Description

Encephalitozoon cuniculi is a mammalian protozoal parasite, which belongs to the phylum Microsporidia and infects a wide range of species worldwide including immunocompromised humans. Infection is widespread in pet rabbit in the UK, with a seroprevalence of 52% in clinically healthy pet rabbits. This webinar will review the pathogenesis and life cycle of this common infection. Clinical signs will be discussed, as associated with the three main disease manifestations – renal disease, ophthalmic disease and central nervous system disease. E.cuniculi infection can be difficult to diagnose and the issues surrounding definitive diagnosis in pet rabbits, including interpretation of serological results will be discussed. Supportive nursing care of affected pet rabbits, as well as more specific therapies, depending on the system or organ affected, will be outlined. Potential benzimidazole toxicity in rabbits will also be discussed. Physical supportive care and alternative therapies will also be touched on. This webinar will be helpful to all vets and nurses in general practice treating pet rabbits, both as refresher on E.cuniculi infection in this species, as well as providing up to date and relevant information.

Transcription

Welcome to this webinar entitled An Update on Econic Cline et Rabbits. Thank you for joining us today. My name's Emma Keeble.
I work at Edinburgh Vet School. I'm a clinician and a lecturer there. And I particularly, enjoy talking about eciculi.
It's. Of my topic really, having sort of over the years, been very intrigued by this disease. And we'll talk today about it and, and often unfortunately, lots of questions come up, because there's, there's a lot of things to discuss and particularly diagnostics, which we'll come on to later.
So I just wanted to let you know what we'll cover. There's quite a lot, as I mentioned, to go through in this hour. We're going to be looking at the parasite itself and how it works and what its life cycle is.
I want to also discuss the main clinical signs that we see in pet rabbits, and also, as I mentioned, how difficult it is to diagnose this infection and all the questions that sort of are, are, you know, come out for having actually got your results, you know, what do these actually mean? A lot of the time we are just providing supportive care for these animals. There is a treatment that I'll come on to discuss as well, but we have been a little bit concerned about possible toxicities.
And I think I'll also touch a little bit on, physiotherapy and perhaps other therapies that, we might employ to help our patient. So I think this will be a really useful webinar, for all veterinary staff. What are you going to learn?
Well, I wanted to try and condense this down into 5 sort of key areas, so that you can come back and think, yeah, what, what was that all about? So a basic sort of understanding of, of the parasite, I want you to be able to recognise the key clinical signs. That we tend to see with the canicular infection, so they're up there with your differential diagnosis.
And then really understand what the sort of pitfalls and positive signs of diagnostic testing are, so that you can discuss that with your staff and also with your, with your clients. We'll also want to know what the main treatment options are and very importantly, what advice are we going to give to owners about the long term care and management of their their rabbits with this disease and particularly if this is in a group situation, how does that impact on the companion animals? So what do we know about Eciculi?
Well, for a start, it's got a long name, hasn't it? Encephalitzouniculi. So I've, I've often abbreviated to EC, just to make it a bit easier for you.
It is a protosoll parasite, particularly of mammals, and it belongs to sy and microsporidia. There's a whole range of species worldwide that can be affected, and it does also include people, but primarily it's been reported immunocompromised humans. In the UK we know that over 50% of rabbits have this or have been exposed to this parasite.
And this work was done by us at the Edinburgh University quite a long time ago, so actually that, that figure could well be higher these days. What are these microsporidia? Well, they are a really difficult thing to classify, and there's been a lot of controversy and changes really over over the years.
They originally didn't think that they had mitochondria, but they've now found that they do have very small, highly reduced mitochondria. And when they've done genetic and phylogenetic analysis of gene sequences, there is thought to be a relationship with atypical fungi and microsporidia. And they do contain these sort of key elements that fungi have, such as, you know, fungal proteins like tubulins, trellos, and chitin, but we're not quite sure the exact position within the fungal tree where microsporidia lies.
So there's still a lot of questions really about this particular organism. What we do know is that they have to parasitize a cell to survive, and they do this by using this really cool organelle called the polar filament, which is basically injected into the cell, and then the infectious particle is released, and but they can't, the second way that it can actually come inside the cell is via the, the cell actually phagocytosing that particular spore. And in the, in the environment they are shared and can be quite resistant and remain as spores.
So it's a direct life cycle, but we do know that it's possible to get horizontal and vertical transmission of this parasite. As well as that, a lot of young rabbits can pick up the infection immediately postnatal. So within the first sort of 6 weeks of life, either from the mother, if they're infected or from contact with other infected animals, the main route.
Of infection is by oral ingestion of the spores, and typically this is from the urine as the most common source of infection, but we do know that it can be excreted in droppings, as well as, in aerosols, so it could potentially be inhaled. Infection usually happens after a couple of weeks post ingestion, and then about 1 month later, the spores are excreted in the urine, and really up to 2 months later, they continue to be excreted in the urine. And these spores can survive for about 6 weeks, typically about a month, but up to 6 weeks at sort of environmental temperatures about 22 °C.
Once we get to 3 months post infection, most of the spores have stopped being shed, but unfortunately, rabbits can intermittently shed these spores throughout their life, and we'll come on to talk about that a bit later. So we've got a little diagram here that hopefully you can see that just gives us an idea of how the life cycle of this parasite works. And once they are ingested into the intestine, then the spores actually invade macrophages, and it's these cells that pass via the blood.
To the target organs. So typically the target organs are those that have a high blood flow, because that then obviously delivers the macrophages to those organs. And then later on, a more sort of chronically within the disease process, we see infection of the nervous tissue.
And we typically talk about the kidney and the central nervous system being affected, but ecicular can also affect things like the heart muscle, the liver, and we'll talk about the eye issues as well later. So this polar tube infects the host cell, and then inside that cell we get development of the parasites and eventually into mature spores. Then the cell has to rupture to release those spores, and it's this cell rupture that is really the problem in our rabbit cases because it creates an inflammatory response.
Most immuno competent rabbits, rabbits that have a good, well functioning immune system, will develop a subclinical infection, and that's a balanced host-parasite relationship. So then we get these horrible granulomatous lesions developing, and typically there are 3 areas that they develop in the brain, the kidney, and the lens of the eye. And what happens then is that these spores erupt and the eruption of those spores causes this, inflammatory response.
So we tend to get cataracts and then lens rupture and a secondary uveitis if this infection is within the lens. But we have got fairly new evidence that euicly can actually infect the lens postnatally, but currently we're not sure exactly how this works and what the mechanism involved is. Once the spores are shed into the environment, they are relatively resistant to change of environment, but the good news is that most routine disinfectants will actually destroy them.
So that, that's really helpful for owners to know. What, how prevalent is this? Well, my feeling is, it's really prevalent, and we, we know initially it was reported in lab rabbits way back in the 1920s, but the, the study that we did at Edinburgh Vet School showed that it was over 52% of normal healthy rabbits had been exposed.
I think this is probably higher now. And the problem is we can have a carrier status. We can also have latent infections, and it really depends on the immune system of that individual where the clinical signs develop.
And I think what I am seeing several times, you know, quite commonly I guess, is that, individuals can be asymptomatic for many years, but then when there's a stress, underlying disease condition or some sort of immunosuppression. Econiculi can become an issue. So often there's concurrent disease in these individuals.
We do also know that in the UK some wild animals have this parasite, and there's been some sort of suggestion potentially pet rabbits could get infected from wild sources. However, I think this, . It's much more common in the pet rabbit population than it is in wild rabbits, and there's unpublished data that we do have it in UK wild rabbits, but I don't think this is likely to be a really major source of infection for our pet rabbits.
We don't fully understand the host parasite relationship, and I think that's, that's the difficulty. You can have two rabbits living together seemingly very similar, and they basically do not one develops clinical signs and the other one does not. They do not show the same process for the disease developing.
And I think this is because it's a bit of a balance between how quickly those spores can develop and rupture the cell and how well the individual's immune system copes with that. So I do wonder, is it more common in, in immunodeficient young rabbits, or is it more common in older rabbits? As their immune system perhaps is waning, and I, and I do think this is possibly the majority of cases I see are either in very young rabbits and we have acute sort of quite severe infections, or in older rabbits that then go on to show the, the neurological signs and perhaps the kidney failure signs.
It is incredibly commonly reported, as, as in general, and there are these three strains now, you know, I find this of interest for me, but, this isn't something that you necessarily need to definitely know, but I think it is interesting that the strain that infects rabbits has also been reported in humans as well. Lots of unclassified strains exist, and they can infect a really high range of, of different species. But interestingly in these species, the symptoms are very rare, very rare to see clinical disease.
We do need to bear in mind about the zoonotic potential, and this is something I get asked a lot about. It is primarily in humans who are immunocompromised. So the cases that have been Described in the literature, a lot of them around the sort of 1980s, early 90s were, were, associated with AIDS, and I think this is hopefully something to reassure owners that, you know, if they have a healthy immune system, if they good hygiene practise, if they wash their hands, wear gloves when emptying litter trays, the, the risk of infection is very, very low.
So what are we going to see in our pet rabbits? That's the key thing, isn't it? What clinical signs might be associated?
Well, I think probably all of us are aware of the neurological signs that can develop. In particular, we see head tilts and circling. Often this is very severe and associated with nystagmus as well, but we can see animals that are a bit attaxic with their gait or maybe a little bit weak on their limbs, particularly the hind limbs.
Kidney disease seems to be fairly common, and this is again a sort of end stage manifestation of the disease and this can present primarily, I feel with a weight loss, you might then get a secondary urine scalding. You can get incontinence as well. So the, the kidneys can become shrunken and small, but we can also get neurological deficits to the bladder which leads to the incontinence and the urinary scaling.
So there are sort of two ways that it can affect the urinary system. With ophthalmic disease, it tends to be in younger animals, and then initially owners will perhaps report that the eye looks cloudy, and we have these cataracts that then, when the lens ruptures leads to a faerclastic uveitis. In some very severe cases, I have had animals that are seizuring and and sadly die, so it can be a very severe disease with fatalities.
So I have some signs just here just to show you some of the cases I've seen. This rabbit has a very severe head tilt, but as you can see in the picture there, he's got a nice dropping in the background, has been eating greens. It's amazing what they will actually cope with.
Even head tilts as severe as this can learn to cope, and quite often we will see improvements in clinical signs, but usually over several weeks rather than days. In some cases we obviously don't, so it's not every rabbit with a severe head tilt as that that will which will cope. This is just showing you that sort of paris that we get.
It used to be called sort of floppy bunny syndromes. We didn't really know what caused it, but the hind limbs in particular can become weak and splayed. This individual had all four limbs that were weak and splayed and, and was finding it very difficult to stand.
Urine scaling and staining, this can be secondary to urinary incontinence or potentially renal issues, high protein in the urine, and then a secondary bacterial infection. So if you've got a rabbit with this sort of clinical manifestation, I would definitely be testing it for econiculi. And here we have a uveitis.
We've got a little bit of corneal opacity as well. You can see the fluorescence stain there too. This could also be a bacterial, you know, such such as pasturella, but do be thinking in young rabbit, is there an underlying echiiculi as well.
So the neurological symptoms I mentioned tend to be head tilt, and one of the things we need to be certain about with this is, is it a middle ear infection or is it actually caniculi? And what's interesting, often you can get concurrent, so you can get e caniculi positive animals that also have a bacterial middle ear infection. We can try and ascertain whether it's central or peripheral.
If it's central, we might have vertical nystagmus. If it's peripheral, we might have a horizontal nystagmus. But it's something that can be quite difficult to ascertain on clinical exam.
And as I said, you know, we can have a, a range in severity of clinical signs affecting the CNS, and some cameras are very quickly, but a lot of them will take a long time to resolve, may not resolve eventually and some will have residual head tilts. With kidney disease, sometimes kidney lesions can be an incidental finding, but if they're very severe, these rabbits tend to present with an increased thirst, increased urination, very obvious weight loss over time, and a reduced appetite or perhaps a picky appetite. With the ophthalmic symptoms, I mentioned about the cataract formation, and then this faoclastic uveitis.
Interestingly, I do think the, the ocular lesions tend to be seen in young rabbits, and perhaps the sort of acute seizureing fitting can also be more young rabbits. With the central nervous system disease and the renal disease, they often seem to be in older animals. It's not an absolute, but it's just something I've observed with the cases that we see.
And most rabbits, the majority of rabbits with the icar, have no symptoms whatsoever, so that's really important to bear in mind. And what's very difficult for us as vets is that that often we have really severe clinical signs, but they don't always link to how severe the lesions are, once we unfortunately look at them at postmortem. So this is really difficult, you know, you can have a rabbit with multiple granulomas throughout the brain, but perhaps not have very severe clinical signs.
So we really don't understand why this happens. It doesn't really make sense. What other differentials might there be?
Well, I want to just have a look at initially the nervous system signs because I mentioned with head tilt and we'd need to be thinking about particularly a middle ear infection. But obviously, any other infection could potentially cause, a head tilt. We could also have neoplasia, perhaps toxicological conditions.
Maybe it's a congenital issue. Other things that perhaps might cause, problems with the hind limbs or forelimbs could be spinal trauma. The middle picture you can see there, this animal had actually fractured its spine and was incontinent secondary to that.
We could have infection within the brain itself, an abscess, either bacterial or fungal. We might have this condition. Splay leg, which is a developmental condition in young rabbits where they, they don't have the ability to draw the legs inwards, and that can be due to sort of deformities of the legs.
And we could potentially have other sort of toxicities or other infections. But then the main take home differential for the head tilt, is a bacterial middle ear infection. With the urinary issues, just have a little sort of chart here to show you.
Interestingly, the problem of urine staining can either be a urinary problem directly associated with the bladder or the urinary tract, but it can also be in rabbits a problem with posturing to void the urine correctly. So usually they lift themselves up on their back legs, and urinate away from the legs so that they don't get urine dribbling down the back end. So in rabbits that have a problem doing that, perhaps they have a, a mild paralysis due to cicli, or they have osteoarthritis or they have spondylosis of the spine, this can happen and it can present as urine staining.
So we've got a bit of a list there and eonicula, as you can see, appears on both in the urinary problems and the problems being able to posture correctly. So, it has to be there in your differentials for urine staining. So how are we going to diagnose this?
Well, this is the, this always seems to sort of come up with more, more questions than answers when I start talking about diagnostics. And it is problematic and hopefully I'll be able to help sort of guide you through how we go back down. Diagnosing this in our pet rabbits.
The problem is we often have to sort of make a presumptive diagnosis based on our clinical history, our signs, excluding all those other differentials, having positive antibody and our response obviously to therapy. The reason it's difficult to diagnose in the live rabbit is that if we get a high antibody tighter, it just indicates the rabbit's been exposed. It isn't actually telling us whether this is an acute active infection.
What we really need, I guess, is biopsies of the organs affected to see that, the sporozoide within those cells, or that inflammatory reaction associated with it. But the problem is that we can have subclinical disease, and yet still find these inflammatory lesions on postmortem. And on top of that, it can be quite difficult on your postmortem specimens to actually identify the spores on histology.
You have to do immunohistochemistry, and we're not all doing that in practise. So I thought I'd have a look at just your normal sort of blood work. So if you take, you know, a, a routine blood panel in your, your pet rabbits, what might be a little bit changed with the knee caniculi case, again, this isn't something I would routinely be using for my diagnosis, but I thought it would be of interest to you.
So these are the sort of changes that people have found in euniculi infected animals with a sort of acute inflammatory response. You can also see increases in C-reactive proteins as well, but that's obviously non-specific for for any sort of inflammatory process. We can also look at spores, and, and these are excreted in the urine usually from day 35 to day 90, but we do need special stains for this, and unfortunately it, it can be quite intermittent, the shedding of those spores in the urine.
So they're not always present. So if you do get a negative on your urine sediment, it doesn't necessarily rule out infection. We can also look at PCR testing on urine as well.
What about performing urinalysis? Well, if you've got a urine scalding animal, I think that's obviously really important. So I would always in those cases, perform full urinalysis including sediment and culture as well, hopefully, if you can, get a cystos and teased or, non-contaminated sample.
What is interesting is there was a study looking at Eicli positive healthy animals, and, negative animals and comparing their UPC urine urine protein creatinine ratio. But there wasn't a difference between Eli positive and negative animals, so it wasn't considered a useful diagnostic tool. However, I would say in these rabbits that are losing weight that are quite end stage, with their sort of neurological signs and their kidney disease associated with the caniculi, these animals often do have, raised UPCs, so that is something I still perform in those cases.
We could potentially also look at our CSF, our cerebrospinal fluid, but unfortunately in studies that have looked at this in rabbits with echiiculi, they're not really specific changes to echiiculi. They're just generalised changes that you see with inflammatory or infectious diseases. So this is quite an invasive technique, that would have to be on an an an anaesthetized animal, and it's not one that we routinely use.
It hasn't been shown to be that helpful. I mentioned PCR, polymerase chain reactions. We can do this, and it is commercially available on urine, on a CSF sample, and on lens material.
And actually, the ocular material that we remove from econic ly cases, we have found a very high positivity to ei on PCR of that lens material. So that it is quite useful in the ocular cases. But again, finding the organism is not necessarily correlated with disease.
I mentioned it's good with the haoclastic euveitis animals, but it can be negative even in clinically ill animals. I mentioned about the urine testing not being too specific. It's the same for the cerebrospinal fluid.
They're not very reliable on PCR testing. But we do know that that the PCR testing for, for the eye, and if you were to take postmortem samples of the brain and kidney, can be very useful. And I popped a little reference up there for you if you're interested in that, you can read up about it a bit further.
We've also performed kidney biopsy in some cases. This is the mainstay of diagnosis using biopsy and histology in human medicine. The only thing I have found is that often these animals are in kidney failure, so anaesthetizing them and then taking a piece of their kidney, they can find this quite, an invasive procedure, and we've had a couple of animals that really haven't done well post this, but obviously it helps in your diagnosis, it helps you evaluate your renal function, but also, obviously you want to make sure that that animal is well enough to have an anaesthetic and this, this procedure.
In theory it should give us a definite diagnosis in early cases, and they've also discussed whether the liver biopsy might be helpful as well. But again, this isn't something that we are routinely using and it's something I just think you should be aware of, and, and obviously know the the theations as well. So our mainstay of diagnosis for reiculi is serological diagnosis, and we do know that typically in a third of cases, echiiculi excretion mimics the trend in the IGG levels on serology, but this isn't the case for every single rabbit.
If you have an early acute infection, then you're likely to have IGM and IGG teta elevated at the same time. But there is a wide variation in in rabbits to the IgG response. We do get about 3% of rabbits continuing to produce a very high IgG almost throughout their life.
We have 3 that produce a sort of medium spike and eventually go down, and we have a third that do the typical rapid spike and then reducing after about 9 weeks. So we could have elevated IgM and normal IgG levels. So this could be an early on in infection within the first sort of 35 days.
If they're both elevated, then obviously that could be an acute infection as well. If IgG levels are elevated and IGM are normal, it's less clear what's going on, so. Mention we've got these different groups of rabbits that respond in different ways, and IgG levels can remain elevated for years, so you have to let owners know this.
It doesn't mean if they've got a high IgG teeta that this is an actual active infection. So it's so variable, and I think it's really due to the host parasite, relationship, and that's individual to each animal. So many rabbits are seropos to Ecicli, particularly IgG levels, even without clinical signs.
So a single test is really difficult to say what, what's, what's going on here. Interestingly, the highest seropositive animals for both IgG and IGM are found with animals with neurological signs. So that's something that's quite helpful.
And . In actual acute infections, the, the IGMT tend to be really, really high, almost 3 times higher than, than you would normally expect, and 2 times higher in IGG. So if you get, if you're getting really high values in your titis, then it's very likely to be an active infection.
I think the most helpful use for serology is in determining a true negative rabbits. So if you've got clinical signs, particularly the nervous system signs associated with a chronic disease process, but it's negative IgG and IGM, it's very, it's most likely that it's not Echiiculi. What other things can we do to help?
So we've got all those panels of, of, serological testing and other, other, adjunctive testing. We do need to perform some diagnostic imaging because I mentioned with the head tilt, that actually this could be secondary to a middle ear infection. I've got a wee rabbit here showing you on the video how severe these head tilts can be.
So this is really a rule out. So, we will. To perform a CT scan in all cases with head tilts.
You might also have access to MR imaging as well. If they're not available, then at least performing radiography and ultrasonography can be useful as well. With the CT imaging, it's mainly to rule out the middle ear disease as otitis media is the main differential diagnosis.
But at the same time, we can use the CT and we tend to do a whole body CT of the rabbit. We can use the CT to look at the skull as well as the vertebral column, the long bones, and the joints to rule out other causes of ataxia like osteoarthritis or spondylosis. And interesting, I put anaesthesia versus conscious.
This is our CT scan. I've got a wee video to show you. This is the rabbit being whole body scanned, and now it's out again.
So that has taken what, 3 seconds to do. So we perform all ours conscious. We have oxygen pipes in, we perform it in a little, unit called a mouse trap, which is a little Perspex box that the animal can sit in.
And we use rolled up towels just to make it comfortable, and also to perhaps restrict it turning round within that little box. Intravenous contrast agent may also be really useful for highlighting areas of inflammation or infection, or high blood supply such as abscesses or tumours. So these are the sort of CT images that we'll see, just really wanting to show you, on, on the screen there on the left, you've got normal tympanic bullies.
So these are the air filled black structures at the very base of the skull. We've taken this as a transverse section at the level of the bully. And then if you look at the other transverse sections here you can see various stages of middle ear disease, so material within that dark air filled bulla filling up and also bony destruction of the tympanic bulla wall.
So these are middle ear cases we can also do . Instead of a cross sectional view, we can do a transverse view, and you can see there on the top right, we've got a lesion in the spine, and this animal had a luxation of the, the spine that was pressing on the spinal cord. So CT can be extremely helpful to rule out other causes.
The same for MRI, this is again something that can be useful, more used for soft tissue problems rather than perhaps bony problems. But the only downside with this is we definitely do need a general anaesthetic and. Animals can be an isla for quite some time in order to get the images that we need.
So this might be a concern in an individual, particularly if it's got neurological signs, or if it's actually got, you know, renal disease and, and therefore the kidneys are not working as well as they should be. So we might see lesions within the cebrum that could be associated with the caniculi, but what's really difficult is that often these lesions don't correlate to the severity or lack of severity of clinical signs. Other techniques that I sort of touched on earlier in, in that slide were radiography and ultrasonography, if you don't have CT or MRI access, they can be very helpful to, as a rule out for other.
Disease processes. So with the radio radiographic imaging, you can look at the kidneys. You can see what size they are.
You can assess the bladder for any increased density that might be crystals within the bladder or bladder stones, and you can see in the top picture there of the radiograph, you can see a little tiny bladder stone there. With ultrasonography again of the urogenesal tract, we can identify issues with the kidneys. They might appear more shrunken and pitted with the caniculi cases, and we can also measure things like the ureter, which you can see being measured there as well as bladder wall thickness.
So all these other things that could be going on can be ruled out with our imaging techniques. So just to sort of try and conclude for you, it can be a real challenge to diagnose this condition, in the live animal. Lots of factors need to be taken into account, and then at the end of all our history taking, clinical exam, diagnostic testing, we pool all that information together and decide whether we need to treat and obviously if we've got a high suspicion and there's a response to treatment, then we are fairly happy that that our diagnosis is correct.
This was just to show you again a rabbit with a right-sided head tilt, and we've gotten a stagmus occurring there. You see, it's quite severe in this individual. And this is, looks like a vertical nystagmus, and therefore, we're worried more about central lesions in this individual.
So how are we going to treat this disease? We, we have really suspicious that this is a problem. We're basically going to try and reduce that inflammatory response and prevent those spores from forming.
And we're, we're in a bit of a catch-up situation by the time we're actually seeing clinical signs, so we need to manage owners' expectations as to how much this individual is going to improve. So the sort of treatments that we're going to employ, often we are using antibiotics systemically, particularly as we're worried about that main secondary differential of otitis media. Benzimidazos are the mainstay of treatment for echiiculi in pet rabbits, and we also might, well, we typically want to include an anti-inflammatory.
If we have an antibiotic, our ideal is to base this antibiotic choice on our culture and sensitivity results, and this is best practise. It might not always be possible, or it might be that you, start some antibiotics pending culture results. So the types of antibiotics that we often use in these head tilt cases, I've put n refluxin and trimethrone sulphur there with some dose rates for you.
We might also start the benzomidazal therapy. I'll talk about this a lot more in detail later. So for example, in the UK we tend to use fenbendazole, and the dose we we typically use is one by mouth and it's 20 mg per gig once a day.
And this is usually for 28 days. We also tend to put these animals onto meloxicam, as an anti-inflammatory. And again, I put a dose rate up there for you.
These are variable and different sort of sources will tell you different dose rates. I tend to use the 0.5 mg per kg per twice a day dose.
But big, big, but, don't forget that some of these animals will have kidney issues, and we should not be giving them meloxicam if we're worried about that. So we have to be happy that the animal is well hydrated, and the renal function is normal before you dispense this drug. So I would hold off that until you have your blood results back, or your, and, and or your urinalysis.
So as I mentioned earlier, much of our treatment is going to be supportive, and these animals can require a lot of intensive nursing. The other thing is they often find it quite difficult to eat, so they may need to be hand fed, very important to keep up the nutrition for this individual, and we also want to make sure the animal's well hydrated so they can find it difficult to drink. So sometimes we'll be syringe feeding food, sometimes a little bit of water, sometimes hand feeding these individuals.
The other thing that I think that really helps is cage confinement. So typically we would pop these into a cage as small as perhaps a cat carrier cage. It's well padded.
We roll up tiles around the side of it, so the individual can't really turn or move too much, and often they feel very secure in this environment. Do be aware that with a head tilt, they often get very, very dry eyes, and so part of your, your treatment and, and, supportive care will be ocular lubricants because they can develop corneal ulceration quite quickly. So obviously check these regularly, check the eyes regularly for ulcers.
And we have used certainly collagen shields, in rabbits, so this is something that could be quite useful. We might also want to perform some physiotherapy with the head tilt cases. I'll come on to discuss this a little bit further later.
So what sort of nutritional support? Well, I mentioned the hand feeding some rabbits with even really severe head tilts will still eat, if they're hand fed. So try that in the first instance.
But we might need to be thinking about syringe feeding, if they're not eating at all, then perhaps even more quickly than every 6 to 8 hours, maybe every sort of 4 hours, 10 to 15 mL per kilo by mouth. And just be careful because we don't want to get an aspiration pneumonia. If they're not eating, then obviously they could develop a secondary GI stasis.
So sometimes we'll give them prokinetics, like such as ranitidine or metoclopramide, and we're not sure whether anti-emetical labyrinthitiss medications could help, but I often do prescribe these in particular procloferazine is one that I quite like, and I, I've popped a doserate up there, but it's quite variable, the meclizine dose rate, as you can see. Another thing that we've been using quite a bit is mropotent. So this is particularly good for, for, pain, and this is given as a 1 mg per kg dose subcut, every 24 hours.
If the individuals are rolling lots, then we might consider either midazolam or diazepam to sort of reduce the rolling, but it's not something I would sort of routinely use. That would only be in very severe cases. So let's talk a little bit about the benzimidazo treatments, the sort of pros and cons and doses and so forth.
Typically in the UK we tend to use benbendazole, but also oxabendazole, and, in the US I do know that albendazole. Has been typically more popular. So both fenbendazole and albendazole are metabolised to oxybendazole.
So it's, it's really up to you and where you are, but we'll come on to discuss, possible worries about these drugs a bit later. We do know that the benziddazos inhibit spore formation. They've been shown to do this, but most of the studies have just been in vitro, not in vivo.
So it's difficult to know in rabbits with clinical signs. There is one study that did show improvement in the majority of cases with neurological signs, but not every case. So, with treatment with benzmidazil.
So this is something we we should definitely consider. So what we're doing is preventing the organism from replicating further. We're not gonna definitely eliminate it, and we're not going to treat the inflammatory changes with this drug.
We're just going to stop the situation getting worse. And I think that's quite important to explain to owners. So fen fenbennzole is what I would classically use and the dose rate's been given there.
There is this study I mentioned that it does reduce clinical signs. It has also been shown, for the duration it's given to prevent infection. And there is a study that showed also that the animals given Fen benzos seem to survive, post day 10 better than animals that didn't.
So I definitely think it's worth considering. The downsides of the benimiddazals is that adverse reactions have been reported, and these are pretty can be pretty severe. They're rare, but when they happen, they can be fatal, and primarily this is an acute bone marrow failure that happens usually about the 30 day mark, which is kind of the length of time we're usually giving the medication for, but it is possible also earlier.
So what we do in our cicli cases usually you're taking bloods anyhow to see what's going on. So we have a, a pre-treatment blood sample, and then we'd either repeat it weekly, if that, that, if we were worried that the white cell count or, or red cell count was low, we'd probably repeat it weekly. If it wasn't too bad, we might consider every 34 weeks, but certainly we need to be repeating that to check that we don't have any bone marrow issues.
. So some vets, well, some vets recommend benz minasals with, with caution. When this has happened with the bone marrow fail, it can be very acute and therefore, it can be very difficult to do anything about it. So I just thought I'd pop a little bit of information about what you do do if you get this side effect, you would need to think about emergency blood.
Transfusions or these other medications. Unfortunately it's only been successful in one rabbit. And if you're interested in these reactions and what happened and a bit more detail there, and I've given you the reference there, that's the one to go and have a look at.
There were 13 cases in this particular report. What was interesting in that report is the doses, there were only 2 animals that were given febendazole. One, the dose rate was 10 times what we would normally give, so really very high.
The other, the clinical signs didn't develop until 8 months later. So I would question whether that was actually related to the fenbendazole treatment. So I do use enbendazol fairly regularly in the UK in.
Rabbits, and touch wood, I have not so far seen any of these, these problems. It doesn't mean it won't occur. You need to be aware of it, but I do feel fairly happy, particularly with taking the blood results that we do regularly, that these animals are going to be OK.
And if we don't give it, they're going to worsen. So, you know, it's that that balance. I want to put a wee note about corticosteroids because I've mentioned about anti-inflammatories and often people think about giving corticosteroids.
I put there that they're controversial. I mean, people argue it either way, but my bottom line feeling is that we should definitely not be using corticosteroids in these cases. And I've given the reasons why they're in this slide, my worry is.
Twofold. One is that we are going to suppress the immune system and could worsen the clinical signs. We could then get secondary bacterial infections happening, and then the second problem is that dexamethasone can reduce the efficacy of the medications that we're giving, so it could actually make things worse.
So I really don't think that they are indicated in these cases. So what else can we do for these pet rabbits that are really struggling? I mentioned housing in the the open top carrier, padded sides.
I've got a picture here just to show you that small space. I don't usually leave the water bottles in because the individual could end up putting its face in and potentially inhaling or drowning. So we offer water regularly throughout the day, or you could attach a little water bottle, but a lot of these individuals can't actually manage to drink from that sipper.
We often medicate them inside the carrier, so we're not having to lift them out, otherwise they start spinning and twisting, and you could have a risk of spinal fracture. We do put that carrier in a pen with the companion animals, so there's contact, with friends, and that can really help. Once the neurological signs are improving, we could start some physiotherapy, some gentle neck massage.
I know that quite a few people with these head tilt rabbits are using acupuncture fairly successfully, and I could, you could also consider cold laser therapy as well, for the sort of neck muscles, cause I think they really go into spasm when they have these head tilts. We also want to think about physical therapy, turning the rabbit gently, turning the head opposite to the tilt, encouraging it to walk, perhaps rubbing the ear on the opposite side of the head tilt. So just some little things that maybe you could help or get the owner to do, or perhaps your, your supportive staff could do to help make that individual feel a bit better.
So I wanted to just talk about the prognosis. I can see here another inquisitive little rabbit here on the right in the picture, with a severe head tilt, but looking quite perky. So it is possibly even in severe cases with the horrendous rolling to rehabilitate these animals.
But I think you need to set a realistic expectation. With your staff and owner. So maybe have very clear cutoffs when you're gonna say enough is enough, because there are some cases that do not improve.
But we need to be letting owners know right from the start that this is going to be an intensive nursing period. It's gonna require patients, a lot of supportive care, and. You know, obviously depending on costs and things, often that supported care has to be given by owner at home, so these animals go home and, and, and they continue to nurse them over a period of weeks to months.
So case by case things will be different. Some will respond, some won't. I do think though you, you can put a sort of cut off period and say, right, you know, it's been 4 to 6 weeks, the animal hasn't improved at all.
This, you know, we need to really reconsider the welfare. We do know that urine incontinence can resolve. I think certainly for mild cases, the prognosis is very good.
Severe cases, they often are left with a residual head tilt and may have sort of chronic balance issues. So we need to be considering that individual's welfare at all stages. I just put a little slide here about educating our clients because I think that's really important right at where go.
They need to understand that this is serious. There's going to be a lot of nursing required. We need to consider what's best for the animal.
There's a risk to any pets that are in contact, particularly obviously. Companion animals, once they recover, they can become a carrier, and re-excrete the parasite. So it's really important to sort of talk about all these different issues, and obviously consider whether euthanasia sadly might might be the kindest option.
So I just wanted to talk a bit about treating both the kidney and renal disease because I covered the central nervous system disease. There's just one slide on chronic renal disease. It can be a difficult thing to treat, but we do have many cases that we've managed to maintain, for quite a long period of time with these sorts of treatments, and they do unfortunately require regular repeat checkups and blood sampling perhaps once a month, depending how the animal's doing.
Initially, obviously, when the animal presents, they may well be very dehydrated. We need to admit them, start intravenous fluid therapy, and potentially if we, we're thinking you caniculi, start treatment for that as well. We do want to avoid nonsteroidals in these individuals, and I think the treatment is very similar really to the head tilt cases.
We, we need to provide nutritional support. We need to think about secondary ileus. But on top of that, if you've got kidney issues, I usually would want to take some blood pressure readings and check that they're not hypertensive if They are, then we might want to start some ACE inhibitors.
We need to be looking at bloods and mention that anyhow for uro creatine, but also looking at PCV, and, and determining whether these animals are anaemic. And then obviously, maybe we're going to, use some thropein in those cases, it can be helpful. I also thought it was really interesting was reading about omega 3 fatty acid supplements like flaxseed or flaxseed oil.
Potentially these could be helpful in reducing injury to the kidneys and delaying kidney disease. So something perhaps to think about. And we also want to avoid any nephrotoxic.
Medications I'd already mentioned meloxicam really shouldn't be used in in these individuals. So it's a supportive care that we're doing. I also adjunctive as well as blood sampling, I would want to be doing regular urine analysis as well, and in particular looking at the urine protein creatinine ratios.
With ocular cases, these are often in very young individuals. We will start oralambenzo, and these cases we might want to use topical prednisone. Now I know I said don't use corticosteroids.
These would be very, very low doses. There is the potential systemic absorption from the eye, but they tend to act fairly. Locally on the eye and systemic absorption is fairly negligible, and this might be just in the interim before you're going to do whatever treatment.
If it's very severe, painful, uveitis, you might want to consider actually removing the eye, but we have had some really good success with lens removal. Via faulsification and the picture at the top here is actually where we're doing this process. We've placed a couple of little sutures back in the cornea on closing up that procedure.
So, these tend to do quite well postoperatively. If you're really interested in ophthalmology, want to know a little bit more about how to treat ocular. Issues and how they present with echiiculi.
We actually published a a review article fairly recently, so I'll pop that up at the bottom of the page, just if you're interested, you can have a look at that yourself, a bit later and that hopefully we will answer most of your questions about ocular echiiculi. So just to sort of finish up with our presentation, how are we going to prevent this and what are we going to do about these, these companion animals? And I mentioned about a single positive blood test, usually it's IGG positivity in a healthy rabbit.
Treatment is not necessary. These individuals may have been exposed a long time ago. There is the potential to produce a disease-free breeding colony, but this is only really practical in the lab animal situation and it's, it's time consuming and costly.
So our mainstay of control and prevention is going to be good hygiene, disinfection of food bowls and litter trays, perhaps raising the food and water bowls so that it's less likely individuals will urinate into them, using water bottles as well as your water bowls, . Hopefully most people don't still continue to house animals in tears, but you know, one above the other where urine can pass between individuals is not a good idea. And I did mention that very, very possibility, low possibility of contact with wild animals, rabbits particularly, just make sure probably that there's no contact with with wild individuals.
We're going to be disinfecting to try and kill the spores, and the good news is even just a sort of quite a a low concentration of, of bleach, 0.1% just for 10 minutes will kill the spores. So, this is good information to give to owners in terms of their, disinfection routine.
What about prophylactic treatments? And this is a question that I get asked lots and lots of times. Do we treat others if one animal is diagnosed with an acute active infection?
I think if you have actually got an animal with clinical signs that you are treating that has high IgG, IGM levels, and is responding to treatment, then I would treat in contact because that individual is likely to be putting out a lot of spores. Some people will give new rabbits when they're mixing with an established group, a 28 day course ofembenzole. There's pros and cons.
So this, it will treat any active infection. It will prevent that rabbit from picking it up from the group, but as soon as you stop that 28 day course, the individual is still, potentially like could pick up the infection is still exposed, because we have this latency, we have carrier status as well. So some people will only treat when there's a stress response or underlying disease, but you know, it, I, I think, I think the mainstay is probably when you're, you're adding a new individual to, to a group, or if you've got an active infection and you want to cover the other rabbits in the group.
Do you remember though that you can get side effects, and that's something important to talk to about with the owner and obviously get signed off label consent, depending on what product you're using. There is a pace that's actually licenced for use in, in pet rabbits in the UK. So what are our conclusions just to finish up this webinar, well, the bottom line is diagnosis can be difficult, and we've gone through the reasons why that that occurs.
We also know that clinical signs can depend on the individual, on their age, on how severe an infection there is, and what their immune status is. We're often presuming that infection and we're basing that on a whole array of findings, to come to that conclusion. And we also know that treatment can vary, and it might depend on what organs are affected.
It might depend on how well that individual can combat the parasite and the host parasite relationship. An important thing to let owners know is that even if we treat this animal, it gets better, relapses, recurrences are common. So this individual may relapse and show clinical signs at a later date, and that can be weeks to years later, but it also may become a carrier, and have subclinical disease and be producing the spores.
We also know that this infection is endemic now in the pet rabbit population in the UK. So, thank you so much for listening to this webinar. I really hope it's been helpful for you and that you can go out into practise and use some of the information that you've learned to help treat your, your bunny cases.
Thank you very much for listening.

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