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H5N1, a highly pathogenic subtype of the avian influenza virus (bird flu), is not new. It has been with us since 1996, when it was first identified in domestic geese in Guangdong, China (CDC). H5N1 is a zoonotic virus, meaning it causes disease transmissible from animals to humans, or vice versa. It circulates primarily in animals (mostly birds) but can infect humans under specific exposure conditions. By 1997, it had already killed six people in Hong Kong. Over the following two decades, it caused recurring waves across Asia, Africa and the Middle East, infecting almost one thousand people (WHO/PAHO).

Human hosts have no prior immunity against the animal virus. The result is extremely high virulence. Historically, for H5N1, one in every two infected people has died. 

A zoonosis that has made the jump from animal to human, combining high virulence with the capacity for sustained human-to-human transmission and respiratory spread, is a recipe for a pandemic. H5N1 as well as other influenza strains, are RNA viruses with a segmented genome consisting of eight separate fragments. When two different influenza strains simultaneously infect the same cell, those segments mix freely and can reassemble into new combinations, a process called reassortment or antigenic shift. The result is a virus with radically different properties. This is distinct from antigenic drift, the gradual accumulation of small mutations that occurs in all RNA viruses over time. Influenza does both, it drifts constantly, and occasionally shifts. This is why influenza viruses, which combine these recombination mechanisms with respiratory transmission, have driven major pandemics in recorded history: 1918 (Spanish flu, 50–100 million deaths), 1957 (Asian flu), 1968 (Hong Kong flu), and 2009 (swine flu, H1N1), which originated through reassortment in pigs in Mexico.

In 2020, a new variant of H5N1 emerged, first detected in the Netherlands: clade 2.3.4.4b (Frontiers in Veterinary Science). This descendant managed to establish itself permanently in wild aquatic bird populations across Europe and Asia, shifting from seasonal to year-round circulation. Unlike previous H5N1 variants, which disappeared from wild bird populations each summer and had to be reintroduced each winter by migratory birds arriving from Asian reservoirs, clade 2.3.4.4b established itself permanently in resident wild bird populations, no longer dependent on seasonal migration to survive.

It then crossed the Atlantic, reaching Canada in autumn 2021, and spread to Central America and South America in 2022. Between 2022 and 2023, massive die-offs of marine mammals (sea lions, elephant seals) and birds (penguins) began appearing along the Pacific and Atlantic coasts of South America. Thousands, then tens of thousands of carcasses on the beaches of Peru, Chile and Argentina. At Península Valdés, 97% of elephant seal pups born that season died (Uhart et al., Nature Communications, 2024). These deaths implied that the virus was not producing isolated spillover cases, jumping from birds, its natural reservoir, to marine mammals, but it was already transmitting from mammal to mammal, something H5N1 had never demonstrated at this scale in wildlife.