A Bird Flu Pandemic Hovering on the Horizon

Could the worst outbreak of avian influenza on record lead to another pandemic?
14 February 2023
Presented by Chris Smith
Production by Will Tingle.


chicken and a globe


With over a billion birds dead and signs that the influenza virus is now spreading among mammalian species in the wild, are we at risk of another pandemic, just as we thought Covid was over?

In this episode

A flock of geese

01:02 - What is bird flu?

How does influenza normally affect us, and why is this strain different?

What is bird flu?
Ed Hutchinson, University of Glasgow

A new strain of this H5N1 virus - which infects birds but has thankfully so far only rarely infected humans, albeit with very high mortality rates of around 70% - has been spreading widely since late 2021, leading to the most severe bird flu outbreak yet documented. Globally, more than a billion birds are said to have been killed or culled over the last 2 years. So why is this happening, and, as cases of H5N1 are now also being found in mammals, is the virus edging closer to us and possibly a pandemic? Human influenza that you're probably more familiar with is a virus that attacks our body by infecting the cells in our respiratory system. The proteins on the surface of the virus act as a key that unlocks access to cells in our nose and throat. The influenza virus hijacks these cells and uses them to make copies of itself. In most cases, the inflammation caused by this process alerts the body’s immune response and the virus is eventually destroyed and removed, but often not before we cough it out onto someone else. Most people, because they've been vaccinated, caught flu in the past, or both, are at least partially immune to the infection, which limits its intensity and how fast it can spread through the population. It is still, nevertheless, a serious infection that kills over 650,000 people per year, usually the frail elderly. That though is a tiny number compared with how many could potentially become infected during a pandemic. This happens when a "new flu", with a totally different appearance to the viruses that we catch normally, begins to circulate. The usual source is a bird form of the virus that may have jumped directly into humans, or come via an intermediate, like farm livestock. Because no one has seen the virus before, no one is immune and everyone can catch it, producing very high rates of infection very quickly, just like with the Covid-19 coronavirus pandemic. And because these viral newcomers are not well adapted to humans, they tend to produce very severe infections with high mortality rates, even among young, healthy people, which is why H5N1 human infections have been lethal in 70% of cases. But how does avian flu transfer from bird to bird, and how do potential pandemics come about? I spoke to Glasgow University flu virologist, Ed Hutchinson.

Chris - A new strain of this H5N1 virus, which infects birds, but has thankfully so far, only rarely infected humans, albeit with very high mortality rates of around 70%, has been spreading widely since late 2021 and produced the most severe bird flu outbreak that we've documented yet globally. More than a billion birds have said to have been killed or culled in the last couple of years. So why is this happening? And as cases of H5N1 are also being found in mammals, is the virus edging closer to us and possibly a pandemic? The human influenza that you are probably more familiar with is a virus that attacks our body by infecting the cells of our respiratory systems, the proteins on the surface of the virus act as a key that unlocks access to cells in our noses and throats. The influenza virus hijacks these cells and uses them to make copies of itself. In most cases, the inflammation caused by this process alerts the body's immune response and the virus is eventually destroyed and removed, but often not before. It's had a chance to be coughed or sneezed onto somebody else. Most people, because they've been vaccinated, caught flu in the past or both are at least partially immune to the infection, which limits its intensity and how fast it can spread through the population. It is still nevertheless a serious infection though, and one that kills over 650,000 people a year. Usually the frail elderly. That though is a tiny number compared to how many could potentially become infected during a pandemic. This happens when a new flu with a totally different appearance to the viruses that we catch normally begins to circulate. The usual source is a bird form of the virus that may have jumped directly into humans or come via an intermediate like farm livestock. And because no one has seen this virus before, no one is immune and everyone can catch it, producing very high rates of infection very quickly, just like with the Covid 19 Coronavirus pandemic. And because these viral newcomers are not well adapted to us humans, they tend to produce very severe infections with very high mortality rates, even among the young and healthy people, which is why H five N one human infections have been lethal so far in up to 70% of cases. But how does avian flu transfer from bird to bird and other reports of H5N1 getting into mammals? Anything we should worry about? I spoke to Glasgow University flu virologist, Ed Hutchinson.

Ed - Influenza viruses cause seasonal influenza for us every winter, but they can also grow in many animals. In fact, they're not primarily a human virus at all. They are a virus of birds and particularly of wild waterfowl where they mainly spread through what we call the fecal oral route, which means it comes out the back end of a bird and then goes back in through the front. And most of the time it doesn't make them particularly sick as far as we can tell. Some of those strains do make them more sick. And there's been a strain of bird flu, which has been on the march recently, which has been making wild birds extremely unwell and wiping out huge numbers around the world.

Chris - And that's H5N1.

Ed - Yes.

Chris - The other thing birds do of course is move. They don't need a passport to do it. And presumably they are therefore a really powerful vector for moving the virus from where they pick it up to where they may go and spend the winter, spend the summer or where they may just stop for a rest among other birds.

Ed - Absolutely, yes. So we can follow the spread of influenza along the bird migration route. We can detect it in ponds where migrating water birds settled. But the other thing birds do is that they won't respect the keep out signs on the edge of farms so that if you have poultry farms, the birds there are at risk of being infected by influenza as well.

Chris - And what's the difference between what's going on in these birds and pandemic flu?

Ed - A pandemic is when a new infection, in this case a new virus, gets into humans and spreads all around the world. So pandemic literally means all the people. There are two things which might stop a virus from doing this. One is that it's just not very good at growing in people. So viruses take over the machinery of ourselves and use them to make more copies of themselves. And what that means is that they get really used to growing in one particular type of host, one particular species and are a bit rubbish when it comes to most other species. So a bird virus wouldn't normally grow well in humans, but influenza has an unusual trick in the way it copies itself, which is it has broken its genes into eight physically separate segments. These are a bit like chromosomes. This basically allows the virus to have sex in the slightly boring genetic sense of having sex, which is that you have parents and they exchange genes to produce offspring. So imagine that you were infected by a human influenza virus and then an influenza virus virus from a bird. An infected cell might produce a virus where almost all of those genes are from a human influenza virus. And so it's good at growing in humans, but the genes for the proteins on the outside of a virus, the ones which the immune response can most easily recognize an attack from, are from a bird virus and human immune systems have never seen them before. You won't be vaccinated against them, and that's when a new pandemic virus can appear and spread rapidly around the world. That's what happened in 1957, 1968, 2009. So the recent influenza pandemics have come about that way.

Chris - And this is why various people including yourself are concerned that if we've got human flu circulating at the moment, which we have, and you've got this bird flu circulating, then it's possible that a farmer looking after a big flock of birds could be exposed to a bird flu. And then you get this, this sort of genetic pick and mix that you are talking about, and we could end up with a human adapted bird flu strain that will then spread as a pandemic.

Ed - Yeah. So that's the situation we want to avoid. Now although influenza is unusually good at doing this, it still finds it very difficult to do. There's a huge amount of influenza out there, a huge amount of humans, a huge amount of birds, and we still only tend to get pandemics every few decades. So this is still a hard thing to happen. But in a situation where you have a lot of avian influenza and then get into farms where there are people and other mammals, that increases the risk of those rare events happening.

Chris - So how does the point that was made or made public by the UK Health Security Agency last week, that they were detecting cases of this bird flu virus among wildlife mammals like foxes and badges, for example, in the UK countryside. How does that fit this formula that you've been setting out for us? Because if it's not going straight into a human, it's into one of those animals. What does that mean? What are the implications of that and how's that happening?

Ed - So in all likelihood that happened from scavenging. So we've got this very aggressive strain of bird flu. Birds will die and their bodies will be riddled with the virus. And then an animal like a badger or a dog will come along and will take a chunk out of that and get a mouthful of virus. That animal may or may not get sick, but in any case, it's quite unlikely to pass any virus onto another mammal so the virus will not have many chances to adapt to mammals. We do focus on farms though, because the whole setup of farming is to take mammals and house them together at unnaturally high densities and unnaturally close to people. That's probably where the human influenzas we have originally came into humans through exposure to farmed animals. And it's why if we look at, for example, the case in the mink farm in Spain recently, which didn't take off, but that was a case where mink got infected. But because it was living very, very close to other mink, there was a chance to infect others and others and others, and the virus had some extra chances to adapt to mammals. Now in that case it didn't, but that's the sort of situation where we would worry about how an avian virus could adapt to humans.

Chris - I'm sort of reading between the lines and forgive me for almost putting words in your mouth, but are you saying then that if we keep an eye on farms and minimize the chance of the virus, establishing that sort of chain of transmission under that sort of pressure, we reduce the risk of it becoming a human infection?

Ed - Yeah, so I think farms are the biggest place where we need to look for controlling the risk. Obviously, you know, from a conservation perspective, we should be concerned about what's happening with wild bird populations as well. But looking to where it's going to spread over into humans, biosecurity on farms is a really important issue right now.


A poultry farm

09:54 - Why is this bird flu outbreak so bad?

What about this strain of avian flu has meant it can be so infectious and fatal to birds?

Why is this bird flu outbreak so bad?
Louise Moncla, University of Pennsylvania

What’s surprising is that H5N1 influenza is not a new kid on the biological block. We’ve known about it for nearly 30 years. So why is it surging so significantly now. As Ed was just saying, poultry farming is critical to the equation here, because it looks like the virus has passed back and forth between wild birds and poultry farm stock, now with devastating effects, as Will Tingle heard from the University of Pennsylvania’s Louise Moncla…

Louise - The first reported case of avian influenza was reported in 1996. So in 1996, geese in Guangdong China came down with this highly pathogenic avian influenza that we now know was an H5N1 influenza virus. This led to a series of outbreaks among domestic poultry in China that then sparked infections in humans. Since that initial introduction event, highly pathogenic avian influenza of the H5 subtype has spread worldwide. And so that brings us to our outbreak that we're having now. The outbreak that we're currently experiencing in North America began in December of 2021. The birds were infected in Newfoundland and Labrador that then has spread throughout North America. The European outbreak began a little bit before that, but this has been ongoing since 2021.

Will - And as you said earlier, the first instance of this ever recorded was in 1995. Why has it then taken so long for avian flu to spread so far with such a devastating impact compared to something like COVID 19, which didn't take nearly as long?

Louise - COVID 19 was able to propagate really, really quickly because it was transmitting really well among people. And humans move around a lot. We're highly, highly interconnected. And so if a virus that infects a person in China can rapidly spread through airline travel across many continents in a very short period of time. Avian influenza is different because predominantly it's sustained by birds, and they on average travel a lot less far. What we think happened is that this initial introduction event in 1996 led to these viruses being introduced into domestic bird poultry populations in China. These then spread outward into Southeast Asia, and then they've spread outward from there into Asia, Africa. And this has happened when these viruses that were circulating in domestic birds got transmitted back into wild birds and then these wild birds because their migratory can spread these viruses very long distances. So what we think is that introduction to these wild birds then allows these viruses to spread into Europe and now into North America.

Will - And there have been outbreaks in the past, but this one is particularly harmful to avian species. What do you think is different about this strain that makes it so much more impactful than the previous ones?

Louise - The thing that has differentiated this outbreak from past ones is that it appears that this virus is much better at replicating and transmitting among wild birds. And that makes it much more challenging to control. The US, in North America as a whole, had a large outbreak a few years ago, and in that outbreak when we saw these outbreaks in domestic bird populations, the country just employed this mass culling approach. So they killed a ton of birds and this stopped transmission. What's different about this outbreak is that despite employing that same protocol, detections keep occurring in domestic birds. And it appears that the reason for that is that this virus is just being transmitted much more efficiently among wild birds. Another thing about this outbreak that is unique is that we're seeing a much larger number of mammal infections. So in past outbreaks we've seen that most of the animals that are infected are these poultry or wild bird species. But in this outbreak we've had this weird number of mammal infections. So we've seen infections in foxes, bears, and a couple of people have been infected. And then of course we had the recent mink outbreak, which was totally unprecedented.

Will - And I'm sure a lot of people have noticed that egg and chicken shortages are starting to appear at supermarkets. But what has been the effect on poultry farms of this spread?

Louise - Highly pathogenic avian influenza is very severe in chickens in particular. And so these chickens who get high path avian flu have very, very severe symptoms. So these chickens will often die really quickly. But as part of outbreak control, when you detect high path avian influenza on these poultry farms, the protocol is generally to cull the entire flock. So the US alone has, I think, culled at least over 50 million poultry just from this outbreak alone. So as you can imagine, all of this culling really impacts the agricultural industry.

Will - Do poultry farms themselves act as a vector or a hotbed of spreading this virus?

Louise - They absolutely do. So chickens in particular have this unique feature where when these highly pathogenic H5N1 viruses are transmitted through chickens, they often acquire this highly pathogenic phenotype. So we think that actually this high pathogenicity phenotype was acquired after these viruses were introduced from wild birds into domestic birds. And so what can happen is that a low pathogenic virus can get into chickens, it can acquire this high pathogenicity phenotype, and it's spilled back into wild birds. So there is transmission going on between wild and domestic birds, and then chickens and domestic birds in general are also clearly important because they're the species that we interact with the most. So most past human infections of H5N1 viruses have been linked to people who directly interact with sick birds, often through the poultry industry.

Will - And not just poultry, or livestock and domesticated animals as well. There's been a massive impact on wild bird species as well, and particularly endangered ones as well have seen themselves quite threatened.

Louise - Yes, this is one of the saddest things about the outbreak in my opinion, is that we've had these widespread outbreaks among these quite charismatic wild birds. So we've had these huge die-offs of cranes and raptor species and pelicans. And so yeah, the integration of high path avian influenza into our American flyways and the impacts on these wild bird species has been really devastating. I mean as a hopeful note, we do have these really wonderful mRNA vaccines that were developed for the SARS COV two pandemic. And I believe that there's some hope that we could deploy these strategies to vaccinate populations, for example, poultry workers or to vaccinate domestic birds or to have ready in case there ever were a human transmissible, H5N1 strain. So that's one bright note.

A free-range chicken on a farm

16:57 - Stemming the spread of bird flu

What measures are in place to reduce the transmission of avian influenza?

Stemming the spread of bird flu
Ian Brown, APHA

So far, sixty-five bird species in the UK have been confirmed with avian flu infection, and tens of thousands of birds have been reported dead - almost certainly an underestimate - and internationally the number is north of a billion. So what should we be doing to stem the spread? The focus is very much on farming. Will Tingle spoke to Head of Virology at the Animal and Plant Health Agency, Ian Brown…

Ian - The first primary thing is to consider that this is a disease of birds with a large impact on poultry. So the focus of course is to control the disease in poultry. So the first key thing is to work closely with keepers of birds to report suspicion of disease early. That means that then investigations and veterinary inquiries can be conducted, samples can be taken, and rapid testing done, which means we get early detection. The earlier you detect a case, the better chance you've got of mitigating its spread and its consequence for that flock. Second thing is, upon confirmation of a case of bird flu in a flock of birds that are domestic, then there's a whole raft of measures that are put in place that follow international guidelines. The farm is effectively locked down. It can't move birds, people, equipment off. The effective population is rapidly culled, so the remaining live birds, and the premises are thoroughly cleansed and disinfected. And then there's a fallow period before that farm can go back into business. In the premises around the location within three and 10 kilometers, we talk about control zones, so this is where there's enhanced surveillance and monitoring to ensure there hasn't been any further spread of infection from that infected premise.

Will - And there are flu vaccines that do exist for poultry and other birds. How effective are they at combating the spread of avian flu?

Ian - Vaccination works effectively when it's part of a larger control program. So if you vaccinate and do nothing else, you will likely still have a problem because vaccinated birds can still get exposed and infected to the virus and they can still shed the virus and pass it onto other birds. However, when it's used in conjunction with other control measures, it can successfully reduce infection. But considerations for vaccination are complicated. It's not a simple fix. You need the right vaccines. You need to be able to administer them on scale, need to be able to administer them relatively cheaply. And importantly, you need to monitor all of your birds that you've vaccinated on a very frequent basis because you need to be confident that wild type virus hasn't entered your vaccinated flock. When you vaccinate, of course, your ability to clinically look for sick birds is compromised because by definition the birds won't get sick. So that means you have to do active testing and monitoring, which still needs to be fully worked out at international scale, how that can be done in a way that gives confidence.

Will - Are there any things that can be done to prevent the spread in wild birds? Because they seem to be the problem. They seem to be the ones taking it from farm to farm.

Ian - The disease or infection will ultimately probably die out in wild birds at some point. We know that for some species of wild birds, this has high lethality and it can get into discrete populations with biodiversity impact. So it is important that we can reduce that source infection. We have to be realistic. There is little we can do to actually protect the wild birds themselves. They will go through natural cycles of epidemic and recovery. And this is about making sure that where we can, we apply best practice to reduce contact between poultry and wild birds. And that means more education, more awareness. But recognizing that in some poultry production systems around the world is easy to say, it's not easy to do.

Will - At an economic level. Are there safeguards in place to protect farmers who could potentially lose their entire livelihood, should their farm get infected with this avian flu?

Ian - Well of course the first important thing is that the farmer's vigilant and he knows his birth and any changes that signal early signs of disease, it's important that those producers report. Because the earlier they report, the earlier we can confirm disease and if we do confirm disease, then the faster the birds can be culled. And then of course there's a valuation at that point, which will lead to some compensation. Obviously if a farmer reports a problem late and this is a very devastating, fast spreading disease, then he could have lost his entire flock. So early reporting is really important. Making sure they've got stringent biosecurity practices, and education of anybody that comes onto the farm. So limiting visitors and making sure that the operatives on the farm are well trained and well versed in biosecurity practice, that they have a protocol and that it's followed. Sadly we've seen a number of cases where there are protocols but they're not being followed by staff, or the protocols are inadequate. So that biosecurity is a really, really important investment for the producer of birds.

Will - There's been many reports now of the flu slowly creeping into mammalian species. Do you think the protocols will now have to change because the disease is now in some mammal species?

Ian - This has been observed in many countries around the world, including the uk and it's a consequence obviously of extensive spreading of wild birds. So what is being done in the UK and indeed probably in many other countries is we have ramped up our surveillance. So we are now running an in real time program to track and understand this spread from wild birds into mammals. So from January this year, DEFRA and the involved administrations supported a program delivered by Animal Plant Health Agency to actively target mammals that we think have a higher probability of exposure and infection with the virus. Once we detect positive animals, we will then analyze that virus, dissect it, look at its genetics, and determine whether we believe there are changes in that virus that might change what we call the risk profile, both for mammals and potentially of course for humans. So what we're looking for is changes in the virus that might signal some form of adaptation. So at the moment, all of the cases we've detected in the UK, which is now 13 over the last 12 months or so in several species of mammal to date, and not all the data is complete. We've seen some changes. Yes, we've seen a consistent change in the virus when it switches from birds to mammals, but what we've not seen yet is evidence that the virus is transmitting from one mammal to another. So that is very important. So are these just isolated spillovers, which lead to what we call dead end infection, or could they go from one fox to another or one otter to another? Now we have no evidence of that yet. So to date we haven't got any evidence of that. But that's obviously why we're doing the surveillance.

A mink

24:22 - Could bird flu be the next pandemic?

What has to happen for bird flu to make it transmissible between humans?

Could bird flu be the next pandemic?
Wendy Barclay, Imperial College London

A major concern about the present bird flu outbreak is the potential for the virus to jump into humans and - because no one has immunity to bird forms of the virus, the disease can spread very rapidly, like Covid, triggering a pandemic. Those fears intensified recently when scientists reported outbreaks of the virus among farmed mink in Spain, and last week the UKHSA reported detecting the virus in British wildlife, including in mammals like foxes. There were claims that the virus had also mutated to make spread in these animals more efficient. With us to unpick this is virologist Wendy Barclay from Imperial College, London.

Chris - Is the virus showing signs of taking a step closer to us with these recent infections in mammalian species?

Wendy - Yes it is. What we have to understand is that the adaptation of a bird flu to be human to human transmissible requires two different genetic changes, two different changes. So Ian was talking there about adaptations that have been seen. And it's fair to say that both in the foxes and in the mink in Spain, one type of the sort of change, which is the prelude to the pandemic has been seen. And that is an enabler. That is the adaptation that allows the virus to actually replicate inside the cells of the mammals. That's why you get quite a lot of severe disease in those cases, and you can see a lot of viruses accumulating. But the good news is that we have not yet seen the second change, which is the real tough barrier, if you like, for the virus to cross. And that is a change which helps the virus transmit through the air from one mammal to the next or from one person to the next. That change occurs in a different part of the virus in the outside of the virus, in the way it latches onto cells in order to infect us in the first place, and also the way it can be carried in airborne droplets. And so what everybody needs to look out for at the moment are those second types of changes, which are really difficult for the virus to achieve. But if it does, then that's quite a big game changer.

Chris - Many people argue that this is often a numbers game and that this constitutes a role of the genetic dice. And the more roles of the genetic dice, the more likely it is to happen with this scale of bird flu infestation among birds, and now getting into wildlife that is nature rolling that dice. So does this mean that really, the odds have risen that we are gonna see those very changes that you are talking about?

Wendy - You're absolutely right that it is a numbers game and the more exposures and the more incursions of the bird virus into mammals, the more chances that this could happen that risk goes up and up. The one that we are really concerned about, I think, is the mink farm. Because actually your listeners may know that we use ferrets as a model for human flu because the way the virus moves from one ferret to the next is very much the same way that it would move from a person to the next. And of course, ferrets are very closely related to mink, and we believe that the same kinds of barriers would exist there. So the fact that the virus has been in that situation is on the one hand extremely worrying. But on the other hand, the fact that it didn't evolve any of those adaptive changes, even though it was clearly in a situation where the selective pressures may have been acting, might be telling us that the genetic barriers that the virus needs for this adaptation are pretty high.

Chris - Some people argue that because the virus has had 30 years nigh on to do that, having emerged in the 1990s and it still hasn't done it. Perhaps the odds are that it's an insurmountable barrier for it and we don't need to worry.

Wendy - Yes. And that's sort of partly what I was implying. It's been given this opportunity, if you like, in this mink farm situation, and it hasn't done it, but it's very difficult, isn't it, to be confident about something that hasn't happened and say, well, it's not going to. And as you've said before, the frequency of exposures and the opportunities that the virus currently has in terms of the numbers of birds and the interface between those birds and mammals and humans is at a very high level at the moment. So I think we are right to be on an alert system.

Chris - And speaking of that, what can we do to mitigate it? Obviously there's the surveillance side of it, which Ian was referring to, but in terms of being prepared for if this does jump into people, do we have vaccines? Are they relatively easy to make against this virus? Will they work against this virus? Where do we stand on that?

Wendy - Back in the early 2000s when this H5N1was first becoming a problem and a bigger and bigger worry, a lot of testing was done on H5 vaccines and how they would or could be used. And one of the things we did learn from that is that it actually is quite difficult to get people to make a good immune response to a completely new avian influenza. We give people seasonal flu vaccines every year and we know how to make those vaccines work pretty well. But the avian flu was a little bit more difficult. Because it was brand new the immune system needed a bigger kickstart, if you like, and people talked about using adjuvants, et cetera. I think where we are in a different position today is that we do have, as Louise Moncla mentioned earlier, mRNA. And so the concept of going very quickly from a sequence to a vaccine is the case, but we still don't really know how those mRNAs would work in people against the completely new avian virus, if you like. And I think it would be wise to start thinking about that though.



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