another country, drove the spread of this virus.

• 48:25Speaker 04

  Mm-hmm.

• 48:26Speaker 03

  So consider, if you will, the sequence of events. Someone is working on the construction of a road through a newly deforested region of the Amazon, for instance, like the road that we discussed in our first hand. One day, they're bitten by a midge that's infected with Oropouche virus. A few days later, they take their day off to drive back to their nearby city to visit with some friends and family. There, a midge bites them, picks up the virus. That midge then bites someone else, infecting them. Another midge bites that person, and suddenly you've got an epidemic on your hands. This is how one spillover event can lead to sizable outbreaks.

• 49:02Speaker 04

  Right.

• 49:03Speaker 03

  And the story doesn't end there. So now, let's say, somebody else was in town during this outbreak, and they also happened to be working on road construction in a newly deforested area, but in another part of the country, or another country entirely, where Oropouche virus is not present. They get infected during this city outbreak, head back to their work site, where another midge bites them, becomes infected, then bites a sloth or a howler monkey, another midge or mosquito picks up the virus, and then suddenly Oropouche is endemic in this new forested region.

• 49:33Speaker 04

  Right.

• 49:34Speaker 03

  This is spill back.

• 49:37Speaker 04

  Spill over into humans.

• 49:39Speaker 03

  Spill over, spill back into wildlife. Spill back doesn't get talked about enough, I feel like.

• 49:44Speaker 04

  No, it doesn't. It really doesn't. But yeah, it's an important part.

• 49:48Speaker 03

  It is a really important part. And I wanted to mention, before I forget, that I'm wearing my spillover, I'm gonna call it my spillover sweater today.

• 49:55Speaker 04

  Yep.

• 49:55Speaker 03

  It's got, if you're watching on YouTube, you can see this. It's got a woodpecker.

• 49:59Speaker 04

  It's very cute.

• 50:00Speaker 03

  And some little squirrels.

• 50:03Speaker 04

  There you go, show us that squirrel.

• 50:04Speaker 03

  You see the squirrels? They're very cute.

• 50:06Speaker 04

  So cute.

• 50:07Speaker 03

  So it's from now on, anytime we do another spill over.

• 50:11Speaker 04

  Oh, I love it. You've got a uniform.

• 50:12Speaker 03

  I've got it. I've got it. It cuts down on decision making. It's wonderful.

• 50:16Speaker 04

  Fantastic.

• 50:18Speaker 03

  Spill over and spill back for Oropouche virus, they're not just like likely to happen, but they're they have happened. And they are likely to result in sustained transmission or turning an uninfected area into an endemic one. And this is for for all the things that we've already talked about, right? The wide host range, the recombination, multiple potential different species of vectors. We don't really know. I mean, this virus is like, has never heard of a dead end host. It's just like.

• 50:51Speaker 04

  That's what it seems like.

• 50:52Speaker 03

  What's that? It's all about those borders between humans and wildlife becoming more porous due to human activities like deforestation.

• 51:00Speaker 04

  Yeah.

• 51:01Speaker 03

  In fact, deforestation in the Amazon rainforest in Brazil from the 1950s to the 1980s coincided with 200 arboviruses being discovered in the region. So Oropouche is not the exception, but it is rather the rule. In fact, roughly 75% of all emerging infectious diseases have an animal origin.

• 51:23Speaker 04

  Yeah.

• 51:24Speaker 03

  And 70% of those come from wildlife.

• 51:27Speaker 04

  Yeah.

• 51:28Speaker 03

  Wildlife.

• 51:29Speaker 04

  I've got some good stats, too.

• 51:30Speaker 03

  You've got some good stats, yeah. Wildlife like the sloth, who is the subject of our third question. Why were people looking at sloth viruses, anyway?

• 51:40Speaker 04

  I love that someone funded this, so give it to me.

• 51:42Speaker 03

  OK, OK. So given what I just said about the high proportion of human pathogens that come from animals, maybe the answer is self evident, like why someone was looking at a sloth. Well, because wildlife can carry viruses. But I want to dig a bit deeper, exploring not only why researchers were examining wildlife for new pathogens in the mid 20th century, but also the infrastructure that allowed them to do so. Both the first described case of Oropouche virus and this isolation from a three-toed sloth took place at two viral research institutes, one in Trinidad and one in northern Brazil. Both of these institutes, the Trinidad Regional Virus Laboratory and the BiLAM

• 52:23Speaker 03

  Virus Laboratory, were established and funded, at least in part, by the Rockefeller Foundation in the mid-20th century. Okay, interesting. We've encountered the Rockefeller Foundation before on this podcast, maybe most notably during our hookworm episode. Mm-hmm. The organization, which was started by one of the wealthiest people in history, it played a pivotal role in eliminating hookworm in the early 1900s in the southern US. Or at least, if that part is controversial or up for debate, sure, that's, that's fine. What it did is it at least elucidated some of the factors that sustained its transmission. And over the following decades, the foundation broadened its goals beyond the US.

• 53:05Speaker 03

  Its mandate, as set out in 1909, was, quote, "to promote the well-being and to advance the civilization of the peoples of the United States and its territories and possessions, and of foreign lands in the acquisition and dissemination of knowledge, in the prevention and relief of suffering, and in the promotion of any and all of the elements of human progress." End quote. Okay. It's a notable goal. Yeah. I wish more billionaires would take up philanthropy instead of the other... Alternatives. Yeah, yeah. But I, I think it would be incomplete to view this foundation, or the field of tropical medicine as a whole, as solely philanthropic, whether in intent or impact.

• 53:50Speaker 03

  Philanthropy was part of it, but it was not all of it, right? Why were people trying to better understand how yellow fever was transmitted, or how to prevent leishmaniasis? So they could build the Panama Canal. Exactly. So that imperialist powers like the US and England could install local governments without people dying of infection. Yeah. Infectious disease in these regions became the first hurdle to overcome in, you know, settlement. Right. Whatever that meant. Right. Like you must first conquer infectious diseases before you can conquer this nation. Conquer the land. Yeah. Scientific and medical knowledge may have benefited the populations under imperialism. It did not always, and if it did, it often came, those benefits came much later on.

• 54:34Speaker 03

  And it came with tremendous costs. That knowledge was not freely shared, and in some cases, it wasn't shared at all. The colonizers were often the only ones to benefit from that knowledge or have the capacity to implement it. Oh, screens prevent mosquitoes, which could then prevent yellow fever. Let's put those screens in our houses. In our houses, yeah. Yeah. Yeah. Clean water, screens, bug spray, medications, stuff like that. That was not like, oh, and then now here it is, everyone. Right. It was not, in the age of imperialism from the late 1800s to the early 1900s, scientific progress was not democratized. And the concurrent rise of germ theory enabled the use of tropical medicine as a tool of

• 55:19Speaker 03

  imperialism. The Rockefeller Foundation, which emerged as this period was winding down, as the imperialist, age of imperialism was winding down, it seemed, from my reading, less focused on conquer and more on capitalism, which is unsurprising, given Rockefeller's prowess as a businessman. He saw progress, particularly economic progress, as viewed from a capitalistic Western perspective, he saw this progress as being hindered by poor health. It wasn't just that life was being cut short, it was also labor and productivity, similar to how today we use the metric disability-adjusted life years to measure the impact of a disease. Right, right. Rockefeller saw that improving the overall health of a region through public

• 56:04Speaker 03

  health interventions would ultimately lead to greater economic prosperity, which was great if the region was under the control of the US. But if it wasn't, then that also meant more money to be pumped into like the global capitalism machine, which predominantly benefited Western imperialist powers. Okay. So it's kind of a yes and situation. Yeah. Like, so the virus labs and other Rockefeller initiatives absolutely reduced the overall disease burden in certain areas, and they advanced scientific and medical knowledge, and the US, and probably Rockefeller and his descendants, enjoyed some of the economic benefits from those efforts. Yeah. Maybe that feels like a touch cynical or something.

• 56:44Speaker 04

  I mean, but we've always said like how much money you save with public health and how investment in public health is like, it's just like, that's, it's a clear example of someone having enough money to do that, which is really interesting.

• 56:59Speaker 03

  It's really.

• 57:00Speaker 04

  Even if it's cynical.

• 57:01Speaker 03

  Right. And it's like, it's kind of one of these things where it's like, we're money or public health is, is money saving. It's not revenue generating.

• 57:08Speaker 04

  Right.

• 57:09Speaker 03

  And so investment in public health ultimately is like the smartest thing that you can do as an economic power.

• 57:17Speaker 04

  Are billionaires listening?

• 57:19Speaker 03

  Right, right. And so it's like, okay, if we can't convince you to do this out of the good, you know, good for mankind, just to have a like, leave a legacy that means something more than just consumer and profiting off of people, whatever.

• 57:33Speaker 04

  Right.

• 57:34Speaker 03

  All of that, then let us convince you because it makes more financial sense to do so.

• 57:39Speaker 04

  It will eventually save us a lot of money.

• 57:41Speaker 03

  Yeah, yeah. But it still feels like, it still feels a little bit cynical. And, and so I also, I don't know, I wanted to also add that I think that the researchers and probably the, the organizers, the administrators of this foundation who were involved and wanted to take part in these efforts, I think that they probably or possibly had good intentions, like the purest of intentions, right?

• 58:07Speaker 04

  Hundred percent.

• 58:08Speaker 03

  Maybe they went into this field to reduce human suffering, to devise new vaccines, to identify pathogens, or simply just add to this body of knowledge to help make the world a better place.

• 58:16Speaker 04

  Well, and like a bunch of nerds getting to actually do this important science? Like, are you kidding me?

• 58:22Speaker 03

  It's the dream. Yeah. And it's not like local populations where these labs were established were just like passive players. Many citizens and regional governments became directly involved in primary research as well as the application of that knowledge and in funding. It was often like meeting the funding need.

• 58:40Speaker 04

  Yep, right, right.

• 58:41Speaker 03

  From 1950 to 1970, the Rockefeller Foundation provided the arbovirus program with $30 million in funding, which is worth about $230 million in today's money. And many local governments directly matched that funding.

• 58:56Speaker 04

  Wow.

• 58:57Speaker 03

  It's kind of staggering when you think about what a force that must have been and how investment in basic research really pays off.

• 59:07Speaker 04

  It pays off. I just still can't get over the fact that they found this virus from one dude and then, within a couple of years, were able to identify outbreaks that easily. I mean, how many times have you told a story on this podcast, Erin, where it's like, yes, someone found this virus and named it, but then decades later, someone else found this virus and they thought they were the first person ever to identify it? Like, that's usually how these stories go.

• 59:30Speaker 03

  It's usually how it goes. I think part of it has to do with when this, like, the historical context of when this was happening. And so, in a lot of those cases, there was not the technology or the scientific know-how to be like, this is a virus at all.

• 59:43Speaker 04

  Right. Or to be able to share that information widely.

• 59:45Speaker 03

  Share the information, yeah. And so, I think this was sort of a confluence of, we have the equipment to do this, we have the interested minds to do this, we have the funding, and we have this network of information that can be spread.

• 1:00:00Speaker 04

  Right.

• 1:00:01Speaker 03

  And the incentive to identify this. Like, hey, here's this money, find out what you can about arboviruses.

• 1:00:08Speaker 04

  And so, that's what they were doing with this sloth. They were like, we've got money to find viruses, and so, we're going to test a bunch of animals everywhere, all over.

• 1:00:16Speaker 03

  Yeah.

• 1:00:16Speaker 04

  Well, that was my dream job for a time, so.

• 1:00:20Speaker 03

  So, these Rockefeller Foundation virus laboratories were established initially to keep better track of the yellow fever virus, which had caused deadly outbreaks in Central and South America in the early decades of the 20th century, and had hindered the US's progress in building the Panama Canal. Check out our yellow fever episode. It also had been in the US for a long time, blah, blah, blah. Anyway.

• 1:00:42Speaker 04

  Hamilton.

• 1:00:43Speaker 03

  Hamilton, field laboratories were established not just in Trinidad and Brazil, but also Egypt, India, South Africa, Nigeria, and Colombia. And as researchers uncovered more information about the ecology of yellow fever, its mosquito vector, its vertebrate host, how climate induced its transmission, two things happened, at least. The first was that in their ecological studies of yellow fever, they were also finding other arthropod-borne viruses that had never been described. You know, test this mosquito, screen this monkey, sloth, et cetera. Oh, that's something we haven't seen before. Let's dig a little bit deeper.

• 1:01:18Speaker 04

  Okay.

• 1:01:19Speaker 03

  The second is that they were leveraging their knowledge about yellow fever to make meaningful, sustained progress in its control. If you could make such headway against a long-feared deadly disease, maybe you could do the same for these new viruses that you were finding. Identify the arthropod vectors, figure out which vertebrates act as reservoir hosts, measure infection against climatic or seasonal variables, and then use all that information to disrupt the chain of transmission and prevent disease. Even though it wasn't called that at the time, this embodies a one-health approach.

• 1:01:54Speaker 04

  Yes, it does.

• 1:01:55Speaker 03

  Where animal, human, and environmental health are all taken into consideration. Historically, after the early years of germ theory and epidemiology, where animals and the environment were more likely to feature in studies alongside human disease, these different fields were often siloed. So like, it was pre-germ theory, it was like, oh, the weather has turned. This might lead to an outbreak of plague, you know? That kind of thing. Once we found one bacteria, one disease, that sort of segmented, segmenting, chopping up these diseases into discrete entities, that also meant that specialties were also segmented and siloed. Like, a biomedical researcher wasn't necessarily inclined to observe a disease

• 1:02:40Speaker 03

  under natural conditions if a lab environment and an experimental animal could suffice. Like, you could control the ecological noise much better that way. And collaborations between physicians and veterinarians dwindled as the fields grew more specialized. Who's got the time? Or you would have to learn a lot more about like, a horse's guts than you were prepared to.

• 1:03:05Speaker 03

  One area, though, that resisted such rigid boundaries among disciplines was that of medical entomology and tropical medicine.

• 1:03:12Speaker 04

  Oh, love that. Love that for them.

• 1:03:15Speaker 03

  And these were the two areas in which the Rockefeller Foundation was heavily involved. How could you predict the movement of a mosquito-borne virus without considering the mosquito itself?

• 1:03:25Speaker 04

  Right, you cannot.

• 1:03:26Speaker 03

  You cannot.

• 1:03:27Speaker 04

  And all the other things they're feeding on and their environment and where they're living.

• 1:03:29Speaker 03

  Yes.

• 1:03:30Speaker 04

  And how hot it is and how long it takes for their larvae to develop and how long they live and...

• 1:03:35Speaker 03

  It's the environment, it's the wildlife, it's the domestic animals, it's humans, it's all of these things.

• 1:03:40Speaker 04

  Yeah.

• 1:03:41Speaker 03

  And so the Rockefeller Virus Labs, staffed as they were by researchers interested in cycles of infectious disease in natural environments, they were well-positioned to ask and answer these questions of what about the mosquito? What about the wildlife? What about the environment? What about the climate and the weather? And so hopefully that answers the question of why people were looking at sloth viruses in the first place.

• 1:04:04Speaker 04

  Yeah.

• 1:04:06Speaker 03

  This one health approach is not just one lens through which to view a disease like orapoosh fever. It's the only lens that we should be looking at this, right? Fortunately, that is the framework that many researchers are using today to better understand what this virus might have in store for the future. Speaking of the future, Erin, could you tell me where we stand with orapoosh virus today?

• 1:04:31Speaker 04

  I would love to, Erin.

• 1:04:57Speaker 04

  I have some stats to start you off with.

• 1:04:58Speaker 03

  Great.

• 1:04:59Speaker 04

  It's very similar to some of the ones that you hit us with, Erin. According to a paper from 2024 in the Lancet Infectious Diseases, vector-borne disease specifically, vector-borne diseases, account for nearly 29% of all emerging infectious diseases.

• 1:05:18Speaker 04

  30% of all emerging infectious diseases are vector borne. And arboviruses specifically, so viral vector diseases, are 40% of all pathogenic viruses found in humans from the late 1800s through 2010.

• 1:05:36Speaker 03

  Yeah.

• 1:05:40Speaker 03

  Yeah, I feel like I'm doing a research for my dissertation.

• 1:05:44Speaker 04

  I know, and it is bringing me back in a way that I didn't realize how much I miss this. The true burden of arboviral diseases is not known, period. However, we do know that over the last several decades, the global burden has been increasing, not decreasing.

• 1:06:02Speaker 03

  Yeah.

• 1:06:03Speaker 04

  And Oropouche virus, I am just so shocked that I did not know about this. Like, when we were in grad school, I had not heard of Oropouche virus, which is so weird because we were so deep in this world.

• 1:06:15Speaker 03

  Well, I think that also just shows silos again. Like, it wasn't directly applicable to our readings and our research.

• 1:06:22Speaker 04

  Exactly. It is and has been considered one of the most prevalent arboviruses, where it's documented second only to Dengue virus.

• 1:06:31Speaker 03

  It's very prevalent.

• 1:06:33Speaker 04

  It's very, very prevalent. We think that there has been at least half a million cases, at least 500,000 cases. And that is almost certainly an underestimate because of so much of what you talked about, Erin, that like, we didn't know, until we were able to identify this, we didn't know that it existed, how many times between then and before then and now has this been misidentified as malaria, as Dengue, as Zika, as Chikungunya, as so many other viral illnesses. But even as of 2017, the research, at least to that time, had suggested that it was only found in a few countries, which were not all geographically that close.

• 1:07:20Speaker 04

  Because by then, in 2017 paper, it was like Panama, Brazil, Peru, Trinidad and Tobago. And that's not the entire, the entirety of its range. And we know now from the most recent outbreaks that that is definitely not the entirety of its range. We also know from a few more recent outbreaks that the attack rate of this virus, so if it gets into a community, how many people is it likely to infect? Might be quite high. Seems like it. It seems like it. There was an outbreak in 2020 in French Guyana, where about 43% at least of a population was infected in one outbreak. And there haven't been that many seroprevalence studies,

• 1:08:04Speaker 04

  but the ones that have been done in Colombia and Brazil have found between 10 and 16% of people in the regions that they've studied show evidence of prior infection with Oropouche virus. Wow. I know, I know. But the biggest news with Oropouche virus, and the reason that we started getting email requests for this back in 2024, is that there was a very, very large multi-country outbreak that spanned, really, it started in like the end of 2023, but especially 2024 and 2025, that spread across at least 11 countries, including Bolivia, Brazil, Colombia, Cuba, Ecuador, Guyana, Panama, Peru,

• 1:08:47Speaker 04

  and with travel-associated cases in the US, Canada, Cayman Islands, and multiple countries in Europe. By the end of 2024, there had been over 16,000 confirmed cases, 39,000 suspected cases. And that was not the end of the outbreak. Because in 2025, an additional 13,000 confirmed cases were reported across the Americas, and another 17,000 suspected cases were identified that, that year. And like we talked about in terms of the seasonality of this, the vast majority, like we saw several kind of outbreak waves. If you look at the graphs, the Pan American

• 1:09:30Speaker 04

  Health Organization, PAHO, has a really great, you can go in and look like month by month and look at these graphs of all of these reported cases. But the vast majority of these cases were in the rainy seasons, which kind of do vary depending on where you are. This is a very large range geographically from like the mid Central America and the Caribbean all the way into South America. But the outbreak seemed to kind of wane by June, July of 2025. And since then, there have just been sort of sporadic reports. It seems like that particular outbreak is over, but was incredibly large.

• 1:10:05Speaker 03

  And it won't be the last.

• 1:10:06Speaker 04

  No, absolutely not. And in those two years, some really big changes also seemed to have happened with Oropouche. Not just how much more widespread this was, right? We saw it in countries like Cuba, where we didn't even know that this vector species existed. It has now been found in Cuba. But when the first cases appeared, people were like, what the heck is vectoring it in Cuba? Culecoides parensis doesn't exist there. Maybe it does, or maybe it was a different vector species. It's still a little bit unclear.

• 1:10:34Speaker 03

  Okay.

• 1:10:35Speaker 04

  But so the geographic spread was astonishing in that it was in so many places that we had not previously seen it. We also saw the first ever reported deaths from Oropouche virus.

• 1:10:48Speaker 03

  Yeah.

• 1:10:48Speaker 04

  In 2024, there were two deaths reported, both of them from Brazil, and the vast majority of these cases were in Brazil across both of these years, 2024 and 2025. In 2024, there were two deaths in Brazil, both in two otherwise young women in their 20s, healthy, with not any known conditions that would put them at high risk. And in 2025, there were six additional deaths, five in Brazil and one in Panama.

• 1:11:16Speaker 04

  And that does not count the miscarriages or pregnancy losses and stillbirths, which we saw that we think were associated with Oropouche virus, or the congenital malformations that we think might be associated. So microcephaly and the lack of brain development that we have seen in a handful of cases as well.

• 1:11:32Speaker 03

  Yeah.

• 1:11:33Speaker 04

  So huge changes that we saw with Oropouche virus in the last couple of years compared to anything that we had seen previously.

• 1:11:43Speaker 04

  Why?

• 1:11:45Speaker 04

  We don't really have great answers. There was El Nino years during some of that time. And so we think that, you know, the seasonality and the increase in rainfall and things are likely associated with that particular outbreak and will be in the future.

• 1:12:01Speaker 03

  Right, just higher numbers of midges, for example.

• 1:12:03Speaker 04

  Exactly. And like I said, there are still questions to be answered about what was different about this particular viral strain, but it does seem like the, almost all the cases in 2024, 2025, these large outbreaks were from this kind of novel reassortment where we saw a virus that looks quite different than Oropouche viruses that we have seen in the past. And so that, and how big of a role that played, and what about this novel reassortment made it so that this outbreak could happen, we still don't know. But it is very likely that that played at least part of a role in addition to the vectors and the rainfall and the climate and the deforestation and the travel and the globalization and all of the things.

• 1:12:49Speaker 03

  I feel like some, some things are, could be, if you're thinking about this in terms of like a fire, right? Some things are the matches and some things are the kindling.

• 1:12:59Speaker 04

  Exactly.

• 1:12:59Speaker 03

  And so it's like what the El Nino year is not the match, but it's the kindling, you know, like that, that kind of stuff.

• 1:13:06Speaker 04

  Yeah.

• 1:13:07Speaker 03

  I'm curious, for the genetic diversity of these viruses in that outbreak, was it all the same?

• 1:13:14Speaker 04

  As far as I could tell, it does seem to be kind of all this big novel restortment that is quite different than any of the other Oropouche viruses that we've seen in the past.

• 1:13:22Speaker 03

  Okay, we have covered a lot of mosquito borne and arboviruses on this podcast and there are many, many, many more out there that we have not covered. And I think sometimes the number, just like the sheer diversity of sort of like how I was like, well, this is not the, Oropouche is not the exception, it's the rule, can paradoxically make you go, oh, well, then there are so many, like, whatever. But Oropouche is, it is exceptional in many ways. It is exceptional in its, its ability to spread, in its vector prevalence and distribution, and in the increasing frequency, and just sort of also the fact that like,

• 1:14:05Speaker 03

  we're not, I worry that the, that we all have maybe a little bit of headline fatigue when it comes to things like this. And it's like this inclination to go, oh, it's just an exaggeration or whatever. But like, no, I really, these things will continue to happen.

• 1:14:21Speaker 04

  Yep.

• 1:14:22Speaker 03

  Modern medicine won't prevent us if it's not, if it's not able to be accessed and not shared equitably.

• 1:14:29Speaker 04

  Right.

• 1:14:31Speaker 03

  Yeah.

• 1:14:32Speaker 04

  Yeah. And I mean, we still, from what I can tell, it's not like this has led to a huge boost in Oropouche funding. And now we have all these vaccines on the horizon. There's not, there's none. There's nothing.

• 1:14:42Speaker 03

  No, I mean, I certainly don't see that happening with this administration. So.

• 1:14:46Speaker 04

  Definitely not.

• 1:14:47Speaker 03

  Yeah.

• 1:14:48Speaker 04

  Yeah, no, it's, I think Oropouche is, is another example of so many that we have seen of these will just keep coming.

• 1:14:58Speaker 03

  Mm hmm.

• 1:14:59Speaker 04

  Viruses will just keep coming. They will keep spilling over. We will keep seeing new ones. And.

• 1:15:06Speaker 03

  And the end. Great stuff.

• 1:15:09Speaker 04

  Yeah, yeah, we've got lots if people want to read more about Oropouche virus.

• 1:15:15Speaker 03

  We do. Okay, so I, there was a paper from 2024 that I really liked. It was by Tilston Lenell from 2024, Oropouche Virus and Emerging Orthobunia Virus. That was great. There were a few more, there are, honestly, I have a lot of, a lot of papers. If you're interested in reading more about sort of like the Rockefeller and public health imperialism perspective, there's a paper from 1976 by Brown titled Public Health and Imperialism: Early Rockefeller Programs at Home and Abroad. And then finally, I just want to recommend these papers because it was really interesting to think about the One Health and where did this, where did this idea come from?

• 1:15:56Speaker 03

  From Ancheta et al. from 2021, there are two papers, The Origins and Lineage of One Health, Part One and Part Two.

• 1:16:03Speaker 04

  Love it. I also had a number of papers, one from 2017 by De Rosa et al. from the American Journal of Tropical Medicine and Hygiene, I really liked, that was called Oropouche Virus: Clinical, Epidemiological, and Molecular Aspects of a Neglected Orthobunia Virus, Orbunia Virus? I don't know. There was also a review from the Lancet Infectious Diseases from 2024 by Wesselmann et al. It was titled, yeah, that was a good one.

• 1:16:28Speaker 03

  That was a good one.

• 1:16:29Speaker 04

  Emergence of Oropouche Fever in Latin America: A Narrative Review. And then if you want more detail on this novel reassortment, there was a Nature Medicine article from 2024 by Naveka or Navesa et al. titled Human Outbreaks of a Novel Reassortment Oropouche Virus in the Brazilian Amazon Region. And then I also want to shout out one that was more focused on the vectors themselves by Galichot, I'm probably pronouncing that wrong, and I'm really sorry.

• 1:16:57Speaker 04

  And it was from Plas Neglected Tropical Diseases, that was called Vector Competence for Oropouche Virus: A Systematic Review of Pre-2024 Experiments. It was, it was a really good one. It was like, we don't know anything.

• 1:17:09Speaker 03

  I know, I mean, I feel like it's like, despite the fact that we've kept saying, well, we don't, we don't, we don't know, it's understudied, it's undersudied, people, a lot of people have done a lot of great work on it.

• 1:17:17Speaker 04

  Oh, totally.

• 1:17:17Speaker 03

  And so check out these papers.

• 1:17:18Speaker 04

  Totally, there's a lot, there is a lot there, we just, we still don't know. Comparative to other viral and arboviral illnesses, this has not gotten the attention or recent funding that it deserves. Okay.

• 1:17:30Speaker 03

  Yeah. Okay. Um, thank you to Blood Mobile for providing the music for this episode and all of our episodes.

• 1:17:37Speaker 04

  Thank you to Tom and Leanna and Pete and everyone at Exactly Right for everything you do to make this possible.

• 1:17:43Speaker 03

  Thank you, thank you. Thank you to anyone who enjoys this podcast in any way or participates or partakes or whatever.

• 1:17:50Speaker 04

  Yeah.

• 1:17:51Speaker 03

  Yeah.

• 1:17:51Speaker 04

  Yeah, thank you. And especially thank you to our patrons for your support over on Patreon. It really, really does mean a lot to us.

• 1:17:58Speaker 03

  Does, it does. Until next time, wash your hands.

• 1:18:02Speaker 04

  You filthy animals.

• 1:18:31Speaker 05

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