In February 2025, a new and highly pathogenic strain of avian influenza A(H5N1) was detected in Argentina, sparking concerns about its potential impact on both animal and human health. This novel virus, which we'll refer to as H5N1-Arg_Feb2025, has a unique genetic composition, revealing a complex story of evolution and adaptation.
The H5N1-Arg_Feb2025 virus is a triple reassortant, meaning it combines genetic material from different sources. Our genomic sequencing revealed that it contains gene segments from Eurasian H5N1 and low pathogenicity viruses from both South and North American lineages. This finding highlights the continued evolution and diversification of the H5N1 virus in the Americas.
The trajectory of H5N1 in South America has been distinct from its spread in North America. In South America, nearly all outbreaks can be traced back to a single introduction of the virus from North America, whereas in North America, multiple independent introductions from Europe and Asia have occurred. Additionally, the South American outbreaks have been driven by a single, genetically stable genotype (B3.2), which is not the case in North America, where frequent reassortment with low pathogenicity avian influenza (LPAI) viruses has led to new genotypes.
One of the most concerning aspects of the South American H5N1 epizootic is its ability to transmit between mammals, particularly marine mammals. This is due to the H5N1 (B3.2) virus acquiring specific mutations in its polymerase basic (PB) 2 gene, which allows it to adapt to mammalian hosts. This pattern has not been observed in North America, where spillover into terrestrial and marine mammals has been transient, with the exception of dairy cattle in the United States.
In 2023, the H5N1 (B3.2) virus spread extensively across mainland South America, leading to outbreaks in poultry and wild birds. While HPAI outbreaks occurred in Brazil and Peru in 2024, Argentina had no detections from March 2024 to January 2025. However, on February 11, 2025, an outbreak was reported in a mixed backyard flock in Chaco Province, northern Argentina. The flock experienced high mortality, with two-thirds of the remaining chickens showing diarrhea and one duck appearing lethargic. The household was located within a unique Dry Chaco biome, a hot and semi-arid tropical dry forest, surrounded by agricultural cropland.
Our investigation involved collecting oropharyngeal and cloacal swab samples from eight birds to test for influenza A virus. Real-time PCR and next-generation sequencing were performed, revealing the novel 4:3:1 triple reassortant nature of the H5N1-Arg_Feb2025 viruses. Four gene segments belong to the South American LPAI lineage, three segments cluster with the original Eurasian H5N1 lineage, and one segment groups with North American LPAI viruses. This reassortment event between HPAI H5N1 and endemic South American LPAI viruses has expanded the diversity of H5N1 polymerase genes.
Despite the substantial genomic changes, the novel reassortant viruses caused illness and death rates comparable to those observed with the B3.2 genotype. The primary clinical manifestation was diarrhea in chickens, which was less common during H5N1 poultry outbreaks in Argentina in 2023. This suggests possible shifts in tissue tropism or virulence. The detection of a North American NP segment in South American LPAI viruses highlights the need for strengthened regional AIV surveillance, even in the absence of active HPAI circulation.
Further research on the diversity of LPAI viruses in Neotropical wildlife is crucial to understand potential interactions with H5N1 and South American lineage strains. Our findings emphasize the importance of sustained influenza surveillance and whole-genome sequencing to track the evolution of HPAI H5N1 and support efforts to control and mitigate its impact on domestic animals, wildlife, and human health.
This research was led by Dr. Vanstreels, a veterinarian and associate researcher with a special interest in the ecology and effects of highly pathogenic avian influenza H5N1 on wild bird and marine mammal populations. The study was supported by various organizations, including the Administración Nacional de Laboratorios e Institutos de Salud and the Servicio Nacional de Sanidad y Calidad Agroalimentaria in Argentina, the Department of Health and Human Services, and the National Institutes of Health.
The discovery of this novel H5N1 virus in Argentina underscores the ongoing challenge of avian influenza and the need for continued vigilance and research to protect both animal and human health.
