We were having hat day at school, and I'm not normally a hat person. I had this like numb spot on my head all day long and it just was like like a not scratchable itch. It was all day, all day, all day. But I thought like at first, I was like, oh, it's just hat day. Like I'm just not comfortable wearing this ridiculous Christmas tree hat at school.
By the weekend, so that like started midweek. By that weekend, it had started to move down my forehead to like my eyebrow area, and that's when it just became this burning itchy, couldn't really make it go away thing. A few days went by, and so this is all at Christmas time. That's when we were driving from where we live in Buffalo down to my parents on Law Island, and that drive, my forehead felt like someone had a
match to it. I think I kind of lucked out with shingles because it was a really small patch that I had, But it just feel like someone had a lighter on my forehead for as long as it did. Was just the craziest thing. I had no idea what it was though, So I started doing like the web MD thing and I was searching for like, what's a large red spot, red spot with blisters, because it started
to get these really small spots over time. And that's kind of when I started to see other pictures of people who had the same thing, and people were saying, its shingles, shingles at shingles. So I finally called my doctor and I said, hey, I have all these symptoms, but like, I don't know what this is. And they said that sounds like shingles. You need to get to you need to come see us right away. But we
were traveling for Christmas. By the time I kind of got all that together, we were already en route from Long Island up to r Island for the weekend. So that's when I ended up at an out of state urgent care and I walked in. The receptionist looked at me and she's like, oh, look at that. You have shingles. And it was just as fast. And then as soon as they saw that, they were able to prescribe medication
and get it under wraps. So by the time I got that, they were like, it's probably too late because it had been a week since I started showing the first symptom. But the really scary thing that they kept sounding the alarm on was this is really close to your eye, This is really close to your eye. So when I came home, I had follow ups with my eye doctors. I had to go back to my primary care just to continue watching it to make sure that at whatever it was wasn't going to affect the optical
nerves and all of those forehead things. But like I said, it was just the craziest thing because I didn't know anybody who had ever had it. I didn't know like, was I going to pass this on to my mom? Was my sister going to get it? I think everybody here is you get shingles from chicken pox, and of my generation, like I think I was the end of
like the chicken pox party. So I was just so afraid that I was going to pass this on to all of my family members, and they were just kind of like, no, You're everything's going to be fine, like just kind of cover it up then go about your day. So that was my That was my shingles experience, I guess.
Thank you so much for taking the time to chat with us and for being willing to share your story. Thanks Hi, I'm Erin Welsh and I'm Aaron Oman Updike, and this is this podcast will kill you. Welcome, Welcome, this is a fun one.
I'm honestly thrilled. I don't know. I don't know exactly why, but I have been looking forward to covering this for a really long time.
I have two and I've been kind of like daunted because I don't I didn't know anything about the history, and it turns out there's like kind of not that much to it. So I hope you don't fall asleep, I'm sure, or if you're listening to this podcast to fall asleep, I hope you do fall asleep. But yeah, I think it's like it's one of like we all
have experienced it or know someone that's experienced it. And I think Aaron, you and I are part of the generation like the last remnants that didn't get the vaccine exactly.
We definitely are the last cohort that just got chicken pox, which is the subject of today's episode.
There we go plus shingles, slash zoster whatever you want to call it, exactly, Yeah, basically the vercella zoster virus.
Yeah.
Uh, Erin, when did you get chicken pox?
I don't remember exactly how old I was, but it had to have been after nineteen ninety four or five, and we all four got it in a row. It went boom boom, boom boom, like down the row of older brother than me, than my younger brother, than the baby brother. We all got it in age order. And I have a very distinct memory of my first poc oh. I had my very first chicken pox was on my left side, like right on my ribs, on my left side, and obviously, like my brother was already sick with it,
so I knew this is chicken pox. And I showed my mom and I was like, Mom, I found this is this chicken pox? And she was like, uh, yeah, it's chicken pox. And I was like, okay, but can I still go to gymnastics?
Did you go?
I did? As far as I can remember. Maybe my memory is off, but my mom was like, you've already exposed everyone. Just keep it covered.
That's hilarious.
She might dispute that memory of it. We'll see, mom, is that what happened? That's how I remember it. I have the scar that I know that that was my first pop.
I really should have called my mom to ask her my chicken pox story, because I don't remember, and I don't even know if I think I might have been too young like to actually remember, but I think it was my older sister and I at the same time got it, and then my two younger brothers got it, and then I honestly don't know about my younger sister whether she got it or whether she got vaccine. Yeah. Yeah, anyway, should.
We should we move on to like actual podcasts, actual business of our podcast?
Maybe is it quarantiny time?
I think it's definitely quarantin any time. What are we drinking this week, Aaron, We're drinking chicken scratch.
I love this. It works on so many levels. It's like people always complain about how doctors have chicken scratch handwriting. It's true and also if you have chicken pox, you're definitely gonna be scratching.
Yeah, and what's in a chicken scratch?
There is tequila, there is kiwi, there is ginger, and there is mint.
Kind of just a fun summary, bev.
Yeah.
We'll post the full recipe for that quarantiney as well as our non alcoholic plusy Burta on our website. This podcast will kill you dot com and our social media.
And on our website. You can find so many different things, like transcripts, like alcohol free episodes, like promo codes for all of the ads that we do, like the links to Bloodmobile, who does the music for all of our episodes. We've also got a Patreon. I mean, it's endless. Just go in there, explore it, and I'm sure we'll come up with something interesting.
Definitely. All right, that was the longer intro than we usually do. Yeah, it was.
It was kind of fun, though, it was.
That's fun getting to relive my chicken pox story. Anyways, should we dive into the biology of.
This thing, let's do it.
We'll take a quick break first, so vercella zoster or herpes zaster or if you want to be very official, human alpha herpes virus three. So this virus that we're dealing with is a herpes virus, which I think some people might not realize because it's called chicken pox. People might think it's a pox virus. It's a herpes virus, and in fact it's very closely related to herpes simplex one, which is a common cause of oral herpes, can also cause genital herpes. Check out our herpes virus episode for
more on that. And so, like all of the herpes viruses, this is a DNA virus. It has a double stranded genome blah blah blah. Like many of the human herpes viruses, this is a very human specific virus. It doesn't infect any other animals, which, as we'll see, is part of why we don't have a lot of answers about some of the specifics of the diseases that this virus causes because we don't have great animal models in which to study it.
That makes sense, Yeah.
Yeah, this particular virus doesn't have a lot of variability. There aren't a lot of different strains of varicella. There doesn't seem to be a lot of variation in the virulence across outbreaks or over time. It's a pretty stable virus and aarin. You asked me something before we started researching this, which is why is chicken pox often called vericella zoster and shingles is called herpes disaster? Yeah, did you find an answer to that?
Well, so, the only thing I could think of is
the etymology of it. So vericella is another word for chicken pox, like that rash that happens for that initial infection, and in a lot of other languages besides English, it tends to be not like the equivalent of chicken pox, but some sort of variation of vericella, right, And the word veriicella might come from like the diminutive form of variola, which is the word for smallpox, and so it might just be like, you know, there's it's analogous where chicken
pox is to smallpox as veriicella is to variola. Etymologically, does that makes sense?
Yeah, it totally makes sense. No, I genuinely makes sense.
And then herpe'saster herpees from herpes is like the old you know, word that was used by ancient Greeks like Hippocrates and whatnot to describe those rashes.
So it seems to just boil down to the fact that even though we're talking about one single pathogen, we're talking about two completely different clinical diseases exactly. Yeah, So
I think that that's something that's interesting. I feel like we've covered a lot of pathogens that just cause like one disease, where we're like, here's the disease we're talking about, and here's the pathogen that causes it, and then we've talked about some things like staph oreas, for example, that can cause any number of diseases.
Yeah, or strip piogenies exactly, right.
So yeah, I don't know. I just feel like that's an interesting aspect of this, that there's this big distinction between the pathogen and the diseases or the illnesses that they might cause. Yeah, well, let's get into the pathogen and both of these diseases, shall we.
Let's do it.
So I talked about how similar already this human herpes viruses to other herpes viruses. Let's start to talk about how it's a little different. Unlike many other herpes viruses, Viicella is transmitted primarily via the respiratory route.
What.
Yeah, isn't that interesting?
I want to know? And I didn't find the evolutionary history, Like what about it? How did that happen?
It's a really good question that I still don't fully understand, aside from the fact that we've talked on this podcast a number of times about the tropism of different viruses. Right, So, viruses, because they are dependent on host cells to be able to replicate. Oftentimes, specific viruses can only infect a limited range of cell type popes. It seems like vericella can
infect a pretty wide range of cell types. So is it just that that's a really easy route of transmission, and it happens to be good at invading and replicating within not just our respiratory epithelium, but also it's very good at invading and replicating in our white blood cells, in lymph nodes, and so a big thing where it replicates is in the lymph nodes in our chest and things like that.
Oh, that's very interesting because I thought that like it also though, does have a tropism towards nerves or is that just later?
Oh? Certainly, certainly, let's let's get into all of this.
Okay.
Basically, I think the bottom line is that it can infect all of those cell types.
Interesting, okay, cool, yeah, all right.
But primarily the way that people become exposed via respiratory. So a kid, because it's usually kids who are infected, comes up and it's like I don't feel good, and like breathes right on your face and you inhale those viral particles. They you speak from experience, I guess I do it, uh, And they travel, those viral particles travel
to those regional lymph nodes and they replicate. And what's really important about the fact that they can infect these white blood cells is from there they can travel anywhere and everywhere, right, So they travel throughout our body and they're able to continue replicating as they invade different cells. In general, the incubation period is about two weeks. It can be from ten to twenty days after exposure to
when you first start to show symptoms. But what's important, especially for a respiratory virus, is that you become infectious and able to infect others at least two days before those first symptoms start.
Aha.
And this is quite an infectious pathogen. It's pretty contagious. I've seen anywhere from sixty to ninety percent of susceptible household contacts are likely to become infected.
What is the estimated are not?
According to a lecture from Johns Hopkins School of Public Health, the r NOT for chicken pox is nine to ten. Oh that's a lot higher than I realized.
Goodness, So when you say respiratory transmission, is it respiratory droplets or is it like aerosolt like air?
Good question. I didn't find this specific answer to that. They just say respiratory route, So I don't know how long it can hang out in the air. I don't think that it's quite as bad as something like measles that can stay airborne for like hours at a time. But with an attack rate that's so high, I would guess that it's probably pretty well airborne. Like it's aerosolizing pretty well. Okay, those chicken pox parties that people used
to have, those are probably pretty effective. It's spreading disease. Oh yes, not a good idea. Let's talk about why should we?
Let's do it.
So, once this virus has disseminated throughout our body, one of the main cells that they tend to infect are our epidermal cells, our skin cells. Inside of our skin cells, it begins to replicate, and this is what causes the typical chicken pox rash that we all know and don't love. So what's really common is that one to two days, like twenty four to forty eight hours before this rash kids,
I say kids. Of course this affects adults too, but most often kids will have like they'll feel kind of cruddy for a day or so beforehand, maybe a headache, maybe a little tummy ache, maybe like a fever probably, But then comes the rash, which is very characteristic and
kind of what we call chicken pox. The rash starts, for anyone who hasn't experienced this, starts as very very itchy, red flat patches, and then these patches become raised or get little bumps within them, and then those little bumps develop into small fluid filled vesicles, tiny little blisters, and these tiny little blisters are chock full of virus. So this is not only a respiratory pathogen, but it can also be transmitted by direct contact.
Okay, it's just covering all the bases.
It's covering all the bases exactly. This rash can also be present on mucous membranes like in the mouth or even the eyes, and there the lesions can kind of ulsterrate a bit more and be really quite painful. Not unlike the lesions that we see with Herpes simplex. These all cause a very similar looking lesion. And these this
rash spreads anywhere and everywhere. It's pretty common that they might start on the head or face, or like centrally on the trunk, but will pretty quickly spread across the entire body and new lesions this rash essentially continues to develop over the course of three to five days, although the range can be anywhere from one to seven days, where you're continually getting more and more little pox.
Oh yeah, I mean, I don't remember any of this, but sounds obnoxious.
It's not great, and of course they're incredibly itchy if you don't scratch the heck out of them. Then eventually, after a few days, these vesicles kind of cloud over, so it's not like a clear fluid anymore, and then they'll encrust usually if you don't scratch them off. This will only take about a day or two per blister, kind of and once every vessel is crusted over, that's
when someone is no longer infectious. So you're able to spread this disease from about two days before you got that fever and headache, so up to four days potentially before the rash, until every blister is crusted over. Now, chicken pox is generally considered a very benign childhood disease. That's why people had things like chicken pox parties because
it was generally considered, you know, a pretty benign. Yes, your kid is miserable for a week, maybe, but they get over it, and most of the time that's true. Chicken pox is an annoying but self limited disease.
But I knew there was a butt.
If there's always a butt. There are a number of potential complications associated with veriicella, and that's before we're even going to talk about shingles. Okay, mm hmm, let's just focus on this primary infection with Varislla virus aka chicken pox. So, first of all, these lesions are itchy, itchy, itchy, itchy, itchy, and especially for kids, it's very difficult to not scratch at an inch, so this inevitably leads to open wounds all over the skin, which can lead to a very
easy route for a secondary bacterial infection to establish. Our bodies are covered in bacteria, especially all over our skin, and bacteria like Strep Pyogenes and staff aureus can both invade deeper tissues and cause very serious and potentially fatal infections. So that's one probably the most common complication.
Number two.
Veriicella, like we've talked a lot about, is this respiratory pathogen, right, except that for most people who are infected, it doesn't actually cause any respiratory symptoms. However, it's certain can and in kids who are immuno compromised, especially, but also in older teens and adults who are exposed to veriicella for the first time, infection tends to be more severe and
primary infection. This first time being exposed to varicella virus can cause a viral pneumonia which can be very severe or even fatal.
Wow.
Yeah, So the numbers that I saw were that of otherwise healthy seeming people who were infected with vericella. Up to sixteen percent of those people had radiographic evidence, so if you took an X ray of their chest, you saw that something was going on in their lungs. So even in people who maybe don't have respiratory symptoms, this virus is still doing stuff in their lungs. But only
about a third of those would have any respiratory symptoms. Okay, but before the advent of antivirals, so before we had any kind of antiviral therapy, mortality from varicella pneumonia was as high as thirty percent, and even today with treatment, it's still around ten percent. So even though this is a small, a very small proportion of people who would go on to develop vercella pneumonia. It's pretty serious when it doesn't. Right.
I feel like I have heard, you know, a lot of people be like chicken pox vaccine, Like why do we need a chicken pox vaccine? Everyone gets it, It's totally fine. And I mean I was kind of like, well, I had the chicken pox, should I have gotten the vaccine somehow? But it totally makes sense.
Yeah, So I think that's one thing I hope that everyone can learn, especially in talking about all these complications of veriicella as well as shingles, which we'll get to in a little bit. Even though all of these complications are very very rare, because vericeella is such or was
such a wide spread pathogen. Literally almost one hundred percent of adults in the US, for example, and in most temperate regions across the world were exposed and infected by the time they reached adulthood, almost like ninety nine percent of the population. And so when you have that large of a population that's exposed, even these small numbers like proportionally lead to pretty severe morbidity and mortality.
Yeah, right, because.
Again it's not just death, there's other complications. So speaking of other complications. We haven't even really talked about it, but we'll talk about it in more detail. That this is a virus that is good at infiltrating our nervous system. Right, All herpes viruses are good at kind of getting into our nervous system and lying latent. So it's not surprising then that neurologic complications are another potential serious complication of
verricilla infection. Overall, the incidence of neurologic complications is low. It's estimated at about one to three per ten thousand cases have some kind of neurologic involvement, whether that's encephalitis or inflammation of the cerebellum which leads to a taxia that kind of wobbly, not being able to walk and move normally. And so it's low incidents one to three per ten thousand. But of all those neurologic cases, anywhere from five to eighteen percent of those are fatal.
Wow.
Yeah. And these complications how usually from encephalitis, okay, Yeah, And these complications are most common in very very young kids like under five, and then adults over age twenty, and then there's a lot of other things. This is a virus that can infect almost anyone of our cells, so it can infect the liver or the kidneys, cause liver failure kidney failure. It can infect your heart muscle
and cause myocardie or pericarditis. If it infects the lining of your heart, it can lead to low platelet counts, which can lead to hemorrhage. And all of these complications are rare, but they happen, especially for children who are immunocompromised or adults who get infected for the first time
who weren't exposed as children. And if that's not enough, veriicella can also cross the placenta and infect a developing fetus, So infection during pregnancy is very bad and can result in congenital vercella syndrome if it happens early in pregnancy, which can lead to neurologic development problems, limb development problems, Scarring of the skin can be pretty serious, and infection later in pregnancy can result in pneumonia in the newborn that is often fatal, Oh my gosh, as well as
leading to premature delivery. It's not as benign as I think people think it is.
Yeah, definitely, definitely a lot worse than I thought it was.
Yeah, and all of that is just chicken pox. What about shingles?
What about shingles?
Okay, Shingles, like other herpes viruses like herpie simplex that we talked about, Vericella zoster is able to invade our nerve cells, hang out there and chill, just hang out in our little ganglia, not be detected by all the antibodies that we make against this virus. We make a lot of antibodies. Yeah, I want to make that clear. It's not like the people who get shingles didn't develop antibodies.
They totally did. But this virus just hangs out in their nerve cell bodies, and eventually, when the time is right, this virus can travel back out again along those nerves, back up to the skin surface and cause a similar but different disease that is shingles. So, shingles starts out as a pain, most often a pain or like a burning sensation, a tingling sensation, and this nerve pain usually is along one nerve route. This is what we call a dermatome, which is the fancy word for the area
of skin that your sensory nerve innervates. Like each one of your sensory nerves only innervates like one like triangle or one section of your skin, right, and so this virus you can think of it as traveling along that nerve and irritating just the skin just where that nerve is.
Gotcha, Okay, that makes sense based on the spread and interesting.
And then following this pain or this burning sensation, usually a few days later, blisters start to appear. These blisters look a lot like the initial blisters of chicken pox. They have like irregular red borders, these raised fluid filled vesicles, and they can be itchy, but they're often just super painful, and they're often in that same dermatome where that pain is.
Yeah, I feel like, if there's one word to describe chicken pox, it's itchy, itch And if there's one word to describe shingles, it's painful.
Painful. Absolutely, I agree, hundred percent. And it is possible to get lesions like away from just this one dermatome, or you could even have like multiple dermatomes involved, but most of the time it's just like one. So for example T eleven, so like you're tenth and eleventh thoracic vertebrae T ten and eleven. That dermatome goes kind of right around your belly button right, and you've got one nerve on the left and one nerve on the right,
so it's usually just one or the other. So you'll get pain and a rash on one side, going wrapping around your belly, wrapping around your back to your belly, and stopping at the midline.
Interesting, isn't it? I feel like that?
Then?
Does that make diagnosis like fairly straightforward?
Yeah, if it looks like clinic classic shingles, it's a pretty classic shingles presentation. The other very classic area besides the trunk, and of course this can happen anywhere anywhere. You have nerves everywhere, but very classically it happens on the trunk or on your head because the other place that they like to hang out is the trigeminal ganglia, So that's your nerve that innervates all of the sensory of your face, and there it'll just be in like
one section. So let's say it's V one that's like just the head, forehead and nose, but not probably like your cheeks and ears, and most likely just on the right side or the left side, but not both sides, and as uncomfortable as that probably sounds, shingles can be a lot more debilitating than just an uncomfortable, painful rash, especially in those who are immuno compromised or the very elderly.
This rash can become quite widespread, so you could have involvement of a number of different nerves, or this reactivation can spread beyond just these nerves and cause a disseminated disease just like primary infection, just like the first time you got exposed to verisella. It can leave those nerves and go anywhere, and even in folks who aren't immunal compromised,
there's a phenomenon called post herpetic neuralgia. This is when this pain, this numbness, this pain, this tingling can persist long after the rash has come and gone and result in chronic, sometimes lifelong pain.
So this is like reason five hundred why the vaccine is so crucial.
Yeah, So, overall of people who get shingles, I think it's about ten percent people might go on to develop post herpetic neuralgia, but in people over sixty the risk can be as high as forty to fifty percent.
Now, what proportion of people get shingles.
About thirty percent of people will go on to develop shingles.
Okay, if you've been naturally infected, now, if.
You've been now, if you've gotten chicken.
Pox, right, yeah, And is there something like is it sort of like a stress type thing that triggers it or is it kind of question?
Mark such a good question because my next thing I have written is like, the question is how does this virus do this? And I can't really answer that. Aaron Dang, Yeah, you know, this virus, like many other herpes viruses, can have these long latent periods. But exactly how it gets into our nerves in the first place, how it's so good at evating our immune system, what causes it to come back out? And who is going to get shingles and who isn't going to get shingles and when and why?
We don't fully know. Fascinating And like I said earlier, a lot of the reason we don't is because we don't have super great animal models. So there are a number of different sort of theories and ideas out there, but we just don't fully understand these exact mechanisms. Yeah, the good news is that there is treatment. It's the same kind of treatment that we use for Herpie's simplex virus. So it's acyclavier or valley cyclavier. It's a specific drug
for treating these Herpe's viruses. Yeah, it reduces the severity of symptoms and can prevent severe complications like verceilla pneumonia. But it doesn't ridge your body of the virus, just like if you use it to treat herpie simplex right, right, right, So that's the biology erin Ooh, there's a vaccine, but I'm not going to talk about it yet because I've already talked enough. So tell me what's up with this virus? Where did it come from? And what's going on?
I can't wait to try to answer those. We'll take a quick break first. So you always ask where does this pathogen whatever come from? I always want to know. Well, it turns out that we've actually been down this before with our Herpes simplex one and two episode that we did last season, which was aaron that was less than a year ago. Now that was six years ago, I am, I know was before we start a podcasting.
Yeah, But just.
Like with every other episode, I end up forgetting so much of what we talk about, like as soon as the editing is done and the episode is released, and it's just like gone from my brain. Yeah, And so then I like come across things that I've read or I've learned before and I'm like, oh, yeah, that's right, which was absolutely the case for this episode. I hate
to admit, but it's the truth. So maybe you remember from the herpes episode, but in case you don't, the group Herpes very day, which the Verricella zoster virus is part of, is very old, like millions and millions of years old group, and this group of viruses in general tends to be, like you mentioned, super species specific, meaning that a lot of the diversification events where like a new species of herpes virus emerges, those happen right alongside
their host diversifying as well. So that might all be a bit of a review, but I did learn one new,
very fascinating thing. So in the biology section you talked about how Vicel's ostrovirus it's a herpes virus, and like all herpes viruses, they tend to infect nervous tissue or nerves, And it turns out that that characteristic the neurotropism dates back almost five hundred million years what, uh huh, which kind of like, so that's based on how the abalone herpes virus infects nervous tissue, leading to ganglio neritis and eventual necrosis of the nervous tissue and ultimately death.
I'm sorry, avaloni herpes huh. Oh my goodness, I.
Know, I know it is. It's amazing. And I think that that kind of also goes a little bit towards explaining why we, like, why this is so good at evading our immune system.
Yeah, it's been doing it for a literally ever forever.
Yeah, And so that also gives you a sense of just how old these are. And to underline that point, I read that the alpha herpees virus group, which includes herpie simplex one HSV two and Vera Cella's oster virus, as well as other mammalian and avian viruses, that dates back to around one hundred and eighty to two hundred and ten million years ago, stop very old.
Wow.
And so like Herpes simplex one and two viruses, it seems reasonable then to assume that the chicken pox virus Vera Cela's oster virus, I'm gonna use those interchangeably also evolved with humans, like alongside humans, right, And that is what it was thought for a while that the vera cells oster virus originated in Africa, where modern humans evolved. This wasn't just like a passing thought, though, it wasn't just an assumption. This origin story is backed up by
several pieces of evidence. First is that this would follow the trend of like all herpes viruses co evolving or cospeciating with their hosts. Second, the closest relative of varicella's ooster virus is the Simian varocell virus, which infects Old World monkeys. And so the VZV ver cells ooster virus and the Simian varicell virus they share about seventy percent identity,
which is like pretty similar. And it turns out that immunization of monkeys with human vera cells oster virus prevents later infections with simian var cell virus, all right, all right, So that's like kind of I think suggestive, right. And the third piece of evidence is that some genetic dating analyzes put the evolutionary origin of veriicel disoster virus at about one hundred and ten thousand years ago. Although I also saw like older numbers mentioned a few times, like
in the millions of years. In either case, it was before humans started moving out of Africa, which happened around sixty thousand years ago. All right, seems pretty straightforward, right, Yeah, maybe not so much. A recent paper from twenty twenty seems to question this assumption that the Veraceel dixoster virus, like other herpes viruses, evolved with humans in this out
of Africa way. Instead, they present some evidence that places the emergence of ver cell's aster virus in Europe and also like much more recently, but their estimates were a little bit all over the place. So within vari cell's aster virus there are several clades, with virus strains in one clade more so molar to each other than to strains in other clades. Right, And these clades follow some
pretty strong geographic distribution patterns. So, for instance, clade five is found pretty much only in Africa, Clade two is found mostly in Eastern Asia, and so on. And the authors of this paper then compare these different clades and then the strains within them to try to trace, Okay, when did they diverge from one another? And what is like the oldest one, like, what do we think the oldest one was, which led them to conclude that it was actually the clades found in Europe that seemed to
be the oldest. I think there are though, I really want to point out a couple of important caveats to this. One is that they had very few strains from Africa that they included in the analysis, just.
Like not great sampling.
No, it was from a very limited geographic range, but they had tons of North American and European strains included, which of course would have biased those results. And the second thing, and the authors noted this one as well, is that it's totally possible that of all the clades of Verisola's aster virus that are present today, that they did originate in Europe, but that even older clades from Africa just went extinct, which is I think, like really
fascinating to think about. We don't talk a lot about like extinction, accidental extinction of We talk about eradication, but we don't really talk about extinction of pathogens just like happenstance.
Yeah, just happening, which it totally makes sense that it could happen.
It totally does. And I remember when I was doing my PhD. There are like sloth ticks, and there are also like ticks that are very specific to certain animals, and they're you know, like one of the things as well. If this endangered animal goes extinct, then the ticks and everything else, and the sloth moths and everything will go extinct too.
Happened with California condors. Right when they rehabilitated California condors from a very small population they lost I think it was I don't know if it was more than one species of Laos bird laos that was specific to the California condor, but at least one.
Yeah, it's so it's so interesting. But yeah, So going back to Veracell's ooster virus, like there's there's really only I think this kind of just shows how there's really only so much we can tell about viral or bacterial evolution because so much of it is based on, you know, the currently circulating strains and the samples that you collect, right, And in the case of Veracell's oster virus, things might get trickier as the vaccine strain continues to become more
widespread and as recombination events might happen that's kind of a question mark. I don't I don't know, all right, So I don't know if I like gave a satisfactory answer for your where did this come from? Question? There's a lot of murky origins, but I think I can at least try to answer how did we get here? Right, So, regardless of where precisely it came from, the vercella zoster virus is now globally distributed and probably has been so
for a long time, like thousands of years. And this type of widespread distribution is something we've seen for a lot of the typical childhood illnesses or what we would think of as childhood illnesses, things like measles, rubella, et cetera. And in many ways it follows the same epidemic pattern two Right, you get a critical mass of susceptible individuals in a population and then boom, like one exposure, the virus just races through, especially with an r not of nine to ten. Oh my gosh.
Oh mg.
Yeah. But there's one key difference between chicken pox and these other childhood diseases, and that is that, unlike measles, for instance, which it needs a certain population size in order to in order for it not to go extinct, which is why like measles and these other crowd diseases took off after the agricultural revolution, chicken pox doesn't need
that because aaron, because shingle, because shingles. Yes, so, because this virus, like herpies simplex virus one and two, it hangs out in US forever and it can pop up later in life as shingles slash zhauster. It has this amazing survival strategy that allows it to persist in these and even small nomadic populations rather than needing the agricultural revolution to take hold.
Because if we didn't say this already, and if listeners you didn't realize this, shingles rash is absolutely contagious by contact. Yes, so the virus can persist in a population even in decades later. Mmm mm hmm.
But where Varicell's oster virus is like other human herpes viruses in this way, in this sort of like latent
period and then reactivation. In another sense, it's kind of an outlier alongside Herpes simplex two, I guess because of its transmission so many herpes viruses like HSV one cytomegalavirus human herpesvirus six and epstein bar virus is are often or mostly transmitted vertically within the first few years of life, often through saliva transmission, like for instance, premastication of solid
food or through breast milk. But like you said, the Varicell's ooster virus doesn't follow this pattern, and it's you know, it's respiratory transmitted, which I just thought is so fascinating because instead of being vertically transmitted like so many other herpes viruses, this is still a horizontally transmitted pathogen. So from like an unrelated adult with zauster to some kid to then give them chicken pox.
Yeah, and then from that kid to like ten other kids.
Yeah. Yeah. Literally. So with seemingly no minimum population size and this incredibly high transmissibility, it seems like the Veraceella zoster virus would have made itself pretty well known among humans for as long as it's been around.
I mean, I could see it going one of two ways here, Aaron.
Okay, well, what did people say about it. It's kind of like not much, to be honest.
Yeah, that was going to be my fear.
Yeah yeah, it was my fear too. And then it was realized I was like, oh boy, here's the history. So the link between chicken pox and shingles wasn't really known, or at least it wasn't widely suspected until the eight eighteen hundreds, and I'll get to that later. But both
diseases had been recognized long before that. So we get the first mention of chicken pox, or rather veriicella as it was first called, in the fifteen fifties, when an Italian physician named Giovanni Filipo Engracia differentiated it from scarlet fever. The first thorough description, though, came from English physician William Heberden in seventeen eighty five, and at the same time
he distinguished it from smallpox. And I already went through like the etymology so veriicella as this diminutive form of the word variola. But why do we call it chicken pox? I didn't go through that etymology.
Yeah, can you tell me?
I mean, no, one really knows for sure, but there are plenty of guesses. One popular guess is that the bumps resembled chickpeas, and so it was called chicken pox. That was like not very well supported. Yeah, But another like more popular one is that chicken pox kind of resembles smallpox but is way less deadly and horrible, and so it was called chicken pox as like the lesser version, the small fry version of the big bad smallpox.
Like you're just a chicken, yeah, pop.
Yeah, I mean chicken. Chickens are cool, though, Like, I don't know why they get such a like. I wonder why the negative connotation of chicken began.
It's a good question.
It's a good question anyway, let us know if you know. But shingles goes even further back than chicken pox in terms of its name, So Herbie's zaster, the reactivation of the virus was named by Hippocrates from the words for to creep and girdle zoster meaning girdle, and shingles, which is the other name for this reactivation is from the Latin word singulus for belt, where it typically happened.
Yeah, girdle, Yeah, very common.
But I also want to mention that in Norway they had a bit more colorful or evocative description for the rash, the belt of roses from Hell, which I love. I love that. It's great. So I'm not sure exactly when the first like description of shingles was but by the eighteen sixties it's neural qualities were recognized and its focus in the dorsal root ganglion was identified.
Wow, that's impressive. I know, I am.
I was very surprised by that too. It was sort of like, you know, autopsies were still if you remember from our people for episode.
It's just so interesting that they were able to find like I mean, they didn't know virus, right.
No, they didn't know virus, but I think it was like actually physical change, like changes, right.
Yeah, like the inflammation and things that you exactly starting there. So they were like, well, this is obviously the root of the route. Yeah.
Wow, that's pretty that's pretty cool. It is in this period.
Like so from the eighteen sixties on sort of kicked off a growth in the interest of zoster and chicken pox, which you know probably was just sort of alongside the growth of interest in all diseases that appeared to be infectious, right, And so it makes sense then, given this high interest that it was around eighteen seventy five that the transmissibility of chicken pox was first demonstrated through inoculation of human quote volunteers.
Quote quote volunteers.
We all know what vounteers. And then in eighteen ninety two, the link between chicken pox and zoster was first suggested after the Viennese physician Jano's von Bouke noticed that chicken pox tended to pop up in susceptible children in a household where there happened to be a zoster.
Casek Hey, I was wondering how they finally made that connection, because.
Yeah, I mean, it makes sense, but it was still at that point a hypothesis, right, Yeah, And it did gain a bit more support when the next year the antigens for the two diseases were shown to be similar, but it wasn't until the nineteen forties that it was finally shown that chicken pox and zauster were caused by the same virus.
Wow.
So I talk a lot on this podcast about germ theory and how that reshaped our concept of disease, really altering the way that people saw the world and themselves. But what I haven't really given much time to unless I'm forgetting that I've talked about it, which is entirely possible, is where viruses fit into all of this. Because microscopes and microbiology labs in the eighteen hundreds, when germ theory
first really gained traction. Those allowed researchers to grow cultures primarily of like bacteria or fungi and visualize them under either the scope or in the dish, and colonies and parasites, which are another big contributor to disease, were also pretty easily seen. But where does that leave viruses? Very difficult, very difficult, And so there's this whole chunk of diseases measles, smallpox, polio, yellow fever, influenza, at chicken pox, diseases that were super prevalent,
but they still lacked a tangible causative agent. You couldn't see it what was causing it. The infectiousness of these diseases could be demonstrated again mostly through these human quote volunteers, but what exactly was being transmitted remained a mystery for decades after the rise of germ theory, in part because human beings and other animals and plants are riddled with bacteria, and so it was really easy to culture bacteria from someone's sputum who was sick with like influenza and assumed
that the bacteria you cultured were the responsible ones. And also in part because we lacked the technology that would let researchers actually visualize these causative agents of disease, these viruses.
But that didn't stop some people from digging deeper when their proposed bacterial species failed to meet all four of cox postulates, which is what happened in the late eighteen hundreds when a disease was sweeping through tobacco farms in the Netherlands, leaving plants withered with patches of dead and living tissue. The farmers were understandably distraught about this, and so they enlisted the help of a scientist named Adolph Meyer.
And Meyer couldn't find any bacteria or fungi or parasites on the disease plants that weren't on the healthy ones, but he knew there had to be something, so he injected SAP from diseased plants into healthy ones, which then
also grow diseased. But the bacteria he isolated from the SAP wasn't the culprit, and so he grew frustrated and dropped the project, which was then picked up a few years later by a couple of other scientists who decided to grind up the plants and pass them through a filter that would block plant cells and bacteria and fungi and parasites, so like what was even left?
Right?
They then injected that fluid into healthy plants, and voila disease. So they called this contagious living fluid a virus or transmissible filterable agent, which is what the term was for a lot of these viral diseases later.
On filtered transmissible agent.
I love it. I love it. And then there like that is when the field of virology was born, basically what it's It just really was the first time doing this episode where I actually thought, wait a second, like we just assume we lump viruses in with bacteria and parasites and fungi as like you know, human pathogens of disease. But it took a lot longer than these other ones. It's terms of like germ theory.
It's just so fascinating that they thought to do that. I know, you know, they thought, let's let's use a filter that we know is going to keep back all of the plant tissue, all of the bacteria even, and just see what's left. What an idea, I.
Know, I know, it's it's amazing. It is amazing and so you know, at this time, though, like when virology was first started as a field scientist, virologists still lacked the tools to actually see what they were working with, right, But it didn't stop them from writing papers or books about these viral diseases. But in nineteen thirty one, the of the electron microscope by Ernst Ruska and Max Noll
would change all of that. And also, I have to shout out X ray crystallography one of my favorite things still. Go and listen to our radiation episode. That also helped in terms of like somewhat of the structure of viruses or their composition. Okay, But anyway, so Ernst Ruska employed his brother Helmut, who was a medical doctor in his lab and had him look at some various samples under
this new electron microscope. Among these samples was tobacco mosaic virus okay, and vesicle fluid from chicken pox and zoster rashes. And so a Helmut Ruska became the first person to see the varicella zoster virus and to definitively link the two diseases together.
That is so cool.
It's very cool to think about, like the first time seeing that yeah, oh my goodness, and the development of the electron microscope would reveal that viruses in general were not just like particles of protein, which is what had been thought, but that they had complex and varied structures, which was an enormous step forward in virology and molecular biology, and it earned the two inventors the Nobel Prize in nineteen eighty six, like a long time after yeah wow, yeah,
And this Nobel Prize would not be the last one associated with veracell zoster virus, which was very surprised to learn the development of the electron microscope was a pretty incredible new tool for this already rapidly growing field of virology, and other molecular biology techniques like tissue culture made it just a matter of time really before various viruses were isolated and then characterized, and one of these, of course, was the Veracell's oster virus in nineteen fifty two, which
was given its name by the virologist Thomas Weller, who Nobel Prize number two was given a Nobel Prize along with John Enders and Frederick Robbins for their viral discoveries, primarily poliovirus. That's why that name is familiar, yeah, from our vaccines episodes way back in the day. And while the Vicella zoster virus may not have been as like sexy of a thing to research as something like measles or smallpox, it still did attract a fair bit of attention.
A researcher named Edgar Hope Thompson spent fifteen years, so from nineteen forty seven to nineteen sixty two, studying this virus in a small, isolated community and from this amazing data set, I imagine made a ton of really important observations about its incidents, rate, its pathogenesis, the reactivation of latent virus leading to zoster, and the role of the
immune system in infection. And then Nobel Prize number three, our last Nobel Prize in nineteen seventy seven, Gertrude Elion discovered a cyclavier as an effective treatment for herpes viruses, which that Nobel Prize was awarded in nineteen eighty eight.
Wow.
Okay, yeah, so that's like three Nobel Prizes linked in some way to this virus which doesn't have like much of a big oh, and then it caused this pandemic in this epidemic, but still I think it's really cool because it shows just how many different fields of research
are involved in understanding, like gaining and understanding about a disease. Yeah. Absolutely, But we still have one more major development in the history of Arisol's osterrovirus before I turn it back over to you, which is the vaccine.
The vaccine.
In the early nineteen seventies, a Japanese researcher name Michiaki Takahashi isolated a strain of the vari cell's oster virus from a three year old boy and developed a live attenuated vaccine, aka the Oka vaccine, which was after the last name of the boy. Within a few years, Maurice Hillman, if you remember that name from our Vaccines episode.
Maurice, Let's hear it from Maurice.
Let's hear it from Maurice. Maurice and colleagues worked on one in the US based off of this Oka strain, and in nineteen eighty four, the first v CELLA vaccines became commercially available. But this was a pretty controversial vaccine at the start, with many scientists in disagreement about the duration of immunity, whether the virus was attenuated enough, and the modeling showing that there might be an increase in shingles, which Aaron, I know you'll go into.
I'm so excited to talk about it.
But ultimately, study after studies showed that the vaccine was safe and was effective, and so the vaccine was introduced to Korea and Japan in nineteen eighty eight and eventually became available in the US as of nineteen ninety five. And I think it's really cool that we're doing this episode now, twenty six years after it became routine in the US, because it's probably only now that we're getting a true sense of the impact that it's had. Aaron,
tell me about that impact. Where do we stand with chicken pox and shingles today?
I am literally so excited. We'll take a quick break and then talk all about it. Okay, So let's just talk about vaccines, all right, because it turns out, like you kind of mentioned Aarin, there's a lot of nuance to this discussion, and I'm excited about it.
I am too.
So the vaccine that we use against verriceella in the US, like you mentioned Aarin, it was licensed in nineteen ninety five. Since two thousand and six, two thousand and five, two thousand and six. The recommendations in the US are for two doses, the first at age like twelve to fifteen months and the second dose at age four to six.
When they first started giving this, they found it was pretty effective, but there were still a good number of like breakthrough infections, and so that is why about ten years later they added that second dose, and it's much more effective after two doses. Okay, And like you mentioned, AARIN, this vaccine is a live attenuated virus vaccine. That means it's a live, whole real virus. But even though Verceella, like wild type vercella, is benign, this virus is even
more benign. It doesn't cause disease, but it does provide you with the antibodies that protect against wild type Verceella. At this point, like you said, Aarin, we have pretty good long term data that shows that in a lot of populations immunity actually is quite good up to twenty years. So amazing, it's very good immune and that's awesome. But the biggest question.
There's always a butt.
That's the title. The biggest question that I hear from people is if you get the vericella vaccine instead of getting chicken pox as a kid, are you more susceptible to shingles later on in life because you only got the vaccine? And I think that that idea itself is a little bit off base, and I'll talk about why, but I think that this idea came about because of
these math models that you mentioned aarin. So when this veriicella vaccine was first introduced, and even before it was introduced in the US, but after it was shown to be quite effective, there were a lot of math models that suggested that by introducing this vaccine, what would happen is that we would see a huge increase, a very
rapid increase in shingles in adults. Because the prevailing thought is that part of what protects you against the development of shingles is repeat exposure to veriicella in the population.
Oh my gosh, that makes sense, right, right, So it's like a natural booster that, like, you're an adult, you're exposed to kids coming home with chicken.
Pox, and your body's like, hey, I remember that chicken pox because the kid just breathed in your face. And then your body's like, well, I'm going to make sure to just re up my immunity and then you're less likely to get shingles.
But is that? Is that how it works?
So there is data that suggests that people who have frequent or have higher numbers of exposures to varicella are less likely to get shingles, And so that was the data that these math modelers used to predict this increase in shingles. And these math models had such strong data that that's part of the reason that it took quite a long time before this vaccine was introduced into childhood vaccination campaigns, well after it had been shown to be
safe and effective against preventing vericella disease. So, now that this vaccine has been introduced for so long, what has happened with shingles? That's the question, right, Yeah, let's talk about it big picture since the introduction, and I'm focusing on the US because first of all, I have good data. There was a lot of studies published on the US, but also not every country, Like there's not a ton of countries that have had this as part of their
regular childhood vaccine campaign for as long. So anyways, that's why a lot of this data is from the US. Since the introduction of the vaccine in the US, the cases of chicken pox vericella have declined by like ninety five to ninety seven percent. And these declines have even been seen in a adults over the age of twenty
as well as in infants. And what that tells us is that not only have we prevented illness in the people who have been vaccinated, but we have in fact done what these math models predicted, which is decreased the potential for community exposure because infants under age one and anyone over twenty something likely was never vaccinated. So what's
going on with shingles? Well, shingles rates have been increasing, but age specific rates of shingles were increasing before we even started any vaccination campaigns, before any of these vaccines were used widespread in the US.
Well, that is fascinating, isn't it?
And we don't know why since the introduction of these vaccines there haven't been any additional increases in this already increasing incidence. Like, there's no acceleration of shingles since the introduction of the vaccines.
What kind of increase are we talking about?
Oh gosh, I don't have good numbers on it. And the truth is, we just don't have good numbers for shingles overall, because not everyone who gets shingles is going to go to the hospital. It's not necessarily a reportable disease, et cetera, et cetera.
Okay, but it's like a is it a mild slope or like a you know.
Clush, it's a relatively mild slope. I will link to the paper which was published in twenty nineteen called do Varicella vaccination programs change the epidemiology of herpe' sauster? It was a really comprehensive review.
Its great.
So to make things even a little bit more complicated, we don't just have one vaccine. We also have vaccines against shingles.
Yeah, how does that work?
Yeah, so we have two different vaccines against shingles. The first came out in two thousand and six, and this one, like the vericell vaccine, was a live attenuated vaccine. But there's been a newer one that has come out in twenty seventeen, and this one is a recombinant vaccine. So it's just I think, just one of the surface proteins of veriicella, and so it's not a live virus. It doesn't replicate in you. Okay, and that one came out in twenty seventeen. But the roll out in the US
especially has been very slow. There's been a lot of like backlog where people just couldn't get vaccines because there just wasn't enough supply. But in the last like five years or so, there has actually been a slight decline in the incidence of shingles. But we don't know why that is either, and it's probably not just because of these shingles vaccines.
Okay, but I have a question about these vaccines because usually when we talk about vaccines, we're talking about pathogens, and with these two vaccines, we're using disease these names, even though they're both against the same virus ver cells lost virus. Yeah, I don't get it.
I quite honestly also don't get it.
So if you like, for the shingles vaccine, right, if you gave that to someone who has never been exposed to varro cel's lostter virus period, what would happen?
You would protect them against verisella and shingles. As far as I know, I think what you're getting at is, like, what is the real difference between especially the original shingles vaccine that was developed in two thousand and six, or that was licensed in two thousand and six, that was a live attenuated vaccine. What's the difference between that vaccine
and the vericeella vaccine that we give to kids. Yeah, probably not much, right, It's just who do we give it to, Who was it tested on, and who do we give it to and why. The data that we have so far, what they tell us about these new, relatively new vericella vaccines, the ones that we give to kids. Somebody who gets vaccinated with this vericella vaccine is far less likely to develop shingles in their lifetime than someone
who gets chicken pox naturally as a kid. So we've seen this in vaccinated cohorts compared to unvaccinated years previous, that the vercella vaccine strain is less likely to develop this latent infection and reactivate into shingles. So giving someone as a child the vercella vaccine is protective against both chicken pox and shingles. That much we know, and it
does not appear. In the almost thirty years now twenty five plus years that this vaccine has been in use in the un giving this vaccine to children has not increased the incidence of shingles in the adult population, like the math models predicted.
Right, So what are the recommendations like for shingles vaccination right now?
In the US, the newer shingles vaccine has been shown to be a lot more effective than the older one. So the recommendation is that starting at age fifty. At age fifty is when you get it. It's a two dose series and I don't know if there's data on whether or not you need boosters after that. Right now, it's a two dose series starting at age fifty. Yeah,
but that's just in the US. Vaccine uptake for veriicella across the world is pretty spotty, But there are a number of different papers that really highlight just how big of an impact vaccination campaigns child like adding vericella to the childhood vaccination campaigns can really have have on a population, and that is chicken pox and shingles.
Wow, it was interesting.
Good right, I think it's a good episode.
I think so too. Well. Should we wrap up the way we.
Usually do with our sources?
Absolutely, So I'll shout out just a few papers I have more, but by Gross from twenty twelve, Pangaea and the out of Africa model of veri Cela's aster virus evolution and philogeography, and then also by Oaklander from nineteen ninety nine the pathology of shingles head in Campbell's nineteen hundred monograph, and another one Pontremoli at All from twenty twenty possible European origin of circulating Vericela's aster virus strains.
And I have more and I will post more on our website This podcast will kill You dot Com.
Yeah, I mentioned a couple of my sources already. I have a lot more as well as those two papers I already mentioned, one by dol and DaCosta in the American Journal of Bioethics and the other by Harpause that was about the epidemiology of herpexhauster. Check them out on our website This podcast will kill You dot Com.
Thank you again so much for sharing your first hand account with us. We really appreciate it.
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We hope you liked this episode. Well, until next time, wash your hands.
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