Case of B.C. teen with avian flu shows 'worrisome' mutation of virus

A biosecurity warning sign is seen on a locked gate at a commercial poultry farm in Abbotsford, B.C., on Nov. 25, 2024. THE CANADIAN PRESS/Darryl Dyck

Infectious disease experts say the avian flu case that infected a 13-year-old in British Columbia shows “worrisome” signs that the virus could be mutating to more easily infect humans, but that the treatment approach taken can help inform future cases.

In a letter published in the The New England Journal of Medicine Tuesday, Canadian health officials identified changes in the viral genome sequence of specimens collected from the teenager who tested positive for avian flu and was treated in Vancouver.

The case study says the teen was taken to a pediatric intensive care unit with respiratory failure and pneumonia on Nov. 8, endured a long hospital stay, and recently was taken off of supplemental oxygen on Dec. 18.

B.C. health officials said in a statement to The Canadian Press Thursday that the patient has not been discharged from BC Children’s Hospital, but that she is no longer in intensive care. They said they still don't know how the teen got infected.

The report in The New England Journal of Medicine said the girl, who has a history of mild asthma, first went to the emergency room with a fever and conjunctivitis on Nov. 4.

A genome sequence taken eight days after the onset of her symptoms showed three mutations in the specimen, including in genes that "facilitate viral entry into cells in the human respiratory tract and enable viral replication," the case study says, adding evidence of the change is "worrisome."

Physicians initiated a multiprong approach, giving the teen all three of the approved antiviral treatments available for avian flu, in addition to intubation and ventilation.

There are limited reports of avian flu, otherwise known as H5N1, spreading between humans in other parts of the world, according to Health Canada. In most cases, human infections of avian flu are contracted after a human interacts with an infected bird.

The reason avian flu is not easily spread from person-to-person is because it has difficulty binding to human airway receptors in the upper respiratory tract, Dr. Brian Conway, medical director of the Vancouver Infectious Diseases Centre, said.

However he noted, “These mutations — the three mutations they describe in the article — increase the likelihood or the ease with which the virus combined to human airway receptors and that would be the key to it being infectious to humans: That it binds more easily.”

Conway said the challenge with drawing conclusions about avian flu is that there's a small pool of human cases. The 13-year-old patient was the first human case of H5N1 acquired in Canada. That's a good thing, but it makes it difficult to identify virus mutation trends beyond a single case, he said.

But south of the border, a severe human avian flu case in Louisiana showed the same mutation in the hemagglutinin gene as the specimen collected in B.C, according to a genetic analysis published by the Centers for Disease Control and Prevention last week, "suggesting they emerged during the clinical course as the virus replicated in the patient."

Dr. Jesse Papenburg, a pediatric infectious diseases specialist in Montreal, says the reassuring thing is there's been no evidence of human-to-human transmission both in the B.C. and the Louisiana case and that the risk to humans remains low, outside of those who work in poultry industry. The case study notes there have been no secondary cases of transmission of the virus at home or at the hospital.

"It's important for public health officials and infectious disease specialists to keep a very close eye on changes in the virus that could lead to a potential for human-to-human transmission," Papenburg said.

Dr. Tim Uyeki, chief medical officer of the CDC's influenza division, says this is the first patient who he's aware of that has received a triple combination antiviral treatment for H5N1, which included neuraminidase inhibitors, amantadine and baloxavir. Uyeki, who was also a co-author on the case study, said the 13-year-old patient's doctor called him the day of her admission and they've been in regular contact on the case ever since.

The patient's condition subsequently improved, but Uyeki cautioned that this is just a single case study of one patient’s experience, who also received other treatments, such as renal replacement therapy.

However, he said that the approach of giving a patient three antivirals can help inform clinical management of other critically ill patients. The CDC has confirmed 66 human cases of avian flu in the United States, 37 of which are in California.

Typically one medication is prescribed at a time to a patient, but in the B.C. teen's case, two others were added due to the exceptional nature and severity of this case, Papenburg said based on details included in the case study.

“Thankfully, mortality due to influenza in children is very infrequent. It does happen and you can see in this case ... it got as close to death as one can get.”