This Podcast Will Kill YouWhat does it take to make the WHO’s list of high priority pathogens of pandemic potential? Ask Nipah virus. Extremely deadly with a wide host range and no effective treatments or vaccine (yet), Nipah virus has certainly earned its place on this list. In this episode, we explore where this virus came from, how it can make us so very sick, and the 1998 outbreak in peninsular Malaysia that put Nipah virus on the map. But we don’t stop there! We bring on expert guest, Dr. Clifton McKee, research associate at Johns Hopkins Bloomberg School of Public Health to guide us through the ecological factors that drive Nipah virus spillover events and outbreaks. With Dr. McKee’s help, we explore what a One Health approach to Nipah virus looks like and how it integrates study across animals, humans, and the environment to help predict and control when and where this virus might spill over. Tune in to learn more about this deadly virus that inspired the 2011 movie Contagion.
I was so overcome by sadness that as soon as we completed capturing the required electron micrograph images, I requested doctor Crop to use the phone in CDC and called up my head in Malaysia. I managed to get him at home. I still remember vividly what I told him over the phone. Professor lamb Tua hear calling from CDC for Collins. Professor listen, listen carefully under the electron microscope. The virus has the morphology of a paramixavirus. For God's sake, please do not talk about Japanese encephalitis anymore. I'm quite sure now it's a paramixavirus. Most likely it is a new paramixavirus. The control measures for paramixavirus are totally different from Japanese and cephalitis virus. Please, I want you to urgently pass this message to the Ministry of Health to stop all the Japanese encephalitis control measures and switch over to the following control measures. Professor listen carefully. You must pass the information of what I have just said to the Ministry of Health as soon as possible. I'll get doctor Bruce Crop to process the electron micross could be photographed and fax it to you as soon as it is ready. There was a fairly long silence and he did not reply to my words.
Wow, Aaron, Wow.
Yeah. So that was from a paper titled the Discovery of Nepavirus, a personal account, written of course by Chua Copping doctor Chua, who, well you'll hear later from him more in the episode, played a really pivotal role in the discovery of nepovirus. And I just like this paper. It's a personal account of his experience. It's amazing and so like, this is just a small little excerpt from it, but really the whole thing is so invaluable because I think it shows what was he feeling, what was he thinking every sort of step of the way, what was it like to be there? And we don't really get that very much.
Yeah, to like understand from a first person account of someone who was actively working on this during this outbreak, on this infection, trying to help trying to figure out what was going on, Like, Yeah, what did that feel like? What was that like? We don't get to see that very much anymore.
We don't, And that's why I just I love it. Go read it. Hi.
I'm Aaron Welsh and I'm Erin Alman Upday.
And this is this podcast will kill You.
Welcome to today's episode.
Today to today's episode today on Nepa virus.
Nepa virus.
Yeah, at least a few of you have suggested this. It's been on our list for a really long time, and it's been It's been really interesting to kind of finally dig into Like I knew what it was, I'm like, oh, yeah, okay, this really deadly virus spillover, et cetera. That's whatever. But then to actually read about it, I'm like, oh, all right, Yeah.
To actually get to spend the time to dig into it, It's it's going to be a great episode. I'm super excited.
It's going to be a great episode. Also because we are going to be chatting with an expert guest later in the episode.
Our favorite thing to do, Kearn's gone to get this season, I know, I know.
And also we're gonna ask them to pick up the slack that we will be dropping when it comes to talking about the ecological factors that contribute to outbreaks of nepavirus. So doctor Cliff McKee, who is a research associate at Johns Hopkins Bloomberg School of Public Health will be joining us to talk about the dynamics of pathogen spillover events from bats to humans. So excited, So excited? I wait, me too, But we have a lot to cover before we get there, including it's quarantine eytime. What are we drinking this week?
We're drinking when pigs fly, which will make sense. It'll make sense later in the episode. It will, it will, it will. It's you know, bats, pigs whatever.
We'll get there, and the quarantining itself is quite a delicious one. It has rum, it has mangos, it has lime, passion fruit. You know, it's tasty, and we will post the full recipe on our website. This podcast will kill you dot com as well as on our social media channels, which if you're not following us on there, you really should because we're coming up with some pretty fun content. You know, who doesn't love some short form media. We've got some reels for you if you're interested.
We're trying really hard.
We are. We're trying to be cool and keep up with the kids. Be hard.
We're elder millennials. We don't really know what we're doing.
True, It's very true.
On our website though, this podcast will kill You dot com. You can find lots of other non short form content. You can find the sources from all of our episodes. You can find bookshop dot org affiliate account, and our Goodreads list for lots of deep reading. You can find Bloodmobile, who does the music for every single one of our episodes. You can find our transcripts. You can find our merch. We have some pretty great merch right now, we do. You can find our peach on you can find anything that you want. We've got a first hand account for him. If you would like to submit your first hand account or request an episode like doesn't check it out, check it out. It's a great, It's great, and that's it. That's all I got. Oh and rate, review and subscribe if you if you haven't done that already. If you have, thank you so much. We really really appreciate it. It helps us keep making the pod.
It's true. Let's get started, Aaron, Okay, right after this break.
So, NEPA virus is an RNA virus in the family paramix of your which a longtime fans of the pod might be familiar with, because we've actually covered some other PARAMIXA viruses on this podcast before Measles is a paramix of virus, mumps is a paramix of virus. Other ones you might have heard of include the para influenza viruses, which cause common colds. Can't forget about Render.
Pests, Render Pest one of I think one of my favorite episodes. A great success story when it comes to public health or wildlife health, or veterinary health, One Health Health, One Health. That's the thing, One Health.
Also, Hendra virus, which we have not yet covered but we will someday, is the most closely related to NPA virus. So nepa virus and hendravirus are both in the family paramix of Iriday and the genus they kind of have their own, which is called henipa virus. I think it's a combination of hendra and NPA virus. It stands creative. Now. I don't want to bury the lead here too much for anyone who didn't request nepavirus, who's maybe never heard of this thing and is wondering why the heck we're covering this virus that they've never heard of. Nepovirus has been named one of the top ten highest priority pathogens for the World Health Organization to focus on in terms of the development of countermeasures. That means focus on vaccines, focus on developing treatments, focus on prevention. And the reason is because NEPA virus has huge pandemic potential, so not to jump ahead too much. But not only is this virus capable of spreading person to person, not only has it continued to pop up and spread to new places year after year, as we'll talk about, but Nepa virus is also one of the most fatal infections that we've seen in humans. Case fatality rates on the low end tend to be around at least forty percent, and in many outbreaks they've been upwards of ninety percent of cases.
It is unreal.
It is terrifying in all honesty. Yeah, yeah, So it's a big deal virus and you're gonna learn all about it today. So NPA virus primary reservoir is bats, so in nature, in the wild, it lives specifically in bats in the genus Teropis terrapus terrapus. I think I decided it's terrapists.
We had a conversation about this, and I have forgotten what we landed on.
I looked it up several times and then I pronounced it wrong the first time. I just said it it's terrapists. These are flying foxes, fruit bats. Right, There's a few different species, but for much of the distribution of NEPA virus that we've studied so far, it's predominantly Terrapus medius that's been implicated in NPA transmission thus far, and NEPA has outbreaks in humans in a number of different countries across South and Southeastern Asia and the Pacific, including India, Malaysia, Singapore, the Philippines, and Bangladesh. But the bats that carry these viruses are distributed really widely across Asia, the Pacific, Australia, even parts of Africa. The majority of cases thus far, like by far, have occurred as the result of spillover events, So this is a zoonotic disease primarily, and most of the spillover events have happened either from bats to humans like a little bit directly, or from bats to domestic animals, especially pigs, and then to humans. But like I mentioned, this virus has also shown that it is entirely capable of being transmitted person to person as well. So let's get into a little bit more detail about how this virus makes its way into humans. What's interesting is that so far in different geographic areas where we have seen NIPA, there seems to be different modes of transmission that kind of predominate. And maybe we'll ask doctor McKee a little bit more detail about the ecology of this. And it also might have to do with the viral strains, because there's two different major viral strains in Malaysia where NEPA was first detected. And I know you're going to talk all about it.
How dare you?
How dare I mention that this was first detected at some point in time?
Why do I even do anything on this podcast? I just kidding.
So in Malaysia, where it was first detected, outbreaks have been associated with contact specifically with intermediate hosts, mostly pigs, and it's thought that these pigs got infected by eating fruit that was mostly bitten or possibly poopter peed on by bats, and then humans got infected via direct contact with those domestic animals, either through things like slaughterhousework or farm work, or through even contaminated meat. Then in the Philippines we have seen outbreaks that have been associated also with an intermediate host between bats and humans, but there it seems to be horses and horse meat that has been involved. And then in Bangladesh the primary as well as India to a certain extent, the primary root of transmission seems to be a little bit more directly due to bat contact, but via raw date palm SAP that's contaminated with either the saliva or perhaps the urine or feces from infected bats because apparently bats also love raw date palm sap just like humans do. So then humans essentially ingest this contaminated SAP and then become infected that way. There also have been cases where humans might have come in direct contact with bats or bat feces, bat urine something like that and gotten infected, like truly directly from bats.
And this is ingestion. This is through ingestion.
As far as I could tell. Yeah, I mean it's coming in contact with this date palm sap and what you do with it is you drink it.
So yes, But like when we're like thinking about pigs and stuff like that, like is the contact again through or is it respiratory?
Like what great question? Great question with pigs and intermediate hosts. No, it's not necessarily ingestion. You could get infected from contaminated meat, but even then it isn't necessarily from ingesting the meat, because if you cook it then you're going to be killing this virus. It's it's heat labile, but it's getting in contact with things like respiratory secretions or bloodborne products, like anything from this animal that has virus in it could then be transmitted to people. But the part that makes this virus a BSL for a Biosafety Level four pathogen, a pathogen of pandemic potential is that in many of the outbreaks there is also evidence of person to person transmission, and this is usually with contact with respiratory secretions, but it's very likely that other bodily fluids can also transmit. It's just that respiratory secretions are thought to be the main component of transmission when it's person to person.
Question, does the strain or the root of transmission originally if it's a spillover event, does the strain then impact the ability of it to become transmitted person to person? And is that more likely from like the like from that direct to human rather than batpig human?
Excellent questions. So yes, the first part of the question. So the first part of the question is do the strains seem to make a difference in whether they're transmitted person to person. The two main strains are the strain from the kind of original outbreak or couple of outbreaks in Malaysia, and then the strains that were first identified in Bangladesh. Those are kind of the two main lineages. It seems we have a lot more data on strains from Bangladesh, like you know, sub strains or whatever from Bangladesh than we do from Malaysia. But in those initial outbreaks, there was very limited evidence of person to person transmission from what I could tell, not even like definitive evidence of person to person transmission in those first Malaysian outbreaks. So is that because those strains are less likely to be transmitted person to person? Perhaps, but I don't know that we have as much evidence to say for sure the strains in Bangladesh are more likely to be a transmitted person to person, But I don't think that we have data, at least I didn't see any on whether it's more likely to happen like how that primary person got infected, whether it was from date palm, SAP or from an intermediate host or from a bat. However, it's only about ten percent of people that seem to be spreading this person to person, which is very interesting. Overall, it's a pretty low rate of person to person transmission in the outbreaks that have been studied. However, there is plenty of evidence that that chain of transmission can live on for like several viral generations, if that makes sense. So one person out of every ten who gets infected is going to transmit it to someone else, but then the person that they transmit it to can transmit it to someone else as well.
So it's like there's something about that person that makes them makes the virus like, hey, this is great.
Exactly we saw. I think everyone's familiar with the idea of a super spreader after COVID. It's that same kind of idea. We don't know right now. Is that a characteristic of the virus that happened to infect that person, or is it a characteristic of certain people that makes them super spreaders in this case, we definitely do not know. Okay, okay, yeah, So that's kind of how this is transmitted, right It's a lot of different ways, and it really does depend on the circumstances, and we'll get into more of the ecology of this virus later when we talked to doctor Murckey, But let's then talk about more of what this actually looks like when a human does get infected, and I'm focusing on humans, but again, this is a zoonotic pathogen, so this is infecting and living amongst bats very readily. And when it infects our domestic animals like daw cats, pigs, horses, it does tend to cause symptomatic disease for the most part, but it really varies how sick these animals get, So I'm not going to get into detail on all of that. Let's focus on humans, shall we.
Let's do it.
Once a human gets infected, the incubation period tends to be between four days to two months, which is a huge range, but over ninety percent of people who have symptoms will have them within two weeks. Now, how many people are going to have symptoms, We have no idea. You can find numbers, but this is such a rare and understudied pathogen still that estimates range between one percent and forty five percent of people that are asymptomatic, depending on what the study is so it's.
The biggest range we've encountered on this podcast.
It's a meaningless range.
It's entirely it's not one hundred percent.
Not everyone we know that this is true. So in any case, there are some proportion of people who are likely asymptomatic based on like ero logic studies that we have seen. Okay, but for people that are symptomatic, this is a really terrible pathogen. Symptoms tend to start after this incubation period with pretty nonspecific kind of prodrome. These are symptoms like a fever, headaches, muscle aches, maybe even vomiting, but really nothing that would make you go, oh, this sounds like nepavirus, right, It sounds like any other of a million infections that we've covered on this podcast, or like one hundred and something that we've covered on this podcast. But generally within a week, within a number of days, you start to see signs of central nervous system infection. So this looks like things like altered mental status. Very often we can see signs of brainstem involve and so you might see changes in reflexes. Usually it would be like a loss of reflexes or a decrease in reflexes. But there's some literature where we can see like loss of very specific reflexes that are associated with that brain stem or that lower part of your brain dysfunction. These are things like if you turn someone's head side to side, in a person whose brainstem is intact but who maybe isn't all the way conscious, their eyes should move in the opposite direction that their head is turned, like a like those creepy dolls that you had in your grandma's house growing up. This is called the doll's eye reflex. If this doesn't happen, then the eyes just stay midline as the head moves. That's a loss of that reflex, which is very severe, so it suggests loss of brain stem function. There's a lot more detail to that that. Don't please ask me about that reflex because I learned it once.
But there are other like what I guess, other diseases that affect the brain stem, right, what examples.
You know, that's a good question. Any kind of meningitis that is affecting the brain stem. Yeah, yeah, okay, But you also see things like other reflexes, like your pupillary reflex or even just loss of muscle tone. You can also get instead of a loss of muscle tone, you can get these jerks like myoclonic jerks. You can see seizures, you can see any number of these neurologic signs and symptoms which are just telling us how severe the brain infection is in this case, and people tend to deteriorate very rapidly. Nepavirus, like I said, is an incredibly fatal disease and usually within a matter of days. Forty to ninety percent of people in most outbreaks die within a number of.
Days, So it's two weeks you get infected, two weeks later you start to have these sort.
Of nonspecific specific symptoms, and within a couple of days in nervous system involvement, coma and death. Death. In some outbreaks, there also does seem to be a substantial amount of respiratory involvement, though not all outbreaks, which is very interesting. So respiratory involvement looks like a cough, it can look like an atypical pneumonia, which we've talked about on this podcast, just means that on a chest X ray it doesn't look like a very classic pneumonia. You can have.
I know, these are words you can't define h typical pneumonia by saying it's just not your classic pneumonia.
So on a chest X ray, it would look like kind of patchy involvement in the whole lungs rather than one area of your lungs that's fully infected with a bacterial pathogen. That's okay, I think of when we think of pneumonia.
Of classic pneumonia.
Okay, But in general, you're going to see some degree of respiratory distress if you have a respiratory involvement. But this hasn't happened in all the outbreaks, so we don't really have a great sense of like when or why this is happening. And because this is such a fatal infection, we don't have that much data in all honesty on a lot of these signs and symptoms. What we do know is that in people who survive, something like twenty percent of them have some degree of like residual neurologic dysfunction, which can again really range, and some proportion in some of these outbreaks seem to also have like a relapsing encephalitis, so looks like a new infection, but it's just a relapse months or even years after the initial infection. How does this happen? I have no idea.
Yeah, and they've cleared the virus from their system.
That's a great question. Do we know that for sure? I don't know that we know that for sure.
Okay, Okay, two questions. Okay, how environmentally stable is this virus?
I knew you were going to ask.
Okay, number two, when is someone? If someone is infectious person to person, at what point are they infectious? Pre symptoms, et cetera.
Yeah, these are really good questions. So this virus is fairly environmentally stable, which is part of how it can be transmitted In things like date palm SAP. This virus can persist for days outside of a host. One paper that I read said that on some fruits and juices that they have studied, it can live for up to three days and still be transmissible in some cases. In some studies where they have kept it colder, like around twenty two degrees celsius, it can last for up to seven days in something like a date SAP, But even at higher temperatures it can survive for like a couple of hours. So it's a pretty environmentally stable virus.
Okay, Now, how.
Transmissible are people or like when are people most transmissible? We don't really know. That's a great question because we know that there is some degree of asymptomatic infection. There's a really important question of if you are asymptomatic, can you still spread this person to person. I don't think that we even know that necessarily. I haven't seen a lot of data on that. But it doesn't mean that it doesn't exist. It just means that I didn't see it. What we can try and look at is where is this virus replicating to try and understand where are you most likely to be able to spread it from? Like where is this virus living in ourselves? And even there we don't fully know. What we think is that because MEPA virus is often spread via rest inspiratory droplets, like via respiratory secretions, it was long suspected and it seems to be the case in studies so far that the epithelial cells that line our respiratory tract are the first target for infection and viral replication. So that would mean that potentially early on, if this virus is infecting the respiratory epithelium, someone could potentially be infectious relatively early in their infection, if that makes sense, yes, okay, right, because it's invading right there, replicating, and then potentially being able to be spread. But NIPA is also particularly adept at invading past our respiratory epithelium and specifically going into our microvasculature, so our blood vessels and the cells that line our blood vessels are endothelial cells. It's one of our favorite cells on this podcast, sure, and that essentially means that NEPA has direct access to our blood stream. And while we certainly don't know everything, not even most things about the pathophysiology of this virus, we do know that it induces a lot of direct viral damage and immune related damage to these endothelial cells, which means that as it spreads via these endothelial cells in our blood stream, it can damage things like our heart, our spleen, our liver, our kidneys. These are all areas where our blood is going very rapidly, and it's also causing a lot of disruption to our blood brain barrier, which is what allows for it to have such easy access to our central nervous system. So how much can this continue to spread if all of these other bodily fluids are getting infected potentially quite a bit, But I don't know like how infectious someone is early in the course of their infection versus late. I didn't see data on that.
Okay.
Another thing though about NEPA virus that is just so fascinating is that it's also thought that a secondary way that it's getting into our brains, into our central nervous system, is actually by traveling up our olfactory nerve. Our olfactory nerve, which is obviously in our nose, it's what we use to smell, is one of the nerves that gives direct access to our brain. It's not covered by the blood brain barrier, and so NEPA virus can essentially just hitch a riot on this and travel up and get direct access to our brain.
It's thought, how like, how does it get there to our olfactory nerve?
Yeah, well, it's in our respiratory epithelium, which is in our nose and our throat and our lungs, And how does it get there without causing all of the flags that our body would usually use to counter any virus. Right, That is what makes NEPA have such a high fatality rate. It happens to be incredibly good at if evading our immune response. It has a protein and I think a number of proteins that specifically inhibit a number of our cytokines, including interferon, which basically reduces the ability of our immune system to clear this infection. So that combined with the fact that it's then or or because of that rather who knows chicken and egg. But the ability to cross our blood brain barrier and infect our central nervous system and evade our immune system so well is what results in such significant mortality.
So does our immune system ever recognize it? I know, with like case fatality rates upwards of ninety percent, Like you know, obviously at that point, either that our immune system recognizes it too late or it doesn't recognize it ever. Like the bottom line is, can a vaccine be made against this?
Yeah, great question. As far as we know, we so like people do eventually mount an antibody response to it, and there's a lot of work being done on vaccines. So it's very good at evading our innate immune response. But if you could have a faster onset antibody response, then perhaps you would be successful at not getting a severe infection from NEPA virus. See our episode on vaccines if you'd like to know more about these different immune responses, because we did it in detail there way back.
When, way back when. What about like, yeah, other, are there any immune therapies or anything like that.
Yeah, right now, we have absolutely no specific treatment for anita at all. Okay, So nepavirus treatment is all about supportive care. And because this is an infection that causes such severe disease so quickly, supportive care is really like ICU level of care, right making sure that you can support someone airway if they stop breathing, making sure that their fluid balance is good, like whatever is needed, but it's very high level of care that's needed. There's a lot of research being done on things like antivirals. Sometimes there are antivirals that are used even though there's not really any evidence so far that they are effective. But it's one of those cases where medicine often feels the need to like do something even if we don't have any evidence that it's effective when you have nothing else to do. But right now, that's all that we have that is nepavirus.
It's wild. It is one of the most I mean, besides rabies. I'm trying to think of a more preons I guess, like a more deadly pathogen that we've covered.
I mean mnemonic plague, right, but yeah, yeah, yeah, it's a really scary. It's a really scary. That is probably why Contagion used NEPA as a model system in the movie, because it is terrifying. Yep, yeah truly.
And they're like, you know, I feel like we used to end this podcast episodes of this podcast with do you remember that? How scary?
Yeah?
Yeah, I forgot about This's been a minute since we've done that.
I think we could bring it back for this episode.
We could. We can talk about it at the end. Yeah yeah. So Aarin, tell us, how did NEPA come to be with us here?
I will attempt an answer right after this break. Peninsular Malaysia nineteen ninety seven to nineteen ninety eight. Okay, at first, it was just the pigs. Sick pigs were not a totally unfamiliar site in this part of the country. There were occasional outbreaks of classical swine fever aka hog cholera, caused by a flava virus called pesti virus C.
In case you were interested, I'm sorry, just like I don't want to interrupt, but like, why do we have to call things that are not the same thing the same thing? Hog colera not being cholera. That's annoying, stomach flew. I can't, I can't think of anything else, but yeah, yeah, okay, anyways, anyway, no.
I totally I hear you. Something called Auzeski's disease aka pseudo rabies. Oh my god, caused by a type of vercella virus.
Okay, are you serious?
I'm serious.
It gets worse, Sarah, I know, I know.
And poor scene reproductive and respiratory syndrome caused by a type of virus called beta art teary virus sued one. If you're interested. There are so many pig pathogens, okay, and the disease that was making its way through pig farms in this region of peninsular Malaysia didn't seem super different than those more familiar ones. A few symptoms stood out, pronounced neurological syndrome, including agitation and head pressing, tetanus like spasm and seizures, uncontrollable eye movements, trembling in twitches, uncoordinated gait, and generalized pain. And then in the pigs there were also some acute respiratory signs, rapid and labored breathing developing into a loud, harsh cough, which later then gave the common name for the disease and pigs called barking pig syndrome. But even though there were some cases of sudden death in infected pigs, the rates of infection and mortality weren't all that high, or at least not high enough to cause immediate and pressing concern, and so the new disease wasn't immediately identified or recognized to be a new disease. Then people started to get sick. In late September of nineteen ninety eight, several people who worked on pig farms in the suburbs of epo A City and the state of Perak in the northwest part of the peninsula also began to show signs of illness headache, fever, drowsiness, vomiting, altered mental state, sometimes progressing to fatal encephalitis, and this, while absolutely cause for concern, it also didn't immediately throw up red flags as a new illness. Initially, people thought this was an outbreak of Japanese encephalitis virus, which we have not done yet.
No, it's on our list, but I don't even know if it's on our short list for this season.
I don't think that it is, which is kind of surprising. But there's a yeah anyway, there's a lot. Yeah, there's a lot Japanese andencephalitis virus. Though the relevant thing here to know is that it's transmitted through mosquitoes, and this wasn't a wild guess. Japanese encephalitis virus was present in the area. Four of twenty eight samples from patients with encephalitis tested positive for antibodies against Japanese encephalitis virus, and as people continued to get sick, their serum contained not just antibodies against the virus, but also Japanese encephalitis virus nucleic acids, which suggested current or recent infection with the virus. Later, many of these samples were actually found to be false positives, so it's probably a case of like the threshold being too low for throwing up a positive sign. Given this evidence suggesting that the region had an ongoing Japanese encephalitis virus outbreak, the Ministry of Health took action against it to try to prevent additional cases, which involved intensive fogging with insecticides in the outbreak, areas administering thousands of doses of Japanese encephalitis virus vaccine to those who lived near or worked on the pig farms because that's where the concentration of cases seemed to be happening. But after all of these measures, instead of cases dropping as you might expect if it was caused by Japanese encephalitis virus, they continued to rise and making matters even scarier. The disease was no longer restricted to just the area outside of the city of Epo. Some of the farmers who were affected in this outbreak had sold their pigs in a fire sale, which led to pigs being burst across the country, and these types of sales were a common occurrence in Peninsular Malaysia, which at the time had a pig population of two point four million. But unfortunately, some of the pigs sold brought with them this mysterious infection, and in December of nineteen ninety eight and January of nineteen ninety nine, cases of encephalitis in humans began popping up elsewhere in the country, especially in an area about three hundred kilometers south of Epo in the state of Negrius and Balon. Still the thought was this is Japanese and cephalitis virus. Like it was still like, well, it has to be this. We just have a bad year for mosquitoes, the viruses in the mosquitoes. This is how it is. Yeah, And so more prevention measures were carried out, more fogging, more insecticide, more administration of Japanese and cephalitis virus vaccines, and according to a researcher involved in the outbreak, the governmental authorities seemed really intent only on confirming that this was Japanese encephalitis virus, not so much exploring other options, like, for instance, if this was a totally new pathogen that needed completely different containment strategies than those used for Japanese and cephalitis virus. By the end of February nineteen ninety nine, the outbreak was still raging with no end in sight, and the evidence that this probably wasn't Japanese and cephalite as virus started to be too much to ignore. The control measures weren't doing anything to reduce the incidents of cases, infections, seemed to be limited to people who had direct close contact with pigs, mostly adults, were getting sick. There was household clustering with multiple people in the same household getting sick, which you wouldn't necessarily expect clustering with Japanese and ccephalitis virus. There was a really high in this particular outbreak, a really high disease attack rate, So most people who were infected became symptomatic. So for every one person who stayed asymptomatic, three developed symptoms is what I read. Japanese and cephalitis virus, on the other hand, causes symptomatic encephalitis in one in three hundred of those infected.
So like, wow, very different, totally different.
And perhaps the most glaring piece of information suggesting that this wasn't Japanese encephalitis virus was that some of the people who were getting sick and dying had already received multiple doses of the vaccine. Can you imagine how terrifying and awful getting the vaccine and being told, Okay, you're safe to go back to work, and then it turns out you weren't. And some governmental authorities did actually try to explain that away by saying Oh, well, it's because this vaccine was faulty. We need to replace this inactivated virus vaccine with the live attenuated version and then we'll have better results. But fortunately some public health officials and researchers were like, okay, you keep working on that and in the meantime, we're going to see what this actually might be because it doesn't seem to be Japanese and cphalitis virus. And the lead researcher on this, doctor Cobbing Chua at the University of Malaysia, who first hand account you heard from he would eventually make the discovery of nepavirus. He was pretty sure at this time that it was a novel agent, not Japanese and cphalitis virus, but the head of his department was convinced that it was Japanese and cephalitis virus. So how could he persuade him that he needed to isolate this virus. Chua ended up saying, well, if it's a new genotype of Japanese encephalitis virus, that could be important, that could be really relevant to our control efforts and to determining whether the vaccine is whatever, And he got permission SMO move a smooth move indeed, and so he got permission to run tests on the cerebrospinal fluid and serum samples from a few patients on March fifth, nineteen ninety nine, so the first cases were in September of the year before. On March fifth, Chua saw something unexpected in one of his samples. The virus seemed to kill the cells in a way that was very similar to that of respiratory sensicial virus, not something that Japanese encephalitis virus does. So he ran to the head of his department and was like, come look at this, and the head was like, Nah, it's just contamination. Get rid of it, throw it away, ignore it. Chuat didn't. He continued his work, and he went around to get his colleagues's opinions, some of whom agreed with his thought that this was something new, this was something interesting, This was not contamination, and so he ran tests that were available to see whether this was a known virus like herpie simplex virus RSV, measles Mom's para influenza virus all negative, and then he was like, well, maybe I should check whether the patients that I've sampled have antibodies to this virus that I cultured, because then it's like, is this just contamination or is this a virus? And they have antibodies against it, all positive, like perfect match. And so this time with these results, he was able to convince his department head that this was probably a new virus and that they needed international help to figure out what kind virus. It was two days later after he had these results, after he'd had done the testing of the virus against the antibodies and the patients, and this was one week after he first saw this weird cell killing effect of this virus in his samples. Chiua was on a plane samples in hand, headed to Fort Collins, Colorado, where the Division of Arbovirus Born Diseases branch of the CDC was located. Why Fort Collins and not Atlanta, because the department head was still convinced in his heart of hearts that it was Japanese encephalitis virus, which is an arbovirus virus. Yeah, so hence Fort Collins. Less than ten hours after arriving in Fort Collins, Chiua was at the lab looking at the samples under the microscope, and what he saw terrified him. He saw the concrete ring like structures characteristic of PARAMICS viruses. Why was that so scary? We've kind of touched on that a bit. For one, it showed that this was not Japanese andencephalitis virus, which very clearly, very clearly, and that confirmed that none of the control efforts that they had spent months trying had actually done anything. I mean, it is possible that maybe there would have been an outbreak of Japanese andencephaliteis virus that they prevented from these control measures. I guess we won't know, but it didn't do anything to stop this particular outbreak. And for two, it's because it was a PARAMIX virus. These are as we've talked about a very scary group of viruses with clear pandemic potential. They infect a wide range of animals. There RNA viruses, which typically means for most RNA viruses, they have high mutation rate, and nepavirus does. Indeed, they're spread through airborne droplets and close contact, and they have some of the highest infection rates that we've ever encountered. Measles, as we've talked about before, has an ar not of twelve to eighteen, which still I still it still blows my mind. Yeah. Yeah. And this new paramixavirus had an incredibly high case fatality rate nearly forty percent, which pales in comparison to some of the later outbreaks, but still forty percent of people who were infected died.
Like that's I know, huge, it's also yeah, it's it's it's really interesting to then put this particular outbreak in the context of it was not nearly as bad as it could have been based on all of the further outbreak, Like it's.
Just I know, I know, yeah, it's like forty percent that seems low.
And it's terrifyingly high.
It's terrifyingly high. Yeah, And this was incredibly terrifying, alarming, horrifying for the situation in Malaysia, the fact that it was a new virus and a new Paramix virus, and it was also terrifying and horrifying for doctor Chua and the other researchers who had been handling these virus samples, just like without the safety measures that they warranted, right, Like nepavirus requires the highest level of biosafety precautions biosafety Level four, which the CDC in Fort Collins did not have. And so once they realized, oh god, we have a paramix of virus on our hands, we need to get these things to close that tube. Fanol those hands you might need, might need more than that. Bleach those hands. Send the samples, bleach everything, Send samples to the CDC in Atlanta. There they can be studied safely. And in Atlanta, researchers confirmed that yes, this was a novel paramixa virus, and it's one that seemed to be closely related to Hendra virus, which had been discovered just a few years earlier in nineteen ninety four in Australia.
Which is also so interesting because these are like Hendra and Nepa are very different than other paramixa viruses. Yeah, so it's very interesting that like Hendra was just discovered a few years prior, and then here comes Nepa on the scene.
Like I know, I know, I feel like the nineties had a lot of these kinds. We'll get into it in a second, Okay. The name Nepa was given to the virus after the village Kampung Sungai, Nepa, where the patient whose samples were used to detect the virus had lived. So it was like this person, that's where they had lived. An international team of experts traveled to Malaysia to learn more about this novel virus, how it was being transmitted, and helping with like containment measures, and they ultimately concluded that it was from the pigs. By the end of the nineteen ninety eight to nineteen ninety nine outbreak, two hundred and sixty five people had been infected with nepavirus in peninsular Malaysia and eleven people in Singapore, which had imported pigs from Malaysia, and one hundred and five people died, which is, like I said, a case fatality rate of around forty percent. The majority of those infected, around seventy percent, were directly involved in pig farming, and there was significant association between people who had worked closely with pigs and piglets, like giving injections or medications, assisting with birth, handling of dead pigs, and so on. Just to think about this like, okay, yes, it was an outbreak among people who farmed pigs, but you also have to think about where these were entire communities. I watched in one video someone describing how there would be a street where you know, homes on a street, and every single home had a funeral happening like the same week because it had hit that farm, and all of the people who had lived on that street worked in the farm. And it's just like everyone, yeah, everyone, it's it's really awful. And it wasn't over. Once this a link between the pigs and the infection was made, the government ordered all pigs and affected areas to be cold, so in total, around one point one million pigs were killed in a process that was described as just utterly horrific. One person said, I don't think that I could do this again. I could participate in this again.
It sounds absolutely awful.
Yeah, and one point one million pigs. That was nearly half of the population. And while the culling did seem to halt transmission, so five point six percent of all pig farms in peninsular Malaysia were positive for a nepavirus, it was also catastrophic for people who had made their livelihoods out of this. I don't know anything about whether there was compensation for cold pigs, but I did read that very few people were able to continue with pig farming after this, maybe because testing restrictions were too difficult to meet afterwards, or the financial burden was placed entirely on the farmers and workers, or maybe because they didn't want to get sick and die if there was another outbreak, maybe they had horrible like trauma from that other outbreak. Before the outbreak, there were one thousand, eight hundred and eighty five pig farms in peninsular Malaysia, and by July of nineteen ninety nine there were eight hundred and twenty twenty nine.
Wow.
Right, And I think an outbreak like this really shows how far the impacts of a disease can ripple outward. On the personal scale, people lost their lives or their loved ones, their neighbors, their support system, their livelihood. On the regional scale, this virus resulted in a major hit to an important industry, which led many people to move or entirely change their way of life. And globally, NIPA virus I think represented another terrifying reminder that our interactions with domestic and wild animals can have deadly consequences. Throughout the nineteen eighties and nineteen nineties, outbreaks of a new deadly virus spilling over from animals seem to happen over and over again. HIV growing to pandemic level in the nineteen eighties, sinnombrae virus in the southwestern US in nineteen ninety three, the hendrovirus outbreak in nineteen ninety four, and incredibly deadly outbreak of ebola virus in nineteen ninety five with a case fatality rate of eighty one percent, highly pathogenic av and influenza H five N one spilling over into humans in nineteen ninety seven. And I'm sure that there are others that I'm forgetting. Spillover events happen, and they can be incredibly deadly, and this is catching up to us. The nineteen ninety eight to nineteen ninety nine nepavirus outbreak in Malaysia represented in this regard, another point in the timeline, another deadly emerging zoonotic pathogen, another confirmation that this would keep happening, This will keep happening, and that we have to approach science in a new, much more collaborative and interder disciplinary way if we want to have any chance at prediction, prevention, and control. And one piece of that puzzle was finding out where nepavirus came from how it got into pigs in the first place. Given what was known about Nipa's close relative, hendrovirus, which was transmitted from flying foxes to horses to humans, seemed like bats would be a good place to start the hunt, and long story short, that was the right call. A team of researchers collected urine samples and swabbed fruit that had been partially eaten by fruit bats, specifically those in the Terrapus Is that right genus? Yeah? I think so, and found both antibodies to nepavirus as well as the virus itself. But how did it get from these bats into pigs? Long story short, again humans. The leading hypothesis this seems to be that over the nineteen nineties, pig farms in peninsular Malaysia grew quite a bit in size and density, and many of these pig farms also cultivated mango and other fruit trees, and so this created opportunities for the virus to repeatedly spill over from the bat reservoirs to pigs. Deforestation is also thought to have maybe played a role too, because it can drive movement and clustering of bats to the diminishing number of places with resources, so like there's only one stand of trees left, all the bats are going to go there, much more pathogen exchange, et cetera. It also appears that the September nineteen ninety eight cases weren't the first of nepavirus. Samples from five people who got sick in nineteen ninety seven were retested and found to be positive. It's possible that it was even older than that. I just those are the early samples that, as far as I know, have been found. How did the virus get into the bats? We've gone, like now back the chain of transmission. I mean, it probably had been there for quite some time. Seems like it evolved with its bat hosts and doesn't really seem at least as far as I read, to cause substantial disease in bats. So in that way, it's similar to hendrovirus. The nineteen ninety eight nineteen ninety nine outbreak of nepavirus in peninsular Malaysia seems like it was the virus getting its foot in the door because nearly every year since, like I was going to go through all the subsequent outbreaks one by one, but it's like every.
Single every single year.
Almost every single year. It's it's remarkable outbreaks have happened, especially in Bangladesh and India. But these outbreaks are different from the nineteen ninety eight to nineteen ninety nine outbreak in Malaysia in a couple of alarming ways, and we've kind of touched on this already. The first being that the case fatality rate is substantially higher than the forty percent reported in Malaysia, so on average it's been around seventy percent, with that one outbreak in twenty one people in Kerala, India in twenty eighteen reporting a ninety one percent case fatality rate. And the second is that unlike the outbreak in Malaysia, which seemed to mostly be from pigs to people, these later outbreaks involved much more human to human transmission, which has set off some alarm bells in terms of epidemic or pandemic potential for this virus, which after nineteen ninety nine has for the most part only been involved in outbreaks in the double digits, But will it stay that way right? To help answer that question, we need to better understand how these outbreaks happen in the first place, What increases the likelihood that nepavirus will spill over into humans and what seems to reduce that risk. Yeah, I can't answer these questions.
How do we stop this? How do we stop this?
But luckily there is someone.
Who can m H and we've got them here.
We've got them here today, let's chat with doctor Cliff McKee all about the ecological drivers of nepavirus outbreaks.
So I'm doctor Cliff and McKee. I'm a disease ecologist and a research associate at the Johns Hopkins Bloomberg School of Public Health. I came here in twenty twenty to study nepavirus in bats in Bangladesh. And before that, I was a PhD student at Colorado State University studying bacterial infections of fruit bats kind of the diversity of these bacteria and theracology. And I've worked on kind of some other projects on bacterial infections in felines and I think generally my research focuses on one health and trying to understand the dynamics of pathogen spillover at human animal interfaces and prevention efforts and epidemiology across scales.
Thank you so much for joining us today. We are thrilled, like so super brighted to have an actual expert here to talk about the ecological drivers of nepavirus outbreaks and then also some of the strategies for predicting and controlling, Like this is going to be such a fun time. If we can start off with the bats that are at the center of all of this nepavirus mess, the ones in the terrapists, the terrap Is genus, the flying foxes. What are some of the ecological characteristics of these bats that lead to spill over events of nepavirus and does it differ across the different species of the terrapusts.
So, the different Turopus species that carry nepovirus, including Tropus medius, Tropis lilly, Tropus hypomelanus, and Theropus vampirius, have a lot of similarities in their ecology that could factor into spillover of nepovirus. All four of these species are known to roost and forage near human settlements and even in highly urbanized areas, and they commonly feed on cultivated fruit like mango, banana, and guava, and roosting sites for these species can range from sort of intact forests to a large tree in a village area or even a park in the middle of a city, and in some countries like Thailand and Vietnam, roosts are often situated on temple grounds where they receive some sort of some detection from disturbance. But the common denominator seems to be that these species all tolerate human presence really well and are opportunists. They feed on sort of a mixture of cultivated and wild fruit and nectar resources that are available in their area in a given season. Now, there are some species that are more urbanized than others, such as turope As medius that's found in India and Bangladesh, But I don't think we have really any indication that these species are gravitating towards humans per se, or rather that land use change has stripped away sort of the native forests and the bats have found ways to adapt to this modified landscape. So the amount of potential contact between turop as bats and people has a lot to do with the amount of modification that's gone on in some regions versus others, and maybe has less to do with the fundamental difference is in their ecology.
Okay, interesting, Yeah, NEPA virus outbreaks have occurred in only a fraction of the geographic range of Taropis bats, suggesting that does this suggest I guess that we're only seeing the tip of the iceberg when it comes to possible outbreaks, or maybe a more specific question is do we know what set or sets of circumstances lead to a spillover event and then what allows or causes a spillover event to turn into an outbreak?
Speaking first towards sort of like these sets and or set of circumstances that lead to a spillover. Having bats living near humans is a necessary prerequisite for spillover to happen, but proximity alone really isn't sufficient. In the NIPA outbreaks that have happened in Malaysia in Bangladesh as well as another probable outbreak in the Philippines, there was this added element that allowed spillover to happen. I kind of think of it as as a channel. Perhaps in Malaysia that channel was pigs which were likely exposed when bats came to feed on mangoes and other fruits on farm premises that were doing mixed agriculture, and so these bats dropped mango, you know, partially eaten mangoes or fruit pits into the pig sties. In the Philippines the channel was horses which may have encountered dropped fruit or pasture grass that was contaminated with bat urine similar to what we see with hindrovirus. And in Bangladesh the channel is date palm sap. The sap is collected from date palm trees during the night and then it's sold fresh, often with the sap cellar going door to door to different households. And we know from infrared camera footage that Tropis bats frequently come to date palm sap trees to consume the sap and probably contaminate the sap with their saliva or urine potentially containing nepovirus. So in all of these cases, there's some novel ecological element that creates this channel for nepovirus to get from bats into humans, either via some bridging hosts like pigs or horses that humans interact with more frequently than bats, or a food item that allows humans to have direct contact with the virus. So the absence of NEPA cases in other Asian countries that Tropis bats live in is maybe a bit of a mystery, but I think the simplest explanation is that it's these novel ecological elements that widen this pathway for NEPA to get from bats into humans. They're missing or they might function differently than in areas with known outbreaks. And then there are other interactions with bats that could plausibly be involved with spillover, including bat hunting or humans eating dropped fruit directly from the ground. In Bangladesh, these exposures haven't been significantly associated with infection. In case control studies, only date palm SAP consumption was associated. So there's there's some speculation that the dropped fruit consumption is the cause of recent outbreaks in Kerala, India, but there just aren't enough cases yet to draw really strong conclusions. And to get to this question about sort of the tip of the iceberg part of your question, I do think there are potentially spillovers that we're missing, especially those that only cause you know, a handful of cases. This is because hospital based surveillance for NIPA virus was for a long time only happening in Bangladesh, but large outbreaks of severe respiratory disease or encephalitis. I think those are hard to miss. So while I think I think there's probably some spillovers that are going on undetected in countries you know, across the range of Taropa's bats, we're probably not talking about you know, thousands or hundreds of thousands of cases that are going undetected. And speaking to what takes a spillover to become an outbreak, this mostly depends on the epidemiological conditions that facilitate human to human transmission. So NEVA virus doesn't really transmit that well between humans, less than ten percent of cases actually transmit to another person, but in areas where there aren't good hygiene practices in hospitals, there have been outbreaks that happen inside of hospitals, and in one large outbreak in Bangladesh, person to person transmission largely centered around a local religious leader whose followers came to visit them while the while they were sick. So these epidemiological conditions could change in the future and open up you know, new risk actors or even you know, with the introduction of a new strain of the virus, But for now, the major source of human cases is directly from spillover and not person to person transmission.
So you mentioned surveillance, which initially was happening only in Bangladesh, and it's our understanding that the threat of nepavirus is also not consistent year round and there was at least for a time increased surveillance or surveillance that only happened during certain parts of the year. Can you talk a little bit about the seasonality of nepavirus in Bangladesh and how it's driven or is it driven by the ecology of flying foxes.
Yeah, So the seasonality of nepavirus spillovers in Bangladesh is tied really closely to when date palm SAP is harvested for fresh consumption. Almost all human outbreaks have happened in winter, and that's between November and April, and this coincides with the sap harvesting season. In areas where sap harvested for fresh consumption, bats only have access to the sap during these winter months, and in areas where sap is harvested for other purposes like molasses production and trees are tapped year round, we do see that bats will feed on the sap in summer months because it's available, but they do make more visits during winter, and we think this has to do with just the bat's opportunistic feeding behavior. But you know, maybe they're they're shifting towards drinking this sap because they lack other fruits during winter. You know, there's just not as much that's ripe during that time of year. But going back to this idea of date palm SAP being this channel, it seems like this channel for spillover is only open for a very limited time. Now, what's interesting is that the bats are not more likely to be infected with nepavirus during winter, So detections of nepavirus and bats are pretty sporadic throughout the year, and at least in the large roosts that we've that have been monitored or for multiple years, there might even be more detections in spring and summer months. So there's this disconnect. It could be that date palms at this channel is just good enough or well timed enough during winter to let some trickles of virus through into humans, but there might be an alternative explanation. We did a study where teams investigated NEVA spillovers in Bangladesh where the teams identified the nearest Turopis bat roost to a human spillover, and then collected urine samples to test for NEPA in a handful of roosts. They were able to detect NEPA virus in bat urine, often weeks after the human case had been reported. And mind you that these investigations were all happening in winter. The roosts with detected virus we're not these really large bat roosts, but rather smaller roots of a few hundred bats. This indicates that bats can be shedding the virus in winter, but perhaps it's happening in some of these smaller roosts. And so what we need to understand better is how bats are moving within this network of large versus small roosts, the seasonality of these movements, and the effects of nepovirus transmission among bat populations on sort of a whole landscape scale.
There are so many factors, I feel like that go into this. It makes it incredibly complicated. And you've kind of touched on one already, which is human land use change and these other ways that humans have sort of changed the ecology or the landscape of these bats. And I was wondering if you could kind of dive a little bit deeper into that and talk about how habitat loss or deforestation, what role these play in setting the stage for a spillover of nepavirus from bats to domestic animals or from bats straight to humans, and sort of what that looks like or the different ways that could look.
Well, I keep going back to this idea of channels. None of those would exist if it weren't for humans putting them there. The intensive pig farms in Malaysia, or horses in the Philippines, or even date palm sap in Bangladesh. None of these occur naturally. Date palm trees are native to Bangladesh, but access to sap requires carving out a section of the trunk, which is not something that bats can do. So a key landscape change is definitely the placement of these channels for spillover into the system, be it domestic animals acting as bridging hosts, or foods that can carry the virus directly from bats to humans but zooming out a bit further though, these key pathways may just be sort of the finishing touches in the process of landscape change, historical loss of forests and conversion of land for human agriculture is really the ultimate force that's bringing humans into closer proximity with fruit bats. You take a native forest forest where bats feed on wild fruit and nectar, then cut those trees down and replace them with fields and places to raise domestic animals, and also put in cultivated fruit trees. The bats end up just sticking around in the remaining trees and eat mangoes, you know, and other things in people's backyards. So really humans have inserted ourselves into bat habitat and the bats just tolerate it, but it becomes this recipe for virus spillover.
Now.
I think the timeline of this process differs slightly among the outbreak countries. For Malaysia, the process of clearing land for agriculture and increasing production of pigs and mangoes was something that was ramping up a lot in the nineteen seventies, eighties, and nineties, setting the stage for the outbreak in nineteen ninety eight. But in Bangladesh, the majority of forests have been gone since the seventeen hundreds and date palms have been cultivated for sap and molasses. Production over that whole time, because we know that the British colonialists in Bangladesh encouraged planting of date palms at trees, So the conditions for spillover in Bangladesh have been present for a long time, but we didn't know to look for human cases of NEPA until we knew there was a virus and we had tests to detect it.
Kind Of going along with that, is there evidence that nepavirus outbreaks are increasing in either frequency or severity and kind of maybe zooming out even further. What are the possible effects of things like climate change on the ecology of nepavirus or on these spillover events.
I don't think outbreaks are increasing in frequency or severity. There haven't been any more spillovers in Malaysia since the nineteen ninety eight outbreak, and in Bangladesh, the number of cases linked to date PALMSAP consumption kind of goes up and down and has been a bit slower since twenty sixteen, and the outbreaks haven't been as large as in previous years, which might speak to the effectiveness of control efforts that have gone on. But what is interesting is that the number of spillovers we see in Bangladesh is correlated well with how cold a winter season is, which likely links back to date palmsapp production and consumption practices. So date palmsapp collectors anecdotally report that they get higher quality SAP during colder winter nights, and we also know from household surveys that consumption of SAP is higher in cooler years. Now, this might be caused by something about the physiology of the trees producing more SAP or higher quality SAP, or just that the SAP is less likely to spoil in cooler weather, but something about weather is driving this system. So as climate continues to warm, this suggests that NEPA spillovers through date palm SAP consumption in Bangladesh might decline. However, I don't really want us to become complacent about NIPA in Bangladesh. We know that NEPA virus can take other pathways to get to humans, like through domestic animals, so I think we need to need to remain vigilant with surveillance. Case in point is India. Those outbreaks in Kerala came out of left field in twenty eighteen, and we don't completely understand the ecology of what's happening there, the pathway that the virus took from bats into humans, and any of the effects of land juice change that might be at play in India, And of course every single spillover event is a new chance for a strain of nepavirus that has higher transmissibility in humans, for that strain to emerge, or for higher transmissibility to evolve in humans or some bridging host. And of course climate change could alter the range of Turope's bats and cause some species to shift their roosting locations and food resources to overlap even more with humans, leading to potentially more spillovers. We honestly don't really know what's in store for us, So I think extending human surveillance efforts modeled in Bangladesh to other Asian countries that have Turopus bats could be a first step, but also sort of expanding surveillance to domestic animals, for example on large pig farms could be a good step.
Problems like nepavirus outbreaks really require a one health approach, which is something that we love on the podcast. We're always mentioning, We're always talking about we're such big fans, and this involves people working collaboratively across disciplines and organizations and different levels of government and with community involvement too, to address the health of humans, animals, and the environment. Even though we're always talking about one health on the podcast, I don't know if we've ever really talked about like what an actual one health approach looks like on the ground, And I was hoping you could talk a little bit about that, like what does a one health strategy for nepavirus look like and why is it so important for this particular pathogen.
Nepovirus is really kind of a perfect example of the power of a one health approach for emerging diseases. And at the heart of one health is is shared focus on human health, animal health, and environmental health. So with NIPA, you have to think beyond just the human outbreaks and dig into bat ecology and the health of bats, agricultural systems and those interfaces between bats, domesticated animals and humans, and the economic forces that are at the root of things like land uice change and choices to harvest certain food products like date palmsap NIPA touches on all of these things and you have to address them holistically, and a key part of this implementation of one health is with the formation of project teams, not only including sort of epidemiologists and virologists in investigations, but also ecologists and veterinarians, anthropologists and other social scientists. Teams not only have to be interdisciplinary, but ideally transdisciplinary, with individuals on the team that have gone beyond their specialized training to work in other disciplines and can act as liaisons and facilitate this really collaborative work and then speaking to one health approaches Tanita in Bangladesh. In addition to ongoing human surveillance efforts at hospitals, we're also looking into the frequency that nepovirus might be spilling over into domestic animals, including cows, goats, pigs, cats, and dogs, because this might be another pathway for the virus to jump into people outside of the winter date palm season and might not be currently captured by the existing surveillance efforts which are really optimized for spillover through this date palmsapp channel. We also should be researching kind of more about how the health of bats varies over time in space and how much this contributes to spill. There's this hypothesis out there that bats might shed more viruses when they're experiencing stress, either during food shortages or during pregnancy and lactation. So if we knew more about when bats are stressed, then we can inform public education campaigns about not drinking SAP or ramping up surveillance on domestic animals. We could also use this information to find ways to support the health of bats, maybe by restoring forest habitat and wild food resources. And lastly, I think the social sciences are crucial for implementation of prevention. For example, getting people not to drink SAP has been difficult to do in Bangladesh because it's such a strong cultural practice and people preceed it to be low risk. So identifying ways to protect SAP from contamination by bats, using things like bamboo or plastic coverings, or economic incentives to encourage SAP producers to maybe shift from selling raw sapp to selling molasses. Any work we can do to make these more acceptable could go a long way to prevention of NIPA virus.
Billovers.
That was that was so great.
I loved it.
I loved it. Yeah, yeah, thank you, thank you so much much. Jinks, doctor McKee away for chatting with us about this. It really is. So it's just so great to talk to like an expert who actually is there doing the work on one health.
Stuff, doing the thing. Thank you for your work.
Thank you for your work and your time.
Yeah. So let's wrap this up, shall we with just looking at where we stand with nepavirus today.
Let's do it.
So the good news, there's a few good news is good news is there's some good news to be had in this case. Thus far, as of twenty twenty four, or I should say as of twenty twenty three, when the papers that I read were written, nepovirus has still caused less than seven hundred human cases. But I think that we've also made the case through this whole episode that that doesn't mean that it's not worthy of study. This is a virus that has a lot of potential to cause quite a number of more cases than that, and because of that reason, a lot of people are working on nepavirus. Like I said at the very top, this has been named one of the top ten high priority path gins for the World Health Organization because the truth is that this these spillover events are not something that is happening rarely. Right between two thousand and one to twenty eighteen, in Bangladesh alone, over one hundred and eighty three spillover events have happened.
That's a lot, one.
Hundred and eighty three individual spillover events. And there have been additional outbreaks and spillover events that have happened in more and more places in different parts of India, in Singapore, in the Philippines. This is a virus that exists, persists, and luckily a lot of people are trying to understand it, both from the one health approach that we heard about already and also vaccines and therapeutics. So while there are still not vaccines yet, this is one of the few times where I get to say that there are a lot of candidates that are moving through the clinical trials press, which is really exciting. There are a few different ones that I found, two of which have started trials in humans as of the end of twenty twenty three and early twenty twenty four. Both of these, from what I can tell, are mRNA based vaccines, which is kind of exciting. And there are also people who are developing vaccines for animals for example, there's already a hindrovirus vaccine for horses, and so the idea that you could use a nepavirus vaccine to vaccinate things like pigs might be helpful in preventing spillover into domestic animal populations.
That's really cool.
Yeah, there's also a lot of work being done on additional therapeutics and anti virals and monoclonal antibodies. Right now, there still aren't any that have actually come to market, but there is. There is just so much focus, I think, on nepavirus and on understanding that it can't be just one of these things. It's vaccines in combination with therapeutics, in combination with prevention strategies, in combination with a one health approach, and really looking at this virus as it truly exists, which is something that is in the environment that we don't have complete control over and we can never actually eradicate. So I think that this is one of the times where if we go all the way back to first season and we say, how scared do you need to be? If I'm being honest, MEPA virus has scared me since twenty eleven.
Is that when Meme out Okay, Yeah, I think it's a very very terrifying virus.
But I think there's a lot of really incredible people that also think that this is a terrifying virus who are doing everything that they can to prevent it from ever becoming something that most people ever have to hear about.
That's a great answer. It is. It is. Yeah, It's like, yeah, this is scary. A lot of people think. So that's why we're working really hard on it, and hopefully we'll have therapeutics or vaccines or detection or a combination, right in case something like this does lead to a larger epidemic, right, pandemic.
Yeah, and that's NEPA.
That's NEPA. That's sources.
Sources, I've got a lot, shall.
We I have so many I'm shouting out just a couple here and all of the rest will be on our website. So there are several papers by doctor Chua. One that I really liked was in Science called nepavirus a recently emergent deadly paramixavirus. That's from two thousand and then there is a paper on the evolution and origin of nepavirus by lol Presty at All from sixteen called Origin and Evolution of Napavirus. And I will also on our website linked to some of doctor McKee's work on napavirus and sort of the bat spillover dynamics of pathogen's one health, all that good stuff.
Yeah, he's got some really great papers.
Also, I referenced a paper of his in our Bartnella episode. Just got to shout it out.
We go way back, just get it for the biology section. I had also quite a number of papers detail on the like true biology and pathophysiology of this pathogen. I really liked a paper in the New England Journal of Medicine called Transmission of Npavirus fourteen years of investigations in Bangladesh by Nikola at All And honestly there was there were so many more and Aaron, like you said, a couple by doctor McKee that were also phenomenal. We will post all of our sources from this episode and every one of our episodes. There's some about the vaccines. There's so much on our website this podcast will kill you dot com under the episodes tab.
Thanks again, Jess. Got to say it one more time to doctor McKee. You're a champion.
Thank you We really appreciate it. Thank you also to Bloodmobile for providing the music for this episode and all of our episodes.
Thank you to Tom and Leanna for the wonderful audio mixing.
Love it. Thank you Exactly Right Network.
And thank you to you listeners for listening. We hoped that you learned something new.
This is like one of our our first episode this season of like a real classic TP and KY classic.
Yeah yeah, longtime, long time coming. Yeah.
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Until next time, wash your hands.
You feel the animals.
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