Update on H5N1 bird flu in Canadian teenager

On November 26, 2024, The government of British Columbia in Canada issued an update on the recent H5N1 case and the ongoing epidemiological investigation. This H5N1 case was first reported on November 9, 2024, in a teenager from Fraser Valley, located in Southwest British Columbia.

By way of background, an initial press conference was held on November 12, 2024, where details about the case and the ongoing investigation were provided. Read my article on that first report for the full context and the key details.

Patient status: critical

In the most recent update, it is reported that the teenager remains hospitalized in critical condition. Provincial health officer Dr. Bonnie Henry stated: “Our thoughts continue to be with this young person as they remain in critical condition, and their family.”

 

Contact investigation: no further cases

Health authorities report that a contact investigation has shown no additional H5N1 human cases. So there really is no concern about human to human transmission with this case.

Source of exposure / infection: unknown

As to the source of infection, the report states that testing of household pets, birds, and “other animals” from nearby premises was conducted along with soil and water testing. According to the report, all these tests were negative, and the source of this teen’s infection is unknown.

The across-the-board negative results from animals in contact with this patient is a bit puzzling to me. That would seem like a clear route of infection considering the reports that this person had no exposure to poultry or wild birds. There was even an initial report of the teen’s pet dog having been ill around the same time. So if not that route, then how? One outstanding question I have is will there be serology tests done on pet animals that this teen had contact with, or was this just looking for active H5 infection?

 

What we do know comes from the genetic makeup of the virus. The H5N1 virus from this case most closely matches the strain circulating in wild birds in the Fraser Valley area of British Columbia. These viruses were detected in the area in October 2024, and are of the genotype D1.1 of clade 2.3.4.4b. As the virus from this teen closely matches those from wild birds, rather than poultry, that would suggest the route of infection was likely “not directly related to outbreaks at poultry farms in B.C.” That’s an interesting development, as in the initial press release there seemed to be a heavy focus on the poultry farms in the area and on the recent H5N1 detections in poultry. It was almost as if that was where the investigators thought the source of this infection would be found. But it wasn’t.

So we still don’t know how this teenager was exposed to an H5N1 clade 2.3.4.4b virus, nor do we know how exactly this teenager was infected with the virus. Unfortunately, it seems like we might never know. But the information gleaned from the investigation can rule out sources of infection, which may in turn reveal some not thought of before. As stated by Provincial health officer Dr. Bonnie Henry: “Though we have not been able to determine definitively the source of exposure, we were able to rule out many potential risks and ensure there are no further cases related to this young person.”

 

 

Mutations with implications for human health:

One aspect of this human case that is getting some attention are certain mutations in the HA gene of the virus sampled from the patient. Specifically, the initial sequence of the virus from this case shows mutations at certain key sites in the HA gene: Q226 and E190. These sites are associated with receptor binding, and thus these mutations may signal viral adaptation for binding to human-type receptors.

What do the studies say?

Interestingly, the mutations found in this virus were both referenced in a recent study that used “deep mutational scanning” to examine all potential amino acid mutations in H5 viruses. I think the fact that we even have this technology is amazing. The paper is quite technical, and I won’t pretend to grasp everything in it, but it was a fascinating read that provided very helpful context to what these mutations mean.

Some key points include the following:

 

• • “The HA mutations that specifically enhanced entry into α2–6 versus α2–3 cells were mostly at a handful of sites in the sialic-acid binding pocket.”

• • “Multiple mutations to site Q226 strongly increased HA’s preference for α2–6-versus α2–3-linked sialic acids in our deep mutational scanning.”

So that’s one of the mutations in the Canadian case, Q226. According to this study, amino acid position Q226 and mutations therein contribute to binding to α2–6 receptors, which is what humans have in their upper respiratory tract.

 

• • “Mutations at several other sites also markedly improved entry into α2–6 cells, including sites 137, 190, 193, 225, and 228.”

And there’s the other mutation from the Canadian case: 190. Again, according to the study, contributes to binding with human-type, α2–6 receptors.

Notably, the study also found that mutations Q226L/R, E190Q/A, N224K/Y, G228A, are part of a select club that “strongly enhance entry into α2–6 cells” and can occur with only “a single nucleotide change” in the current clade 2.3.4.4b H5 HA gene sequence. So what that means is these mutations, which can alter receptor binding, may only be a single change away in some viruses currently making their way through North America.

As always, I wish for the recovery of this teenager and hope for the best.

Until next time.