Encephalitozoonosis (Encephalitozoon cuniculi)

Encephalitozoonosis is a significant, often subclinical, opportunistic infectious disease of domestic rabbits (Oryctolagus cuniculus) caused by the obligate intracellular microsporidian parasite Encephalitozoon cuniculi. This organism, now classified within the fungal kingdom (Microsporidia), is a ubiquitous pathogen with a worldwide distribution, capable of infecting a wide range of mammals, including immunocompromised humans. In rabbits, the disease is characterized by a chronic, latent infection that can manifest as a spectrum of clinical signs, most notably neurological deficits (vestibular disease, paresis, paralysis), renal insufficiency, and ocular lesions (phacoclastic uveitis). The parasite has a predilection for epithelial cells of the renal tubules and the endothelial cells of the brain, leading to granulomatous encephalitis and interstitial nephritis. The disease is of paramount importance in rabbit medicine due to its high seroprevalence in rabbitries and pet populations, its challenging diagnosis, and its potential zoonotic implications. The clinical presentation is highly variable, ranging from asymptomatic carriers to acute, fatal neurological crises, often triggered by stress or immunosuppression. Understanding the complex life cycle, transmission dynamics, and host-pathogen interactions is essential for effective diagnosis, treatment, and prevention in exotic animal practice.

The sole causative agent of encephalitozoonosis in rabbits is Encephalitozoon cuniculi, a microsporidian parasite belonging to the phylum Microsporidia, class Microsporea, order Microsporida, and family Encephalitozoonidae. It is an obligate intracellular, spore-forming organism. The infectious form is the mature spore, which is environmentally resistant and can survive for extended periods in the environment (weeks to months) under favorable conditions. Spores are typically 1.5-2.5 micrometers in size, oval to pyriform in shape, and possess a characteristic polar filament that is extruded to inject sporoplasm into host cells. Three strains of E. cuniculi have been identified based on molecular and antigenic differences: strain I (rabbit strain), strain II (mouse strain), and strain III (dog strain). In rabbits, strain I is the most common, but all strains can potentially infect rabbits. The parasite has a direct life cycle, with both merogony (asexual multiplication) and sporogony (spore formation) occurring within host cells, primarily in the cytoplasm. Spores are shed in urine, feces, and respiratory secretions, and transmission occurs via the fecal-oral route, inhalation of aerosolized spores, or transplacentally. Ingestion of contaminated food or water is the most common route of infection. The parasite's ability to evade the host immune system and establish latent infections is a key feature of its pathogenesis.

Encephalitozoonosis is a globally distributed disease with a high seroprevalence in domestic rabbit populations. Serological surveys have reported prevalence rates ranging from 20% to 80% in pet rabbits and up to 50-75% in commercial rabbitries. The disease is more common in rabbits housed in groups or in facilities with poor hygiene, as spores are shed in urine and can contaminate the environment. Young rabbits (weanlings to young adults) are more susceptible to clinical disease, but infection can occur at any age. There is no breed or sex predilection, although some studies suggest a higher incidence in dwarf and lop-eared breeds, possibly due to anatomical factors (e.g., facial conformation) that predispose to ocular and dental issues. Wild rabbits (Oryctolagus cuniculus) also serve as a reservoir, and transmission to domestic rabbits can occur through contact with contaminated soil or vegetation. The disease is more prevalent in rabbits kept outdoors or in environments with high spore loads. Immunosuppression, whether due to stress, concurrent disease, or corticosteroid therapy, can reactivate latent infections and lead to clinical disease. In addition to rabbits, E. cuniculi can infect other mammals, including rodents (mice, rats, guinea pigs), carnivores (dogs, foxes), and humans, particularly immunocompromised individuals (e.g., HIV/AIDS patients, organ transplant recipients). However, rabbits are considered the primary reservoir host. The zoonotic potential, though low, underscores the importance of proper hygiene and handling precautions in veterinary settings.

The pathogenesis of encephalitozoonosis begins with the ingestion or inhalation of spores. Spores germinate in the gastrointestinal tract, extruding the polar filament and injecting sporoplasm into intestinal epithelial cells. The parasite then undergoes merogony and sporogony within these cells, leading to cell lysis and release of spores into the intestinal lumen and bloodstream. The parasite disseminates hematogenously to target organs, particularly the kidneys and brain, but also the liver, lungs, and eyes. In the kidneys, E. cuniculi infects renal tubular epithelial cells, causing chronic interstitial nephritis. The infection leads to tubular degeneration, fibrosis, and granuloma formation, which can progress to chronic renal failure. In the brain, the parasite infects endothelial cells and macrophages, leading to granulomatous encephalitis, particularly in the periventricular white matter and brainstem. The inflammatory response, characterized by lymphocytic and plasmacytic infiltration, results in microgliosis, astrocytosis, and the formation of granulomas. The neurological signs are primarily due to the destruction of neural tissue and the inflammatory response, which can cause edema and increased intracranial pressure. The vestibular signs (head tilt, nystagmus, ataxia) are often attributed to lesions in the brainstem and vestibular nuclei. Ocular involvement, specifically phacoclastic uveitis, occurs when the parasite infects the lens epithelium, leading to lens rupture and a severe granulomatous uveitis. The exact mechanism of lens infection is unclear but may involve hematogenous spread or direct extension from the ciliary body. The clinical signs are often exacerbated by stress, immunosuppression, or concurrent infections, which can trigger the reactivation of latent cysts and increased parasite replication.

Several intrinsic and extrinsic factors predispose rabbits to clinical encephalitozoonosis. Intrinsic factors include age (young rabbits, especially weanlings, are more susceptible due to an immature immune system), genetic susceptibility (some breeds may have a higher incidence, though not definitively proven), and immune status (immunosuppression from stress, concurrent disease, or corticosteroid therapy can reactivate latent infections). Extrinsic factors include poor husbandry, such as overcrowding, inadequate sanitation, and high environmental contamination with spores. Rabbits housed outdoors or in contact with wild rabbits are at higher risk. Stressful events, such as transport, weaning, surgery, or changes in social groups, can precipitate clinical disease. Nutritional deficiencies, particularly vitamin C deficiency (though rabbits synthesize their own vitamin C), and poor overall health can weaken the immune system. Additionally, the use of immunosuppressive drugs, such as corticosteroids, can lead to recrudescence of latent infection. The presence of concurrent diseases, such as pasteurellosis or dental disease, can also increase susceptibility. In terms of husbandry, the use of bedding materials that retain moisture and organic matter can promote spore survival and transmission. Inadequate ventilation and high humidity can also increase the risk of inhalation of spores.

Clinical signs of encephalitozoonosis in rabbits are highly variable and depend on the severity and location of lesions. Many rabbits are asymptomatic carriers, showing no clinical signs despite being seropositive. When clinical disease occurs, it can be acute, chronic, or episodic. The most common clinical signs are neurological and include: head tilt (torticollis), which is often the most prominent sign; nystagmus (involuntary eye movements), which may be horizontal, vertical, or rotary; ataxia (incoordination); paresis or paralysis of the hind limbs; tremors; seizures; and circling. Vestibular signs are common due to brainstem involvement. Behavioral changes, such as depression, lethargy, and anorexia, may also be observed. Renal disease may manifest as polyuria, polydipsia, and signs of chronic renal failure, such as weight loss, poor coat condition, and uremic breath. In advanced cases, rabbits may develop azotemia and renal failure. Ocular signs, particularly phacoclastic uveitis, are characterized by a white or opaque lens (cataract), uveitis (inflammation of the uveal tract), and sometimes lens rupture. The affected eye may be painful, and rabbits may show blepharospasm and epiphora. In some cases, the disease can cause sudden death, especially in young rabbits. The clinical signs can be exacerbated by stress, and rabbits may have episodes of acute deterioration followed by partial recovery. It is important to note that clinical signs can be unilateral or bilateral, and the severity can range from mild head tilt to severe, incapacitating neurological deficits.

The differential diagnoses for encephalitozoonosis in rabbits include a wide range of infectious, inflammatory, neoplastic, and toxic conditions. Key differentials include: 1) Pasteurellosis (Pasteurella multocida) - can cause head tilt, otitis media/interna, and neurological signs; however, it is often accompanied by respiratory signs (rhinitis, pneumonia) and abscesses. 2) Otitis media/interna (bacterial, often secondary to Pasteurella) - presents with head tilt and vestibular signs; diagnosis via otoscopy, radiography, and culture. 3) Toxoplasmosis (Toxoplasma gondii) - can cause neurological signs, but is less common in rabbits; serology and PCR can differentiate. 4) Listeriosis (Listeria monocytogenes) - causes encephalitis and septicemia; rare in rabbits, but can be transmitted via contaminated feed. 5) Rabies - a fatal viral encephalitis; consider in endemic areas with exposure to wildlife. 6) Neoplasia (e.g., lymphoma, meningioma) - can cause progressive neurological signs; imaging (CT/MRI) and biopsy are needed. 7) Trauma (e.g., spinal injury, head trauma) - can cause acute paresis or head tilt; history and radiography are helpful. 8) Toxicity (e.g., lead poisoning) - can cause neurological signs; blood lead levels can confirm. 9) Hepatic encephalopathy - due to liver disease, can cause neurological signs; liver function tests and bile acids are useful. 10) Nutritional deficiencies (e.g., vitamin E deficiency) - can cause neurological and muscular signs; dietary history and response to supplementation. 11) Encephalitozoonosis is also a differential for renal disease, so other causes of renal failure (e.g., nephrolithiasis, pyelonephritis, toxic nephropathy) should be considered. Definitive diagnosis of encephalitozoonosis requires specific testing (serology, PCR, histopathology) to rule out these other conditions.

The diagnostic approach to a rabbit suspected of encephalitozoonosis should be systematic and comprehensive. Step 1: Clinical triage and history - obtain a thorough history including signalment, husbandry, diet, recent stressors, and onset/progression of clinical signs. Step 2: Physical examination - perform a complete physical exam with emphasis on neurological assessment (mentation, posture, gait, cranial nerve function, proprioception), ophthalmic examination (including slit-lamp biomicroscopy to evaluate the lens and anterior chamber), and palpation of the kidneys (which may be irregular or shrunken in chronic renal disease). Step 3: Baseline diagnostics - collect blood for hematology and serum biochemistry, including renal parameters (BUN, creatinine, phosphorus, potassium) and liver enzymes. Urinalysis should be performed to assess urine specific gravity, protein, and sediment. Step 4: Serology - perform serological testing for E. cuniculi antibodies (IgG and IgM) using ELISA or immunofluorescence antibody (IFA) tests. A positive IgM or a rising IgG titer (paired samples 2-4 weeks apart) is suggestive of active infection. However, serology can be negative in early infection or in immunocompromised animals. Step 5: Molecular testing - PCR on urine, cerebrospinal fluid (CSF), or aqueous humor can detect parasite DNA and is more sensitive than serology for active infection. Urine PCR is non-invasive and can be useful, but shedding may be intermittent. Step 6: Imaging - radiography of the skull (to evaluate the tympanic bullae for otitis media/interna) and spine (to rule out trauma or spondylosis) may be indicated. Advanced imaging (CT or MRI) of the brain is the gold standard for detecting granulomatous lesions and can help rule out other intracranial diseases. Step 7: CSF analysis - if neurological signs are present and no contraindications, CSF collection (cerebellomedullary cistern tap) can be performed under anesthesia. CSF may show lymphocytic pleocytosis and elevated protein. PCR on CSF can be diagnostic. Step 8: Ocular examination - if uveitis or cataracts are present, aqueous humor aspiration for PCR and cytology may be considered, though it is invasive. Step 9: Renal biopsy - in cases of suspected renal involvement, ultrasound-guided renal biopsy can provide histopathological confirmation, but it is invasive and carries risks. Step 10: Response to treatment - a therapeutic trial with fenbendazole and supportive care may be initiated if diagnostic tests are inconclusive, and clinical improvement can support the diagnosis. It is important to note that a definitive diagnosis often requires a combination of serology, PCR, and response to treatment, as histopathology is rarely available antemortem.

Laboratory findings in encephalitozoonosis are variable and often non-specific. Hematology may be normal or show mild anemia (non-regenerative) due to chronic disease. White blood cell count may be normal or slightly elevated with lymphocytosis or monocytosis. In cases of secondary bacterial infection, a neutrophilic leukocytosis may be present. Serum biochemistry may reveal elevated BUN and creatinine, hyperphosphatemia, and hyperkalemia in cases of renal failure. Hypoalbuminemia and hyperglobulinemia may be seen due to chronic inflammation. Liver enzymes (ALT, AST) may be mildly elevated if there is hepatic involvement. Urinalysis may show isosthenuria (specific gravity < 1.030), proteinuria, and occasionally hematuria or pyuria. The presence of E. cuniculi spores in urine can be detected by modified trichrome stain or PCR. Serological tests (ELISA, IFA) are the most commonly used diagnostic tools. A positive IgG titer indicates exposure, but not necessarily active infection. A positive IgM titer or a four-fold rise in IgG titer over 2-4 weeks suggests active or recent infection. However, serology can be negative in early infection (within the first 2-4 weeks) or in immunocompromised animals. PCR on urine, CSF, or aqueous humor is highly specific and can detect parasite DNA, but sensitivity may be limited by intermittent shedding. In CSF, analysis typically reveals lymphocytic pleocytosis (10-100 cells/µL) and elevated protein (50-200 mg/dL). PCR on CSF is more sensitive than serology for neurological disease. Histopathology of affected tissues (brain, kidney) shows granulomatous inflammation with intralesional spores, which can be visualized with special stains (e.g., Gram stain, Giemsa, Warthin-Starry silver stain, or immunohistochemistry).

Imaging plays a crucial role in the diagnostic workup of encephalitozoonosis, primarily to rule out other causes of neurological signs and to assess the extent of organ involvement. Radiography: Skull radiographs (lateral, dorsoventral, and oblique views) are useful to evaluate the tympanic bullae for evidence of otitis media/interna (thickening of the bulla wall, increased opacity). Spinal radiographs can rule out vertebral fractures, spondylosis, or discospondylitis. Thoracic and abdominal radiographs may reveal cardiomegaly, hepatomegaly, or renomegaly, but are often unremarkable. Ultrasonography: Abdominal ultrasound is valuable for assessing renal size, echogenicity, and architecture. In chronic renal disease, kidneys may be small, irregular, and hyperechoic. Renal cysts or mineralization may be seen. Ultrasound-guided renal biopsy can be performed if needed. Echocardiography may be indicated if cardiac disease is suspected. Advanced Imaging: Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the brain are the most sensitive imaging modalities for detecting encephalitozoonosis-associated lesions. MRI findings may include multifocal, asymmetrical hyperintensities on T2-weighted and FLAIR images in the periventricular white matter, brainstem, and basal ganglia, with variable contrast enhancement. These lesions represent granulomas and inflammation. CT may show hypodense areas with contrast enhancement. MRI is also useful to rule out other intracranial diseases such as neoplasia or abscesses. In cases of ocular involvement, ocular ultrasound can assess lens integrity and the presence of uveitis. Endoscopy: In some cases, rhinoscopy or bronchoscopy may be performed if respiratory signs are present, but this is not a primary diagnostic tool for encephalitozoonosis.

Cytological and histopathological examination is essential for definitive diagnosis of encephalitozoonosis, especially when other tests are inconclusive. Cytology: Fine-needle aspiration of renal lesions or aqueous humor may reveal spores, which are small (1.5-2.5 µm), oval, and stain with modified trichrome or Gram stain. However, spores are often difficult to visualize on routine cytology. In CSF, cytology may show lymphocytic pleocytosis, but organisms are rarely seen. Histopathology: On post-mortem examination, the brain and kidneys are the primary organs affected. Grossly, the kidneys may be pale, shrunken, and have a granular surface. The brain may show no gross lesions or may have areas of softening. Microscopically, the hallmark lesion is granulomatous encephalitis, characterized by perivascular lymphocytic cuffing, microgliosis, astrocytosis, and the presence of granulomas with central necrosis. Organisms (spores and meronts) can be identified within macrophages, endothelial cells, and glial cells. In the kidneys, there is chronic interstitial nephritis with lymphoplasmacytic infiltration, tubular degeneration, fibrosis, and granuloma formation. Spores may be seen within tubular epithelial cells or in the interstitium. Special stains, such as Gram stain (spores are gram-positive), Giemsa, Warthin-Starry silver stain, or immunohistochemistry using anti-E. cuniculi antibodies, can enhance visualization of the organism. Electron microscopy can confirm the diagnosis by demonstrating the characteristic polar filament and ultrastructural features of the parasite. In cases of ocular disease, histopathology of the lens shows phacoclastic uveitis with lens rupture and granulomatous inflammation.

Treatment of encephalitozoonosis in rabbits is challenging and often focuses on managing clinical signs, reducing parasite load, and providing supportive care. The primary antiparasitic drug used is fenbendazole, a benzimidazole that inhibits microtubule polymerization and is effective against microsporidia. The recommended dosage is 20 mg/kg PO q24h for 28 days. Some protocols use a higher dose (50 mg/kg) or extend the duration to 30-60 days. Albendazole (30 mg/kg PO q24h for 30 days) is an alternative, but it has been associated with bone marrow suppression in rabbits and should be used with caution. It is important to note that these drugs are parasitostatic rather than parasitocidal, and they may not eliminate the infection completely, but they can reduce clinical signs and shedding. Supportive care is crucial. For neurological signs, anti-inflammatory doses of corticosteroids (e.g., dexamethasone 0.1-0.5 mg/kg SC or IM q12-24h) may be used to reduce brain inflammation, but they should be used cautiously due to the risk of immunosuppression and potential exacerbation of the infection. Non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam (0.3-0.6 mg/kg PO q24h) can be used for pain and inflammation. Fluid therapy is essential, especially in cases of renal disease, to maintain hydration and promote diuresis. Subcutaneous or intravenous fluids (e.g., lactated Ringer's solution or 0.9% saline) at maintenance rates (100 ml/kg/day) are recommended. In cases of severe neurological signs, hospitalization and intensive care may be required. Assisted feeding with a high-fiber diet (e.g., Critical Care) is important if the rabbit is anorexic. Ocular disease, particularly phacoclastic uveitis, may require topical anti-inflammatory therapy (e.g., prednisolone acetate or flurbiprofen) and mydriatics (atropine) to manage uveitis and prevent synechiae. In severe cases, surgical removal of the affected lens (lensectomy) may be necessary. Environmental management is critical: thorough cleaning and disinfection of the rabbit's enclosure with agents effective against spores (e.g., 1% hydrogen peroxide, 70% ethanol, or 1% sodium hypochlorite) is recommended. Reducing stress and providing a quiet, comfortable environment can aid recovery. It is important to note that treatment may not result in complete resolution of clinical signs, especially if there is significant neurological damage, and some rabbits may have permanent deficits.

The prognosis for encephalitozoonosis in rabbits is guarded to fair, depending on the severity of clinical signs and the extent of organ damage. Many rabbits with mild neurological signs (e.g., slight head tilt) can recover with treatment and supportive care, although some residual deficits may remain. Rabbits with severe neurological signs, such as paralysis or seizures, have a poorer prognosis. Renal disease, if advanced, can be progressive and lead to chronic renal failure, which is ultimately fatal. Ocular disease, if untreated, can lead to blindness. The response to treatment is variable; some rabbits show significant improvement within days to weeks, while others may not respond. Early diagnosis and treatment are associated with a better prognosis. The presence of azotemia at the time of diagnosis is a negative prognostic indicator. The overall mortality rate is low, but euthanasia may be considered in cases of severe, unresponsive neurological disease or advanced renal failure. It is important to counsel owners that the infection may not be completely eliminated, and relapses can occur, especially during periods of stress. Long-term management may be necessary, including regular monitoring of renal function and neurological status. With appropriate care, many rabbits can have a good quality of life despite the disease.

Follow-up care for rabbits with encephalitozoonosis is essential to monitor response to treatment and manage chronic complications. A re-check examination should be scheduled 2-4 weeks after initiation of treatment to assess clinical improvement and monitor for adverse effects of medication. Serial blood work (BUN, creatinine, electrolytes) should be performed every 2-4 weeks initially, then every 3-6 months if renal disease is present. Urinalysis should be repeated to monitor proteinuria and urine specific gravity. Serological testing (IgG and IgM) can be repeated to assess the response to treatment; a decrease in IgM and stable or decreasing IgG titers may indicate a favorable response. PCR on urine can be repeated to monitor shedding, but it may remain positive even after treatment. Neurological assessments should be performed at each re-check to document improvement or progression of deficits. In cases of ocular disease, ophthalmologic examinations should be repeated every 2-4 weeks until the uveitis is controlled, then every 3-6 months. Long-term management includes maintaining a stress-free environment, providing a high-quality diet (timothy hay, fresh vegetables, limited pellets), and ensuring adequate hydration. Owners should be educated on the importance of hygiene to prevent environmental contamination and potential zoonotic transmission. If the rabbit is on long-term fenbendazole, periodic blood work to monitor liver enzymes and complete blood count is recommended. In cases of chronic renal disease, dietary modifications (low protein, low phosphorus) and phosphate binders may be necessary. The prognosis should be re-evaluated at each follow-up visit, and adjustments to treatment should be made based on the rabbit's response.

Pearls: 1) Encephalitozoonosis is a great mimicker; always include it in the differential list for any rabbit with neurological signs, especially head tilt. 2) Serology is useful for screening, but a negative result does not rule out the disease; PCR on urine or CSF is more sensitive for active infection. 3) Fenbendazole is the treatment of choice, but it is parasitostatic; prolonged treatment (28 days or more) is necessary. 4) Corticosteroids can be used to reduce brain inflammation, but they should be used with caution and only in acute, severe cases. 5) Supportive care, including fluid therapy and assisted feeding, is crucial for recovery. 6) Ocular disease may require topical therapy and, in severe cases, surgery. 7) Always assess renal function in suspected cases, as renal disease is common and may be subclinical. 8) Educate owners about the zoonotic potential, especially for immunocompromised individuals. Pitfalls: 1) Do not use ivermectin or other antiparasitics that are ineffective against microsporidia. 2) Avoid the use of corticosteroids in rabbits with suspected bacterial infections, as they can exacerbate the infection. 3) Do not rely solely on serology for diagnosis; false negatives can occur. 4) Do not overlook the possibility of concurrent diseases, such as pasteurellosis or dental disease, which can complicate the clinical picture. 5) Avoid the use of albendazole in rabbits due to the risk of bone marrow toxicity; fenbendazole is safer. 6) Do not assume that a rabbit with a positive titer is clinically affected; many rabbits are asymptomatic carriers. 7) Do not forget to disinfect the environment, as spores are resistant and can cause reinfection. 8) Do not delay treatment pending diagnostic confirmation; a therapeutic trial with fenbendazole is often warranted in suspected cases.

Based on Carpenter's Exotic Animal Formulary (5th edition) and current literature, the following drug protocols are recommended for encephalitozoonosis in rabbits: 1) Fenbendazole: 20 mg/kg PO q24h for 28 days (some sources recommend 50 mg/kg for 30 days). It is the first-line treatment. 2) Albendazole: 30 mg/kg PO q24h for 30 days (use with caution due to bone marrow suppression). 3) Oxibendazole: 30 mg/kg PO q24h for 30 days (alternative). 4) For anti-inflammatory/immunomodulatory effects: Dexamethasone: 0.1-0.5 mg/kg SC or IM q12-24h for 3-5 days, then taper. 5) Meloxicam: 0.3-0.6 mg/kg PO q24h for pain and inflammation. 6) Fluid therapy: Lactated Ringer's solution or 0.9% saline, 100 ml/kg/day SC or IV. 7) For ocular disease: Topical prednisolone acetate 1% or flurbiprofen 0.03% (1 drop q6-8h), and atropine 1% (1 drop q12-24h) for mydriasis. 8) For renal support: If azotemia is present, consider phosphate binders (aluminum hydroxide 30-100 mg/kg PO q12h) and a low-protein diet. 9) Nutritional support: Critical Care (Oxbow) or other high-fiber recovery food, 10-20 ml/kg PO q6-8h if anorexic. 10) Antiemetics (if nausea): Metoclopramide 0.2-0.5 mg/kg PO or SC q8h. 11) In cases of secondary bacterial infection, appropriate antibiotics (e.g., enrofloxacin 10 mg/kg PO q12h) may be indicated. It is important to note that all dosages should be adjusted based on the individual patient's condition and response to therapy.

The literature on encephalitozoonosis in rabbits is extensive, with numerous studies on epidemiology, diagnosis, and treatment. Key findings include: 1) Seroprevalence studies have consistently shown high rates of exposure in rabbit populations, with some studies reporting >50% seropositivity in healthy rabbits (Kunstýř et al., 1986; Keeble & Shaw, 2006). 2) The clinical presentation is highly variable, and many infected rabbits are asymptomatic (Harcourt-Brown, 2004). 3) Diagnosis is challenging; serology is useful for screening, but PCR on urine or CSF is more sensitive for active infection (Csokai et al., 2009). 4) Fenbendazole has been shown to reduce clinical signs and shedding in experimentally infected rabbits (Suter et al., 2001). 5) The use of corticosteroids in acute neurological cases is controversial, but some studies suggest benefit in reducing inflammation (Keeble, 2006). 6) Ocular disease, particularly phacoclastic uveitis, is a well-recognized manifestation, and surgical intervention may be necessary (Felchle & Sigler, 2002). 7) The zoonotic potential is low but real, especially for immunocompromised individuals (Didier et al., 2004). 8) Consensus guidelines from the American Board of Veterinary Practitioners (ABVP) and the European College of Zoological Medicine (ECZM) recommend a combination of serology, PCR, and response to treatment for diagnosis, and fenbendazole as the first-line treatment. 9) Recent research has focused on the molecular epidemiology of E. cuniculi strains and the development of more sensitive diagnostic tools, such as real-time PCR (Csokai et al., 2009). 10) Long-term follow-up studies indicate that many rabbits with neurological signs can have a good quality of life with appropriate management (Harcourt-Brown, 2004). Overall, the evidence supports a multimodal approach to diagnosis and treatment, with a focus on supportive care and environmental management.