Speaker 1: H five N one is an interloper, an unrefined newcomer,
Speaker 1: all fury without the seasoning of age in human cells.
Speaker 1: It has discovered a fresh target, and it pursues its
Speaker 1: prey deep into the body, penetrating much farther than ordinary flu.
Speaker 1: This novel virus advances on the lungs themselves, attacking the
Speaker 1: branches of the bronchial tree and the myriad little buds
Speaker 1: on their tips called alveoli, where the life sustaining task
Speaker 1: of exchanging carbon dioxide for oxygen occurs. The pathogen infects
Speaker 1: the coating of mucus that protects the membranes of the lungs.
Speaker 1: This newcomer penetrates into the tissue itself. It spreads farther,
Speaker 1: often infecting both lungs at nearly the same time. As
Speaker 1: the pathogen relentlessly erodes the cells of the deep lung,
Speaker 1: you find yourself increasingly short of breath. Your cough is
Speaker 1: often bloody, and you may bleed from your nose and
Speaker 1: even gums. The human body, which has never encountered anything
Speaker 1: like it, has no ready arsenal of antibodies to choke
Speaker 1: off the process. The body can still marshal its innate
Speaker 1: all purpose defenses, but in doing so, it mounts a
Speaker 1: counter attack so furious that some scientists believe it's more
Speaker 1: lethal than the virus itself. The body throws everything it
Speaker 1: has at the intruder, without regard to the tremendous collateral damage.
Speaker 1: This causes the lungs themselves ever more. Immune cells are
Speaker 1: summoned to the front and continue to blast away. The
Speaker 1: carnage mounts. The lung cavities fill with dead and damaged tissue,
Speaker 1: mutilated mucous cells, and other cellular wreckage. The lungs become
Speaker 1: rigid as the cells that make the liquid to keep
Speaker 1: the lungs flexible are annihilated. The seal between the bloodstream
Speaker 1: and the air passages ruptures, red blood cells and plasma
Speaker 1: leak into the lungs. The alveoli sacs are swamped with
Speaker 1: fluid and debris and are no longer able to exchange
Speaker 1: carbon dioxide for oxygen. If you listen closely, you can
Speaker 1: hear the liquid crackling. Your breathing accelerates. You desperately press
Speaker 1: all your chest muscles into helping you suck down precious oxygen.
Speaker 1: You're gasping for air. You're drowning. But the virus is
Speaker 1: not content to remain a solely respiratory disease. It invades
Speaker 1: the digestive tract, often causing diarrhea and sometimes vomiting. It
Speaker 1: can assault the liver in kidneys, it can provoke heart failure.
Speaker 1: It can attack the eyes. It can even breach the
Speaker 1: brain and spine. Yet, in the end, the lungs are
Speaker 1: where this microbe concentrates its energies and takes its heaviest toll.
Speaker 1: The lungs are also the means by which it casts
Speaker 1: its net for further prey. In this one regard, it
Speaker 1: is much like its seasonal cousin. They both spread their
Speaker 1: sickness through contaminated droplets coughed or sneezed into the air,
Speaker 1: one of the most efficient forms of transmission known.
Speaker 2: It is so terrifying.
Speaker 1: Is it somehow scarier because of covid or just scarier
Speaker 1: because we've read more about other pathogens and finally have
Speaker 1: a like more of a respect or appreciation for flu
Speaker 1: I think both.
Speaker 2: I think.
Speaker 3: I think in large part it's probably COVID. I think
Speaker 3: it's living something that is in many ways so similar
Speaker 3: and so terrifying, and knowing that it not just has
Speaker 3: happened again historically, but like it just happened, and now
Speaker 3: we're going to talk about how it can happen again
Speaker 3: and potentially be much worse.
Speaker 1: Yeah, And by can happen again, likely will happen again. Yeah,
Speaker 1: it's yeah. So that first hand account was from a
Speaker 1: book titled The Fatal Strain on the Trail of Avian
Speaker 1: Flu and the Coming Pandemic, and that was written by
Speaker 1: Alan Cipres and it was published in two thousand and nine.
Speaker 3: I think I read that for our first influenza episode.
Speaker 1: I think you did. I think it's on our sources. Yeah. Hi,
Speaker 1: I'm Aaron Welsh and I'm Erin Alman Updyke, and this
Speaker 1: is this podcast will Kill You, And.
Speaker 3: Today we're revisiting our very first ever topic, influenza.
Speaker 2: We are.
Speaker 1: It's our season finale celebration. Yeah, kind of a somber celebration.
Speaker 1: But I think that, you know, given the news about
Speaker 1: Avian influenza this year and the timeliness of this, we
Speaker 1: really wanted the opportunity to kind of go back and
Speaker 1: redo re explore this pathogen that is is so utterly
Speaker 1: terrifying and there's so much information out there about it
Speaker 1: that it really deserves not only like just a second episode,
Speaker 1: but also an entire series.
Speaker 3: Yes, one could certainly argue that.
Speaker 1: Yeah, yeah, so that's what we're doing this episode, kind
Speaker 1: of like talking about all of the different bits that
Speaker 1: we didn't cover in our first episode, which is quite
Speaker 1: a lot. And I think also one of our aims
Speaker 1: is to bring us up to speed more about today
Speaker 1: with a particular focus on Avian influenza.
Speaker 3: Yeah, a lot has changed since Tantine and we've learned
Speaker 3: a lot more, so it's going to be exciting to
Speaker 3: kind of bring it all back together.
Speaker 1: Well, should we start off with quarantiny time?
Speaker 3: We should?
Speaker 2: We certainly should.
Speaker 1: What are we drinking this week?
Speaker 3: Well, we're drinking none other than H one Drink Too.
Speaker 2: I love it.
Speaker 1: So for those of you who haven't listened to our
Speaker 1: very first Influenza episode, we can't blame you.
Speaker 4: First of all necessarily recommending it, Nope, But it is
Speaker 4: maybe pertinent to this part of the episode to know
Speaker 4: that our very first Quarantini was called H one Drink one.
Speaker 2: So this time stage one drink two. Yeah, and what
Speaker 2: is in H one drink too?
Speaker 1: Erin it is kind of a play on the Corpse Survivor,
Speaker 1: So we did the corp Survivor number two for our
Speaker 1: H one Drink one, our very first quarantini, and this
Speaker 1: one we're kind of just doing a variation includes Apricot Liquor,
Speaker 1: light rum, Lemon juice, and lil Itt Blanc and we
Speaker 1: will post the full recipe on our website. This podcast
Speaker 1: will kill You dot Com as well as on all
Speaker 1: of our social media channels, so check it out.
Speaker 3: And as a reminder, this is our season finale, so
Speaker 3: do make sure that you are subscribed to whatever podcast
Speaker 3: app you're listening to this on and to our social
Speaker 3: media so that you don't miss when we drop our
Speaker 3: next season.
Speaker 1: We don't have an exact date for you yet. We're sorry,
Speaker 1: but don't be worried. It won't be too It won't
Speaker 1: be too long.
Speaker 2: Yeah, any other business here?
Speaker 1: I feel like there should be, but I don't think
Speaker 1: there is. So let's just get started.
Speaker 2: We've got a lot to cover.
Speaker 3: Let's take a break and get started. So today we're
Speaker 3: not going to repeat everything that you may have learned
Speaker 3: in our very first episode, which covered influenza. But what
Speaker 3: I do want to do in this biology section is
Speaker 3: take what we learned in that episode and then expand
Speaker 3: on it, but also realizing that that was five years ago,
Speaker 3: and so most of us have probably forgotten or maybe.
Speaker 2: Skipped over the first episode.
Speaker 3: So what I'm going to do in this section is
Speaker 3: talk about influenza viruses in general and then focus primarily
Speaker 3: on bird flu or highly pathogenic avian influenza strains.
Speaker 2: So it's going to be a lot of fun and
Speaker 2: fun meaning.
Speaker 3: Terrifying, okay, as we usually mean, but fascinating all right. So,
Speaker 3: as a perhaps recap for many of us influenza viruses,
Speaker 3: these are RNA viruses, not retroviruses, as I called them
Speaker 3: in our very first ever episode. One of the most
Speaker 3: biggest embarrassments of my life.
Speaker 2: To this day.
Speaker 1: Is it like one of those things that pops into
Speaker 1: your head as you're trying to fall asleep.
Speaker 2: Yeah, sometimes.
Speaker 3: I called it a retrovirus on the internet.
Speaker 1: Forever is tscript.
Speaker 3: I did see the transcript that I was like in
Speaker 3: the transcript, I like made jokes about it, like I
Speaker 3: full on like went hard.
Speaker 2: Okay, it's not a retrovirus, but it is.
Speaker 3: They are RNA viruses in the family Orthomixoviridae, and RNA
Speaker 3: viruses in general not always, but is true for influenza
Speaker 3: viruses tend to mutate much more rapidly than, for example,
Speaker 3: DNA viruses, in large part because they lack good proofreading mechanisms.
Speaker 3: So what happens very commonly with influenza viruses is that
Speaker 3: small mutations can accumulate over time. And if these mutations
Speaker 3: happen to be in regions of the genome that encode
Speaker 3: the major surface proteins of influenza we'll talk about those
Speaker 3: more in a second, aka the antigens, then that can
Speaker 3: make it harder for our immune system to recognize those
Speaker 3: antigens or recognize that virus, and this process is known
Speaker 3: as antigenic drift.
Speaker 2: This is one of the ways that influenza.
Speaker 3: Viruses are particularly adept at evading our immune system and
Speaker 3: why they're so tricky to target and interesting. But on
Speaker 3: top of that, influenza virus genomes are made up of
Speaker 3: multiple short strands of RNA rather than one big long strand.
Speaker 3: And because as we'll talk in a lot of detail about,
Speaker 3: there are so many different strains of influenza viruses. If
Speaker 3: an animal like say a bird, is coinfected with multiple strains,
Speaker 3: which is not at all uncommon. These segments of RNA
Speaker 3: can mix and match inside of their cells and recombine
Speaker 3: to form essentially brand new versions, brand new, unrecognizable strains
Speaker 3: of influenza.
Speaker 2: This is the.
Speaker 3: Process of antigenic shift, and this amazing amount of variation
Speaker 3: in viral strains is why influenza remains such a challenging
Speaker 3: virus to combat in the form of vaccines, etc. But
Speaker 3: let me actually back up even further for a second,
Speaker 3: because when we say influenza virus, we're not talking about
Speaker 3: a single influenza virus. There's actually four major classes of
Speaker 3: influenza viruses ABC and also D, and when we talk
Speaker 3: about influenza viruses in humans, we mostly mean influenza A
Speaker 3: and to a lesser extent, influenza B. Influenza C does
Speaker 3: circulate and causes disease in humans, but it's more like
Speaker 3: a mild cold rather than what we think of as
Speaker 3: the flu, and influenza D is mostly in cattle. Okay,
Speaker 3: So influenza B has two major lineages that circulate only
Speaker 3: among humans. It's not a zoonotic virus, and while it
Speaker 3: can cause a decent amount of disease in epidemics, seasonally
Speaker 3: it's not a zoonotic virus, and it's not like the
Speaker 3: major player in general when we think about influenza.
Speaker 1: SO, I have a question about influenza B. So, from
Speaker 1: my understanding, the vaccines that target you know, seasonal influenza A,
Speaker 1: the influenza A strain that's in there might change from
Speaker 1: year to year depending on what is predicted. But B
Speaker 1: doesn't really seem to change. Why doesn't really change that much?
Speaker 2: That's a good question.
Speaker 3: There's only two major lineages of influenza B, so I
Speaker 3: don't know as much detail because I didn't dig hardcore.
Speaker 2: Into influenza B.
Speaker 3: But it's likely just that there simply isn't as much
Speaker 3: variation as what we see with influenza A.
Speaker 1: Okay, so like fewer opportunities for combination are exactly gotcha.
Speaker 3: Because it's not a zoonotic virus, it's only circulating among humans. Right. Interesting,
Speaker 3: But let us now focus for pretty much the rest
Speaker 3: of this episode on the biggest player, and that is
Speaker 3: influenza A. So most people are probably familiar with classifications
Speaker 3: of influenza A viruses, and those are H one N
Speaker 3: one or H three N two. You've probably heard those
Speaker 3: circulating around every time that there's a new strain that
Speaker 3: causes an epidemic. Right, So those letters H and N
Speaker 3: refer to two specific antigens on the influenza virus surface itself,
Speaker 3: the H antigen hemaglutinin and the N antigen neuraminidase. You
Speaker 3: don't have to remember those names, you could just remember HNN.
Speaker 3: So the H proteins, you can think of these as
Speaker 3: the proteins that bind to our cells and allow influenza
Speaker 3: virus to actually enter our cells. Remember, of course, that
Speaker 3: all viruses have to get into our cells in order
Speaker 3: to be able to replicate. They rely on our machinery
Speaker 3: to finish that process of replication. Influenza viruses are respiratory viruses, right,
Speaker 3: so they predominantly are infecting the cells that line our
Speaker 3: upper and lower respiratory tract. These H proteins on their
Speaker 3: surface are what allow them to bind to these cells
Speaker 3: in particular and enter those cells, Which means that these
Speaker 3: H antigens especially are the ones that in theory and
Speaker 3: in practice our immune system recognizes and if we are
Speaker 3: able to block it, we can stop this virus from
Speaker 3: entering our cells entirely.
Speaker 1: Question. Okay, so the difference between upper and lower respiratory
Speaker 1: tract and the differences in the HS, and are some
Speaker 1: more adept at invading both the upper and lower or just.
Speaker 3: The upper or yeah, a thousand percent?
Speaker 1: Yes, okay? Which ones?
Speaker 2: Okay?
Speaker 3: I can't give you an easy answer on that because
Speaker 3: it varies. The answer to all of these questions of
Speaker 3: detail are probably going to be it depends because let
Speaker 3: me keep going, and we'll see not just how much
Speaker 3: variation there is, but like how terrifyingly much variation is Okay,
Speaker 3: love it? So we can't also forget about the n antigens.
Speaker 3: These are involved in the process of once that virus
Speaker 3: has replicated in our cells and is all packaged up
Speaker 3: and ready to burst forth to go infect more cells,
Speaker 3: the n antigens are what help influence a virus actually
Speaker 3: release from inside of ourselves. That's what the n antigens
Speaker 3: are doing. So another potential target, but a harder one
Speaker 3: given that it's an intracellular site of action.
Speaker 2: So it's really this.
Speaker 3: H antigen that is the one that when we think
Speaker 3: of vaccines, we're predominantly potentially targeting. And we'll get to
Speaker 3: all of that much later in the episode.
Speaker 1: It's interesting to think about from an evolutionary perspective, because
Speaker 1: it seems clear why there would be variation in H
Speaker 1: in the hema glutenants, right, but the neuromidida is like,
Speaker 1: what is the variation in that functionality?
Speaker 3: Ooh, that's a really good question. Yeah, I don't know, Okay, Yeah,
Speaker 3: it's really interesting though, Like what's the benefit of like
Speaker 3: having different receptors to do the binding and releasing?
Speaker 2: Right?
Speaker 1: What is N one versus N two? Is there a
Speaker 1: functional difference or is it just these are different enough different?
Speaker 4: Right?
Speaker 2: Yeah, yeah, it's a good question.
Speaker 3: So there are eighteen different major h antigens sixteen if
Speaker 3: you don't count the ones that are mostly only found
Speaker 3: in bats, and there are eleven or again nine if
Speaker 3: you don't count the ones that are mostly only in
Speaker 3: bats major n antigens. Knowing that you can combine h's
Speaker 3: and ns in pretty much any configuration, that alone is
Speaker 3: a huge amount of potential for recombination and change, right,
Speaker 3: eighteen and eleven or even sixteen and nine, that's a
Speaker 3: ton of variation.
Speaker 2: I can't do that.
Speaker 3: Math no air and math, no air and math this episode.
Speaker 3: But on top of that, you asked, like, what are
Speaker 3: the differences between the different H andigens. Yeah, there is
Speaker 3: not just a difference between say H one and H two,
Speaker 3: but because of the buildup of changes to these H
Speaker 3: and antigen via that antigenic drift, via those small point mutations.
Speaker 3: What that means is that not every version of H
Speaker 3: three and two is exactly the same. There are parts
Speaker 3: of the H antigen and parts of the end antigen
Speaker 3: that are more conserved, and there are other parts that
Speaker 3: are much more variable even within like say H one
Speaker 3: or H five. Interesting, it's fascinating, and yes, absolutely, these
Speaker 3: different H antigens are going to have different affinities for
Speaker 3: specific receptors on our epithelial cells, and that is going
Speaker 3: to determine which cells they invade and how readily. So
Speaker 3: as we see with particular strains like H five N
Speaker 3: one in our first hand account that are able to
Speaker 3: invade lower respiratory tract very rapidly and even invade beyond
Speaker 3: our respiratory tract, that's likely something that's largely mediated by
Speaker 3: particular changes to H or possibly N antigen, allowing it
Speaker 3: to release more readily from certain cells than others.
Speaker 2: So that's all of this variation.
Speaker 3: Let's get into more details of what we know about
Speaker 3: influenza as a as an illness.
Speaker 1: Okay, yeah, So.
Speaker 3: Influenza viruses, of course are respiratory viruses, which means that
Speaker 3: they're transmitted by droplets or aerosols when we cough, sneeze, talk, laugh,
Speaker 3: et cetera. There is also a lot of indirect transmission
Speaker 3: via fomites like door handles, shared coffee cups, whatever you like,
Speaker 3: lick your hand and then touch, and this route of transmission,
Speaker 3: in particular fomtes or like in more indirect transmission seems
Speaker 3: to be and is thought to be a pretty important
Speaker 3: route of transmission, although because I figured you were going
Speaker 3: to ask aarin, I did not get a sense. And
Speaker 3: the papers that I read actually suggested that influenza is
Speaker 3: not actually a very environmentally stable virus. And despite how
Speaker 3: much we know about influenza, we still don't know enough
Speaker 3: to be able to say, like the relative contribution of
Speaker 3: this transmission rate versus that transmission route.
Speaker 2: Does that make sense? Yeah?
Speaker 1: You know me so well. These were literally the two
Speaker 1: questions that was brimming like on the top of my touch.
Speaker 2: Yeah, preem to do you this time?
Speaker 1: You did?
Speaker 3: But in any case, you're breathing and sneezing this stuff
Speaker 3: out because this is a virus that's primarily infecting our
Speaker 3: respiratory cells, the respiratory epithelium, and in general, the incubation
Speaker 3: period for influenza is remarkably short. People are often symptomatic
Speaker 3: by day two after inoculation, sometimes by day one, and
Speaker 3: almost always by day four, So like very short incubation period,
Speaker 3: especially compared to a lot of things we've covered recently,
Speaker 3: and people are generally infectious that is, high viral tiders
Speaker 3: in their nasal epithelium up to twenty four hours before
Speaker 3: symptoms begin.
Speaker 1: Which is where the trouble starts.
Speaker 3: It sure is, And if you think about it too,
Speaker 3: that's like incredibly rapid how quickly this virus gets into ourselves,
Speaker 3: starts replicating, bursts out, and is ready to spread. In
Speaker 3: terms of who gets infected, everybody gets infected with influenza.
Speaker 3: Some data suggests that it's actually children who are the
Speaker 3: most likely to become infected, and the older you are,
Speaker 3: the less likely you are to become infected. But when
Speaker 3: it comes to severe infection and mortality, it's both children
Speaker 3: and older adults over age sixty five that are at
Speaker 3: highest risk of severe infection and death.
Speaker 1: It's that classic U shaped mortality.
Speaker 2: Yeah, yeah, in all but the nineteen eighteen pandemic.
Speaker 1: And of a few others.
Speaker 3: But yeah, other people who are at particularly high risk
Speaker 3: of severe infection include people who are pregnant, and then
Speaker 3: a lot of other comorbidities like heart failailiar pulmonary disease
Speaker 3: of various kinds, cigarette smoking, immunal compromising conditions. All of
Speaker 3: these things essentially just make it harder for our bodies
Speaker 3: to fight off this infection or easier for us to
Speaker 3: get infected with it in the first place. And I
Speaker 3: think we're all probably familiar with the symptoms of the flu,
Speaker 3: although I think a lot of people might confuse it
Speaker 3: with any of another million viruses that we just call
Speaker 3: the common cold, because influenza is not the common cold. No,
Speaker 3: with influenza, you are sick. You are if you are symptomatic,
Speaker 3: which not everyone.
Speaker 1: Is, right, Okay, question real quick, well how many? Yeah,
Speaker 1: thank you?
Speaker 2: I don't know.
Speaker 3: I actually didn't see that number reported very commonly.
Speaker 1: That's so interesting because I feel like we know that
Speaker 1: so well now for things like COVID.
Speaker 3: Yeah, like we should know that, and I just somehow
Speaker 3: missed it, but I didn't see it.
Speaker 1: I mean, I mean, but presumably there are there's a
Speaker 1: subset of people who are asymptomatic.
Speaker 3: Absolutely, and asymptomatic carriers can still shed for even up
Speaker 3: to six days, which is generally how long people shed.
Speaker 2: Okay, but yeah, you're sick.
Speaker 3: You have a fever, you have muscle aches, full body,
Speaker 3: like your entire body is aching. Your throat is sore
Speaker 3: and it's red. Your nose is probably runny. You're coughing.
Speaker 3: You're possibly coughing so hard that you're hurting your ribs.
Speaker 3: You feel like you're coughing your brains out. And this
Speaker 3: is if you have a mild infection. In this case,
Speaker 3: symptoms last seven to ten days, so it's not just
Speaker 3: a few days that you're feeling creuddy. You're feeling bad
Speaker 3: for a long time.
Speaker 1: Yeah, And if.
Speaker 3: Or when this virus makes its way into your lower
Speaker 3: respiratory tract, it can then cause a viral pneumonia. It
Speaker 3: can progress to an acute respiratory distress, which can then
Speaker 3: progress to shock and potentially death. One of the primary
Speaker 3: drivers that determines if someone is going to have a
Speaker 3: severe infection versus a less severe infection Besides just what
Speaker 3: strain of the virus is, it is how far down
Speaker 3: into that respiratory tract did the virus invade? And this
Speaker 3: is probably determined by a whole number of factors, like
Speaker 3: our individual immune response, largely how well did we tolerate
Speaker 3: versus resist that virus in the upper respiratory tract before
Speaker 3: it tried to travel down, What strategies did our immune
Speaker 3: system employ.
Speaker 2: Like and how effective were they?
Speaker 3: But then also likely some degree of infectious dose, like
Speaker 3: how much of the virus were we exposed to, how big.
Speaker 2: Of a load did we have to fight off?
Speaker 3: And then of course the strain of the virus itself,
Speaker 3: like how virulent is it, how big of an affinity
Speaker 3: does it have for those lower cells versus our upper cells.
Speaker 3: And on top of that, because this virus and our
Speaker 3: immune response to it can cause so much damage to
Speaker 3: our lungs, Influenza virus, especially viral pneumonia, can put people
Speaker 3: at significantly higher risk of a superimposed bacterial pneumonia, especially
Speaker 3: from a Staph aureus or a Streptococcus pneumonia.
Speaker 1: Right, okay, question about the nomenclature I guess of influenza
Speaker 1: A viruses, So we know the h's, we know the ends,
Speaker 1: but then there are variations within a particular H and
Speaker 1: N pairing, So like how does that work and how
Speaker 1: do we refer to those?
Speaker 3: Yeah, there's not good ways to refer to them.
Speaker 2: The ones I've seen.
Speaker 3: It's usually like H three and two strain B three
Speaker 3: dot four dot five dot two two two.
Speaker 1: Or something like that.
Speaker 3: So there's like there are like specific strains and sometimes
Speaker 3: two they're still named by like the first place that
Speaker 3: they were discovered or the year that they were discovered.
Speaker 3: So there's a lot when we have particular strains that
Speaker 3: have say become epidemics or have caused really big outbreaks
Speaker 3: in birds, or or spilled over into humans a particular
Speaker 3: number of times or something like that, then they do
Speaker 3: tend to get more specific names. But they're not like
Speaker 3: nice friendly names, yeah, to like easily be liked, you know, right,
Speaker 3: They're very very viral names, if that makes sense.
Speaker 1: Unfriendly names.
Speaker 2: Yeah.
Speaker 3: But so this is where I want to kind of
Speaker 3: shift focus and talk more specifically about the bird flu
Speaker 3: or highly pathogenic avian influenza strains. So it turns out
Speaker 3: that when you hear talk about avian influenza in some respects.
Speaker 3: We're kind of talking about nearly all influenza A strains.
Speaker 1: Oh yeah, yeah.
Speaker 3: The primary natural reservoirs for influenza A viruses are birds,
Speaker 3: especially aquatic birds like ducks and geese and swans and
Speaker 3: gulls and like those cute little sandpiper things on the beach.
Speaker 2: Lots of cute little water birds.
Speaker 3: With the exception of a few strains that are found
Speaker 3: predominantly in bats and not really other places, the vast
Speaker 3: majority of influenza A strains have birds as their natural reservoir.
Speaker 3: These strains, the vast majority of them in both wild
Speaker 3: and domestic birds, are what we call low pathogenicity strains
Speaker 3: or LPAI, So in the birds they infect, they don't
Speaker 3: cause a lot of disease. They might not cause any disease,
Speaker 3: but they can circulate very readily. However, some strains, especially
Speaker 3: those of the H seven and H five and I
Speaker 3: think H nine varieties, have emerged as being highly pathogenic
Speaker 3: aka HPAI. And it's very likely that the strains emerge
Speaker 3: by a number of mechanisms, but antigenic shift and antigenic
Speaker 3: drift that I talked about earlier play a really big role,
Speaker 3: especially reassortment leading to antigenic shift, and this can happen
Speaker 3: in a couple different ways. In wild birds. Many of
Speaker 3: the aquatic bird species that I mentioned, like ducks and
Speaker 3: geese and gulls, tend to roost in really large numbers,
Speaker 3: and because many of these influenza virus strains are low pathogenicity,
Speaker 3: it's easy for a lot of these different strains to
Speaker 3: circulate in a particular population. But one thing that can
Speaker 3: happen is that these low pathogenicity duck strains, for example,
Speaker 3: can pop over into our lovely food system aka poultry farms,
Speaker 3: which are also extremely dense, generally quite unsanitary, beautiful mixing
Speaker 3: grounds for viruses.
Speaker 2: In both of.
Speaker 3: These scenarios, both in large roots of wild birds and
Speaker 3: in poultry farms, it's very easy for these different strains
Speaker 3: to mix in a single animal, recombine, and potentially gain
Speaker 3: traits that lend themselves to higher pathogenicity or virulence in
Speaker 3: the process. And what we can see then happen when
Speaker 3: these highly pathogenic avian influenza strains emerge is kind of
Speaker 3: three major things, all of which are terrifying. Number one,
Speaker 3: it can result in outbreaks in wild birds, which can
Speaker 3: result in massive die offs of wild birds, which is
Speaker 3: not good for the environment or the birds. Number Two,
Speaker 3: we can see outbreaks in poultry at domestic poultry, either
Speaker 3: directly from spillover events or because these highly pathogenic strains
Speaker 3: emerged in the domestic birds themselves, which can.
Speaker 2: Cause massive die offs.
Speaker 3: That also can result in the culling of flocks, which
Speaker 3: means people might lose substantial income. This can also result
Speaker 3: in spill back into wild bird populations, so you then
Speaker 3: have both domestic and wild bird deaths. And then, of
Speaker 3: course there's the thing that makes public health professionals so worried,
Speaker 3: and that is number three. These highly pathogenic avian influenza
Speaker 3: strains can spill over into human populations and potentially cause
Speaker 3: very severe disease. And this has happened.
Speaker 1: Oh, it happens, and it's scary. And I think that
Speaker 1: we've definitely touched on this topic several times. The evolution
Speaker 1: of virulence and why not all viruses or not all
Speaker 1: pathogens will just become nicer to us over time. Yea,
Speaker 1: they may evolve to become more virulent. And poultry farms
Speaker 1: are a great example of this. Right when you have
Speaker 1: like a ton of birds crowding in one space and
Speaker 1: it's really dirty and they're there's no escaping. Yeah, then
Speaker 1: it makes more sense to like ramp up as a virus.
Speaker 1: It makes more sense to ramp up your replication and
Speaker 1: just cause widespread infection. And there aren't many drivers for
Speaker 1: decreased virulence necessarily.
Speaker 3: Right, because that virus is going to be able to
Speaker 3: spread so easily and quickly through a population. It doesn't
Speaker 3: matter if it kills its host really rapidly, it's still
Speaker 3: going to have time to spread, especially in the case
Speaker 3: of an influenza virus which is replicating so rapidly to
Speaker 3: begin with exactly.
Speaker 1: And there have been different estimates of the mutation rate
Speaker 1: or the rate of evolution of influenza viruses based on
Speaker 1: different hosts, and certainly domestic poultry is top.
Speaker 3: That's terrifying, it is. And what's even more terrifying is,
Speaker 3: like we said, this has happened one strain in particular.
Speaker 3: Though several HPAI strains have spilled over into humans, one
Speaker 3: strain in particular, H five N one has spilled over
Speaker 3: handfuls of times, dozens of times into human populations, either
Speaker 3: usually from domestic.
Speaker 2: Or wild birds.
Speaker 3: And when this strain has spilled over into humans, it
Speaker 3: has caused severe infections, with mortality rates of fifty to
Speaker 3: sixty percent. In general, so far, these outbreaks have shown
Speaker 3: relatively limited human to human transmission, which is good for now.
Speaker 3: But the real worry is how many additional mutations would
Speaker 3: it take in a human or even in the bird
Speaker 3: before it makes it into humans.
Speaker 2: For one of.
Speaker 3: These highly pathogenic avian strains to maintain that same level
Speaker 3: of virulence but with more efficient human to human transmission,
Speaker 3: that would be something devastating. And then there's really interesting
Speaker 3: questions as to why do these particular strains cause such
Speaker 3: severe disease in humans? And part of it, as we
Speaker 3: actually heard in our first hand account, is that in
Speaker 3: the case of H five N one, we have evidence
Speaker 3: that this strain in particular causes extra pulmonary infection a
Speaker 3: lot more readily than most other influenza viruses. So it's
Speaker 3: not only infecting the respiratory tract, it's infecting other tissue
Speaker 3: types as well.
Speaker 1: How is it doing that We don't know.
Speaker 3: Necessarily, there's a relatively limited number of human cases that
Speaker 3: have happened so far, and so there's not a ton
Speaker 3: of data on like in VVO anything when it comes
Speaker 3: to age five N one, so we still don't know. Also,
Speaker 3: how much of the damage of this virus in this
Speaker 3: strain is due to direct viral cytopathic effects versus what
Speaker 3: a huge amount of immune system response it stimulates. But
Speaker 3: in either case, the mortality rate is it's terrifying. Yeah,
Speaker 3: and we'll talk a lot more later on about how
Speaker 3: much these viruses continue to circulate and spread among domestic
Speaker 3: foul populations in particular. So it's really something that worries
Speaker 3: a lot of public health professionals.
Speaker 1: Oh yeah, when we talk about species barriers and why
Speaker 1: some influenza viruses that infect birds don't infect humans, what
Speaker 1: is that barrier specifically, Like, what is it about that
Speaker 1: H or that N or whatever that prevents that virus
Speaker 1: from infecting humans.
Speaker 3: Yeah, a lot of it is likely the H factor,
Speaker 3: and just what particular residues on, say duck respiratory or
Speaker 3: GI epithelial cells, because in birds, influenza viruses infect both
Speaker 3: the respiratory and the GI tract often, So it's probably
Speaker 3: just that we don't have as many of those same receptors,
Speaker 3: or we don't have receptors in places that are as
Speaker 3: easy for that virus to get to and that's the
Speaker 3: biggest That would be the biggest barrier. It would be
Speaker 3: the receptors and being able to actually get into ourselves
Speaker 3: in general.
Speaker 2: Okay, there could be others interesting.
Speaker 3: Yeah, So that is the biology of influenza and influenza
Speaker 3: a Aaron terrifying, terrifying. You want to tell me where
Speaker 3: this sucker came from? And you know how all.
Speaker 1: The rest, all the rest. I will do my best.
Speaker 1: Right after this break, before getting too deep into the
Speaker 1: research for what I wanted to cover or this influenza
Speaker 1: go around, I figured I should first check back through
Speaker 1: the transcript from our first influenza episode, our very first
Speaker 1: episode ever.
Speaker 3: Yeah, and then you immediately regretted it, just like I did.
Speaker 1: One hundred percent. How how can anyone make any sense
Speaker 1: of this? It's yeah, But I also wanted to see
Speaker 1: what I covered, if anything, so that I didn't talk
Speaker 1: about it again, like you said. Turns out I didn't
Speaker 1: have to worry all that much about it because there
Speaker 1: was just kind of disorganized mess everywhere. But it was
Speaker 1: really interesting to skim through to see what I didn't cover,
Speaker 1: like what questions I still had about the history of
Speaker 1: the influenza virus, especially in terms of its evolutionary history
Speaker 1: and avian influenza, and then that is sort of what
Speaker 1: I based this part of the episode on, and it
Speaker 1: was also really interesting to read it through the lens
Speaker 1: of today, after we've been in a pandemic for two
Speaker 1: plus years. That episode came out in October twenty seventeen. Wow,
Speaker 1: we're recording this in October twenty twenty two, which is amazing. Yeah,
Speaker 1: five years later. And at the time of that first recording,
Speaker 1: we were horrified by the choices that people made during
Speaker 1: the nineteen eighteen pandemic, like the parade in Philadelphia, for instance.
Speaker 1: We seemed shocked at the idea of everyone wearing masks.
Speaker 1: And we talked about the very real and very scary
Speaker 1: possibility that the next pandemic that we could see would
Speaker 1: be caused by an influenza virus, in particular H five
Speaker 1: N one. And although we were wrong about the causative
Speaker 1: agent of the next pandemic, we were right to be
Speaker 1: scared to still be scared. Frankly, my intention today is
Speaker 1: not to scare you, and I think our intention is
Speaker 1: to scare you, but to present what we know about
Speaker 1: the evolutionary history of influenza viruses, take a brief jount
Speaker 1: through the history of past influenza pandemics pandemics multiple because
Speaker 1: there were many of them, and then turn towards the
Speaker 1: highly pathogenic Avian influenza virus H five and one and
Speaker 1: how its epidemiology has changed over the past decades. And
Speaker 1: it's in this last part that I want to draw
Speaker 1: attention to the parallels between the emergence of this H
Speaker 1: five and one virus and the emergence of other pathogens
Speaker 1: of pandemic potential, things like the nineteen eighteen influenza virus
Speaker 1: SARS covid one and of course SARS covid two, Because
Speaker 1: those stories, from initial appearance to sweeping the globe public
Speaker 1: health responses and political commentary, they're disturbingly similar, I know,
Speaker 1: and I say disturbing because even though we know how
Speaker 1: these pandemics happen, applying that knowledge to prove seems almost impossible.
Speaker 1: But before I fall further into this pit of pessimism fatalism,
Speaker 1: let's start back at the evolutionary roots of influenza viruses,
Speaker 1: specifically influenza A. Like most other pathogens we talk about
Speaker 1: on this podcast, coming up with a timeline for the
Speaker 1: origins and evolution of influenza viruses.
Speaker 5: That's pretty difficult, I can imagine, despite.
Speaker 1: The fact that to quote Will and Holmes twenty twenty
Speaker 1: quote from an evolutionary perspective, more is known and more
Speaker 1: sequence data have been generated about influenza viruses than arguably
Speaker 1: any other group of pathogens and.
Speaker 2: Quote I'm not surprised by that.
Speaker 1: Yeah, what does seem likely is that influenza viruses have
Speaker 1: been around for hundreds of millions of years, hundreds of
Speaker 1: millions of years, and that they have infected their natural reservoirs,
Speaker 1: these water birds, specifically the orders and Seriformis, which are ducks,
Speaker 1: and Charadriformis, which are shore birds and gulls. I hope
Speaker 1: I'm pronouncing that right.
Speaker 3: I didn't say those orders because I knew I couldn't
Speaker 3: pronounce the second one, so I was like, you know,
Speaker 3: gulls and cute little pipes.
Speaker 1: That's actually probably what I should have done. Regretting it now,
Speaker 1: I think you did a great job. Thank you, Thank you. Anyway,
Speaker 1: these these influenza viruses have been infecting those birds for
Speaker 1: thousands and thousands of years, and of course birds aren't
Speaker 1: the only animals where influenza viruses can be found pigs, bats, amphibians, fish,
Speaker 1: even hagfish and more. I know your faces, hagfish, I know,
Speaker 1: and more are likely to be discovered the more we look,
Speaker 1: of course, and the patterns in the relatedness of these
Speaker 1: influenza viruses suggest that coevolution between influenza viruses and their
Speaker 1: hosts has been going on as long as vertebrates have
Speaker 1: been vertebrates.
Speaker 2: Wow. I know, that's kind of nice. That's pretty fun.
Speaker 1: Yeah, But a paper from twenty fourteen concluded that all
Speaker 1: of the influenza A viruses that we see today in
Speaker 1: mammals minus bats, and birds descended from a common ancestor
Speaker 1: dating back to the late eighteen hundreds.
Speaker 2: So interesting.
Speaker 1: Yeah, all of the existing diversity, which is highah in
Speaker 1: influenza viruses that we see today in mammals minus bats
Speaker 1: and birds came from a lineage branching off in the
Speaker 1: late eighteen hundreds. Okay, but what does this mean? Like,
Speaker 1: why does this matter? It matters because it highlights a
Speaker 1: very important characteristic of influenza virus evolution, their tendency to
Speaker 1: undergo selective sweeps. Basically, what happens is that a new
Speaker 1: advantageous mutation emerges in one strain that leads to all
Speaker 1: other strains being outcompeted eliminated, so that all future come
Speaker 1: from this one mutant branch.
Speaker 2: Oh my gosh, I love this so much.
Speaker 1: And also we have a present day example or like
Speaker 1: a present day illustration of this. Think about COVID nineteen
Speaker 1: and how the dominant variant of SARS COVID two is
Speaker 1: constantly changing. We don't really see COVID infections caused by
Speaker 1: delta anymore. Delta was displaced by omicron, and even the
Speaker 1: original Omicron lineage has been displaced by a later one.
Speaker 2: Yeah.
Speaker 1: Yeah, and this will keep happening, like this is just
Speaker 1: how it's going to go. The one that is the
Speaker 1: most transmissible and causes the most infections, that's going to
Speaker 1: outcompete the rest, and then that's the only lineage that
Speaker 1: will survive and on and on and on.
Speaker 2: Okay, love this, I know, right.
Speaker 1: And selective sweeps are interesting in light of how we
Speaker 1: look at existing diversity and evolutionary relationships or the evolutionary
Speaker 1: history with different influenza viruses, but they're also important from
Speaker 1: a public health standpoint. Virus is seed when there are
Speaker 1: susceptible individuals to infect, and the more novel a mutation
Speaker 1: makes a strain or variant compared to previous ones, the
Speaker 1: more susceptibility there is going to be in the population.
Speaker 1: And that holds for humans, or birds, or pigs or
Speaker 1: what have you. What determines the level of susceptibility in
Speaker 1: a population is not just how different the viruses from
Speaker 1: previous variants, but also how many people were exposed to
Speaker 1: those previous ones, how novel the virus is to them,
Speaker 1: and that's what separates seasonal flu from pandemic flu. With
Speaker 1: the circulating seasonal influenza viruses, they usually only undergo small
Speaker 1: changes from year to year, and so most of our
Speaker 1: immune systems have seen them or have seen similar strains before,
Speaker 1: either through vaccination or infection, So we don't get infected
Speaker 1: with this new slightly different strain, or if we do,
Speaker 1: we just experience a mild infection. But let's say a
Speaker 1: new influenza virus strain is introduced, maybe spilled over from
Speaker 1: pigs or birds, and none of our immune systems have
Speaker 1: seen it before. That's when you have the potential for
Speaker 1: a pandemic. The four influenza pandemics that we've seen since
Speaker 1: nineteen eighteen demonstrate this. In nineteen eighteen, that usual U
Speaker 1: shaped mortality curve that we talked about was flipped upside down,
Speaker 1: hitting the younger and middle aged generations the hardest, which
Speaker 1: suggested to some that the older generation had encountered an
Speaker 1: influenza virus similar to the nineteen eighteen strain. The nineteen
Speaker 1: fifty seven, nineteen sixty eight, and two thousand and nine
Speaker 1: influenza pandemics were caused by viruses that had undergone reassortment
Speaker 1: from previously circulating viruses. And reassortment, by the way, is
Speaker 1: just when influenza viruses swap bits of their genome and
Speaker 1: create new strains like antigenic shift. Exactly people hadn't encountered
Speaker 1: these new reassorted viruses, and so boom pandemic. This is
Speaker 1: a source of grave concern for highly pathogenic avian influenza
Speaker 1: H five N one that it will swap genes, maybe
Speaker 1: with a human influenza strain, gaining high human to human
Speaker 1: transmissibility and retaining its highly pathogenic nature. The influenza pandemics
Speaker 1: of nineteen fifty seven and nineteen sixty eight were caused
Speaker 1: by viruses that had undergone reassortment between previously circulating avian
Speaker 1: and human influenza viruses, so it can happen. And let's
Speaker 1: not also discount the role of the humble pig as
Speaker 1: a little mixing bowl for influenza viruses.
Speaker 2: The humble pig, the humble pig.
Speaker 1: That's going to be the name of my bar whenever
Speaker 1: I make it. But let me rope those fears of
Speaker 1: H five and one in a bit and instead take
Speaker 1: us briefly through the history of influenza, as I didn't
Speaker 1: really do in our first episode. Although influenza viruses are
Speaker 1: as old as time, it's unclear when humans were first exposed,
Speaker 1: but it's certainly plausible that a passing interaction with ducks
Speaker 1: or with pigs during domestication could have led to small
Speaker 1: outbreaks growing in size as settlements got larger. And while
Speaker 1: some researchers have pointed towards the Hippocratic texts as having
Speaker 1: the first description of an influenza pandemic, specifically the cough
Speaker 1: of parenthus in four to twelve BCE, the symptoms don't
Speaker 1: really match up all that well, and diphtheria has also
Speaker 1: been proposed as a more likely explanation other possible but
Speaker 1: debated influenza epidemic descriptions can be found throughout the hundreds
Speaker 1: of years that followed in eleven seventy three to eleven
Speaker 1: seventy four, c in fifteen ten, and in fifteen fifty seven,
Speaker 1: which some argue was a pandemic, but they agreed upon
Speaker 1: date for the first clear influenza pandemic is fifteen eighty.
Speaker 1: The disease broke out initially in Asia and then spread
Speaker 1: to Africa and then Europe before being brought to the Americas,
Speaker 1: and in all places, infection rates were reported as being
Speaker 1: incredibly high, with a sizable mortality rate eight thousand deaths
Speaker 1: in Rome alone, and some Spanish cities were described as
Speaker 1: being decimated who Two quick asides here The first test
Speaker 1: to do with assessing historical influenza epidemics. Influenza has some
Speaker 1: fairly general symptoms, So how can you tell whether a
Speaker 1: pandemic is caused by influenza in historical accounts When you
Speaker 1: can't do molecular testing, Of course, you can't be certain,
Speaker 1: but you can look for clues that are suggestive of influenza.
Speaker 1: One is that it occurs in the winter months. Another
Speaker 1: is its pattern of spread, which has tended to be
Speaker 1: though not always from somewhere in Asia, to move on
Speaker 1: then west to Africa and Europe, and then the Americas.
Speaker 1: That it explodes rapidly, with a high infection rate and
Speaker 1: often high mortality rate, at least compared to seasonal flu
Speaker 1: and of course the symptoms have to match. If you've
Speaker 1: got all that, influenza seems likely. But those characteristics are
Speaker 1: not unique to influenza alone, and more recently, some researchers
Speaker 1: are re examining these past influenza pandemics and asking whether
Speaker 1: they could have actually been caused by a different respiratory virus,
Speaker 1: say perhaps a type of coronavirus.
Speaker 2: Dump done it now?
Speaker 1: Okay, a side number one over a side number two.
Speaker 1: Here we are the etymology of influenza. Oh, which I
Speaker 1: didn't talk about. I'm pretty sure I don't think you
Speaker 1: did either. Okay, Well I'm talking about it now. Surprisingly
Speaker 1: difficult to track down. I mean, it seems like there
Speaker 1: should be an easy explanation, and generally speaking, people do
Speaker 1: seem to that it comes from Italian, ultimately derived from
Speaker 1: the Latin word influentia, meaning either to flow into or influence,
Speaker 1: both suggesting that the influence of the stars, or like
Speaker 1: the influence of the fluid from the stars would flow
Speaker 1: into you to make you sick. Huh yeah, yeah, something
Speaker 1: to that effect. Okay, but when it was first used
Speaker 1: seems up for debate. So I've read that it was
Speaker 1: first used in thirteen fifty seven from an epidemic in Florence, Italy,
Speaker 1: sometime in the fifteenth century, seventeen forty three during an
Speaker 1: epidemic in Rome, or my favorite quote, way way way
Speaker 1: back in the day.
Speaker 3: Quote that sounds like my answer. It was like way
Speaker 3: back in the day.
Speaker 1: I mean, that could be any one of those dates.
Speaker 3: So they're not wrong, they're not.
Speaker 1: It's true.
Speaker 2: It's the most correct answer.
Speaker 1: Technically, right is the best way to be right. The
Speaker 1: precise year that it was first used may not really
Speaker 1: matter all that much, but I do think it would
Speaker 1: be helpful to understand how well known or distinguishable this
Speaker 1: disease was. Yeah, yeah, okay, But back to pandemics. The
Speaker 1: next influenza pandemic occurred in seventeen twenty nine, starting in Russia,
Speaker 1: before covering the entirety of Europe within six months and
Speaker 1: the rest of the world within three years.
Speaker 3: It's also so impressive to think of these influenza pandemics
Speaker 3: so long ago when travel was not as easy, given
Speaker 3: how rapidly this virus spreads, and that the vast majority
Speaker 3: of people are not infectious for that long after they
Speaker 3: start to show symptoms.
Speaker 1: But if it is that infectious of a virus or
Speaker 1: that transmissible that anyone you come into contact with.
Speaker 3: I know, it's just still so impressive that you can
Speaker 3: make it from Russia to like anywhere else, I know,
Speaker 3: in the seventeen hundreds.
Speaker 1: Impressive and scary. I guess it's just like, but did
Speaker 1: it then, Like, you know, does air travel really make
Speaker 1: that much of a dent?
Speaker 2: We've all seen contagion.
Speaker 1: Anyways, yep, I have not watched that since COVID, But yeah, Interestingly,
Speaker 1: this pandemic, the one starting in seventeen twenty nine, which
Speaker 1: had high mortality, also had recognizable waves of infection with
Speaker 1: increasing severity. Forty years later. The next pandemic occurred in
Speaker 1: seventeen eighty one to seventeen eighty two, beginning in China,
Speaker 1: spreading to Russia within a few months, and then onto
Speaker 1: Europe and the rest of the world within eight months.
Speaker 1: As is characteristic of influenza, pandemics attack rate was super high,
Speaker 1: especially among young adults, notably with two thirds of the
Speaker 1: population of Rome falling ill three quarters of the population
Speaker 1: of Britain, and at its peak, thirty thousand got sick
Speaker 1: each day in Saint Petersburg.
Speaker 2: Wow. Yeah.
Speaker 1: Also, I just thought of something about what you brought
Speaker 1: up in global travel and how long it would have
Speaker 1: taken to get from Russia to Europe. For instance, we
Speaker 1: may not be dealing with the same influenza viruses that
Speaker 1: we see today, so you could have potentially been infections
Speaker 1: so longer.
Speaker 2: That's a really good point. Yeah, yeah, yeah, or shedding. Yeah.
Speaker 1: But anyway, Okay, So going back to pandemics. So the
Speaker 1: next pandemic happened about fifty years after that one in
Speaker 1: seventeen eighty one. So this was in eighteen thirty to
Speaker 1: eighteen thirty three. This one originated in China and spread
Speaker 1: south to Indonesia and the Philippines, and then west to India,
Speaker 1: Russia and onto Europe and the Americas. This pandemic reportedly
Speaker 1: had infection rates comparable to those in the nineteen eighteen
Speaker 1: influenza pandemic, with twenty to twenty five percent of the
Speaker 1: population becoming infected again in waves, though not with a
Speaker 1: super high mortality rate. Sixty years went by before the
Speaker 1: next pandemic in eighteen eighty nine to eighteen ninety and
Speaker 1: this was the first since the rise of germ theory
Speaker 1: and the enormous shifts in medicine and medical training that
Speaker 1: had occurred in the nineteenth century. And this marks the
Speaker 1: first influenza pandemic for which we have detailed records, statistics, timing,
Speaker 1: and a better sense of the pathology. For this disease,
Speaker 1: the virus reached Europe from Russia and spread across the
Speaker 1: Atlantic to the Americas, then onto Australia and New Zealand,
Speaker 1: Southeast and Southern Asia, and Africa, all within about a year,
Speaker 1: which is again pretty fast. Infection rates were high, but
Speaker 1: the case fatality rate was low. Despite this, the scale
Speaker 1: of death was enormous one million people in a global
Speaker 1: population of one point five billion.
Speaker 2: Wow.
Speaker 1: The world wouldn't have to wait another fifty or sixty
Speaker 1: years for the next influenza pandemic, though, because a short
Speaker 1: twenty eight years later, the deadliest influenza pandemic the world
Speaker 1: had seen would result in five hundred million infections and
Speaker 1: fifty to one hundred million deaths worldwide. Although I'm tempted
Speaker 1: to redo the coverage of the nineteen to eighteen influenza
Speaker 1: pandemic from our first episode, I want to make sure
Speaker 1: that I get to what I really want to talk
Speaker 1: about today, which is the emergence of highly pathogenic avian influenza,
Speaker 1: and so I'm just going to glance over it. Essentially. So,
Speaker 1: the nineteen eighteen influenza pandemic left the world reeling, and
Speaker 1: if you want to read more about it, there are
Speaker 1: countless resources. I'll post them. And although many researchers tried
Speaker 1: to isolate the causative agent of the nineteen eighteen pandemic
Speaker 1: while it was happening, the technology just wasn't there yet,
Speaker 1: and it was only in nineteen thirty three that the
Speaker 1: influenza virus was finally isolated. Almost immediately afterwards, research on
Speaker 1: a possible vaccine began, with a live attenuative vaccine first
Speaker 1: being reduced and used in factory workers in the USSR
Speaker 1: in nineteen thirty six. Four years later, the inactivated bivalent
Speaker 1: vaccine containing H one N one and influenza B was
Speaker 1: developed and deployed, likely contributing to reduced influenza morbidity and
Speaker 1: mortality during World War Two. The history of influenza viruses
Speaker 1: could genuinely be an entire episode all of its own.
Speaker 1: Oh I bet, and I'm definitely not doing it justice here.
Speaker 1: But essentially, it was a good thing that influenza vaccines
Speaker 1: were around for the nineteen fifty seven and nineteen sixty
Speaker 1: eight influenza pandemics, which had one to four million deaths
Speaker 1: and one million deaths respectively, and forty years would pass
Speaker 1: before the most recent influenza pandemic, which was in two
Speaker 1: thousand and nine, resulting in eight hundred million to one
Speaker 1: point four billion infections and one hundred and twenty to
Speaker 1: two hundred and three thousand deaths. Although I've seen higher estimates.
Speaker 3: I do not think that I realized is how large
Speaker 3: those numbers were. I didn't swine flu.
Speaker 1: I didn't either yet. There's a paper all post that
Speaker 1: sort of modeled these estimates.
Speaker 3: Okay, yeah, because yeah, that's I mean, you always hear
Speaker 3: like it wasn't as bad as we expected.
Speaker 1: Right, Those are likely not confirmed cases, but estimated and modeled.
Speaker 3: But interesting though, Yeah, that's a lot.
Speaker 1: I didn't read too much about the two thousand and
Speaker 1: nine pandemic because there were just way too many rabbit
Speaker 1: holes to fall down into in this entire episode. But
Speaker 1: I did come across something very interesting that I don't
Speaker 1: remember if we've ever mentioned, and I think that we did,
Speaker 1: and that is the apparent increase in narcolepsy on set
Speaker 1: following the pandemic.
Speaker 2: I don't remember ever talking about that.
Speaker 1: Okay, Well, that of course brought to mind the encephalitis
Speaker 1: lethargica episode and that thing, and so it made me
Speaker 1: really really want to do a narcolepsy episode next season, definitely.
Speaker 3: And maybe we did talk about it a little bit
Speaker 3: in cephalitis lethargica.
Speaker 1: I wonder we must have.
Speaker 2: We must have, we must have.
Speaker 3: We talked about influenza like nineteen eighteen. Yeah, okay, all right,
Speaker 3: yeah yeah, narcolepsy okay.
Speaker 1: Yeah, all right, back to pandemics. Maybe it's just been
Speaker 1: a while since we've covered a really pandemic ye pathogen.
Speaker 1: But I was struck by just how many pandemics that
Speaker 1: influenza viruses have caused, and it made me wonder whether
Speaker 1: we could draw any patterns at all, and what those
Speaker 1: patterns might be from these pandemics. Yeah, so some researchers
Speaker 1: have suggested that there's a set interval between flu pandemics,
Speaker 1: ranging from ten to fifty years, and that we are
Speaker 1: due for the next one in X number of years.
Speaker 1: That travel and increased population size hasn't seen unificantly impacted
Speaker 1: this interval, so it must be something intrinsic to the
Speaker 1: virus itself. Yeah, your face and my face. I'm also
Speaker 1: inclined to disagree. I don't believe that pandemics happen on
Speaker 1: a schedule, or that influenza virus evolution is anywhere near
Speaker 1: predictable enough to know when the next pandemic strain might emerge. Yeah,
Speaker 1: but to borrow a quote from a paper by Potter
Speaker 1: from two thousand and one, quote, it is self evident
Speaker 1: from the history of pandemics that each year that passes
Speaker 1: brings the next pandemic one year closer.
Speaker 2: That I would agree with.
Speaker 1: One hundred percent. Speaking of which, let's now turn to
Speaker 1: highly pathogenic avian influenza. It may be futile to seek
Speaker 1: to predict exactly when the next pandemic influenza will occur,
Speaker 1: but we already know some of the likely circumstances under
Speaker 1: which the next pandemic virus could emerge, namely humans interacting
Speaker 1: with domestic foul Most papers put the first recognition of
Speaker 1: avian influenza in eighteen seventy eight, when Parencido described a
Speaker 1: deadly disease sweeping through chickens and other poultry in Italy.
Speaker 1: It's really unlikely that this is the first actual instance
Speaker 1: of avian influenza, but as often happens, this publication and
Speaker 1: the nickname foul plague led to Isn't that Great? Led
Speaker 1: to additional reports of the disease, which was distinguished from
Speaker 1: other well known avian infections like foul cholera. The pathogen
Speaker 1: responsible for causing foul plague was found to be a
Speaker 1: filterable transmissible agent in nineteen oh one and isolated as
Speaker 1: a virus in nineteen thirty four. Of course, the more
Speaker 1: people looked, the more foul plague viruses they found, which
Speaker 1: were recognized as influenza viruses but not demonstrated to share
Speaker 1: internal antigens with influenza A viruses infecting mammals until the
Speaker 1: nineteen fifties, so it took a while to make the
Speaker 1: connection between like oh, these are all closely related to
Speaker 1: one another, highly pathogenic av and influenza viruses were found
Speaker 1: in domestic poultry, like H five N one, which was
Speaker 1: isolated from a small and self limiting but extremely deadly
Speaker 1: outbreak on a chicken farm on the east coast of
Speaker 1: Scotland in nineteen fifty nine, and these viruses were also
Speaker 1: found in wild birds, particularly migratory birds. The more viruses
Speaker 1: that researchers found, and the more birds they found these
Speaker 1: viruses in, the more they realized they had to worry about,
Speaker 1: especially with the evidence suggesting the nineteen sixty eight H
Speaker 1: three and two pandemic virus had gotten a couple new
Speaker 1: genes from an influenza virus found in ducks. Surveillance studies
Speaker 1: conducted from nineteen seventy three to nineteen eighty six involving
Speaker 1: over twenty thousand birds revealed a prevalence of avian influenza
Speaker 1: of about ten percent, with ducks and geese most infected.
Speaker 1: Another study found that twenty six percent of forty eight
Speaker 1: hundred ducks about to migrate were infected, and with even
Speaker 1: higher rates sixty percent in juveniles. The high prevalence, incredible diversity,
Speaker 1: and extreme virulence of some influenza viruses in domestic and
Speaker 1: wild birds did ring alarm bells for many public health researchers,
Speaker 1: but that ringing was kind of faint for a while
Speaker 1: because there had been no apparent instances of these deadly
Speaker 1: viruses being transmitted directly from birds to humans. But that
Speaker 1: ringing would grow a whole lot louder in nineteen ninety seven.
Speaker 1: In the spring of that year, in Hong Kong, three
Speaker 1: year old lamb Hoycob became increasingly sick with what seemed
Speaker 1: like a severe respiratory infection fever, cough, sore throat, and
Speaker 1: the infection wasn't getting any better. Although doctors tried everything
Speaker 1: they could, he got worse and worse, his lungs, liver,
Speaker 1: and kidney's failing, and a week after he was admitted
Speaker 1: to the hospital he died. Samples had been taken from
Speaker 1: Hoyka while he was still alive and sent to the lab,
Speaker 1: where they were expected to confirm that his illness was
Speaker 1: caused by seasonal influenza, which is generally mild but can
Speaker 1: cause severe infection in some cases, of course, but nothing
Speaker 1: was a match. The virus was definitely influenza A, but
Speaker 1: it didn't seem to be any of the subtypes they
Speaker 1: were testing against the chief of the virology lab at
Speaker 1: the Queen Mary Hospital sent off the samples to other
Speaker 1: researchers around the world to see if someone else could
Speaker 1: solve the puzzle. Two months later, one of those researchers
Speaker 1: showed up in person to reveal what they had found.
Speaker 1: It wasn't an H one or a weird H three.
Speaker 1: It was an H five, specifically H five N one,
Speaker 1: that had up to that point only been known to
Speaker 1: cause infections and deadly ones in birds. It turned out
Speaker 1: that earlier that year, a horrifically deadly disease had swept
Speaker 1: through some poultry farms northwest of Hong Kong, killing most,
Speaker 1: if not all, of the chickens at these farms. That
Speaker 1: virus turned out to be H five N one, but
Speaker 1: this news didn't really register as public health news. After all,
Speaker 1: this strain had never been known to infect humans. Could
Speaker 1: this poultry outbreak have been the source of infection for
Speaker 1: lam Hoyca. The connection wasn't immediately obvious. The family lived
Speaker 1: in an apartment building fifteen miles away from the farms,
Speaker 1: so how could he have been exposed. It turned out
Speaker 1: that a few weeks before he had gotten sick, the
Speaker 1: teachers at his nursery school brought in baby chicks and
Speaker 1: ducklings into the classroom to keep his class pets. They
Speaker 1: didn't last long. Over a couple of weeks, both ducklings
Speaker 1: and two of the three chicks had died. The remaining
Speaker 1: chick was long gone by the time epidemiologists arrived on
Speaker 1: the scene to test for H five and one. But
Speaker 1: that classroom exposure seems the likeliest source for lam hohoica,
Speaker 1: and epidemiologists would have more opportunities that year to track
Speaker 1: down cases of H five and one spillover from domestic
Speaker 1: poultry to humans, because over the course of that year,
Speaker 1: eighteen people became infected with the virus, six of whom died.
Speaker 1: In this outbreak. Even though it seems really small in size,
Speaker 1: only eighteen people, it sent the world into high alert
Speaker 1: and for good reason, could this be the start of
Speaker 1: the next influenza pandemic? In response, one point two million
Speaker 1: chickens in Hong Kong were called to try to stop
Speaker 1: the spread, which was a controversial and unpopular decision for
Speaker 1: many people because of the tremendous economic impact. It was
Speaker 1: your livelihood gone. But it turned out that one in
Speaker 1: five of those chickens had been infected with the virus,
Speaker 1: and once the culling had ended, the human deaths and
Speaker 1: infections also seemed to stop, but the worry remained. This
Speaker 1: outbreak turned what we thought we knew about avian influenza
Speaker 1: on its head. We thought that a species barrier prevented
Speaker 1: avian influenza from infecting humans and human influenza from infecting birds.
Speaker 1: Not so the other assumption that spillover could happen, but
Speaker 1: human to human transmission of an avia influenza virus was unlikely.
Speaker 1: That was also about to be challenged. Even though the
Speaker 1: culling of those one point two million chickens in Hong
Speaker 1: Kong arrested the spread of H five and one to humans,
Speaker 1: there was no eliminating it from bird populations. Highly pathogenic
Speaker 1: avian influenza viruses popped up in the early two thousands,
Speaker 1: again in domestic poultry, after causing huge outbreaks, some of
Speaker 1: which were successfully controlled by culling, but the cat was
Speaker 1: long out of the bag. H five and one was
Speaker 1: detected in wild birds in Asia in two thousand and three,
Speaker 1: and over the next few years the virus had spread
Speaker 1: to poultry in Africa. The Middle East and Europe, causing
Speaker 1: deadly outbreaks and birds, as well as spilling over to
Speaker 1: humans where instances of human to human transmission seem to occur,
Speaker 1: although in very limited chains. Up to this point, it's
Speaker 1: somewhat debated what led to the spread of H five
Speaker 1: and one, which is now globally distributed, but it seems
Speaker 1: likely that it was migratory birds. Outbreaks on domestic poultry
Speaker 1: farms seem to follow the timing and location of where
Speaker 1: migratory birds are flying over, as do some human cases.
Speaker 1: And Aaron, I'll leave it to you to give us
Speaker 1: the final numbers on how many cases of H five
Speaker 1: and one have occurred in humans, but I know it's
Speaker 1: been in the hundreds, maybe eight hundred or so. With
Speaker 1: that staggeringly high mortality rate you quoted, like fifty to
Speaker 1: sixty percent in the age of COVID, A thousand or
Speaker 1: so infections may seem like nothing at all, just a
Speaker 1: day in your county, but it's truly not, especially when
Speaker 1: the mortality rate is so high. Some people take comfort
Speaker 1: in the fact that H five N one hasn't yet
Speaker 1: evolved to be more transmissible of human to human, while
Speaker 1: others feel it's just a matter of time. Complacency is
Speaker 1: not acceptable. COVID showed us just how unprepared we were
Speaker 1: and I worry still are for a pandemic. Public health
Speaker 1: isn't just about control and containment. It's also about prevention.
Speaker 1: It's the centers for disease control and prevention. Although people
Speaker 1: often forget to include that last part, including us, we
Speaker 1: often leave it off. Some viruses are extremely difficult to
Speaker 1: control or contain once they emerge, especially if they're infectious
Speaker 1: before causing symptoms, which makes them great pandemic viruses, as
Speaker 1: we saw with SARS, Coby two nineteen eighteen, influenza virus,
Speaker 1: and many other pandemic viruses, and so our best shot
Speaker 1: lies in preventing them from emerging in the first place.
Speaker 1: The good news is that we know the circumstances under
Speaker 1: which these viruses are most likely to emerge and the
Speaker 1: places where viral evolution and spillover is most.
Speaker 4: Likely to happen.
Speaker 1: The bad news is that these circumstances, the breeding grounds
Speaker 1: for pandemic pathogens, not only still exist, but are likely
Speaker 1: increasing in size and number, making spillover more likely and
Speaker 1: monitoring for these pathogens more difficult. That combined with globalization. Well,
Speaker 1: we know the rest massive unregulated farms where poultry or
Speaker 1: pigs or cows all crowd together, wet markets where viruses
Speaker 1: can commingle freely before spilling over to humans. Over use
Speaker 1: of anti virals or antibiotics, and poultry leading to resistant strains,
Speaker 1: fear of stigma or economic impact into the suppression of
Speaker 1: disease reports. What's shocking to me is not that avian
Speaker 1: influenza has spilled over into humans, but that there hasn't
Speaker 1: yet been a pandemic. Reading about highly pathogenic avian influenza
Speaker 1: filled me with such a creeping dread because it's the
Speaker 1: same thing that we've seen time and time again. It's
Speaker 1: what we saw with stars, it's what we saw with COVID,
Speaker 1: and it's what we're going to see with the next
Speaker 1: influenza pandemic. From the book I read that was published
Speaker 1: in two thousand and nine, quote, the moral of SARS
Speaker 1: is clear. The flu virus must be controlled in birds,
Speaker 1: whatever it takes. The microbial agent must be extinguished before
Speaker 1: a readily transmissible flu strain jumps to people, because once
Speaker 1: it does, global spread is inevitable. There won't be any
Speaker 1: way to stop it.
Speaker 2: End quote.
Speaker 1: I think the biggest question that remains is what exactly
Speaker 1: will it take to prevent the next influenza pandemic? And
Speaker 1: are we equipped to do those things? Are we equipped
Speaker 1: to do more than just react?
Speaker 2: I don't know.
Speaker 3: I don't have the answer to that either, so I
Speaker 3: hope you're not.
Speaker 2: I'm not I can answer that.
Speaker 1: I don't know if anyone has the answer. I hope
Speaker 1: people do. I won't ask you to answer, but I
Speaker 1: will hand it over to you at this point to
Speaker 1: fill me in on where we stand with influenza today.
Speaker 2: Oh my gosh. I will try and do my best.
Speaker 3: Right after this break, we'll talk briefly because I think
Speaker 3: it's still deserving about epidemic flu and then get into
Speaker 3: the details on the status of highly pathogenic Evian influenza,
Speaker 3: and I will try to not end on the most
Speaker 3: of downers, but no guarantees, so sorry. Every year, World
Speaker 3: Health Organization estimates that anywhere from three to five million
Speaker 3: people worldwide become severely ill from influenza. So I'm not
Speaker 3: just talking like global numbers. I'm talking like sick enough
Speaker 3: to matter to things like hospital systems and work systems,
Speaker 3: et cetera. Three to five million people globally just from
Speaker 3: epidemic every year seasonal influenza. And it's estimated that anywhere
Speaker 3: between two hundred and ninety thousand and six hundred and
Speaker 3: fifty thousand people die worldwide from the flu every year.
Speaker 2: These are not small numbers, no, they're not.
Speaker 3: In the US, it's estimated that between three and eleven percent,
Speaker 3: depending on the year of the US population is symptomatic
Speaker 3: from the flu, so not necessarily severely ill, but at least.
Speaker 2: Symptomatic, okay.
Speaker 3: And the estimated economic burden in the US alone is
Speaker 3: between six to twenty five billion dollars a year from
Speaker 3: both direct medical costs as well as indirect like time
Speaker 3: missed from work, et cetera type costs. Dang, So, I
Speaker 3: hope that we can all be on the same page
Speaker 3: that even apart from the terror that is highly pathogenic
Speaker 3: avian influenza, even apart from novel strains and pandemic potential,
Speaker 3: annual flu epidemics are a big deal, and they're incredibly
Speaker 3: costly in terms of.
Speaker 2: Lives and dollars. So that's flu. It matters.
Speaker 3: But then, of course there is highly pathogenic avian influenza,
Speaker 3: and there is like you described, aaron massive pandemic potential,
Speaker 3: and we all probably not just from your terrifying descriptions, sorry,
Speaker 3: but also from currently living through a global respiratory viral pandemic.
Speaker 3: I think we have a renewed appreciation for just how
Speaker 3: serious and real this threat really is. So there is
Speaker 3: a group of organizations, the World Health Global Influenza Program
Speaker 3: developed a tool that's called the Tool for Influenza Pandemic
Speaker 3: Risk Assessment, which basically joins together the World Health Organization,
Speaker 3: the World Organization for Animal Health WOE like their acronym
Speaker 3: used to be called the OIE, as well as the
Speaker 3: Food and Agricultural Organization or the FAO, and these groups together,
Speaker 3: and I would say predominantly the WOE attempt to monitor
Speaker 3: and assess the risk of pandemic influenza from a one
Speaker 3: health perspective.
Speaker 2: We love to see it right.
Speaker 1: One health is.
Speaker 2: Great, One health is great.
Speaker 3: But I will say, as much as I did find
Speaker 3: data on the WOE page, I was a little bit
Speaker 3: disappointed that the World Health Organization page on Avian influenza
Speaker 3: hasn't been updated since twenty eighteen, and the most recent
Speaker 3: maps that you can find of HPAI from them at
Speaker 3: least are actually dated all the way back to twenty fourteen,
Speaker 3: so it's a little bit difficult at least if you're
Speaker 3: just going directly to the World Health Organization to try
Speaker 3: and access the more current data.
Speaker 1: That's disappointing.
Speaker 2: It's a little disappointing. Let's move on.
Speaker 3: When we look at human infections as of a paper
Speaker 3: that was published in twenty twenty, so these numbers are
Speaker 3: likely from twenty nineteen and maybe early twenty twenty, there
Speaker 3: have been eight hundred and eighty three officially reported highly
Speaker 3: pathogenic avian influenza cases in humans. Eight hundred and sixty
Speaker 3: of those have been caused by H five and one,
Speaker 3: and twenty three of them from H five and six.
Speaker 3: And these numbers are only slightly higher than what I
Speaker 3: actually reported back in twenty seventeen in our very first episode. However,
Speaker 3: it is also still true that of those over four
Speaker 3: hundred and fifty have died as a result of their infection,
Speaker 3: which is an over fifty percent mortality rate, and that's terrifying. Yeah,
Speaker 3: But where it gets way more terrifying is just if
Speaker 3: we look at what's happening in birds. So if we
Speaker 3: look just at the US alone, because it was easy
Speaker 3: to get really good numbers.
Speaker 2: In the US.
Speaker 3: As of October thirteenth, twenty twenty two, two pm Eastern,
Speaker 3: there have been forty seven million, three hundred ninety two thousand,
Speaker 3: four hundred ninety eight cases of highly pathogenic avian influenza
Speaker 3: in domestic birds since January of this year, forty seven
Speaker 3: million across forty two states in five hundred twenty eight
Speaker 3: different reported outbreaks since January in the United States, and
Speaker 3: two thousand, nine hundred and thirty in wild birds in
Speaker 3: five hundred eighty three separate outbreaks across forty six states.
Speaker 1: So some pretty terrible numbers there h So.
Speaker 3: Far, only one human case has been reported in the US,
Speaker 3: in someone who was working directly with calling infected back
Speaker 3: in April in.
Speaker 1: Colorado Shout out and shouta yep.
Speaker 3: They survived and had a relatively mild infection. But this
Speaker 3: is continuing to spread, including among wild birds, many of
Speaker 3: which have now begun their migrations south, and therefore this
Speaker 3: is not the end. If we look globally, this is
Speaker 3: not something that this year is just happening in the US.
Speaker 3: According to the WOE, the World Organization on Animal Health,
Speaker 3: there have been outbreaks either singular or more commonly plural,
Speaker 3: that are ongoing in Mexico, Canada, the US of course.
Speaker 3: In Europe, outbreaks have been reported in Bulgaria, Hungary, the UK, Germany, Netherlands, Russia, Moldova, Spain, France,
Speaker 3: and Poland. In Africa, outbreaks have been reported in Nigeria.
Speaker 3: In Asia, they've been reported in Japan, Taipei, and the
Speaker 3: Philippines so far in twenty twenty two.
Speaker 2: And to be.
Speaker 3: Completely honest, that might not actually be all of them,
Speaker 3: because the way that the WOE reports things out is
Speaker 3: monthly or sometimes every couple of months, but they report
Speaker 3: out current outbreaks that have new cases and new outbreaks,
Speaker 3: but not necessarily if there were outbreaks that don't have
Speaker 3: new cases reported and I couldn't find nice like cumulative
Speaker 3: summary reports from twenty twenty two so far, Okay, so
Speaker 3: there may be countries that had outbreaks earlier in the
Speaker 3: year that I missed, But in short, in this year alone,
Speaker 3: twenty twenty two, we are looking at hundreds, if not thousands,
Speaker 3: of individual outbreaks.
Speaker 2: Accounting for millions.
Speaker 3: Of cases in both wild and domestic birds in dozens
Speaker 3: of countries across the globe.
Speaker 1: I mean how many more times this episode can we
Speaker 1: say it's terrifying.
Speaker 3: Well, we can say it one more time after this,
Speaker 3: because right now it's October, and September tends to be
Speaker 3: the lull of cases, and then it often picks back
Speaker 3: up in October with peaks in February. And what's been
Speaker 3: really scary about this season in particular is that what
Speaker 3: we saw throughout all of these outbreaks is that they
Speaker 3: didn't go away in the summer. Even in places like
Speaker 3: the US, where usually you would see like really low,
Speaker 3: almost no numbers of avian influenza across the summer months,
Speaker 3: we didn't see like complete elimination during those months like
Speaker 3: we usually have in the past. Why they just have
Speaker 3: continued to spread. Why they've made it into particular bird populations.
Speaker 2: That have allowed it?
Speaker 3: Why?
Speaker 2: Why?
Speaker 3: And like you said, Aaron, prevention.
Speaker 2: Is incredibly difficult.
Speaker 3: Of course, there are recommendations things like separating wild and
Speaker 3: domestic birds to reduce contact between these populations, ensuring good
Speaker 3: hygienes and poultry facilities, but we know that's very difficult.
Speaker 2: It doesn't always happen.
Speaker 3: Vaccination of birds can be helpful to some extent, but
Speaker 3: it doesn't do anything for wild bird populations, and the
Speaker 3: same limitations on vaccines for birds exist as those for humans,
Speaker 3: which I'll talk more about in just a minute. But
Speaker 3: our vaccines are not perfect, and rapid containment once we've
Speaker 3: identified outbreaks is really important. But like you mentioned, Aaron,
Speaker 3: this usually involves culling, which is a difficult thing to
Speaker 3: ask of people because that's a huge financial stressor. And
Speaker 3: not everywhere, like not every government financially compensates people for
Speaker 3: the loss of their flocks.
Speaker 1: Yeah.
Speaker 3: On top of that, just to make it a little
Speaker 3: bit worse, is pile it on you want to pile it.
Speaker 3: Urbanization and habitat loss for wild birds, especially waterfowl, means
Speaker 3: that both humans and our domestic animals are naturally put
Speaker 3: into closer and closer contact with these birds on a
Speaker 3: regular basis, and so it's just so much easier for
Speaker 3: transmission to cross species.
Speaker 2: Yep. So none of that was.
Speaker 3: Good news, but that is the truth of where we
Speaker 3: stand with highly pathogenic avian influenza. Twenty twenty two has
Speaker 3: been a particularly bad year, especially in the US. We
Speaker 3: haven't seen an outbreak like this since twenty fifteen, when
Speaker 3: we had an outbreak of fifty million birds, and we're
Speaker 3: almost there and it's October. So let's see if we
Speaker 3: can find any good news, any silver linings.
Speaker 1: Vaccines.
Speaker 3: But yeah, not so, I guess I wouldn't say silver
Speaker 3: linings with just like things to look for.
Speaker 5: Would do things to have to cling to hope, There
Speaker 5: we go, hope clingers. Yeah, vaccines, you're right erin so
Speaker 5: everyone knows that every year we have to get a
Speaker 5: new flu shot. Every year, your doctor's like, did you
Speaker 5: get your flu shot?
Speaker 3: And every year, at the end of flu season, we
Speaker 3: find out how effective or not so effective that year's
Speaker 3: vaccine was. The reason that we have these different shots
Speaker 3: every year is because of how much variety there is
Speaker 3: in the genome of influenza viruses, because of that antigenic drift,
Speaker 3: especially those small mutations that are happening every year, and
Speaker 3: so every year the vaccine aims to cover the most
Speaker 3: likely circulating strains. But the current vaccines that we have
Speaker 3: are far from perfect. A. We don't always get strains right.
Speaker 3: Sometimes they continue to mutate and we get them wrong. B.
Speaker 3: The vaccines themselves are not the most immunogenic, and so
Speaker 3: we don't actually mount like that incredible of an immune
Speaker 3: response to them and see, because of the way that
Speaker 3: we currently produce influenza vaccines, which is using eggs as incubators,
Speaker 3: sometimes these viral strains actually mutate in the eggs to
Speaker 3: become less effective during the process of replication.
Speaker 1: Fantastic.
Speaker 3: Yeah, So that's why effectiveness can vary anywhere from ten
Speaker 3: to sixty percent year to year. Now, I will say
Speaker 3: that even a less effective flu vaccine tends to still
Speaker 3: provide good protection against severe disease and death and hospitalization,
Speaker 3: even though it may not protect as well against infection itself.
Speaker 3: So don't think that I'm saying don't get your flu shot.
Speaker 3: It is imperfect, but for right now, it's the best
Speaker 3: that we have, and something is a lot better than nothing.
Speaker 3: But the real question is, and has been for a
Speaker 3: long time, like can we do better, and especially can
Speaker 3: we develop a universal flu vaccine, something that protects against
Speaker 3: a wider variety of strains and does so more effectively,
Speaker 3: a vaccine that could, in theory even protect against these
Speaker 3: pandemic potential strains that we don't even know about yet.
Speaker 3: And the answer is, there's a lot of people who
Speaker 3: think we can, and so they've dedicated their lives to
Speaker 3: working towards it. We still don't have one that I
Speaker 3: can say in the next X number of months or years,
Speaker 3: we're going to have a universal flu vaccine.
Speaker 2: There are I think two that.
Speaker 3: I found in the last couple of years that have
Speaker 3: made it either two or through phase one clinical trials
Speaker 3: that have a lot of potential. One of them is
Speaker 3: from a paper that was published in twenty twenty and
Speaker 3: I tried to get a sense of where it stands today,
Speaker 3: but I couldn't quite, but I'll post the paper so
Speaker 3: that you can read it. It's a really interesting vaccine
Speaker 3: that is made of chimeric h antigens beautiful. So what
Speaker 3: they did is that they linked those conserved portions of
Speaker 3: the H antigen which are similar across a whole bunch
Speaker 3: of different strains H one and two and three, et cetera.
Speaker 2: But usually isn't.
Speaker 3: The part that our immune system responds to and makes
Speaker 3: antibodies against, because it's usually the head, the different part
Speaker 3: of the H anigen that is the most immunogenic, so
Speaker 3: that we are making the most antibodies towards.
Speaker 2: So this vaccine it makes.
Speaker 3: Specific hs that have a less immunogenic head, but a
Speaker 3: very immunogenic stock that is conserved across all of these
Speaker 3: different strains, so it allows for you to mount a
Speaker 3: really good amount of immune response against that stock.
Speaker 1: Interesting.
Speaker 3: I love it. And so in phase one trials it
Speaker 3: did really well. People mounted a really great immune response.
Speaker 3: But what we don't know yet, because we need more trials,
Speaker 3: is to know how does that play out in actual
Speaker 3: flu infections? How well does that protect you against actual infection? Right,
Speaker 3: but it's exciting. The other vaccine that actually started phase
Speaker 3: one trials with NIH this year is a whole virus
Speaker 3: vaccine that is made of low pathogenicity avian influenza viruses,
Speaker 3: and the hope at least this is what happened in mice,
Speaker 3: is that these mice mounted very robust immune responses that
Speaker 3: then actually were protective against a wide variety of strains,
Speaker 3: including those not included in.
Speaker 2: The vaccine, which is fascinating.
Speaker 1: That's cool.
Speaker 3: Yeah, And so that vaccine is currently undergoing phase one
Speaker 3: trials right now twenty twenty two, so we'll see what
Speaker 3: comes of it.
Speaker 2: But it's hopeful. That's where we stand.
Speaker 1: I mean, it's I feel like that's that's pretty good.
Speaker 1: I feel like I was a little bit down on
Speaker 1: humanity and that that might be from COVID, you know,
Speaker 1: living through the COVID pandemic.
Speaker 3: Yeah, and I think it's reasonable. I think I think
Speaker 3: that the idea of in the paper or the book
Speaker 3: that you cited of like we must eliminate this microbe,
Speaker 3: like that's not realistic. No, I don't think that that's
Speaker 3: a thing that is possible, given how widespread influenza is,
Speaker 3: given how rapidly it mutates, it's just not possible. I
Speaker 3: do think that creating a vaccine that does a really
Speaker 3: good job at preventing severe illness, at preventing death, I
Speaker 3: do think that that's possible, and so I have hope.
Speaker 1: I think that's possible. I think that raises the issue
Speaker 1: of access and equitability across different countries. And so you're
Speaker 1: right in that it's in the birds. It's not going
Speaker 1: to leave the birds. It's going to keep evolving and
Speaker 1: mutating in the birds and spreading and so on and
Speaker 1: so forth and more spillovers. And I think that the
Speaker 1: most important thing to target is those opportunities for spillover
Speaker 1: and the opportunities for mixing and like reassortment of different viruses.
Speaker 1: And that's difficult to do. There are a lot of
Speaker 1: different drivers. It's not just about Okay, we'll just stop.
Speaker 2: This right, Nope, it's complicated.
Speaker 1: Yeah, application always is.
Speaker 2: Well, that was a lot.
Speaker 1: That was a lot.
Speaker 2: That was a lot of influenza talk.
Speaker 1: I have one more question. Okay, how scared do we
Speaker 1: need to be? Oharin, I'm just kidding because right now
Speaker 1: I have open on my computer screen the transcript from
Speaker 1: our Influenza episode from twenty seventeen to quote you.
Speaker 2: Okay, what did I say? Go ahead and.
Speaker 1: Get your seasonal flu shot, wash your hands, and just
Speaker 1: be a little afraid. I guess. Oh, then you add
Speaker 1: don't hang around birds?
Speaker 2: Yeah? I love that, love it.
Speaker 1: Do you echo those sentiments today?
Speaker 2: I would say, way to go twenty seventeen, Aarin, you
Speaker 2: knew it? Yeah, yeah, yep.
Speaker 1: Well sources, yeah, I have, unlike our twenty seventeen episode,
Speaker 1: a ton of sources for this episode.
Speaker 2: So embarrassing. How few sources we had for like what
Speaker 2: we didn't?
Speaker 3: You know?
Speaker 1: We hadn't hit our stride. Yeah, I will shout out
Speaker 1: again the Book of the Fatal Strain by Alan Cippras.
Speaker 1: And I have a ton of paper that I will
Speaker 1: post on our website post for this episode.
Speaker 3: I also had quite a number of papers for this episode.
Speaker 3: One that I did really like was actually from twenty
Speaker 3: twenty one and it was called Influenza virus and SARS
Speaker 3: CoV two Pathogenesis and Host response in the Respiratory Tract.
Speaker 3: Super interesting because it compared influenza virus and SARS CoV two,
Speaker 3: so that might be of interest to a lot of people.
Speaker 3: Had a number of other papers on the specific pathogenicity
Speaker 3: and a few if anyone wants to deep dive, especially
Speaker 3: on the transmission aspects of influenza viruses, and then of
Speaker 3: course a number of other papers on the current status
Speaker 3: as well as where we stand with universal flu vaccines.
Speaker 2: So we will post all of.
Speaker 3: Our sources from this episode and every one of our
Speaker 3: five entire seasons on our website, This podcast will kill
Speaker 3: You dot Com.
Speaker 1: Thanks to Bloodmobile for providing the music for this episode
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Speaker 3: I hope that y'all enjoyed this season and we're really
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Speaker 3: Your support means more than we can possibly say.
Speaker 1: Think it means the world. It means the world. Well
Speaker 1: until next season, so Weird. Wash your hands, you filthy animals.
Speaker 3: U u U