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E. Cuniculi
This information was written by Kathy Smith and is presented
here with her kind permission. It first appeared in the
House Rabbit Connection's spring
newsletter.
E. cuniculi Treatment Success Stories
When I first became involved in the rabbit world twelve years ago, a
symptomatic rabbit who was diagnosed with E. cuniculi had a
very poor prognosis. While there is still no cure, today there are
several treatment options that veterinarians have used with success.
Since no single treatment has proven effective in all cases, it is
important for all of us, both caretakers and veterinarians, to keep
abreast of new treatment options and be open to new ideas. The
treatments discussed in this article vary from
"widely-used-over-almost-a-decade" to
"promising-in-very-limited-testing." If your veterinarian is open to
trying one of the newer treatments, don't be surprised if she wants to
do additional research and/or consult with those veterinarians who
have already used these treatments.
What is E. cuniculi?
E. cuniculi is a protozoan parasite that is spread through
spores that are shed in the urine of infected rabbits. A rabbit may
contract it at a young age from an infected mother or from cage mates
who are shedding spores, or later in life from an infected
companion. The parasite attacks the nervous system and major organs,
causing a variety of symptoms including head tilt, liver disease,
kidney disease, cataracts, incontinence, loss of function in the legs
(back, front, or both), nystagmus (eye twitching), and/or other
neurological symptoms.
Diagnosis
E. cuniculi is diagnosed by a blood test that is not part of
routine blood-work. A positive result (often referred to as a positive
"titer") only means that the rabbit has been exposed to
E. cuniculi resulting in antibody
production. E. cuniculi is often kept in check by a rabbit's
immune system and many rabbits that test positive for
E. cuniculi never develop symptoms. However, if the rabbit's
health (mental or physical) is compromised, he may start to develop
symptoms.
Some caretakers choose to have all rabbits in their family
tested. Knowing whether your rabbit has tested positive can be
helpful, especially if he develops symptoms that may (or may not) be
caused by E. cuniculi, such as head tilt or a wet
bottom. However, keep in mind that in a multi-rabbit household, a
rabbit that has tested negative may test positive at a later
date. This is especially important to remember if his companion has
tested positive and has recently developed symptoms! Spores are
thought to be shed only briefly, in the early stages of an active
infection.
Common Treatments: The -bendazoles
The most common treatments used for symptomatic E. cuniculi
today are benzimidazole derivatives used to treat intestinal parasites
in various species. While these drugs have been used successfully on
many rabbits, there have been some reports of mild to moderate
elevation of liver enzymes. Although values usually return to normal
after medication is discontinued, please discuss periodic blood
testing with your veterinarian.
The action of benzimidazoles is slow, and the length of a rabbit's
gastrointestinal tract further delays absorption by the body. In many
rabbits, symptoms return when medication is stopped. Recently, several
caretakers who have been treating rabbits long-term with oxibendazole
have reported that the treatment gradually seems to stop working over
time, perhaps indicating that the parasite eventually develops a
resistance to it.
Albendazole
Albendazole, a drug used in humans to treat lesions caused by certain
tapeworms, was the first of the benzimidazole derivatives to be used
to treat symptomatic E. cuniculi. It was first used with some
success in the mid-1990's by several veterinarians including Dr. Jeff
Jenkins, a well-known rabbit veterinarian in the San Diego
area. Albendazole is the only benzimidazole that is quickly absorbed
and eliminated by the body, but also may have more side-effects than
the others.
Oxibendazole
In the late 1990's several HRS members and their veterinarians began
treating a significant number of symptomatic cases of
E. cuniculi with oxibendazole, a horse worming paste. For many
rabbits, treatment led to remarkable improvement and in many others it
stopped progression of the disease. Today oxibendazole is a commonly
prescribed treatment for symptomatic E. cuniculi. It has been
used by hundreds of veterinarians around the world to extend life
(with quality) for thousands of rabbits.
Unfortunately, oxibendazole is not successful in treating all cases of
E. cuniculi. Despite the large number of rabbits who have been
treated with it, there is no compilation and/or analysis of data on
rabbits who have been treated and whether treatment was successful
(either symptoms improved or rate of progression of symptoms was
reduced).
Fenbendazole
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.
Baytril
My veterinarian, Dr. Noella Allan (Lakewood Animal Health Center,
Lee's Summit, MO) has had significant success using Baytril, in
conjuction with oxibendazole, in the treatment of symptomatic
E. cuniculi. She frequently prescribes both treatments while
waiting for test results in cases where symptoms pointed equally to
E. cuniculi or a bacterial infection. Over the years, Dr. Allan
noticed that in her practice, rabbits with E. cuniculi that had
been treated with Baytril showed more improvement or slower disease
progression than those who were treated with oxibendazole alone. In
addition, when symptomatic E. cuniculi rabbits on long-term
oxibendazole showed progression of symptoms, the addition of Baytril
often resulted in overall improvement in their condition.
Although Dr. Allan is not sure of the exact mechanism for this
improvement, she suggests the following possible modes of action:
- Baytril (or its interaction with oxibendazole) may actually
interfere with the protozoan or its replication
- Improvement may be an anti-inflammatory response
- By treating co-existing bacterial infections, Baytril might
strengthen the overall immune system
I admit I was skeptical about using Baytril to treat
E. cuniculi. However, when Henrietta developed head tilt just
before Christmas 2001, Dr. Allan started her on both Baytril and
oxibendazole while we waited for the results of the E. cuniculi
test. Henrietta tested positive, but by the time we had the test
results her symptoms had significantly improved. We continued both
treatments for several months and eventually the only way I could tell
which direction her head had tilted was to remember which side of the
toilet she would lean against!
Pyrimethamine "Cocktail"
A promising new treatment was suggested by Esther van Praag, Ph.D., a
Swiss biologist, in her paper Can Encephalitozoon cuniculi, a
protozoal parasite of the nervous system, be treated with
pyrimethamine? (The complete text of this article is available at
www.medirabbit.com.) Dr. van Praag based her study on the similarities
between E. cuniculi in rabbits and Sarcocystis neurona, an
equine protozoal parasite, which lives in the nervous system and
spinal cord, and causes equine protozoal myelitis (EMP). According to
Dr. van Praag, EMP is routinely treated with the antiprotozoal drug
pyrimethamine.
Knowing that pyrimethamine has been safely used in rabbits to treat
both toxoplasmosis and hepatic coccidial infections, Dr. van Praag
suggested the possibility of using pyrimethamine to treat
E. cuniculi in rabbits. The protocol, documented in her
article, is based on one for treating toxoplasmosis in horses and
includes the following drugs:
- Folic acid
- Pyrimethamine
- Sulfadiazine
- A non-steroidal anti-inflammatory (NSAID)
Note: Pyrimethamine should not be given by itself!
The drug dosages for use in rabbits were determined by Mark Lennox,
DVM (Crossroads Animal Hospital, El Paso, TX), who based them on the
treatment of toxoplasmosis in cats. This treatment should be used for
a full month, assuming the rabbit is able to safely tolerate the
treatment.
According to Dr. van Praag's article, the pyrimethamine both blocks
the metabolism of folic acid in the parasite and increases the
effectiveness of the sulfadiazine in combating the parasite. It is
important to note Dr. van Praag's warning that compounds containing
trimethoprim, which is combined with sulfadiazine in many sulfa drugs,
should not be used because trimethoprim may increase the toxicity of
pyrimethamine. Her article also points out that the combination of
pyrimethamine and sulfadiazine may affect the function of bone marrow,
causing a decrease in both red and white blood cell counts. Folic acid
is an important part of the protocol because it helps minimize this
side effect. However, regular blood work is suggested when using this
treatment. The administration of an NSAID (e.g. Banamine or meloxicam)
helps reduce the inflammatory response induced by the death of large
numbers of parasites at one time.
At this time (February 2006), this treatment has been used on a very
small number of rabbits, all of which had previously been treated with
one or more of the "-bendazole" treatments and all of which had
stopped responding to these treatments. All the rabbits showed a very
high titer for E. cuniculi and were not suffering from other
health issues, except in one case. The results, while very
preliminary, seem quite promising.
Heather McMurray's rabbit Sweetie is one of the success stories for
this protocol. Sweetie is a 10-year-old rabbit who had one leg
amputated several years ago. In 2002 he lost the use of his remaining
rear leg and was found to have a very high E. cuniculi
titer. He was treated first with fenbendazole. When this treatment
stopped working after about six weeks, he was switched to oxibendazole
for several months, until it, too, stopped being effective. Heather's
veterinarian, Dr. Lennox decided to try the pyrimethamine protocol on
Sweetie. Heather noticed visible improvement within six days of the
start of treatment, and treatment was continued for a full four
weeks. Although Sweetie has not regained full use of the leg, the
paralysis has not worsened since Thanksgiving when he completed the
treatment.
Lufenuron
For several years, lufenuron, an oral chitin inhibitor, has been used
safely in rabbits as a short-term flea treatment. Dr. Dean Beyerinck
(Irving Street Veterinary Hospital, San Francisco, CA) has treated
more than 50 symptomatic cases of E. cuniculi with lufenuron
and has been pleased with its success rate. The scientific explanation
of this treatment is based on information in an article by Elizabeth
S. Didier in the July, 1998 issue of Clinical Infectious Diseases
which suggests that the endospore of the E. cuniculi spore is
composed of chitin. Thus, while lufenuron probably does not kill the
existing organisms, it may be quite effective in keeping them from
reproducing!
The long term effect of lufenuron on the body of rabbits (and other
mammals) has not yet been established. Recently, it has been found
that mammals possess chitin-like enzymes, and the interaction of
lufenuron with these enzymes has not been studied.
Dr. Beyerinck began treating Susan's rabbit Toby with lufenuron in the
spring of 2002. At the time treatment was started, Toby's titer had
risen dramatically over a two year period. Although she had been
warned that it might be two or three weeks before there was visible
improvement, Susan began noticing slight improvement after only three
days and significant improvement after eight days. The original plan
was to treat Toby every four weeks, but in his case symptoms seemed to
return like clockwork after about three weeks. Toby received a
lufenuron treatment every three to four weeks until his death (from
causes unrelated to his E. cuniculi. According to Susan, Toby's
overall health and quality of life improved significantly with this
treatment.
Ivermectin
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.
Future Directions
As rabbit caretakers and their veterinarians share their experiences
and pool both their data and their scientific and analytic skills,
there is reason to hope that some day we will be able to both
effectively control symptoms and halt the spread of this disease. To
accomplish this, it is important to begin collecting and analyzing
clinical data on individual rabbits receiving various treatments, with
the understanding that there is as much to be learned from treatment
failures as from success.
It is also important to understand that in medicine (both human and
veterinary) it is not unusual for a treatment that appeared promising
in a controlled, laboratory setting to fail miserably in a real-world
clinical setting. Similarly, new indications for existing treatment -
or combinations of treatments - are often discovered by observant
clinicians who notice trends in their practice.
If you have an idea about a treatment that might be effective against
E. cuniculi, I urge you to discuss it with your veterinarian,
keeping in mind that all ideas - even bad ones - should be explored
and discussed. When we were reaching the end of the road treating
Goldie in 1998, my husband George and I "brainstormed" possible
treatments for her. Dr. Allan quickly vetoed trying quinine because it
would be too harsh to use on a rabbit's delicate system, but agreed it
was worth trying George's suggestion to use the leftover
beta-interferon from his MS injections. While this treatment had no
noticeable effect, at least we had tried something!
The ultimate treatment or cure for E. cuniculi will probably
not be one of the options discussed in this article. But perhaps it
will come from a seed planted by a thought process discussed here, or
by a reader daring to toss out an "outlandish" idea for discussion
with her veterinarian.
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Last update: Sun Jun 28 21:49:23 EDT 2020
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