Highly pathogenic avian influenza (HPAI) viruses cause substantial economic losses to the poultry industry, and pose a significant threat to animal and human health. HPAI first came to prominence in the late 1990s with the emergence from Asia of the H5N1 lineage, which resulted in the culling of 100s of millions of birds and more than 500 human deaths. HPAI resurfaced as a global threat in 2013, with the emergence in China of a novel strain belonging to subtype H5N8. The speed of global H5N8 spread since 2014 has surprised scientists. The strain spread rapidly through Asia, North America, Europe, and most recently, Africa. The spread to North America is unprecedented, at an estimated cost of ~$3.3 billion to businesses there. A report published last October concluded that H5N8 global spread was driven primarily by long-distance bird migration. Reports of H5N8 outbreaks in both wild and farmed birds across Europe increased in autumn 2016, spreading westwards until they reached the UK in late December. Cases in wild birds have been reported in Wales, Scotland and England. The largest outbreak to date is ongoing within a large population (~750) of wild mute swans in Abbotsbury, on the Dorset coast in southern England. Although only 9 swans (so far) have laboratory confirmed H5N8 infections, more than 175 untested swans have died since the start of the outbreak, vastly in excess of normal mortality. The first H5N8 infection was detected in a dead swan found at the Swannery on 23rd December 2016. Although mortality appears to have decreased from the apparent peak in the second week of January 2017, an above-normal number of dead birds are still being recovered and the outbreak is still considered to be current and ongoing by the authorities (2nd February 2017). This outbreak, whilst devastating for the bird population, could tell us much about how HPAI spreads in wild birds. The long-lived swans have been subjected to long-term ecological study by ornithologists at the University of Oxford and are individually ringed; for most birds we know age, sex, parentage and other variables. Crucially, exactly the same population suffered an outbreak of H5N1 HPAI in early 2008. However, in 2008 only 10 swans died, almost all of which were <3 years old. Our research after the 2008 outbreak showed that older birds were more likely to have antibody responses that might help give immunological protection against avian influenza. Specifically almost all birds >3 years old harbour influenza antibodies and older birds have antibodies to a broader range of different influenza strains. Thus we hypothesise that previous exposure to common, mild forms of influenza may have protected these wild birds against H5N1 infection. The current outbreak offers the potential to directly compare H5N1 and H5N8 HPAI epidemiology in the same population of wild birds, an opportunity that we think is unique worldwide. High bird mortality during H5N8 outbreaks have been reported elsewhere in Europe, and by comparing the ecology and epidemiology of the H5N8 and H5N1 outbreaks at Abbotsbury we may be able to find out the cause of this. We aim to find out how, and from where, the H5N8 virus entered the population, how long it was present locally before it was detected, and how the virus spread through the population. To do this we will sequence the genomes of the viruses recovered from affected birds, and analyse these genomes using established statistical methods. We will look at the antibodies that birds in the population carry, to see if some birds, particularly the older ones, are protected against severe disease as a result of previous exposure to harmless strains of avian influenza. This will help us understand if immunity to flu in humans and long-lived birds is similar or different, and extend our understanding of how this virus spreads in wild birds.

The global spread of H5N1 highly pathogenic avian influenza viruses and their ability to infect not only birds but humans emphasises that human and animal health are unavoidably linked. At present avian influenza remains an animal disease problem under urgent need for control but control in birds will also reduce the potential for a human influenza pandemic. Our knowledge of the behaviour of avian influenza viruses in domestic fowl and wild birds is limited. This proposal poses some fundamental questions that address how the easily the virus can infect chickens, turkeys and ducks; how much, and for how long, virus is shed following infection in each species; and how avian influenza virus infection is controlled by the immune response of birds. Fundamental studies of this type will be critical to the design and implementation of control measures in the short term and the long term.

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Bovine tuberculosis (bTB) is one of the most difficult animal health problems that the farming industry in Great Britain faces today. The number of cattle infected with bTB has been increasing year on year by 18%, which leads to serious losses for affected farms due to the slaughter of infected animals and the imposition of cattle movement restrictions. Government spending on disease surveillance and compensation to farmers has also been following this upward trend, with spending over 2004-2012 expected to top £1 billion. From these statistics it is clear that the current disease control strategy is not working, yet the reasons for this are not obvious. One possibility is that new forms of the causative agent of bTB, Mycobacterium bovis, have evolved in GB that are able to circumvent the current control measures. Research by the VLA has found that evidence for this latter scenario is supported by the presence of a range of different types of M. bovis circulating in GB that seem to be successful in spreading around the country from their original place of isolation. This proposal sets out to determine whether these diverse types of M. bovis interact with the immune system of cattle in different ways, and so explain their success. To achieve this we will take advantage of the recent availability of the complete DNA sequences of both M. bovis and the bovine host. This will allow us to explore how the host and pathogen interact with each other at the level of individual molecules, and to build up a more detailed picture of how M. bovis causes disease in cattle. The information coming from this project will help government policy makers to develop new control strategies based on the exploitation of epidemiological information, and offers the chance to stop the upward spiral of bTB disease burden and linked expenditure in GB.

Invasive Non Native Species (INNS) are animals and plants that have been introduced (as a result of human activity) outside their normal range, and which have negative effects on our economy, biodiversity and even health. Aquatic ecosystems (rivers, streams, lakes) are particularly affected by INNS which may be spread by activities such as trade, transport and recreation. The cost to GB of INNS is ~£1.7bn per year (GB Non Native Species Secretariat). Once INNS become established in a river, it is often difficult and expensive to manage them. It is far more cost effective to prevent their introduction in the first place, and to prevent the wider spread of INNS that have established. Such prevention is termed biosecurity. Good biosecurity to prevent the introduction and spread of INNS is a core requirement of the recent EU legislation on Invasive Species and of the GB Invasive Non Native Species strategy. AIM The aim of this proposal is to reduce the risk of the introduction and spread of aquatic INNS in Yorkshire (medium term) and the UK (long term). We will use results from recent research at the University of Leeds and work with project partners from government, charities and business to develop good biosecurity practice in the day-to-day activities of partner organisations as well as the wider community. OBJECTIVES - Identify key invasion pathways by which INNS may arrive - Establish good biosecurity practice/protocols for a range of activities - Develop a biosecurity risk assessment process for events/projects/sites/activities - Promote and disseminate training materials on biosecurity and evaluate uptake and effectiveness. OUR PROJECT PARTNERS ARE: Members of the Yorkshire Dales INNS strategy steering group: The Environment Agency (EA), Yorkshire Water (YW), Yorkshire Wildlife Trust (YWT), Yorkshire Dales National Park Authority (YDNPA), Nidderdale Area of Outstanding Natural Beauty (NAONB), Natural England (NE), Forestry Commission (FC), National Trust (NT), Yorkshire Dales Rivers Trust (YDRT), Ribble Rivers Trust (RRT), Dales to Vale River Network (DVRN) Other partners: Yorkshire Invasive Species Forum (YISF), Animal and Plant Health Agency (APHA). The project also has the support of the GB Non Native Species Secretariat. OUTCOMES The outcomes that we envisage from this project are twofold; 1) improved regional biosecurity practice adopted by our project partners; 2) improvement of INNS biosecurity nationally through adoption of evidence informed approaches and policy. Both have the impacts of reducing risks and associated costs to our biodiversity and economy of INNS introduction and spread