Ep 133 Parvoviruses: Who let the dogs (and their viruses) out?

00:00:00
Speaker 1: So it was a Monday in November. I woke up just fiddling like ordinarily unwell. I thought it was a strange slide of cold or flew. I felt a bit feverish, had some aches and pains, but I didn't think too much of it. What I did notice at the time, though, was I had a bit of a strange rash on my lower legs that looked like the tiki. So I went down to see my GP and just said, hey, look, I'm feeling unwell, lovedating the day off work. I've also got these strange little red dots on my legs. Can we just get some bloods and see what's happening? And so that was it. I went and did a blood test. I went home, woke up the next day. On the Tuesday, I was still feeling quite on well, took another day off work. Didn't think too much of it. The little red dots the petik I was still there on my lower legs. That'd spread a little bit more there, getting quite numerous, but I'd already done the bloods with my doctor, so I wasn't too concerned. So I just spent the rest of the day in bed. I then woke up on the Wednesday, thought I was feeling slightly better, but still really really off. The fevers were coming and going, but I'd already taken two days off work.

00:01:06
Speaker 2: I was a nurse.

00:01:07
Speaker 1: I didn't want to leave my workplace shot staffed, so I thought, all right, I'm just going to crack on with it. I'm going to head into work and I'll see what happens. Within ten minutes of driving to work, I was like, I cannot possibly do this. I am so unwell, I'm feverish, I'm sweating, I'm.

00:01:25
Speaker 2: Covered in this rash.

00:01:27
Speaker 1: I ended up turning up to work and going I'm just having like I have to go home, and they said someone else has already gold and sick, like, You've got to stay for a bit until we can get someone to cover for you. So I just sat around in my job, just sort of waiting for another nurse to turn up, which was about five pm at that stage. It was an afternoon shift. So I actually this nurse turned up and I was able to go home. And I was really itchy at that stage, so I took an any histamine and I was laying in bed and I realized I was really, really thirsty. So I went up to go get some water. I made it to the fridge and I just hit the ground and that was that. I just completely passed out. I sort of came to and started calling out for help from my family, and they came downstairs and grabbed me. And my mum at the time had just been diagnosed with high blood pressure. So there was an automatic bloo pressure machine just on the kitchen bench, and I just sort of remember kind of vaguely gesturing towards this blood pressure machine going put it on.

00:02:28
Speaker 3: Put it on.

00:02:29
Speaker 1: So my mom took my blood pressure and at the time I wasn't really able to vocalize or say anything, but my blood pressure was seventy over forty, and I just remember trying to explain to my family, you need to call an ambulance. This will kill me, and they didn't. I remember being carried into bed and I woke up in the morning and I just remember thinking, oh my gosh, I've made it. I'm awake, I'm alive. I honestly didn't expect I was going to wake up. And of course my family aren't health practitioners. They didn't they weren't aware that that was an incredibly dangerous blood pressure to have, and that I might not have made it that night. But thankfully that blood pressure was hopefully any postural, and I ended up being okay, and I woke up. So I went back to my doctor that day because I was starting to get a really stiff pain in my neck and I was a bit light sensitive, and my doctor had warned me to be a bit careful about meningitis. I was in that sort of age or age where it was possible, and I went, oh, yeah, okay, this is a bit of a concern. So I went back to my GP and I said, look, this rush is getting worse. I'm now covered in these partiqui all over my legs, my arms, I've got this strange little red sort of rashes all over my torso as well. I was really flushed. The fever kept coming, my aches and pains were getting much worse. And he looked at my bloods and he goes, oh, Eliza, your platelets are in your boots. You need to go to the hospital. And I said, oh, okay, but now do I have to go right now? He said, look, you need to go as pretty much today. You have to go get some things. When you go home, I expect you to be admitted as an impatient. This isn't looking fantastic, so make sure you get there as soon as you can. And at the time, the closest hospital to me was also the one that I worked at, which is a lot of fun. So they were able to rule out meningitis in the ED, but they were obviously really concerned about the platelets that I had, and they wanted to admit me because they were concerned that if the platelets dropped any further, they be potential for needing a blood transfusion, which was a lot of fun. So I got admitted into a general medical unit. It was one of the units that was used mostly for managing older people and palliative care, and this particular unit I was admitted into overlooked the ward that I worked at, so I could see the comings of go of my fellow coworkers, which was quite amusing. So what happened on that first night was obviously I was quite distressed. I'd never spent a night in a hospital before. I was a young and healthy woman. I was only twenty two, just graduated basically from nursing, so I was a bit startled and concerned that I'd gotten myself into this predicament so quickly, where I'd suddenly declined so far down and I was the one now needing care and having nurses look after me. It was a really startling experience. So that was a Thursday. I got admitted On the Friday. The fevers kept going, the aches and pains were still there. The batiki I just kept spreading every time they wanted to take my blood pressure or it'd end up with these welts under the blood pressure cuff with the batiki I whilch is bloom from all the bruising they were causing. Eventually, the fever started to drop, and on the Saturday they were like, look, your platelets aren't great, but we can see the starting to improve. We can look at maybe letting you go home. So my mum came to pick me up, and then I spiked another fever and they did my bloods again and the platelets had dropped yet again, and the joint aches and pains kept getting worse. So I was then in the hospital for another night. What kept happening was every time the fever would pick up, the joint aches and pains would get worse. And worse, And eventually what had happened was my fingers became quite gnulled. I was unable to use my hands. I developed quite severe pain in my knees, my hips, my shoulders, and I lost my ability to walk very well. So I was needing strong pain medications just to get me up and moving. But what ended up happening was I was even able to attend to my your own sort of personal needs in a safe manner. It was a very humbling experience, I would say, to have that happened to you at such a young age, when you'd been like the week prior, so you know, be the person providing that care, to be the one having to receive it so quickly and rapidly, it was quite a challenging experience. It took a long time for the dienosis of parvovirus to occur. I think it was probably on the Tuesday, So by that time I'd been sick for over a week. I'd been in hospital for four days. When they were finally able to say, oh, we think we found the cause of what's happening for you. You have parvovirus, I did say to them, isn't that what dogs have I get my dog vaccinated for parvovirus? Had I gotten this from an animal? And they said, no, that's not what's happened. Like there's humans. I get parovirus. It's normally seen in kids in daycare. You've just somehow ended up with it. Their fevers kept coming and going. But I was slowly getting better, and eventually I was able to reduce down on the paid medication, and by the Friday, so I'd been in hospital for just over a week, they were able to discharge me home. Finally that all started to clear. But what did happen was they did warm me. I could still get the joint aches and pains for a couple of weeks, but it could last a bit longer. I was unlucky, and they did last a bit longer. I would have days where I would be absolutely well, I could move about just fine, and then suddenly everything would just stop working. I remember going to a Christmas party and I was feeling absolutely fine.

00:08:09
Speaker 2: That day.

00:08:10
Speaker 1: I had a couple drinks. I was dancing for about an hour in a club, and I sat down because I was like needing to get a breath. I just won some water. I sat down and I could not stand back up. My friends had to carry me out of this club and explain to the bounces and the security that no, she's not eeebreated. She has this virus and her joints aren't working. She can't move, and I had to be carried into this Uber driver. This poor Uber driver had to basically carry me into my house and get my mom to meet me at the door and put me into bed because my legs just just stopped working. But for about two months I was in and out of my physio, having to relearn basically how to lift my arm over my head, how to take a normal stride because my pace would suddenly start getting shuffling, how to open and close my hand well enough, because every now and then hands would just seize and my fingers wouldn't cooperate. It took about two months all up, but in the end I was completely fine. The the tiki or resolved, the rash resolved, the joint akes and pains finally left. It did leave a bit of a lasting impact that now every time I seem to get a virus, I do respond with that sort of viral arthralgia. It's just part of it now, So I know, whenever I get you a colder flu or even COVID. The first time I had COVID, it did kick in, but it's never that intense anymore. It's always pretty mild, and it's something that can easily be managed with neurofin. But yeah, it was quite a fun experience.

00:10:25
Speaker 2: Oh my gosh. I first of all, I had just had no idea about parvo viruses. But also, what a wild story, what a wild ride. Terrifying, terrifying, honestly, Yeah, yeah, thank you so much for sharing your story with us.

00:10:42
Speaker 3: Yeah, my goodness, thank you.

00:10:45
Speaker 2: Hi.

00:10:45
Speaker 3: I'm Aaron Welsh and I'm Erin Allman Updike.

00:10:48
Speaker 2: And this is this podcast will Kill.

00:10:50
Speaker 3: You Today we're talking about parvo.

00:10:52
Speaker 2: Yeah, and all the different kinds. Well a couple of the many different kinds. We will mention the many different kinds and focus on a few yep, yep, yep, but there are so many more than I expected.

00:11:08
Speaker 3: Yeah, I mean part of the course this podcast will kill you.

00:11:11
Speaker 2: Come on, I know, I know, why are we surprised by anything at this point?

00:11:16
Speaker 3: We can't be, We can't be. But it's gonna be an interesting episode. I am excited to learn about the history of this virus that I know nothing about.

00:11:25
Speaker 2: I'm excited to learn about the biology of this virus I know nothing about.

00:11:29
Speaker 3: It's really interesting, so I'm excited to tell you about it.

00:11:31
Speaker 2: And I'm also really excited that we get to talk with another expert. We are bringing on later in the episode, a very special guest, doctor Steph Horgan Smith, who is a veterinarian, to answer some of your burning questions about parvoviruses and dogs.

00:11:51
Speaker 3: Yeah. I'm really excited about that because I am not a vet.

00:11:57
Speaker 2: Nor am I but I have a dog, and so I'm interested. Even if I didn't have a dog, I'd still be interested. This is a mess. Let's just get to the quarantine.

00:12:08
Speaker 3: It's Quarantini time. Yes shall we?

00:12:11
Speaker 2: Yes, we shall? What are we drinking this week?

00:12:14
Speaker 3: We're drinking Sick as a Dog.

00:12:16
Speaker 2: Yeah, I mean so named because yeah, parvo infects a bunch of different animals, but it is terrifying and deadly in dogs, as we'll learn more about. But before we do that, what is in Sick as a Dog?

00:12:30
Speaker 3: It is tequila and lime juice and ginger syrup and it's quite refreshing.

00:12:36
Speaker 2: Yeah, simple and delicious, can't go it could be better.

00:12:39
Speaker 3: We'll post the full recipe for that quarantini as well as the non alcoholic plusy burrita on our website, this podcast okity dot com, and on our social media.

00:12:48
Speaker 2: On our website you can find all sorts of cool things. Let me just pull it up to confirm. Confirm it's still there. It's still it's still functional. Find the sources for each of every one of our episodes. You can find transcripts. You can find a submit your first hand account form, which to all the people that have done that, thank you, it's been amazing. You can find things like our bookshop dot org affiliate account, our Goodreads list. Merch. There's amazing merch. We have excellent merch. You can find links to music by Bloodmobile, Patreon. You know, there's a lot of such, so much there. Yeah, can we get to the actual content.

00:13:30
Speaker 3: Now, can we?

00:13:31
Speaker 2: Okay?

00:13:31
Speaker 3: Was this long enough intro?

00:13:33
Speaker 2: Yeah?

00:13:33
Speaker 3: I think it's okay. Let's take a quick break and then talk about the biology of parvoviruses. I want to talk very briefly about parvoviruses as a general group of viruses, because I think that understanding some of their common characteristics will be informative to understand how variable the presentation can be when we talk about parvaviruses in different animals with our vet later on, but we'll focus for this biology section on human parvovirus aka parvovirus BE nineteen, and then I'll briefly mention some of the other parvaviruses like K nine parvavirus and things like that. But to understand parvaviruses in general, At first, parvaviruses are DNA viruses. They happen to be really tiny DNA viruses, which I just find cute. And as always, we're not talking about one virus. The family Parvovirida includes a number of different genera of viruses that infect a huge range of animals and insects and all kinds of things. And as a very broad general rule, one thing to know about parvoviruses is that they tend to infect preferentially rapidly dividing cells. That is a key characteristic of parvaviruses, and it makes sense then why they infect the cells that they do and therefore cause the diseases that they cause. Very interesting, Yeah, they can infect a wide variety of cells, when you look across all the parvaviruses, and different parvaviruses are more specific, they have a more specific tropism for individual types of cells. But across the board it's rapidly dividing cells.

00:15:49
Speaker 4: You know.

00:15:49
Speaker 2: I find that so interesting to think about, like the pros and cons of infecting rapidly dividing cells versus not rapid dividing cells. But I know, it's not like the viruses are not all sat there in a boardroom being like, all right, put that one on the pros list. But you know, something like rabies that infects nerve cells, nerve cells, Like yeah, what yeah, yeah, it is really anymore and go with that thought.

00:16:18
Speaker 3: But it is really interesting, especially because parvavirus is killing and destroying cells' that's what they do, these parvaviruses. So they're infecting cells and then they're absolutely killing and destroying them. So it makes sense then that for them to be able to have a fresh supply of cells to invade that they are invading rapidly dividing cells. Again, they didn't make that as a decision, but they kind of go together well with the cell types that they infect A lot.

00:16:48
Speaker 2: I wonder too, if it has anything to do with like the host immune system and how rapidly they're detected, Like how do you outrun the immune system? Do you do the snake and hide approach or do you go in, you know and go ham? Yeah, go ham.

00:17:06
Speaker 3: So that is what they do. In general. Canine parvovirus and feline panlucopenia virus and a number of others are in the genus proto parvovirus as is like poor sine parvovirus. A lot of kind of the famous parvaviruses. One that kept coming up in research that I don't know if most people have heard of, but it literally kept coming up was the allucion mink virus disease virus. Yeah, of course, the illusion minks. This is in a whole different genera of parvovirus called the amdo parvovirus. There's a few other genera of parvoviruses. One of which I will mention because I'll talk about it at the very end, is called the dependo parvovirus genus.

00:17:53
Speaker 2: I'm so excited that you're talking about these.

00:17:55
Speaker 3: Yeah, these are viruses that depend on other viruses. I didn't do that pun but somebody did. These viruses depend on the presence of other viruses to be able to infect cells. Will get to it, I promise. And then there's human parvovirus aka parvovirus B nineteen, and this is a member of the genera called erythrovirus genus. The reason that it got the name erythrovirus is because this virus, parvavirus B nineteen and a few other related viruses that infect primates have very strong tropism, aka they preferentially infect erythroid precursor cells. What does that mean? Our erythrocytes are our red blood cells. So parvovirus B nineteen is infecting and replicating in preferentially and close to exclusively, though not entirely exclusively, in the cells in our bone marrow that become red blood cells, like our baby red blood cells. These are cells that are very rapidly dividing, right, because we make new red blood cells all the time. So the way I'm going to structure this is, let's go over the nitty gritty path of physiology of what is happening in our human bodies when we're exposed to parvo BE nineteen, and then how that effect can manifest in what turns out to be a really wide spectrum of illness, and then I'll briefly touch at the end on some of the other animal parvoviruses. Cool, So BE nineteen can we just call it that?

00:19:37
Speaker 1: Yeah?

00:19:38
Speaker 2: Sure?

00:19:38
Speaker 4: Not?

00:19:38
Speaker 3: Okay, great, it's our podcast. We can do whatever we want.

00:19:42
Speaker 2: So why we do this?

00:19:45
Speaker 3: So BE nineteen is a human specific virus. That's first off, it's transmitted in respiratory droplets primarily, though, since this is a virus that's in red blood cells and their precursors, it can also be transmitted in blood products, and it can cross the placenta during pregnancy and infect a developing fetus, which is an important part of the parvavirus story. But once this virus makes it into our body, it hones in really quickly and specifically on our bone marrow, since it's really specific to these precursor red blood cells. And the reason why this is the cell that it infects is because the receptor that it binds too to be able to enter our celves happens to be found on our erythroid precursor cells is called blood antigen P. Anyways, so once it's in our cells, over the course of a few days to a few weeks, this virus is just replicating, replicating, replicating, and as it does this, it induces a complex series of changes within the cell within these erythroblast precursor cells that leads to DNA damage a rest of the cell cycle, so they stop dividing and death of these cells. And during this time, while this virus is replicating in our blood cells, if you were to check what's called a reticulous site count, this is some really nerdy fun stuff. Reticulous sites are what we call like immature red blood cells when we look at them on a blood smear, okay, and their measurement is something that we check in the case of things like anemia. Right, if a person doesn't have enough red blood cells, then they should have an increase in this reticulous site count, because that means their body is going into overdrive to make more red blood cells. They're like making more babies to eventually make more adults.

00:21:42
Speaker 2: Okay, what is the timeline between reticulous site and red blood cell?

00:21:46
Speaker 3: That's a great question. The total life span of a red blood cell is usually about one hundred and twenty days, but I don't actually remember how many days it takes to become a mature red blood cell. It's probably saying I should have googled because it's googleable.

00:22:00
Speaker 2: And what happens if you have a low reticulous site count, Like, what does that mean?

00:22:04
Speaker 3: Well, great question, because that's what we see in parvovirus. Oh, the reticulous site count plant. It really wasn't, but that's what we see because parvavirus is infecting these reticulous sites and are erythroblasts. The reticulous site count if you were to check it in someone in an early part of their parvavirus disease course, it drops to almost zero. This virus is attacking and killing off all of these reticulous sites very specifically. So because of that, you also would then see very often a drop in our hemoglobin. And the hemoglobin is the way that we measure how many red blood cells we have. It's not a direct measurement, but it's the way that we see do you have enough red blood cells. Usually this is a pretty small drop by say about one point, which is not a lot for most people, and most of the time for most people with this infection, this is transient. This virus is killing off a whole bunch of our reticulous sites all at once. But then our body responds by very quickly making neutralizing annabodies that are highly effective. We neutralize this infection, kick this virus out, and then our reticulous site count will bounce back, and then eventually so will our hemoglobin.

00:23:19
Speaker 2: Okay, but if you said I know that, you're poised to say, but I am.

00:23:23
Speaker 3: You can see the bee on my lips.

00:23:26
Speaker 2: I can see it, and I'm going to preempt it by asking a question, which is so you said that the life span of a red blood cells like one hundred and twenty days, and so how what is the lag time then between when this parvovirus, when B nineteen starts killing off those reticulous sites, and then when symptoms are being felt.

00:23:49
Speaker 3: Ooh, erin, I just can't wait to tell you. It's so much more detailed than that. Okay, Okay, now I'll let you continue with your butt. Yes, I uh by, the just googled it just so that we have a little bit more information.

00:24:02
Speaker 2: Okay.

00:24:03
Speaker 3: According to the Google, it's like two days from when reticulous sites are first sent out of the bone marrow into our bloodstream to then become red blood cells. But there is also a maturation process within the within our bone marrow itself.

00:24:19
Speaker 2: Okay, because this is all happening within the bone marrow and not in like our circulatory system exactly exactly.

00:24:25
Speaker 3: So these are this virus is infecting the cells that are precursors in our bone marrow and causing them to not be able to release any more of those reticulous sites. So then the red blood cells that are mature already in our body are just doing their normal death process, you know, they die in waves. And then that's why the reticulous sites aren't there for a time period to be able to make up for the natural course of our red blood cells, so that hemoglobin drops and then once we can bounce back because we've fought off this infection, then no problem. Okay, Oh, but sometimes it doesn't happen that way. So that is kind of what is happening in our body. And now that we understand that, we can talk about what it looks like when we have symptoms of this disease and how wide of arrange these symptoms can present us. Yeah, there are so many different ways that this can present that there are a lot of different names for the syndromes that are caused by B nineteen. The first is erythema infectiosome. I think is how you say that? Or fifth disease? Which are you going to get into this in the history arin I sure, am okay, good because I have like a sentence, But I was like, maybe L won't say it out loud.

00:25:49
Speaker 2: I mean I have like two sentences.

00:25:51
Speaker 3: Okay, well more than me. So Arithema infectiosome or fifth disease is the classic little cure disease that's caused by parvovirus B nineteen. The way that it tends to look is this early on, like in that early phase of viral infection and replication, which takes maybe a few days to a week after exposure. Now we're talking timeline. Most kids that get infected with parvo will have a mild, very nonspecific illness. You may or may not even notice that they're sick. They'll have some fevers maybe already knows, maybe not headaches, maybe some nausea, and that's it. This is the timeframe in which people are viremic. So this is the timeframe when they're just feeling kind of cruddy. That they are getting their friends and family sick. And by the way, if you'd like to ask, how infectious is this how contagious is this disease?

00:26:50
Speaker 2: Yeah, I'd love to ask that I.

00:26:51
Speaker 3: Couldn't find like an r not reliably. But the attack rates, especially like among household contacts, are very high. So up to fifty percent of kids among exposed household contacts who haven't had PARVOB nineteen will get PARVOB nineteen, and twenty to thirty percent of adults in like a household or a classroom setting if they haven't yet been exposed.

00:27:16
Speaker 2: Okay, and so having yet been exposed, so there is pretty good Like how durable is the immunity?

00:27:23
Speaker 3: Yeah, great question. As far as I can tell, quite durable. And most of the studies of like the epidemiology really just looks at like zero conversion, where like by old age, eighty five percent of people have been exposed and have antibodies to PARVOB nineteen.

00:27:39
Speaker 2: So what's the rate of asymptomatic versus symptomatic?

00:27:42
Speaker 1: Then?

00:27:42
Speaker 3: Excellent question. I didn't see this exact. I saw one paper that said about twenty percent of people won't have any symptoms whatsoever. But I think that it's probably even more variable than that because of especially how different the disease can present in children versus as adults.

00:28:01
Speaker 2: Okay, if that makes sense, Yeah, and we'll get into it. But at least at least.

00:28:07
Speaker 3: Twenty percent and possibly more percent of the time people might be entirely asymptomatic, at least from my reading. Great question, but that's just the initial Like I am feeling a little bit creddy from a nonspecific illness, and I'm exposing all of my friends. Then kids get better, and then about two weeks after exposure, at least after this initial infection, will come a rash. And the rash is on the face. It's this red splotchiness on the cheeks that usually doesn't extend down to the mouth. So what it looks like is like you got slapped on the cheek and your cheek turned red. It's literally called a slapped cheek rash. Yep, And it really does look like that because it's so isolated to the cheek and just this kind of red splosh on the cheeks, and then over the course of like one to four days thereafter, it can extend down the body, down the you know, the arms and the trunk and things. And this rash as it moves looks like a lot of viral rashes. It's like these pink little splotches. They're not usually raised. Sometimes they can be kind of lacy looking. And this rash, especially the one that kind of extends down the body, it can kind of come and go, So it can be there for a day or so and then go away for a few days and then come back, maybe under a time of stress, and then eventually over a few weeks or so, you might not see the rash anymore at all.

00:29:43
Speaker 2: All right, why why why does it come and go? And why does it start on your cheeks? Great question?

00:29:51
Speaker 3: I don't know. A's always. But what's interesting is that a all of these symptoms that we associate with this specific syndrome arithema, infectiosume or fifth disease, these are immunologically mediated. This is our body's response post viral Like if you were to check a viral load at this point, most of the time you can't find one in kids with this. So this is all from our bodies and bodies and immune response causing this rash and these rashes that kind of come and go.

00:30:31
Speaker 2: Wow, so it's coming in and just like letting somebody spread everything with these very generic mild symptoms and very okay.

00:30:39
Speaker 3: Exactly isn't that fascinating? Now? I think we've talked about doing like a whole thing on rashes, because I do think it's very interesting. There's a lot of rashes that we see associated with viral syndromes, and they usually are this immune mediated kind of rash. And I don't understand why some viruses tend to cause a more specific rash than other viruses, but still in general, there's like a look to these viral rashes, and this is one of those viruses that causes one of these viral rashes with the addition of the specific slapped cheekness of it. Okay, yeah right, yeah, So no, that's in kids and in adults. As per usual, when adults get a quote childhood illness, it tends to be a bit more severe, and in the case of parvovirus, this comes with joint pain. So adults may still have that initial nonspecific illness or they may not, but the part of parvovirus that's more severe in adults tends to be joint pains and inflammation. You can see this in kids as well, but almost always, if an adult gets PARVOB nineteen, you're going to have some degree of arthritis and arthriat as like the common presenting feature like this. Why again, it's immune mediated. Again, So is it just the difference between a child's immune system and an adult's immune system, which are totally different.

00:32:14
Speaker 2: Yeah, but what are those differences?

00:32:16
Speaker 3: Oh that we could do a whole episode on. Okay, Yeah, but in adults, it's this bilateral arthralgia. It can be the hands, it could be the knees, the ankles, the wrists, really anywhere. And sometimes this can really mimic rheumatoid arthritis. And there was some thought back when that parvo B nineteen might be one of the kind of triggers for something like rheumatoid arthritis. There's not really a lot of data for that from what I can tell, okay, but the symptoms can be really similar. And what's really tough is that for many people, these joint pains resolve over time, but time could mean weeks or months or even years. So the mechanism here is still immunologic. It's our bodies making these antibodies and then these antibodies getting deposited in our joints and causing joint pain and inflammation, very similar to a lot of autoimmune disorders that cause arthritis and arthrogias. Okay, isn't that interesting? That is fascinating. So that is all the mild cases of parvo be nineteen right, But as we heard in our first hand account, parvo is not always a mild illness. It can also cause very severe disease, both acutely and chronically. So let's get into it. Because this is a virus infecting and destroying remember our red blood cell precursors. In most people, it results in a transient reduction in humanemoglobin. Most of the time, you probably would never even see that because people aren't getting sick enough to have their hemoglobin measured multiple times over the course of this illness. However, in some people, especially in people who have any kind of baseline either decrease in their red blood cell production capacity or a baseline of a higher than typical red blood cell destruction, this transient small hemoglobin drop can actually result in profound anemia in what's called a transient aplastic crisis or aplastic anemia, and by profound, I mean that this can cause a hemoglobin drop that is so low that it can be lethal. And if this happens, the symptoms of this disease are vastly different. People are incredibly weak, they're lethargic, they have very significant pallor so, their skin is incredibly pale, even if they have dark skin, their mucous membranes, the palms of their hands, these things are just like without color because they have no hemoglobin. And if you checked their hemoglobin, they would be incredibly low. And I don't know exactly how low, but I do know that I have seen people present with very very low hemoglobins in other contexts, and the hematology specialists are always thinking, could this be from parvovirus? Be nineteen? So a normal hemoglobin can range from like twelve to sixteen, depending on depending on the situation. And so we're talking about hemoglobins less than seven six five incredibly low. WHOA yeah, Okay, So a big question is like, what are the conditions that put you highest risk of this?

00:36:01
Speaker 2: Yeah?

00:36:02
Speaker 3: And the list can be really long. Things that result in a decrease in red blood cell production are things as simple as iron deficiency, anemia, which many people who menstraight have some degree of iron deficiency anemia. It can be genetic things like thallacemia's and then we also can see things that cause an increase in red blood cell destruction, like hereditary spherrocytosis, which is when your red blood cells have a slightly different shape and so as they pass through the spleen they're more likely to get destroyed and sheared, or not having a spleen altogether, or sickle cell disease, or chronic hemolytic anemia. There's a whole lot of different things that cause an increase in the turnover of red blood cells. So instead of existing for one hundred and twenty days, their lifespan is shorter, and therefore this drop in hemoglobin is more significant even if it's short. That makes sense, yeah, it does.

00:36:59
Speaker 2: There are so many different ways, yeah, for this to have an impact, right.

00:37:04
Speaker 3: The good news is that even in this case, this tends to be a transient phenomenon, so if it is identified, it can be treated with supportive care red blood cell transfusions, fluids, supportive care in general. However, even though it's self limited and eventually most of the time in this aplastic crisis case, people's immune system will mount an antibody response and will fight off this infection, and their red blood cell count will be able to come back. It can be so severe that it can be fatal, because this significant anemia can result in heart failure, it can result in strokes. It can really be significant. So it's quite scary.

00:37:55
Speaker 2: What would some of the signs and symptoms be that somebody would experience when like things are getting really bad that would prompt them to go to the hospital for instance.

00:38:07
Speaker 3: Yeah, it's a great question. Really, it would be things like fatigue, weakness, lethargy. There's nothing that looks particularly infectious per se, So it's not necessarily like fevers, chills, that kind of a thing. It's more about the signs of anemia, so poller, fatigue, lethargy, those kinds of things.

00:38:28
Speaker 2: And but by this time, again, the virus is no longer there, or is it could be.

00:38:35
Speaker 3: It's a good question. I saw mixed answers to that in some of the literature. But I think that given that this is the timeframe in which the virus is still replicating and destroying your red blood cells, you would likely still see some degree of viremia. Okay, yeah, just depends on when in that course of time you get super sick.

00:38:55
Speaker 2: Mm hmm.

00:38:56
Speaker 3: Yeah. So that's one of the severe manifestations. There's more a few more. Parvovirus BE nineteen is also one of the torch infections, and these are infections that are considered incredibly severe in pregnancy that lead to severe fetal infection and potentially pregnancy loss or significant congenital manifestations in the fetus. So during pregnancy, especially in the second trimester ish, so like eleven to twenty three weeks, a primary infection, so a first time infection with parvovirus B nineteen, can cross the placenta and infect the fetus. And in a fetus it does a very similar thing that it does in a grown person or a child, and that is that it can cause severe anemia. It can cause this transient aplastic crisis. In the case of the fetus, it's by this virus infecting the fetal liver because that is the site of red blood cell production for a lot of development in the fet But as you can imagine, severe anemia in a fetus can be incredibly dangerous. The anemia can lead to a form of high output heart failure. Because our red blood cells are carrying oxygen with less oxygen delivery capacity in the fetus, that fetus's heart has to start pumping overtime in an effort to increase blood flow enough to make up the difference. Right, like your capacity's down, there's not as many trains running, so they're running the trains faster, but eventually the conductors the heart just can't keep up with running trains at this pace, and so it burns out and it can't pump, and that leads to heart failure. Heart failure leads to blood backing up in the vessels because it's not getting pumped out, and this leads to an increase in pressure in the blood vessels, which leads to leaky blood vessels, which causes edema. And edema in a fetus that gets like this is called hydrops fetalus. It's incredibly serious and it is very often fatal. It's a sign of really severe disease. Parvovirus is by no means the only thing that can cause hydrops fetalus, but it is one of them, and that is kind of the mechanism by which it happens. In this case, parvovirus BE nineteen in a fetus also seems to sometimes infect their myocytes, the heart cells themselves, which is especially fascinating since normally this is only infecting rapidly dividing cells, but apparently the viral receptors in the red blood cells are also on fetal heart cells, which is just interesting. And this can cause a myocytis or an inflammation in the fetal heart and contribute to that development of heart failure.

00:41:53
Speaker 2: Okay, that's awful.

00:41:55
Speaker 3: It's awful. It's really scary, and so a parvovirus B nineteen infection is one of those that is kind of scary in pregnancy. I will say that it is still very rare, and it's rare not only because it's estimated that about fifty percent of people by the time that they get pregnant are still able to get infected. Essentially, like fifty percent of people are already immune to parvo. But even in those fifty percent of people, if an infection occurs during pregnancy, most sources that I read estimated that it's only about five percent of the time that there's any abnormality as a result, even though it can be up to thirty percent of the time that the fetus does end up getting infected, so kind of just like with parvovirus in kids or adults, most of the time it doesn't cause this severe outcome, but some of the times it can.

00:42:48
Speaker 2: Okay. I have a few questions. Okay, you said torch, what does that stand for?

00:42:54
Speaker 3: So torch stands for toxoplasma, the O is other which in include syphilis, parvovirus, vericella, and listeria okay, and then rubella is the R cytomegalovirus CMV is the C and then the H is herpie simplex virus.

00:43:13
Speaker 2: Okay, torch.

00:43:14
Speaker 3: So these are all viruses that can cross the placenta and then result in pretty severe disease in the fetus. We've covered quite a lot of these on the podcast already we have okay.

00:43:24
Speaker 2: Another question was sort of the timeline of infection in these severe cases where heart failure does happen. What is the timeline of that? And follow up question is it is there any treatment?

00:43:38
Speaker 3: Excellent question. So the timeline of it, I actually don't fully know in terms of like, once the fetus is infected, what's the timeline to development of severe disease. I don't know, Okay. It is infection in the second trimester of pregnancy that we know is highest risk because that's when the fetus is like making a lot of these red blood cells and things like that, whereas later on they have enough of a reserve that they might be less affected by an infection, and earlier than that they don't have as much of a circular student system yet kind of a thing. But there is treatment that can be done, which is great. Okay, It's definitely not something that is available everywhere, but things like intrauterine transfusions are things that can be done, especially if you identify an infection, and then what you do is you serially monitor with ultrasound to see how the fetus is doing and if there's any evidence of infection, and then you would be able to treat it with things like transfusions and it can significantly reduce mortality in the case of the development of hy drops. Okay, yeah, is.

00:44:48
Speaker 2: There a vaccine for humans?

00:44:52
Speaker 3: No? Okay, yep, that would so easy answer. Unfortunately.

00:44:57
Speaker 2: Yeah.

00:44:58
Speaker 3: There's one more thing that I want to mention, and that is what's called chronic red cell aplasia, and this is very similar to transient a plastic crisis, except that, like the name implies, it's chronic. And so in individuals that already have a severe bone marrow deficiency for one reason or another, like they already have leukemia, or they've had an organ transplant so they're on immunosuppressives, or they're undergoing cancer treatment. In these cases, infection with parvob nineteen can cause not a transient, but a chronic anemia that can be pretty profound but can improve if, like, for example, the chemotherapy is stopped, then things can kind of bounce back. But that's just kind of one last thing. And in this case, what's interesting is that it does tend to result in a chronic viremia where this virus is still present, you can still detect it, and it's still causing this damage. Okay, yeah, fascinating. Fascinating is right. So that is kind of most of all of the manifestations of parvo B nineteen in humans.

00:46:13
Speaker 2: There's a lot.

00:46:14
Speaker 3: That's a lot, and that's that's just the human parvovirus.

00:46:20
Speaker 2: Right, that's just one virus. It's one virus, one host.

00:46:24
Speaker 3: There's a few like subgroups of it nowadays, but that's parvob nineteen. But this is a huge group of viruses that infect a huge variety of mammals, and a lot of pet owners are probably even more familiar with canine parvovirus or with feline pan lucopenia virus than they are or were with human PARVOB nineteen. Now, just like with human parvovirus, these animal parvoviruses are infecting rapidly dividing cells, but in most cases they happen to have tropisms that are more specific for the limit m foid tissue in the intestinal crypt cells. So this is rapidly dividing lymph tissue in the intestines of these animals. And because of that, there's some pretty notable differences in the disease course and the mode of transmission when it comes to these animal viruses compared to human parvoviruses. So animal parvoviruses tend to be transmitted fecal oral because these viruses are infecting the intestinal cells rather than bone marrow cells and then being transmitted in our respiratory secretions and as our lovely vet we'll talk more about later, the symptoms of the disease tend to be more gastintestinal, but there's a lot more to it than just that, and we'll talk about that later on. But Aarin, now, can you tell me where the heck this virus came from and how we got to this point?

00:47:56
Speaker 2: Yeah? I mean kinda or these recent I guess right, all of them. We'll see what exactly I can tell you right after this break. I want to start off the history section with possibly the cringiest opener yet, but I couldn't help myself.

00:48:39
Speaker 3: I can't wait.

00:48:41
Speaker 2: The history of parvoviruses begins not with a bang, not even with a whimper, but rather a squeak. That's hilarious, Aaron, I just I don't know. I had to. I wrote it down, and I was like should I should I not?

00:49:00
Speaker 3: Wait? Then here's my question, Yeah, did you write that quote or did you find that quote?

00:49:06
Speaker 2: I mean, I like the whole not with a bang, yeah, wimp, but with a whimper or whatever. Yeah, that's old. But like I added the squeak part, Oh, I love it. Okay, I loved it, But I said squeak. I say squeak because the first parvo virus described, which was isolated in nineteen fifty nine came from a rat.

00:49:32
Speaker 3: It's nerdier than you would think.

00:49:34
Speaker 2: Right right, I mean I don't know how to do it any other way.

00:49:38
Speaker 3: Oh, I wouldn't want it any other way.

00:49:41
Speaker 2: It's discoverers Killim and Olivier named it fittingly rat virus.

00:49:47
Speaker 3: Okay, but like, why imagine anything else?

00:49:51
Speaker 2: You imagine being a virologist during this time and being able to name something rat virus? What a time?

00:50:00
Speaker 3: A lot of time wow.

00:50:03
Speaker 2: Later, presumably because people quickly realized that there wasn't just one rat virus, it became known as kill em rat virus. Killim and Olivier found the virus while looking for a tumor inducing virus in rats, and what they found was rat virus, which did not appear to make the rats sick or cause tumors, or seem to be able to infect other species. But the researchers still did find the virus interesting enough to write up, and over the next ten or so years, their paper describing this rat virus would be referenced in more papers describing similar viruses also newly discovered, first primarily detected in like immuna suppressed lab rodents or in cell culture lines with a very wide range of pathogenesis, from asymptomatic infections to neonatal death and rodents, for instance, and later they began to find these viruses from non lab settings and non lab mammals like the greater wax moth, and subsequently a whole bunch more arthropod species and at least one crustacean. For the most part, these small, seemingly related viruses didn't make too much of a stir in the virology community until the mid nineteen sixties. Epidemics of enteritis, pan leucopenia, and congenital cerebellar ataxia had been popping up in domestic cats for decades, and around nineteen sixty five nineteen sixty six researchers identify the causative virus as being similar to these small rodent and arthropod viruses that they had found, and they named it feline pan leucopenia virus, which I think was also the first real indication that this group of viruses might have a substantial effect on their hosts in like natural settings. But what was this group? It still needed a name. I mean, we know that what it is now, but I'll tell you how we got there. So Carlos Brelowski proposed the name parvovirus rati or RATI for a Latin naming system for rat virus parvo, from the Latin parvs for small, and he suggested that this group of small DNA viruses be designated the parvaviruses very small. You know, seems reasonable, But somehow this seemingly innocuous reasonable suggestion got a whole lot of people upset. Like I saw the phrase quote somewhat rancorous debate used to describe it.

00:52:40
Speaker 3: Interesting.

00:52:41
Speaker 2: Yeah, and so on one side was the pro parvovirus and the other side was pro picodna virus kind of like in parallel with pocornaviruses small RNA viruses, but then like you have coornaviruses and codnaviruses, like all you have to do is have one type of D for the R and then so picodna sounds silly, I mean, I know, but I mean if it had been that, we wouldn't think it sounded silly.

00:53:15
Speaker 3: Today I still think it sounds silly. I'm going to stand by that. I'm want to die on that hill.

00:53:23
Speaker 2: Well, in any case, to quote from a paper, reason and clarity prevailed and the name parvovirus was adopted.

00:53:32
Speaker 3: I like that.

00:53:35
Speaker 2: Throughout the rest of the nineteen sixties and into the nineteen seventies, the parvovirus family continued to grow one by one, with the first human parvoviruses ad novirus associated viruses or ad NO associated viruses akaaa v's so called because they're dependent upon adnoviruses for their own replication. The dependoviruses, the dependoviruses. These were discovered in the mid nineteen sixties. Oh okay, but and I know you'll talk more about these later, and I'm really excited for that These were considered are considered nonpathogenic question mark. We'll see if that stands, I guess, but a human pathogenic parvovirus was just around the corner waiting to be identified. In nineteen seventy five, researchers were evaluating a newly developed test that was used to detect hepatitis B virus in donor serum, and they found a different antigen that had like precipitated with this test. And this was not definitely not the hepatitis B antigen, and it more closely resembled a parvovirus than a hepatitis virus. So they wrote it up a new human parvovirus that seemed to infect a not small proportion of samples that they tested, but whose pathogenicity was totally unknown. And I feel like, Okay, this it does happen from time to time, and I know we've talked about it on the podcast before, but it does seem uncommon for a pathogen to be discovered before not discovered, but like the pathogen was discovered not in association with a particular disease.

00:55:14
Speaker 3: Right, like completely independently.

00:55:15
Speaker 2: Yeah.

00:55:16
Speaker 3: Yeah, I don't think that happens very often, at least from what we've talked about on the podcast, but it is really interesting and I feel like in this case kind of makes sense.

00:55:29
Speaker 2: Yes, yeah for sure.

00:55:31
Speaker 3: Yeah.

00:55:32
Speaker 2: So this virus would become known as B nineteen, which the name allegedly comes from the fact that the virus was found in specimen nineteen of Panel.

00:55:42
Speaker 3: B so boring logical.

00:55:49
Speaker 2: Yeah, Now that part of a virus B nineteen was identified, all that was left to do is find out, like, did it make people sick? What did it make people sick with? Yeah, so, Aaron, you mentioned a plastic crisis in people with sickocelenemia and many other types of blood disorders. Instances of aplastic crisis often happen in families concurrently and are often preceded by symptoms of viral infection, and so for decades physicians had thought, Okay, maybe it's triggered by some sort of infectious agent, but we just don't know what it is. Then in the early nineteen eighties, researchers found parvovirus B nineteen or antibodies to parvovirus B nineteen in the serum of people with syco celenemia who were experiencing a plastic crisis, and the evidence that this virus was a principal cause of a plastic crisis as well as hemolytic anemia began to mount. But along I love that still, it's like we're finding the most severe manifestations first for us, and not like literally the most common cause or the most common manifestation. Making the link between B nineteen and the most common and often mild manifestation did happen like shortly after, so researchers were finding B nineteen in simultaneous outbreaks of aplastic crises and arithema infectiosum and then they were like, okay, let's look for just in Ritheum infectiosum in children, and of course they found the virus again. As you mentioned, Aretheum infectiosim is also called fifth disease. I love brief history.

00:57:34
Speaker 3: I love this. I love it so much. I don't know why, because it's silly.

00:57:38
Speaker 2: I really like it so silly. It never would have occurred to me that this was the reason why it was called this. Yeah, like, it's just what, okay. So the earliest possible mention of this common infection of childhood comes from the late seventeen hundreds early eighteen hundreds, with the description of a disease called Rubiola sin katar. So it wasn't called fifth disease then, right, and you know it's that seems to be debated whether it was actually fifth disease, but whatever. The first real reference to fifth disease or Aretheuma infectiosum comes from eighteen ninety nine, when Shamer described a childhood rash characterized by the slapped cheek appearance. The disease came to be known in Western Europe as Arithema infectiosome, and then in nineteen oh five Fifth disease to distinguish it from the other four rashy illnesses common in childhood m measles, scarlet fever, rubella, and epidemics pseudoscarletina Duke's disease, which is a variant of scarlet fever related to staphlococcal exotoxin.

00:58:46
Speaker 3: Yeah, apparently people are now like Duke's disease doesn't exist, fourths is not real, and now there's also a sixth disease, rosiola.

00:58:54
Speaker 2: Okay, but are people still using one two, like first, second, third, fourth?

00:59:00
Speaker 3: First? So first, second, third, no, okay, Fourths no, I've never heard anybody use but fifth and sixth yes, I can't get over it.

00:59:11
Speaker 2: So yeah, Arithema infectiosum B nineteen whatever that was fifth. I It seems like the most confusing naming system because not only do you have to remember the order, like it's just why yeah, Well.

00:59:24
Speaker 3: It's also in part because we now we have vaccines against measles, we don't get scarlet fever, because we can treat bacterial infections rubella, we also have a vaccine again, so really it's just like it's just fifth that's left and then yeah, rosiola as well.

00:59:39
Speaker 2: But still like even pre vaccines a kid would come in and you would go, oh, that's measles. Oh wait, no, that's first, or is that second? I don't know, like you know what I mean.

00:59:49
Speaker 3: Well, wasn't it more just like, oh yeah, that's this rash is first, this rash is second, this rash is third.

00:59:58
Speaker 2: I mean, maybe there was a method to the the order of these, but I feel strongly opposed. Well, anyways, over the first half of the twentieth century, people would have plenty of reason at least to remember the name fifth disease because it grew more and more common. So one paper said, quote fifth disease is now annoyingly familiar to pediatricians, school administrators, and public health officials throughout the United States.

01:00:30
Speaker 1: Wow.

01:00:30
Speaker 2: Quote Yeah, it was clear that it was an infectious disease of some sort, contagious just given the nature of outbreaks, but the root of transmission and the causative agent parvovirus BE nineteen wasn't linked to it into like nineteen eighty three, nineteen eighty four, which is kind of amazing.

01:00:49
Speaker 3: Yeah.

01:00:50
Speaker 2: Yeah, And it took another twenty or so years after that, thirty years since the discovery of B nineteen that another human parvovirus was discovered, So we're still very much in an active area of research and discovery with human parvoviruses. But these are only one branch of this big parvovirus family, arguably not even the most famous branch. So should we get into the famous one?

01:01:17
Speaker 4: What?

01:01:18
Speaker 3: Okay?

01:01:20
Speaker 2: Throughout the nineteen sixties and into the nineteen seventies, additional parvoviruses were isolated from new animal species, and the known host ranges of parvoviruses were expanding, like feline pan lucopenia virus, which was also found in mink and raccoons. But despite the creeping realization that parvoviruses were a globally distributed and b that the name of a specific virus like raccoon parvovirus, for example, might not capture the full host range of that virus, the public, I think, for the most part, was unfamiliar with this new group of pathogens. Maybe maybe you know feline panlikopenia virus, but that's it until nineteen seventy eight, when blurbs about a deadly new disease in dogs began popping up in newspapers, first small little paragraphs on page twelve or whatever. But later, as the extensive spread of this disease became apparent, these articles began showing up in countries around the world, simultaneously making headline news. From an article in the Schenectady Gazette on May twenty seventh, nineteen seventy eight, quote a serious viral disease affecting dogs has been reported to have reached this area. A representative of the Capital District Veterinary Medical Society said the virus has been identified as belonging to the Corona virus group. It causes yeah. It causes acute gastro enteritis, exhibiting vomiting and several hemorrhagic diarrhea, resulting in severe dehydration and an imbalance of the dog's electrolytes, which leads to death. The Veterinary Society recommends that any dog exhibiting symptoms be immediately taken to a veterinarian for treatment, especially dogs who have been to dog shows or among other groups of dogs such as that classes, et cetera. The progress of the disease and its serious effect on the dogs is extremely rapid. After the first sign of symptoms, dogs have died within twelve hours. According to a report in the American Kennel Gazette Purebred Dogs Magazines April nineteen seventy eight issue, the problem with this virus became widely known in February following a specialty show sponsored by a national parent club, and it has rapidly spread throughout the country since then. End quote longo, Yeah.

01:03:50
Speaker 4: It was.

01:03:51
Speaker 2: I found it very like jarring to see coronaviruses like suggested. Obviously it wasn't a coronavirus's parvovirus, But I saw that and my heart went, I know another one. No, yeah, it gave me this little jolt of anxiety. But yeah, so this would this is what the first one of the first descriptions of parbovirus. And so I want to read some snippets from later news articles to kind of trace the spread of parvo and awareness of it. That's kind of fun, like history through headlines.

01:04:21
Speaker 3: I don't know.

01:04:23
Speaker 2: This is from a Canadian Press article from October twenty fifth, nineteen seventy eight, titled virus kills dog in five days. Quote. Dog owners are being warned to watch for signs of a new virus, which can kill a healthy animal in five days. Veterinarians say they don't know much yet about the virus, called enteritis, except that it is an intestinal infection and appears to dehydrate a dog mainly through vomiting and diarrhea. Entertis has been found from the Maritimes to Saskatchewan and is reported to be widespread in the United States. It does not pose a threat to other animals or to humans. Gary Thompson, a pathologist at the University of Guelph, said the problem first appeared among show and kennel dogs, but now has shown up among dogs who get no further than their own neighborhood end quote.

01:05:12
Speaker 3: No further than their own neighborhood.

01:05:14
Speaker 2: I know, it's really scary to like read about the spread. A few months later, in January nineteen seventy nine, there's an article from the Associated Press titled quote new virus infects dogs cats maybe to blame.

01:05:30
Speaker 3: Quote oh my gosh, so rude, right.

01:05:35
Speaker 2: And this article mentions that scientists are calling the virus canine part of a virus, and that it is similar to quote unquote feline distemper aka feline pan lukopenia, which is also confusingly called cat plague.

01:05:51
Speaker 3: It's just like, what, why do you have to have so many names?

01:05:55
Speaker 4: I know.

01:05:55
Speaker 2: Also, distemper is like a difference, it's a completely different thing entirely.

01:06:00
Speaker 3: We'll do it someday, I swear we will. Yeah, it's been on our list. Yeah yeah.

01:06:05
Speaker 2: But this was clearly not the same exact virus as feline pan lucopenia virus since a this is like the first time that people were seeing it in dogs. And also there were studies from the nineteen sixties showing that experimental infection of dogs with feline pan lucopenia virus were unsuccessful, Like the dogs didn't get infected. Nor was it the minute virus of canines. I'm assuming it's minute, not minute.

01:06:33
Speaker 3: Yeah. I think it's minute because they're little virus.

01:06:35
Speaker 2: There's little viruses.

01:06:36
Speaker 3: Yeah.

01:06:37
Speaker 2: I was like reading it, I was like, oh, wait, I guess I never considered anyway English is I'm right, it's yeah. Yeah. But the minute virus of canines is now called canine parvovirus type one, and that was discovered in nineteen sixty seven and not really considered to be of great concern, like it did seem to possibly cause infertility and pregnancy loss in dogs, but not enteritis or this super high mortality from its first identification and description as you know, quote unquote show dog disease which was what it was called in its early days, to canine parvovirus that took less than a year, and another big development was not far behind, a vaccine. Once researchers made the link between this new deadly canine parvovirus and feline pan lucopenia virus, the next natural step was to wonder whether the vaccine for feline pan lucopenia virus, which had been developed in the late nineteen sixties, would work on this new virus. Seem like they're related, It's worth a shot. The answer can be found in another news article title from March nineteen eighty, again by the Canadian Press. Quote cat vaccine helps quell dog disease end quote.

01:08:00
Speaker 3: Oh full and eighty. I love it.

01:08:02
Speaker 2: I know I do have some I do have more from that article quote. Some Canadian veterinarians, in an effort to quell a disease that killed an estimated one thousand dogs in Canada last year, have turned to an unlikely source for help. They're using a cat vaccine, which, although not yet licensed for use in Canada has met with success and is licensed for use in the United States. End quote an unlikely sources and unlikely. Actually it's like fairly likely likely. It's okay. So this was excellent news, right, especially since this new canine pervovirus were starting to show signs of being able to infect cats. But where did it come from? Were cats to blame?

01:08:51
Speaker 3: No?

01:08:55
Speaker 2: And so okay, we have this vaccine control as possible, But we have a lot of unnswered questions about the origins of canine parvovirus. And so now I want to get into a bit of the history of canine parvovirus type two. I should say, not as the general public was reading about it like over coffee and cereal, but as the virologists and evolutionary biologists pieced together using molecular clues of it. The knine parvovirus that began making headlines around the world in nineteen seventy eight was, like I mentioned, the second canine parvovirus to be identified, hence the type two attached to its name. Most people call it canine parvovirus because it is like the one you know, But anyway, it's number two. It's number two and canine parvovirus type two did not evolve from the minute virus of canines aka canine parvavirus type one. And it probably comes as no surprise that nineteen seventy eight was certainly not the first year that it began and circulating in dogs. Researchers tested SIRA from dogs from nineteen seventy four nineteen seventy six and found antibodies to the virus. And it's pretty amazing, maybe not surprising for this covid world that within a few years this virus had become global, a true pandemic virus. Like, yes, it had been circulating, but I think that like the earliest signs were nineteen seventy four, nineteen seventy six, and then it was global.

01:10:31
Speaker 3: It's this I feel like, I don't know, I don't know why I feel this way, but it feels especially impressive that it's dogs and then it's spread. But I guess like wild animals. Yeah, I don't know, Yeah, no, I think I think it.

01:10:47
Speaker 2: Actually that aspect of it was really concerning to a lot of people because we have all you know, all these countries have specific like quarantine restrictions and like legal limit on can you bring a dog in here? Can you bring this animal? How many animals can you bring in? Like the contact signs of disease steps, Like how did this happen? Yeah, And I'm not going to talk about it from like a disease control perspective, but that is something that I think still people are making sure like where were the cracks in the system?

01:11:21
Speaker 3: Yeah?

01:11:22
Speaker 2: Yeah. But anyway, so, once this virus had become pandemic, it underwent some genetic tweaking to reach its full potential, as pandemic viruses do. A few amino acid changes here and there led to a new genetic variant called parvovirus type two A, which emerged in nineteen seventy nine. So just like a year after sort of the first rumblings in newspapers and so on, and in a short time, just a couple of years, really parvovirus type two A completely replaced parvovirus type two.

01:12:00
Speaker 3: Wow.

01:12:01
Speaker 2: Yeah. Since then there have been a few more variants like B and C and so on, and I'm not going to get into those. Type two A was definitely from a pandemic virus perspective, a level up from type two not only was it better adapted to its canine hosts. It also had an expanded host range, able to infect cats and wild carnivores, and it seemed deadlier. After a decline in cases of canine parvovirus in like nineteen eighty and nineteen eighty one, as herd immunity kind of slowed transmission a bit, things exploded again in nineteen eighty one nineteen eighty two, but this time the disease seemed more severe. Quote pups collapsed suddenly in a shock like state and died with or without enteric signs. Many pups also developed an acute, rapidly progressing illness with exceptionally severe haemorrhagic enteritis that was not commonly seen in the initial outbreaks end quote goodness.

01:13:03
Speaker 3: Yeah.

01:13:04
Speaker 2: Fortunately, though, another improved vaccine was developed pretty quickly, but the sudden shift with a new deadly variant was obviously really concerning, Yeah, because it kind of begged the question like, Okay, what next? Would this virus keep evolving until it could escape a vaccine, until it could infect other animals outside of its existing host range. Could that eventually include humans? And, as always with this podcast, to understand where we might be going, we have to look back at where we came from. Perhaps untangling the origins of canine parvovirus type two would help researchers to predict whether or not this virus was likely to expand its host range beyond what currently existed. Initially, when canine parvovirus type two first appeared, most scientists thought it had jumped hosts from cats the feline pan lucopenia virus evolving to infect dogs, and maybe even it was like the vaccine strain of that virus that had sort of turned into a virus capable of infecting dogs. But it doesn't have a whole lot of support ooh, and it seems actually unlikely. So first, canine parvovirus type two was unrelated to those vaccine strains.

01:14:26
Speaker 3: Well, that's that's a big fat no.

01:14:28
Speaker 2: Then it's a big fat no. Second, despite the long history of cats and dogs being in proximity, this was the first detected instance of this virus or another kind of similar virus hopping from one species to the other, at least that we know of. Of course, there's always that, you know, hedge. But the third reason I think is the strongest, which is that intermediate viruses between feline pan lucopenia virus and canine parvovirus type two have not been detected in domestic cat or dog populations, and that's what we would expect to see if the virus evolved from cats to infect dogs, we would see those in between strains. So canine parvovirus type two is seen as a host range variant of feline parvovirus. So if it didn't come from cats, like, where did it come from? How is that possible? Yeah, well the answer is a different host range variant of feline pan lucopenia virus. So feline pan lucopenia virus is actually comprised of a bunch of strains of virus which can infect other hosts besides cats, including mink, raccoons, and foxes. And so maybe this taxonomy is like I read a paper about like the history of the taxonomy of parvoviruses, but it was from two thousand and eight, so maybe this is a little bit out of date, but in any case, that was my understanding of the organization of these viruses. Yeah, so researchers think that canine parvovirus type two may have evolve from one of those feline pan lucopeniavirus variants. So like dogs somehow got into contact with raccoons or make foxes, whatever, and then that virus infected dogs and then yeah.

01:16:13
Speaker 3: I feel like this just shows the problems. But the way that we name things, sure, and the way that we name viruses, because like the parvoviruses especially seem like what a mess, what a mess?

01:16:27
Speaker 2: And it's clearly named after like the first animal that it was detected pain, which.

01:16:31
Speaker 3: Is just what and like also why like this one is called pan lucopenia virus and then this one is called parvovirus, and then this one is called like something else and I'm just like stop it, I know, stop. Well anyways, anyways, it's just me.

01:16:50
Speaker 2: No, it's not definitely not just you. And so I don't think that at least I couldn't get a clear answer on what they think that animal was that was the source of sort of like the initial spillover.

01:17:06
Speaker 3: I guess like, don't blame the cats.

01:17:08
Speaker 2: Don't blame the cats. Okay, we can blame the raccoons though, because it does seem there is some research to suggest that once canine parvovirus type two emerged from whatever you know, feline panlicopenia virus variant. It then further evolved, possibly in raccoons, so like spilled over from dogs into raccoons and then kind of you know, evolve tweaked things a little bit more to become canine parvovirus type two A. Ah, yeah, so the parvovirus that infects raccoons seems to fall between canine parvovirus type two and type two A.

01:17:50
Speaker 3: Oh my gosh.

01:17:50
Speaker 2: Well, okay, this is like a lot of nitty gritty and I'm done, so you're welcome. But the bottom line is that we don't know exactly which animal feline panlikopedia virus jumped from into dogs, probably not cats. And the other bottom line is that canine parvovirus type two evolved into type two A, possibly with the help of raccoons. But why is all this nitty gritty important? Why am I like stumbling over the taxonomy all of all of this Because anytime a pandemic virus emerges, we want to know how it happened. We want to be able to trace that roadmap to understand how a virus mutated, how it was able to come into contact with another host aka spillover, how it continued to evolve to infect that host, and how it was able to rapidly spread around the world. Looking at both the biological properties of a virus as well as the societal or political or infrastructural properties that allowed the pandemic to happen, I also think that the canine parvovirus pandemic is especially interesting given that it's a single stranded DNA virus, where we tend to think of RNA viruses as the ones of pandemic potential because of their high rate of mutation. But hey, don't forget about the single stranded DNA viruses.

01:19:17
Speaker 3: It's not.

01:19:18
Speaker 2: Yeah, So clearly the story of parvoviruses is very much ongoing. We're finding new parvoviruses or variants of existing parvoviruses and new species, and canine parvovirus very much remains a threat to domestic dogs and cats and wild animal populations around the world. But before we get into where we are with the human side of parvoviruses today, we wanted to bring on a very special guest who can share some insight from the veterinary side of things. We'll take a short break here and then jump in. So far in this episode, we've covered a lot of ground. But what we haven't gotten into, and this is probably especially obvious to those dog and cat owners out there, is the animal side of things. Like we've mentioned, parvaviruses are quite a diverse group and if we went into each and every one of them, we'd be here all day and probably tomorrow too. So instead, what we're going to do is spend a bit more time on two parvoviruses, in particular, canine parvovirus and feline pan lucapinia virus. And to help us do that, we've enlisted the help of the amazing doctor Steph Horgan Smith. Doctor Steph graduated from Ontario vetter Andary College in twenty eleven and now owns and runs a veterinary hospital in York Region in Ontario, Canada, and we are so excited to chat with her today. And just to note, this interview was recorded on November twentieth, twenty twenty three. Doctor Steff, thank you so much for joining me today. I can't wait to talk about parvoviruses from the veterinary side of things.

01:21:22
Speaker 4: Thank you for having me.

01:21:23
Speaker 2: I'm very excited, so let's just like jump right into it. We talked a little bit about cana and parvovirus throughout the biology and the history, but we didn't really get into like what it looks like in dogs. So what are some of the signs and symptoms of infection.

01:21:38
Speaker 4: So the classic what we see in clinic is with puppies. Really it's mostly in puppies. Adult dogs can get it, but their immune system is definitely better at fighting it off. So the classic is a puppy that comes in and by the time we see them that they're sick, they're vomiting, they're having some diarrhea, and most of the time that diarrhea is bloody. They're sometimes by that point or not, they're pretty sick and flat. So as soon as we get a puppy that's vomiting diarrhea, we're all testing for parvo. A lot of them are actually pretty painful in their stomach and their intestinal track just from the virus kind of getting through that area.

01:22:16
Speaker 2: When we talked about parvo B nineteen, which is one of the viruses that infect humans, we talked about it being spread through respiratory droplets, but that's not the same for dogs. So how is parvo spread between dogs?

01:22:30
Speaker 4: So in dogs there's actually more fecal oral the virus has shed way more in feces, and so the virus itself is pretty stable in the environment and will last on surfaces or toys or chowes that I've walked through with virus attached and can be spread to other dogs that way. That can be passed in utero, sometimes from to puppies, but that's I would say not as common. We see mostly in puppies that are out in the environment and they're catching it that way.

01:23:03
Speaker 2: Durability, it's pretty dang durable, right, Like, yes, months, even longer.

01:23:10
Speaker 4: Up to a year in the right conditions. Okay, So if there's organic material that's still left over, it's going to survive in that organic material. So actually scrubbing, cleaning is a big one, and making sure that all the organic material is gone. UV rays will actually kill the virus eventually, so indoors it can stay a long time.

01:23:32
Speaker 2: We talked a little bit about how one of the newer variants that emerged well you know, several decades ago, could also be spread to cats. But what about other animals?

01:23:43
Speaker 4: So yeah, there are reports. They're not sure if it's a canine parbavirus or feline like pan lukopenia, which type, but there have been reports in like coyotes, wolves, pumas, bobcats even and then raccoons and skunks, so all of those animals seem to get some type of parvo and then separate to the canine and feline parvavirus. Porcine parvavirus is a really important virus in pigs and pig production because mostly it actually just causes fetal death, so it changes your litter size. So yeah, there's a vaccine for that also, so at least we can help try and prevent that prognosis.

01:24:26
Speaker 2: So canine parvovirus obviously a very severe disease, but like what is the prognosis and how does that vary based on the age of the dog or puppy and other factors like overall health status or breeds or anything like that.

01:24:42
Speaker 4: Yeah, the younger the puppy, the more susceptible they're going to be to the virus because it's infecting those rapidly dividing cells. It runs through the immune system and the bone marrow and infects all their immune cells, and then to the GI tract and it just wipes out the villa, all the little intestinal villa that are absorbing all the puppies food. So then we basically support of care have to just keep that puppy alive until the cells regenerate in you know that kind of ten to fourteen day mark where the new cells grow up from the cryps. That's where survival kind of depends on how young they are, how prone to other complications like hypobolemic shock or low blood sugar because they can't keep up their sugar and stuff. And then unfortunately with venory medicine, cost comes into it. So what level of care an owner can do. If they can do intensive management in a hospital setting for two weeks, that's pretty pricey, but generally survivals about ninety percent. It kind of goes down from there again depending on age of the puppy. But you know, if we have to do outpatient treatment, it can work, but survivals a little bit lower than kind of the ideal gold standard. But obviously not everybody has that much money to keep a puppy in intensive care for two weeks.

01:26:07
Speaker 2: It's a lot, right, and treatment is sort of like you said, just supportive. Does that just mean like fluids and monitoring. Yeah.

01:26:15
Speaker 4: Yeah, So that puppy is hooked up to ivy fluids nutritional support, so either a feeding tube or down right into their belly. We do that. They're getting their electrolytes checked all the time to make sure that those are staying normal and supplementing whatever they need, and then keeping them in the hospital keeping them monitored. That's always been our classic mean treatment. There is actually a new monoclonal antibody that has been licensed that sounds quite exciting. It's showing some really promising quick turnarounds that maybe those puppies won't be as sick for as long, which is amazing in so many ways. So that's really exciting that we might actually have a specific treatment where it's blocking the virus from being able to get in to the cells. WHOA, So that's really exciting potentially on the future horizon.

01:27:06
Speaker 2: That's amazing. Oh, that's really cool. Oh, I love that. In the history section, I talked about how canine parvovirus likely evolved from a related parvovirus. One of the host variants of the feline pan lucopenia virus Can you tell me a little bit about that virus and what are some of the signs and symptoms and cats.

01:27:28
Speaker 4: Yeah, so that one actually is maybe a little bit more similar to the human one because it can be infectious through any body secretion, so saliva or potentially respiratory droplets as well. Also can be fecalral so it kind of just arranges the whole thing anything. But yeah, that one, again, it's going to infect those rapidly dividing cells. We see not as severe gastrointestinal symptoms with cats. What a lot of the time we see is some times the queen gets infected, so then vertical transmission to the kittens or very very young kittens while they're still nursing. One of the classic symptoms that we learn about and we see sometimes is the virus actually goes and starts affecting their cerebellar development, so that specific part of the brain. Kittens are still developing that for like about two weeks after they're born, So even if they get infected really young, they can get this Sarahbella hypoplasia where it just doesn't develop completely normally and they'll have these tremors because that's movements and fine movements is part of what the seahbellum helps with. So these kittens will grow up and they'll have these intention tremors probably for life. But if they recover from the virus, then they can survive, they can kind of be normal. But yeah, they get this very specific symptom that you can kind of look at them later and say, oh, that cat probably had panikipedia when it was a kitten because it has this very specific intention tremor.

01:29:08
Speaker 2: Is pan lcopenia in kittens as severe as canine parvo is in puppies. Is the prognosis pretty similar?

01:29:16
Speaker 4: No, I'll say, for whatever reason, we see it more in extra young kittens, so when they're still nursing, and so unfortunately some of those kittens, when they're that young, they kind of just get this fading kitten and some of them will just not survive. And then again with the cerebellar hypoplasia. But we just don't see it as often as we would like a parvo puppy. I think partly because of how we keep cats in general. They're not out in the environment meeting other cats, right, so if they're picking it up, it's because someone in their households has it and hasn't been vaccinated for it, so it's not as widespread as puppies who are seeing other dogs all the time or being introduced to other environments.

01:30:00
Speaker 2: Okay, so when do puppies and kittens get vaccinated for parvovirus or pan likopinia and how many rounds of vaccination are there?

01:30:11
Speaker 4: So luckily it's the same for cats and dogs, so we can talk about it at the same time. We start at anywhere between six to eight weeks to get that vaccine into them. That's where it's a bit tricky, depending on the whole situation with mom, because if mum is well vaccinated, she's giving those puppies or kittens her maternal antibodies in the milk and they are still active at definitely six to eight weeks for most of those babies. We start then just in case mom doesn't have great immunity. We want to catch those ones that are not getting immunity from mom. But then we have to revaccinate every four weeks up until they're about sixteen weeks old. At sixteen weeks old, mom's maternal antibodies won't be there anymore and we'll be stimulating that puppy or kitten's own immune system to fight the virus. It's generally a series of three to four vaccinations starting.

01:31:05
Speaker 2: At sixty eight weeks.

01:31:07
Speaker 4: Parvo's the main reason that most vets will recommend being really careful with where you take your new puppy until they get at least a couple vaccines into them, because parvovirus can be anywhere, it can be shed and then just left in the environment. So that's the main reason why we have to be careful with where puppies are going and who they're meeting, right when they're really young.

01:31:31
Speaker 2: During COVID the last ten twenty thirty years even we've seen a big upward trend, especially here in the US, but I think globally as well in vaccine hesitancy and anti vaccine sentiment for human vaccines. But have you seen something like this as well for people and their pets.

01:31:53
Speaker 4: Yes, we definitely have clients that are vaccine hesitant and just not one hundred percent sure what the science is and what's going on. But the one thing I will say about parvo vaccination, and especially in dogs, but in cats as well, it's really effective getting those puppies in when they're young, and bringing them back every month for that booster vaccine. I couldn't find an actual number when I looked at it, but there's very rare breakthrough actual parvovirus infections in dogs that have been fully vaccinated. They do need revaccination though the immunity we don't know exactly how long it lasts in every dog. Their own immune system is going to be different, So we generally do a booster at a year later, and then revaccination is every one to three years after that.

01:32:41
Speaker 2: So I have one last question for you, and it's not about parvovirus, but it's instead about this new canine respiratory illness that seems to be popping up throughout the United States, at least all over. It's here in the Front Range in Colorado. What do we know about this infection and why has it gotten pe so concerned?

01:33:01
Speaker 4: I hate to say, but we're not sure yet.

01:33:05
Speaker 2: It's all right, we say it all the time on the Potomacast. We don't know.

01:33:10
Speaker 4: There's Yeah, it's been around. There's been reports of some kind of respiratory infection since I would say late spring in different parts of the US. We've been tracking it I personally haven't seen any reports. I'm up in Ontario, haven't seen too many things here. But it started with is it kennel cough for some type of kennel cough kind of organism that is just not responding to normal treatment. Most of the labs that we use have a pretty extensive respiratory panel, so if we get samples, we can send that out to our labs and try to see all the common stuff is on there, including influenza, bordo tella, hair and fluenza, things that cause kennle cough, and other common respiratory infections, and it's testing negative for all of those, and then it just seems to be unfortunately the dogs own immune system whether they get this cough and it just lingers, but they're okay Otherwise. I've heard reports if it lasting for like six to eight weeks in some dogs and then some unlucky ones it does seem to turn into more of a pneumonia and those dogs are needing some of them hospitalization, pretty intensive management to help get them through it. So they haven't really even found what the difference is between those cases, why some dogs are just getting a cough or and then some of them are getting quite sick with pneumonia. It's a bit scary that we don't know still what it is.

01:34:36
Speaker 2: Yeah, for sure, it's very scary. It definitely has echoes of like the early parvovirus news articles, like there's this mysterious thing that's spreading, you know, and we don't know what it is. But yeah, anyway, well, thank you so so much for taking the time to chat and answer all of our questions about canine parvovirus and pan leukopenia virus. I mean, I feel like we definitely could have talked for hours, and I really really appreciate it. You're very welcome.

01:35:08
Speaker 4: I'm glad that I could help and hopefully shed some light on the canine and feline pet side of parvovirus.

01:35:32
Speaker 3: Thank you so much, doctor Steph for walking us through that. I love getting to hear about animal diseases from someone who actually knows.

01:35:42
Speaker 2: Yes, yeah, totally, Yeah, I really appreciate its great.

01:35:46
Speaker 3: Thank you. So let's talk a little bit about where we stand with parvoviruses today.

01:35:53
Speaker 2: Let's do it again here.

01:35:54
Speaker 3: I'm going to focus on human parvavirus BE nineteen in part because I couldn't find data on the prevalence of feline pan lucopina virus or canine parvovirus too, like except studies that were like this country in these years, you know what I mean, That was like very specific. Like the point is those viruses are everywhere all the time, yeah the end. So for humans, the story is almost exactly the same. I couldn't get a handle on breaking things down much more than letting you know that when we look at zerology studies, by age, by the time someone is about six years old, anywhere from like two to fifteen percent of kids will have antibodies. But by the time you get to adulthood, over sixty percent of adults have antibodies to parvob nineteen and by the time you get to be geriatric, over eighty five percent of people have antibodies. So like, everyone gets parvo at some point, and there is at least in temperate regions, seasonal variation in parvovirus infection, So peak incidence tends to be late winter early spring, which makes sense. That's when a lot of viruses circulate, and like we have seen with other childhood infections, there can be these outbreak years where every three to four years or so will see an increase in infections overall, and they call these epidemic years. Okay, now, during these outbreaks, in these epidemic years, we see that about ten percent of all the cases will occur among children that are about five years old, and seventy percent of them will be in kids between age five to fifteen, and then twenty percent of cases are in people older than fifteen. So that's like the age breakdown where the youngest of kids might be a little bit more protected, and it's that middle like school age kids that are the highest risk for infection. Okay, Now, what I wanted to be able to get a handle on is like what percentage of kids or people who get infected will have more severe manifestations like aplastic crisis. Yeah, I don't know. Okay, I don't know. I mean we try, but that is Parvo B nineteen epidemiology. When I tried to get a handle on where we stand in terms of vaccines or treatments, I also didn't find very much. It was kind of disappointing. I found one paper that was talking about a few different vaccines that are kind of in trials, which are made from these what are called virus like particles is kind of weird and interesting. Basically, like parvo proteins, parvavirus proteins do weird stuff essentially, and like form these little nuggets that look like viruses, and so people are taking these and trying to use them to make vaccines.

01:39:18
Speaker 4: I don't know.

01:39:19
Speaker 3: I don't know a lot of details about it, but apparently they haven't worked great so far in clinical trials. And so a paper that I found, which is old now, like twenty thirteen, was trying to make different virus like particles that would cause less illness in people and still be able to induce a good immunity. But they were still in animal model stages, and I really couldn't find anything more recent. So if someone knows of more actual parvo B nineteen vaccine research going on, hit me up. I'd like to know. Okay, but I have more to talk about. I'm not done, I know excited. I want to give a shout out to some very important parvaviruses that we haven't talked in detail about, and that is the Adino associated viruses, the dependoviruses or AAVs. And these are parvaviruses that can't infect cells without a concomminant coinfection with either an adenovirus or a herpes virus.

01:40:24
Speaker 2: What yeah, it's I yep, keep.

01:40:29
Speaker 3: I love it. I love it. We mentioned this concept even like very briefly in our hepatitis B episode, yep, because hepatitis D is a similar virus that requires the presence of hepatitis B persistently to be able to cause infection because it needs hepatitis B to leave the cells or whatever. So okay. These AAVs are super tiny parvaviruses, and their genomes essentially, they're very simple. They in code for like a capsid protein and a couple of other proteins, and that's it. They're really basic, and they generally are considered, to everyone's knowledge asterisk to not cause any disease in humans, but they infect humans quite readily in the presence of a helper virus. They're really efficient at getting into our cells and replicating and specifically integrating into our genome and laying latent, particularly in this one specific place on chromosome nineteen at least when we're talking about wild type AAV and this characteristic being able to infect our cells and get into our DNA and hang out there makes them an ideal candidate for BUMPAA bamb gene therapy.

01:41:55
Speaker 2: Uh huhn amazing.

01:41:58
Speaker 3: So AAVs have actually been the kind of leading platform for gene therapy thus far. And I think I've probably said the words ADNO associated virus on this podcast in the past, because additionally, one of the covid virus vaccines is an ADNO associated virus vector vaccine, but I didn't even really know what that meant before researching this episode. So essentially, you can make recombinant AAVs that use this same capsid protein, but you can replace the rest of their tiny little genome with genes that code for whatever proteins you want. And now you have this really efficient little machine that yeah, needs some help from an adnovirus to get into our cells, but then can be in our cells churning out whatever proteins we asked it to make and not causing any disease. This is pretty cool.

01:42:55
Speaker 2: It's like a whole new world of like, I just I love it.

01:42:59
Speaker 3: Yeah, there are already gene therapy platforms that are out there that are being used for things like spinal muscular atrophy, some forms of congenital blindness, and there are more in the pipeline for so many genetic conditions. It's phenomenal. You can read a lot more about it. I have a few papers, but there's even more out there. But one last thing, there was an asterisk.

01:43:23
Speaker 2: Yeah, I saw that.

01:43:25
Speaker 3: Historically this adino associated virus or add no associated viruses in general have never been shown to cause disease. But just these past years, in twenty twenty two, the end of twenty twenty one, twenty twenty two, and twenty twenty three, it has recently been shown that AAV two has been associated with some pretty severe outbreaks of hepatitis among kids. So in like thirty five different countries, several hundred kids got very super sick and in some cases died. And after some really intense investigation and these extensive case control studies in a few different countries, what they have found so far is that AAV two is at least associated in some ways with these outbreaks. But what's really interesting is that we don't know still if there's a causative link as to why kids got so sick, or whether AAV two existing was a marker of like a primary adnovirus infection, but we don't often see as severe disease with primary adnovirus infections. One really interesting part of this story, and I know this is like such an abbreviated story, it's like wow, But one part of it is that some thought was that this all happened kind of just post pandemic, right, Like, obviously COVID still exists, y'all. But once all of the restrictions from COVID were lifted, one hypothesis is that susceptible kids may have had a higher chance at all of a sudden at the same time being exposed to both an adenovirus and AAV two at the same time. That caused this like synchronized wave of severe disease, where previously kids might have been exposed to one virus and then another and then another, like on a larger time scale, if that makes sense.

01:45:39
Speaker 2: Right.

01:45:40
Speaker 3: So it's we still like this is very early. These papers were just published like a few months ago. Yeah, but it's really interesting because it shows just how much we still don't know about so many viruses that exist.

01:45:57
Speaker 2: Yeah down the line repercussions, Yeah.

01:46:05
Speaker 3: Yeah, it's fascinating. Yeah, but again, you can read so much more.

01:46:10
Speaker 2: I've got papers, We've got sources for you. Let us go through some of those sources I have, Aaron, I have so many for this, I like kept finding little snippets here and there and just trying to peace through it all. Whatever. I'll just name a few of them right now, and then the rest I'll post. So there's one by Carmichael from two thousand and five called an Annotated Historical Account of Canine Parvovirus by Parish and Kawaoka from two thousand and five, The Origins of New Pandemic Viruses the Acquisition of New Host Ranges and by Thurn from nineteen eighty eight. Human parvo Virus B nineteen Historical and Clinical Review.

01:46:52
Speaker 3: Love it. I actually most of my papers were kind of old for this, but they were solid. So there was a paper called Human Parvovirus B nineteen in Clinical Microbiology Reviews from all the way back in two thousand and two, and another one on parvo B nineteen from the New England Journal of Medicine from two thousand and four. A few others on more specific aspects like parvo in pregnancy, et cetera, and then a bunch on the AAVs, both as platforms for gene therapy and this association with hepatitis et cetera. Plus I threw in a few on K nine and feline parvaviruses as well. You can find all of the sources from this episode and all of our episodes on our website, This podcast will Kill You dot com, and all of our social media channels.

01:47:39
Speaker 2: Thank you again so much to Eliza for sharing your story with us.

01:47:44
Speaker 3: Thank you again, Doctor Steph for providing our veterinary expertise for this episode.

01:47:49
Speaker 2: Thank you to Bloodmobile for providing the music for this episode and all of our episodes.

01:47:54
Speaker 3: Thank you to Tom bry Fogel for the incredible audio mixing.

01:47:57
Speaker 2: Thank you to Exactly Right.

01:47:59
Speaker 3: And we have so many people to think, especially thank you listeners. Thanks for listening yes to all these Thank yous.

01:48:06
Speaker 2: I hope you learn more about parvaviruses.

01:48:10
Speaker 3: Yeah yeah, yeah.

01:48:12
Speaker 2: And especial thank you as always to our wonderful, generous, amazing patrons. Your support really means the world to us.

01:48:19
Speaker 3: It does, We love it. Thank you well.

01:48:22
Speaker 2: Until next time, wash your hands, you filthy animals.