About a dozen years ago, in November of 1999, a very wonderful little bunny named “Snickers” got a very horrible disease called “Wry Neck” or sometimes “Head Tilt”. It is caused by a protozoan named E. Cuniculi. This is an obligatory intracellular parasite of mammals.
The protozoan can be asymptomatic in some animals, have no infective ability in others, or, in some rabbits in particular, be lethal. It can infect the brain of rabbits causing them to lose orientation to up and down, lose control of their limbs, have nystagmus, that involuntary twitching of the eye back and forth at you see in folks who are sea sick, and eventually even death. In those that survive the attack, spores are shed in the urine from infected kidneys and it is those spores that infect other bunnies.
Most likely, Snickers had picked up the spores at the County Fair where she was “on display” with hundreds of other bunnies. We bought her there, and just about the incubation period later, she developed nystagmus, stopped eating, had head tilt, and generally was One Sick Bunny. As I’d bought her for my (then) 12 year old daughter, needless to say, this was a bit traumatic. I made an appointment with the Vet then “hit the computer” and about 2 hours later we were seen by the vet, me with about 1/4 inch stack of printouts in hand and a newly forming understanding of this class of disease.
It is often lethal to Rabbits. So as soon as Snickers started showing symptoms, we ran off to the Vet. We were lucky enough to get a Great Vet named Dr. Sato. She was the only Vet at their office who treated rabbits, and was not strongly familiar (but was somewhat familiar) with E. Cuniculi. That I walked in with a sheaf of web pages printed out (and not just folklore pages, but including scientific papers…) probably did not hurt.
I’d already identified the disease, and the likely cure of Albendazole. But Dr. Sato did a very complete exam. Came to her own conclusion. Checked her own sources, then prescribed the meds she thought were appropriate. Baytril as a general antibiotic (in case it was a bacterial infection of the ear – pasturella), an injection of Albendazole and then Valbazen oral suspension for 10 days (an oral version of Albendazol) to assure long enough treatment to kill off the bugs.
Snickers had also picked up some fur mites, so was given Ivermectin to treat them as well. An injection under the skin, and then a repeat 2 weeks later. Ivermectin kills all sorts of mites and some other odd things too. It can kill Dutch Pattern bunnies. The Dutch rabbit has a panda like look to them. Black eye patches and a white shoulder band.
Ivermectin works in a rather odd way. Mammals use Acetylcholine as a neurotransmitter in most of the body. We also use something called GABA but mostly in the brain. (Though it does a lot of other interesting things in mammals and is well worth the time spent learning about it). In arthropods, like mites, it is a Very Important Thing, and if you muck it up, they die. So, put something that screws up GABA function into a mammal and the bugs die, but IFF it gets into the brain, you die too… Lucky for us (and most Rabbits) Ivermectin is stopped by the blood brain barrier. Something that the bugs don’t have, and that stops Ivermectin transport. EXCEPT in a few “sensitive” animals like some dogs, and Dutch breed Rabbits…. SO Ivermectin is typically used with caution, or not at all, in those populations.
But Snickers was not a Dutch, she was a Netherlands Dwarf, so “no problem”.
Snickers recovered fully, and lived a normal bunny life, loved and loving. Eventually she died at a normal “old age” time. THE key bit here? She had been cured of E. Cuniculi.
Now I’ve been through dozens (maybe hundreds?) of hours of research on this. There are countless cases and testimonials of treatment of E. Cuniculi with a LOT of different things, including Albendazole, that “help for a while” then the treatment stops being effective and the animal dies. It is widely talked about as a “sometimes cure” but often just a “delay of the inevitable”. I’d just figured we “got lucky”.
Now, a dozen years later, another bunny got E. Cuniculi. Partly I credited the recovery to very early treatment. In later stages, damage has been done, cells are dead, spores are formed on the brain and throughout the body, and often the drugs that kill spores are not the same as the drugs that kill adult protozoans. So I was “quick to act” as with Snickers and wasted no time getting treatment or getting to the vet.
It was 6 pm last Friday, so the regular vet was closed, but I went to the Emergency Animal Clinic that all the Vets pointed to as the “Don’t bother me after 9 to 5, I’ve got dinner plans” place to go.
To say it was a disappointment is not even close. $163 later, we’ve had an inspection, a prescription for Baytril, a subcutaneous saline (that is nice to have as bunnies will die fast from dehydration) and some Meclozine for the potential nausea from the nystagmus. BUT no Albendazole, as they don’t carry it.
Now Albendazol is NOT some odd bizarre drug. It is readily available as sheep wormer at about $40 / pint. The family of Benzimidazole drugs is, IMHO, the most common type of “wormer” used in cattle, sheep, goats, pigs, horses, you name it.
So WHY does THE “emergency clinic” to which the local Vets DUMP their responsibility not have one of the more common wormers, antihelminthics, and the drug that kicks protozoans butts? Is $40 for a few thousand doses too much to spend?
As near as I can tell, they exist to charge twice as much and deal with cats and dogs… so the regular vet can pretend they are not in the medical field and have dinner out without a beeper.
I’d Be Pissed, But…
I’d started the bunny on Valbazen oral suspension at 6:20 pm as soon as I’d done an inspection and diagnosis. I had a small quantity left from 12 years before. Stored carefully all these years in ideal conditions. And not wanting any more neurological damage, started treatment immediately, then went to the Vet for a “confirm and more meds”. Instead I got “Well, donno, we don’t do rabbits and don’t have the meds… here’s your Baytril and go see your Vet tomorrow”…. But maybe the saline was worth the $163…
OK, I figured a Saturday run to Dr. Sato would be OK, and I could keep the “old Valbazen” going for a few days more. It was Friday 10 pm by the time I was done at the Emergency Clinic (having “only” sat for 3+ hours to be “seen and treated”… and told to go see some other vet that actually can treat a rabbit…)
I declined the Baytril (more on why in a later posting. For “non-special knowledge” circumstances, I’d go with it, but this case was “special” in a way I’ll talk about in a few days). And figured Dr. Sato would prescribe ‘next day’.
Next day was several hours of calling and getting a message of “Go away kid, you bother me” as the voicemail said “Open for Saturday appointments only between 9am and 1pm” and nobody ever picks up the phone….
I probably ought to have just driven over and barged in, but had enough Valbazen to make it through the weekend, so why not? Besides, the bunny was responding to treatment and nystagmus was near zero, energy was up, and he was eating and drinking.
I call Cambrian Vet Hospital and find out “Dr. Sato is off until tomorrow”. After a half dozen “on hold” moments and being dropped and calling back once, I am told they don’t actually HAVE albendazole in stock any more and Dr. FOOBAR who owns the hospital thinks I ought to find “a vet who treats rabbits”. I point out that “I thought I had one”, and hang up.
OK. I’m on my own. Bunny is getting better, but the last dose of Old Valbazen was given. This is day 4. 10 Days is normal. If I stop now, it’s likely just going to come roaring back, but less sensitive to Albendazole…. So (having been told that Cambrian Animal Hospital can’t actually give me a referral to a vet that does treat bunnies, so I ought to just “call arround”…) I start “dialing for dollars”. I eventually find a vet that DOES treat bunnies, and says they have an E. Cuniculi treatment on stock, and I can have an appointment … Thursday… SO I take it. It’s nearly a week after first symptoms, and the bunny would have most likely been dead by then but for my treatment with Valbazen, and I’m out, so there will be a 3 day gap in dosing, but probably “livable” (literally…).
The Quest Begins
But being not so inclined to roll dice with life, I go looking for other sources of Valbazen. NOBODY in 40 miles of me carries it anymore. Some mention “fenbendazole” wormers. I do more research and find out it, too, has been used with E. Cuniculi.
To shorten a long story, I run off to a “ranch supply store” and buy “Cattle Parasiticide” that is Ivermectin in Giant Size dose ( treats 10 x 550 lb doses) and “Horse Wormer” that is fenbendazole 10% paste suited to treating 1000 lbs of horse.
And figure out that 3.4 “drops” of the Ivermectin “drench” on the skin is enough for my 1.7 lb bunny (guess that $163 also bought a precise weight…) and, knowing the Dutch issue, do one drop per day for 4 days to assess any bad reaction without having a “lethal full dose” in one go as the vet does it… The bunny has tolerated it Just Fine, so as he is all of about 1/2 Dutch, I guess Dad gave him a good non-Dutch blood brain barrier….
I also figured out that 0.17 CC of “paste” was the right fenbendazole dose, and using the 10 CC syringe (that was for making a slurry of the meclozine and administering it… no needle, just a fancy squirt gun into the mouth) made a 0.17 ish sized squirt of the paste and rubbed it on the bunnies teeth / lips where he licked it off.
A Few Days Later
It is now Wednesday. 6 days after first symptoms. The Bunny is symptom free, as far as I can tell. He has a tiny bit of residual head tilt, but even cured bunnies sometimes hold the head a bit tilted. He is full of energy. Eating well. Impatient at being in the cage (he has been ‘free range’ his whole life, and while he did not mind the hutch when dizzy, is looking longingly at the garden now…) On the other hand, he has decided I’m “an OK guy” and even gives “mutual grooming” behaviour as I comb him out. He is rid of fleas and lice ( I’ve been trying to give him that gift for a couple of years, but this is the first time I could pick him up). He is, as near as I can tell, cured.
So I canceled the Vet appointment for tomorrow.
At this point, we will do fenbendazole (“Safe-guard” horse worming paste) for 4 more days, and I’ve given the last drop of Ivermectin.
The Punch Line
Doing some web searching showed some efficacy for Ivermectin against E. Cuniculi. It showed reasonable, but not lasting, effectiveness from the Benzimidazole class of drugs (Albendazole, Fenbendazole, and Oxybendazole – where an oxygen is swapped for a sulphur on the non-active tail of the molecule) but with guarded prognosis and frequent relapse.
So WHY have I had such quick and complete success?
I think it is due to using BOTH Ivermectin and Albendazole / Fenbendazole together. While in the first case (Snickers) it was accidental, in the second case it was a deliberate act. There will be a bit more on why I think the Ivermectin treatment is an important part in “Part Two” of the E. Cuniculi story; but for now, the working thesis is that “each whacks MOST of the bugs but both together are curative”.
A nice article that pulls some bits together:
Last fall, while searching online for information on E. cuniculi, a friend discovered Barbi Brown’s article about her experiences treating (and perhaps preventing the spread of) E. cuniculi using Ivermectin. Ms. Brown is a breeder who keeps excellent health records and who believes in regularly treating her rabbits with Ivermectin at three month intervals. She noticed that the rabbits she saw with symptoms of E. cuniculi had either never been treated with Ivermectin or had not been treated for at least six months.
Ms. Brown’s philosophy of regularly treating her rabbits with Ivermectin is similar to the widely-accepted practice of de-worming horses. Twenty years ago, the preferred horse wormer was fenbendazole; today it is Ivermectin. Given the biological parallels between rabbits and horses, it seems worth pursing the possibility that Ivermectin might help stop the spread of E. cuniculi.
Ms. Brown’s article states that Ivermectin “paralyzes the parasite and stops the migration to the brain.” Her protocol calls for a second treatment seven days after the initial treatment, with follow-up treatments every three months, presumably for the remainder of the rabbit’s life.
Despite the current lack of scientific evidence that Ivermectin is effective in treating – and perhaps preventing – attacks of E. cuniculi, this may be an option worth discussing with your rabbit’s veterinarian. Ivermectin has an excellent safety profile, having been used to treat fur mites in many rabbits for many years with very few side effects. The major concern Dr. Allan had with Ms. Brown’s protocol is that her dosage is almost four times greater than the upper limit of the (widely accepted) dose range for rabbits. Dr. Allan has agreed to try this treatment with the rabbits who have joined my family at a young age, but at half the dose used by Ms. Brown.
This was the link that gave me the “Ah Hah!” moment that Albendazole / Fenbendazole WITH Ivermectin might just be the “magic bullet” and would explain my 100% success with a 2 week regimen that has resulted in “cure” instead of “endless treatment and eventual resistance” that others have experienced.
I know I’m being a bit premature, as only Snickers has had the life to show “cure”, but the other bunny has had an astounding return to health (days) and at this point, it’s pretty clear he is “just fine”. There is also “part 2” to give more evidence “soon”.
The same site notes some activity of Baytril against E. Cuniculi, so I’ve got a tiny bit of remorse about declining that baytril for bacteria prescription… part of why I say “get the baytril to assure it’s not Pasteurella” then add the fenbendazole and ivermectin…) but I think it’s not the major part of the “cocktail” that’s doing the heavy lifting.
It goes on to note:
In 2001, a study published in the Veterinary Record (April 14, 2001, pp.478-480) suggested that fenbendazole, a drug used to treat roundworms, might be effective in both preventing and curing E. cuniculi infections. This was a major breakthrough, both because there was scientific data to support the findings and because this was the first treatment that was believed to cure (rather than simply control) the condition. In rare cases, long term treatment with fenbendazole may be associated with the onset of bone marrow failure.
Some veterinarians who had been skeptical of albendazole and oxibendazole because of the lack of scientific data began treating symptomatic cases of E. cuniculi with fenbendazole and others switched to prescribing fenbendazole. I have recently heard from several individuals that their veterinarians were going back to oxibendazole because they considered it to be more effective than fenbendazole once symptoms emerge. Again, however, this conclusion is based on each practitioner’s individual experience rather than on a pooled scientific data.
That was the data that sent me off to the “horse wormer” and let me give up on finding Valbazen in the local “animal feed and cattle stuff” shops. As near as I can tell, at least locally, Fenbendazole has replaced Albendazole thus making it hard to find the Valbazen on the shelf. OK, knowing that, I can “work with that”…
(That same link has a discussion of Albendazole and Oxybendazole as well.)
A little appreciated symptom of E. Cuniculi in Rabbits can be hind quarters paralysis:
Along the way, I had to convert a Ivermectin dose from a 250 ml “drench” or “pour on” for Cattle to a dose the right size for a dwarf bunny. The package lists the dose as “1 ml per 22 lbs of body weight”. Or 1 ml / 10 kg. But if your bunny is less than a kg? … So I needed to take a 1 cc “dose” and meter it even smaller. This site:
Gave me the conversion of 0.05 ml / “drop”. I confirmed that 1 tsp was 100 drops (a tsp is 5 ml, so 100 x 0.05 ml = 5 ml and that was what I found testing my ‘dropper’ against a US tsp. (I also found that it is 4.9289 ml / US tsp, but 5 ml / “metric teaspoon” that seemed rather oxymoronic ;-) and that the English Teaspoon is 1/4 of a tablespoon while the US teaspoon is 1/3 of a tablespoon, so an English Teaspoon is a bit smaller. ( 3/4 of 5 ml or 3.75 ml) so be very careful to use metric measures or be aware of just which teaspoon you are using…)
At any rate, using a ‘dropper’ measured against a tsp standard of 5 ml, I was able to calibrate to 3.4 “drops” / 1.77 lb bunny. Do the math twice. Then do it again twice more. You don’t want to be off by a decimal point and shut down their brain…
Notes on Fenbendizole
The package of “Safe-guard” says:
Safe-Guard (fenbendazole) Paste 10% is administered orally at a rate of 2.3 mg/lb ( 5mg / kg) for the control of large strongyles, small strongyles, and pinworms.
A related “horse wormer” is “Panacure” at 18.75% and ought to work as well, but with slightly harder ‘dilution’ to get the right dose.
In a couple of places I saw the dose of “20 mg / kg / day” quoted for use against E. Cuniculi. That is the dose I used. We are not just trying to get a worm to “let go” in the gut and be pooped out, but to kill a bug well inside cells.
While this is higher by a factor of 4 than the “wormer” dose, it looks like it is well tolerated by the patient. Fenbendazole is not as rapidly or efficiently absorbed as Albendazole, so that may be a factor in the toleration of the high dose. It is also the case that I’m only doing a 2 week treatment, not “ongoing” or “months” as others have done.
A landmark study published in the Veterinary Record in April 2001(see reference)offered perhaps the first evidence that treatment of E cuniculi with fenbendazole (Panacur) in rabbits really does work – and has led to a more pro-active approach in treating this problem in rabbits. This study considered the use of fenbendazole (at a dose of 20 mg/kg body weight daily for 28days) for preventing an experimental infection of E. cuniculi in rabbits. Fenbendazole given prior to exposure to the parasite successfully prevented infection, and this may be a way of controlling infection in colonies/groups of rabbits where some animals have the disease and others aren’t yet infected.
The second part of the same paper looked at rabbits with naturally acquired E. cuniculi infection. Following treatment with fenbendazole, E. cuniculi parasites were no longer present (detectable). The authors of the paper went on to suggest that in order to improve the treatment of E. cuniculi in rabbits, the combination of fenbendazole and glucocorticoids (steroids) could be valuable and should be examined in a controlled study.
There’s a catch, though. Although the parasite may be killed by drugs such as fenbendazole, the bunny may not actually get any better. This is because the brain inflammation associated with the parasite may have already caused irreversible damage. This is why steroid treatment has been suggested, in an effort to damp down this inflammatory response. Opponents point out that “damping down” the immune system with steroids could allow the underlying parasitic infection to get worse. Hence, it is probably safest to use steroids only in conjunction with fenbendazole and not as sole therapy, until more evidence is available.
Thus my desire to “jump on it quick”. IF at the very first moment of nystigmus you “jump on it” with immediate administration of a parasiticide ( or 2..) it looks like all the problems are avoided. If you wait a week for a vet to have a “slot” to see you, IMHO, it’s just too late. Again, IMHO, the local vets and the way they run their practice is nearly criminal and amounts to animal cruelty. That I was able to “work around them” does not excuse it for the other 100 folks who are not so “gifted” with technical skills and dogged persistence.
The antiparasitic actions of Safe-Guard (fenbendazole) Paste 10% is believed to be due to the inhibition of energy metabolism of the parasite
In fact, the -bendazoles seem to work by blocking glucose metabolism in the little buggers. SO, a spore is not metabolizing much, and Ivermectin can’t do a lot about it, but the -bendazoles screw up the GABA function and make it not develop correctly, while the Ivermectin causes the active ones to “run out of gas” and be easy prey for the immune system. That, in a nutshell, is my thesis. It may be that a “2 weeks on” and retreat in two weeks; would work best. I’m not seeing the need right now, though.
At any rate, screwing up the GABA internal controls of development and function while shutting of the gas supply looks to me like a darned good “double tap” and the “facts on the ground” seem to indicate it does work well.
OK, that’s where we are “today”. I’ve got 4 more days of treatment. If I’ve figured this all out correctly, that 10 days of fenbendazole (actually, 4 of Albendazole, 6 of Fenbendazole) is a short fast “wallop” that does not lead to the bone marrow failure of long term treatment, and the adjunct of Ivermecten makes the pair work as a “2 week cure” instead of months long ordeal. So far it has one confirmed success, and a second “sure looks like it at this point”.
I would also note that “Very Early and Immediate” treatment might well be a critical factor to success. I’ll now be “stocking” Ivermectin and “Safe-Guard” just so I never have to deal with “Professional veterinarians” again in this time critical circumstance….