Statutory and Exotic Viral Diseases

The Statutory and Exotic Viral Diseases Programme provides expert consultancy and diagnostic services for statutory and exotic virus diseases of animals, including those that may affect human health.

VLA has fifteen International Reference Laboratories of the World Organisation for Animal Health (OIE), six of which are for statutory and exotic viruses: avian influenza, Newcastle disease, rabies, enzootic bovine leukosis, equine viral arteritis and classical swine fever.
We also hold formal status within WHO and FAO for some of these diseases and provide national diagnostic and consultancy services for exotic viral diseases including many zoonoses, both on behalf of Defra and the Health Protection Agency. All diagnostic testing is accredited to UKAS ISO17025.

Avian Influenza and Newcastle Disease

There were three outbreaks of notifiable avian influenza this year and our detailed forensic analysis provided government epidemiologists with strong lines of enquiry in relation to their origin. These outbreaks also provide us with unique insights into many research topics, for example: virus survival on free-range production sites, tissue tropism, genetic diversity and evolution.

Our experimental studies on the H7N1 strain of the highly pathogenic notifiable avian influenza (HPNAI) virus revealed the transmission dynamics of the virus and mortality of hosts varied greatly amongst different poultry species. Turkeys were the most susceptible species, with 100% mortality in both infected birds and naïve contacts. In chickens, mortality was 95% in infected groups, but there was little evidence of transmission. No mortality was observed in ducks, however, in either infected or in-contact birds, even though infection of all ducks was established with evidence of transmission (70% of birds). This data allows assessment of the potential duration and evolution of infection and disease during the ‘high risk period’ following introduction of virus. Further mathematical modelling analyses are being progressed to establish data at a population level.

We confirmed that the current industrial pre-treatments used to decontaminate feathers (used for trading purposes) were appropriate for the destruction of infectious influenza viruses. A wider programme of research is in progress, aimed at producing robust scientific data on the physical parameters affecting survival of contemporary influenza and Newcastle disease viruses.

Our activities continue to support improved understanding of zoonotic threats, together with development of better intervention strategies. The Department of Health has approved funding for a multi-institute collaborative project to develop pre-pandemic vaccines for use in a national immunisation programme, which will involve significant input from VLA to develop and use animal models for evaluating future candidate vaccines.

Rabies and Wildlife Zoonoses

Our strategy concerning surveillance and research activities on European bat lyssaviruses has taken the form of a ‘One Health’ approach, from both a veterinary and medical perspective. International highlights include our re-designation as a WHO Communicable Disease Surveillance and Response Collaborating Centre for a further four years and our pivotal role in co-organising the ‘Rabies in Eurasia’ conference. This was held at the OIE headquarters in Paris and brought together world-wide policy makers, scientists, veterinarians and clinicians.

EU Pet Travel Scheme

In collaboration with our colleagues from the Universities of Manchester and Liverpool, we assessed the antibody response to vaccines used to immunise dogs within the EU Pet Travel Scheme. One observation was that young animals, less than one year of age, generated a lower antibody response to rabies vaccination compared with adult dogs. Considerably higher failure rates were also observed for different vaccines tested. The data needs to be considered in the context of minimising the risk of rabies being re-introduced into Great Britain, especially if the requirement for serological testing for rabies vaccinated dogs is removed.

European Bat Lyssavirus

We reported the sixth case of a European bat lyssavirus type-2 (EBLV-2) positive Daubenton’s bat, identified in Shropshire UK. Genetic analysis of the nucleoprotein gene of this isolate compared to a previous UK EBLV-2 isolate from a Daubenton’s bat (identified in Surrey in 2004) demonstrated that both sequences shared 100% identity. We also reported the full-length genomic sequences for European bat lyssavirus type-1 (EBLV-1) and type-2 (EBLV-2). Genetic differences between lyssavirus strains are likely to affect transcriptional activity and RNA stability and hence, host pathogenicity.

Tick and Mosquito-borne Flaviviruses

Two separate surveys to detect the presence of West Nile virus (WNV) in birds from the UK revealed no evidence of infection. The first targeted the assumed peak period of vector activity, from April to October, and included samples from wild bird mass mortalities, birds showing neurological signs and susceptible species. A second study, undertaken at the University of Liverpool, tested brain and kidney tissue samples from wild birds representing 43 species (submitted between 2005 and 2007). These samples were also tested to detect WNV RNA by RT-PCR, using the same procedures as VLA, and all samples were found to be negative.

Surveillance for neurological disease in horses is ongoing and Defra has produced a draft contingency plan for specified type equine exotic disease (STEED). This provides a strategy for response to suspect or confirmed cases of equine encephalitides, including WNV and other emerging diseases, such as borna and hendra viruses. VLA plays a key diagnostic and consultancy role in this plan. WNV infection, which is now notifiable in horses, has never been detected in animals that have exhibited neurological signs in the UK. Further surveillance studies will continue in Great Britain and cases of viral encephalitis in humans will be monitored for the presence of WNV.

The pathogencity of WNV was assessed in an experimental chicken model and no clinical signs or gross pathological changes were seen in any of the inoculated chickens throughout the study. Following primary inoculation of the chickens, there was a weak antibody response 15-days post-inoculation. However, following re-inoculation with inactivated WNV and adjuvant there was a substantial increase in the neutralizing antibody titres, when tested two weeks later. Based on detection of virus and serology, there was no evidence of viral transmission to the close contact controls.

A RT-PCR test has been developed for the differentiation of flaviviruses circulating in Europe, particularly WNV, tick-borne encephalitis virus (TBEV) and louping ill virus (LIV). The test is highly sensitive and specific, with the ability to discriminate among flaviviruses circulating in Europe.

Classical Swine Fever Virus

Classical swine fever (CSF) still represents a major threat to the UK pig industry and we are aiming to add to our current test portfolio by introducing a modified multiplex real-time PCR to simultaneously detect CSF and African swine fever. This is caused by an unrelated virus, but with similar clinical signs and has recently spread from Africa to Eastern Europe.

CSF virus has the ability to persist in the face of the host response and one of the mechanisms used is the inhibition of apoptotic cell suicide, by which undisturbed replication is achieved. We have analysed some of the underlying pathways and interestingly found that the virus uses several mechanisms to interfere with host cell responses, one of which is the mitochondrial pathway of apoptosis triggered by the protein t-bid.

Viral Diseases of Other Species

While the UK is free of enzootic bovine leukosis (EBL), the disease is still widely present throughout the EU and other parts of the world. In its OIE role, the VLA is working to improve the efficiency of detection and last year we hosted a meeting of all OIE Reference Laboratories where a scheme for improving diagnostic tests was discussed. We also support other countries to resolve diagnostic cases of special importance to improve our awareness of the global situation.

VLA staff have been instrumental in the fight against FMD and bluetongue. VLA scientists at our Regional Laboratories were the first to diagnose bluetongue post-mortem and staff at VLA Weybridge have analysed several thousand sera for these two diseases in support of their control and eradication.

Our preparedness against new and emerging viruses is a key element of our responsibilities. We are now part of a Defra consortium (BioChip) to adopt and employ a micro-array for virus detection for use in a diagnostic environment, particularly to detect emerging viruses.