It swirls in Asia, Europe and Africa, it smolders and spreads secretly, it cuts curves, makes big jumps and sometimes flares up sky-high. Like a fire, but even more like the cold breath of a many-headed monster: bird flu. The virus has always been, and always has been, in harmless variants in wild birds and poultry. But sometimes a dangerous variant arises in poultry kept closely together. Traditionally, it has been so deadly to birds that migratory birds don’t get very far with it. But for the past two decades, dangerous variants have been roaming the world, piggybacking on migratory birds, descending into poultry, always capable of smoldering, further changing – and posing a risk to humans.

In the past four months alone, hundreds of outbreaks worldwide, on companies and in nature. Hundreds of thousands of chickens were culled in Friesland and Overijssel in the past ten days after confirmed infections. In December, hundreds of red knot sandpipers died on Schiermonnikoog, thousands of barnacle geese in Scotland and more than 8,000 cranes in Israel. And: worldwide the number of human infections is increasing, especially in Asia. Officially, the counter stands at around a thousand cases, for all variants together, but there is a good chance that many infections go unnoticed.

“Until now, no variants have emerged that are easily transmissible from person to person,” says Ron Fouchier, professor of molecular virology at Erasmus MC and world authority in the field of bird flu. “But we know that only five mutations are needed. We are already seeing some of these in mammals that have been infected.”

There is always the risk of a pandemic virus developing. It is no bigger now than ten or twenty years ago, says Fouchier. “But now, since corona, we are much more aware of the dangers of viral diseases that we share with animals. Rightly so.”

Pattern of infections

Theoretically, the risk may be just as great now as it was in previous decades – the fact is that the pattern of human infections is changing. The problems started in Asia in 1997 with the first human infections with a variant labeled H5N1. Since then, 883 people have been infected, mainly in Egypt, Indonesia, Vietnam, Cambodia and China. 473 of them died. But while the numbers were fairly constant until 2019, the number of infections fell to almost zero in the past two years.

“That is partly thanks to poultry vaccination in Africa and Asia,” says Fouchier. “But over the past few years we have seen an increase in other variants, such as H5N8 and H5N6. The first has infected only a few people, but H5N6 is now a cause for concern.” Since 2014, 58 people have been infected with an H5N6 variant in Asia, mainly in China. Half died. More than half of all those infections were in the past year.

“It is not yet clear why this acceleration suddenly takes place,” says Fouchier. “We do know that it always concerns new infections from poultry – not human-to-human infections.”

Avian flu viruses multiply in birds mainly in the gut. There they penetrate intestinal cells via a receptor: a part of the cell membrane. The intestinal cells then produce new virus particles, which spread through the faeces. “But that receptor in the avian gut cells is very similar to a receptor in human lung cells,” says Fouchier. “The virus can therefore relatively easily infect human lung cells and thus cause severe pneumonia. That is generally what kills human victims.”

In a bird’s gut

In order to then be able to jump to other people, three changes are needed, the professor continues. The virus must be able to multiply in high concentrations in our upper respiratory tract, and at much lower temperatures than the 42 degrees in a bird’s gut. The virus must remain stable in aerosols: tiny droplets that are released when coughing, sneezing, talking. And in the next person, the virus should easily take hold in the upper respiratory tract.

“It only takes five genetic changes to get those traits,” says Fouchier. In 2012, he made world news with it. “Since then, this principle has proved true in all past pandemics that originated in birds.” For example, the Asian flu of 1957, which killed 1 to 4 million people worldwide, and the Hong Kong flu of 1968 with a comparable number of deaths. “These viruses were no more deadly than Covid-19,” Fouchier casually notes, “and they were not dangerous to poultry. But they were very dangerous for us, and very contagious.”

In the Israeli nature reserve Hula Valley dead cranes are culled. The area is closed to prevent the spread of bird flu.

Foto Ronen Zvulun/Reuters

That was because they were mixtures between avian and human flu strains. “We strongly suspect that this also applies to the Spanish flu of 1918,” says Fouchier. “But we cannot conclusively determine that.” Virus has been isolated from the bodies of people who died in 1918, which is very similar to bird flu viruses. “But it is only possible to determine the origin with certainty if you can trace the virus further back. Then you need older virus samples – and there are none.”

In 2014 there was an outbreak of a virus among seals in the Wadden Sea, which killed thousands of animals. “That was bird flu,” says Fouchier, “with four of the five changes the virus needs to become airborne between mammals. One of these has been found in bird flu in foxes. And we sometimes see one such change in infected people in China.”

Mixed molds in pigs

Fouchier is afraid to say how great the risk is that a virus strain will undergo all five changes, and thus become pandemic. “But any mammalian infection can cause changes through natural selection.” New mixtures sometimes arise in pigs. That was probably the case with the 2009 swine flu, which contained elements of bird, swine and human flu.

A variant that can be transferred between people does not necessarily have to be dangerous. Fouchier: “But in practice we see that this is often the case – partly because we do not yet have immunity against it.” And he reiterates that – especially in Asia – there is little insight into the scale of the problem. “In China, this has been investigated,” he says. “Then blood tests show that the number of people with bird flu is many times higher than the number of official reports. The only question is: how much higher? The estimates of the underreporting vary by a factor of thirty.”

And a new variant could also arise with us. That happened in 2003, during the outbreak in which a Dutch vet died. The chance of this is relatively high, because we have the highest poultry densities in the world. “That’s something we have to look at very critically,” says Fouchier. “And to vaccinate that poultry. We don’t do that in Europe now, because of export agreements. But virologists hold their breath. If the virus ends up in poultry in the Gelderse Vallei, or around Venlo, it will be difficult to stop.”

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