Clade 2.3.4.4b of the highly pathogenic avian influenza (HPAI) virus causing outbreaks in wild and domestic birds around the world, continues to spread in dairy cows, poultry and other animals across the United States. Since April, the U.S. CDC confirmed 58 human cases through genome sequence analysis. In three of these cases, the amino acid substitution NA-S247N was identified that may slightly reduce susceptibility to the neuraminidase inhibitor oseltamivir in laboratory tests. The CDC also identified a different change in the polymerase acidic (PA) protein of a virus collected from a recently confirmed human case of H5N1 bird flu in California.

The current outbreak validates the unpredictability of HPAI viruses, as the route of exposure in dairy cows and mode of virus transmission remains unknown. The virus RNA was found at high concentrations in raw milk. Several animal species at dairy and poultry farms, as well as a growing number of farm workers are affected. Data from the USDA’s Animal and Plant Health Inspection Service show that the viruses in infected cows, other animals and the farm workers are closely related. A mammalian adaptation marker (E627K) was noted in only one farm worker so far, with nearly all farm workers developing mild eye symptoms, alongside respiratory symptoms. Although over a thousand genomes from this outbreak have been made available on EpiFlu, the lack of timely sharing of actionable data collected from farming animals remains a cause for concern.

Since the last update, specimen data from seven human cases collected in California between 7 - 18 Nov and one in Oregon collected on 5 Nov, have been made available by the U.S. CDC. While the cases from California appear closely related to viruses collected in dairy cows, the case from Oregon clusters with cases of poultry farm workers in Washington State.

In addition, specimen data collected from 138 dairy cows and some poultry have been made available by the USDA, giving only 2024 as collection date and the U.S. as location. Ten out of those dairy cow specimens, clustering near sequences from California, do presented a HA S110N amino acid substitution at a position, previously associated with host receptor binding changes. The latest trees, based on representative subsamples, are dated to 5 December 2024