How dangerous is the bird flu to humans? (Patreon)

[This is a transcript with links to references.]

A lot of birds have had the flu recently. You may have seen the headlines about it. This winter we’ve seen a severe outbreak of the bird flu, or avian flu. How much should we worry about that? I’ve tried to figure out what’s going on, and, well, let me just say I’ve learned a lot of really scary things that I don’t want to withhold from you. What’s the bird flu? Is it dangerous to humans? And if so, what can we do? That’s what we’ll talk about today.

First things first, what’s the bird flu? The bird flu is a type of virus that infects birds, would you have guessed it. If you want to sound particularly smart you call it avian influenza, which means the same but with more Latin.

The poor birds suffer quite a bit from the flu. Symptoms begin with lack of energy or movement, loss of appetite, tremors, or disorientation. Then comes a swelling around the head, neck, and eyes, coughing, sneezing, and gasping for air. Sometimes that’s accompanied by a blue discoloration of the head. The infection frequently leads to multiple organ failure and sudden death. Highly pathogenic strains kill more than ninety percent of the infected birds within 48 hours. When a flu outbreak happens at a chicken farm, farmers must usually euthanize most of the birds.

That the infection kills the poor birds so quickly and dramatically is tragic, but it’s partly good news because it means that those outbreaks are usually discovered very quickly. For this reason, the risk of infected poultry entering the food chain is extremely low. So at least there’s one thing you don’t need to worry about.

Flu outbreaks among birds are nothing new. There are records of them dating back at least 500 years, with reports of pandemics approximately every 40 years. Other types of animals, such as pigs, bats, or dogs, also have their own strains of flu viruses. Like the flu among humans, the bird flu usually flares up in autumn before fading away in spring and summer.

You might think that the worst that can happen is that egg prices go up, but think again. Influenza viruses areusually adapted to a particular species of animal, to the tissue and respiratory system, and it’s rare that they jump to other species, but it does happen, and bird viruses can infect humans. Indeed, most scientists believe that the so-called Spanish influenza pandemic of 1918, was caused by a mutation of a bird flu virus.

The Spanish flu was the most fatal influenza pandemic so far. It infected about 500 million people, which was, at the time, a third of the world population. An estimated 50 million people died, which is about 10 percent of those infected. Though accurate estimates are hard to come by because back then virus tests were rare and unreliable and most wireless routers had a miserable bandwidth.

All the influenza A viruses circulating in humans today are variants of this bird flu virus, and they make up about three quarters of all flu cases. Some researchers have claimed that if you look back in the history of evolution far enough, then influenza originated in fish. Which brings up the very interesting question whether fish with a runny noses fancy chicken soup, results of this study will soon be published in Nature.

Scientists have estimated that nearly two-thirds of infectious diseases among humans originate in animals. But most of them have been spillovers from wild mammals not from birds or fish.

A few technical details. Avian flu viruses are encoded by two numbers, that stand for variants of two proteins on the surface of the virus. The one number is for the type of hemagglutinin, that’s an H followed by a number. The other is for a type of neuraminidase, that’s an N followed by another number. Together you get a strain classification like H1N1, H6N3, and so on.

At present we know about a hundred of them.  And some of those strains have also been able to infect humans. Most infections in humans have been caused by the strains H5N1 and H7N9.

H5N1 was first isolated from a farmed goose in China in 1996. Migratory birds spread it from there to Europe, Africa, and North America. In 2003 it started affecting poultry farms all over the world. From the farms it spread to populations of wild birds and also to humans.

According to the World Health Organization, there have so far been about 900 confirmed infections in humans, most of them in Egypt and Indonesia, the vast majority in people working with poultry. About half of them died. This 50 percent fatality rate is compatible with what’s been observed in earlier outbreaks.

The reported symptoms begin, well, similar to the flu. Fever, cough, sore throat, runny nose, body aches, headaches, fatigue, and difficulty breathing. People eventually die from pneumonia, respiratory failure, or multiple organ failure.  

Since the numbers are so small, there’s very little data about the demographics, but in 2007 the World Health Organization analysed about 200 cases and found that most of them were children or young adults.

The highest fatality rate, 73 percent was that in the age group of 10 to 19 years. A study from 2016 found however that while younger people were more often affected, older people were at higher risk of dying. The virus seems to affect men and women the same way.

These data are very difficult to interpret because they’re throwing together people from all over the globe and you have no idea how they were treated, if they were treated at all. But either way you look at it, this is clearly not a disease that kills only the old and sick.

The estimate of a 50 percent fatality rate might not be accurate because some infections might have gone unnoticed and therefore don’t show up in the WHO statistics. However, for the fatality rate to be much different there’d have to be a lot of people with symptoms so mild no one takes much notice, and then very few people who get severely ill but survive, which isn’t what we see in other viruses. So, while no one knows the exact fatality rate, the bird flu is really bad news, and you don’t want to have it.

This was the H5N1 strain, but it’s not the only strain that’s scary. Outbreaks of the H7N9 and H7N7 have also been bad, though with small differences in incubation period and symptoms.

Okay, you may think, this is a bad virus, alright, but it can’t be transmitted from one human to another, so it’s not going spread. Well, look, if humans can get it by handling birds, then they can also get it from handling infected humans. Indeed, there have been several reports of transmission among humans already.

For example, a paper published in the Journal of Infectious Diseases in 2000 presents the cases of health care workers in Hong Kong. They were taking care of patients who had contracted bird flu, the H5N1 strain, during the first outbreak among humans in 1997.

Antibody tests revealed that 8 of the 217 health care workers who had been in contact with patients but not with birds were seropositive. They even found two more cases among health care workers who had not been directly in contact with the patients but with other health care workers. That’s not enough transmission to cause an outbreak, but it’s clearly happening.

Human-to-human transmission has also been reported in Europe. In 2003, an outbreak of highly pathogenic avian influenza -- this time H7N7 -- began in poultry farms in the Netherlands. Virus infection was detected in 86 workers of these farms. Researchers set out to test household members and found 33 testing positive.

There are many more examples of human-to-human transmission, most of them in Asia. It would be tedious to go through all of them, so let me just say it’s well-documented that it does in fact happen. At the moment, transmission among humans is rare, and the transmission rate so small that it doesn’t lead to outbreaks, but it’s a thing.

And this is very worrisome, because in 2014 scientists found that the H5N1 virus needed only five mutations to achieve airborne transmissibility between ferrets. And that when these changes emerged, the adapted virus became dominant rapidly. So, chances are, we’re just a few mutations away from a virus that easily travels among humans and that is very fatal.

So, the avian flu is basically a disaster waiting to happen. Epidemiologists have known this for two decades, but this winter they got particularly worried. There are several reasons for this.

First, a recent variant of the bird flu has spread very widely very efficiently. It’s a variant of the H5N1 strain with the number 2.3.4.4b. It was first documented in in October 2020 in the Netherlands. Within a few months it had spread to many countries in Europe, Africa, Asia, and America  

Second, while bird flu outbreaks are usually seasonal, the outbreak that began in the fall of 2021 didn’t fade away in the spring of 2022. It lasted throughout the summer and picked up again in the fall last year.

According to the US Department of Agriculture, this variant has by now affected more than 50 million farmed birds in the US who either died or were killed to prevent the disease from spreading. The number in the European Union is similar.  The World Organisation for Animal Health has estimated that globally the outbreak has already killed more than 200 million birds.

The next reason to worry is that this bird flu has infected other species. It has been documented in sea lions in Peru, 3000 of which died miserably, it’s infected otters and foxes in the UK, and was found in three grizzly bears in Montana. The bears were in extremely bad condition and had to be euthanized. And there’s been a big outbreak on a mink farm in Spain.

This mink farm has attracted a lot of attention, because researchers at location found that the minks carried a virus with a mutation that might be a sign of adaptation to mammals. In a recent paper a group of Spanish researchers explain how things developed.

On the first week of October 2022, the farm workers detected a sudden increase in the mortality rate of the minks. The veterinarians tested the animals for COVID but the tests came out negative. They then tested for avian influenza, and the results came out positive. The tests on human workers, luckily, came out negative. The authors looked at the genome of the virus samples and found an uncommon mutation that they say makes the virus better adapted to mammals.

Spanish authorities immediately placed workers on the mink farm under quarantine restrictions. The more than 50,000 minks were killed, and their carcasses destroyed. They Spanish have so far not closed other mink farms because the international health organizations haven’t recommended it, but it’s under discussion.

The mink farm’s got scientists worried because minks are similar to humans in some regards. Indeed, ferrets, which are very close relatives of minks, are widely used as animal models for the study of influenza A infections. That’s because in ferrets the distribution and type of virus receptors in the respiratory tract is similar to that of humans. .

The reason why bird flu is not highly transmissive among humans, they think, is that it infects a different part of the respiratory system. In birds, it affects the upper respiratory tract and then wanders deeper into the lung. Viruses that sit in the upper respiratory tracts are easily spread by coughing, sneezing, and even speaking, which is why the virus spreads so quickly among birds.

But humans don’t have the receptors that this virus binds to in the upper respiratory system. We only have a few of them in the lower lung. Now, if you’re unlucky and the virus gets into your lower lung, you are at a high risk of getting severely ill. But it also means that you’re unlikely to spread the virus.

This was first discovered by a team of American and Japanese researchers who published their finding in 2006  in the journal Nature.  Interestingly enough, the distribution of these receptors in the human lung is also age-dependent. Children have more of them which might explain why they’re more often affected.

When it comes to those virus receptors, minks are in between humans and birds. They are mammals, but the infections in minks also occur in the upper respiratory tract, like in birds, which allows for easier transmission to other minks.

And here’s the important bit: That minks catch the bird flu is bad news because they are known to also catch the human flu. And a double infection can allow viruses to swap genes. If you have a mink which carries both the bird flu and the human flu, that could become a host for a new virus that’s as deadly as the bird flu and as transmissible as the human flu. All it takes is one mink, and a bit of bad luck.

Ok, we have seen that the bird flu is bad news for humans and it’s creeping up on us. So, what can we do? Are there vaccines?

There are vaccines for poultry and some of them are really good, reporting 100 percent efficiency in lab tests. These vaccines have been used in Asian poultry farms in the past, and the US is thinking of doing the same now, though the vaccines first have to be adapted to the current strain.

How well vaccinating birds works partly depends on the country and its culture. In some countries in Asia you have a lot of unregistered backyard poultry, and the virus has many places to hide, and vaccination is difficult. But vaccination campaigns have been successful to limit previous outbreaks in France, the Netherlands and Hong Kong.

A problem with the existing bird vaccines is that the vaccinated birds test positive for the virus, meaning farmers can’t guarantee their birds are free of H5N1. Though scientists are trying to find a solution to that by developing better tests.

And, yes, there are also vaccines for humans.  Different vaccine types have been tested in clinical trials since the mid 2000’s. Some of them have been approved for use both in the United States and in the European Union. However, no one knows how well those vaccines work, because accidental infections are extremely rare, and you don’t deliberately infect people with a virus if the infection has a 50 percent fatality rate.

And there is a problem with some of those vaccines. Except one they’re all produced from, wait for it, chicken eggs.

This has nothing to do with the bird flu in particular. 90 percent of flu vaccines are made using chicken eggs. That’s because viruses can’t reproduce on their own, they need to infect cells. So, scientists inject viruses into an embryonated egg, let the virus replicate, collect the replicates, purify them, and then kill them.

Those inactivated viruses are the most common way to make flu vaccines. This is why, if you’re severely allergic to eggs you should tell your doctor before getting vaccinated, and this is also why the US government keeps hundreds of thousands of chickens in secret farms with bodyguards just in case you suddenly need vaccines.

It might have occurred to you that maybe relying on birds for vaccines isn’t the greatest idea if the disease is killing birds. Luckily there are alternatives.

The Australian company Seqirus developed the first and so far only vaccine against the H5N1 strain that is produced from mammalian cell cultures. So, no eggs. It was approved by the U.S. Food and Drug Administration in 2020 for people six months and up. The vaccination requires two doses, three weeks apart.

For this vaccine, clinical safety data have been collected for adults. In a 2022 paper  the company presented test results for about 3000 adults. They found that three weeks after the second dose more than 95 percent had antibodies. However, again, no one really knows how well this protects against falling severely ill because none of those people have been infected.

Last year, the US Government designated a Manufacturing Facility in North Carolina as pandemic ready, which means they are able to deliver 150 million doses of this influenza vaccine to the US government if necessary.

mRNA vaccines would be a possibility, but there are currently no approved mRNA vaccines for influenza, neither avian influenza nor any other one. There is some evidence that the antiviral drug   oseltamivir, sold under the brand name Tamiflu, helps against some strains of H5N1. And, yeah, that’s pretty much it.

So how much should we worry?

The H5N1 variant that’s responsible for the current outbreak among birds has so far infected only about a dozen people in total, none of them due to human-to-human transmission. One of the infected people died, but from samples so small you shouldn’t extrapolate.The American Centre for Disease Control, the European Centre for Disease Prevention and Control, and the World Health Organization all assess the current risk as low for the general population.

However, it is clear that this virus could become very dangerous and it’s inching closer to becoming more transmissible between humans. Just because virologists have warned that this could happen, and it hasn’t happened for 20 years, doesn’t mean it’s never going to happen.

Measures that scientists have proposed are: better tracking the spread among wild birds, stricter bio-safety measures for farms that host animals at risk – such as mink, pig, and poultry –, vaccinations for birds, and, yes, vaccine preparedness for humans. And maybe we should for once listen to the scientists when they first raise the alarm and not wait until it’s too late and then try to find someone else to blame.