Avian Flu Update

Mati Hlatshwayo Davis: [00:00:13] Hello, I'm Dr. Mati Hlatshwayo Davis. Welcome to Let's Talk ID. I am the director of health for the City of St. Louis. And joining me today for a discussion on avian flu are Dr. Demetre Daskalakis, director of CDC's National Center for Immunization and Respiratory Diseases. Welcome, Dr. Daskalakis.

Demetre Daskalakis: [00:00:32] Thank you. Nice to be here.

Mati Hlatshwayo Davis: [00:00:34] We also have Dr. Andrew Bowman, a veterinarian, epidemiologist and influenza expert at the Ohio State University. Welcome, Dr. Bowman.

Andrew Bowman: [00:00:42] Thanks.

Mati Hlatshwayo Davis: [00:00:43] Last but certainly not least, Dr. Katelyn Jetelina, an epidemiologist and author of, "Your Local Epidemiologist." Welcome, Dr. Jetelina.

Katelyn Jetelina: [00:00:51] Yeah, thanks for having me.

Mati Hlatshwayo Davis: [00:00:53] So let's dive in. In late March, the Department of Agriculture announced that a form of avian flu had been confirmed in dairy cattle in both Texas and Kansas. So, Dr. Daskalakis, I'm going to start with you. Can you give us an update on what we know today on how far this is actually spread?

Demetre Daskalakis: [00:01:11] Sure. There are a couple of different ways to talk about where we are with this today, and it's one that requires a one health approach, talking about what we know in animals, as well as what we know in humans. So as of the 20th of May, 51 herds have been detected in the United States. So that's herds of dairy cows in nine states. That's where we are in terms of what we're seeing on the dairy cow side. And we can talk more about that on the human side. We have detected one individual with an HpaI, or highly pathogenic avian influenza H5n1 infection. It was diagnosed by the folks in Texas and subsequently has been confirmed at the US CDC. That individual was someone who had close interactions on a dairy farm working with cows, we presume with an infected herd again, but that herd had not been detected by the USDA at the time of the detection in the human. The good news is that this single individual who has had infection presented with conjunctivitis. So, red eyes. There's actually a case report in the New England Journal of Medicine that goes into it in a lot more detail, had very mild ocular symptoms only, and was tested again using both a nasopharyngeal specimen as well as an ocular specimen.

Demetre Daskalakis: [00:02:29] And both of those were positive for H5n1 and confirmed at CDC, notably that the conjunctival specimen had lower CT values than the respiratory specimen. In terms of where we are, along with the 51 herds in nine states, CDC has been working really closely with local health departments, state health departments, as well as departments of agriculture and the we means the Royal we of public health, meaning really with the effector of the state health department are monitoring over 300 people with potential exposures and have to date tested over 37 people who have developed some kind of symptom, either respiratory or ocular. Also note going back to the single case in Texas that that individual was connected to the local health department ultimately was treated with oseltamivir had a couple of close household contacts. They were also treated with oseltamivir as post-exposure prophylaxis, and none of them developed symptoms, nor did they ultimately test positive. I think that's where we are today, and I think we can cover other areas, but I think that's at least a quick overview of the epi.

Mati Hlatshwayo Davis: [00:03:36] So I love what you're saying so far. It's like I plugged you as the director of a local public health department because you said public health department about 50 times, which is what should be said, because coming out of Covid, it's so important for us to have these conversations early to help people who, quite frankly, have been coming from an alarmist state, understand where to contextualize this, but also understand that the CDC has been working so phenomenally with health departments, and it's really helped with the messaging. So I appreciate that. Katelyn or Andrew, anything you want to add?

Katelyn Jetelina: [00:04:05] Thanks, Demetre, for that update. I need to update my numbers now knowing that, but one of the biggest still questions we have in EPI is how big is the true outbreak rate? And we really don't know, partly because symptomatic testing of animals and humans is voluntary. Unless those cows are going across states and asymptomatic testing is not happening. Us epidemiologists are kind of trying to put this fuzzy puzzle together on how much this is spread. And we do that by triangulating multiple different data sources. So, for example, FDA testing milk in retail stores was one clue that this is bigger than we thought because positive milk wasn't supposed to be going to market. So that means that there were some cows with milk going to the market. The second was genomic surveillance. USDA shared viral sequences that showed that this was probably spreading even before we detected it and late last year. And then the third clue is wastewater surveillance. CDC just put a wastewater dashboard together really quickly for this and published at last week showing that there are actually some states with high levels of flu A that may indicate H5, although we need a whole lot more clarity on what those spikes and what wastewater show. We're still trying to get a handle on actually how big this is and the importance of keeping track of it.

Mati Hlatshwayo Davis: [00:05:33] Really helpful. Back to you, Dr. Jetelina. Have we ever seen this strain of avian flu before? You talked a little bit about how long we've been tracking it, but can you be specific about, like, how long it's actually been for folks who may not be clear?

Katelyn Jetelina: [00:05:45] Yeah and I think this is a really important comparison to, for example, Covid, right. We're getting off the heels of Covid. We feel like there's a lot of parallels, but this is actually really different from Covid because we have been tracking H5 for about 20 years, so much so that we actually know exactly where on the virus it needs to mutate to become more human to human transmissible. I don't like the comparison that this is March of 2020, or even January of 2020, right? This is way before and perhaps we're watching a spillover event in real time. And so that brings my anxiety down a little bit. And I think it does for a lot of public health people. And also we have a stockpile of vaccines for H5. We're not starting from zero like Covid. This has been around and we've been tracking it. The most concerning thing is that it's just changing pretty quickly and going in animals. We didn't really expect it to go in, and so it's really raising the flag for a lot of us in public health that we need to really stop this now before it becomes a problem for humans.

Mati Hlatshwayo Davis: [00:06:47] So, Dr. Bowman, what do we know about what precipitated the jump from birds to mammals and then to humans?

Andrew Bowman: [00:06:53] Yeah, I think that's a $10 million question at this point. I mean, I would love if we could understand a "when" exactly. We've got our guesses but realize that's built upon the surveillance data that's available. And trying to connect the dots is only as good as the dots you have. Trying to figure out when and how that spilled over would be huge to understand. How do we keep this from happening again? I mean, great point has been made, right? I mean, if you asked us eight weeks ago, influenza and cattle, no one thought of that. And, you know, as this kicked off and everyone asked, you know, well, who are the bovine influenza experts? There were none, right? I mean, exactly zero. That was not a thing. And so, you know, from the veterinary world, we did not routinely test cattle for influenza. That was not on any veterinarian's diagnostic test. You know, this is much, much to the contrary of TV, right. We have to order which pathogens we want to test for. And flu was not on the list of any bovine screen. And so, was it flying under the radar for a while? Certainly. How long? We don't know. But we're all quickly getting up to speed on that. So yeah, when and where the spillover occurred, I sure would love to know. And then I don't think I can overstate how different this is, moving into a different host that we didn't think was particularly susceptible to influenza. And we've added the mammary gland to this, which was again, nothing. Okay. Apparently in 1953, someone put some influenza into a cow's udder. But after that, no one has really thought about this in great detail. And so it's a steep learning curve in animal agriculture because this species and these producers, this is new territory for them. And so trying to reconstruct where and how transmission has occurred both intra and interspecies is a lot of work that's happening. But, uh, you know, it's slow.

Mati Hlatshwayo Davis: [00:08:55] So, Dr. Daskalakis, has the human case been genotyped?

Demetre Daskalakis: [00:08:59] Great question. I just want to say I've learned a lot about cow flu, too. [laughs] Like, I know as a human provider, I was like, there's a flu D? And all of my veterinary friends were teaching me about flu D, and it's really speaks to this sort of one health approach that's really important in this. So back to the actual question [laughs], beyond my voyage in veterinary infectious disease, which is new, it's to say that yes, we heard about the case. We released, I think, our press release on April 1st with the Texas Department of Health. That sample flew over to Atlanta, and we confirmed and then genotyped it very quickly. We also phenotyped it, and I'll talk a little bit about that as well. But the rapid thing we did was sequence it. And the sequencing was important for a couple of reasons. One, it demonstrated, just like Dr. Jetelina said, that we actually do have two candidate vaccine viruses that have been produced that can be flexed up into available vaccine fairly quickly. So on the order of weeks now, before I talk more about the genotyping, I just want to talk about what flu does because like every infectious disease provider should know, like what this is all about. So all year long we can get flu viruses and we figure out what's going on with them.

Demetre Daskalakis: [00:10:11] We see trends and we decide if there's any that get elevated to sort of producing candidate vaccine viruses. So before this, there were viruses that we detected that we then made candidate vaccine viruses. Why is that important? It shaves off between 8 to 12 weeks of what can be a several months process of actually developing a vaccine to a new virus. So that genotype first told us we have a couple of strains, two CVVs, candidate vaccine viruses that are in the bank that we can use. The second thing is we looked at known mutations that would imply resistance to any of the FDA approved antivirals, and we're not seeing those, which is another really important thing. And then lastly, Dr. Bowman And Dr. Jeteline sort of implied this. We also looked to see in that specimen whether there are any sort of changes that happen in the genome that would make us concerned for the potential for more expeditious mammalian spread or specifically human spread. We found one change in the polymerase that's associated with mammalian infection, but not necessarily enhanced transmission. Now, that's where we leave the human piece for a moment. Now, we've been working with USDA, and I think Dr. Jetelina mentioned this, they've been releasing lots of sequence of lots of virus, and we're monitoring that with them, looking at it from the human lens to make sure that there's nothing in there that makes us concerned that we have changes.

Demetre Daskalakis: [00:11:35] And as she said, the virus, we think HIV is twitchy in terms of mutations. Flu is even twitchier. So that's why we're watching it very carefully. We've also phenotyped this. So we've phenotype this virus against the FDA antivirals, confirming that the genotype matches the phenotype. It looks susceptible. And then we're also doing a series of other things, including ferret sera that have been done already that are ferret sera that are in ferrets immunized with those candidate vaccine viruses, and using the correlative protection that we have for those, it appears as if those vaccines in ferret sera appear to meet the criterion for protection, and then also are working with our friends at BARDA and others to do human sera from the trials from those candidate vaccine viruses as well. So all of that is happening. I'll just say, really importantly, to emphasize, within four days of getting the virus, we had put up at CDC, a pretty good description of the genotype, as well as an assessment of risk. Dr. Jetelina said lessons from Covid, speed, efficiency and transparency are really important so we're trying to do that.

Mati Hlatshwayo Davis: [00:12:41] I have to say that as a consumer of that, I could not underscore just how incredible it's been. We got the information early. We got the communication tools. I mean, from a public health perspective, it has been a joy to see how this has been handled, quite frankly. So you talked a little bit about the work that's being done around vaccines. But from a public health perspective, the simple question I always get is a vaccine for humans or animals available for H5n1? So you started talking about it. Can you talk about the work that's being done there specifically, and what we should be telling the public at this time?

Demetre Daskalakis: [00:13:13] The most important message right now for the public is that the risk to the general population is low, but we are concerned for individuals who have very close exposure to animals who could have the highly pathogenic avian influenza. So specifically thinking dairy cows. Oh, and footnote, poultry because we also keep doing that as well. So that's the first message. In terms of vaccine, this is where that candidate vaccine virus, or that CVV thing, becomes really important, because there is a small supply of the vaccine available if we have to sort of flex into a vaccine strategy. Along with that, there's all the work that we're doing. There's sort of different kinds of vaccine available. There's vaccines that's already vialed and ready to go. There's vaccine that is available in bulk that needs to get vialed. So there's like a middle term process. If the decision is that we need to sort of move to a vaccine stance, we have some things that need to happen to move the CVVs into a place where we can use them in folks arms. That really is like some regulatory steps. And then there's for the bulk vaccine, there is also the need to then vial that vaccine and get it ready if we need to do something bigger. And so those are the conversations that are happening across the US government with a lot of sort of scientific collaborators to identify what the right sort of strategy is. But again, the simple answer is that there are vaccines, they're not on the shelf. There are some steps that need to happen before they come to the shelf, but we've identified the two that we would implement if we had to.

Mati Hlatshwayo Davis: [00:14:41] Excellent. So, Dr. Bowman, when you hear that, do you think we should consider vaccinating animals on a massive scale?

Andrew Bowman: [00:14:48] Yeah so that's a loaded question. You have to understand that there's a lot of trade implications around vaccinating animals and how we're going to do that. Specifically, if you think about poultry, right. There's a definite issue there about trade implications for folks that countries that do or do not vaccinate for highly pathogenic avian influenza. And so for the most part, right, the US poultry industry has taken a zero tolerance stance on HpaI and the birds. And so we have not vaccinated. And likewise cattle is a totally unchartered territory, right. Because no one had even a cattle influenza vaccine anywhere in a thought process, let alone dialed into a CVV. There's going to be a lot of hurdles to jump through if we go down that path. One of the major drivers of if we're going to vaccinate cattle or not for influenza is we need to understand the transmission. And as we're sitting here trying to figure out, are we going to go into prevention, control or elimination mode? We really have to understand where we at. Where's that needle sitting? And can we push it out and will we turn this into an elimination program, or is it essentially the farm gate is open and it's everywhere, and we need to go into control mode.

Andrew Bowman: [00:16:04] And I think that will dictate then do we go into vaccine or not. Realize getting vaccines approved for food producing animals is a rather long process we can look at through history, even getting the 2009 influenza pandemic vaccine approved for pigs, that was not a quick process, and we already knew about flu in pigs. Flu and cattle is a whole other thing. And so we don't have a backbone vaccine that we can just slide a new antigen into. We're going to have to develop this from the ground up. So it will not be a quick process. And then expectations of efficacy, we really don't know. If this is largely your memory. That may be tough right. Getting good immunity there that's going to reduce viral replication may be a tough ask for vaccine. So there's a lot of things we have to consider diving into this first which is regulatory. I think that will be a big one, especially as we think about trade implications. Will our trade partners take milk from animals that have been vaccinated, or meat from animals that have been vaccinated?

Mati Hlatshwayo Davis: [00:17:10] I really appreciate the transparency in that answer, because I think it helps people to contextualize the way we should be moving forward. And quite frankly, and obviously I'm biased, the fact that the foundational preventative tools of public health are where we need to be while we work on both the human and the animal side. Um, so, so I want to pose this to each of you. If the strain makes the jump to humans, what lessons can we take from Covid 19 and apply to a potential outbreak or pandemic? What preparation, if any, should clinicians make? Because our audience is very weighted to our clinicians here as well. So just interested in what you guys think about lessons learned and what preparations, if any, clinicians should be making.

Demetre Daskalakis: [00:17:50] The first things that clinicians should do, I think, is stay informed. That's a really important first step. So again, the risk is low for most folks. But when we think about especially the role of ID doctors in my clinical history, it's the sort of perceptive clinician tends to be a really important piece of what we do in terms of disease surveillance, making sure that folks get a good story from people like, are they working on dairy farms? Have they had an exposure? And then thinking quickly that if there is concern to call their local public health department, but that's not about the Covid lesson. The Covid lesson for me is use the resources that we're able to give through public health so that clinicians have an awareness. Dr. Jetelina mentioned, we are putting up wastewater to sort of give a sense of sort of what's happening in the world in terms of flu activity. We're overlapping that with our syndromic surveillance. That gives us a sense of who's coming to the E.R. with influenza-like illness. We're looking at our test percent positivity, both in public health labs and commercial labs. And we're putting that all on our website, along with a weekly spotlight at CDC that says, like, what's going on with highly pathogenic avian influenza. By lesson from Covid, after having been incident manager in New York for a long time of it, as well as working in federal public health for some of the vaccine campaign is, it's important that we continue the information flow, be really clear about our thought process even when we don't know everything, and just give people the tools for awareness that they need, as well as an easy way to figure out, like, what's the next step? Those are the lessons from Covid transparency and ease of data access and communication, and lead into our local public health partners. Since they're so important in terms of what actually happens on the ground. I'm going to tag in my friend Dr. Jetelina to take it from there.

Katelyn Jetelina: [00:19:36] Bringing the public and bringing physicians along for the scientific discovery ride and anticipating concerns and being responsive to questions on the ground is a key lesson we learned during Covid. I think the other thing I would add on to Demetre's answer is, especially with physicians, to recognize that we are at a very low time in trust, and physicians and local health departments are one of the most trusted sources of health information for the public today. And so, yeah, we have this top down, trickle down information impact, but we really need to figure out how to leverage the bottom up as well, and equip these trusted messengers like the physicians that are listening right now. One really other important lesson is that a vaccine does not mean vaccination. And so if we do turn the dial and say, hey, we need to start vaccinating, even if it's only frontline workers or just health care workers, that we really need to think about vaccine hesitancy, this decline in trust, access problems, fully relying on vaccines and the overconfidence were one of the biggest mistakes of the Covid 19 emergency. It's best to face these threats with humility and determination when talking to patients.

Demetre Daskalakis: [00:20:55] Can I double click on that? I need to double click on that. One of the things that we do in public health is confuse supply with access, right? So it's not just do you have it. It's and how are you going to give it, in a way that's contextualized to the humans that need it. And so I just want to double click on what you said because it's so important. And then this one different than Covid, it's partnering with our veterinary colleagues. Since we've got Dr. Bowman on. It's a different story here in terms of what we're seeing. So I just wanted to I had to give you a high five.

Mati Hlatshwayo Davis: [00:21:26] And Dr. Bowman, since your name was mentioned with such love and adoration, I'll be honest and say as the director of health, I never talked to my veterinary colleagues much, if at all, during Covid. So what lessons did you learn specifically in your field, and what would you say to your clinical partners as well.

Andrew Bowman: [00:21:44] The lesson from Covid really is the use of molecular tools, especially as we're looking at this, and this could be veterinary or human health. This virus will trip a rapid flu A test, undoubtedly, and it will be easy to just call it flu A and let it go. I think the key that we actually get sequences and figure out what's going on, as we mentioned, the astute clinician. I think the molecular tool is going to be huge in this. And so it's really easy to bypass it and let it go and say, hey, it's just flu A um, or, you know, the proverbial, oh, it's some virus and let it fly. I can't underscore in this one, you know, we learned from Covid as we're looking for a new variants emerging, as we're looking for those changes, sequence is key. And so the only way that happens is samples get submitted for sequencing.

Demetre Daskalakis: [00:22:32] We're actually also, you know, generally this time of the season we start to downscale some of the work that we do around getting flu A that's not subtyped in the field. And so we're actually not scaling back. So we're keeping that going throughout the summer and into the next season for exactly that reason.

Mati Hlatshwayo Davis: [00:22:50] Oh that's so important to know okay. So I have some nerd questions to round this out. So samples of mammary alveoli from deceased cows had been found to contain the virus. Have intact copies of the virus been found in raw milk labeled for sale to other livestock? Do we know?

Andrew Bowman: [00:23:08] To my knowledge, none in labeled for sale milk. All the milk that I know of that has had viable virus in it has been collected on affected farms.

Mati Hlatshwayo Davis: [00:23:17] Okay, great. Because we've been actually getting quite a few questions with concern understandably, especially from lactating mothers and folks with young children. Is there a concern that cats and cows can act as mixing vessels, given the association of wild animal droppings in feed and with cats drinking raw colostrum, as well as infections spread between sick and healthy cows?

Andrew Bowman: [00:23:38] Yeah, so that's got the loaded question of reassortment, right, which is a major issue for influenza. The way that influenza can evolve by switching out the the genomic pieces and parts. Could reassortment occur? Yeah, reassortment occurs every day across the world, especially in some species. The good news is that for the most part, we don't have another endemic influenza virus in cattle, we don't have another endemic influenza virus in cats. And so reassortment requires that you have two viruses co-infecting at the same time. So could it happen? Potentially. But you got to have the partner to dance with. And right now I don't think we've got the partners in either of those species. That being said, we do have to consider reassortment occurring in other species if this virus ends up in another host species that does have endemic influenza, of which there are plenty, right, that that's something we would have to consider. But I don't think we're we're too concerned at present about at least major reassortment in bovine or feline species.

Demetre Daskalakis: [00:24:41] That's why it's fun to talk to your veterinary colleagues.

Mati Hlatshwayo Davis: [00:24:44] I'm telling you! This has been, I mean, obsessed, quite obsessed at this point. So B3 13 is circulating primarily in dairy cows. And Aphis reports that a wild birds in Michigan have been infected primarily with the Eurasian H5n1 lineage. That's the clade 2344B. Do we anticipate B3 13 infecting wild birds as well as domestic poultry?

Andrew Bowman: [00:25:10] So influenza right, is a giant game of who's giving what to whom. I mean that that is influenza. And we know every time we have interspecies transmission we have trouble. Whether that's a one hit wonder and it doesn't go anywhere, or results in sustained transmission, that's a whole other thing. But generally, interspecies transmission is not good. Where it will go. Who knows? I mean, we don't know how it got into cattle, so we don't know where it's going to go from there. We do have to understand that there are a large number of animals on some of these farms, and if they're producing high viral loads, the potential for transmission in other species, whether that's avian or mammalian, is there. And we have to understand that risk. But we're so early in this outbreak, it's really hard to tell who's going to give give the virus to to whom.

Mati Hlatshwayo Davis: [00:25:56] Thank you. So with that, I would love to close with each of you having a closing statement, if you will, on one takeaway point that you'd like to close us out with. So I'll come to you first, Dr. Jetelina.

Katelyn Jetelina: [00:26:11] When I talk to the general public, I think it's really important to consider that risk is not uniform right now. And to the general population, I tell them, you know, keep this in about 2 to 7% of your brain space. This is not a 100% brain space thing right now, like Covid was at the height. That's very different for veterinarians, for farm workers that are at higher risk right now. And you really need to have laser focus on helping them be as healthy as possible and the most feasible way. And we'll see, you know, keep this in the back of your mind and we'll see how it plays out, because it is playing out in real time, which I think as an epidemiologist is really exciting but can also be confusing at the same time. So to be determined.

Mati Hlatshwayo Davis: [00:26:55] I love that as a final word, risk stratification and definitely stealing the 2 to 7% of brain space for those of us not in the high-risk category.

Katelyn Jetelina: [00:27:03] [laughs]

Mati Hlatshwayo Davis: [00:27:03] That is like public health messaging genius. Dr. Bowman, what would be your closing statements for us today?

Andrew Bowman: [00:27:10] We have to understand that on the veterinary side, we are not just running, we are sprinting and we are trying to get up this steep curve quickly. And the good news is there's a lot of great influenza folks that, you know, we were using our influenza knowledge for all sorts of other species. And we are quickly pivoting to cattle. It's kind of all hands in the barnyard, let's get to this sort of thing. And we are more than happy to talk to our public health colleagues because yeah, we certainly have some lessons and have some ideas of ways to prevent this. And maybe we're not so good. We kind of shake our heads and keep our head down. But there's definitely some great opportunities for collaboration across the animal human interface, both the, you know, as we're looking at viral surveillance and potential ways to control this.

Mati Hlatshwayo Davis: [00:27:56] You heard it, folks, our veterinarian friends are sprinting, not walking or running. So give them give one a hug the next time you see them. And don't worry, Dr. Bowman, unfortunately for you, I know how to get a hold of you now. So as a close public health friend now, you will be hearing from me. Dr. Daskalakis, can you bring us home?

Demetre Daskalakis: [00:28:12] Sure, so I'm going to take the infectious disease clinician approach and say you should have memory T cells that about 10% of them are aware. So if you're exposed to a human who has the right exposure, that you expand that and actually respond quickly by saying this is a human who potentially has respiratory symptoms, who works on a farm or has been around cows or poultry. I, as a clinician, need to do the thing, which is to call my friends at local public health to make sure that I do the right testing, to make sure that we're not missing any people when we have the opportunity. So I think it is do the thing infectious disease clinicians do, which is to keep your eyes and ears open, connect to the data, and when you link the two really help us to make sure that we're not missing any cases and how to sort of both identify and test folks who potentially have this exposure.

Mati Hlatshwayo Davis: [00:29:01] Ah, just a brilliant way to end the podcast. I cannot thank all of you enough for joining me today. Such a phenomenal message made easily accessible to our community. My hope is that this is all I'll need from you, but as this progresses, just keep your calendars open for a part two as needed. Thanks everybody!