Speaker 1: I was so overcome by sadness that as soon as
Speaker 1: we completed capturing the required electron micrograph images, I requested
Speaker 1: doctor Crop to use the phone in CDC and called
Speaker 1: up my head in Malaysia. I managed to get him
Speaker 1: at home. I still remember vividly what I told him
Speaker 1: over the phone. Professor lamb Tua hear calling from CDC
Speaker 1: for Collins. Professor listen, listen carefully under the electron microscope.
Speaker 1: The virus has the morphology of a paramixavirus. For God's sake,
Speaker 1: please do not talk about Japanese encephalitis anymore. I'm quite
Speaker 1: sure now it's a paramixavirus. Most likely it is a
Speaker 1: new paramixavirus. The control measures for paramixavirus are totally different
Speaker 1: from Japanese and cephalitis virus. Please, I want you to
Speaker 1: urgently pass this message to the Ministry of Health to
Speaker 1: stop all the Japanese encephalitis control measures and switch over
Speaker 1: to the following control measures. Professor listen carefully. You must
Speaker 1: pass the information of what I have just said to
Speaker 1: the Ministry of Health as soon as possible. I'll get
Speaker 1: doctor Bruce Crop to process the electron micross could be
Speaker 1: photographed and fax it to you as soon as it
Speaker 1: is ready. There was a fairly long silence and he
Speaker 1: did not reply to my words.
Speaker 2: Wow, Aaron, Wow.
Speaker 1: Yeah. So that was from a paper titled the Discovery
Speaker 1: of Nepavirus, a personal account, written of course by Chua
Speaker 1: Copping doctor Chua, who, well you'll hear later from him
Speaker 1: more in the episode, played a really pivotal role in
Speaker 1: the discovery of nepovirus. And I just like this paper.
Speaker 1: It's a personal account of his experience. It's amazing and
Speaker 1: so like, this is just a small little excerpt from it,
Speaker 1: but really the whole thing is so invaluable because I
Speaker 1: think it shows what was he feeling, what was he
Speaker 1: thinking every sort of step of the way, what was
Speaker 1: it like to be there? And we don't really get
Speaker 1: that very much.
Speaker 2: Yeah, to like understand from a first person account of
Speaker 2: someone who was actively working on this during this outbreak,
Speaker 2: on this infection, trying to help trying to figure out
Speaker 2: what was going on, Like, Yeah, what did that feel like?
Speaker 2: What was that like? We don't get to see that
Speaker 2: very much anymore.
Speaker 1: We don't, And that's why I just I love it.
Speaker 1: Go read it. Hi.
Speaker 2: I'm Aaron Welsh and I'm Erin Alman Upday.
Speaker 1: And this is this podcast will kill You.
Speaker 2: Welcome to today's episode.
Speaker 1: Today to today's episode today on Nepa virus.
Speaker 2: Nepa virus.
Speaker 1: Yeah, at least a few of you have suggested this.
Speaker 1: It's been on our list for a really long time,
Speaker 1: and it's been It's been really interesting to kind of
Speaker 1: finally dig into Like I knew what it was, I'm like, oh, yeah, okay,
Speaker 1: this really deadly virus spillover, et cetera. That's whatever. But
Speaker 1: then to actually read about it, I'm like, oh, all right, Yeah.
Speaker 2: To actually get to spend the time to dig into it,
Speaker 2: It's it's going to be a great episode. I'm super excited.
Speaker 1: It's going to be a great episode. Also because we
Speaker 1: are going to be chatting with an expert guest later
Speaker 1: in the episode.
Speaker 2: Our favorite thing to do, Kearn's gone to get this season,
Speaker 2: I know, I know.
Speaker 1: And also we're gonna ask them to pick up the
Speaker 1: slack that we will be dropping when it comes to
Speaker 1: talking about the ecological factors that contribute to outbreaks of nepavirus.
Speaker 1: So doctor Cliff McKee, who is a research associate at
Speaker 1: Johns Hopkins Bloomberg School of Public Health will be joining
Speaker 1: us to talk about the dynamics of pathogen spillover events
Speaker 1: from bats to humans. So excited, So excited? I wait,
Speaker 1: me too, But we have a lot to cover before
Speaker 1: we get there, including it's quarantine eytime. What are we
Speaker 1: drinking this week?
Speaker 2: We're drinking when pigs fly, which will make sense. It'll
Speaker 2: make sense later in the episode. It will, it will,
Speaker 2: it will. It's you know, bats, pigs whatever.
Speaker 1: We'll get there, and the quarantining itself is quite a
Speaker 1: delicious one. It has rum, it has mangos, it has lime,
Speaker 1: passion fruit. You know, it's tasty, and we will post
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Speaker 1: It's true. Let's get started, Aaron, Okay, right after this break.
Speaker 2: So, NEPA virus is an RNA virus in the family
Speaker 2: paramix of your which a longtime fans of the pod
Speaker 2: might be familiar with, because we've actually covered some other
Speaker 2: PARAMIXA viruses on this podcast before Measles is a paramix
Speaker 2: of virus, mumps is a paramix of virus. Other ones
Speaker 2: you might have heard of include the para influenza viruses,
Speaker 2: which cause common colds. Can't forget about Render.
Speaker 1: Pests, Render Pest one of I think one of my
Speaker 1: favorite episodes. A great success story when it comes to
Speaker 1: public health or wildlife health, or veterinary health, One Health Health,
Speaker 1: One Health. That's the thing, One Health.
Speaker 2: Also, Hendra virus, which we have not yet covered but
Speaker 2: we will someday, is the most closely related to NPA virus.
Speaker 2: So nepa virus and hendravirus are both in the family
Speaker 2: paramix of Iriday and the genus they kind of have
Speaker 2: their own, which is called henipa virus. I think it's
Speaker 2: a combination of hendra and NPA virus. It stands creative. Now.
Speaker 2: I don't want to bury the lead here too much
Speaker 2: for anyone who didn't request nepavirus, who's maybe never heard
Speaker 2: of this thing and is wondering why the heck we're
Speaker 2: covering this virus that they've never heard of. Nepovirus has
Speaker 2: been named one of the top ten highest priority pathogens
Speaker 2: for the World Health Organization to focus on in terms
Speaker 2: of the development of countermeasures. That means focus on vaccines,
Speaker 2: focus on developing treatments, focus on prevention. And the reason
Speaker 2: is because NEPA virus has huge pandemic potential, so not
Speaker 2: to jump ahead too much. But not only is this
Speaker 2: virus capable of spreading person to person, not only has
Speaker 2: it continued to pop up and spread to new places
Speaker 2: year after year, as we'll talk about, but Nepa virus
Speaker 2: is also one of the most fatal infections that we've
Speaker 2: seen in humans. Case fatality rates on the low end
Speaker 2: tend to be around at least forty percent, and in
Speaker 2: many outbreaks they've been upwards of ninety percent of cases.
Speaker 1: It is unreal.
Speaker 2: It is terrifying in all honesty. Yeah, yeah, So it's
Speaker 2: a big deal virus and you're gonna learn all about
Speaker 2: it today. So NPA virus primary reservoir is bats, so
Speaker 2: in nature, in the wild, it lives specifically in bats
Speaker 2: in the genus Teropis terrapus terrapus. I think I decided
Speaker 2: it's terrapists.
Speaker 1: We had a conversation about this, and I have forgotten
Speaker 1: what we landed on.
Speaker 2: I looked it up several times and then I pronounced
Speaker 2: it wrong the first time. I just said it it's terrapists.
Speaker 2: These are flying foxes, fruit bats. Right, There's a few
Speaker 2: different species, but for much of the distribution of NEPA
Speaker 2: virus that we've studied so far, it's predominantly Terrapus medius
Speaker 2: that's been implicated in NPA transmission thus far, and NEPA
Speaker 2: has outbreaks in humans in a number of different countries
Speaker 2: across South and Southeastern Asia and the Pacific, including India, Malaysia, Singapore,
Speaker 2: the Philippines, and Bangladesh. But the bats that carry these
Speaker 2: viruses are distributed really widely across Asia, the Pacific, Australia,
Speaker 2: even parts of Africa. The majority of cases thus far,
Speaker 2: like by far, have occurred as the result of spillover events,
Speaker 2: So this is a zoonotic disease primarily, and most of
Speaker 2: the spillover events have happened either from bats to humans
Speaker 2: like a little bit directly, or from bats to domestic animals,
Speaker 2: especially pigs, and then to humans. But like I mentioned,
Speaker 2: this virus has also shown that it is entirely capable
Speaker 2: of being transmitted person to person as well. So let's
Speaker 2: get into a little bit more detail about how this
Speaker 2: virus makes its way into humans. What's interesting is that
Speaker 2: so far in different geographic areas where we have seen NIPA,
Speaker 2: there seems to be different modes of transmission that kind
Speaker 2: of predominate. And maybe we'll ask doctor McKee a little
Speaker 2: bit more detail about the ecology of this. And it
Speaker 2: also might have to do with the viral strains, because
Speaker 2: there's two different major viral strains in Malaysia where NEPA
Speaker 2: was first detected. And I know you're going to talk
Speaker 2: all about it.
Speaker 1: How dare you?
Speaker 2: How dare I mention that this was first detected at
Speaker 2: some point in time?
Speaker 1: Why do I even do anything on this podcast? I
Speaker 1: just kidding.
Speaker 2: So in Malaysia, where it was first detected, outbreaks have
Speaker 2: been associated with contact specifically with intermediate hosts, mostly pigs,
Speaker 2: and it's thought that these pigs got infected by eating
Speaker 2: fruit that was mostly bitten or possibly poopter peed on
Speaker 2: by bats, and then humans got infected via direct contact
Speaker 2: with those domestic animals, either through things like slaughterhousework or
Speaker 2: farm work, or through even contaminated meat. Then in the
Speaker 2: Philippines we have seen outbreaks that have been associated also
Speaker 2: with an intermediate host between bats and humans, but there
Speaker 2: it seems to be horses and horse meat that has
Speaker 2: been involved. And then in Bangladesh the primary as well
Speaker 2: as India to a certain extent, the primary root of
Speaker 2: transmission seems to be a little bit more directly due
Speaker 2: to bat contact, but via raw date palm SAP that's
Speaker 2: contaminated with either the saliva or perhaps the urine or
Speaker 2: feces from infected bats because apparently bats also love raw
Speaker 2: date palm sap just like humans do. So then humans
Speaker 2: essentially ingest this contaminated SAP and then become infected that way.
Speaker 2: There also have been cases where humans might have come
Speaker 2: in direct contact with bats or bat feces, bat urine
Speaker 2: something like that and gotten infected, like truly directly from bats.
Speaker 1: And this is ingestion. This is through ingestion.
Speaker 2: As far as I could tell. Yeah, I mean it's
Speaker 2: coming in contact with this date palm sap and what
Speaker 2: you do with it is you drink it.
Speaker 1: So yes, But like when we're like thinking about pigs
Speaker 1: and stuff like that, like is the contact again through
Speaker 1: or is it respiratory?
Speaker 2: Like what great question? Great question with pigs and intermediate hosts. No,
Speaker 2: it's not necessarily ingestion. You could get infected from contaminated meat,
Speaker 2: but even then it isn't necessarily from ingesting the meat,
Speaker 2: because if you cook it then you're going to be
Speaker 2: killing this virus. It's it's heat labile, but it's getting
Speaker 2: in contact with things like respiratory secretions or bloodborne products,
Speaker 2: like anything from this animal that has virus in it
Speaker 2: could then be transmitted to people. But the part that
Speaker 2: makes this virus a BSL for a Biosafety Level four pathogen,
Speaker 2: a pathogen of pandemic potential is that in many of
Speaker 2: the outbreaks there is also evidence of person to person transmission,
Speaker 2: and this is usually with contact with respiratory secretions, but
Speaker 2: it's very likely that other bodily fluids can also transmit.
Speaker 2: It's just that respiratory secretions are thought to be the
Speaker 2: main component of transmission when it's person to person.
Speaker 1: Question, does the strain or the root of transmission originally
Speaker 1: if it's a spillover event, does the strain then impact
Speaker 1: the ability of it to become transmitted person to person?
Speaker 1: And is that more likely from like the like from
Speaker 1: that direct to human rather than batpig human?
Speaker 2: Excellent questions. So yes, the first part of the question.
Speaker 2: So the first part of the question is do the
Speaker 2: strains seem to make a difference in whether they're transmitted
Speaker 2: person to person. The two main strains are the strain
Speaker 2: from the kind of original outbreak or couple of outbreaks
Speaker 2: in Malaysia, and then the strains that were first identified
Speaker 2: in Bangladesh. Those are kind of the two main lineages.
Speaker 2: It seems we have a lot more data on strains
Speaker 2: from Bangladesh, like you know, sub strains or whatever from
Speaker 2: Bangladesh than we do from Malaysia. But in those initial outbreaks,
Speaker 2: there was very limited evidence of person to person transmission
Speaker 2: from what I could tell, not even like definitive evidence
Speaker 2: of person to person transmission in those first Malaysian outbreaks.
Speaker 2: So is that because those strains are less likely to
Speaker 2: be transmitted person to person? Perhaps, but I don't know
Speaker 2: that we have as much evidence to say for sure
Speaker 2: the strains in Bangladesh are more likely to be a
Speaker 2: transmitted person to person, But I don't think that we
Speaker 2: have data, at least I didn't see any on whether
Speaker 2: it's more likely to happen like how that primary person
Speaker 2: got infected, whether it was from date palm, SAP or
Speaker 2: from an intermediate host or from a bat. However, it's
Speaker 2: only about ten percent of people that seem to be
Speaker 2: spreading this person to person, which is very interesting. Overall,
Speaker 2: it's a pretty low rate of person to person transmission
Speaker 2: in the outbreaks that have been studied. However, there is
Speaker 2: plenty of evidence that that chain of transmission can live
Speaker 2: on for like several viral generations, if that makes sense.
Speaker 2: So one person out of every ten who gets infected
Speaker 2: is going to transmit it to someone else, but then
Speaker 2: the person that they transmit it to can transmit it
Speaker 2: to someone else as well.
Speaker 1: So it's like there's something about that person that makes
Speaker 1: them makes the virus like, hey, this is great.
Speaker 2: Exactly we saw. I think everyone's familiar with the idea
Speaker 2: of a super spreader after COVID. It's that same kind
Speaker 2: of idea. We don't know right now. Is that a
Speaker 2: characteristic of the virus that happened to infect that person,
Speaker 2: or is it a characteristic of certain people that makes
Speaker 2: them super spreaders in this case, we definitely do not know. Okay, okay, yeah,
Speaker 2: So that's kind of how this is transmitted, right It's
Speaker 2: a lot of different ways, and it really does depend
Speaker 2: on the circumstances, and we'll get into more of the
Speaker 2: ecology of this virus later when we talked to doctor Murckey,
Speaker 2: But let's then talk about more of what this actually
Speaker 2: looks like when a human does get infected, and I'm
Speaker 2: focusing on humans, but again, this is a zoonotic pathogen,
Speaker 2: so this is infecting and living amongst bats very readily.
Speaker 2: And when it infects our domestic animals like daw cats, pigs, horses,
Speaker 2: it does tend to cause symptomatic disease for the most part,
Speaker 2: but it really varies how sick these animals get, So
Speaker 2: I'm not going to get into detail on all of that.
Speaker 2: Let's focus on humans, shall we.
Speaker 1: Let's do it.
Speaker 2: Once a human gets infected, the incubation period tends to
Speaker 2: be between four days to two months, which is a
Speaker 2: huge range, but over ninety percent of people who have
Speaker 2: symptoms will have them within two weeks. Now, how many
Speaker 2: people are going to have symptoms, We have no idea.
Speaker 2: You can find numbers, but this is such a rare
Speaker 2: and understudied pathogen still that estimates range between one percent
Speaker 2: and forty five percent of people that are asymptomatic, depending
Speaker 2: on what the study is so it's.
Speaker 1: The biggest range we've encountered on this podcast.
Speaker 2: It's a meaningless range.
Speaker 1: It's entirely it's not one hundred percent.
Speaker 2: Not everyone we know that this is true. So in
Speaker 2: any case, there are some proportion of people who are
Speaker 2: likely asymptomatic based on like ero logic studies that we
Speaker 2: have seen. Okay, but for people that are symptomatic, this
Speaker 2: is a really terrible pathogen. Symptoms tend to start after
Speaker 2: this incubation period with pretty nonspecific kind of prodrome. These
Speaker 2: are symptoms like a fever, headaches, muscle aches, maybe even vomiting,
Speaker 2: but really nothing that would make you go, oh, this
Speaker 2: sounds like nepavirus, right, It sounds like any other of
Speaker 2: a million infections that we've covered on this podcast, or
Speaker 2: like one hundred and something that we've covered on this podcast.
Speaker 2: But generally within a week, within a number of days,
Speaker 2: you start to see signs of central nervous system infection.
Speaker 2: So this looks like things like altered mental status. Very
Speaker 2: often we can see signs of brainstem involve and so
Speaker 2: you might see changes in reflexes. Usually it would be
Speaker 2: like a loss of reflexes or a decrease in reflexes.
Speaker 2: But there's some literature where we can see like loss
Speaker 2: of very specific reflexes that are associated with that brain
Speaker 2: stem or that lower part of your brain dysfunction. These
Speaker 2: are things like if you turn someone's head side to side,
Speaker 2: in a person whose brainstem is intact but who maybe
Speaker 2: isn't all the way conscious, their eyes should move in
Speaker 2: the opposite direction that their head is turned, like a
Speaker 2: like those creepy dolls that you had in your grandma's
Speaker 2: house growing up. This is called the doll's eye reflex.
Speaker 2: If this doesn't happen, then the eyes just stay midline
Speaker 2: as the head moves. That's a loss of that reflex,
Speaker 2: which is very severe, so it suggests loss of brain
Speaker 2: stem function. There's a lot more detail to that that.
Speaker 2: Don't please ask me about that reflex because I learned
Speaker 2: it once.
Speaker 1: But there are other like what I guess, other diseases
Speaker 1: that affect the brain stem, right, what examples.
Speaker 2: You know, that's a good question. Any kind of meningitis
Speaker 2: that is affecting the brain stem. Yeah, yeah, okay, But
Speaker 2: you also see things like other reflexes, like your pupillary
Speaker 2: reflex or even just loss of muscle tone. You can
Speaker 2: also get instead of a loss of muscle tone, you
Speaker 2: can get these jerks like myoclonic jerks. You can see seizures,
Speaker 2: you can see any number of these neurologic signs and
Speaker 2: symptoms which are just telling us how severe the brain
Speaker 2: infection is in this case, and people tend to deteriorate
Speaker 2: very rapidly. Nepavirus, like I said, is an incredibly fatal
Speaker 2: disease and usually within a matter of days. Forty to
Speaker 2: ninety percent of people in most outbreaks die within a
Speaker 2: number of.
Speaker 1: Days, So it's two weeks you get infected, two weeks
Speaker 1: later you start to have these sort.
Speaker 2: Of nonspecific specific symptoms, and within a couple of days
Speaker 2: in nervous system involvement, coma and death. Death. In some outbreaks,
Speaker 2: there also does seem to be a substantial amount of
Speaker 2: respiratory involvement, though not all outbreaks, which is very interesting.
Speaker 2: So respiratory involvement looks like a cough, it can look
Speaker 2: like an atypical pneumonia, which we've talked about on this podcast,
Speaker 2: just means that on a chest X ray it doesn't
Speaker 2: look like a very classic pneumonia. You can have.
Speaker 1: I know, these are words you can't define h typical
Speaker 1: pneumonia by saying it's just not your classic pneumonia.
Speaker 2: So on a chest X ray, it would look like
Speaker 2: kind of patchy involvement in the whole lungs rather than
Speaker 2: one area of your lungs that's fully infected with a
Speaker 2: bacterial pathogen. That's okay, I think of when we think
Speaker 2: of pneumonia.
Speaker 1: Of classic pneumonia.
Speaker 2: Okay, But in general, you're going to see some degree
Speaker 2: of respiratory distress if you have a respiratory involvement. But
Speaker 2: this hasn't happened in all the outbreaks, so we don't
Speaker 2: really have a great sense of like when or why
Speaker 2: this is happening. And because this is such a fatal infection,
Speaker 2: we don't have that much data in all honesty on
Speaker 2: a lot of these signs and symptoms. What we do
Speaker 2: know is that in people who survive, something like twenty
Speaker 2: percent of them have some degree of like residual neurologic dysfunction,
Speaker 2: which can again really range, and some proportion in some
Speaker 2: of these outbreaks seem to also have like a relapsing encephalitis,
Speaker 2: so looks like a new infection, but it's just a
Speaker 2: relapse months or even years after the initial infection. How
Speaker 2: does this happen? I have no idea.
Speaker 1: Yeah, and they've cleared the virus from their system.
Speaker 2: That's a great question. Do we know that for sure?
Speaker 2: I don't know that we know that for sure.
Speaker 1: Okay, Okay, two questions. Okay, how environmentally stable is this virus?
Speaker 2: I knew you were going to ask.
Speaker 1: Okay, number two, when is someone? If someone is infectious
Speaker 1: person to person, at what point are they infectious? Pre symptoms,
Speaker 1: et cetera.
Speaker 2: Yeah, these are really good questions. So this virus is
Speaker 2: fairly environmentally stable, which is part of how it can
Speaker 2: be transmitted In things like date palm SAP. This virus
Speaker 2: can persist for days outside of a host. One paper
Speaker 2: that I read said that on some fruits and juices
Speaker 2: that they have studied, it can live for up to
Speaker 2: three days and still be transmissible in some cases. In
Speaker 2: some studies where they have kept it colder, like around
Speaker 2: twenty two degrees celsius, it can last for up to
Speaker 2: seven days in something like a date SAP, But even
Speaker 2: at higher temperatures it can survive for like a couple
Speaker 2: of hours. So it's a pretty environmentally stable virus.
Speaker 1: Okay, Now, how.
Speaker 2: Transmissible are people or like when are people most transmissible?
Speaker 2: We don't really know. That's a great question because we
Speaker 2: know that there is some degree of asymptomatic infection. There's
Speaker 2: a really important question of if you are asymptomatic, can
Speaker 2: you still spread this person to person. I don't think
Speaker 2: that we even know that necessarily. I haven't seen a
Speaker 2: lot of data on that. But it doesn't mean that
Speaker 2: it doesn't exist. It just means that I didn't see it.
Speaker 2: What we can try and look at is where is
Speaker 2: this virus replicating to try and understand where are you
Speaker 2: most likely to be able to spread it from? Like
Speaker 2: where is this virus living in ourselves? And even there
Speaker 2: we don't fully know. What we think is that because
Speaker 2: MEPA virus is often spread via rest inspiratory droplets, like
Speaker 2: via respiratory secretions, it was long suspected and it seems
Speaker 2: to be the case in studies so far that the
Speaker 2: epithelial cells that line our respiratory tract are the first
Speaker 2: target for infection and viral replication. So that would mean
Speaker 2: that potentially early on, if this virus is infecting the
Speaker 2: respiratory epithelium, someone could potentially be infectious relatively early in
Speaker 2: their infection, if that makes sense, yes, okay, right, because
Speaker 2: it's invading right there, replicating, and then potentially being able
Speaker 2: to be spread. But NIPA is also particularly adept at
Speaker 2: invading past our respiratory epithelium and specifically going into our microvasculature,
Speaker 2: so our blood vessels and the cells that line our
Speaker 2: blood vessels are endothelial cells. It's one of our favorite
Speaker 2: cells on this podcast, sure, and that essentially means that
Speaker 2: NEPA has direct access to our blood stream. And while
Speaker 2: we certainly don't know everything, not even most things about
Speaker 2: the pathophysiology of this virus, we do know that it
Speaker 2: induces a lot of direct viral damage and immune related
Speaker 2: damage to these endothelial cells, which means that as it
Speaker 2: spreads via these endothelial cells in our blood stream, it
Speaker 2: can damage things like our heart, our spleen, our liver,
Speaker 2: our kidneys. These are all areas where our blood is
Speaker 2: going very rapidly, and it's also causing a lot of
Speaker 2: disruption to our blood brain barrier, which is what allows
Speaker 2: for it to have such easy access to our central
Speaker 2: nervous system. So how much can this continue to spread
Speaker 2: if all of these other bodily fluids are getting infected
Speaker 2: potentially quite a bit, But I don't know like how
Speaker 2: infectious someone is early in the course of their infection
Speaker 2: versus late. I didn't see data on that.
Speaker 1: Okay.
Speaker 2: Another thing though about NEPA virus that is just so
Speaker 2: fascinating is that it's also thought that a secondary way
Speaker 2: that it's getting into our brains, into our central nervous system,
Speaker 2: is actually by traveling up our olfactory nerve. Our olfactory nerve,
Speaker 2: which is obviously in our nose, it's what we use
Speaker 2: to smell, is one of the nerves that gives direct
Speaker 2: access to our brain. It's not covered by the blood
Speaker 2: brain barrier, and so NEPA virus can essentially just hitch
Speaker 2: a riot on this and travel up and get direct
Speaker 2: access to our brain.
Speaker 1: It's thought, how like, how does it get there to
Speaker 1: our olfactory nerve?
Speaker 2: Yeah, well, it's in our respiratory epithelium, which is in
Speaker 2: our nose and our throat and our lungs, And how
Speaker 2: does it get there without causing all of the flags
Speaker 2: that our body would usually use to counter any virus. Right,
Speaker 2: That is what makes NEPA have such a high fatality rate.
Speaker 2: It happens to be incredibly good at if evading our
Speaker 2: immune response. It has a protein and I think a
Speaker 2: number of proteins that specifically inhibit a number of our cytokines,
Speaker 2: including interferon, which basically reduces the ability of our immune
Speaker 2: system to clear this infection. So that combined with the
Speaker 2: fact that it's then or or because of that rather
Speaker 2: who knows chicken and egg. But the ability to cross
Speaker 2: our blood brain barrier and infect our central nervous system
Speaker 2: and evade our immune system so well is what results
Speaker 2: in such significant mortality.
Speaker 1: So does our immune system ever recognize it? I know,
Speaker 1: with like case fatality rates upwards of ninety percent, Like
Speaker 1: you know, obviously at that point, either that our immune
Speaker 1: system recognizes it too late or it doesn't recognize it ever.
Speaker 1: Like the bottom line is, can a vaccine be made
Speaker 1: against this?
Speaker 2: Yeah, great question. As far as we know, we so
Speaker 2: like people do eventually mount an antibody response to it,
Speaker 2: and there's a lot of work being done on vaccines.
Speaker 2: So it's very good at evading our innate immune response.
Speaker 2: But if you could have a faster onset antibody response,
Speaker 2: then perhaps you would be successful at not getting a
Speaker 2: severe infection from NEPA virus. See our episode on vaccines
Speaker 2: if you'd like to know more about these different immune responses,
Speaker 2: because we did it in detail there way back.
Speaker 1: When, way back when. What about like, yeah, other, are
Speaker 1: there any immune therapies or anything like that.
Speaker 2: Yeah, right now, we have absolutely no specific treatment for
Speaker 2: anita at all. Okay, So nepavirus treatment is all about
Speaker 2: supportive care. And because this is an infection that causes
Speaker 2: such severe disease so quickly, supportive care is really like
Speaker 2: ICU level of care, right making sure that you can
Speaker 2: support someone airway if they stop breathing, making sure that
Speaker 2: their fluid balance is good, like whatever is needed, but
Speaker 2: it's very high level of care that's needed. There's a
Speaker 2: lot of research being done on things like antivirals. Sometimes
Speaker 2: there are antivirals that are used even though there's not
Speaker 2: really any evidence so far that they are effective. But
Speaker 2: it's one of those cases where medicine often feels the
Speaker 2: need to like do something even if we don't have
Speaker 2: any evidence that it's effective when you have nothing else
Speaker 2: to do. But right now, that's all that we have
Speaker 2: that is nepavirus.
Speaker 1: It's wild. It is one of the most I mean,
Speaker 1: besides rabies. I'm trying to think of a more preons
Speaker 1: I guess, like a more deadly pathogen that we've covered.
Speaker 2: I mean mnemonic plague, right, but yeah, yeah, yeah, it's
Speaker 2: a really scary. It's a really scary. That is probably
Speaker 2: why Contagion used NEPA as a model system in the movie,
Speaker 2: because it is terrifying. Yep, yeah truly.
Speaker 1: And they're like, you know, I feel like we used
Speaker 1: to end this podcast episodes of this podcast with do
Speaker 1: you remember that? How scary?
Speaker 3: Yeah?
Speaker 2: Yeah, I forgot about This's been a minute since we've
Speaker 2: done that.
Speaker 1: I think we could bring it back for this episode.
Speaker 2: We could. We can talk about it at the end.
Speaker 2: Yeah yeah. So Aarin, tell us, how did NEPA come
Speaker 2: to be with us here?
Speaker 1: I will attempt an answer right after this break. Peninsular
Speaker 1: Malaysia nineteen ninety seven to nineteen ninety eight. Okay, at first,
Speaker 1: it was just the pigs. Sick pigs were not a
Speaker 1: totally unfamiliar site in this part of the country. There
Speaker 1: were occasional outbreaks of classical swine fever aka hog cholera,
Speaker 1: caused by a flava virus called pesti virus C.
Speaker 2: In case you were interested, I'm sorry, just like I
Speaker 2: don't want to interrupt, but like, why do we have
Speaker 2: to call things that are not the same thing the
Speaker 2: same thing? Hog colera not being cholera. That's annoying, stomach flew.
Speaker 2: I can't, I can't think of anything else, but yeah, yeah, okay, anyways, anyway, no.
Speaker 1: I totally I hear you. Something called Auzeski's disease aka
Speaker 1: pseudo rabies. Oh my god, caused by a type of
Speaker 1: vercella virus.
Speaker 2: Okay, are you serious?
Speaker 1: I'm serious.
Speaker 2: It gets worse, Sarah, I know, I know.
Speaker 1: And poor scene reproductive and respiratory syndrome caused by a
Speaker 1: type of virus called beta art teary virus sued one.
Speaker 1: If you're interested. There are so many pig pathogens, okay,
Speaker 1: and the disease that was making its way through pig
Speaker 1: farms in this region of peninsular Malaysia didn't seem super
Speaker 1: different than those more familiar ones. A few symptoms stood out,
Speaker 1: pronounced neurological syndrome, including agitation and head pressing, tetanus like
Speaker 1: spasm and seizures, uncontrollable eye movements, trembling in twitches, uncoordinated gait,
Speaker 1: and generalized pain. And then in the pigs there were
Speaker 1: also some acute respiratory signs, rapid and labored breathing developing
Speaker 1: into a loud, harsh cough, which later then gave the
Speaker 1: common name for the disease and pigs called barking pig syndrome.
Speaker 1: But even though there were some cases of sudden death
Speaker 1: in infected pigs, the rates of infection and mortality weren't
Speaker 1: all that high, or at least not high enough to
Speaker 1: cause immediate and pressing concern, and so the new disease
Speaker 1: wasn't immediately identified or recognized to be a new disease.
Speaker 1: Then people started to get sick. In late September of
Speaker 1: nineteen ninety eight, several people who worked on pig farms
Speaker 1: in the suburbs of epo A City and the state
Speaker 1: of Perak in the northwest part of the peninsula also
Speaker 1: began to show signs of illness headache, fever, drowsiness, vomiting,
Speaker 1: altered mental state, sometimes progressing to fatal encephalitis, and this,
Speaker 1: while absolutely cause for concern, it also didn't immediately throw
Speaker 1: up red flags as a new illness. Initially, people thought
Speaker 1: this was an outbreak of Japanese encephalitis virus, which we
Speaker 1: have not done yet.
Speaker 2: No, it's on our list, but I don't even know
Speaker 2: if it's on our short list for this season.
Speaker 1: I don't think that it is, which is kind of surprising.
Speaker 1: But there's a yeah anyway, there's a lot. Yeah, there's
Speaker 1: a lot Japanese andencephalitis virus. Though the relevant thing here
Speaker 1: to know is that it's transmitted through mosquitoes, and this
Speaker 1: wasn't a wild guess. Japanese encephalitis virus was present in
Speaker 1: the area. Four of twenty eight samples from patients with
Speaker 1: encephalitis tested positive for antibodies against Japanese encephalitis virus, and
Speaker 1: as people continued to get sick, their serum contained not
Speaker 1: just antibodies against the virus, but also Japanese encephalitis virus
Speaker 1: nucleic acids, which suggested current or recent infection with the virus. Later,
Speaker 1: many of these samples were actually found to be false positives,
Speaker 1: so it's probably a case of like the threshold being
Speaker 1: too low for throwing up a positive sign. Given this
Speaker 1: evidence suggesting that the region had an ongoing Japanese encephalitis
Speaker 1: virus outbreak, the Ministry of Health took action against it
Speaker 1: to try to prevent additional cases, which involved intensive fogging
Speaker 1: with insecticides in the outbreak, areas administering thousands of doses
Speaker 1: of Japanese encephalitis virus vaccine to those who lived near
Speaker 1: or worked on the pig farms because that's where the
Speaker 1: concentration of cases seemed to be happening. But after all
Speaker 1: of these measures, instead of cases dropping as you might
Speaker 1: expect if it was caused by Japanese encephalitis virus, they
Speaker 1: continued to rise and making matters even scarier. The disease
Speaker 1: was no longer restricted to just the area outside of
Speaker 1: the city of Epo. Some of the farmers who were
Speaker 1: affected in this outbreak had sold their pigs in a
Speaker 1: fire sale, which led to pigs being burst across the country,
Speaker 1: and these types of sales were a common occurrence in
Speaker 1: Peninsular Malaysia, which at the time had a pig population
Speaker 1: of two point four million. But unfortunately, some of the
Speaker 1: pigs sold brought with them this mysterious infection, and in
Speaker 1: December of nineteen ninety eight and January of nineteen ninety nine,
Speaker 1: cases of encephalitis in humans began popping up elsewhere in
Speaker 1: the country, especially in an area about three hundred kilometers
Speaker 1: south of Epo in the state of Negrius and Balon.
Speaker 1: Still the thought was this is Japanese and cephalitis virus.
Speaker 1: Like it was still like, well, it has to be this.
Speaker 1: We just have a bad year for mosquitoes, the viruses
Speaker 1: in the mosquitoes. This is how it is. Yeah, And
Speaker 1: so more prevention measures were carried out, more fogging, more insecticide,
Speaker 1: more administration of Japanese and cephalitis virus vaccines, and according
Speaker 1: to a researcher involved in the outbreak, the governmental authorities
Speaker 1: seemed really intent only on confirming that this was Japanese
Speaker 1: encephalitis virus, not so much exploring other options, like, for instance,
Speaker 1: if this was a totally new pathogen that needed completely
Speaker 1: different containment strategies than those used for Japanese and cephalitis virus.
Speaker 1: By the end of February nineteen ninety nine, the outbreak
Speaker 1: was still raging with no end in sight, and the
Speaker 1: evidence that this probably wasn't Japanese and cephalite as virus
Speaker 1: started to be too much to ignore. The control measures
Speaker 1: weren't doing anything to reduce the incidents of cases, infections,
Speaker 1: seemed to be limited to people who had direct close
Speaker 1: contact with pigs, mostly adults, were getting sick. There was
Speaker 1: household clustering with multiple people in the same household getting sick,
Speaker 1: which you wouldn't necessarily expect clustering with Japanese and ccephalitis virus.
Speaker 1: There was a really high in this particular outbreak, a
Speaker 1: really high disease attack rate, So most people who were
Speaker 1: infected became symptomatic. So for every one person who stayed asymptomatic,
Speaker 1: three developed symptoms is what I read. Japanese and cephalitis virus,
Speaker 1: on the other hand, causes symptomatic encephalitis in one in
Speaker 1: three hundred of those infected.
Speaker 2: So like, wow, very different, totally different.
Speaker 1: And perhaps the most glaring piece of information suggesting that
Speaker 1: this wasn't Japanese encephalitis virus was that some of the
Speaker 1: people who were getting sick and dying had already received
Speaker 1: multiple doses of the vaccine. Can you imagine how terrifying
Speaker 1: and awful getting the vaccine and being told, Okay, you're
Speaker 1: safe to go back to work, and then it turns
Speaker 1: out you weren't. And some governmental authorities did actually try
Speaker 1: to explain that away by saying Oh, well, it's because
Speaker 1: this vaccine was faulty. We need to replace this inactivated
Speaker 1: virus vaccine with the live attenuated version and then we'll
Speaker 1: have better results. But fortunately some public health officials and
Speaker 1: researchers were like, okay, you keep working on that and
Speaker 1: in the meantime, we're going to see what this actually
Speaker 1: might be because it doesn't seem to be Japanese and
Speaker 1: cphalitis virus. And the lead researcher on this, doctor Cobbing
Speaker 1: Chua at the University of Malaysia, who first hand account
Speaker 1: you heard from he would eventually make the discovery of nepavirus.
Speaker 1: He was pretty sure at this time that it was
Speaker 1: a novel agent, not Japanese and cphalitis virus, but the
Speaker 1: head of his department was convinced that it was Japanese
Speaker 1: and cephalitis virus. So how could he persuade him that
Speaker 1: he needed to isolate this virus. Chua ended up saying, well,
Speaker 1: if it's a new genotype of Japanese encephalitis virus, that
Speaker 1: could be important, that could be really relevant to our
Speaker 1: control efforts and to determining whether the vaccine is whatever,
Speaker 1: And he got permission SMO move a smooth move indeed,
Speaker 1: and so he got permission to run tests on the
Speaker 1: cerebrospinal fluid and serum samples from a few patients on
Speaker 1: March fifth, nineteen ninety nine, so the first cases were
Speaker 1: in September of the year before. On March fifth, Chua
Speaker 1: saw something unexpected in one of his samples. The virus
Speaker 1: seemed to kill the cells in a way that was
Speaker 1: very similar to that of respiratory sensicial virus, not something
Speaker 1: that Japanese encephalitis virus does. So he ran to the
Speaker 1: head of his department and was like, come look at this,
Speaker 1: and the head was like, Nah, it's just contamination. Get
Speaker 1: rid of it, throw it away, ignore it. Chuat didn't.
Speaker 1: He continued his work, and he went around to get
Speaker 1: his colleagues's opinions, some of whom agreed with his thought
Speaker 1: that this was something new, this was something interesting, This
Speaker 1: was not contamination, and so he ran tests that were
Speaker 1: available to see whether this was a known virus like
Speaker 1: herpie simplex virus RSV, measles Mom's para influenza virus all negative,
Speaker 1: and then he was like, well, maybe I should check
Speaker 1: whether the patients that I've sampled have antibodies to this
Speaker 1: virus that I cultured, because then it's like, is this
Speaker 1: just contamination or is this a virus? And they have
Speaker 1: antibodies against it, all positive, like perfect match. And so
Speaker 1: this time with these results, he was able to convince
Speaker 1: his department head that this was probably a new virus
Speaker 1: and that they needed international help to figure out what
Speaker 1: kind virus. It was two days later after he had
Speaker 1: these results, after he'd had done the testing of the
Speaker 1: virus against the antibodies and the patients, and this was
Speaker 1: one week after he first saw this weird cell killing
Speaker 1: effect of this virus in his samples. Chiua was on
Speaker 1: a plane samples in hand, headed to Fort Collins, Colorado,
Speaker 1: where the Division of Arbovirus Born Diseases branch of the
Speaker 1: CDC was located. Why Fort Collins and not Atlanta, because
Speaker 1: the department head was still convinced in his heart of
Speaker 1: hearts that it was Japanese encephalitis virus, which is an
Speaker 1: arbovirus virus. Yeah, so hence Fort Collins. Less than ten
Speaker 1: hours after arriving in Fort Collins, Chiua was at the
Speaker 1: lab looking at the samples under the microscope, and what
Speaker 1: he saw terrified him. He saw the concrete ring like
Speaker 1: structures characteristic of PARAMICS viruses. Why was that so scary?
Speaker 1: We've kind of touched on that a bit. For one,
Speaker 1: it showed that this was not Japanese andencephalitis virus, which
Speaker 1: very clearly, very clearly, and that confirmed that none of
Speaker 1: the control efforts that they had spent months trying had
Speaker 1: actually done anything. I mean, it is possible that maybe
Speaker 1: there would have been an outbreak of Japanese andencephaliteis virus
Speaker 1: that they prevented from these control measures. I guess we
Speaker 1: won't know, but it didn't do anything to stop this
Speaker 1: particular outbreak. And for two, it's because it was a
Speaker 1: PARAMIX virus. These are as we've talked about a very
Speaker 1: scary group of viruses with clear pandemic potential. They infect
Speaker 1: a wide range of animals. There RNA viruses, which typically
Speaker 1: means for most RNA viruses, they have high mutation rate,
Speaker 1: and nepavirus does. Indeed, they're spread through airborne droplets and
Speaker 1: close contact, and they have some of the highest infection
Speaker 1: rates that we've ever encountered. Measles, as we've talked about before,
Speaker 1: has an ar not of twelve to eighteen, which still
Speaker 1: I still it still blows my mind. Yeah. Yeah. And
Speaker 1: this new paramixavirus had an incredibly high case fatality rate
Speaker 1: nearly forty percent, which pales in comparison to some of
Speaker 1: the later outbreaks, but still forty percent of people who
Speaker 1: were infected died.
Speaker 2: Like that's I know, huge, it's also yeah, it's it's
Speaker 2: it's really interesting to then put this particular outbreak in
Speaker 2: the context of it was not nearly as bad as
Speaker 2: it could have been based on all of the further outbreak,
Speaker 2: Like it's.
Speaker 1: Just I know, I know, yeah, it's like forty percent
Speaker 1: that seems low.
Speaker 2: And it's terrifyingly high.
Speaker 1: It's terrifyingly high. Yeah, And this was incredibly terrifying, alarming,
Speaker 1: horrifying for the situation in Malaysia, the fact that it
Speaker 1: was a new virus and a new Paramix virus, and
Speaker 1: it was also terrifying and horrifying for doctor Chua and
Speaker 1: the other researchers who had been handling these virus samples,
Speaker 1: just like without the safety measures that they warranted, right,
Speaker 1: Like nepavirus requires the highest level of biosafety precautions biosafety
Speaker 1: Level four, which the CDC in Fort Collins did not have.
Speaker 1: And so once they realized, oh god, we have a
Speaker 1: paramix of virus on our hands, we need to get
Speaker 1: these things to close that tube. Fanol those hands you
Speaker 1: might need, might need more than that. Bleach those hands.
Speaker 1: Send the samples, bleach everything, Send samples to the CDC
Speaker 1: in Atlanta. There they can be studied safely. And in Atlanta,
Speaker 1: researchers confirmed that yes, this was a novel paramixa virus,
Speaker 1: and it's one that seemed to be closely related to
Speaker 1: Hendra virus, which had been discovered just a few years
Speaker 1: earlier in nineteen ninety four in Australia.
Speaker 2: Which is also so interesting because these are like Hendra
Speaker 2: and Nepa are very different than other paramixa viruses. Yeah,
Speaker 2: so it's very interesting that like Hendra was just discovered
Speaker 2: a few years prior, and then here comes Nepa on
Speaker 2: the scene.
Speaker 1: Like I know, I know, I feel like the nineties
Speaker 1: had a lot of these kinds. We'll get into it
Speaker 1: in a second, Okay. The name Nepa was given to
Speaker 1: the virus after the village Kampung Sungai, Nepa, where the
Speaker 1: patient whose samples were used to detect the virus had lived.
Speaker 1: So it was like this person, that's where they had lived.
Speaker 1: An international team of experts traveled to Malaysia to learn
Speaker 1: more about this novel virus, how it was being transmitted,
Speaker 1: and helping with like containment measures, and they ultimately concluded
Speaker 1: that it was from the pigs. By the end of
Speaker 1: the nineteen ninety eight to nineteen ninety nine outbreak, two
Speaker 1: hundred and sixty five people had been infected with nepavirus
Speaker 1: in peninsular Malaysia and eleven people in Singapore, which had
Speaker 1: imported pigs from Malaysia, and one hundred and five people died,
Speaker 1: which is, like I said, a case fatality rate of
Speaker 1: around forty percent. The majority of those infected, around seventy percent,
Speaker 1: were directly involved in pig farming, and there was significant
Speaker 1: association between people who had worked closely with pigs and piglets,
Speaker 1: like giving injections or medications, assisting with birth, handling of
Speaker 1: dead pigs, and so on. Just to think about this like, okay, yes,
Speaker 1: it was an outbreak among people who farmed pigs, but
Speaker 1: you also have to think about where these were entire communities.
Speaker 1: I watched in one video someone describing how there would
Speaker 1: be a street where you know, homes on a street,
Speaker 1: and every single home had a funeral happening like the
Speaker 1: same week because it had hit that farm, and all
Speaker 1: of the people who had lived on that street worked
Speaker 1: in the farm. And it's just like everyone, yeah, everyone,
Speaker 1: it's it's really awful. And it wasn't over. Once this
Speaker 1: a link between the pigs and the infection was made,
Speaker 1: the government ordered all pigs and affected areas to be cold,
Speaker 1: so in total, around one point one million pigs were
Speaker 1: killed in a process that was described as just utterly horrific.
Speaker 1: One person said, I don't think that I could do
Speaker 1: this again. I could participate in this again.
Speaker 2: It sounds absolutely awful.
Speaker 1: Yeah, and one point one million pigs. That was nearly
Speaker 1: half of the population. And while the culling did seem
Speaker 1: to halt transmission, so five point six percent of all
Speaker 1: pig farms in peninsular Malaysia were positive for a nepavirus,
Speaker 1: it was also catastrophic for people who had made their
Speaker 1: livelihoods out of this. I don't know anything about whether
Speaker 1: there was compensation for cold pigs, but I did read
Speaker 1: that very few people were able to continue with pig
Speaker 1: farming after this, maybe because testing restrictions were too difficult
Speaker 1: to meet afterwards, or the financial burden was placed entirely
Speaker 1: on the farmers and workers, or maybe because they didn't
Speaker 1: want to get sick and die if there was another outbreak,
Speaker 1: maybe they had horrible like trauma from that other outbreak.
Speaker 1: Before the outbreak, there were one thousand, eight hundred and
Speaker 1: eighty five pig farms in peninsular Malaysia, and by July
Speaker 1: of nineteen ninety nine there were eight hundred and twenty
Speaker 1: twenty nine.
Speaker 2: Wow.
Speaker 1: Right, And I think an outbreak like this really shows
Speaker 1: how far the impacts of a disease can ripple outward.
Speaker 1: On the personal scale, people lost their lives or their
Speaker 1: loved ones, their neighbors, their support system, their livelihood. On
Speaker 1: the regional scale, this virus resulted in a major hit
Speaker 1: to an important industry, which led many people to move
Speaker 1: or entirely change their way of life. And globally, NIPA
Speaker 1: virus I think represented another terrifying reminder that our interactions
Speaker 1: with domestic and wild animals can have deadly consequences. Throughout
Speaker 1: the nineteen eighties and nineteen nineties, outbreaks of a new
Speaker 1: deadly virus spilling over from animals seem to happen over
Speaker 1: and over again. HIV growing to pandemic level in the
Speaker 1: nineteen eighties, sinnombrae virus in the southwestern US in nineteen
Speaker 1: ninety three, the hendrovirus outbreak in nineteen ninety four, and
Speaker 1: incredibly deadly outbreak of ebola virus in nineteen ninety five
Speaker 1: with a case fatality rate of eighty one percent, highly
Speaker 1: pathogenic av and influenza H five N one spilling over
Speaker 1: into humans in nineteen ninety seven. And I'm sure that
Speaker 1: there are others that I'm forgetting. Spillover events happen, and
Speaker 1: they can be incredibly deadly, and this is catching up
Speaker 1: to us. The nineteen ninety eight to nineteen ninety nine
Speaker 1: nepavirus outbreak in Malaysia represented in this regard, another point
Speaker 1: in the timeline, another deadly emerging zoonotic pathogen, another confirmation
Speaker 1: that this would keep happening, This will keep happening, and
Speaker 1: that we have to approach science in a new, much
Speaker 1: more collaborative and interder disciplinary way if we want to
Speaker 1: have any chance at prediction, prevention, and control. And one
Speaker 1: piece of that puzzle was finding out where nepavirus came
Speaker 1: from how it got into pigs in the first place.
Speaker 1: Given what was known about Nipa's close relative, hendrovirus, which
Speaker 1: was transmitted from flying foxes to horses to humans, seemed
Speaker 1: like bats would be a good place to start the hunt,
Speaker 1: and long story short, that was the right call. A
Speaker 1: team of researchers collected urine samples and swabbed fruit that
Speaker 1: had been partially eaten by fruit bats, specifically those in
Speaker 1: the Terrapus Is that right genus? Yeah? I think so,
Speaker 1: and found both antibodies to nepavirus as well as the
Speaker 1: virus itself. But how did it get from these bats
Speaker 1: into pigs? Long story short, again humans. The leading hypothesis
Speaker 1: this seems to be that over the nineteen nineties, pig
Speaker 1: farms in peninsular Malaysia grew quite a bit in size
Speaker 1: and density, and many of these pig farms also cultivated
Speaker 1: mango and other fruit trees, and so this created opportunities
Speaker 1: for the virus to repeatedly spill over from the bat
Speaker 1: reservoirs to pigs. Deforestation is also thought to have maybe
Speaker 1: played a role too, because it can drive movement and
Speaker 1: clustering of bats to the diminishing number of places with resources,
Speaker 1: so like there's only one stand of trees left, all
Speaker 1: the bats are going to go there, much more pathogen exchange,
Speaker 1: et cetera. It also appears that the September nineteen ninety
Speaker 1: eight cases weren't the first of nepavirus. Samples from five
Speaker 1: people who got sick in nineteen ninety seven were retested
Speaker 1: and found to be positive. It's possible that it was
Speaker 1: even older than that. I just those are the early
Speaker 1: samples that, as far as I know, have been found.
Speaker 1: How did the virus get into the bats? We've gone,
Speaker 1: like now back the chain of transmission. I mean, it
Speaker 1: probably had been there for quite some time. Seems like
Speaker 1: it evolved with its bat hosts and doesn't really seem
Speaker 1: at least as far as I read, to cause substantial
Speaker 1: disease in bats. So in that way, it's similar to hendrovirus.
Speaker 1: The nineteen ninety eight nineteen ninety nine outbreak of nepavirus
Speaker 1: in peninsular Malaysia seems like it was the virus getting
Speaker 1: its foot in the door because nearly every year since,
Speaker 1: like I was going to go through all the subsequent
Speaker 1: outbreaks one by one, but it's like every.
Speaker 2: Single every single year.
Speaker 1: Almost every single year. It's it's remarkable outbreaks have happened,
Speaker 1: especially in Bangladesh and India. But these outbreaks are different
Speaker 1: from the nineteen ninety eight to nineteen ninety nine outbreak
Speaker 1: in Malaysia in a couple of alarming ways, and we've
Speaker 1: kind of touched on this already. The first being that
Speaker 1: the case fatality rate is substantially higher than the forty
Speaker 1: percent reported in Malaysia, so on average it's been around
Speaker 1: seventy percent, with that one outbreak in twenty one people
Speaker 1: in Kerala, India in twenty eighteen reporting a ninety one
Speaker 1: percent case fatality rate. And the second is that unlike
Speaker 1: the outbreak in Malaysia, which seemed to mostly be from
Speaker 1: pigs to people, these later outbreaks involved much more human
Speaker 1: to human transmission, which has set off some alarm bells
Speaker 1: in terms of epidemic or pandemic potential for this virus,
Speaker 1: which after nineteen ninety nine has for the most part
Speaker 1: only been involved in outbreaks in the double digits, But
Speaker 1: will it stay that way right? To help answer that question,
Speaker 1: we need to better understand how these outbreaks happen in
Speaker 1: the first place, What increases the likelihood that nepavirus will
Speaker 1: spill over into humans and what seems to reduce that risk. Yeah,
Speaker 1: I can't answer these questions.
Speaker 2: How do we stop this? How do we stop this?
Speaker 1: But luckily there is someone.
Speaker 2: Who can m H and we've got them here.
Speaker 1: We've got them here today, let's chat with doctor Cliff
Speaker 1: McKee all about the ecological drivers of nepavirus outbreaks.
Speaker 3: So I'm doctor Cliff and McKee. I'm a disease ecologist
Speaker 3: and a research associate at the Johns Hopkins Bloomberg School
Speaker 3: of Public Health. I came here in twenty twenty to
Speaker 3: study nepavirus in bats in Bangladesh. And before that, I
Speaker 3: was a PhD student at Colorado State University studying bacterial
Speaker 3: infections of fruit bats kind of the diversity of these
Speaker 3: bacteria and theracology. And I've worked on kind of some
Speaker 3: other projects on bacterial infections in felines and I think
Speaker 3: generally my research focuses on one health and trying to
Speaker 3: understand the dynamics of pathogen spillover at human animal interfaces
Speaker 3: and prevention efforts and epidemiology across scales.
Speaker 2: Thank you so much for joining us today. We are thrilled,
Speaker 2: like so super brighted to have an actual expert here
Speaker 2: to talk about the ecological drivers of nepavirus outbreaks and
Speaker 2: then also some of the strategies for predicting and controlling,
Speaker 2: Like this is going to be such a fun time.
Speaker 2: If we can start off with the bats that are
Speaker 2: at the center of all of this nepavirus mess, the
Speaker 2: ones in the terrapists, the terrap Is genus, the flying foxes.
Speaker 2: What are some of the ecological characteristics of these bats
Speaker 2: that lead to spill over events of nepavirus and does
Speaker 2: it differ across the different species of the terrapusts.
Speaker 3: So, the different Turopus species that carry nepovirus, including Tropus medius,
Speaker 3: Tropis lilly, Tropus hypomelanus, and Theropus vampirius, have a lot
Speaker 3: of similarities in their ecology that could factor into spillover
Speaker 3: of nepovirus. All four of these species are known to
Speaker 3: roost and forage near human settlements and even in highly
Speaker 3: urbanized areas, and they commonly feed on cultivated fruit like mango, banana,
Speaker 3: and guava, and roosting sites for these species can range
Speaker 3: from sort of intact forests to a large tree in
Speaker 3: a village area or even a park in the middle
Speaker 3: of a city, and in some countries like Thailand and Vietnam,
Speaker 3: roosts are often situated on temple grounds where they receive
Speaker 3: some sort of some detection from disturbance. But the common
Speaker 3: denominator seems to be that these species all tolerate human
Speaker 3: presence really well and are opportunists. They feed on sort
Speaker 3: of a mixture of cultivated and wild fruit and nectar
Speaker 3: resources that are available in their area in a given season. Now,
Speaker 3: there are some species that are more urbanized than others,
Speaker 3: such as turope As medius that's found in India and Bangladesh,
Speaker 3: But I don't think we have really any indication that
Speaker 3: these species are gravitating towards humans per se, or rather
Speaker 3: that land use change has stripped away sort of the
Speaker 3: native forests and the bats have found ways to adapt
Speaker 3: to this modified landscape. So the amount of potential contact
Speaker 3: between turop as bats and people has a lot to
Speaker 3: do with the amount of modification that's gone on in
Speaker 3: some regions versus others, and maybe has less to do
Speaker 3: with the fundamental difference is in their ecology.
Speaker 1: Okay, interesting, Yeah, NEPA virus outbreaks have occurred in only
Speaker 1: a fraction of the geographic range of Taropis bats, suggesting
Speaker 1: that does this suggest I guess that we're only seeing
Speaker 1: the tip of the iceberg when it comes to possible outbreaks,
Speaker 1: or maybe a more specific question is do we know
Speaker 1: what set or sets of circumstances lead to a spillover
Speaker 1: event and then what allows or causes a spillover event
Speaker 1: to turn into an outbreak?
Speaker 3: Speaking first towards sort of like these sets and or
Speaker 3: set of circumstances that lead to a spillover. Having bats
Speaker 3: living near humans is a necessary prerequisite for spillover to happen,
Speaker 3: but proximity alone really isn't sufficient. In the NIPA outbreaks
Speaker 3: that have happened in Malaysia in Bangladesh as well as
Speaker 3: another probable outbreak in the Philippines, there was this added
Speaker 3: element that allowed spillover to happen. I kind of think
Speaker 3: of it as as a channel. Perhaps in Malaysia that
Speaker 3: channel was pigs which were likely exposed when bats came
Speaker 3: to feed on mangoes and other fruits on farm premises
Speaker 3: that were doing mixed agriculture, and so these bats dropped mango,
Speaker 3: you know, partially eaten mangoes or fruit pits into the
Speaker 3: pig sties. In the Philippines the channel was horses which
Speaker 3: may have encountered dropped fruit or pasture grass that was
Speaker 3: contaminated with bat urine similar to what we see with hindrovirus.
Speaker 3: And in Bangladesh the channel is date palm sap. The
Speaker 3: sap is collected from date palm trees during the night
Speaker 3: and then it's sold fresh, often with the sap cellar
Speaker 3: going door to door to different households. And we know
Speaker 3: from infrared camera footage that Tropis bats frequently come to
Speaker 3: date palm sap trees to consume the sap and probably
Speaker 3: contaminate the sap with their saliva or urine potentially containing nepovirus.
Speaker 3: So in all of these cases, there's some novel ecological
Speaker 3: element that creates this channel for nepovirus to get from
Speaker 3: bats into humans, either via some bridging hosts like pigs
Speaker 3: or horses that humans interact with more frequently than bats,
Speaker 3: or a food item that allows humans to have direct
Speaker 3: contact with the virus. So the absence of NEPA cases
Speaker 3: in other Asian countries that Tropis bats live in is
Speaker 3: maybe a bit of a mystery, but I think the
Speaker 3: simplest explanation is that it's these novel ecological elements that
Speaker 3: widen this pathway for NEPA to get from bats into humans.
Speaker 3: They're missing or they might function differently than in areas
Speaker 3: with known outbreaks. And then there are other interactions with
Speaker 3: bats that could plausibly be involved with spillover, including bat
Speaker 3: hunting or humans eating dropped fruit directly from the ground.
Speaker 3: In Bangladesh, these exposures haven't been significantly associated with infection.
Speaker 3: In case control studies, only date palm SAP consumption was associated.
Speaker 3: So there's there's some speculation that the dropped fruit consumption
Speaker 3: is the cause of recent outbreaks in Kerala, India, but
Speaker 3: there just aren't enough cases yet to draw really strong conclusions.
Speaker 3: And to get to this question about sort of the
Speaker 3: tip of the iceberg part of your question, I do
Speaker 3: think there are potentially spillovers that we're missing, especially those
Speaker 3: that only cause you know, a handful of cases. This
Speaker 3: is because hospital based surveillance for NIPA virus was for
Speaker 3: a long time only happening in Bangladesh, but large outbreaks
Speaker 3: of severe respiratory disease or encephalitis. I think those are
Speaker 3: hard to miss. So while I think I think there's
Speaker 3: probably some spillovers that are going on undetected in countries
Speaker 3: you know, across the range of Taropa's bats, we're probably
Speaker 3: not talking about you know, thousands or hundreds of thousands
Speaker 3: of cases that are going undetected. And speaking to what
Speaker 3: takes a spillover to become an outbreak, this mostly depends
Speaker 3: on the epidemiological conditions that facilitate human to human transmission.
Speaker 3: So NEVA virus doesn't really transmit that well between humans,
Speaker 3: less than ten percent of cases actually transmit to another person,
Speaker 3: but in areas where there aren't good hygiene practices in hospitals,
Speaker 3: there have been outbreaks that happen inside of hospitals, and
Speaker 3: in one large outbreak in Bangladesh, person to person transmission
Speaker 3: largely centered around a local religious leader whose followers came
Speaker 3: to visit them while the while they were sick. So
Speaker 3: these epidemiological conditions could change in the future and open
Speaker 3: up you know, new risk actors or even you know,
Speaker 3: with the introduction of a new strain of the virus,
Speaker 3: But for now, the major source of human cases is
Speaker 3: directly from spillover and not person to person transmission.
Speaker 2: So you mentioned surveillance, which initially was happening only in Bangladesh,
Speaker 2: and it's our understanding that the threat of nepavirus is
Speaker 2: also not consistent year round and there was at least
Speaker 2: for a time increased surveillance or surveillance that only happened
Speaker 2: during certain parts of the year. Can you talk a
Speaker 2: little bit about the seasonality of nepavirus in Bangladesh and
Speaker 2: how it's driven or is it driven by the ecology
Speaker 2: of flying foxes.
Speaker 3: Yeah, So the seasonality of nepavirus spillovers in Bangladesh is
Speaker 3: tied really closely to when date palm SAP is harvested
Speaker 3: for fresh consumption. Almost all human outbreaks have happened in winter,
Speaker 3: and that's between November and April, and this coincides with
Speaker 3: the sap harvesting season. In areas where sap harvested for
Speaker 3: fresh consumption, bats only have access to the sap during
Speaker 3: these winter months, and in areas where sap is harvested
Speaker 3: for other purposes like molasses production and trees are tapped
Speaker 3: year round, we do see that bats will feed on
Speaker 3: the sap in summer months because it's available, but they
Speaker 3: do make more visits during winter, and we think this
Speaker 3: has to do with just the bat's opportunistic feeding behavior.
Speaker 3: But you know, maybe they're they're shifting towards drinking this
Speaker 3: sap because they lack other fruits during winter. You know,
Speaker 3: there's just not as much that's ripe during that time
Speaker 3: of year. But going back to this idea of date
Speaker 3: palm SAP being this channel, it seems like this channel
Speaker 3: for spillover is only open for a very limited time. Now,
Speaker 3: what's interesting is that the bats are not more likely
Speaker 3: to be infected with nepavirus during winter, So detections of
Speaker 3: nepavirus and bats are pretty sporadic throughout the year, and
Speaker 3: at least in the large roosts that we've that have
Speaker 3: been monitored or for multiple years, there might even be
Speaker 3: more detections in spring and summer months. So there's this disconnect.
Speaker 3: It could be that date palms at this channel is
Speaker 3: just good enough or well timed enough during winter to
Speaker 3: let some trickles of virus through into humans, but there
Speaker 3: might be an alternative explanation. We did a study where
Speaker 3: teams investigated NEVA spillovers in Bangladesh where the teams identified
Speaker 3: the nearest Turopis bat roost to a human spillover, and
Speaker 3: then collected urine samples to test for NEPA in a
Speaker 3: handful of roosts. They were able to detect NEPA virus
Speaker 3: in bat urine, often weeks after the human case had
Speaker 3: been reported. And mind you that these investigations were all
Speaker 3: happening in winter. The roosts with detected virus we're not
Speaker 3: these really large bat roosts, but rather smaller roots of
Speaker 3: a few hundred bats. This indicates that bats can be
Speaker 3: shedding the virus in winter, but perhaps it's happening in
Speaker 3: some of these smaller roosts. And so what we need
Speaker 3: to understand better is how bats are moving within this
Speaker 3: network of large versus small roosts, the seasonality of these movements,
Speaker 3: and the effects of nepovirus transmission among bat populations on
Speaker 3: sort of a whole landscape scale.
Speaker 1: There are so many factors, I feel like that go
Speaker 1: into this. It makes it incredibly complicated. And you've kind
Speaker 1: of touched on one already, which is human land use
Speaker 1: change and these other ways that humans have sort of
Speaker 1: changed the ecology or the landscape of these bats. And
Speaker 1: I was wondering if you could kind of dive a
Speaker 1: little bit deeper into that and talk about how habitat
Speaker 1: loss or deforestation, what role these play in setting the
Speaker 1: stage for a spillover of nepavirus from bats to domestic
Speaker 1: animals or from bats straight to humans, and sort of
Speaker 1: what that looks like or the different ways that could look.
Speaker 3: Well, I keep going back to this idea of channels.
Speaker 3: None of those would exist if it weren't for humans
Speaker 3: putting them there. The intensive pig farms in Malaysia, or
Speaker 3: horses in the Philippines, or even date palm sap in Bangladesh.
Speaker 3: None of these occur naturally. Date palm trees are native
Speaker 3: to Bangladesh, but access to sap requires carving out a
Speaker 3: section of the trunk, which is not something that bats
Speaker 3: can do. So a key landscape change is definitely the
Speaker 3: placement of these channels for spillover into the system, be
Speaker 3: it domestic animals acting as bridging hosts, or foods that
Speaker 3: can carry the virus directly from bats to humans but
Speaker 3: zooming out a bit further though, these key pathways may
Speaker 3: just be sort of the finishing touches in the process
Speaker 3: of landscape change, historical loss of forests and conversion of
Speaker 3: land for human agriculture is really the ultimate force that's
Speaker 3: bringing humans into closer proximity with fruit bats. You take
Speaker 3: a native forest forest where bats feed on wild fruit
Speaker 3: and nectar, then cut those trees down and replace them
Speaker 3: with fields and places to raise domestic animals, and also
Speaker 3: put in cultivated fruit trees. The bats end up just
Speaker 3: sticking around in the remaining trees and eat mangoes, you know,
Speaker 3: and other things in people's backyards. So really humans have
Speaker 3: inserted ourselves into bat habitat and the bats just tolerate it,
Speaker 3: but it becomes this recipe for virus spillover.
Speaker 1: Now.
Speaker 3: I think the timeline of this process differs slightly among
Speaker 3: the outbreak countries. For Malaysia, the process of clearing land
Speaker 3: for agriculture and increasing production of pigs and mangoes was
Speaker 3: something that was ramping up a lot in the nineteen seventies, eighties,
Speaker 3: and nineties, setting the stage for the outbreak in nineteen
Speaker 3: ninety eight. But in Bangladesh, the majority of forests have
Speaker 3: been gone since the seventeen hundreds and date palms have
Speaker 3: been cultivated for sap and molasses. Production over that whole time,
Speaker 3: because we know that the British colonialists in Bangladesh encouraged
Speaker 3: planting of date palms at trees, So the conditions for
Speaker 3: spillover in Bangladesh have been present for a long time,
Speaker 3: but we didn't know to look for human cases of
Speaker 3: NEPA until we knew there was a virus and we
Speaker 3: had tests to detect it.
Speaker 2: Kind Of going along with that, is there evidence that
Speaker 2: nepavirus outbreaks are increasing in either frequency or severity and
Speaker 2: kind of maybe zooming out even further. What are the
Speaker 2: possible effects of things like climate change on the ecology
Speaker 2: of nepavirus or on these spillover events.
Speaker 3: I don't think outbreaks are increasing in frequency or severity.
Speaker 3: There haven't been any more spillovers in Malaysia since the
Speaker 3: nineteen ninety eight outbreak, and in Bangladesh, the number of
Speaker 3: cases linked to date PALMSAP consumption kind of goes up
Speaker 3: and down and has been a bit slower since twenty sixteen,
Speaker 3: and the outbreaks haven't been as large as in previous years,
Speaker 3: which might speak to the effectiveness of control efforts that
Speaker 3: have gone on. But what is interesting is that the
Speaker 3: number of spillovers we see in Bangladesh is correlated well
Speaker 3: with how cold a winter season is, which likely links
Speaker 3: back to date palmsapp production and consumption practices. So date
Speaker 3: palmsapp collectors anecdotally report that they get higher quality SAP
Speaker 3: during colder winter nights, and we also know from household
Speaker 3: surveys that consumption of SAP is higher in cooler years. Now,
Speaker 3: this might be caused by something about the physiology of
Speaker 3: the trees producing more SAP or higher quality SAP, or
Speaker 3: just that the SAP is less likely to spoil in
Speaker 3: cooler weather, but something about weather is driving this system.
Speaker 3: So as climate continues to warm, this suggests that NEPA
Speaker 3: spillovers through date palm SAP consumption in Bangladesh might decline. However,
Speaker 3: I don't really want us to become complacent about NIPA
Speaker 3: in Bangladesh. We know that NEPA virus can take other
Speaker 3: pathways to get to humans, like through domestic animals, so
Speaker 3: I think we need to need to remain vigilant with surveillance.
Speaker 3: Case in point is India. Those outbreaks in Kerala came
Speaker 3: out of left field in twenty eighteen, and we don't
Speaker 3: completely understand the ecology of what's happening there, the pathway
Speaker 3: that the virus took from bats into humans, and any
Speaker 3: of the effects of land juice change that might be
Speaker 3: at play in India, And of course every single spillover
Speaker 3: event is a new chance for a strain of nepavirus
Speaker 3: that has higher transmissibility in humans, for that strain to emerge,
Speaker 3: or for higher transmissibility to evolve in humans or some
Speaker 3: bridging host. And of course climate change could alter the
Speaker 3: range of Turope's bats and cause some species to shift
Speaker 3: their roosting locations and food resources to overlap even more
Speaker 3: with humans, leading to potentially more spillovers. We honestly don't
Speaker 3: really know what's in store for us, So I think
Speaker 3: extending human surveillance efforts modeled in Bangladesh to other Asian
Speaker 3: countries that have Turopus bats could be a first step,
Speaker 3: but also sort of expanding surveillance to domestic animals, for
Speaker 3: example on large pig farms could be a good step.
Speaker 1: Problems like nepavirus outbreaks really require a one health approach,
Speaker 1: which is something that we love on the podcast. We're
Speaker 1: always mentioning, We're always talking about we're such big fans,
Speaker 1: and this involves people working collaboratively across disciplines and organizations
Speaker 1: and different levels of government and with community involvement too,
Speaker 1: to address the health of humans, animals, and the environment.
Speaker 1: Even though we're always talking about one health on the podcast,
Speaker 1: I don't know if we've ever really talked about like
Speaker 1: what an actual one health approach looks like on the ground,
Speaker 1: And I was hoping you could talk a little bit
Speaker 1: about that, like what does a one health strategy for
Speaker 1: nepavirus look like and why is it so important for
Speaker 1: this particular pathogen.
Speaker 3: Nepovirus is really kind of a perfect example of the
Speaker 3: power of a one health approach for emerging diseases. And
Speaker 3: at the heart of one health is is shared focus
Speaker 3: on human health, animal health, and environmental health. So with NIPA,
Speaker 3: you have to think beyond just the human outbreaks and
Speaker 3: dig into bat ecology and the health of bats, agricultural
Speaker 3: systems and those interfaces between bats, domesticated animals and humans,
Speaker 3: and the economic forces that are at the root of
Speaker 3: things like land uice change and choices to harvest certain
Speaker 3: food products like date palmsap NIPA touches on all of
Speaker 3: these things and you have to address them holistically, and
Speaker 3: a key part of this implementation of one health is
Speaker 3: with the formation of project teams, not only including sort
Speaker 3: of epidemiologists and virologists in investigations, but also ecologists and veterinarians,
Speaker 3: anthropologists and other social scientists. Teams not only have to
Speaker 3: be interdisciplinary, but ideally transdisciplinary, with individuals on the team
Speaker 3: that have gone beyond their specialized training to work in
Speaker 3: other disciplines and can act as liaisons and facilitate this
Speaker 3: really collaborative work and then speaking to one health approaches
Speaker 3: Tanita in Bangladesh. In addition to ongoing human surveillance efforts
Speaker 3: at hospitals, we're also looking into the frequency that nepovirus
Speaker 3: might be spilling over into domestic animals, including cows, goats, pigs, cats,
Speaker 3: and dogs, because this might be another pathway for the
Speaker 3: virus to jump into people outside of the winter date
Speaker 3: palm season and might not be currently captured by the
Speaker 3: existing surveillance efforts which are really optimized for spillover through
Speaker 3: this date palmsapp channel. We also should be researching kind
Speaker 3: of more about how the health of bats varies over
Speaker 3: time in space and how much this contributes to spill.
Speaker 3: There's this hypothesis out there that bats might shed more
Speaker 3: viruses when they're experiencing stress, either during food shortages or
Speaker 3: during pregnancy and lactation. So if we knew more about
Speaker 3: when bats are stressed, then we can inform public education
Speaker 3: campaigns about not drinking SAP or ramping up surveillance on
Speaker 3: domestic animals. We could also use this information to find
Speaker 3: ways to support the health of bats, maybe by restoring
Speaker 3: forest habitat and wild food resources. And lastly, I think
Speaker 3: the social sciences are crucial for implementation of prevention. For example,
Speaker 3: getting people not to drink SAP has been difficult to
Speaker 3: do in Bangladesh because it's such a strong cultural practice
Speaker 3: and people preceed it to be low risk. So identifying
Speaker 3: ways to protect SAP from contamination by bats, using things
Speaker 3: like bamboo or plastic coverings, or economic incentives to encourage
Speaker 3: SAP producers to maybe shift from selling raw sapp to
Speaker 3: selling molasses. Any work we can do to make these
Speaker 3: more acceptable could go a long way to prevention of
Speaker 3: NIPA virus.
Speaker 4: Billovers.
Speaker 1: That was that was so great.
Speaker 2: I loved it.
Speaker 1: I loved it. Yeah, yeah, thank you, thank you so
Speaker 1: much much. Jinks, doctor McKee away for chatting with us
Speaker 1: about this. It really is. So it's just so great
Speaker 1: to talk to like an expert who actually is there
Speaker 1: doing the work on one health.
Speaker 2: Stuff, doing the thing. Thank you for your work.
Speaker 1: Thank you for your work and your time.
Speaker 2: Yeah. So let's wrap this up, shall we with just
Speaker 2: looking at where we stand with nepavirus today.
Speaker 1: Let's do it.
Speaker 2: So the good news, there's a few good news is
Speaker 2: good news is there's some good news to be had
Speaker 2: in this case. Thus far, as of twenty twenty four,
Speaker 2: or I should say as of twenty twenty three, when
Speaker 2: the papers that I read were written, nepovirus has still
Speaker 2: caused less than seven hundred human cases. But I think
Speaker 2: that we've also made the case through this whole episode
Speaker 2: that that doesn't mean that it's not worthy of study.
Speaker 2: This is a virus that has a lot of potential
Speaker 2: to cause quite a number of more cases than that,
Speaker 2: and because of that reason, a lot of people are
Speaker 2: working on nepavirus. Like I said at the very top,
Speaker 2: this has been named one of the top ten high
Speaker 2: priority path gins for the World Health Organization because the
Speaker 2: truth is that this these spillover events are not something
Speaker 2: that is happening rarely. Right between two thousand and one
Speaker 2: to twenty eighteen, in Bangladesh alone, over one hundred and
Speaker 2: eighty three spillover events have happened.
Speaker 1: That's a lot, one.
Speaker 2: Hundred and eighty three individual spillover events. And there have
Speaker 2: been additional outbreaks and spillover events that have happened in
Speaker 2: more and more places in different parts of India, in Singapore,
Speaker 2: in the Philippines. This is a virus that exists, persists,
Speaker 2: and luckily a lot of people are trying to understand it,
Speaker 2: both from the one health approach that we heard about
Speaker 2: already and also vaccines and therapeutics. So while there are
Speaker 2: still not vaccines yet, this is one of the few
Speaker 2: times where I get to say that there are a
Speaker 2: lot of candidates that are moving through the clinical trials press,
Speaker 2: which is really exciting. There are a few different ones
Speaker 2: that I found, two of which have started trials in
Speaker 2: humans as of the end of twenty twenty three and
Speaker 2: early twenty twenty four. Both of these, from what I
Speaker 2: can tell, are mRNA based vaccines, which is kind of exciting.
Speaker 2: And there are also people who are developing vaccines for
Speaker 2: animals for example, there's already a hindrovirus vaccine for horses,
Speaker 2: and so the idea that you could use a nepavirus
Speaker 2: vaccine to vaccinate things like pigs might be helpful in
Speaker 2: preventing spillover into domestic animal populations.
Speaker 1: That's really cool.
Speaker 2: Yeah, there's also a lot of work being done on
Speaker 2: additional therapeutics and anti virals and monoclonal antibodies. Right now,
Speaker 2: there still aren't any that have actually come to market,
Speaker 2: but there is. There is just so much focus, I think,
Speaker 2: on nepavirus and on understanding that it can't be just
Speaker 2: one of these things. It's vaccines in combination with therapeutics,
Speaker 2: in combination with prevention strategies, in combination with a one
Speaker 2: health approach, and really looking at this virus as it
Speaker 2: truly exists, which is something that is in the environment
Speaker 2: that we don't have complete control over and we can
Speaker 2: never actually eradicate. So I think that this is one
Speaker 2: of the times where if we go all the way
Speaker 2: back to first season and we say, how scared do
Speaker 2: you need to be? If I'm being honest, MEPA virus
Speaker 2: has scared me since twenty eleven.
Speaker 5: Is that when Meme out Okay, Yeah, I think it's
Speaker 5: a very very terrifying virus.
Speaker 2: But I think there's a lot of really incredible people
Speaker 2: that also think that this is a terrifying virus who
Speaker 2: are doing everything that they can to prevent it from
Speaker 2: ever becoming something that most people ever have to hear about.
Speaker 1: That's a great answer. It is. It is. Yeah, It's like, yeah,
Speaker 1: this is scary. A lot of people think. So that's
Speaker 1: why we're working really hard on it, and hopefully we'll
Speaker 1: have therapeutics or vaccines or detection or a combination, right
Speaker 1: in case something like this does lead to a larger epidemic, right, pandemic.
Speaker 2: Yeah, and that's NEPA.
Speaker 1: That's NEPA. That's sources.
Speaker 2: Sources, I've got a lot, shall.
Speaker 1: We I have so many I'm shouting out just a
Speaker 1: couple here and all of the rest will be on
Speaker 1: our website. So there are several papers by doctor Chua.
Speaker 1: One that I really liked was in Science called nepavirus
Speaker 1: a recently emergent deadly paramixavirus. That's from two thousand and
Speaker 1: then there is a paper on the evolution and origin
Speaker 1: of nepavirus by lol Presty at All from sixteen called
Speaker 1: Origin and Evolution of Napavirus. And I will also on
Speaker 1: our website linked to some of doctor McKee's work on
Speaker 1: napavirus and sort of the bat spillover dynamics of pathogen's
Speaker 1: one health, all that good stuff.
Speaker 2: Yeah, he's got some really great papers.
Speaker 1: Also, I referenced a paper of his in our Bartnella episode.
Speaker 1: Just got to shout it out.
Speaker 2: We go way back, just get it for the biology section.
Speaker 2: I had also quite a number of papers detail on
Speaker 2: the like true biology and pathophysiology of this pathogen. I
Speaker 2: really liked a paper in the New England Journal of
Speaker 2: Medicine called Transmission of Npavirus fourteen years of investigations in
Speaker 2: Bangladesh by Nikola at All And honestly there was there
Speaker 2: were so many more and Aaron, like you said, a
Speaker 2: couple by doctor McKee that were also phenomenal. We will
Speaker 2: post all of our sources from this episode and every
Speaker 2: one of our episodes. There's some about the vaccines. There's
Speaker 2: so much on our website this podcast will kill you
Speaker 2: dot com under the episodes tab.
Speaker 1: Thanks again, Jess. Got to say it one more time
Speaker 1: to doctor McKee. You're a champion.
Speaker 2: Thank you We really appreciate it. Thank you also to
Speaker 2: Bloodmobile for providing the music for this episode and all
Speaker 2: of our episodes.
Speaker 1: Thank you to Tom and Leanna for the wonderful audio mixing.
Speaker 2: Love it. Thank you Exactly Right Network.
Speaker 1: And thank you to you listeners for listening. We hoped
Speaker 1: that you learned something new.
Speaker 2: This is like one of our our first episode this
Speaker 2: season of like a real classic TP and KY classic.
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Speaker 1: Until next time, wash your hands.
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