The bird flu virus isolated from a girl who died from the disease had mutations that made it better adapted to human cells, Sky News has learned.
The 11-year-old is believed to have been infected by poultry kept by her family in Prey Veng province, in the south of Cambodia.
Her father also tested positive for the H5N1 virus, but did not develop symptoms.
Dr Erik Karlsson, who led the team at the Pasteur Institute of Cambodia that decoded the genetic sequence of the girl’s virus, said it differed from samples taken from birds.
“There are some indications that this virus has gone through a human,” he revealed in an exclusive interview.
“Any time these viruses get into a new host they’ll have certain changes that allow them to replicate a little bit better or potentially bind to the cells in our respiratory tract a little bit better.”
He said the mutations were unlikely to have occurred in the girl, but probably existed in a “cloud” of viruses with random genetic changes inside birds.
“Just getting into a new host allows those one or two viruses in that cloud to survive better and become the dominant population,” he said.
But Dr Karlsson added that the virus had yet to fully adapt to humans. “It’s still a bird virus,” he said.
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The virus’s genetic material was sequenced in just 24 hours using technology developed by UK company Oxford Nanopore.
It showed the virus was the 2.3.2.1c variant of H5N1, which is endemic in wild birds and poultry in Cambodia, and not the 2.3.4.4b strain that has spread rapidly around the world and begun to infect some mammals.
But Dr Karlsson said it would be wrong to downplay the threat from the variant in Cambodia.
“This was a zoonotic spillover [of a virus infecting a new species] and needs to be treated with the utmost concern,” he warned.
According to the World Health Organization (WHO), there have been 873 human cases of H5N1 with 458 deaths.
But so far there is no evidence that the virus spreads easily between people.
A key reason is that bird flu viruses latch on to receptors found only in cells deep in human lungs.
Widespread transmission would require a mutation that allows it to bind to a receptor found on cells in our nasal passages, as human flu viruses do.
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The cells are more vulnerable to infection by an airborne virus, but also release a cloud of infectious material with every breath.
But Dr Karlsson said the world must carefully monitor changes in the virus.
“Something may be happening here in Cambodia and something may be happening on the other side of the world in South America, but we don’t really know what could cause the problem tomorrow,” he said.
“It’s critical we all work together to respond to all of those at once. We would love to be off the hook for zoonotic disease, but it will remain a major problem.”
The UK Health Security Agency reported a human case of bird flu in January 2022, though the individual did not develop symptoms.
So far this winter there have been more than 3,100 exposures to the H5N1 virus in people working closely with sick birds. None of them tested positive.
Health officials are also analysing a small number of samples taken from patients with flu symptoms to check the bird virus is not spreading below the radar.
Dr Karlsson said: “It’s concerning that it’s gone global so quickly.
“In Europe, as well as North America and South America, there have been massive poultry infections and spillovers to mammals.
“Each one of those spillovers is a concern.”