Difference between revisions of "Team:Exeter/BovineTB"

 
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  <h2>Bovine TB</h2>  
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  <h2>Bovine tuberculosis - the problem</h2>
<p>TB in cattle is caused by <i>Mycobacterium bovis</i>, which is just one of several members within the <i>Mycobacterium tuberculosis</i> group. Bovine tuberculosis is a zoonotic disease with the potential to transmit infection between animals and humans. Transmission to humans usually occurs via infected milk, however, in developed countries where milk pasteurisation is routine, most bacteria within infected milk is killed meaning actual infections in humans are rare within these areas. Conversely, in areas of the developing world <i>M. bovis</i> is a relatively common cause of human tuberculosis.
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<h3>An introduction to bTB</h3>
Bovine TB is a disease which affects a broad range of mammalian hosts. In addition to humans and cattle, it can also cause disease within deer, llamas, pigs, foxes and possum, just to name a few. Depending on the species involved, spread of infection can occurr via direct contact, contact with the excrement of an infected animal, or inhalation of even one aerosol droplet. Importantly, high rates of infection have been found in Eurasian badgers (Meles meles) (Proud and Davis, 1998) and the general consensus between scientist with the TB community is that badgers are a significant source of TB in cattle (Clifton-Hadley et al., 1995; Denny and Wilesmith, 1999; Eves, 1999; Martin et al., 1997; Martin et al., 1998). Badgers in particular are a topic of controversy, causing discrepancy between farmers, vets, politicians and activist groups.</p>
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<p>TB in cattle is caused by <i>Mycobacterium bovis</i>, which is one of several members within the <i>Mycobacterium tuberculosis</i> group. The disease affects a broad range of mammalian hosts, including humans and cattle, as well as natural reservoirs such as badgers, foxes, and deer<sup>1</sup>. In different areas, the major natural reservoir differs, for example in New Zealand the disease is carried predominantly by possums, in the USA white tailed deer are carriers, and in the UK the badger has a high rate of bTB<sup>1, 2</sup>. Depending on the species involved, spread of infection can occur via direct contact, contact with the excrement of an infected animal, or inhalation of even one aerosol droplet. Badgers in particular are a topic of controversy in the UK, causing discrepancy between farmers, vets, politicians and activist groups. This makes bTB a difficult subject to approach, due to strong opinions on the topic.</p>
<h2>Badger-Cattle transmission</h2>
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<p>Badgers have been implicated as a potential source of M. Bovis for cattle since an infected badger was identified in GB in 1971. Since then, there has been evidence published which supports a role for infectious badgers in bovine TB epidemiology. Some observations that have been made include:</p>
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<h3>bTB in the southwest</h3>
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<li>The routes of transmission proposed between badgers and cattle, predominantly direct aerosol infection, are plausible given the current understanding of the badger-cattle interface</li>
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<img class="imgright" src="https://static.igem.org/mediawiki/2015/2/2e/MAP2Exeter%281%29.png">
<li>Molecular typing data supports a local epidemiological association between M. bovis in cattle and badgers. Badgers and cattle tend to share the same M. bovis genotype in the same area. This is was evident in GB data obtained during the Randomised Badger Culling Trial as well as within trials in other areas including Northern Ireland (NI) and the Republic of Ireland.</li>
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<p style="float:right; clear:both"><i>Figure 1</i></p>
<li>Badger culling trials conducted in GB and the ROI demonstrated indirectly that badgers contribute to the prevalence of TB in cattle. However, even with these large scale, expensive trials it has not been possible, and may not be possible to accurately quantify the extent of transmission between badgers and cattle, or vice versa.</li>
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</ul>
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<p>Furthermore, it has been noted that there appears to be a relationship between the type of landscape (e.g. Southwest England) and the risk posed by badgers (White et al., 1993). The preferred badger habitat in the UK is well-drained soil close to deciduous and mixed woodland (Clements et at., 1988), bordering large areas of grassland (Wilson et al.,1997). When you take into account the fact that this is the type landscape most favoured in the UK for cattle grazing, it is no surprise that badgers, which are natural reservoir of M. Bovis, would be suspected of transmission to cattle.</p>
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<h2>Badger protection</h2>
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<p>Although European badgers are not an endangered species, they are among the most legally protected wild animals in the UK. Due to the implementation of Protection of Badgers Act 1992, as wells as the Wildlife and Countryside Act 1981, and the Convention on the Conservation of European Willife and Natural Habitats, badger are thoroughly shielded by the government, and badger culling is banned.</p>
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<h2>What Can We Do?</h2>
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<p>As part of our human practices we as a team have made every effort to tailor our test to the people who are who will be using the final product. By looking at the TB debate from different perspectives, we were able to make sure that we developed a test that catered to the both the local farmers and the local veterinary community while taking into account the ethical implications that were brought to our attention by environmental activists.</p>
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<p>bTB is a problem devastating the global cattle industry, but the UK is particularly affected. In 2006, the UK and Irish Republic had an incidence of TB which exceeded that in any other European country by more than 5 times<sup>3</sup>. Within the UK, there are several areas which consistently produce high levels of bTB - the main area being the southwestern UK, which includes Devon, Cornwall, and Gloucestershire<sup>4</sup>. These areas contain a large proportion of the UK’s beef and dairy farms, which are placed under harsh restrictions if any bTB infected cattle are detected. These include trading restrictions which have crippled the beef and dairy industries in the UK.</p>
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<p>Despite its destructive impact on local industries, bTB is on the rise in the UK. Since 1990, bTB levels in New Zealand have been significantly reduced, whereas in the UK levels have increased almost exponentially<sup>5</sup>. Figure 1 uses government data to illustrate the rapid spread of bTB in the UK from 1986 to 2010. It also shows that the disease has its highest incidence in the southwest UK, although other areas are beginning to be more severely affected as the disease advances.</p>
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<p>The University of Exeter is based in Devon, a region with a strong farming community and a major bTB problem. The percentage of TB infected herds in Devon increased from 4% to 25% n ten years<sup>6</sup>. Investigating a local issue meant the team had access to nearby vets, farmers, and other parties affected by the disease.</p>
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<h3>Strategies to eradicate bTB</h3>
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<p>The branch of the UK government that tackles bTB is <a href=”https://www.gov.uk/government/organisations/department-for-environment-food-rural-affairs”>Defra</a>, the Department for Environment Food & Rural Affairs. Historically, Defra has used a simple strategy to control bTB: identify and remove infected cattle. However, with increasing herd sizes and higher incidence of bTB, this solution is no longer viable. In 2014 Defra released <a href=”https://www.gov.uk/government/publications/a-strategy-for-achieving-officially-bovine-tuberculosis-free-status-for-england”>‘A strategy for achieving Officially Bovine Tuberculosis Free status for England’</a><sup>7</sup>, which details a plan to invest £1 billion of taxpayer money over the next ten years in an effort to eradicate bTB.</p>
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<p>New Zealand is a region which has managed to almost completely eradicate bTB from cattle over ten years. The New Zealand government spends 70% of its bTB budget on controlling the natural reservoir in the region - possums<sup>6</sup>. In comparison, badgers are a protected species in the UK and cannot legally be culled due to the Protection of Badgers Act 1992, as well as the Wildlife and Countryside Act 1981, and the Convention on the Conservation of European Wildlife and Natural Habitats. Defra has begun several pilot badger culls in the UK, although they have not provided data on their success or cost.</p>
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<h2>Current methods of bTB detection</h2>
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<p>The current test used to detect bTB in cattle is the tuberculin skin test, in which cattle are injected with two strains of TB and then diagnosed 72 hours later by their reaction to the infection. However, the test has two major problems:</p>
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<p>Firstly, the test has <b>only 80% sensitivity</b><sup>8</sup> This means 20% of infected animals may be left in a herd. As the size of the average UK dairy herd has increased in recent years, infected animals can easily spread the disease to other cattle in the herd.</p>
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<p>In addition, the test is <b>incompatible with the BCG vaccine</b>. The BCG vaccine provides immunity to bTB, however it interferes with the tuberculin skin test - a vaccinated animal will give a false positive result. As a result, the BCG vaccine is banned for use in cattle in the European Union. </p>
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<p>These clear issues highlight the need for a sensitive DIVA (Differentiate between Infected and Vaccinated Animals) test. An RNA-based toehold test would be compatible with the BCG vaccine, allowing for the vaccine to be reintroduced to control bTB in cattle.</p>
 +
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<h2>Our work</h2>
 +
<p>As part of our human practices we, as a team, have made every effort to tailor our test to the people who will be using the final product. By looking at the TB debate from different perspectives, we were able to make sure that we developed a test that catered to the both the local farmers and the local veterinary community while taking into account the ethical implications that were brought to our attention by environmental activists.</p>
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<h3>References:</h3>
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<p>[1] Proud, A.J. and Davis, R. 1998. Tuberculosis in Roe deer, cattle and badgers: a study of infection in populations on an estate in South-West England. <i>Journal of the British Deer Society</i>.<b>10</b>(7), pp. 417-419.</p>
 +
<p>[2] Clifton-Hadley, R.S. <i>et al.</i>1995. The occurrence of Mycobacterium bovis infection in
 +
cattle in and around an area subject to extensive badger (Meles meles) control. <i>Epidemiology and Infection</i>, <b>114</b>(1), pp. 179-193.</p>
 +
<p>[3] de la Rua-Domenech, R. 2006. Bovine Tuberculosis in the European Union and other countries: current status, control programmes and constrains to eradication.<i>Government Veterinary Journal</i>, <b>16</b>(1), pp. 19-45.</p>
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<p>[4] Defra, 2013. <i>Email to www.bovinetb.info</i>, 24 June. Available from: <a href=”http://www.bovinetb.info/docs/bovine-tb-free-commercial-dairy-herds.pdf”>http://www.bovinetb.info/docs/bovine-tb-free-commercial-dairy-herds.pdf</a></p>
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<p>[5] www.bovinetb.info <i>Bovine TB in the UK, England, Ireland, Wales and New Zealand</i>[Online] [Accessed 5 September 2015]. Available from: <a href=”http://www.bovinetb.info/spend-on-culling.php#source”>http://www.bovinetb.info/spend-on-culling.php#source</a></p>
 +
<p>[6] www.bovinetb.info <i>Bovine TB in the UK, England, Ireland, Wales and New Zealand</i>[Online] [Accessed 5 September 2015]. Available from: <a href=”http://www.bovinetb.info/”>http://www.bovinetb.info/</a></p>
 +
<p>[7] Defra, 2014. <i>The Strategy for achieving Officially Bovine Tuberculosis Free status for England</i>. [Online] [Accessed 3 September 2015] Available from: <a href=”https://www.gov.uk/government/publications/a-strategy-for-achieving-officially-bovine-tuberculosis-free-status-for-england”>https://www.gov.uk/government/publications/a-strategy-for-achieving-officially-bovine-tuberculosis-free-status-for-england</a></p>
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<p>[8] Regatieri, A. <i>et al</i> 2010. Testing for Tuberculosis: The Roles of Tuberculin Skin Tests and Interferon Gamma Release Assays. <i>Lab Med.</i>, <b>42</b>(1), pp. 11-16.</p>
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Latest revision as of 03:09, 19 September 2015

Bovine tuberculosis - the problem

An introduction to bTB

TB in cattle is caused by Mycobacterium bovis, which is one of several members within the Mycobacterium tuberculosis group. The disease affects a broad range of mammalian hosts, including humans and cattle, as well as natural reservoirs such as badgers, foxes, and deer1. In different areas, the major natural reservoir differs, for example in New Zealand the disease is carried predominantly by possums, in the USA white tailed deer are carriers, and in the UK the badger has a high rate of bTB1, 2. Depending on the species involved, spread of infection can occur via direct contact, contact with the excrement of an infected animal, or inhalation of even one aerosol droplet. Badgers in particular are a topic of controversy in the UK, causing discrepancy between farmers, vets, politicians and activist groups. This makes bTB a difficult subject to approach, due to strong opinions on the topic.

bTB in the southwest

Figure 1

bTB is a problem devastating the global cattle industry, but the UK is particularly affected. In 2006, the UK and Irish Republic had an incidence of TB which exceeded that in any other European country by more than 5 times3. Within the UK, there are several areas which consistently produce high levels of bTB - the main area being the southwestern UK, which includes Devon, Cornwall, and Gloucestershire4. These areas contain a large proportion of the UK’s beef and dairy farms, which are placed under harsh restrictions if any bTB infected cattle are detected. These include trading restrictions which have crippled the beef and dairy industries in the UK.

Despite its destructive impact on local industries, bTB is on the rise in the UK. Since 1990, bTB levels in New Zealand have been significantly reduced, whereas in the UK levels have increased almost exponentially5. Figure 1 uses government data to illustrate the rapid spread of bTB in the UK from 1986 to 2010. It also shows that the disease has its highest incidence in the southwest UK, although other areas are beginning to be more severely affected as the disease advances.

The University of Exeter is based in Devon, a region with a strong farming community and a major bTB problem. The percentage of TB infected herds in Devon increased from 4% to 25% n ten years6. Investigating a local issue meant the team had access to nearby vets, farmers, and other parties affected by the disease.

Strategies to eradicate bTB

The branch of the UK government that tackles bTB is Defra, the Department for Environment Food & Rural Affairs. Historically, Defra has used a simple strategy to control bTB: identify and remove infected cattle. However, with increasing herd sizes and higher incidence of bTB, this solution is no longer viable. In 2014 Defra released ‘A strategy for achieving Officially Bovine Tuberculosis Free status for England’7, which details a plan to invest £1 billion of taxpayer money over the next ten years in an effort to eradicate bTB.

New Zealand is a region which has managed to almost completely eradicate bTB from cattle over ten years. The New Zealand government spends 70% of its bTB budget on controlling the natural reservoir in the region - possums6. In comparison, badgers are a protected species in the UK and cannot legally be culled due to the Protection of Badgers Act 1992, as well as the Wildlife and Countryside Act 1981, and the Convention on the Conservation of European Wildlife and Natural Habitats. Defra has begun several pilot badger culls in the UK, although they have not provided data on their success or cost.

Current methods of bTB detection

The current test used to detect bTB in cattle is the tuberculin skin test, in which cattle are injected with two strains of TB and then diagnosed 72 hours later by their reaction to the infection. However, the test has two major problems:

Firstly, the test has only 80% sensitivity8 This means 20% of infected animals may be left in a herd. As the size of the average UK dairy herd has increased in recent years, infected animals can easily spread the disease to other cattle in the herd.

In addition, the test is incompatible with the BCG vaccine. The BCG vaccine provides immunity to bTB, however it interferes with the tuberculin skin test - a vaccinated animal will give a false positive result. As a result, the BCG vaccine is banned for use in cattle in the European Union.

These clear issues highlight the need for a sensitive DIVA (Differentiate between Infected and Vaccinated Animals) test. An RNA-based toehold test would be compatible with the BCG vaccine, allowing for the vaccine to be reintroduced to control bTB in cattle.

Our work

As part of our human practices we, as a team, have made every effort to tailor our test to the people who will be using the final product. By looking at the TB debate from different perspectives, we were able to make sure that we developed a test that catered to the both the local farmers and the local veterinary community while taking into account the ethical implications that were brought to our attention by environmental activists.

References:

[1] Proud, A.J. and Davis, R. 1998. Tuberculosis in Roe deer, cattle and badgers: a study of infection in populations on an estate in South-West England. Journal of the British Deer Society.10(7), pp. 417-419.

[2] Clifton-Hadley, R.S. et al.1995. The occurrence of Mycobacterium bovis infection in cattle in and around an area subject to extensive badger (Meles meles) control. Epidemiology and Infection, 114(1), pp. 179-193.

[3] de la Rua-Domenech, R. 2006. Bovine Tuberculosis in the European Union and other countries: current status, control programmes and constrains to eradication.Government Veterinary Journal, 16(1), pp. 19-45.

[4] Defra, 2013. Email to www.bovinetb.info, 24 June. Available from: http://www.bovinetb.info/docs/bovine-tb-free-commercial-dairy-herds.pdf

[5] www.bovinetb.info Bovine TB in the UK, England, Ireland, Wales and New Zealand[Online] [Accessed 5 September 2015]. Available from: http://www.bovinetb.info/spend-on-culling.php#source

[6] www.bovinetb.info Bovine TB in the UK, England, Ireland, Wales and New Zealand[Online] [Accessed 5 September 2015]. Available from: http://www.bovinetb.info/

[7] Defra, 2014. The Strategy for achieving Officially Bovine Tuberculosis Free status for England. [Online] [Accessed 3 September 2015] Available from: https://www.gov.uk/government/publications/a-strategy-for-achieving-officially-bovine-tuberculosis-free-status-for-england

[8] Regatieri, A. et al 2010. Testing for Tuberculosis: The Roles of Tuberculin Skin Tests and Interferon Gamma Release Assays. Lab Med., 42(1), pp. 11-16.

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