Good evening, everybody and welcome to tonight's webinar. My name is Bruce Stevenson and I have the privilege of chairing this webinar. Tonight, we are going to do things a little differently for those of you who have been on webinars before.
We're going to start with a poll question while we are introducing our speaker and everything. And then the other thing that we are going to ask you tonight, please is if you wouldn't mind in your Q and A box, if you would just type in the name of the country that you are in while you are watching this webinar, please. And we'll use that information later on and we'll discuss it with our presenter.
So for those of you that are new on the webinar, it's very simple. If you move your cursor around a little control bar pops up and you can just click on the Q and A type in any questions and they will come through to me. And we will hold those over to the end of the presentation as far as the poll goes, I'm going to launch the poll now, it's quite simple if you can just click on the answer that most suits your situation.
So the question is quite simple. Have you ever seen a case of scrapy in either sheep or goats? So go ahead and, and start clicking away there.
In the meantime, it is my absolute privilege to introduce tonight's speaker. Tim Conal studied veterinary medicine in Munich in Germany and he graduated in 1993. He received his Dr Med vet degree in recognition of his contribution to toxoplasmosis diagnosis.
Three years later, following work as a veterinary surgeon in Germany, Italy and Northern Ireland. Oh, sorry, is in Northern Ireland, he joined the veterinary Laboratories Agency in Weybridge and it's now known obviously as the Animal and Plant Health Agency of Weybridge. This he did in 1999 and he carried out research in transmissible spongiform encephalopathies in farm animals and has been the author of more than 40 publications on this topic.
He was awarded a phd for his studies of the relationship between clinical science and pathological findings in bovine spongy form encephalopathy in 2011. And he is currently working as the named veterinary surgeon and veterinary researcher at the animal and plant health agencies in Weybridge. So it gives me great pleasure to welcome you to the webinar and I'm going to end the poll so that you can have a look and see and share those results.
So 24% of people have seen a case in sheep, none in goats and 76% of our participants haven't seen one in either over to you. Thank you very much for that. Ok.
So if you listen to my previous presentation back in October, you heard a little bit about tec so transmissible spongy encephalopathies that was in cattle. And now we concentrate on sheep and goats and now I'm stuck because nothing happens. So if you just click anywhere on your screen, then it should start.
So the first question is why is it important? So, first of all, it's a notifiable or reportable disease, it's notifiable in the UK. Since 1993 you have to be familiar with the clinical presentation because it's a legal requirement in the European Union.
And that's just the extract that shows you why it's important. It has an impact on trade. For example, if you want to trade with embryos or semen and sourcing of raw materials for bio pharmaceutical industry, that's particularly important in Australia and New Zealand, which are considered to be free from classical scraping.
And there's an increased interest since the discovery of bovine spongiform encephalopathy in cattle. And it's simply because PC is a zoonotic is a zoonotic and there's a concern that it might be that contaminates meat and BME was also fed to sheep. And we also know that BC has been discovered naturally in two goats.
So the one was in France and the other one was in Scotland. So it has been basically present in goats in sheep. We haven't found it yet.
So that's obviously AAA major concern. When I just going back to the impact on trade, there's, there are two different forms and I will cover that later on. Atypical scrapy and classical scrapy with atypical scrapy does not require oie notification and cases do not impact on trade.
And that is the reason why Australia and New Zealand who have cases of atypical scrapy are normally not really too concerned about the impact on trade because classical scrape is the important one for the trade. So just to give you a background, so tu CS are slowly progressive neurological diseases and you have spongiform changes of Oculus neuro in, in the neurons in the brain. There's a misfolding of the physiological form of PR P.
So the cellular PR P which is in an alpha helix form, turns into a disease associated form which is a better sheet, which is resistant to proteinase K or protein, a general enzymes. And that causes a disease which is an a brain disease. There are different protein conformations and that might explain why you've got different strains and you've got infectious forms and possibly spontaneous or sporadic forms in small ruminants.
And if you look at scrapie, the susceptibility in small rooms is influenced by the Brian protein genotype, historical, we had classical scrapy. We know that for, for centuries. So it was in the British Parliament debated in 1755.
There's also a German agricultural book that deals with the disease. It, it actually describes it quite accurately and it also tells you that you shouldn't keep or keep sheep that have the disease so you should get rid of them. So they already knew that it was probably infectious.
So the question always, is it a genetic or is an infectious disease or is it both? And at the moment, we think it's an interaction of one or more strains of an infectious agent with one or more host genetic factors. So basically, the gene, there's a genetic susceptibility, but it's an infectious agent, certainly for classical scrapy.
Now we've got a scrapie in addition, which was first observed in observed in Norway in 1998 they called it at that time, nor 98 published in 2003. And we subsequently found it retrospectively in a clinical suspect from 1987. Now, you have to keep in mind that you can't just dig out brains from, from the eighties.
So normally you can only scan brains retrospectively that were stored by informally and usually, and these are usually clinical suspects. So for example, that case from 1997 was actually a clinical suspect. A scrapy suspect at that time, it was classified as not scrapy because they couldn't find any evacuation.
At that time, it was just based on evacuation and it, it was basically negative. But when you then retrospectively looked at the brain again and used an pr P antibodies, it was certainly scrapy and it turned out to be a scrapy. Then looking at the epidemiology, scrip is a long incubation period that can last for months, up to several years.
The susceptibility, the incubation period, the transmission is dependent on the protein genotype. And for example, if you got a long if if you got a more resistant genotype, you've got a much longer incubation period, that could be years because it takes even you, you, you find for example, pro protein in the lymphoreticular system, but that doesn't seem to cause any disease, but it's once in the brain and then disseminates. Then you see clinical disease, there's a difference between classical and atypical scraping.
And in the uie chapter 14 8, you see basically the difference that atypical scrap is clinically pathologically biochemical and epidemiology unrelated to classical scrapy may not be contagious and may in fact be a spontaneous degenerative condition of older sheep. That's why it's not considered to be that important. Simply because if it's a spontaneous disease, there's not really anything you can do about it.
So if you just look at the differences between both types of classical gray, which transmits vertically and horizontally in a square, we don't know, and susceptibility is dependent on the genotype in both forms, but it's different between classical and at scraping and I will cover that later. Then there's also a difference. So if you've got usually younger sheep in class with classical scrapy, there were clinical cases even under 12 months in shape and for atypical square, they generally older.
So I just have here a few the mean ages in in the eu you can see that several years spaces and the age between sheep and goats for a scrape is fairly similar where there's a difference in sheep and goats for classical scrape. Yeah. In fact, I've, I've never seen a goat, a clinical case of a goat that was less than 30 months of age, but I'm sure they exist.
But if you're, if you're really unlucky, then how often do you see it, if, if it occurs in a flock or in a herd, then you usually have a group of animals affected class Rey. It obviously depends on the genotype distribution in your herd or flock. And for HIV, scribe, it's only usually only single animals.
We had a few farmers where we had more than one. So usually two cases. I don't think it's very common to have more than two cases at all.
So, and then here we got the important thing about the genotypes. We've got susceptible genotypes which form the basis for the breeding and the CALIB programs in the EU and certainly also in the UK and you, you look at the brain protein chain and you see different types of brain protein chains. So the, these lets stand over for amino acids that the brain protein gene that codes for certain positions.
So you got polymorphisms. So basically different proteins that are or amino acids that the, the code on in codes. And you have got at one position 136, you got either an A which stands for Alanine or Vallin B.
Then we've got a position 154, either an algen or his and a position 171. You got a, again, his, you might have a glutamine or you've got a alg again and we, we know that a Rrar Sheba, the most resistant to classical re cases have been reported, but it's very, very rare. And we also know that via Qveq sheep.
So that's on the bottom. Basically that they are the most susceptible ones and certain breeds don't have va Q va Q sheep. For example, Suffolk are more common with a Rqaiq, but they are equally quite susceptible to scrapy.
Then you've got additional polymorphisms that are normally not forming a basis for a breeding program, but it was discovered later, for example, code on 112, you've got either met or thine which three associated with increased resistant. And you've got a code on one for one you've got either Fenny alanine or a leucine and that affect the susceptibility to at scrapy or classical scrapy. So, l is more classical scraping, f more at scrapy.
And A two describe is more or less the other way around. So you've got a Rrarr sheep that are most commonly affected or a HQ A HQ, whereas VRQVRQ sheep, they are very rarely affected. So I am not aware of any Viqvrq sheep that was naturally infected with HIV Gray.
As far as I know from a publication that what we've done in our lab, there was one VRQ and a RQ sheep that had a case of a scrape here. So, and the cra scrape incident was just one out of 10,000 a layer. So that's very, very rare.
Once you got a viq allele, then it's quite uncommon that the sheep has a to scrapy when we did experimentally challenge animals. Then you could infect via QVIQ sheep. They had a long incubation periods.
But normally a challenge, you have to use basically one sheep brain that you get. And that's normally a sheep from a sheep brain from a naturally infected animal. And you won't find A, as I said, it's very rare to have A via Q via Q sheep.
I never seen one or I've not heard of one. So you have to use a, a sheep with a different genotype we use in the HQ HQ sheep brain that lead and inoculate into a viqviq sheep. And we don't know or we assume that this also changes the incubation period.
Because usually if you have the same genotype to transmit from one genotype to this within the same genotype, then no, normally the incubation period is, is probably small, shorter than, than using a different genotype in goats. Well, a few years ago, we didn't think there was any, any point in, in drawing a, a genotyping program because we were always assuming that goats are susceptible and there's nothing you can do about it. If you look at the same coons as for shape, they are fairly, the same goats are mainly a RQAQ, you might see some A HQ HQ.
So you have to look at different areas of the prime protein chain and it's the coon 222. So you, you have either li which is A K or you've got the serine or asperate in, in position 146, the or glutamine again at position 2, 211 that makes it more resistant. Then you've got immediate here in position 154 and 142 only in combination with, with a, a prole at 240.
These codes have some genetic resistance to scrapy. And then you've got basically Y types that are highly susceptible, scraping. So they have basically this position or these and code for these amino acids are shown below.
And if you look at ATS gray, so his, at one position, 154 is associated with increased susceptibility to a gray. There hasn't been an at scrapy case in goats in the UK. So far there have been a few reports in other European countries.
But yeah, I haven't seen one. We try to replicate by infecting or we tried to inoculate animals, goats with a scrapy from sheep, but we haven't succeeded to a replicator. These animals didn't have a confirmed disease for more on the epidemiology.
There's vertical transmission. So that's for classical scraping, you know, and it's, it transmits in utero. We know it transmits via the placenta and via, via the fluids.
And we also know it's transmitted via colossal and via milk. And that's the same for goats and sheep. Then there's horizontal transmission via several secretions and excretions of urine feces and saliva.
They're all sh have shown to be infectious. Most of the studies now are used in vitro test the test basically for Brian protein. In, in the past, you always use transmission.
So you had to use these fluids and inoculate transgenic mice or mice in general with its normal white type mice are not as sensitive. So now that you use different tests, use either transgenic mice that carry the ovine prime protein gene or you use more sensitive brain protein based tests that you can use as one called P MC A which is protein misfolding cyclic amplification, which is similar to the PC R. The polymer chain reaction just amplifies protein instead of DNA.
And then there's a sim similar method which is called R TW, which is real time quaking induced conversion. A similar method where you just amplified minute amount of protein brine protein. And with that, you can detect basically brian protein, urine feces and saliva and is then assumes that once you detected, it's also infectious.
Basically, the risk of infection is through environmental contamination. If you share pasture or bars or sheep that have been in a in a pasture and have been infected, they will pass it on sh shared water and food troughs are certainly a risk. And so also pen fences and post.
And we did a study where we had fences from our scrapy affected flock and put a fence post in a building that never had any scrapy cases and just put sheep in it, clean sheep and they got infected. So they just by licking or scratching or whatever they do on that post, they got infected. And we also know there's an age dependent susceptibility.
So younger animals are more susceptible and that's associated with the pious patches evolution and the density of the follicular dendritic cells because they are denser in younger animals. And that's how the pro protein is, is believed to go into the or spread into the animal just look at the population. Europe.
That's from the Eurostat, statistics. There's a little bit strange that Switzerland is not supposed to have any sheep, but I think that's just because it wasn't, recorded. So they definitely have sheep, sheep and goats.
I had different figures from 2013, they had four or 10,000 sheep and 90,000 goats. But what you can see there's quite a range of, of the population in different countries. And that's probably important for if you look at the surveillance because I come back to that later.
So, so scrape your surveillance. It is, it is determined by the number of sheep and goats you have. So the more sheep you have to sheep you've got or more goats, you've got, the more you have to test.
So the how is disease monitored? You got the passive surveillance system which relies on the reporting of clinical suspects. It's an eu requirement since 1998.
It's obviously depending on people knowing all this disease looks like and the willingness of people to report cases if you report a case and you have scrapy, certainly classical scrapy. There are certain restrictions and that's sometimes not very good for farmers. So it's people are probably farmers are probably more reluctant to report a case simply because of the restrictions that are imposed.
And because of that there's active surveillance because then you can actually find more cases. So you look at healthy slaughter animals and risk animals, which are these ones that fall in stock, for example. So animals that die or they're not used for human consumption because they are sick.
And the animals are checked over the age of 18 months. And that was introduced in the Eu in January 2002. And here, the healthy slaughter, that's just not everybody has to mo monitor healthy slaughter animals.
And that's the eu regulation which tells you that the number of breeding females, if they exceed 750,000 animals, then you need to assemble a minimum annual sum of 10,000 ovine animals. Now, we don't have that in the UK, we don't, well, we have enough O vine but not goats. So that's the reason why we don't test healthy slaughter goats anymore.
The only test fallen, fallen stock in goats. So here it's even more important to, while you rely basically on the pass more in goats, the vast majority of scrape K are found by active surveillance now. So there's more 22, between two and six cases are diagnosed per 10,000 tested animals in 2016.
And that was based on the EFS a opinion or publication. Classical scrap is still more frequent than at scrape in the EU that hasn't changed. So you see the ratio here, so you got 4.5 classical scrape or four more four classical scrapy case against one at scraping case in sheep.
And you got four more classical scrapy cases and goats compared to atte scraping gods. Then the most classical describe case are found in Greece, Spain, Italy, and Romania and Cyrus has most of the goat cases. And that's why there's currently a breeding program in, in place to, to see if you can breed for resistance in Cyprus.
So in the, in the Great Britain here, you just see a statistics. So you've got here, what, here on the left hand side is this is the classical scrapy flock scheme or the compulsory scrapy flock scheme. That's when you have a case of scrapy, you basically have these restrictions imposed.
Your flock is basically then monitored for, for as long as you don't have any cases anymore than you. And if you're free for two years, then it's the monitoring stops. So you can, well, it's for the goats or sheep.
And as you can see here, you got 579 tests and only you found only one in she sheep with atypical scrape for goats. There were seven found classical scrape out of 7, 374 tested and that was in 2000. Well, seven in 2016 for 597 and four, out of 374 they were tested for positive surveillance.
You see, that's quite disappointing because there has hardly any, any animal being reported, there's only one tested in shape and that was negative in 2016. And goats were two tested at two po positive in 2016 and one was tested but it was negative. These were actually passive surveillance cases from those flocks that were or herds that were already part of the compulsory scrapy flock scheme.
So that's not a new case, but these were based on farms where people actually knew how the disease looked like we had already cases before. Then you look at the active surveillance. Well, a lot of animals were tested and you, you basically see that you've got one scrape decay in, in 2017, 8 of the scrape decays and 11 for active surveillance.
So you see more for the for the fallen stock, you see more animals that have a scrapy than by testing healthy slaughter cattle. That's what sheep, that's what you would expect anyway. So, diseased sheep are more likely to have the disease than healthy slaughter animals.
And here it just tells you that that's, it's fairly disappointed. The number of passive surveillance cases are active surveillance definitely is more effi efficient ef figure. Well, the effie of finding animals with scrap is better when you look at or active surveillance, looking at diagnosis.
All the current screening or confirm tests use PR P as a male disease in the older times, it was histology. I look for v now you look for pr P, there's no zoological tests and there's also no reliable anti modem test. Some animals depending on the genotype have pre and protein and lymphoid tissues.
So you couldn't see you would take a biopsy and test, but some might not have it in the lymphoid tissue. So a negative result doesn't necessarily mean that the animal hasn't been affected. So the confirma confirmatory diagnosis is usually made made postmortem.
You can you test on based on, on antibody detection and you detect host as well as disease specific PR P. So you can either then measure the amount of PR P which is abnormal or you remove the cellular PR P and you just have basic proteinase resistant PR P which you then measure and there are different tests. You can use a laser, a Western plot or you can, you know, use immune history chemistry, which is our preferred method simply because you can detect tiny amounts in a small sample and you can localize it.
Whereas with Western plotting or laser based test to digest the sample and you just hope that there's something in the in the sample that you can then detect look in the pathogenesis in class square. You have invasion of the peloton tonsil, the pious patches that then spreads to other lymphoid tissue. The neuro invasion starts from the enteric nervous system.
It goes via the parasympathetic and sympathetic nerve fibers. And it enters the dorsal motor nucleus of the vagus nerve, or it's also called the parasympathetic nucleus in the meat or the ECs and in the spinal cord is the inter medi lateral column of the thoracic spinal cord. Then the dissemination of the scrape A is dependent on genotype and strain.
So if you have a VA QVRQ shape, for example, you have a very wide distribution all over the lymphoreticular tissue. Whereas if you use a more resistant genotype, like an A Rqarr shape, it's very limited to find you, it's very difficult to find anything in the lymph Vergo tissue. If you use for example, IHC immuno histochemistry, there's also another type of scrapy, which is called ch 1641 based on a it was discovered in a Chevy sheep.
That's what the CH stands for. And the number was 1641. This is also a scrapy type that is a little bit concerning because it is more difficult to differentiate from pe C.
That's why it's important to different, yeah, to diagnose it. And there's a limited preferable distribution of pop. And this as well, the question mark is because there's not a limited limited studies have been done actually.
So to determine often they were inoculated into sly. So you don't know if that's then the natural or or limit mimics the natural route of infection. So for atypical square we have got actually a limited knowledge about the pathogenesis.
We assume it's a spontaneous disease originally in the brain. That's why we also, if you want to reproduce it experimentally, we use normally in the intercerebral route. Assume that it starts in the brain.
There's no detectable brain protein in the lymphoid tissue. If you use Venus to chemistry or any other brain protein based test, although the infectivity might, may be detectable by bio assays. So, so far we haven't been able or nobody has been able to de detect PR P.
Also using these more sensitive tests. As I mentioned earlier, the in vitro tests that doesn't seem to work that you can detect PR P with these tests either. So you have to use other means.
And that is normally the bio as I use transgenic mice to de detect infectivity. So we know there's something the lymph tissue but you can't detect it by normal test and the infectivity in peripheral tissues we have that has been discovered. So lymph lymphoid tissue is infected may is that due to the spread from the brain.
So that's just a picture about the diagnosis. You can take a rectal biopsy. There's a speculum you can use and you basically see here the rectal folds and then you just take a biopsy and then you make a slide basically and stain it with APR anti PR P antibody, which is in this case R 145 and you see these little brown spots here.
Yeah. So this is basically in protein in it, either in the macrophages or in the follicle generic cells. And that's diagnostic.
You can also, if you wanna remove the brain, there's a, this one was, I think it's a Norwegian spoon, but you can use a plastic spoon that's used in the abattoir. So you just remove basically the Metula Lanka. You want also a bit of cerebellum for a scrapy diagnosis.
So you move the brain and then you use again pr P that, that's immuno histochemistry. Again. Here you see basically labeling here in this, this area which is the those motor nucleus of the vagus nerve.
Or you hear you've got the immuno la in the cerebellum that's particular in Attu Scrapie. So you won't find that in Abu Scrapie, that's more classical scrapy. That's why most of the cases probably weren't diagnosed initially because you concentrate more in the cerebellums or more in, in more Rusal structures.
You got pr P a combination at the scrap. When you use the Western plot, you see your differences using the that antibody show 31 you see these, these different protein bands that remain after you digest it basically. And you see here, the difference is you can see there's a slight difference between classical BC, which is if you use basic classical BC in shape, that's the bands are the molecule.
This is the molecular mass marker. Here, you see that the bands are a little bit different. Sometimes it's difficult to distinguish.
That's the reason why you can use different antibodies. So you can use a P four antibody which doesn't detect B CPR P protein resistance PR P. So you can distinguish the BC from scrape and A TV, scrap is completely different because you've got these different protein bands.
So if you want to diagnose it clinically, you have to do a physical or neurological examination, a physical examination to exclude other infectious diseases which may cause a rise in temperature. We don't expect anything to happen in scrapy. We, I test the cranial nerve function, although the function of the cranial is just usually not impaired in the disease.
So the what I concentrate usually is the menace response. So you move the hand or the fingers towards the eye and it should, the animal should blink. You can blind fold the animal, which is quite, in my opinion, quite good to diagnose a scraper.
So you cover the eyes with the hood to evaluate the, the function of the vestibular system. I also do ophthalmological examination. The only problem is if it's too bright, you can't see anything because I don't use normally a meteoric.
But I use a torch. If, if it's dark enough, I use a torch and retina lens and just assess the popular light reflex. And I look for eye disease.
That may cause blindness. Then you can take additional symbols for laboratory tests more as to exclude other diseases. So, how does it look like clinically?
Well, it's a progressive neurological disease. You've got abnormal behavior and mental status so that animals might be nervous, dull, they might teeth grind or they might be just separate from the, the rest of the flock. You've got an abnormal sensation, apparatus, overactivity, external stimulus, less pronounced than sheep.
I've seen it more in goats and you've got a positive scratch test. Some people call it nibble reflex. I don't think it's really a reflex.
So that's the reason why I call it a positive scratch test. And you've got an abnormal movement and abnormal posture, animals might be Atex or hyper metric with a high stepping gate. They might stand white based or they might crouch as you can see on the picture on the right, or they might display head tremor and you might see other neurological signs like an absent menace response that's usually seen in more advanced stages or animals might suddenly collapse.
It's some sort of form of narcolepsy where they basically lose their control of their muscle and just fall to the ground. They might also tool and you had physical changes like a loss of weight or body condition. And then because of the pruritus that fleece changes w or halos.
So this is classical scraping and you have to keep in mind, this is not always, you don't see all these clinical signs in all cases, especially the pus is scratched as pruritus in general you don't see in all animals. And of course, that's normally associated with scraping because that's also the name that came from scraping or some. Yeah.
Or I think in, in Spain it's, it's probably Perrigo or something that basically you, you name it after the most common sign. But in fact, pruritus might not always be present because the Brian protein genotype or the strain might affect the clinical presentation. So certainly in more resistant genotypes, I've seen less pruritus.
So in Viqviq, it's quite common. But if you got a more resistant genotype, then it's different. I also what you published recently, if you got an A Arqarq shape or if it's an A Frqaf, you got less actually no pruritus where it is in a Lrqalrq, you have Pruritus.
So basically, we know that there's a difference between genotypes and since you don't know the genotype in advance, you, you, you, you can't know really, nobody really checks or does any genotyping anymore that was done. So some years ago, when when the eradication started, when you breed for resistant, but now because most animals are probably resistant or semi resistant, people don't really know the genotype anymore. So you, that doesn't really tell you or help you in any way for the clinical diagnosis.
So now I show you a picture of that two year old you that I saw on a farm. So you can see this is twitching. Then here you see the hair loss and the, it's normally there's no such no skin lesion apart from a abrasions.
But you don't have any lesions. Like what, what do you see maybe in mange and then you, you do the scratch test and what they do the, do the nibbling. Then you see these animals drooling.
It's, it's, it's very, it can hardly walk. Then I show you another one. This is t the shape.
I just have to, I don't know where the course is gone now. Oh, yeah. So, yeah, this is also a toxic, particularly the hind limbs.
Usually the hind limbs are more affected than the forelimbs. Then you scratch this again and you can see it reacts to it and usually you have to test if it's repeatable. So if it just does it once, it probably doesn't mean anything.
But if you repeat, you scratch it and it reacts to that, you see all the, some sort of skin lesions here. So obviously it's, it was itchy and has probably nibbled on these areas. Now.
In goats, it's similar. But here you, that's just a really early sign that I show you and that's animals going in a milking parlor. And it's the one that is, it's the one now on the right as which is slightly difficult by the getting in where you see the, the one on the left was going in the M stands quite willingly.
The other one didn't. And that was basically seen as one of the first signs the farmer saw when, when he reported cases that they had difficulty in getting in the milking stand. So that, that's a fairly early sign.
So how does a scrapy looks like? Again, it's a progressive neurological disease. You've got abnormal behavior and mental status.
So similar, if you got nervousness, but the animals might also be confused and separation from the rest of the flock or herd is also a clinical sign. You might have compulsive circling, which is quite interesting if you think that usually it's a bilateral symmetrical disease based on brain protein distribution. So why they circle to one side?
That would normally mean that maybe there's a lesion more more severe le on one side, you've got abnormal movement and posture, animals might be at toxic hypometric, they might lose their balance. That's why it's quite important use blindfolding then because that's normally makes it more obvious if there's a loss of balance, they might have a white based ST similar to Classico scrapy and the head trimmer, you've got absent minus response again, as an another, another neurological sign similar to classical scrapy. The only difference I think is that absent minus response is, is more, is seen earlier than in classical scrapy and you might also have visual impairment and loss of weight and body condition might also be present.
The difference difference between classical and Atuss scr is that the signs seem to be associated with the pathology in Abu gray so that you've got PP accumulation mainly in this cerebellum and also more in the rosal areas like the frontal cortex. So that almost fits with the clinical signs, which is unusual because we still don't know what actually causes clinical signs. And for some strings, a gray where you have basically hypermetria, which you can probably relate to maybe a white male disease or into a sere Bellar disease.
You've got an absent menace response and it may also something to do with the cerebellum. Again, even the circling, maybe with the frontal cortex disease. And if you got loss of balance of v vestibular system, which is also a part in the cerebellum.
So that would also explain the clinical signs that you normally see. Whereas in classical scrapy, it doesn't really fit with most of the clinical signs because you've got a widespread pr P A accumulation in the brain and it's not just restricted to the cerebellum. Now again, I have to find the cursor first.
Here we go. So this is atypical gray that was reported in a and an abattoir, not the this you might think. Well, first of all, you see the animal circling, you also see it has a high stepping hind limb gate, you also see it as woo loss.
And I think that was the reason why it was found originally or detected in an abattoir. Now, I, I, at that time, I didn't take a skin scraping, but I very much doubt that this is pruritus due to classic or scrapy. I think this animal had also mange and that's the reason why it was, I think originally detected.
But then of course, it has other neurological signs that you wouldn't associate with men like the circling like the hypermetria. And here this is an experimental disease. And here we've got several animals and that's, it's fair.
It's a fairly long clip, but it shows you quite interesting clinical signs. So these are all a HQ A HQ Sheard sheep, they were intercerebral inoculate. And you see here the first sheep circling.
So HQ HQ is they're fairly susceptible to a scraping. And then before you know it, you got more animals that seem to circle here. So that's 26 months of age.
So these were, as I said, intercerebral inoculate, you probably wouldn't see that in the, in the natural disease because that will normally take longer. But that might be just because it takes longer in a natural situation to for the prime protein to accumulate in the brain. So here you see it, if you just compulsive circling in front of the camera and you, if you see that in, in a farm, you probably wouldn't think of scrap at all.
You'd probably think of other diseases like, you know, maybe an ear infection or maybe listeriosis. So here this animal's blind fold, as you can see now, it's, it's way head from left to right. That indicates some sort of vestibular dysfunction.
It also has a slightly weight based stance on the hind legs and then when you remove the hood, usually, then the animal walks off quite normally. Here, this is more severe. This one loses his balance.
And here you can really see the white based stance just to compensate for the loss of balance. Again, once you remove the blindfold, it doesn't look too bad. But you still see it's, it's aic just by when it moves its hind legs, it seems to stumble a little bit.
Yeah. And as delayed movement of the or compensation of the legs, when it moves from or steps from one foot to the other, he had again, very white based hind legs. I push you to the side just to see what if it loses its balance.
But I mean, you just alone, the fact that it has such white based hind legs indicates there's some sort of dysfunction. Then this one starts circling again. You can also see it doesn't necessarily circle always into one direction.
So the circuit towards the other side. And so this one here is, is quite a toxic, maybe usually at that stage there will be called anyway. But I mean, you have, when I monitor them because sometimes if you're not quite sure you monitor them for a longer time and it's quite interesting that they don't seem to become recumbent so that they seem to be quite happy being, well, not happy.
But I mean, there, there seem to be a taxi or you can see clinical science basically for quite some time before, probably before then they will actually become recumbent. So not that we've seen that, but I mean, you can see that for, for months or for definitely for several weeks that they, that they are taxing and in coordinates and then we usually call them then, but I assume in natural diseases will be similar. So now BS C and, and she and go, it's, it's only important simply because it's a BS C is a sona take and, and because we found BC and naturally in a goat.
So the signs are similar to classical scrip based on experimental, on the experimental model. So the providers in my opinions is the predominant sign in sheep. That's not always the case in goats, but certainly in sheep, they're always poetic.
In my opinion, they have either a positive scratch test or they have full or hair loss or skin lesions. Here you see and basically here that full loss caused by rubbing and there's also an area here and you get frequently loss of body condition or weight loss. And that's fairly early.
And in more advanced cases, you then have an abnormal gait or an abnormal posture like crouching, for example. And here I just show you the code for change. So as you can see, this one doesn't seem to react to the scratch that that's not necessary common in God's testimonies response, which is absent in this case, this had a, this one was the last goat.
So it had a sheep as a companion. But you can see it, it seems to be overreactive. Here again, it's, it's startled.
And here what you probably can't hear is the hands clap. Every time you clap your hands, it startles and you see the shape that doesn't seem to be bothered. And now there's a person coming from the right and here again, it seems to startle.
I've seen it also in scrap. So that's not abc specific phenomenon in, in goats, but it certainly is something you wouldn't necessarily expect in sheep. So goats seem to be more like cattle in that respect, the dare show of reactivity.
So the for the clinical diagnosis, we look at the history. So it's a disease of adult shape. If you know the genotype, it would be a bonus.
Usually we don't know it. So it doesn't really help us a lot if you got previous Keito behavior abnormalities, If you got, if you deal with a recumbent animal that is useful to know. You can either do a full neurological examination if you got the time and the equipment or you do a short clinical examination protocol, which I which is published on in the journal of visualized experiments.
So if you, if you have time, you can, it's a free online, well, this is a free online article. It's a video clip and it tells you everything about classical and at square how you diagnose them with this, with that short clinical examination protocol, concentrating on posture behavior, then the menace response or their response to scratching, evaluating body condition and blindfolding and then evaluating movement. And there's an examination form on the right that I normally use.
And I've got a little picture there of, of a cold weather and normally circle the areas where you see weight loss, hair loss or skin lesions, looking at the clin diagnosis. So what you normally see abnormal behavior in both disease types absent and its response also in both disease types. More in late stage in Classico scraping a positive scratch test, usually in Classico scrapy, not in atys gray again, skin damage caused by pruritis more in Classico scrapy.
I it's, it's not certainly in the experimental disease. I've never s in atys gray. I've never seen pruritic animals.
I never seen alopecia circling when blindfold. I've only seen an atypical scrapey saying that I've also saw it once in a, in a goat. It's, I think it even has been reported that goats might circle a classical scrapy.
But it's it's rather unusual. But you have to keep that in mind. If you have a goat that is circling that it could also be classical scrapy, which you wouldn't expect again because it's, it's more associated with the unilateral disease in coronation.
You see in both disease types, tremor as well and loss of body condition. Classical scrap. It's yeah, probably seen much earlier in earlier disease stage than in a scrap.
And if you got the com combined occurrence of two or more of these signs, then I would consider scrapy. So that's quite suspicious of scrapy. So differential diagnosis, you can either have neurological diseases like that.
These are just a few examples of spinal cord disease, listeriosis. Usually in listeriosis, you wouldn't have facial paralysis. So that that is not something you would expect in a scrap.
We had also lister cases that didn't have facial paralysis. So that would be then more confusing and could, yeah, could be confused with scrapy. Could be a space occupying lesion that causes, for example, then c depending on when, where the space occupation lesion is.
And that could be more confused with aptos gray pregnancy toxemia. Well, these animals might be dull and they might be recumbent and then it's generally more difficult to make a diagnosis in recumbent and dull animals simply because they don't respond anymore. And especially in classical scrape your and yeah, in classical story, if you got the advanced cases, eventually they will be recumbent and don't respond to a lot of stimuli anymore.
So at that stage, you couldn't, you can't rule out at all. You got diseases, affecting the skin or affecting wool, like mange and liver disease, liver disease. You can sometimes pull, just pull out the wool and then lose, basically have hair loss or wool loss.
And you think it's, it's probably due to rubbing, but it might just be that it, it catches itself on, on basically a fence or something and loses the wool that way. So we've, we had cases suspected case of scrap that the only diagnosis was a liver disease and any chronic disease result in the ill thrift could be confused with scrapy if you got dental disease, paratuberculosis. I mean, you, you would normally think that the animal might have diarrhea but you wouldn't expect it creepy.
But we had cases where animals were, were quite thin and skinny and they came in as, as clinical suspects. And in one, I think we found a dental disease. So now here another differential diagnosis, just an example here.
So this one is pic the Cheviot sheep. And here you see that looks similar to the sheep I showed you earlier that had atrial scrapy and had that hair loss is almost identical. And here this animal is obviously itchy.
And it, it also shows that a nipple response are so they nipping its lips while it is scratching itself. Then you do a scratch test and here you can see it is positive. So this, this was the only clinical signs that there, there was no ataxia and you can see a difference.
So that was sarcoptic mange is the difference between classical gray where I told you it's normally a smooth, almost like shaved area. So the the skin is normally smooth and you might have skin lesion eventually due to rubbing operations versus sarcoptic mange. You've got the secretions from the mites that then cause some sort of crust and it looks very different.
Another differential diagnosis that's more for a square P. This one is quite dull and you'll see it's kids as a diagnosis. So this animal doesn't really do a lot anymore.
It's, it's very dull. It is also a toxic and depending on the lesion, you might then see signs of a unilateral disease. This one also has a slightly white based stones.
You see it falls, it falls towards the right. So the stress of a unilateral disease. Yeah, test the blink reflects that's normal.
M is normal on the left hand side and absent on the right hand side. So that, yeah, that was basically a system 10 year multi steps and it's now a differential diagnosis. This is a riddle for me.
This is actually it's also quite a long clip. This is an animal that we actually had in our facility. So this eight year old folk, you basically was standing on its own.
It has slightly impaired menace, certainly on one side. But it worked fairly normal. But again, away from the others, in this case, I thought it might, might be CCNS zero Coron necrosis.
I treated thymine. And 17 later, it, it, it improved. But then 17 days later, it was doing exactly the same again, was standing away from the others.
It and it actually became worse. So it's now starts circling. You see it's in coordinate.
Oh, it certainly, it looks as if it's probably a vestibular disease. This function with civil assist and dysfunction again. Here it's, it falls to one side because he stumbled.
So certainly not walking normally. So your testimonies and this one is absence. Now it's a bit difficult to s difficult to see him.
Ok. No menace that side. Then I check the popular, right?
The flex. So if we look at is the does the pupil constrict, it does. So it looks more like either cerebellar disease or more central and now it's blindfold and you can see it's definitely losing balance and this obviously was cult and, and we actually don't have any diagnosis.
I could have sworn it was ATU scrapy and that makes it more interesting. So, is it a case of a scrapy that we can't diagnose because that might also happen. So the next stage would actually be taking the brain and inoculate mice with it.
So it's an a Rrarr shape, which is susceptible to attu gray. So it's quite possible. But at the moment, yeah, we looked at the brain and we couldn't find anything.
So, it's certainly a brain disease, but we don't know what it is to control a education. We do TC surveillance, you monitor a peasant percentage of healthy animals and fall in stock. You identify risk factors sharing of colossal.
Certainly it could be a danger or lamming in crew pens. Use of the horizontal transmission risk, there's infection if possible. And you have to use sodium hypochlorite and use for, for an hour.
And that not, not even that is always effective and it's quite corrosive. So that's a big problem. The agent can persistently around for many, many years and removal of objects that cannot be disinfected if you got wooden doors or something.
Yeah, you better get rid of them because you can't really disinfect them. And as I told you earlier, so if you use a fence post and from a scrap, your flock and put that into with clean sheep, then they got infected. So it must be the woods.
That's where the brain persisted basically. So you and then selective breathing or you, you join the compulsory scrapy flux scheme and you breed for resistant genotypes or you have and you, you cull or slaughter those ones that are not resistant. And the goats currently that that's not an option, but it will be in the future.
I'm, I'm fairly certain that you can basically, that's an option that you can breath for assistance. You remove the susceptive genotypes and your TC monitor these flocks for. Yeah, until you don't find any cases for two years.
So summary, we've got two scrapy types that occur naturally in sheep and goats as classical and at scrapy, ay scrapy is likely to occur, occur worldwide has been found in New Zealand and Australia. Both types produce different disease, phenotypes. And scrap eradication has become more relevant.
Since the discovery of BC, we don't know a lot about at scrapy pathogenesis. You should consider scraping in the differential diagnosis of neurological diseases, especially if you have a disease that that goes on for quite some time and it doesn't respond to treatment and it's suggestive of a a disease diffuse brain disease if you got a suspect case reported to the relevant government authority and you can visit the TC reference lab website to find more about it. And that's the end of my talk, Tim, thank you so much.
That's certainly one very frustrating disease from a veterinary point of view. We have got a couple of questions coming through folks, just a reminder for those of you that joined us a little bit late. If you wanna just pop in the country that you are, watching or listening to us from, just for interest sake, we will run through those.
So just in the Q and A box for those of you that haven't already done it, if you can just type in the, the country that you are currently in. Tim, we do have a, a question here and it says is the weight loss found in atypical scrape p A primary sign or simply due to reduced food intake and activity levels. I wouldn't, I don't think it's reduced food intake.
In fact, we, we don't, I think that's only a late stage where animals are actually in appetite and don't eat anymore. We, we don't, we think it's more to do with, you basically, the loss of protein, probably muscle wastage, basically, maybe because simply they don't, probably, they don't walk as much anymore. That's quite true.
But they, they're less active. But, in generally classico scrap, I think it's more prominent than Atypia. I think in a way that they work, much better or compensate much better than, than classical scrap.
Sheep do. But usually I think it's associate more with, with muscle wastage rather than, than actually eating less. Ok.
So we've got a fabulous response from everybody who's popping in. Thank you very much for popping in the countries that you're in. And, Tim, you were very interested in this.
So by far and away, the majority of people are in the UK. But we also have, Northern Ireland. We have Scotland, we have Wales, we have Southern Wales.
We've got Greece, we've got Canada. We've got, lots of UK people again, Greece. Wales, California.
Welcome. Sunny California. Also, yeah, the American weather has been a bit strange like ours recently too.
United Kingdom, we've got Croatia, we've got New Zealand. Welcome from Down Under. We've got Ireland again.
We've got Lithuania, Northern Ireland. Jose, one of our regulars from Portugal. Welcome, Jose.
Is Scotland oh, here's a question from Sue in between. What sort of incidents is there in UK flocks and she's from Derbyshire. Well, it, it's, it's not very common.
I mean, I showed the, the picture or the, the table before that you, you hardly find any cases anymore. Certainly classical scrape here. It's, it's very rare nowadays and atypical crape is more frequent and incidents if you got an, a case of Atys grape, again, if it's usually just one case in a, in a flock in a in classical script, it always depends what your genotype distribution is.
We currently have one I know about one goat herd that has a case of scrap. I think the prevalence is around, I think it was, is around 2 to 3% of the goats that are, that are positive. It's it actually, it depends on the, on your genotype distribution for goats.
Obviously, people, most people haven't started breeding for resistance in sheep. It's more difficult. If you got Viqviq shape than in your flock, then you would have more problems.
In 2011. There was an outbreak that was the latest really big outbreak or large outbreak in the UK. And I think there, there were around 50 animals that in a flock of maybe several 100 animals.
So that, that was quite a large outbreak. And that was, that mi A Q va Q sheep that actually didn't use any genotyping program that weren't aware that this could be a problem. So that's, it could be quite large the outbreak.
But usually, you know, that most of people use resistant or half resistant genotypes because of the National scrapy plan where, where people try to breed out, the, the susceptible genotypes, you wouldn't have any, a la any larger outbreaks anymore that might change maybe again in when people then lose interest and don't, look for genotyping anymore, then it might change again. But cases are very rare now and it's so classical scrap, is it? Yeah, not, you find maybe one or two cases now in the UK.
Excellent Tim Emily also asks, with the National Scrapey plan, have there been any long standing implications for bloodlines or genetic diversity? No, there hasn't. I mean, there was initially, there was the big concern that you might breathe something in that you don't want, but there's no evidence for it and people just, we, we don't, well, actually we don't know what the brain protein gene does anyway.
So, so it's not quite clear what the functions does. In fact, there's a goat her in no way that actually has no pre and protein genes or the pre and protein null goats basically, and they seem to cope quite well with it. So I, I don't think there's any problem really having sheep that have a certain genotype.
I don't think there's any evidence that it causes a problem. Excellent. Th I'm scrolling through all these messages that are coming through from all the different countries around the world.
And the one part that I haven't mentioned to you yet is we've got a lot of comments coming through saying what a wonderful presentation and thank you for the opportunity to learn and various other forms of thanking you. So it's it's up to me to once again formally. Thank you for the presentation.
It was very, very interesting and for the time spent and we look forward to having you back on the webinar vet in the future. Thank you very much. Thanks folks.
That's it for tonight. And we look forward to seeing you on another webinar in the future. Remember that all our webinars are recorded and they will be available on the website in the next couple of days.
So from my side to Anna my controller in the background. Thank you for everything and Tim once again, thank you for your time. Good night everybody.
