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. 

The clinical presentation of the human influenza A ranges from mild to severe. A study by Kang and colleagues collected data of human infections globally by different subtypes of avian influenza from 2013 to 2023. According to this study, the fatality rate of H5N1for that period was 37% worldwide, with greater risk of mortality for individuals older than 60 years, those with comorbidities, and those with delayed diagnosis and antiviral treatment. In the 2025 outbreak, the most common symptom reported is conjunctivitis. Other symptoms included fever, cough, sore throat, vomiting, and diarrhoea, with a median duration of 4 days. Studies have shown viral susceptibility to antiviral treatment, such as neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir), but the non-specific symptom profile poses a challenge for physicians, highlighting the importance of taking a detailed medical history and the possibility that mild cases might be under-reported. 

In this issue of The Lancet Regional Health—Americas, a Viewpoint by Bartlett and colleagues summarises the current status in the USA and provides multifaceted recommendations to prevent a widespread outbreak of avian influenza. Some of these recommendations include: (1) enhanced surveillance and monitoring, such as testing not only the people working directly with animals at risk of infection, but also on raw milk and wastewater; (2) faster genomic sharing and resources for rapid sequencing and public sharing of genomic data; (3) improved biosecurity and biocontainment on farms with proper training and use of personal protective equipment, protocols of cleaning and disinfection of the equipment used, animal housing and transportation vehicles; (4) preparedness plans for roll-out of tests, highlighting the need for an availability of rapid tests at high-risk locations (eg, farms) and beyond due to the multiple species transmission capability; and (5) public awareness campaigns with educational measures such as handling and proper cooking of animal products. 

These measures underscore the necessity for the direct involvement of government and clinicians in this outbreak and the importance of drawing attention to the prevention, detection, and management of this virus. The threat of H5N1 transmission to humans is in part due to ongoing mutations and genomic reassortment. The co-circulation with other influenza-type viruses increases the possibility of reassortment, increasing the risk of human spread and posing a moderate risk for a future pandemic. 

To track and contain this outbreak, surveillance and reporting are key. The recent suspension of the US Food and Drug Administration’s programme to test dairy products for avian influenza, due to cuts in the agency, increases the risk of under-reporting and disrupts timely notifications. The spread of H5N1 in other locations outside Canada and the USA (eg, Mexico and Brazil) highlight the need for timely surveillance. The H5N1 outbreak presents significant challenges, and clear communication with the public is necessary to help control the spread of infection. Finally, a coordinated, multidisciplinary approach emphasizing vigilance, testing, rapid response, and preparedness is crucial to mitigate morbidity and mortality as this threat evolves.

Outbreaks of emerging viral diseases have occurred in the Americas region before (eg, Oropouche, Zika, and Chikungunya viruses), highlighting the need for stronger and more coordinated efforts to prevent and control such events in the future.