Something was wrong with the black bear that came waddling out of the Canadian nature park, you could see it right away. Instead of shy and watchful, the animal seemed drunk. The bear, a female, rummaged between parked cars, fell into the water at a harbor, swam in circles, came out, crashed into a wall. Park officials later found her lying on her side in a ditch, panting, exhausted and convulsing. She was put out of her misery.
Typically a case of bird flu, says professor of virology Ron Fouchier (Erasmus MC). ‘That bear had apparently eaten the wrong bird, full of virus, which had infected her. With the well-known neurological symptoms, which we actually always see: confusion, disorientation, convulsions, loss of balance. The H5N1 virus is extremely neurotropic, targeting the nervous system.’
Say bird flu, and usually it’s about the massive bird deaths and the devastating impact on poultry farming around the world. But in the meantime, infections of mammals are also creeping up. Bee more than twenty mammal species H5N1 has now been found, from raccoons and wild cats to otters and seals.
Disoriented polecat
Likewise in our country. At Goeree-Overflakkee, a completely disoriented polecat was found that could only squirm over the ground. In Gelderland, a tie was filmed spinning in circles confused. And in Groningen and North Brabant foxes were found aggressive, confused and blind. All bird flu, it turned out when the animals were killed and at the Dutch Wildlife Health Center in Utrecht investigated in more detail.
Deeply concerned, experts are about that. Because although the virus rarely jumps to humans, according to the World Health Organization WHO, it is fatal in no less than 60 percent of the cases diagnosed. And these are often young people, as evidenced by an earlier near-outbreak in Egypt. In reality, that percentage will be lower because mild infections often go unnoticed, but it is a chilling omen.
Ticking time bomb
“It seems that we have become a bit numb with the massive H5N1 avian flu outbreaks worldwide. But we have to make sure everyone stays sharp’, says Fouchier. “This is a ticking time bomb,” British health care professor Devi Sridhar warned last week, in a flaming op-ed. “The more chance the virus has to jump to humans and mutate, the more likely it is that a dangerous line is created that can trigger a pandemic.”
The virus only needs five fairly simple genetic mutations. This year it is exactly ten years ago that Fouchier pointed this out, in a very controversial study, because it could give bioterrorists bad ideas. One of those mutations, a change called ‘E627K’ to its largest protein that allows the virus to reproduce in the cooler body of mammals, is already popping up regularly.
This is probably more difficult with the other mutations. The virus will have to learn how to attach properly to people’s slightly different throat cells by altering its ‘hemagglutinin’ protein – the ‘H’ from the designation ‘H5N1’. The virus will also have to increase its reproductive speed and learn to detach itself more efficiently from throat cells in order to spread properly through the air.
Hopeful
The fact that these mutations have still not occurred gives hope, says Fouchier. After all, mutations arise by chance, when the virus has billions of copies of itself running in a bird’s body. Small copying errors that arise in the process can then, very occasionally, cause a virus that works slightly differently. But hundreds of millions of bird infections later, the virus apparently still hasn’t found the right combination of mutations. There is still no evidence of mammals (or humans) passing the virus on to each other.
“I think it’s because this virus has picked up the internal genes of avian viruses,” says Fouchier. The virus is said to be so bird-like that more mammal-like adaptations simply don’t ‘catch’ well. “If my suspicions are correct, this virus remains a huge problem for birds and poultry and for individual scavengers, but not so much for humans.”
New variant in China
On the other hand: every multiplication is one, and the situation does not get any safer. Last week, H5N1 spread in Peru, Canada and the Middle East, among others. In Berlin, the zoo was closed after a tropical bird was found to be infected with the virus. In the heart of London, the virus killed dozens of swans in the famous Hyde Park, among others. And in the Netherlands, poultry farms had to be cleared again in recent weeks, in Groningen and Limburg.
In addition, another H5 bird flu virus is rattling at the gate in the distance. That is virus H5N6, an avian flu that is circulating in China. ‘It is much more zoonotic,’ says Fouchier. ‘In China, we have seen dozens of infections in mammals in recent years, as well as in humans. That suggests that there is something wrong with those viruses that makes them better adapted to mammals. Maybe that virus is closer to a pandemic than H5N1.’
Fortunately, there are no confirmed cases of human-to-human transmission for H5N6 either. Victims do: of the dozens of people who contracted the virus, roughly half died, again often remarkably young people. ‘You think: it’s in China, it’s bound to run wild’, says Fouchier. ‘But in the last twenty years, about ten genetic virus lines have already been transported from China to other birds, along with birds. I wouldn’t bet on the fact that H5N6 isn’t next.’
Artificially chasing
Fouchier would prefer to artificially boost the virus again in a highly secured lab, to see what mutations it is capable of and how far it is from jumping to humans. But that is difficult: after all, the so-called ‘gain-of-function’ research is very sensitive. So it is: waiting, paying attention, collecting the virus from any sick animals, and testing it, to see what the virus is capable of.
‘The chance that these mutations all coincide exactly in the right place is extremely small,’ says Fouchier. And flu pandemics are always rare anyway. But the impact is so great that I would like to prevent it.’
Bird flu worldwide
1918
The H1N1 bird flu does a series of mutations, allowing it to infect humans. Result: the ‘Spanish Flu’, with 50 to 100 million deaths.
1957
A series of mutations allow the H2N2 flu to better attach to human throat cells. That leads to the Siberian Flu: 1.1 million deaths.
1968
The H3N2- or the Hong Kong flu breaks out, with an estimated 1 million deaths. With the same changes again.
1997
Hong Kong decides to cull all birds from the entire island after a highly contagious and deadly form of H5N1 has emerged.
2009
An H1N1 virus jumps from pigs to humans, a complicated combination from old and new viruses. Despite the shock and the fact that an estimated 1 billion people become infected in the first year, ‘only’ about 300,000 people die.
2013
Poultry farms are popping up in China new bird flu virus, H7N9. Some 1,600 human infections have since come to light. A third of those infected died.
2015
get to Egypt a total of 134 people infected with bird flu H5N1, of whom 38 die: one unprecedented outbreak for this virus. There appears to be an offshoot of the virus family tree that has acquired an extra ‘mammal mutation’.
On the way: a vaccine against all types of flu
‘The entire flu universe in one vaccine’, says the trade journal Science it already. Researchers at the University of Pennsylvania are working on an mRNA vaccine – based on the corona vaccine model – that protects against all types of flu simultaneously. In tests on ferrets and mice, the vaccine protected the animals against all 20 types of flu virus protrusions known to nature.
That could well give ‘universal immunity against individual influenza lines’, writes the groupled by Professor of Microbiology Scott Hensley, in Science. Influenza viruses can be roughly divided into twenty groups, based on the ‘hemagglutinin’ proteins on their surface – the letter H that identifies flu types. Hensley put all those twenty prongs together in one vaccine.
‘They’re just ferrets and mice, of course. Still, this is wonderful news’, responds virologist Ron Fouchier. ‘You can make those mRNA vaccines very quickly, which in any case means that you could switch gears quickly in a pandemic.’ A twenty-fold vaccine even seems a bit much to him. ‘But you could make sure that you have vaccines ready against all flu variants, so that you can quickly adapt your vaccine to which pandemic it will be.’
The advantage is that mRNA vaccines have amply proven their safety and effectiveness in recent years. A disadvantage is that the injection can cause one or several days of flu. “But in the case of a deadly pandemic, I think you take such a side effect for granted,” says Fouchier.
In mRNA vaccines, the jab consists of a piece of genetic code (messenger RNA), which calls up virus proteins once inside the cell. The cell will secrete those virus proteins and die; the immune system now learns what the flu virus proteins look like and will henceforth recognize the entire flu virus.