Bird flu on the rise

Following the discovery of H5N1 influenza of avian origin in a sheep in the UK this week, Gavin is joined by Dr. Abraar Karan of Stanford University to discuss the current state of bird flu in the US, its impact on public health, and the potential for human-to-human transmission. Dr. Karan analyses the ongoing outbreaks and infections in the US, the challenges in detecting and controlling the virus, and the lessons learned from COVID-19.

We chat about the complexities of viral evolution, the importance of robust testing and surveillance, the critical need for coordinated efforts to prevent a potential epidemic, and how bird flu might end.

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Transcript

This transcript was automatically generated using speech recognition technology and may differ from the original audio. In citing or otherwise referring to the contents of this podcast, please ensure that you are quoting the recorded audio rather than this transcript.

Gavin: Hello and welcome to the Lancet Voice. I'm your host, Gavin Cleaver. It's March, 2025, and today we have timely discussion with Dr. Karan talking about the H five N one bird flu. Dr. Karan is an infectious disease fellow at Stanford University, and I thought with a recent case emerging in sheep in the first time in the uk and ongoing outbreaks in the US over recent months, the threat of bird flu is very much in the public eye.

And so this is a timely discussion that Dr. Karan will shed light on the current situation in the us. We're gonna talk about the complexities of the virus's transmission and evolution, and as well the significant challenges faced on the public health side of things in detection. Prevention is an important conversation.

And I hope you enjoy listening to me in discussion with Dr. Abra Koran.

Dr. Abba Koran, thanks so much for joining us on the podcast, for being with us today on The Lancet Voice. I was super excited to have you with us. It's a particularly interesting time to talk about H five N one bird flu, avian flu, whatever you want to call it. We're gonna call it bird Flu for our purposes because the first case in sheep just happened here in the uk, but a lot of course of detention has been focused on bird flu in the US over the last year or so.

So what's the current lay of the land in the US with regards to bird flu? 

Abraar: So the current lay of the land with bird flu in the US we still have widespread circulation of the virus across multiple different species. We have all 51 jurisdictions with outbreaks in poultry. At some point in the last few years, we've got 17 states that have outbreaks in dairy cows.

We've had a few more states with just recent detections, so we know they're still circulating virus. Since 2025, we've had three cases in humans, three new cases in humans, and one of them was from Gary Cow to human, and two of them were from poultry to human. And this is essentially what we've been seeing is there's been ongoing spillovers from.

Either poultry in commercial culling operations or in backyard poultry flocks that people own or from dairy cattle. So people, farmers that are working directly with dairy cattle have been infected. We've also seen transmission from dairy cattle. Operations into poultry operations. And presumably that has been spread through workers that work in both contexts or from equipment that has been spread and used in multiple different locations.

And so these are some of the hypotheses for how it's being propagated and spread through multiple states and multiple facilities. 

Gavin: There's been quite a few bird flu outbreaks over the last few years, decades even. So what's been the progress of this one over the last year as it's been in the public eye, and I guess what makes it different from previous outbreaks?

Abraar: So the scale is quite large greater than 148 million birds have been called, which is several fold more than the outbreak that we had in 2015 with H five N two which is probably one of the more recent ones in our minds and. We've seen that dairy cattle have been infected, which is a new spillover into a new mammalian species that we had never seen before.

And anytime you have spillover into a new species, particularly one that has close and regular contact with humans there's concern of interspecies transmission and also for viral evolution. So what does that mean for the virus? Is it gonna become. More contagious? Is it going to become deadlier?

What kind of genetic changes are going to happen when you have the virus in a new species? So those are the questions that immediately came to mind when we saw dairy cattle infected for the first time. I. Right, of course. And have we learned 

Gavin: anything from studying those dairy cattle alongside those kind of questions that you put there?

Abraar: Yeah, definitely. We've learned quite a few things from dairy cattle infection. So one thing that we've learned is that the mammary tissue of the cattle has very high viral loads and the mammary tissue in the cow's udders, it has receptors both avian like receptors, which are alpha two, three receptors.

As well as alpha two six receptors, which are human receptors and for everyone to understand the key difference is that H five typically binds, it has what we call tropism, where it basically likes to bind to alpha two, three linked receptors. Those are receptors that are found in birds, they're found in human.

Conjunctiva in the eyes and in human lower respiratory tract. So in the lungs, human upper respiratory tract have what's called alpha two six receptors. So you have alpha two three and you have alpha two six. The utters of cows have both of these receptors, and that's something that we've seen where the virus is able to be replicating in an environment where it's exposed to both of these receptor types.

The reason this matters is that when you have alpha two six binding in the upper human respiratory tract, that is where you have people with symptoms like sneezing, coughing, runny nose, and that lends itself to transmission between people more easily, then someone's eye being infected, or someone having a lower respiratory tract infection.

So we've been following the virus to see if it has been developing any mutations that could lead it to have a switch in receptor troop, meaning it likes to now bind to alpha two six. And we have seen that. We've seen that in some of the human cases that have been infected, and we have been following this to look at different mutations.

In different proteins, surface proteins of the virus, and we've seen that has been occurring. The question becomes at what point will this fully transition into a epidemic amongst humans? And we have not seen transmission between humans as of yet. We have not detected it. Has it happened? It may have happened, it could happen.

There has been previous H five infections in Southeast Asia where. It's very likely there was transmission between healthcare workers and patients. So we know it's possible, but we haven't detected it in the US yet. And I can outline some reason why that may be. 

Gavin: Yeah. I guess the question that I would pose would be like, how far away are we from our understanding of what it looks like in cows and then subsequently in human cases, and how far are we from human to human transmission?

Abraar: So how far are we from human to human transmission is one of the fundamental questions. If you asked me in 20 earlier, 20, 24, I'd say. We may be seeing it last year, and we haven't, and we haven't, despite a lot of virus circulating in dairy, cattle multiple spillover events into humans, and yet we haven't seen it.

So one possibility is that the barrier to evolution is higher than we thought. Perhaps actually, multiple mutations are required, and perhaps it will not be that easy for those mutations to happen. So that's one possibility. The other is that it already has happened and we just didn't pick it up. And part of the reason this could be the case is when you have a spillover event into humans, we've seen mostly that it has been mild symptoms, including conjunctivitis where one's eyes get red and watery.

There's many viral causes of conjunctivitis. So people may not have realized that they had it. Secondly, we know there's been a resistance to testing on farm operations because of the potential implications of a positive test where it could impact a farm. They may be worried that the state will be investigating further that it actually could shut down operations temporarily and affect the bottom line.

There are clear disincentives for farm owners and farm workers to get tested in the United States. Many farm workers also, many of them are not documented. They may not be here legally, and so there is concern from that group to engage with the healthcare system. Thirdly, those same farm workers, they may not be getting very sick, right?

And so in not getting very sick, they may either have not gotten tested or I. They may have gotten tested and the test result shows that they have flu A. So this gets into how do you actually diagnose this? You need to subtype for H five. And initially there was no test except for through the state and CDC for subtyping.

Now I'm an infectious disease clinician at Stanford. I have the privilege of working with closely with colleagues in the Stanford Virology lab. And dr. Ben Pensky's lab here had developed their own subtyping assay that was published, and we've been using that. And so some academic centers like ours have a subtyping assay where you get your flu, a sample, and then you subtype to see what kind of hemagglutinin, is it H one or H three or H five or something else.

So it could be that actually in some of these areas, out in other parts of our state where you have dairy cattle, that they weren't able to subtype properly. And so those samples never really made it somewhere where you would detect this. Because remember, if you're using a point of care diagnostic or a test swab that never gets sent for subtyping, then you'd miss cases.

So it's either that they weren't getting tested, they didn't wanna get tested for privacy reasons, or that they did get tested and. The test didn't get subtype properly, or it could be that they got tested and then others that were near them didn't get tested in time. So we've seen that some of the positive cases, when you look at the tests in their close contacts, they've been negative.

But remember that it takes time for those contacts get tested. Sometimes the delays can be several days or longer. So it could be that by the time those contacts got tested that their test result was negative on a PCR test. But the way you would figure this out is to test them on antibody tests. So there have been antibody tests done in various settings from the CDC and here in California.

And some of those antibody tests have been positive in farmers that never were positive on a PCR. Never got tested in time. So we do know that there have been missed infections. Infections, that someone got sick, they had the right exposures, they never got tested, and then they have antibodies. To H five.

Those are all suggestions that we've not been detecting all the cases, and we may have even missed cases where there could have been some human to human transmission event. But what we do know is that even in the antibody studies in high risk groups, the positivity rate was 8% or 9%. It wasn't 50%. So it wasn't like there was some large scale outbreak that was missed amongst humans.

Now this also begs the question of what happens moving forward, because if we have a setup where the infrastructure is not very good, where it's very reactive, we may be testing people too late. We may not be having widespread antibody testing. There's a good chance that we just miss it altogether until it really gets our attention where people are getting very sick.

And I can talk a little bit more about, what that may look like based on some of the genetic differences between some of the genotypes that are spreading, where one does cause severe illness and. One has not. Yeah, absolutely. That would be really fascinating. It sounds like there's a lot of unknowns at play.

Exactly. There's a lot of known and unknowns. And so let's outline, the two big genotypes that we've been seeing. So we've got genotype B 3.13, and this is primarily what we've been seeing in the dairy cattle. So dairy cattle have primarily been infecting people. And when you sequence it, you get genotype B 3.13, and then you have genotype D 1.1.

And that is from, primarily been from poultry into humans directly. Now they're both part of the same clay, right? So the same grouping, the same overall family you can say. And that's been the 2.3, 0.4 0.4 B. It's a mouthful. So they're all part of the same clade, but then within the clade you've got different genotypes.

So they're slightly different. They're slightly different versions of the virus. What we've seen is that with B 3.13, it's primarily thought to be from dairy cattle. The infected milk from their udder splashes into the eye of workers or workers touch something and then they touch their eyes. And as I had mentioned, the eyes in humans have that alpha two three slic receptor binding.

And so you basically get the virus it, it comes into the IOL and then basically you get infected on the D 1.1 side. So this has been primarily from poultry into humans. We saw two severe cases. We saw the severe case that died in Louisiana, and then we saw the case in British Columbia in a teenager.

They had obesity and they were hospitalized. They actually ended up on ECMO life support. They survived. So we know that. There are versions of this virus that are quite deadly. D 1.1 from poultry likely is from people potentially inhaling dust with feces in it or some other mechanism where it probably is going deep into their lung.

Deep into your lung you have alpha two, three linked receptors. You can get quite sick and you can get bad pneumonia. And that's what we saw in these cases, right? They got pneumonia, they almost died. One died and 1, 1 1 almost died. So the question then becomes, is there something going on when the virus gets into dairy, cattle and then de human where it has become slightly milder?

And so something quite interesting happened recently. So we detected in milk D 1.1 in Nevada. So this was recent few weeks ago, and that was surprising because as I mentioned, milk had primarily been B 3.13. So we said, okay, if we're detecting D 1.1 in milk, then that means that it's spreading in cows now.

So that may have been another spillover from wild birds into cows, but with this more aggressive genotype. But then we saw a worker get sick in Nevada and they confirmed it was D 1.1. That worker, again, only had mild illness with conjunctivitis, even with D 1.1. And so it, it suggests a couple of things.

One is that as the virus gets in and into dairy cattle it's having adaptations into mammals. So like that virus, they isolated from this guy in Nevada, it had a. It had a mutation in polymerase PB two Protein, and basically that suggests mammalian adaptation, that the virus is adapting to spread in mammals better and binding to mammalian cells better.

We also saw that the sky was only mildly sick. So could it be that actually the mechanism, the route of inoculation is really important. So if it's getting into your eyes then it's gonna cause milder disease. If you inhale it deep into your lungs, you get bad pneumonia. And that makes sense. We see that for a lot of bacteria and viruses, that actually route of inoculation ends up determining what happens because it, it has a complex interplay with your immune system.

So what immune cells are coming forward, depending on where you're getting entry, 

Gavin: what are your kind of educated guesses as to how this plays out over the next few months and years in the us? 

Abraar: So here's the big concern. When you have influenza viruses, you can have a slow accumulation of mutations or you can have viral reassortment where you actually have segments of the virus swap in.

A host that's infected with. Two different types of flu virus. So you may have someone infected with H five like a farm worker, and that farm worker may also then get sick with H one or H three because they get just seasonal flu from somebody else. And you may then basically have someone who's.

Basically a mixing pot for these two viruses to swap genetic material and create something very bad. We saw this, right? We saw this in 2009 with H one N one. It was a Reassorted virus. While the overall number of deaths was probably similar to some bad flu seasons, the surprising finding was we saw a lot more deaths in younger people than we normally would expect.

So that's not good, obviously. The other thing is that because we've detected the virus in different species like there was a, a pig that had H five detected in I think October of 2024. Pigs are also very good mixing vessels where they get multiple viruses and they can basically create something really bad on accident that then spills back out into humans.

So that's been one of the big concerns, and I could totally see that happening the next flu season. And I'll highlight something else. Co-infections in humans can be complicated to detect. Imagine if you're sick and you come in and a hospital runs a flu test and it's positive, and then they run their typical subtyping, which detects H one or H three, and they stop there.

You would never know that person also had H five, unless you specifically subtype for the H five. So the CDC has been pushing to say, please start subtyping. They're asking hospitals to please start subtyping. This gets complicated as well because to subtype, if you're a hospital that doesn't have the assay, you need to send it to a commercial laboratory, which often requires a prior authorization from insurance.

So a provider would have to do a prior authorized insurance, send it to the commercial laboratory. They would have to know to even do this. And I think most providers will not realize to do this if they had a patient that already had a H one or H three detected because they wouldn't think to also subtype for H five.

I would say this is an important potential oversight especially in high risk areas where they really should be subtyping. Here at Stanford, for example, we were subtyping all flu a samples. So even ones that were positive for H one or H three, they would still get subtype for H five because that's how you pick up a co-infection.

The point here is that as you dig deeper and deeper, it's complicated. It's not that straightforward, and the system is not designed right now to pick up every co-infection or every transmission event. It's not. I'm working right now on a potential collaboration where with Stanford and the state of California as public health department, we're trying to increase some of the antibody testing capacity.

And so these kind of academic and state partnerships I think can be useful to fill in some of these gaps. But the real issue here is that these are very fast moving viruses. They're respiratory viruses. There's. Constant interaction between humans and animals. That interface is very busy. The chances are very high that this gets out of hand very fast, faster than we can do anything about.

It 

Gavin: sounds like from the broad sleep of what you're saying, that we're a long way away from a sort of ideal testing regime essentially. And so operating a kind of little bit in the dark. 

Abraar: Very much very much I'd say we're very far from that. And the reality is the commercial incentives are not really aligned.

That's gonna require some. Targeted programmatic developments whereby it becomes much easier for providers and hospitals to do the subtyping. Maybe there's financial incentives put in place for these, this type of testing to be done. More education on who should be getting tested and subtype.

This begs a different question, that one that we answered. And I think that this is what we had written about in The Lancet, which is essentially, what if you don't? What if you only do focus subtyping? What if you only are looking at high risk individuals who meet certain exposure criteria like working with dairy cattle, working with poultry or near someone who is known to be infected?

You may be missing something. And so what we did at Stanford is we basically were subtyping all flu a samples for H five. And that's actually how we picked up a case here in a child who had no known exposures. And that essentially is what happened. And so there has now been three cases in the United States with no known exposures, and one of those is the one that we picked up and what we wrote about in the Lancet.

These outliers are really important. If you talk to anybody that works on outbreaks, outliers are very important because they tell you something that you might be missing, right? Some exposure you may be missing. We've wondered about potential routes. We've wondered about if you can get infected from consumption of raw milk, right?

You can, in raw milk, you can find detectable virus. We've wondered about consumption of raw meats. We've wondered about all kinds of things, and I can say that in, in this child, we wondered about if could the child have been infected by a parent or a sibling or someone else, because there was others who had symptoms, but they tested negative on PCR testing.

And they did not have antibody testing done, so we don't know for sure if perhaps someone else could have infected the child. There was a child that was infected in San Francisco that was just just discussed by the C-D-C-M-M-W-R report and that child did have antibodies and they did do antibody testing of the contacts and they were negative.

So we also don't know how this child got infected. So these are the outliers that tell us that we may be missing something, or perhaps it was something obvious that just wasn't characterized well, hard to say. What are the chances on the other end of the scale that this just burns itself out low? I think very unlikely that this burns out because when you have the episodic where you have transmission in animals, so you have wild birds.

We're not getting rid of this in wild birds. You then have wild birds who are infecting backyard poultry flocks That will likely continue to happen. It's not that we have perfect preventative measures in all these backyard operations, nor do we have good oversight over them. Then you've got birds infecting cows.

If you look at any of the dairy farms there's very close contact between wild birds and cows. They're all feeding out in the same area. I highly doubt that anything is gonna happen here, even though the United States government has now put in significant amounts of money, the USDA actually just announced a hundred million dollars in funding for projects to battle abian flu and poultry because of what's going on with egg prices.

I think that if the dairy industry is able to continue without major economic impact. There's a good chance that not much is done here. Now cows have gotten very sick. There's been a reduction in milk in the production of milk. So I know that in the agriculture industry. There is concern about obviously the bottom line, the health of the animals.

Perhaps a little bit less the health of the workers, but, and the ag industry is very po powerful. There's a lot of funding and there are, there is interest from many of the agricultural industry players in better protocols for reducing infection. But I think that the extent to which we need to do this to truly eliminate the virus is massive.

I think vaccination is a area that is, there's been a lot of interest in a lot of that a hundred million dollars actually is focused on vaccines and therapeutics and poultry and dairy ca and also in dairy cattle. And there have been attempts to do this as people probably know, the H five vaccines in the past have not been very immunogenic.

They have not generated the strongest immune response. And in viruses like this, where you have constant mutation, that can be very tricky. There's different attempts at overcoming this problem. So you've got on the hemagglutinin, right? One of the surface proteins. You've got the head and the stock and the stock basically doesn't mutate quite as much.

So if you try to focus on targeting your vaccines towards components of the stock you actually may be able to overcome some of the issues with this constant mutation. It's not quite as strong of a immune response that is generated. But if you focus on the head, the problem is that the head mutates quite a bit and so you may be out of date quickly.

So there's no perfect answer. But the an you may not need something perfect, you may need something that's good enough. People have been looking at mRNA technology where we can get a, Moderna and others have been working on this in the United States. Where could we actually get a vaccine that has a stronger immune response that can be updated very quickly, and where we can now start quickly vaccinating dairy, cattle, and poultry.

There have also been interest in aerosolized vaccine for poultry where you can vaccinate very quickly rather than having to go bird to bird. So there's a lot of developments here, and I think it's gonna be a multi-pronged approach where you have many different factors, right? So reducing the interaction between wild birds and the commercial birds using vaccines, having better testing protocols.

So for instance. With dairy cattle, we've been doing bulk testing of milk. So you get all the milk together from a bunch of operations and you test the whole batch. And if it's negative, you're clear. But if it's positive, you now have to go back and figure out where it's coming from. We use this a lot in Covid as well, so it's gonna be a multi-pronged strategy.

Gavin: And how has the Trump government been compared to the previous administration in dealing with bird flu? 'cause of course, this last outbreak spans both governments, 

Abraar: Gerald Parker. Was the Trump appointed individual to lead the White House Office of Pandemic Preparedness and Response. So he's from Texas a and m University College of Veterinary Medicine, and he has significant experience, given his background in veterinary sciences to approach this from a one health angle.

I think this is pretty important. So at least appointing someone who's well known, who's had a lot of experience in this area, I think is an important move by the Trump administration because there have been some other appointees who don't really have what many of us consider the prerequisite experience to be leading some of the organization they've been appointed to here that seem to be a little bit different.

So I think there has been some hope that this is being taken seriously. This is probably an indication that. The agricultural industry is in line with getting the virus under control because it's bad for the industry in general. We've seen that with egg prices. We've seen that with many of the requirements now imposed on testing milk.

If we end up discovering a case of someone getting infected through consumption of milk. Which is possible, right? It could actually, one of the ways that could happen is that even though the human GI tract does not have receptors does not have a lot of receptors for binding the virus, the, as I mentioned, the upper respiratory tract like the NAS and also the lower respiratory tract do have receptors that can bind the virus.

So if you accidentally inhale it breathe some in aspirate. You get infected that way from someone consuming raw milk and we get a case out in the news that someone got infected through raw milk, that's not gonna look good for the industry. I think that's not gonna look good for raw milk or for pasteurized milk because pasteurized milk, we've detected RNA, so not live virus, but we've detected RNA and I think there's gonna be a misunderstanding from the general public.

All in all the industry I'm sure can see that getting this under control is good for them. And remember, a lot of ag industry is based in states that are pro-Trump or have been voted, are red leaning politically. So in that way, I do think that Trump sees this as something important that needs to get done rather than something that is, liberal media made up kind of stuff.

That's at 

Gavin: least slightly reassuring. You mentioned Covid in one of your previous answers just then, and I guess I was interested to know if we've learned any important lessons versus five years ago that are being used here when dealing with bird flu. 

Abraar: Absolutely. So to give a little bit of background, I worked on the SARS COV to two response for Massachusetts State Health Department as a medical fellow to the state health commissioner.

So we were quite involved with a lot of the res, the key early. Response decisions such as having closed down aspects of our state when to reopen, what kind of policies to implement. So I think there's a lot of lessons that are important for a bird flu. I will comment that I think the bird flu response is more complicated than SARS cov to two response.

And the reason is that you have a response that spans human health. So you have CD, C and state health departments animal health. So you've got the US Department of agriculture, and you've got food products. So you have food and drug administration, right? And so when you have that kind of a cross disciplinary and cross agency collaboration, and then you take into account the fact that you've got state governments, you have local health departments involved, very complicated.

Very complicated. I've worked on some aspects of this with different members of the state health department here and with some of the local health departments and with our acade, our academic enterprise at Stanford. The lessons here are that simple breaches can be very costly. So PPE on the frontline seems like something very simple, wearing eye protection.

Disinfecting equipment, disinfecting one's hands. So that would be a way to prevent spillover from dairy cattle into humans. We saw in Colorado that during one of the culling operations, the conditions were too hot, so workers had to take off there. Respirators and they got sick, a large outbreak there in poultry.

So where was the oversight or where was the biosafety protocols? When you work with a virus like H five in a laboratory setting, and you're in a BSL three laboratory setting there's many protocols in place that have to be followed. But when you're in the field. There's often violations of these protocols, but there's really no oversight, right?

You have workers in very poor conditions, not getting paid well who don't wanna report if they get sick. So that's not an ideal situation, and yet you're dealing with a live virus. So just something as simple as better. PPE respirators reusable respirators or face masks that have air purification or, the PPE that you can actually wear over your head that has fans in place provision of that kind of PPE at the front line, for instance, right?

Would've prevented some of the spillover. Access to regular testing. So why is it that these frontline workers are not getting regular swabs that are getting subtypes so that we can very quickly pick up or pooled testing protocols? So that would've been really important. Just basic stuff that we learned during Covid to prevent spillover from animals to humans.

I think there have been a lot of oversights just on that one part, and that's really 

Gavin: interesting. At 

Abraar: what 

Gavin: point do you think this becomes more concerning for the public? I'd imagine around, of course, human to human transmission, but you said before we could move quite fast, the fast growing outbreak.

At what point do you think it registers more on the public consciousness? 

Abraar: So in the public consciousness, there's two factors that I think people think about. One is, are people getting very sick? So we've seen this already in the cases, the two cases that got very sick. But what that means also to the public is that many people have not gotten very sick.

There've been, you know what, 70 cases in humans, many of them have not gotten very sick. Maybe this is not a big deal. The problem here lies in that's quite an oversimplification because you've got a genotype that was that had a slightly different route of inoculation that caused almost death and death, right?

One death, one near death in a young person. So people are not realizing that actually we're dealing with something that is, things that are very similar with just minute differences that have probably accounted for mild disease versus severe disease, and that can change quite fast. A few more mutations in hemagglutinin, a few more mutations in polymerase.

And now you might have something that is both, and then maybe you have a little bit of viral reassortment and you may now be dealing with something that transmits effectively between people that can infect the upper and lower respiratory tract cells. That can cause severe pneumonia that can be transmitted that evades the current vaccine options that we have that can happen and.

The challenge here actually, I think is one in communicating risk, right? So you have a, if you go to the CDC website, it says risk to the public low. What does that really mean? So would you say that the risk of something is low? If I told you that actually within a matter of weeks, it can become a massive epidemic that could be killing people at a rate of, 20% or higher.

Now you say, what does low really mean here? It's low until it's not. And if it takes very little for it to become not low, then is it really low at all? So that risk communication, I think is very tricky. And then the other thing is the transmissibility factor. So with SARS cov to two, we saw something where you have a low case fatality rate, but something that's very relatively speaking, right?

It's lower than Mers, or it's lower than Ebola. It's lower than typical H five, but it still was relatively high enough that with high transmission, you had millions of people die. So that's the trick here is that you can have a like relatively lower virulence with high transmissibility and you now have a spread across a population and now you have, even though you have a small percentage of people dying, it's a small percentage of a very large number, which is a very large number.

Gavin: Yeah. What are some kind of like 

Abraar: common sense next steps that you hope to see? So co common sense, next steps. So one, I would start really at the basics of preventing transmission into workers. Because that's where this is really going to happen. It's going to be from a backyard poultry flock that infects somebody they don't know that they're what they have.

Um. And so es essentially working closely with people who work with livestock such that there's a protocol in place for them to quickly get tested if needed and make sure that gets sub typed. Similarly, on the dairy cattle front, anybody that gets sick that has dairy cattle protocol for them to easily get tested, gets sub typed some kind of preventative measures in place with oversight.

So if you're someone who's sick we don't know what you have yet, even if it's mild on in, in this kind of a setting where it's high risk. If you're wearing a N95, you have some kind of source control so that you don't potentially start spreading to others or some paid time off until we figure out exactly what you have.

Increasing the throughput so that we get subtyping done very quickly on these cases and make sure they very quickly know if they have this or not. Better surveillance. Genomic surveillance, I, we haven't talked about too much, but basically having a very close eye on how the virus is mutating, so it would be helpful to have.

Some kind of a protocol in place whereby dairy farms poultry operations commercial enterprises in these industries are regularly sending samples that are getting genomic analysis to ensure that we know how the virus is mutating. Where is it heading? Is it adapting? Is it gaining mutations that we think would make it more likely to cause severe disease in humans or in animals?

Or to transmit better. So having a better view of where things are headed. There has been a lot of push from the United States on environmental surveillance, so air sensors, wastewater, surveillance. We've been looking at some of these areas and it can be complicated. I think the technology is getting there, but it can be very tricky to find a needle in a haystack.

So even with wastewater. Or with air surveillance, you're gonna find dominant viral colonies. So you're gonna find the dominant version of the virus, and you may not be getting the minor, what we call basically. So there, so when you think about viruses, right? You've got, you have a lot of replication going on.

And so when you typically use a test, the sample that you get is gonna be what's most dominant. But there's still, if you do deeper sequencing, you'll find subpopulations of virus that could be developing some mutations of interest. And that's what we saw actually in this human case that got very sick.

Only through deeper sequencing did we find mutations of concern. Getting the infrastructure on surveillance even better than we currently have it. And some of those could be technical limitations that will be overcome in time. I think those are some of the key areas. And then decentralizing testing.

So people have some options right now to test at home. There are home flu tests that will tell you if you have flu A or flu B or covid, for example. But there's really not a test that would tell you if you had H five. So if we had something in place where if this were to become a human to human transmission event or outbreak that we had quick decentralized testing where people can know if they're infected with H five.

Now, could this all play out in a different way? Could this play out where we do end up seeing age five, but it causes mild disease and it doesn't end up being something that causes an epidemic that kills many people. That may also be possible, right? It could be that we end up seeing transmission, but it ends up being mild disease only.

Because for viruses to evolve and to have to, for their own fitness they don't wanna kill their host too fast. So for viruses, it's actually better to not kill your host and be able to transmit effectively. So it could play out that way too. I think from Apol, like a health policy or political strategy standpoint, there is some cost involved.

If you cry wolf too many times on infections and there's so many things going on. We had empac, we have Ebola and Marburg outbreaks, we have polio, measles. There's so much stuff going on. So from I think from a political standpoint, there may be some strategy where they're waiting to see if this gets really bad.

And the fact that it hasn't gotten really bad means they don't wanna draw too much attention to it. 

Gavin: It sounds like a pretty serious situation but I'm glad we've had you on Dr. Koran to talk about it and to explain it in such clear terms. Thank you very much for joining me on the podcast, and we really appreciate your time.

Thanks so much for having me.

Thanks so much for listening to this episode of The Lancet Voice. Remember, you can subscribe to the Lancet voice where you usually get your podcast, and if you wouldn't mind going on one of those platforms and leaving us a review, if that's possible, we'd really appreciate that. That would really help us.

Thanks again, and we'll see you next time.