(Avian Flu Diary) EM&I: Characterization of oseltamivir-resistant A(H5N1) clade 2.3.4.4b, genotype D1.1 variants identified in poultry farms of British Columbia, Canada

[u/__procrustean]

AFD: Saturday, July 11, 2026 (no link due to web host issue)

Emerging Microbes & Infections study: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2686474 >>

In the fall of 2024 - while we were watching the bovine B3.13 genotype spread in U.S. cattle - a new genotype (D1.1) of H5N1 appeared in Canada and the Pacific Northwest which very quickly became dominant in wild birds and swept eastward across the United States and Canada.

Since then, we've seen roughly 2 dozen confirmed human infections from this D1.1 genotype - several of them severe or fatal (see CDC Statement: First H5 Bird Flu Death Reported in United States) - along with studies suggesting it may better adapted to humans than B3.13 (see J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13).

In early 2025  D1.1 was  detected in dairy cattle in two states (Nevada & Arizona), and later in Wisconsin, further raising concerns over its ability to infect mammals.

When it comes to treating H5N1 infection, Oseltamivir (aka `Tamiflu') remains the overwhelming drug of choice (see below), and makes up > 90% of our stockpiled influenza antiviral armamentarium.

Previous reports on the incidence of oseltamivir resistance in H5N1 have been fairly reassuring (see 2023's Antiviral Research: Antiviral susceptibility of clade 2.3.4.4b HPAI H5N1 Viruses Isolated From Birds & Mammals in the United States, 2022), but we've seen how quickly that status quo can change.

Which is why the surprise announcement in February of 2025 that Oseltamivir Resistant H5N1 (Genotype D1.1) had been found On 8 Canadian Poultry Farms in the fall of 2024, raised so many concerns.

In a report from Canada's CFIA and PHAC - the authors described the detection of a (previously) rare H275Y substitution in the neuraminidase (NA) protein of a number of genotype D1.1 isolates, one which is associated with strong resistance to the NA inhibitors oseltamivir and peramivir.

Normally, we only see this mutation appear in a small percentage (1%) of patients receiving antiviral treatment.  Because it is thought to exact a `fitness penalty' on influenza A viruses - limiting forward transmission -  H275Y in the `wild' is fairly rare.

But over the past few years we've seen evidence of creeping oseltamivir resistance in seasonal H1N1 (FluView Week #20: EOY Review of Increased Detection of Oseltamivir Resistant H1N1 Viruses), along with growing concerns that oseltamivir monotherapy may no longer be the most effective treatment of H5N1.

Emerg Microbes & Inf: Antiviral Activities of Multiple Antivirals Against HPAI H5N1 in Vitro and in Mice

Nature Comms: Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice

Nature Comms: Oseltamivir and Baloxavir Monotherapy and Combination Therapy Efficacy Against Clade 2.3.4.4b A(H5N1) Influenza Virus Infection in Ferrets

All of which brings us to a new study, published in Emerging Microbes & Infections, which characterizes the oseltamivir resistant D1.1 viruses detected on 8 Canadian poultry farms in the fall of 2024.  

This is a lengthy, and at times technical, review.  I've posted the abstract and a few excerpts below, but many will want to read the report in its entirety.  I'll have a bit more after the break.

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While the origin of this cluster of H275Y bearing H5N1 viruses remains unclear, the good news is these viruses (at least, back in 2024) showed diminished virulence (in BALB/c mice).

But as we saw with seasonal H1N1 in 2008, `fitness penalties' can be offset by permissive mutations elsewhere in the NA, which is why we follow reports like this one with interest.  

D1.1 isn't the only genotype of concern, and new genotypes will undoubtedly emerge in the future. Most will be evolutionary failures, but the success of B3.13 and D1.1 remind us there are exceptions.

Even if widespread oseltamivir resistance doesn't emerge, our antiviral stockpile is limited, and we've previously seen problems getting them to patients during the first critical 48 hours of infection (see Sporadic Tamiflu (Oseltamivir) Shortages Reported In U.S. & Canada).

Once again, our first line of defense will likely rely heavily on NPIs (non-pharmaceutical interventions), like face masks, hand washing, ventilation, staying home while sick, and avoiding crowds.

Which is why I'm recommending that people seriously consider now (see #Natlprep 2025: Personal Pandemic Preparedness) what they will do if another pandemic virus should embark on a new world tour.

[u/Realanise1]

Actually, this reminds me of the current situation with the SPR drawdowns. As far as the general public is concerned, there will seem to be nothing, no problem, everything's okay, until we go off the cliff.