Encephalitozoonosis

TL;DR. Encephalitozoonosis is a common parasitic infection in rabbits that targets the brain, kidneys, and eyes, often causing a characteristic head tilt, hind limb weakness, or urinary issues.

A head tilt is the most common and recognizable sign of E. cuniculi infection in rabbits.

What is it?

Encephalitozoonosis is a infectious disease in domestic rabbits caused by Encephalitozoon cuniculi (often abbreviated as E. cuniculi). Though historically classified as a protozoan parasite, modern genetic analysis has revealed that E. cuniculi is actually a microsporidian, which is a specialized group of single-celled parasites closely related to fungi. This microscopic organism is highly adapted to living inside the cells of its host, where it replicates and eventually causes the host cells to rupture.

Once inside the rabbit's body, the parasite targets organs with high blood flow. It has a strong affinity for the central nervous system (the brain and spinal cord), the kidneys, and the eyes. When the parasite multiplies within these tissues, it triggers a chronic inflammatory response. This inflammation, rather than the parasite itself, causes the majority of the tissue damage and the subsequent clinical signs that owners observe.

For rabbit owners, understanding this disease is vital because E. cuniculi is incredibly common. Many rabbits are exposed to the parasite early in life and harbor it silently in their bodies without showing any outward signs of illness. These rabbits are considered subclinical carriers. However, if the rabbit's immune system becomes compromised due to stress, age, or another underlying illness, the parasite can active and begin multiplying rapidly, leading to sudden and severe neurological or renal disease.

Causes & risk factors

The primary cause of encephalitozoonosis is the ingestion or inhalation of E. cuniculi spores. Infected rabbits shed these microscopic spores in their urine. When a healthy rabbit grooms a companion, eats contaminated hay or food, or inhales dust containing dried urine particles, the spores enter the body. Once ingested, the spores germinate in the intestine, pierce the gut wall, and spread through the bloodstream to the target organs.

Another significant route of transmission is vertical transmission, which occurs from a mother rabbit (doe) to her unborn kits during pregnancy. When transmission occurs in utero, the parasite often invades the developing lens of the fetus's eye. This can lead to ocular problems, such as cataracts and severe eye inflammation, which may not manifest until the rabbit is several months or even years old.

Several risk factors increase the likelihood of a rabbit developing active encephalitozoonosis:

• Multi-rabbit environments: Shelters, breeding facilities, and households with multiple rabbits have higher transmission rates due to shared space and litter boxes.
• Poor sanitation: Inadequate cleaning of enclosures allows urine-shed spores to accumulate, increasing the infectious load in the environment.
• Stress: Environmental changes, the loss of a bonded companion, improper diet, or concurrent diseases can suppress the immune system, allowing a latent infection to flare up.

There are no documented breed predispositions for E. cuniculi infection. Any domestic rabbit, regardless of breed, age, or sex, is susceptible to contracting the parasite and developing clinical disease.

Signs to watch for

The clinical signs of encephalitozoonosis depend entirely on which organ systems are most heavily affected by the parasite and the resulting inflammation. The disease primarily targets the nervous system, the urinary tract, and the eyes.

Cardinal Sign

• Head tilt: This is the classic, most recognizable sign of E. cuniculi infection. The rabbit's head will tilt permanently to one side due to inflammation in the vestibular system of the brain, which controls balance.

Common Signs

• Nystagmus: Involuntary, rapid, rhythmic movement of the eyes, which can be horizontal, vertical, or rotary. This often accompanies a head tilt and indicates severe disorientation.
• Ataxia: A lack of voluntary coordination of muscle movements. The rabbit may wobble, stumble, or appear drunk when trying to walk.
• Hind limb paresis: Weakness or partial paralysis of the back legs. Owners may notice the rabbit dragging its hindquarters or struggling to stand up on slippery surfaces.
• Urinary incontinence: The rabbit may lose control of its bladder, leading to urine scalding on the hind legs and belly, a wet tail area, and a persistent urine odor.

Occasional Signs

• Uveitis: Severe inflammation inside the eye. This is often "phacoclastic" uveitis, caused by the rupture of the lens capsule where the parasite has been dormant since birth.
• Cataracts: A visible clouding of the lens inside one or both eyes, which can lead to blindness.
• Seizures: Uncontrolled electrical activity in the brain, resulting in fitting, paddling of the limbs, or temporary loss of consciousness.

Ocular manifestations, such as cataracts and uveitis, can occur when the parasite infects the eye during fetal development.

How vets diagnose it

Diagnosing encephalitozoonosis in a living rabbit is notoriously difficult. Because so many healthy rabbits are silent carriers and have antibodies against the parasite, simply finding evidence of the parasite or exposure does not automatically mean E. cuniculi is the cause of the current illness. Your vet will perform a comprehensive physical and neurological examination and recommend a combination of tests to build a diagnostic case.

• Serology (ELISA/IFA): This blood test measures the level of antibodies (IgG and IgM) the rabbit's immune system has produced against E. cuniculi. IgM antibodies rise quickly after active infection or flare-up and then decline, while IgG antibodies persist long-term. A high IgM titer, or a significant rise in IgG titers when tested two to four weeks apart, strongly suggests an active, ongoing infection rather than past exposure.
• PCR (Polymerase Chain Reaction): This test looks for actual E. cuniculi DNA in urine or tissue samples. While a positive PCR test confirms the presence of the parasite, a negative test does not rule it out. This is because rabbits shed the spores in their urine intermittently; if a sample is collected on a day when the rabbit is not actively shedding, the test will be falsely negative.
• Biochemical Profile: This blood panel evaluates organ function, focusing heavily on Blood Urea Nitrogen (BUN) and Creatinine. Because the parasite causes chronic interstitial nephritis (kidney inflammation), elevated kidney values help your vet determine if renal insufficiency is present and guide fluid therapy decisions.
• Histopathology: This is the absolute gold standard for diagnosis. It involves examining tissue samples from the brain and kidneys under a microscope to identify the characteristic granulomatous lesions and the physical spores. However, because obtaining brain or kidney biopsies in a live rabbit carries extreme risk, histopathology is almost exclusively performed post-mortem to confirm the diagnosis.

Serology testing helps veterinarians measure antibody levels to determine if an active infection is present.

Treatment options

Treatment for encephalitozoonosis is aimed at halting the replication of the parasite, reducing the destructive inflammation in the target organs, and providing supportive care to keep the rabbit comfortable and eating.

First-Line Therapies

• Antiparasitic Therapy (Benzimidazole Anthelmintics): The primary drug used to treat the parasite itself is fenbendazole. This medication belongs to the benzimidazole class of anthelmintics. It works by disrupting the parasite's cellular structure and preventing it from replicating. A standard course of fenbendazole typically lasts for 28 consecutive days. While it is highly effective at stopping the parasite from multiplying, it cannot reverse physical scarring or tissue damage that has already occurred in the brain or kidneys.
• Anti-Inflammatory Therapy (NSAIDs): To control the severe inflammation triggered by the parasite, non-steroidal anti-inflammatory drugs (NSAIDs), specifically meloxicam, are prescribed. Reducing inflammation in the brain and vestibular system is critical for alleviating symptoms like head tilt and ataxia, and it helps manage the pain associated with joint weakness or uveitis.

Second-Line Therapies

• Sedatives and Anticonvulsants: If a rabbit is experiencing severe vestibular signs—such as continuous rolling, which can lead to self-injury and extreme stress—or active seizures, your vet may prescribe midazolam. This parenteral benzodiazepine acts as a rapid sedative and anticonvulsant to calm the central nervous system and stabilize the patient.

Supportive Care

In addition to specific medications, supportive care is vital for recovery. Rabbits with head tilts or hind limb weakness often struggle to eat and drink. Assisted feeding with high-fiber recovery formulas, subcutaneous or intravenous fluid therapy to support kidney function, and soft, padded bedding to prevent pressure sores are essential components of the treatment plan.

Prognosis

The prognosis for rabbits diagnosed with encephalitozoonosis is guarded. Recovery is highly dependent on how quickly treatment is initiated and the extent of the tissue damage before therapy begins.

Some rabbits respond remarkably well to treatment, showing a complete resolution of clinical signs. Others may survive but are left with permanent, lifelong neurological deficits, such as a residual head tilt or mild hind limb weakness. These rabbits can still enjoy an excellent quality of life, provided their owners make minor modifications to their housing (such as removing ramps, using low-sided litter boxes, and adding padded flooring to prevent slipping).

If the parasite has caused extensive, irreversible damage to the kidneys, the rabbit may develop chronic renal failure. In these cases, the long-term prognosis is poor, and therapy shifts to palliative care to manage kidney disease. Because long-term prognosis data in this species is limited and highly variable, close communication with your veterinarian is necessary to continuously assess your rabbit's quality of life.

Prevention

Because E. cuniculi is highly contagious and can remain dormant for years, preventing infection requires a combination of hygiene, screening, and stress management.

• Quarantine and Screening: Any new rabbit introduced to a household should be quarantined. Performing serological testing (ELISA) on new rabbits before introducing them to existing pets can help identify carriers.
• Sanitation: Regularly clean and disinfect enclosures. Spores are resistant to many mild cleaners, but they can be inactivated using a 10% bleach solution or specialized veterinary disinfectants. Ensure all organic material (feces and soiled bedding) is removed before disinfecting.
• Minimize Stress: Keep your rabbit's environment stable. Avoid sudden changes in routine, provide plenty of hiding spaces, and ensure they receive a balanced diet high in grass hay to keep their immune system strong.
• Breeding Practices: Because the parasite can be passed from mother to offspring, rabbits known to be infected or those that have produced affected kits should be removed from breeding programs.

When to call your vet

Encephalitozoonosis can progress rapidly, and early intervention significantly improves the chances of a positive outcome. You should contact your veterinarian if you notice any changes in your rabbit's gait, posture, or litter box habits.

Seek immediate emergency veterinary care if your rabbit exhibits any of the following signs:

• A sudden, severe head tilt
• Continuous rolling or inability to stand upright
• Active seizures or muscle twitching
• Complete loss of use of the hind limbs
• Anorexia (refusing to eat) for more than 12 hours

Sources

This article is based on standard-of-care veterinary knowledge and clinical consensus for exotic companion mammal medicine. Specific textbook citations were not provided in the reference record for this disease; therefore, the guidance outlined above represents widely accepted protocols within the professional veterinary community specializing in lagomorph internal medicine.