Intensive transmission in wild, migratory birds drove rapid geographic dissemination and repeated spillovers of H5N1 into agriculture in North America.

Since late 2021, a panzootic of highly pathogenic H5N1 has devastated wild birds, agriculture, and mammals. Analysis of 1,818 Hemagglutinin sequences from wild birds, domestic birds and mammals revealed that the North American panzootic was driven by ~9 introductions into the Atlantic and Pacific Flyways, followed by rapid dissemination via wild, migratory birds. Transmission was primarily driven by Anseriformes, while non-canonical species acted as dead-end hosts. Unlike the epizootic of 2015, outbreaks in domestic birds were driven by ~46-113 independent introductions from wild birds that persisted for up to 6 months. Backyard birds were infected ~9 days earlier on average than commercial poultry, suggesting potential as "early warning signals" for transmission upticks. We find that wild birds are an emerging source of H5N1 in North America, necessitating enhanced, continuous surveillance. Prevention of agricultural outbreaks may now require novel strategies that reduce transmission at the wild bird/agriculture interface.