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<p>WHO AFFECTS WHO</p>
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<p>PROFESSOR ANDREW RYCROFT</p>
 
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<p>ANDREW RYCROFT</p>
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<p>DEVICE DESIGN </p>
 
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                    <p>Dr Simon Rushton also highlighted the fact that human health is not the sole contributor to the problem; antibiotics are used in different spheres. Antibiotic usage is prevalent in agriculture as well as domestic veterinary care and these are also big contributors to the problem.</p>
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                  <center><img src="https://static.igem.org/mediawiki/2016/a/a3/T--Sheffield--slider-intro.png"></center>
                    <p>In order for our device to have maximal effect we started thinking about the potential use for it in agriculture and in domestic veterinary care.</p>
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                    <p>This means potentially our device can apply to animals and hopefully address issue of misusing antibiotics in the non-human health sector. To find out if the sector actually needs our device, we went to speak to </p>
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                      <p>We created a network of interactions between individuals in direct contact with antibiotics to better understand the platform of antibiotic use. This also helped us in our next step of determining whether the targets, aims and goals laid down by policy makers, researchers and managers were actually realistic and being met on the ground where individuals dealt with antibiotics on a daily basis.</p>
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                      <li>In <span style="color:yellow">yellow</span>, individuals <span>consuming antibiotics</span>; in the UK patients can only get antibiotics through having a prescription although in other countries it is possible to get them without a prescription. Family pets, cattle and other farm animals also consume antibiotics at the discretion of vets.</li>
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                      <li>In <span style="color:orange">orange</span>, individuals that <span>prescribe or ensure consumption of antibiotics</span>. GPs and hospital doctors prescribe antibiotics to patients with advice from microbiologists whilst nurses ensure patients take the course. Vets also prescribe antibiotics and it is the responsibility of farmers and owners to give antibiotics to their animals.</p>
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                      <li>In <span style="color:red">red and dark red</span>, individuals who are less directly affected by antibiotics but may <span>influence an individual's consumption</span> of them. As stated previously, microbiologists advice doctors on whether to prescribe antibiotics. Family and friends may encourage or discourage an individual to seek antibiotic treatment either though a physician or other means. Likewise, other animals may influence a farmer or owner’s decision to seek antibiotic treatment if they are seen to be ill and in need of antibiotics as can the opinions of friends, family and other individuals around them.</li>
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                         <h2>Professor Andrew Rycroft</h2>
 
                         <h2>Professor Andrew Rycroft</h2>
                         <p>Again, we would like to find out what the reality looks like. For the non-human health sector, we have interviewed Professor Andrew Rycroft at Royal Veterinary College.The professor confirms there is a culture of misuse of antibiotics in the non-human health sector as well. </p>
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                         <p>Veterinary and Agricultural sectors are some of the chief stakeholders who have direct contact with antibiotics. The application of antibiotics towards non-humans is just as important if not moreso. <!--please hyperlink here to the talk and the walk-->(For more information on the Walk, please see "the Talk and the Walk" under global policies.)</p>
                       
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                        <p>On one hand, if we look at companion animals, such as dogs and cats, they received individual treatment, unlike livestock. Owners sometimes are willing to pay for expensive cares for them. In some cases, veterinary surgeons will <span>prescribe antibiotics irrespective of what is wrong with the animals</span>. Since they are considered as “harmless” and cheap, despite the lack of necessity, they will still be prescribed. </p>
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<p>A BLAST <!--define blast in glossary please-->of the human lipocalin-2 gene found that homologous genes were also present in major livestock species. This would suggest that a device that measures lipocalin-2 would be applicable for use in livestock. Our human practices research motivated us to look into applications on other animals. What we found was that, excitingly, other animals do produce lipocalin.</p>
                        <p>Secondly, farm animals, for example, pigs, cattles and poultry, are where antibiotics are most used on. Production of a farm gets affected when there is an infection outbreak, so antimicrobials are seen differently. The use of antibiotics is seen as a business decision as well as a decision for animal welfare.  Vets sometimes give antibiotics not to individual animals but to the entire herd in boxes and bottles of antibiotics. There may be leftover. It increases the likelihood of misusing antibiotics because this means farms could be using without provision of a vet. </p>
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                        <p>Professor Rycroft told us a few stories that highlight the culture of using antibiotics unnecessarily. </p>
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                            <li>The Professor was told one time that about what a farm manager did for what seemed to be an outbreak of an infectious disease. The <span>first thing</span> that the manager did was to give a 100 ml of penicillin-streptomycin mixture and other antimicrobials to the cattles that were not looking well. However, the antibiotics did not do any good because it was not a bacterial infection that causes the problem. This was a case of misusing antibiotics.</li>
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                            <li>Antibiotics are given by Vets on prescription. However, some vets might promote antibiotics <span>because selling them would make profit</span>. This even happens in the UK but not to the same extent it happens in Southern Europe. In the UK, as mentioned, vets may supply antibiotics in a quantity that is more than one course. This means there would be leftover and that farms would not need to contact a vet next time and <span>themselves could decide</span> when to use the drugs.</li>
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                            <li>Pneumonia is a respiratory disease that could kill pigs in 24 hours and could be highly contagious. To prevent it, in Cyprus, some farms will put pigs on antimicrobials from 7-10 days from age. </li>
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                        <p>Finally, we would like to know what Prof. Rycroft think would make a good device.</p>
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                        <p><b><span>What do you think about the idea of using this device on animal?</span></b></p>
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<p><b>Professor Andrew Rycroft</b></p>
                        <p style="padding-bottom:50px"><i> <span>Sounds perfectly good</span>. It’s the kind of thing that the veterinary surgeons really are looking for. Pen-side tests that they want to be able to do the test to ask a question like a pregnancy test would give you the result.. But the reality for veterinary <span>it’s got to be cheap</span>. While for companion animals or even horses, you might spend easily hundreds of pounds on tests or treatments… Now <span>farmer isn’t going to spend</span> that even on a herd of cow.</i></p>
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<p><b>Professor of Clinical and Veterinary Microbiology at the Royal Veterinary College, University College London</b></p>
                        <p><b><span>For the device to be practical for vets, would it need to be able to analyse multiple blood samples at once?</span></b></p>
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                        <p><i>“Yes, if you have an outbreak of infectious disease,each animal should be representative but you would normally sample more than one. When we go on a farm and looking for diease, we might kill three animals and do the post mortems on them… so you want to sample more than one. And for some infectious diseases when you diagnose it with a blood test looking for antibody perhaps a viral infectious something like leptospirosis…, you might have to sample 12 animals. So for your blood sample yes you would probably want to sample several of them.</i></p>
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<img src="https://static.igem.org/mediawiki/2016/7/7a/T--Sheffield--Phylogeny.png" style="width:100%;float:none;">
                        <p style="padding-bottom:50px"><i>“So how rapidly would your blood test be expected to give a result?”</i></p>
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<p><small><b>Figure 6. Phylogeny produced from sequences of lipocalin-2 orthologues in various livestock and pet species.</b> The presence of these orthologues in a wide variety of organisms would indicate that this system may work in many different vertebrates<sup>1-8</sup>.<small></p><br/> <!--can you make it so that the figure description goes underneath the picture? it doesn't in the normal view, but it does here-->
                        <p><b><span>It would depend on our reporter system. We are hoping to bring down to quickly as 20 minutes. For GFP, hopefully less than an hour.</span></b></p>
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                        <p style="padding-bottom:50px"><i>“That’d be marvellous. That’s the kind of diagnostic test that people are genuinely trying to use…” </i></p>
+
<p>This means our device has potential application to animals, and hopefully can address the issue of misusing antibiotics in the non-human health sector. To find out if this sector actually needs our device, we went to speak to Professor Andrew Rycroft at the Royal Veterinary College.</p>
                        <p><b><span>What kind of a percentage would you say is an acceptable range of accuracy for a device like this?</span></b></p>
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                        <p><i>“Anything above 80% sensitivity and specificity would be good.”</i></p>
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<p>Firstly, we were interested to know from a veterinarian point of view if one would view the misuse of antibiotics is an issue. </p>
                        <p><i>“In terms of a pen side test,currently our plan would be a small spectrophotometer that would probably be able to fit into the back of a car,particularly the back of a landover. And then having a smaller test that you will actually take to sample. Would that be alright in terms of portability for a vet going to farm?”</i></p>
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                        <p style="padding-bottom:50px"><i>“Small devices in the back of a landover would be fine.As long as the test didn’t involve <span>more than 2 or 3 steps</span> would be fine. They don’t like it when it’s complicated and require following difficult instructions. That would tend to put them off. You need to be able to offer the test under 10 pounds. For the individual machine, wouldn’t be unreasonable to pay 3000 pounds for such a piece of equipment”</i></p>
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<p><h3>The misuse of antibiotics is an issue in human health. Is it also an issue in agricultural and veterinary settings?</h3></p>
                        <div class="center-text">
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                        <p><span>Practicality for vets</span></p>
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<p><i>“Yes, it is. And you really got to seperate here companion animals, dogs, cats and possibly horses.. Those kinds of companion animals, you can think of them pretty much in the same way as human patients. Because the individual animal is taken to veterinary surgeons and indeed some veterinary surgeons will prescribe antibiotics irrespective of what’s wrong with the animals. Total misprescribing of antibiotics. Because they are thought of as being harmless and relatively cheap. In some cases, but not all by any means, will prescribe these drug when they are not really needed.”</i></p>
                        <p>Result coming in under an hour.</p>
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                        <p><span>Accuracy</span></p>
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<p><i>“On the farm, it is completely different.  Most antibiotics are used on farms’ pigs and poultry a little bit in cattle,but not very much and not very much in sheep or goats. Primarily pigs and poultry because they are the ones that their production suffers because of infectious disease.There is difference. Vets will prescribe for the entire herd and will leave behind bottles and sometimes boxes of bottles of antibiotics. Farmers will then use those drugs and they will misuse them because they have no idea what they are doing with them..."</i></p>
                        <p>Above 80%</p>
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                        <p><b><span>Portability</span></p>
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<p>From this interview, we learned of different perspectives on the antibiotic crisis. We were made aware of the distinction drawn between companion (pets) and farm animals. Pets could be end-users of our device.  We also gained better understanding of antibiotic prescribing culture in veterinary practice on farms.</p>
                        <p>Small devices and no more than 2-3 steps.</p>
+
<h2>References</h2>
                        <p><span>Cost</span></p>
+
<ol><small>
                        <p style="margin-bottom:50px">Each test should be under £10.</p>
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<li>Church DM, Schneider VA, Graves T, Auger K, Cunningham F, Bouk N, et al. Modernizing reference genome assemblies. PLoS Biol. 2011 Jul;9(7):e1001091.</li>
                        </div>
+
<li>Groenen MAM, Archibald AL, Uenishi H, Tuggle CK, Takeuchi Y, Rothschild MF, et al. Analyses of pig genomes provide insight into porcine demography and evolution. Nature. 2012 Nov 15;491(7424):393–8.</li>  
                          <p>We aimed to integrate Prof. Rycroft expert opinions into our designing of the device. Nevertheless, as our findings showed a device that we proposed would have limitations in tackling the problem of antibiotic resistance as a whole. Recommendations and guidelines are not enough to enforce correct behaviors. There would be little  global improvements in antibiotic resistance unless policy changes and attitude changes are taken place.</p>
+
<li>International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004 Oct 21;431(7011):931–45.</li>  
 +
<li>International Sheep Genomics Consortium, Archibald AL, Cockett NE, Dalrymple BP, Faraut T, Kijas JW, et al. The sheep genome reference sequence: a work in progress. Anim Genet. 2010 Oct;41(5):449–53.</li>  
 +
<li>Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature. 2005 Dec 8;438(7069):803–19.</li>  
 +
<li>Lowe TM, Eddy SR. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 1997 Mar 1;25(5):955–64.</li>  
 +
<li>Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, et al. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science. 2009 Nov 6;326(5954):865–7.</li>  
 +
<li>Zimin A V, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, et al. A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42.</li>  
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<p><h2>Device design</h2></p>
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<p>We asked Professor Rycroft what would make a good device for a vet. We summarised the changes that Professor Rycroft suggests for the design of our device.</p>
 +
 
 +
<p><b><u>Practicality for Vets</u></b><p>
 +
<p>An important consideration is the ability to analyse multiple blood samples/animals at once. For some infectious diseases like leptospirosis, to detect the antibody sometimes up to 12 samples are required for detection.</p>
 +
 
 +
 
 +
<p><b><u>Time</u></b></p>
 +
<p>The device should take no longer than an hour to produce a reading.</p>
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<p><b><u>Accuracy</u></b></p>
 +
<p>The device must report an accurate result more than 80% of the time.</p>
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<p><b><u>Portability</u></b></p>
 +
<p>For use in a veterinary practice, the device needs to be relatively small and involve no more than 2-3 steps.</p>
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<p><b><u>Cost</u></b></p>
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<p>Each test should be under £10.</p>
  
 
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Latest revision as of 20:20, 19 October 2016

A template page

AGRICULTURE

Professor Andrew Rycroft

Veterinary and Agricultural sectors are some of the chief stakeholders who have direct contact with antibiotics. The application of antibiotics towards non-humans is just as important if not moreso. (For more information on the Walk, please see "the Talk and the Walk" under global policies.)

A BLAST of the human lipocalin-2 gene found that homologous genes were also present in major livestock species. This would suggest that a device that measures lipocalin-2 would be applicable for use in livestock. Our human practices research motivated us to look into applications on other animals. What we found was that, excitingly, other animals do produce lipocalin.

Professor Andrew Rycroft

Professor of Clinical and Veterinary Microbiology at the Royal Veterinary College, University College London

Figure 6. Phylogeny produced from sequences of lipocalin-2 orthologues in various livestock and pet species. The presence of these orthologues in a wide variety of organisms would indicate that this system may work in many different vertebrates1-8.


This means our device has potential application to animals, and hopefully can address the issue of misusing antibiotics in the non-human health sector. To find out if this sector actually needs our device, we went to speak to Professor Andrew Rycroft at the Royal Veterinary College.

Firstly, we were interested to know from a veterinarian point of view if one would view the misuse of antibiotics is an issue.

The misuse of antibiotics is an issue in human health. Is it also an issue in agricultural and veterinary settings?

“Yes, it is. And you really got to seperate here companion animals, dogs, cats and possibly horses.. Those kinds of companion animals, you can think of them pretty much in the same way as human patients. Because the individual animal is taken to veterinary surgeons and indeed some veterinary surgeons will prescribe antibiotics irrespective of what’s wrong with the animals. Total misprescribing of antibiotics. Because they are thought of as being harmless and relatively cheap. In some cases, but not all by any means, will prescribe these drug when they are not really needed.”

“On the farm, it is completely different. Most antibiotics are used on farms’ pigs and poultry a little bit in cattle,but not very much and not very much in sheep or goats. Primarily pigs and poultry because they are the ones that their production suffers because of infectious disease.There is difference. Vets will prescribe for the entire herd and will leave behind bottles and sometimes boxes of bottles of antibiotics. Farmers will then use those drugs and they will misuse them because they have no idea what they are doing with them..."

From this interview, we learned of different perspectives on the antibiotic crisis. We were made aware of the distinction drawn between companion (pets) and farm animals. Pets could be end-users of our device. We also gained better understanding of antibiotic prescribing culture in veterinary practice on farms.

References

  1. Church DM, Schneider VA, Graves T, Auger K, Cunningham F, Bouk N, et al. Modernizing reference genome assemblies. PLoS Biol. 2011 Jul;9(7):e1001091.
  2. Groenen MAM, Archibald AL, Uenishi H, Tuggle CK, Takeuchi Y, Rothschild MF, et al. Analyses of pig genomes provide insight into porcine demography and evolution. Nature. 2012 Nov 15;491(7424):393–8.
  3. International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004 Oct 21;431(7011):931–45.
  4. International Sheep Genomics Consortium, Archibald AL, Cockett NE, Dalrymple BP, Faraut T, Kijas JW, et al. The sheep genome reference sequence: a work in progress. Anim Genet. 2010 Oct;41(5):449–53.
  5. Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature. 2005 Dec 8;438(7069):803–19.
  6. Lowe TM, Eddy SR. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res. 1997 Mar 1;25(5):955–64.
  7. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, et al. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science. 2009 Nov 6;326(5954):865–7.
  8. Zimin A V, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, et al. A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42.

Device design

We asked Professor Rycroft what would make a good device for a vet. We summarised the changes that Professor Rycroft suggests for the design of our device.

Practicality for Vets

An important consideration is the ability to analyse multiple blood samples/animals at once. For some infectious diseases like leptospirosis, to detect the antibody sometimes up to 12 samples are required for detection.

Time

The device should take no longer than an hour to produce a reading.

Accuracy

The device must report an accurate result more than 80% of the time.

Portability

For use in a veterinary practice, the device needs to be relatively small and involve no more than 2-3 steps.

Cost

Each test should be under £10.