Discerning drivers of highly pathogenic avian influenza virus-associated disease across host species using a One Health approach

The primary causes of international outbreaks, public health emergencies of international concern (PHEICs) and pandemics are zoonotic in origin, and the next pandemic pathogen will likely circulate in animals before causing widespread human disease. The highly pathogenic avian influenza (HPAI) A(H5Nx) virus is causing a panzootic (a pandemic in animals) through waves of viral activity and unprecedented infections and die offs in wild birds, domestic poultry and both terrestrial and marine mammals. The range of species infected HPAI viruses is unprecedented, with recent transmission involving dairy cows and other animals including cats and mice, as well as humans. This unexpected change in viral ecology calls into question the narrow focus of widely used risk assessment tools that focus primarily on human health, and draws attention to the importance of integrating a One Health approach to include other species and novel routes of exposure as novel viruses emerge. To that end, we propose to a) expand surveillance for avian influenza viruses in avian species and mammals to understand viral activity in animals, b) advance an in-depth characterization of new biological tools to rapidly determine whether HPAI viruses infects and damages cells from different animals as well as humans, and c) build a framework for decision making that incorporates risk to both human and animal health based on genomic and biological features to inform surveillance and other key decision-making policies. This work builds on the Wildlife Emerging Pathogen (Wild EPI) initiative that brings together researchers from a range of backgrounds and disciplines, leading to to the discovery of SARS-CoV-2 in Canadian deer and the first case of deer to human transmission of that virus. HPAI is an important emerging pathogen and a multidisciplinary, One Health approach is needed to address this complex threat to wildlife, domestic animal and human health.