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 2024, the U.S. CDC confirmed 70 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.

On 11 February 2025, the USDA released specimen data from the first cases of genotype D1.1 detected in dairy cows. Previously, USDA shared data from deceased animals at a Washington wildlife sanctuary and from raw feline pet food samples that cluster genetically and are of the same genotype B3.13.

On 14 February 2025, the CDC released specimen data from the first human case in Nevada. The specimen sequence clusters with the first cases of genotype D1.1 detected in dairy cows recently released by the USDA. Previously, the CDC released data from the first human fatality involving a patient from Louisiana that had been exposed to non-commercial backyard poultry and wild birds. The CDC had also released specimen data collected from farm workers in Iowa and Wisconsin with exposure to infected commercial poultry, with the same D1.1 genotype detected in poultry and wild birds, in human cases in Washington state and notably a severe human case in British Columbia. The latest trees, based on representative subsamples, are dated to 24 February 2025.