New H5N1 D1.1 variant rapidly spread across North America wildlife.
Study finds human infections rare but mutations emerged during infections.
Scientists warn ecological factors and migration aided dominance requiring preparedness.
A new reassortant highly pathogenic genotype of the avian influenza (HPAI) A(H5N1), commonly known as bird flu, has rapidly spread across the US and Canada, underlining the need for pandemic preparedness.
Clade 2.3.4.4b H5N1 virus, which emerged in late 2021, has affected more than 485 bird species and 48 mammal species worldwide. Now, a new study published in Nature Communications highlights that the new reassortant of genotype D1.1 nearly replaced clade 2.3.4.4b in North America by late 2024.
This genotype was found during the fall migration season of 2024, in September, and was mapped using active and passive methods of avian influenza surveillance across the United States and Canada.
Active surveillance involves samples from apparently healthy birds through live capture or hunter harvest, while passive surveillance includes sick and dead birds.
“These reassortant viruses have caused widespread mortality among wild birds and mammals, with nearly 14,500 wild bird and 650 mammal detections in the US alone,” the study said.
It said that Canada recorded HPAI in animals across 12 taxonomic orders and 80 wild bird species within the first year of introduction, with the true scale of impacts likely to be underestimated.
“Since February 2022, HPAI outbreaks have also severely impacted the poultry industry, affecting more than 2,000 US flocks and 186 million birds, and more than 14.5 million birds across 534 flocks in all Canadian provinces,” the authors of the paper said.
They added that there have been 17 reported human A(H5N1) infections caused by genotype D1.1 viruses, of which four were severe and two fatal.
The emergence of the D1.1 viruses aligned with the autumn migration of birds from North American waterfowl towards the south, assisting their dissemination. But the emergence and spread of the virus across North America, and whether the mammalian-adaptive mutations in the human infections originated from wild bird viruses or arose de novo among humans, remain unclear to scientists.
Researchers found that the viruses in these human cases contained mammalian-adaptive markers (such as HA E190D and Q226H substitutions) that were entirely absent from the D1.1 sequences found in wild birds. Because these markers were not found in the bird population, scientists conclude that these mutations likely arose de novo (anew) within the human hosts during the course of the infection, the study said.
Currently, the possible risk of human-to-human transmission of this genotype remains low.
The team of researchers sourced 926 samples from wildlife populations and noted that infections were spread across all four North American wild bird flyways. The Pacific and Mississippi flyways accounted for the highest proportions of detections, with the majority of samples found in geese and ducks.
“By December 2024, D1.1 was the predominant North American genotype, nearly replacing previously circulating genotypes as it spread across the continent. Although large genotypic sweeps have been common since these viruses began to dominate the HPAI landscape, the co-circulation of other H5 genotypes during and after the D1.1 sweep was low,” they said.
The genomic analyses indicate that this genotype includes a distinct North American-derived neuraminidase (NA) segment, likely providing antigenic advantages. This is because population immunity to this NA is probably lower than to NA segments circulating widely before 2024, the paper said.
It further said that although principal mammalian adaptation markers were absent in the wild bird samples, some D1.1 viruses carried several mutations with reported phenotypic effects, which may have contributed to their dominance.
However, despite the viruses lacking principal mammalian adaptation markers, their consistent replication in mammalian hosts, including US dairy cattle, opens up the possibility of evolving for zoonotic transmission.
The study noted that the D1.1 viruses detected in poultry in British Columbia were found to carry the NA-H275Y mutation — a known marker for resistance to oseltamivir (an antiviral medication used to treat and prevent influenza A and influenza B viruses that cause the flu) — demonstrating that resistance and adaptation markers can emerge stochastically, even without selection pressure.
They said that the current HPAI candidate vaccine viruses were capable of countering the D1.1 genotype strains, supporting the existing pandemic preparedness strategies.
“Increased densities of immunologically naive juvenile birds during southbound migration may have facilitated rapid viral amplification at staging areas,” it added. The high density may have led to a “genotypic sweep” of the D1.1 A(H5N1) virus across North American flyways during the 2024 migratory season.
The authors observed that environmental conditions such as drought persisting during the period, and altered habitat because of it, may also have played a contributing role in the spread of the D1.1 virus genotype.
These conditions may have caused increased interaction, mixing and density among wild birds, favouring interspecies viral transmission.
Ecological conditions, coupled with the novelty of the genotype among wild populations, may have facilitated rapid geographic dissemination of the viruses, the scientists observed.
The paper concluded that the spread of the new genotype highlights the need for an integrated One Health response, aligning wildlife surveillance to detect the emergence of antigenic variants or reassortants with altered pathogenicity or host range, agricultural biosecurity, and public health preparedness.