HPAI: A Changing Disease Dynamic

Discover the challenges presented by highly pathogenic avian influenza (HPAI) and its spillover to mammalian hosts. Drs. Jonathan Runstadler and Wendy Puryear cast light on their groundbreaking research, offering a deep dive into the virus's unpredictable nature. We discuss how staying informed about the ever-evolving threats of influenza requires adaptability, an open mindset, and a readiness to rethink traditional diagnostic approaches. Together, we underscore the need for heightened vigilance and education, not only within the veterinary community but also among the public, to foster a better understanding of our interconnected health.

JAVMA article: https://doi.org/10.2460/javma.24.01.0053

AJVR article: https://doi.org/10.2460/ajvr.24.01.0018

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Transcript

Speaker 1: 0:00

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Speaker 3: 0:30

To learn more, visit nextguardpluscliniccom. You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode we chat about HPAI with our guests Jonathan Runstadler and Wendy Puryear. Jonathan Wendy, thank you so much for being here today. Thank you for having us.

Speaker 4: 0:52

Great to be here.

Speaker 3: 0:53

All right, let's dive right into this very timely topic. Wendy, your JAVMA and HAVR current someone health articles discuss highly pathogenic avian influenza or HPAI. Please share with our listeners the background on the JAVMA article.

Speaker 2: 1:11

Yeah, so really this comes down from starting with the bigger view of influenza in general, and we know that there are a lot of forms of influenza that circulate in the wild and most of these are considered low-path influenza, but there are some that have spilled over into mammalian host as well as farmed poultry generally are considered low-path, low-pathogenicity influenza.

Speaker 2: 1:38

Over the last couple of years we've had a shift and it's come up a lot in the news lately of high path influenza and that has really kind of turned everything on its head. So really everything that we thought we had known about influenza collectively, what we thought we knew, is all the rule books, are just out the window. So we've had this really high level of mortality that has been observed in both wild birds and domestic birds, but spilling over into mammals in levels that had never been observed before. It's completely unprecedented. So the basis of this was really trying to you know, in addition to the fact that there's been this huge impact on birds, both domestic and wild, the focus of this is really to try to get a better idea of what is happening as it's moving into mammals, because that's a space where we haven't seen it very much before.

Speaker 3: 2:33

Like we said, it's very timely, especially with what's happening in today's world. John, can you please share with our listeners the background on this AJVR article?

Speaker 4: 2:43

Yeah, sure, it really comes out of the same sort of background in terms of the history of influenza, particularly over the last 25 to 30 years, and the emergence and the evolution of this lineage that's causing spillover and has been in the news lately.

Speaker 4: 3:08

Lineage that's causing spillover and has been in the news lately. But the AJVR article focused, you know, a little bit more on kind of the research aspects of influenza and spillover and where we think we really need to put in some additional effort to try to understand that and be able to understand what is a risk to public health. So part of that is focusing on, you know, this sort of difference that Wendy mentioned between strains that are low pathogenic or don't cause severe disease in wild animal hosts and strains that are highly pathogenic or do cause severe disease, whether it's in poultry, where the definition of high path avian influenza you know sort of originally came from, or whether it's in these animal hosts that we're seeing this particular lineage of H5 influenza spill over into. So really trying to, you know, understand what the importance is of differences in the strains that are circulating out in the wild to what may occur as spillover into other hosts.

Speaker 3: 4:24

Thank you, sure, and.

Speaker 2: 4:31

Wendy, what were some of the pivotal findings from the JAVMA article? So that was focusing again on the mammalian side of things and trying to really pull together the bits of information that we're starting to collectively gather of how high path is impacting mammalian hosts. And to me, one of the things that really jumped out when we started pulling all that information together was just the dramatic increase in species diversity that has occurred over the last two years since this form of the high path influenza. That 2344B has shifted, coming into sort of late 21, early 22. It shifted and really just has exploded in that number of species impacted. So by the end of 23, we had gone from there being almost no mammals, especially when you're talking about wild mammals. It was a rare exception that you would have virus come into a wild mammalian species, seals being one of the exceptions, but that has even gone off the charts recently, but there was a rare exception. And then, coming into the end of 2023, we now have at least 60 species of mammals that have been confirmed to be impacted by Hypatin influenza and that represents more than double of the number of species that had ever had it previously. So just this rapid increase.

Speaker 2: 5:57

And then the other thing that really stood out as we were pulling together all of the pieces of information on all these different species is the really strong neurologic component and the as it has unfolded over the last couple of years. The reports would come in and people frequently report in on having neurologic signs and seizures and ataxia and and that component. But it was really striking as we pulled it all together just how consistent that component. But it was really striking as we pulled it all together just how consistent that was. That really that is a dominant feature that has shown up until just recently.

Speaker 2: 6:31

Now that it has shown up in cattle since this paper has come out, that is not necessarily holding true in the cattle, but prior to that it had been very consistent in the other mammalian species that it's gone into. That it had been very consistent in the other million species that it's gone into. And it's probably worth noting as well that it's somewhat to the. It's a preferentially central nervous system, even over respiratory and we think of influenza. We think of it as being respiratory in mammals and gastrointestinal in birds, but CNS has really been the dominant and sometimes we don't even pick it up collectively, we don't even pick it up necessarily in the lung. It's going straight up into the brain. So that was to me one of the striking things that came out of this.

Speaker 3: 7:16

It's very interesting. My background is in zoological and aquatic animal medicine so especially with all the seal cases, I found that fascinating and different species manifestations definitely going to keep us on our toes, I think, for a while.

Speaker 4: 7:29

Most definitely yes, yeah, for sure.

Speaker 3: 7:34

And John. What were some of the pivotal findings from the AJBR article?

Speaker 4: 7:41

pivotal findings from the AJBR article. Yeah, so again it really flows out of some of the things that Wendy was talking about in the JABMA article from the research perspective. And I think probably the two biggest things are that you know, with the spillover that we've seen into this tremendous diversity of mammalian hosts and avian hosts. So this virus is, you know, causing disease and infection in a lot of avian hosts that aren't traditionally associated with influenza carriage and we're seeing those animals in, you know, clinical and rehab situations as well in the, the veterinarian research world. And influenza is not, you know it's a well-studied virus. It's an important virus obviously to human health and has received a lot of attention and and funding from, you know, funders like NIH and so forth over the years, uh, funders like nih and so forth over the years. We know a lot about influenza virus uh in in human hosts and how it replicates and so forth. But we have this sort of paradoxical problem in um, in sort of public health and thinking about spillover and potential pandemic influenza, in that we don't have good ways, despite that knowledge, of understanding what the risk of all of these influenza viruses that circulate out in the wild, what the risk of those is to human health or to spilling into another animal and the risk to cause disease in those animals. So, for instance, from the human side, we really understand risk of potential pandemic viruses only by taking those viruses and putting them into an animal model like a ferret or a mouse or a guinea pig or some animal model, and trying to relate the disease that it causes in that animal to what it might potentially do in humans. And that's in itself even a very fraught process to try to translate across species.

Speaker 4: 9:58

And so really, the I think probably the main thing that came out of the ajbr article or I hope, is an emphasis that we need a lot better, uh, understanding of um viral phenotyping.

Speaker 4: 10:12

And so we need we need better ways to characterize individual virus and understand how that relates to their potential to spill over from one host to another Again, whether it's from, you know, birds to a mammal or mammals, other mammals into humans or whatever it is.

Speaker 4: 10:31

And that's an area where, you know, we really haven't done much in the influenza world to this point. And so part of that, given what's happening with this current virus in the natural world, is characterizing what the virus is doing in all of these different hosts. So the need for biological assays to both test those viruses, but also the need for things like veterinary pathology to look at what that virus is doing from a clinical standpoint and an immunopathological standpoint in those various hosts. So really the bottom line is right now we don't know how to prioritize risk of these viruses, even if they're causing these bad impacts in animal populations, and we don't understand what that risk means for human health. Or if you're a dairy farmer, right before a couple of weeks ago you wouldn't have any idea what that meant for potential for cow health. So all of those areas are areas that we need more research effort on.

Speaker 3: 11:47

Sounds like it definitely, like you said, an opportunity for future research and also for future manuscripts too.

Speaker 4: 11:53

Yep, for sure, there's going to be a lot of work coming out of this, particularly with the dairy cattle situation.

Speaker 3: 12:02

A lot of work coming out of this, particularly with the dairy cattle situation Now switching gears a little bit on a more personal note, wendy what sparked your research interest in HPAI?

Speaker 2: 12:13

We're going to start on that question. So we've been studying over a decade of trying to understand what is circulating in wild reservoirs and to try to get a better grasp on all the different variants that are out there and all the different factors that contribute to establishing a reservoir, maintaining a reservoir, viruses reassorting within and between species and what facilitates the shift from one host to another host and what allows the host to be receptive to virus. All of those different questions and you know layers and layers upon that all the way to how does climate change impact the interaction of species and impact their immune health? That impacts susceptibility to virus.

Speaker 2: 13:03

So all of those pieces and High Path was something that was on all of our radars for a while and then you know, of course we're all well aware of now it has made its way into a large number of species and has come to have many of the impacts that several of us have been fearing for a long time. So it was shifting into the high path was sort of a natural transition, but also incredibly interesting to watch it unfold in real time because it has it has expanded and diversified its host populations so rapidly that it's almost been possible to witness that change in real time. Of trying to make those ecological connections of how did it go from one species to the next and what is it looking like as it does that shift, and hopefully to be positioned to try to answer those questions as they're unfolding and get that insight on those species differences and those transmission differences. It has been a very large impact but it's been incredibly informative to be able to be involved in that research.

Speaker 3: 14:26

Yeah, it sounds very interesting and very rewarding. I imagine, too, there's going to be a lot of research also into different biosecurity protocols, especially when managing large populations of animals that could be susceptible to HPAI. And, john, why did you choose to submit these manuscripts to JAVMA and AJBR?

Speaker 4: 14:50

It's a good question.

Speaker 4: 14:51

I mean we and I think the bottom line is this is an important topic to veterinarians.

Speaker 4: 14:53

Both you know, wendy and I are at Cummings School of Veterinary Medicine at Tufts here, and so we're surrounded by veterinarians and we're always having the conversations with folks at our campus about influenza because of the research that we do at our campus about influenza, because of the research that we do.

Speaker 4: 15:14

But I would say, you know, really over even the last 10 to 15 years, influenza has been increasingly an issue to veterinarians, and including practice veterinarians, both because of some of the outbreaks that have occurred in dogs as well as ongoing influenza as a disease in horses, and that situation and sort of has paralleled the evolution of this current high path influenza strain that's causing problems, and now obviously there's a lot more reasons for veterinarians to be interested and informed and understand this virus, its potential, the risk that we think it might pose and the things that we need to be looking out for.

Speaker 4: 16:14

So I think you know both the need to inform veterinarians and the need to attract veterinarians to this type of research. We need people that are interested both in the clinical aspect of what's going on with IPATH influenza in animals, but also people who are interested in helping to understand and find out how we can both prepare and potentially combat a virus like flu as it changes. We're very thankful that you submitted these manuscripts to us. It's such important potentially combat a virus like flu as it changes.

Speaker 3: 16:50

We're very thankful that you submitted these manuscripts to us. It's such important information for our readership. And also thank you two for being on this podcast so we can share it with an even wider audience as well.

Speaker 4: 17:01

You're welcome.

Speaker 2: 17:02

Yeah, absolutely Likewise. Thank you for having us on this podcast so we can share information as widely as possible.

Speaker 3: 17:09

Of course, and as we saw too, your manuscripts have definitely received a lot of attention online too. I think they've been mentioned by 106 X users to date, so there's definitely conversation about HPAI out there. And, john, what have been the most surprising developments with HPAI so far?

Speaker 4: 17:28

Yeah.

Speaker 4: 17:28

So I think we've touched on some of them in our conversation already, and a couple of those that you know Wendy certainly mentioned a minute ago are the diversity of species that this virus has spilled over to and infected.

Speaker 4: 17:49

That's simply, as Wendy put it, unprecedented and surprising and along with that has been the focus point of this disease in causing neurological symptoms and that's not unheard of for flu infection in some circumstances and with some strains.

Speaker 4: 18:13

But again, in the diversity of species that that has been the case and the severity of those neurological signs and the predominance of it as a clinical presentation, I think is really surprising. But maybe in some ways the bottom line is this is a virus, and particularly the high-path avian influenza lineage that's currently circulating, that continues to surprise us in terms of where it goes, who it infects, what it's doing, all of the characteristics of its epidemiology out in the world. So I think we have other surprises to come and, like we've been discussing, you know, the infection of dairy cattle, I'm not sure anybody would have predicted that, despite the fact that dairy cattle are an animal that's outside and there's wild birds around it and so forth, we just haven't seen that kind of spillover of influenza viruses into dairy cattle and suddenly we have it with this high path influenza strain. So it will continue to surprise us, I think, and we need to keep after it.

Speaker 3: 19:35

I think it's a good example, too, of always keeping your mind open when it comes to creating your problem and differential diagnoses list, because I'm sure a lot of people wouldn't have thought about this as a potential differential diagnosis or these clinical signs, but you never know.

Speaker 4: 19:50

Yeah, I think that's really important point.

Speaker 3: 19:54

And for those of you just joining us, we're discussing HPAI with our guests Jonathan Runstadler and Wendy Puryear. Wendy, how did your research and training prepare you to write these articles?

Speaker 2: 20:08

Let's see.

Speaker 2: 20:08

So my initial training really comes down to molecular virology, so I have a pretty good understanding of the inner workings of the virus in general.

Speaker 2: 20:19

But then over the course of time since I've been working with John for quite some time now, getting that broader understanding of the host side of things, particularly with influenza and the ecological context of how the outside factors can impact transmission of virus.

Speaker 2: 20:39

The work that we've been doing related to influenza broadly, but then also with BiPAP, for a while now. For a while now has really been based on a lot of rich collaborations that we have between rehab facilities and wildlife professionals of all sorts of different areas, whether it be state, federal, local, veterinarians, and all of those interactions have really helped to also educate us on the different sorts of things that people see boots on the ground through several different formats. So whether it's somebody who's responding to a seal that is stranded on the beach or somebody who's responding to an eagle that's coming into the clinic or a cat that is presenting with unusual symptoms in the small animal hospice. So having that breadth of interactions with a lot of different professionals has really helped us, I think, to get a better handle on the bigger picture and trying to piece all of this together.

Speaker 3: 21:45

Thank you Now. This next set of questions is going to be very important for our listeners. Thank you Now. This next set of questions is going to be very important for our listeners, john, what is one piece of information the veterinarian should?

Speaker 4: 21:58

know before discussing HPAI with the client. I actually think it's something you mentioned just a minute ago, sarah, and that's that you need to keep an open mind as a clinician for flu, especially now in terms of differential diagnosis and the signs that you're seeing, and the underpinning of that is that I guess the one piece of information to understand if you're a veterinarian is that influenza is always changing, and so having that open mind about what you might see come into the clinic or as a patient may change as well from what we're describing today and what you know is in the media today, and so the next spillover or outbreak or case might be quite different. Presentation and flu can look like a lot of different things. So keep an open mind there.

Speaker 3: 22:57

And, likewise, what's one piece of information the veterinarian should know before discussing HPAI with the general public.

Speaker 4: 23:05

So I think you know with the general public it's a similar context. The general public is much less likely to understand virology as a whole and the sort of cycle of infection, understand virology as a whole and the sort of cycle of infection. But I think the one thing that veterinarians can relay to the general public is that influenza does exist both in humans as seasonal disease and in other animals as seasonal viruses that are endemic to those populations, and that zoonotic disease like influenza is an important and I think that's an easy case to make these days in some ways from our experience with coronavirus. But that zoonotic disease, influenza of which is one of those potential, is a really important thing for public health and public knowledge.

Speaker 2: 24:07

I think one additional thing that I would add for the public perspective is an awareness of the breadth of species that can be impacted by influenza and, in particular, thinking about how people's domestic animals as well may interact with wildlife, which is always important. But this really drives home the importance of whether you know, if you're out walking your dog and you come across a dead bird and the dog wants to roll around in it, that there could be a very real risk of transmission coming into that animal in those sorts of settings.

Speaker 4: 24:45

Yeah, I think that's a really good point that Wendy's making in terms of out in everyday life. There are influenza viruses that are out there. So you know, as somebody the general public needs to be aware of that. You know as somebody the general public needs to be aware of that. You know, with this high path strain of virus, we've seen these occurrences of, you know, dead birds 60, 70 dead birds on the beach where people are out walking their dogs and letting them off leash and so forth and it would be great if people were a little bit more aware of the potential for viral transmission that could impact them severely.

Speaker 3: 25:32

Those are all excellent points. Thank you for sharing. And now, on the other side of the relationship, wendy, what's one thing the general public should consider around HPAI?

Speaker 2: 25:43

Yeah, so really just restating that message of being vigilant and aware that there is influenza that is circulating, in some cases to pretty high levels, within wildlife, some cases to pretty high levels within wildlife, and that it's not at a point where people should be individually paranoid about going about and operating in the world. It's, you know, thankfully has shown a low tendency to come into humans at this stage, but it is something to be vigilant about and, you know, in particular, a reminder again of how people do not interact with wildlife. So, whether it's a live animal or a dead animal, being mindful that that is a possible place where you could be allowing yourself to be exposed or allowing your pets to be exposed, so now moving to the fun part of our podcast, a bit away from the heavier topic of HPAI, so we can learn more about you, John.

Speaker 3: 26:46

what is the oldest or most interesting item on your desk or in your desk drawer?

Speaker 4: 26:53

Well then, it depends whether I'm at my desk in my office here at work or my desk at home. On my desk at home, actually, I have this little notepad that I got from my grandfather, that I'm not quite sure of the origin of, but it's a little leather fold that has an embossed picture of a knight on it. It has an embossed picture of a knight on it and on the inside part of it, in addition to the little 3x4 notepad there, there's a little universal calendar, and this is the only place I've ever seen this type of calendar, where it's a wheel and you can just turn the wheel in a way that the windows are open, that it always gets to the right date, and it's the cleverest calendar I've ever seen in my life.

Speaker 4: 27:52

On my desk here at work I'm just looking at the one thing that I found here is a little truck and I'll show it on the screen for you, sarah. But I don't know if either of you know where that truck is from, but it was given to me by my kids when they were very little a replica of the truck that is in Close Encounters of the Third Kind that the guy experiences the alien ships come and shakes the truck and the lights go on.

Speaker 4: 28:30

That's one of my favorite movies, so that keeps me reminded of that.

Speaker 3: 28:36

Very cool, that calendar is fascinating.

Speaker 2: 28:39

I haven't seen that. I didn't see that, John.

Speaker 4: 28:42

Yeah, I'll bring it in. It's on my desk at home for things.

Speaker 3: 28:47

Wow and Wendy, what is your favorite animal fact?

Speaker 2: 28:53

I'm going to cheat a little bit here and squeeze in a virus fact in addition to my animal fact, virus fact in addition to my animal fact. So one of the coolest factoids that I think regarding viruses and animals is the fact that there are all of these endogenous retroviruses that inserted into the vertebrate genome hundreds of millions of years ago, and one of the proteins from endogenous retroviruses inserted in such a way that it has allowed the development of some of the key proteins for how the placenta functions. So really, the fact that we are here, that mammals were able to go on and exist, is potentially in large part because of the virus. I think that's super cool.

Speaker 3: 29:41

That's awesome. Spoken like a true virologist, that's awesome. And just thank you both, jonathan and Wendy, again for being here today, for sharing your manuscripts with our journals and also for sharing your knowledge today with our listeners.

Speaker 4: 29:57

You're welcome. It was nice talking with you, Sarah.

Speaker 2: 30:00

Absolutely. Thank you again for having us.

Speaker 3: 30:02

Of course, and to our listeners. You can read Jonathan and Wendy's articles in print, javma and online using your favorite search engine. I'm Sarah Wright and I want to thank each of you for joining us on this episode of the Veterinary Vertex podcast. We love sharing cutting edge veterinary research with you and we want to hear from you. Be sure to leave us a rating and review on Apple podcasts or whatever platform you listen to.