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https://aphascience.blog.gov.uk/2024/12/02/aphas-response-to-high-pathogenicity-avian-influenza-threats-in-cattle/

Diagnostic excellence in action: APHA’s response to high pathogenicity avian influenza threats in cattle

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Milk being poured into a glass. The APHA logo is also displayed.

The emergence of a bird flu infection in cattle in the United States (US) in March 2024 was unprecedented.

Until the US event, mass infection of herbivorous mammals with avian influenza had never been described, although there have been occasional infections seen in different mammalian species across the world. For example, infection of farmed carnivores (for example foxes and mink) and mass mortality events in some marine mammals has been observed.

As soon as cattle were reported as being infected with high pathogenicity avian influenza (HPAIV) in the US, a wider risk assessment for Great Britain (GB) was immediately commissioned to understand the risk to cattle across GB. The National Reference Laboratory (NRL) for Avian Influenza (AI) at APHA Weybridge was tasked with providing advice for the risk assessment and undertake rapid reactive diagnostic investigative work.

The main concern regarding transmission of the virus from infected cattle in the US arises from its ability to replicate at extremely high levels in mammary tissue. As a result, milk obtained from these infected animals holds significantly higher amounts of the infectious virus. This situation led to important questions being raised around the threat posed by this virus to cattle outside of the US, and concerns surrounding the potential for the virus to infect cattle in GB.

Image of a cow's udders attached to a milking machine.

In GB, APHA has been at the frontline of testing for HPAI virus since the large outbreaks and deaths in avian species in 2020. This has been supported by collaborative research projects to comprehensively define the genetic composition of the virus and the risks from migratory birds.

In collaboration with colleagues in Europe and around the world, our studies have not demonstrated any evidence in support of HPAIV affecting cattle in the UK or Europe. Importantly, the genotype affecting cattle in the US has not been detected in any sampling across Europe since emergence in cattle in the US.

Historically, the translocation of AI viruses from the Americas to Europe has not been observed. However, as part of a risk assessment, and to future proof against any potential threat, it was important to ensure that the APHA Weybridge diagnostic tests could detect HPAIV in milk, which is not a sample type usually submitted for avian influenza testing and has a high fat content which may interfere with the tests. 

The experiment began with a trip to the local supermarket to buy a bottle of full fat milk. Not something that one might expect to do in a normal day at the laboratory!  As it was a new type of sample, an assessment of extraction of viral genetic material from milk was the first question posed. First, the supermarket milk was spiked with different amounts of non-infectious viral material to check that it would be possible to detect viral genetic material at both high and low concentrations. Viral genetic material was successfully detected in these dilutions using the frontline PCR test.

PCR machine at APHA’s headquarters at Weybridge

As the NRL work to international diagnostic testing standards in all frontline testing activities for notifiable avian disease agents, evidence that all our tests would work with milk was required to ensure high quality standards were maintained. To gather milk samples for testing purposes, and to provide reassurance that HPAIV was not present in cattle in the UK, we worked with the National Milk Laboratories (NML) to sample bulk milk tanks (BMT) from dairy cattle premises across GB with unpasteurised milk being sent to the Avian Virology team for testing.

In total 508 bulk milk samples from 455 farms were tested. All BMT samples were negative for HPAIV using the front-line PCR test, demonstrating conclusively that HPAIV is not in GB cattle, as well as generating valuable diagnostic data to support frontline application of our tests on unpasteurised milk as a sample type. This output mirrored reactive diagnostic evaluation of milk samples across Europe.

Further, staff from the team were rapidly deployed to try and answer another urgent policy question, to determine if pasteurisation processes were able to kill high concentrations of virus in milk. To address this, milk from the BMTs was used and a laboratory-based model of pasteurisation was generated, working within the constraints of using a live HPAIV in secure ‘containment’ laboratories designed specifically for working with these viruses.

Experiments were devised to assess if virus artificially spiked into unpasteurised milk, would remain infectious after simulating a pasteurisation process while working inside our secure laboratories. The experimentation demonstrated that the pasteurisation successfully killed the virus, rendering milk that had been treated in this way safe. Samples were also assessed for virus survival over time in milk to mimic what might occur in a milking parlour where high concentrations of milk may be present in the environment that might act as a source of onward infection. This demonstrated that high levels of virus could be detected over a considerable time period in milk.

Research in this space has high policy significance and the team have plans to undertake further assessments of virus survival in different environments.

Fundamentally, the rapid delivery in this reactive piece of work has demonstrated the APHA influenza teams’ ability to respond to emerging pathogen threats to the UK. This work is critical in helping us to better understand the disease and offering reassurance to the public in the value of something we take for granted; namely, the safety of our milk.

Further reading

This milk pasteurisation work has demonstrated the added value gained from using the classic virological techniques described in our recent publication (Viruses | Free Full-Text | Assessment of Survival Kinetics for Emergent Highly Pathogenic Clade 2.3.4.4 H5Nx Avian Influenza Viruses (mdpi.com)). Outputs from our assessment of pasteurisation processes have fed into collaborative efforts with the University of Glasgow, The Pirbright Institute and the Roslin Institute to generate data for publication in this area (Pasteurisation temperatures effectively inactivate influenza A viruses in milk | medRxiv).

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