Team:Exeter/Practices


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Delving into the problem of Bovine TB in the UK is not something that we as a team took lightly. Bovine TB is a challenging disease that is hard to treat, easily transmitted and currently illegal to vaccinate against. Put these three factors together with the highly complex social, political and economical situation the UK faces with eradicating TB, it is clear that Bovine TB is a National problem that needs a solution.

Extremely early into our project we began to appreciate this. Therefore we agreed that during our project we wanted to make people more aware of the challenges farmers, vets and local communities face when dealing with Bovine TB.

Establishing relationships with various experts early on was extremely important. Not only have these relationships shaped certain areas of our project but also gave us an unprecedented look into the issue of Bovine TB in the UK. In the beginning these experts allowed us to understand everything to do with Bovine TB in the field and as our project has developed we have been able to integrate their experiences, suggestions and feedback into the science we are doing in the lab.

Our Beyond the Bench became as much of a lesson for us as a team as it did have an impact on our Ribonostics project. Vets, farmers, politicians, the NFU and DEFRA are just to name a few of the people/organisations highly involved with our project.

What challenges does the UK face to eradicate Bovine TB?

This is the question that we as a team decided to ask. Not only does this question have many aspects, we believe it is the question that is best able to have a direct impact on the work we are doing. The timeline below shows a breakdown of how we decided to tackle this highly important question and how what we learnt helped shape our Ribonostic work...

Richard Sibley

Right at the start of our project we wanted to understand everything to do with current TB testing. Understanding the Tuberculin skin test, how the test is implemented in the field and some of the current issues with testing are all things we needed to appreciate. To do this we met with Richard (Dick) Sibley, director of a veterinary practice in Devon. Dick has worked directly with Bovine TB, attending multiple Mycobacterium conferences and also focusing the work of his practice towards tackling Bovine TB.

Click below to read how Dick and his practice influenced our team right from day one.

Read more Phase 1: Understand everything to do with current TB testing.

Richard Sibley

Principal Vet and Director of West Ridge Veterinary Practice Ltd

We decided to visit a veterinary practice where we met with the director, Richard (Dick) Sibley, a highly respected vet with over 30 years experience across a wide range of veterinary practice. Dick and his practice have worked extensively with bTB, ranging from testing cattle through to offering bTB free programmes to farmers. After we outlined the concept of our Riboswitch, he explained more about the current bTB detection system, recent research into the disease and the work his practice does to tackle bTB. Below are the main points that Dick made us aware of at the start of our project.

Persistency and Contagiousness

Dick introduced some important concepts to us as a team. Firstly was the R0 value of Bovine TB (bTB) in cows. R0 is the disease reproduction number and is a mathematical way of explaining how contagious an infectious disease is. Although it can be hard to determine exactly, current research estimates the R0 value for TB in cows ranges from 1.0 - 4.9. This means one infectious cow has the ability to infect up to 4 other animals meaning the transmission rate can be extremely high. Combine this with the close conditions farm animals are kept in, bTB spread throughout a herd is fast. Under the current bTB testing law, if a farm experiences a breakdown it has a 60 day period until a second test is conducted. Any false negative individuals that have been left in a herd from the first test won't get a chance to be detected for 60 days - more than enough time for those individuals to transmit the disease.

Persistency and Contagiousness

Mycobacterium bovis (M.bovis) is a very challenging pathogen. Not only is it incredibly difficult to treat, it has the ability to persist in the environment for months. Dust, etc etc are just some of the things that the bacterium is able to survive on. Clearly this creates a very challenging situation for both farmers and vets trying to eradicate bTB. If a farm is finally declared bTB free status, any area of the farm that may have been exposed to an infected animal (silage, buildings, equipment) may be able to transmit the infection back into the herd. Dick explained how some farmers face a situation where they have to isolate their entire farm, keep the cattle indoors and follow a strict regime to minimise the risk of bTB exposure. Also, Dick made us aware of some current research into the ability of M.bovis to persist in the environment.

Herd Size Increase and Sensitivity Issues

Advances in technology has led to a huge increase in the size of farms in the UK. Not only has the number of cattle increased as a whole, the size of individual herds has also greatly increased. In 1996 the average size of a UK dairy herd was 75 cows. In 2014 this had increased to 133 cows. Increase in herd size has highlighted how the current Tuberculin skin test is simply not sensitive enough to allow for a strategy to eradicate bTB in the UK, as shown by the larger dairy farm herds, where recurrent bTB breakdowns are common. Dick highlighted how the current Tuberculin skin test can leave behind cows that are infectious and that in current farming conditions leaving behind even a single infectious animal can lead to bTB breakdown. Large high risk herds are particularly challenging to achieve bTB free status. Dick made it clear that our test would be most useful not as a stand alone, but as a tool that could be used in conjunction with the current test to achieve greater specificity in these high risk large herds.

Points to Consider

Our multiple meetings with Richard (Dick) Sibley helped us as a team understand exactly what situation the UK currently faces with eradicating bTB. Dick made it clear to us the situation of bTB in Devon and Cornwall. With 1.8 million animals tested in Devon and Cornwall in 2014 and 800 farms under bTB restriction, the problem our test is trying to solve is very relevant to our local area.
As well as highlighting some of the fundamental problems with the current Tuberculin skin test, Dick helped us gain an understanding of how our test might best be applied in the field.
CLICK TO SEE HOW THIS WAS INTEGRATED

Saved and Safe

A wide range of parties are involved with tackling TB in the UK. Important to our project was to really engage with those at the forefront of TB eradication. Central to this is a company called Saved and Safe and their director Michael Ross. Michael lives in New Zealand and was highly involved with the strategy that saw a decrease in TB incidence rate across New Zealand of 94% in just 10 years. Following this success Michael has approached the UK with a strategy that brings together all affected parties. With their 31 UK and international partners, Saved & Safe are taking a new and innovative approach in the fight against TB, something our test could offer great potential to.

Read more Phase 2: Look at what projects are at the forefront of tackling TB.

Micheal Ross - Director of Saved & Safe

A company at the forefront of bTB eradication in the United Kingdom

Michael was extremely excited by our project. Having been heavily involved with New Zealand's Animal Health Board's highly successful strategy to eradicate bTB from New Zealand, his unique approach gave us many ideas as a team. Saved & Safe are at the forefront of TB eradication in the UK with 31 UK and international partners involved on a handful of 'demonstration farms' across the UK. A number of University research groups are also involved in this project. Michael explained some of the key principles behind the work that is occurring at these demonstration farms and told us how our project, if successful, would fit into the work they are doing.

Common Goals

Michael made it clear Bovine TB affects a wide range of people from a wide range of backgrounds. For each individual party associated with the fight against bTB comes a different set of priorities. In order for the UK to develop an effective strategy to manage and eradicate bTB it is important that common ground is established between groups. For example, the NFU represents the farming community of the UK. For them, a bTB breakdown has an immediate negative impact on their livelihood, an impact that they have limited control over. For vets, bTB testing is a continuous cycle that has to be highly organised and can be highly time consuming. For academics, bTB is not only a highly challenging disease, it is a disease where advancements have been slow to non existent.
However, each group is working towards the common goal of eradicating bTB, all from different approaches. Saved & Safe is working to bring these approaches together... Something our test may be able to assist with.

Smart Solutions

One of the problems to do with bTB in the UK is the issue of how the disease is dealt with. In its simplest form if an animal tests positive for TB it is immediately sent to slaughter, the farm is put under restriction and a second test will be conducted in 60 days. This routine will continue until the farm has no positive reactors for two successive tests. Apart from restrictions to the farm, no other measures are put in place to try and aid with clearing bTB from the farm. Any further action has to be come from the farmer individually. Where is the solution?
Yes, some farms will take a number of usually expensive and difficult measures. This can involve building a wall around the farmyard to isolate it from the environment outside - something that can cost up to £250,000. Keeping any cattle indoors all year around is also a common method to limit the effects of bTB. However none of these measures offer a genuine solution to the problem of bTB.
Michael made it clear that smart solutions are the way forward. Rather than the situation being left for the farmer to deal with, a coordinated effort that offers a motive for the farmer is needed, and this is where the UK can learn from Saved & Safe...

Providing the Missing Mechanism

Saved & Safe offer the mechanism for coordination of the elements that are needed to eradicate bTB from a farm. Taking a field by field, farm by farm, county by county approach allows for a coordinated, strategic approach to achieving officially bTB free status for the UK. M.bovis has been shown to persist in the environment for up to 21 months - during this time it is crucial an infected farm has a way to manage the infection. Isolation of the farm, disinfection of the entire area and protection of the border around the farm offers this management tool. Taking a strategy that saw a reduction of bTB incidence by 96% in just 10 years in New Zealand and bringing it to the UK makes Saved & Safe a world leader in the fight against bTB.
Click to see exactly how our relationship with Saved & Safe impacted the development of our test.

Phil Leighton

Our test will be cell free meaning all testing can be done 'in the field'. There were a number of important things to consider when designing exactly how our test would work. This is where Phil Leighton came into our project. A highly experienced vet, we accompanied Phil to a TB test on a Cornish farm and also spoke extensively about our project. Blood testing in cattle, the size of needles/tubes to collect samples and also blood clotting were all things Phil highlighted to us.

Click to read exactly how what Phil told us was integrated into our wet lab.

Read more Phase 3: Look at the real life design of our test.

Phil Leighton

Penbode Farm Vets

We hosted Phil Leighton at the University to explain to him what our project aims to do. As Phil is involved with XL Farmcare, a company responsible for all bTB testing in the South West, we wanted to know the practicalities we would have to consider for our test to be effective. Phil invited us to a TB test on a farm in Cornwall where we saw the testing of 11 Bullocks and also got the chance to chat with the owner of the farm.

Sample Collection

The target of our test is RNA meaning a blood sample is required from each animal that is being tested. Prior to our meeting with Phil, we believed as a team that the simplest way to collect blood from a cow would be a skin prick. However Phil made it clear to us that this is not possible due to the depth you would have to penetrate with a needle. Current blood testing is done from the base of the underneath of the tail. As cows are in a crush during bTB testing, collecting a sample of blood from the tail is easier and safer than the current Tuberculin test that occurs at the neck of the animal. Phil explained how cows are much more accepting of a vet approaching and working with their tail as oppose to their necks.

Sample Collection

Furthermore Phil showed us the current needle and tube that is of standard use for collection of blood from a cow. Initially we believed the components of our test would be in a tube the size of a standard Eppendorf. Logistically Phil said this would not be possible. Collection of blood from the tail into a tube the size of an Eppendorf would not only be extremely difficult it would not contain the blood in a sterile environment - something highly important.
As a team this gave us a number of things to consider when designing how best to contain the cell free aspect of our test. The tube has to contain our test, collect a sample in an efficient and sterile manner and also only allow a small amount of blood to reach the area of the tube our test is contained within.

The Public

Bovine TB in the UK is a highly contentious issue with many different sides to the argument of how it is spread, what the current problems are and also what is the best way to eradicate it from our farming industry. As opposed to debating this issue, we as a team took to the streets with some simple facts, aiming to make people more aware of exactly how damaging Bovine TB is to the UK. When we started we believed that not enough people were aware of some of these key facts. The best way for us to demonstrate this as a team was to engage with the general public armed with clipboards and a simple survey. Our results were interesting to say the least...

Read more Phase 4: Understand the public perception of bTB in the UK.

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George Eustice

The Department for Environmental, Food and Rural Affairs (DEFRA) is committed to eradicating Bovine TB from the UK by 2038. As our project developed it was important that we had a clear understanding of the current work DEFRA is doing to eradicate bTB. To do this we met with George Eustice, the Minister of State at DEFRA and also the Conservative MP for Redruth and Camborne. We discussed in detail with George the most recent advancements DEFRA have made with bTB testing as well as explaining how we believe our test may have an impact. Furthermore we wanted to gauge how imminent policy changes may be for the UK.

Read more Phase 5: Look at DEFRA's Bovine TB strategy.

George Eustice

Minister of State at DEFRA

Bovine TB is the UK’s largest animal health problem. As a team we decided it would be important for us to meet Mr George Eustice. We travelled down to the Penryn Campus (Exeter’s Cornwall Campus) where we hosted George. In 2014 DEFRA released the Strategy for achieving Officially Bovine Tuberculosis Free status for England, a document that outlined exactly what the current problems are and how DEFRA is planning to tackle each individual problem. After a long morning we made sure George fully understood our work, and that we fully understood where out test may fit in with DEFRA’s work.

DEFRA Strategy

George told us how the main aim of DEFRA is to get to a stage where it is possible for the BCG vaccine to be used in the UK. Under current EU regulation it is illegal to vaccinate cattle as the Tuberculin Skin test can not differentiate between infected and vaccinated cattle. Development of a DIVA (Differentiated of Infected and Vaccinated Animals) test is a main priority for DEFRA as this would lay foundations for return of the BCG vaccine. Policy change through the EU takes years. George explained how if the UK wanted to bring the BCG vaccine back sooner it would be possible but it would mean that any UK production would be limited to the UK. The strategy states “bTB-vaccinated cattle would not be able to be traded within the EU” until a ban was lifted across the EU. UK Dairy and Beef trade with the EU is vital to the UK economy, particularly in our local South West area. One of the main benefits of our test is the fact it is detection of the causative organism (M. bovis) meaning it would have the ability to act as a DIVA test. Our test relies on the presence of RNA from the bacterium so a positive result will definitively tell you the animal is a carrier of M.bovis, regardless of if the animal has been vaccinated or not.

Genetic Immunity

George explained to us some of the most recent advancements DEFRA has made. One of these that related to our test is the investigation of Genetic Immunity against M.bovis. In research led by the University of Edinburgh, scientists compared the genes of healthy and infected female Holstein-Friesians (cows) to identify any genetic traits that through selective breeding could be easily incorporated to the majority of animals. Selection of animals with genotypes that offer a better resistance to Bovine TB would allow another way of controlling the disease in cattle. However one current problem with this research involves the ability to detect if the animal actually shows a higher degree of bTB resistance or if the animal is simply better at masking the symptoms of bTB. George explained how a test that could definitively conclude if an animal is carrying bTB would allow greater understanding of whether the individual is simply masking the symptoms of Bovine TB or whether the animal actually has a genetic code that offers bTB resistance. Identifying the animals that have a genuine genetic resistance to Bovine TB is highly important for this strategy.

Others

ETC

Phase 6
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