The avian influenza virus is a pathogen that has been well known to the scientific community ever since its first detection in 1996. Avian influenza is caused by a single-stranded RNA influenza A virus, and the current outbreak in North America is caused by the subtype H5N1, with waterfowl serving as its natural reservoir. Waterfowl are often migratory birds, resulting in the spread of H5N1 across the globe. The worldwide spread of the virus, along with its capacity to mutate led to diverse phylogenetic clades and subclades. H5N1 clade 2.3.4.4b was first detected in European and Asian wild populations in 2016, and then in Canada in 2021, with the characteristic of infecting not only birds but also marine and terrestrial mammals. For years, researchers have been monitoring cases of avian influenza across the world, and the high number of cases in both wild and domestic animals in the USA raises concerns about transmissibility to other mammalian species.
Notably, influenza A virus poses major threats to animal health due to its high ability to evolve and spill over to other species. According to the US Centers for Disease Control and Prevention (CDC), the public health risk at present is low, with most human infections resulting from exposure to infected animals. However, the high number of cases in birds (including poultry) and mammals (such as cattle, domestic cats, and humans) are concerning. As of May 29, 2025, the CDC reports more than 173 million infected poultry, 1072 affected dairy cow herds and 70 human cases, with one human death. Human infections have been reported not only from close contact with infected poultry, but also from infected cows, drawing attention to the mammal-to-mammal transmission. Human-to-human transmission has not yet been reported, and would require the virus to acquire human-type receptor specificity, as previously observed in other avian or swine influenza type of viruses, such as the H1, H2, and H3 subtypes, increasing the risk of a pandemic event. Despite the continuous growth in the number of infected animals, the most recent reported human cases were from early February, 2025, in the states of Ohio, Nevada and Wyoming, raising to questions about adequacy of surveillance and disease monitoring.