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In 2020, the highly pathogenic avian influenza (HPAI) virus  subtype H5N1 of clade 2.3.4.4b caused an unprecedented number of deaths in wild birds and poultry in numerous countries in Africa, Asia, and Europe. In 2021, this virus spread through major waterfowl flyways to North America and, in 2022, to Central and South America. By 2023, outbreaks in animals were reported from 14 countries and territories, mainly in the Americas.

In recent years, there has been an increase in the detection of the influenza A(H5N1) virus in non-avian species worldwide, including terrestrial and marine mammals, both wild and domestic (companion and production). Since 2022, 22 countries on three continents, including the Americas, have reported outbreaks in mammals to the World Organisation for Animal Health (WOAH).

Historically, since the beginning of 2003 and as of 22 April 2025, 973 human cases of avian influenza A(H5N1), including 470 deaths (48% case fatality rate), were reported to the World Health Organization (WHO) from 25 countries globally.