Avian Influenza and Zoonotic Risk: Analysis, Mutations and Control Strategies within the One Health Approach

The epidemiological scenario of avian influenza has undergone significant shifts since 1996, when the highly pathogenic avian influenza (HPAI) A(H5Nx) virus of the Gs/Gd lineage (A/goose/Guangdong/1/1996) first emerged in China. This strain has spread extensively among poultry, wild birds, and mammals, occasionally infecting humans. The acquisition of mutations facilitating interspecies transmission and mammalian adaptation has raised concerns about potential reassortment with other avian or seasonal influenza viruses in mammals.  These factors increase the risk of the virus permanently adapting to humans, potentially triggering a global pandemic.

In response to this threat, the European Commission has commissioned the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC) to write a joint scientific opinion to address two key objectives: first, to assess the risk associated with avian influenza viruses (AIV) and estimate the likelihood of mutations enhancing their zoonotic potential; second, to outline effective strategies for preparedness, surveillance, prevention, biosecurity, and infection control.

Based on genetic sequences of avian influenza isolates available in the GISAID database collected from 2020 to 2024, experts from both agencies, in a scientific report published on 29 January 2025 ( EFSA Journal 2025;19(2):9191 ), identified 34 genetic mutations associated with five phenotypic characteristics that enhance viral adaptation to mammalian cells. The preliminary analysis of these mutations was conducted by the Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise (Italy), an EFSA contractor, and detailed the findings in a technical report (Puglia et al., 2024).

These phenotypic traits allow t avian influenza viruses to bind more effectively to mammalian respiratory cell receptors, spread and release new viral particles through neuraminidase activity, withstand higher pH levels and body temperatures, replicate more efficiently due to increased viral polymerase activity, and evade the host immune system. These factors collectively increase the risk of transmission and adaptation to mammals. The scientific opinion also highlights that viral adaptation to mammals is influenced not only by genetic mutations and viral recombination but also by host immune responses. Additionally, human activities and environmental changes, such as intensive farming, inadequate biosecurity, deforestation, urbanization, and global trade, may exacerbate interactions between wildlife, poultry, livestock, and humans, thereby increasing the risk of viral spillover.

In parallel with this scientific opinion, EFSA and ECDC also published a dedicated report on managing zoonotic avian influenza outbreaks through a coordinated One Health approach ( EFSA Journal 2025;19(2):9183). The report presents five key scenarios, supported by flow diagrams, to guide response and containment efforts, emphasizing the interactions between humans, animals, and the environment. Three scenarios focus on outbreaks in domestic and wild species, while two address on virus detection in humans or environmental matrices, such as wastewater or contaminated surfaces.

The report highlights the necessity of an interdisciplinary approach, strengthening communication and coordination across different sectors. Strategies for managing zoonotic outbreaks include biosecurity measures in farms, epidemiological and genetic surveillance, and immediate interventions such as movement restrictions and selective culling. Protective measures for workers, including personal protective equipment (PPE) and targeted vaccination of high-risk animal populations, are also recommended.

Furthermore, the report identifies priority areas for development, including tools for data sharing, cross-sectoral information exchange mechanisms, criteria for beginning joint risk assessments, and the identification of gaps in current scientific knowledge.

These recommendations will contribute to the design of specific operational strategies for each EU Member State, aiming to enhance preparedness, mitigate the zoonotic risk of avian influenza, and prevent potential global health emergencies.

Scientific References

Coordinated One Health investigation and management of outbreaks in humans and animals caused by zoonotic avian influenza viruses

Preparedness, prevention and control related to zoonotic avian influenza  

Analysis of zoonotic mutations of avian influenza viruses