The H5N1 highly pathogenic avian influenza (HPAI) virus has caused severe global losses, reaching South America in 2022 and Antarctica in 2024. Here, we synthesize outbreak reports submitted to the World Organization for Animal Health by South American countries and overseas territories in this continent, and document the virus’s unprecedented expansion into Antarctica, affecting wild birds, wild mammals, and domestic poultry. Phylogenetic and time-calibrated Bayesian analyses were performed on available genomic sequences. Over 6 million domestic birds were lost, mostly from commercial operations. Of the 11 South American countries and overseas territories that reported H5N1 to WOAH, 10 reported infections in wild birds, spanning 104 species, 59.62% of which are migratory and predominantly non-trans-equatorial. Marine mammal outbreaks followed wild bird detections, with the South American sea lion (Otaria flavescens) being the most reported species. Several Antarctic bird species with migratory behavior were also reported in South America. Genomic analyses revealed multiple introduction events, regional viral diversification, and patterns consistent with repeated cross-species spillover events. These findings highlight H5N1’s extensive ecological reach in the Southern Hemisphere and underscore the urgent need for a One Health approach that strengthens wildlife and backyard-poultry surveillance, alongside coordinated regional action to control and prevent further HPAI spread.

Los virus de influenza aviar (VIA) son patógenos importantes en aves acuáticas silvestres a nivel mundial; sin embargo, su presencia en regiones subantárticas sigue siendo en gran medida desconocida. Para abordar esta brecha en el conocimiento, se presentan aquí datos de vigilancia obtenidos en la Reserva de la Biosfera Cabo de Hornos, en el extremo sur de Chile, durante las temporadas reproductivas australes de 2024-2025. En total, se recolectaron 352 muestras fecales de sitios costeros, islotes y aves paserinas en programas de monitoreo a largo plazo. Solo una muestra ambiental obtenida en Punta Gusano en enero de 2024 resultó positiva mediante RT-PCR en tiempo real (Ct 36,78), lo que corresponde a una tasa de detección del 0,625%, mientras que todas las muestras de paserinos y de la temporada 2025 fueron negativas. Este único resultado débilmente positivo sugiere introducciones virales ocasionales, pero no hay evidencia de circulación sostenida. El hallazgo coincide con informes previos que muestran una dinámica activa de VIA en el norte y centro de Chile, pero una actividad muy limitada en la Patagonia. Asimismo, concuerda con los pocos casos confirmados de influenza aviar altamente patogénica H5N1 del clado 2.3.4.4b registrados en el extremo sur de Chile durante el brote de 2023. En conjunto, estas observaciones sugieren que el extremo sur de Chile sigue estando mínimamente afectado por los VIA. No obstante, su proximidad a la Antártida y su ubicación en la intersección de importantes rutas migratorias resaltan la importancia de mantener la vigilancia en estos ecosistemas remotos.

The 2022–2023 outbreak of highly pathogenic avian influenza (HPAI) H5N1 in Chile caused extensive mortality in wild birds, domestic poultry, and marine mammals, highlighting the rapid transboundary spread of this emerging pathogen in South America. However, the evolutionary and ecological processes shaping viral dissemination within Chile have remained insufficiently characterized. Here, we integrated whole‐genome sequencing, Bayesian phylogeographic analyses, and ecological modeling to reconstruct introduction routes, diversification patterns, and environmental drivers of H5N1 circulation in Chile. All analyzed genomes belonged to clade 2.3.4.4b, genotype B3.2. Phylogenetic analyses revealed multiple Chilean subclusters, including a lineage characterized by PB2 F323L and D740N substitutions and a single virus carrying the previously mammalian‐associated PB2 D701N mutation. Phylogeographic inference identified strongly supported viral movements across South America, with Argentina acting as a major regional connector. Key diffusion pathways linked Peru to Chile and revealed extensive connectivity among Argentina, Chile, Brazil, Uruguay, and the Falkland Islands, delineating three interacting transboundary transfer systems along the Pacific Coast, the Southern Cone, and the Southwest Atlantic. Within Chile, viral population structure reflected ecological segregation. Northern lineages were predominantly associated with coastal and raptor species, whereas southern lineages were mainly linked to freshwater birds. Ecological modeling showed that H5N1 detection probability in wild birds increased with temperature and relative humidity and decreased with human population density, with freshwater species exhibiting the highest infection probability. Together, these results demonstrate how integrating genomic and ecological data provides an integrated framework for risk‐based surveillance and early warning, enabling the identification of high‐risk host groups, environments, and transboundary corridors critical for anticipating and mitigating the regional spread of emerging avian influenza viruses.