H5N1 in U.S. Dairy Cattle: An Unprecedented Event in the History of Virology

by Fabrício Souza Campos 

Fabrício Souza Campos is a virologist and professor at the Federal University of Rio Grande do Sul (UFRGS), Brazil. He coordinates the Graduate Program in Agricultural and Environmental Microbiology and leads research on virus surveillance in wildlife and domestic animals, with a focus on zoonotic threats and One Health. He has worked on projects ranging from Antarctica to the Amazon, combining field ecology, molecular diagnostics, and genomic analysis.

Influenza A viruses are classified based on the antigenic properties of two surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA). There are 18 known HA subtypes and 11 NA subtypes, and their combinations give rise to multiple influenza A subtypes, such as H1N1 and H5N1. Among these, H5N1 is a highly pathogenic avian influenza (HPAI) virus, historically associated with severe disease and high mortality in birds, as well as occasional zoonotic transmission to humans.

Initially known for devastating poultry outbreaks, H5N1 gained global attention in 1997 when it caused human infections in Hong Kong. Between 2003 and 2006, it expanded across Asia, Europe, and Africa, affecting both domestic and wild bird populations. The evolution of H5N1 has been characterized by the emergence of distinct genetic clades, classified according to the hemagglutinin (HA) gene phylogeny. In response, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) established a standardized nomenclature system, initially defining ten major clades (0–9). Among them, clade 2.3.4 subsequently diversified into subclade 2.3.4.4, noted for its enhanced adaptability and ability to spread globally.

Since 2020, subclade 2.3.4.4b has become the dominant lineage worldwide. It has been associated with unprecedented levels of mortality in wild birds and marine mammals, particularly seals and sea lions, and has demonstrated an alarming capacity for cross-species transmission. However, in 2024, H5N1 breached a new host barrier with global implications: for the first time, it infected dairy cattle in the United States. This event marked an extraordinary turning point in the history of influenza virology, not only because of the species involved, but also due to the systemic vulnerabilities it exposed.

The virus had been silently circulating in migratory wild birds across North America since at least 2021. These birds follow extensive flyways that intersect with major agricultural and livestock areas, facilitating ecological overlap and spillover risk. Despite having advanced diagnostic capabilities and surveillance programs, the United States relied heavily on passive monitoring and failed to detect early incursions. Once H5N1 entered domestic systems, it infiltrated commercial poultry farms where theoretical biosecurity protocols were inadequately implemented. Workers, vehicles, and shared equipment likely acted as mechanical vectors. Moreover, many facilities resumed production shortly after culling, often without comprehensive environmental decontamination—potentially allowing viral persistence and resurgence.

In early 2024, H5N1 was confirmed in dairy herds in Texas, making it the first known instance of a highly pathogenic avian influenza virus infecting cattle. Infected animals exhibited mild clinical symptoms, including decreased milk production and changes in milk consistency. Genetic sequencing of viral isolates from cattle revealed mutations potentially linked to mammalian adaptation. Subsequent zoonotic infections were reported in humans and domestic cats exposed to raw, unpasteurized milk, raising urgent questions about foodborne transmission routes and the readiness of current surveillance systems to detect such novel transmission dynamics.

The incident highlights a broader challenge: the interplay between epidemiology and policy. In the U.S., the Department of Agriculture (USDA) provides financial compensation to producers for poultry losses in the event of HPAI outbreaks. While this ensures rapid compliance with depopulation protocols, it may unintentionally reduce incentives for rigorous biosecurity implementation. This phenomenon, often described as “moral hazard,” reflects a systemic weakness wherein reimbursement can displace responsibility. In such cases, even the most advanced infrastructure cannot compensate for gaps in institutional coordination and risk accountability.

In contrast, Brazil—operating with more limited economic resources and without a national compensation program—managed to contain a 2025 outbreak of H5N1 in commercial poultry in Montenegro, Rio Grande do Sul. The response was led by the Brazilian Department of Agriculture, Livestock and Food Supply (MAPA), the State Center for Health Surveillance (CEVS/RS), and the National Laboratory for Agricultural Defense of Brazil (LANAGRO). These agencies swiftly coordinated field surveillance, culling, sanitary barriers, and tracing protocols. In the absence of financial indemnification, Brazilian producers may have been more vigilant, knowing that failure to act could result in irrecoverable economic losses. To date, the virus remains restricted to avian species in Brazil.

The contrast between the U.S. and Brazilian responses reveals an important insight: effective outbreak control depends not only on scientific capability or funding, but also on well-aligned incentives, clear governance, and cultural attitudes toward biosecurity. It raises a thought-provoking question: can the United States learn something from Brazil’s approach?

References

– Mena et al. The Impact of Highly Pathogenic Avian Influenza H5N1 in the United States: A Scoping Review of Past Detections and Present Outbreaks. Viruses. 2025; 17(3):307. doi: https://doi.org/10.3390/v17030307

– AVMA (2024). Avian influenza virus type H5N1 in U.S. dairy cattle. https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza/avian-influenza-virus-type-h5n1-us-dairy-cattle

– CDC (2024). Avian Influenza A(H5N1) in Mammals. https://www.cdc.gov/bird-flu/situation-summary/mammals.html

– USDA (2024) – USDA and HHS Announce New Actions to Reduce Spread of H5N1. https://www.usda.gov/media/press-releases/2024/05/10/usda-hhs-announce-new-actions-reduce-impact-and-spread-h5n1

– MAPA (2025) – Painel de Influenza Aviária de Alta Patogenicidade (H5N1). https://www.gov.br/agricultura/pt-br/assuntos/sanidade-animal-e-vegetal/saude-animal/programas-de-saude-animal/influenza-aviaria