H5N1 influenza clade 2.3.4.4b has spread from South East Asia through migratory birds since 2020. The expansion seeded frequent spillovers into wild and domestic mammals including cattle in the United States. While the risk for humans not in direct contact with infected animals is low, the widespread presence and opportunities for evolution constitutes a pandemic threat.
If sustained human-to-human transmission (H2H) would emerge, there is limited time to mount a public health response. Initially, non-pharmaceutical interventions (NPIs) are needed until vaccines are available. Experience with H5N1 viruses since 1997 suggests that infections are seen mostly in people born after 1968, indicating that people under sixty may be at particular risk.
Closely monitoring viral diversity and evolution in wild life, and at the human animal interface, using integrated One Health surveillance and genome-based selection of viruses for further characterization for instance receptor affinity of H5N1 to human receptors is mandatory.