FLU:Trailmap: Transmission and risk of avian influenza: learning more to advance preparedness

High pathogenicity avian influenza virus (HPAIV) is a significant burden on animal health globally and threatens human health. Incursions of HPAIV into the UK have increased significantly since 2020 with over 350 infected premises being detected between 2020 and 2023. Wild bird populations have also suffered significant mortalities across multiple species, with a shift to infection of seabirds enabling over-summering of virus infection in UK birds for the first time. Whilst virus incursions have been restricted to the H5N1 subtype, the ability of these viruses to exchange genetic material means that over 12 different H5N1 viruses have been detected in the UK. Further, the increased infection pressure has meant that the virus has spilt over into scavenging mammalian species with 23 detections of HPAIV in wild mammals since 2020. This project is in response to this extreme increase in detection of HPAIV infection in the UK and is divided across five work packages (WPs) to improve our understanding of HPAIVs, help mitigate incursions and refine approaches to future prevention strategies.

Work-package (WP1) will improve our understanding of on-farm biosecurity practices, to define weaknesses in existing barriers and determine how to implement effective counter measures. Through detailed investigation and by conducting multi-sectorial interviews, the adherence and effectiveness of existing biosecurity interventions will be assessed. Outputs will provide insight into effectiveness and challenges to implementation which will be used to improve biosecurity in the field.

WP2 will improve our understanding of factors which contribute to the circulation of these viruses, including understanding the complex interactions amongst wild bird networks and with poultry. Viral genetic and epidemiological data from the field, and data generated through the other WPs, will be input into models that will provide insight into 'high-risk' activities. Modelling populations and their interactions will link WP1 and WP5 to help understand the effectiveness and impact of existing and future control and mitigation actions.

WP3 will improve our understanding of HPAIV transmission dynamics in both wild birds and poultry. By undertaking biological sampling across wild bird populations, we will develop risk-based surveillance programmes and model interactions at wild bird and poultry interfaces. This will enable a definition of high-risk incursion sites and critical wild bird populations responsible for potential sustained transmission within the environment. Outputs will feed into WP2 and enable a greater understanding of the potential reservoirs of infection as well as factors that drive incursion of disease from bird reservoirs into the poultry sector.

WP4 will assess virological factors that drive differential disease outcomes. Both viral infectivity and factors that dictate infection of different species will be assessed. This will enhance our understanding of virological interactions and define the role of viral factors that contribute to viral emergence. This WP will also link to outputs from other WPs to examine the mechanisms that drive viral diversity and factors that may enable adaptation to different hosts.

Finally, WP5 will assess the role of host factors, including immunity, in governing susceptibility, outcome, epidemiology, and virus evolution. This WP will investigate how molecular differences between species contribute to disease outcomes and define how antibody responses to different virus proteins impact upon the potential of virus emergence including variations across different hosts. Viral domains that are identified as being important in the emergence of escape mutants will be further investigated to define where flex exists within viral proteins targeted by the host immune response. We will also assess how the implementation of vaccination might impact on outbreaks and hence will inform future mitigation strategies.

Highly pathogenic avian influenza viruses (clade 2.3.4.4) are having a significant impact on the poultry industry and wild bird populations across the UK and globally. They have also been associated with mammalian infection and potential zoonotic risk. In this project we will build on the success of FluMap to better understand these viruses and their impacts. Work Package 1 (WP1) will investigate features that impact biosecurity through the lens of farm businesses' and farm workers' perceptions, practices and financial capacity to implement biosecurity and in-depth analysis of the enabling environment. In WP2 viral phylodynamic models will be used to evaluate possible future trajectories of H5Nx in the UK. Outbreak investigation data will be used to populate models to to assess the effectiveness of current and alternative control measures including biosecurity and vaccination. Existing wild bird data will be augmented by WP3 to inform models of cross-species interactions. WP3 will use active methods to detect and map novel HPAIV strains and will generate critical ecological field data in support of other WPs. Samples from killed and found-dead wild birds and mammals and live-sampled passerines will be typed. Viral persistence will be measured in the environment. Avian community structure and behaviour on farms and the surrounding landscape will be measured. WP4 will assess virological factors critical to viral fitness and emergence and link them to differential disease outcomes. Both viral infectivity and factors that dictate infection of different species will be assessed. Finally, WP5 will assess the role of host factors, including immunity, in governing susceptibility, outcome, epidemiology, and virus evolution. Implications of vaccination will also be assessed to help inform future mitigation strategies. Together these WPs will synergise to help understand the Transmission and Risk of Avian Influenza and Learn More to Advance Preparedness (FLU: TRAILMAP).