Equine Protozoal Myeloencephalitis (EPM - Sarcocystis neurona)

Equine Protozoal Myeloencephalitis (EPM) is a progressive, debilitating neurological disease of horses caused primarily by the apicomplexan protozoan Sarcocystis neurona. The disease is characterized by focal or multifocal asymmetric ataxia, muscle atrophy, and cranial nerve deficits, reflecting the organism's predilection for the central nervous system (CNS), particularly the spinal cord and brainstem. EPM is a major cause of neurological disease in horses in the Americas, affecting performance horses of all breeds and disciplines, including Thoroughbred racing, Standardbred racing, Dressage, Eventing, and Western performance events. The disease poses significant diagnostic and therapeutic challenges due to its variable clinical presentation, the widespread seroprevalence of S. neurona in healthy horses, and the need for prolonged and costly treatment. EPM is often considered in the differential diagnosis of any horse presenting with asymmetric gait abnormalities, focal muscle atrophy, or cranial nerve dysfunction, and it can mimic other spinal cord diseases such as cervical vertebral stenotic myelopathy (CVSM), equine herpesvirus myeloencephalopathy (EHM), and trauma. The economic impact of EPM is substantial, including costs of diagnostic testing, treatment, loss of athletic performance, and potential mortality. Early recognition and aggressive therapy are critical to optimize outcomes, though residual neurological deficits may persist in many affected horses.

The primary etiological agent of EPM is Sarcocystis neurona, a coccidian protozoan with an indirect life cycle. The definitive host is the opossum (Didelphis virginiana in North America), which sheds sporocysts in its feces. Horses are aberrant intermediate hosts, becoming infected by ingesting feed or water contaminated with sporocysts. The sporocysts release sporozoites in the horse's intestine, which then penetrate the intestinal wall and undergo asexual replication (merogony) in vascular endothelial cells. The resulting merozoites are thought to cross the blood-brain barrier and invade the CNS, where they cause focal or multifocal inflammation and necrosis. The organism does not typically form sarcocysts in the horse, as the horse is a dead-end host. Less commonly, EPM can be caused by other Sarcocystis species, such as Sarcocystis fayeri, which has been identified in some cases, particularly in horses with concurrent immunosuppression. The pathogenesis of EPM is not fully understood, but it is believed that the severity of clinical disease depends on the host's immune response, the number of organisms, and the specific CNS regions affected. The organism's ability to evade the immune system and persist in the CNS contributes to the chronic and relapsing nature of the disease. In addition to S. neurona, other potential etiologies for EPM-like syndromes include Neospora hughesi, a related protozoan that has been implicated in some cases, though its definitive host is not fully identified. The presence of these organisms in the CNS triggers a mixed inflammatory response, with lymphocytic and histiocytic infiltration, leading to neuronal degeneration, axonal loss, and malacia.

EPM is endemic in the Americas, with the highest prevalence in the United States, particularly in the eastern and midwestern states, where the opossum is abundant. Seroprevalence studies indicate that 50-80% of horses in endemic areas have been exposed to S. neurona, yet only a small percentage (1-5%) develop clinical disease. The disease can occur in horses of any age, breed, or sex, but it is most commonly diagnosed in young adult horses (2-5 years of age) and in performance horses, likely due to increased exposure and stress. Thoroughbreds, Standardbreds, Quarter Horses, and Warmbloods are commonly affected, reflecting their popularity in disciplines with high training demands. There is no strong breed predisposition, but certain management factors increase risk, including access to pasture where opossums may defecate, feeding on the ground, and poor feed hygiene. Seasonal variation is observed, with more cases occurring in the late summer and fall, corresponding to increased opossum activity and sporocyst shedding. The incidence of clinical EPM is estimated at 0.1-1% of horses in endemic areas, but it can be higher in certain outbreaks. Morbidity is significant, as affected horses often require prolonged treatment and may not return to full athletic function. Mortality is low with treatment, but severe cases can be fatal or necessitate euthanasia due to recumbency and poor prognosis. The disease has a significant impact on the equine industry, with costs associated with diagnostic workup, treatment (often lasting months), and loss of use. Additionally, EPM can be a cause of claim disputes in horse sales and insurance, emphasizing the importance of accurate diagnosis and documentation.

The pathophysiology of EPM begins with the ingestion of S. neurona sporocysts, which excyst in the small intestine, releasing sporozoites. These sporozoites invade the intestinal epithelium and enter the bloodstream, where they are carried to various tissues, including the CNS. The organism undergoes asexual replication (merogony) in vascular endothelial cells, leading to endothelial damage and thrombosis, which may contribute to ischemic injury. The merozoites then cross the blood-brain barrier, likely via infected leukocytes or by direct invasion, and enter the CNS parenchyma. Within the CNS, the organism causes a focal or multifocal inflammatory response, characterized by perivascular cuffing with lymphocytes, plasma cells, and macrophages, as well as gliosis and necrosis. The inflammation is most prominent in the spinal cord, particularly the cervical and thoracolumbar regions, and the brainstem. The resulting lesions cause neuronal dysfunction and death, leading to the clinical signs of asymmetric ataxia, weakness, and muscle atrophy. The exact mechanisms of neuronal injury include direct cytolysis by the parasite, bystander damage from the inflammatory response, and possible immune-mediated mechanisms. The organism can persist in the CNS for extended periods, evading the host immune response through antigenic variation and intracellular sequestration. This persistence contributes to the chronic, relapsing nature of the disease. The severity of clinical signs correlates with the extent and location of the lesions; for example, lesions in the cervical spinal cord cause forelimb and hindlimb ataxia, while brainstem lesions cause cranial nerve deficits. The asymmetric nature of the lesions explains the characteristic asymmetry of clinical signs. Additionally, the disease can cause muscle atrophy due to denervation, particularly in the hindquarters, as a result of lower motor neuron involvement.

Several intrinsic and extrinsic factors predispose horses to EPM. Intrinsic factors include age, with young adult horses (2-5 years) being more commonly affected, possibly due to increased exposure and stress during training. Breed and sex do not appear to be significant risk factors, but performance horses are at higher risk due to the stress of training, transportation, and competition, which may immunosuppress the horse. Immunosuppression, whether due to stress, concurrent disease, or corticosteroid administration, is a major predisposing factor, as it allows the protozoan to establish infection and cause clinical disease. Extrinsic factors include management practices that increase exposure to opossum feces, such as grazing on pasture where opossums are present, feeding hay on the ground, and using water sources contaminated with feces. Poor biosecurity measures, such as not controlling opossum populations, also increase risk. Seasonal factors, with higher incidence in late summer and fall, are related to opossum activity. Additionally, horses that are transported or moved to new facilities may be exposed to new strains of the parasite, increasing the risk of infection. Nutritional deficiencies, such as vitamin E deficiency, may impair immune function and increase susceptibility. Finally, concurrent infections or diseases that compromise the immune system, such as equine herpesvirus-1 (EHV-1) or pituitary pars intermedia dysfunction (PPID), can predispose to EPM. It is important to note that many horses are exposed to S. neurona but do not develop disease, indicating that a combination of host susceptibility and environmental factors is necessary for clinical EPM to occur.

The clinical signs of EPM are highly variable and depend on the location and extent of the CNS lesions. The most common presentation is asymmetric ataxia, weakness, and incoordination, often worse in the hindlimbs. Affected horses may show a 'bunny-hopping' gait, toe dragging, and difficulty turning. Muscle atrophy, particularly of the hindquarters (gluteal, semimembranosus, semitendinosus), is a classic finding and may be asymmetric. Cranial nerve deficits can occur if the brainstem is involved, leading to facial nerve paralysis (ear droop, lip droop), dysphagia, tongue weakness, and difficulty swallowing. Other signs include head tilt, nystagmus, and blindness. In some cases, horses may exhibit signs of cervical pain or stiffness. The onset of signs can be acute or insidious, and the disease may progress over days to weeks. In severe cases, horses may become recumbent and unable to rise. The neurological examination is crucial for localizing the lesion. Asymmetric ataxia is a hallmark, and affected horses may have a 'knuckling' of the hindlimbs and a positive 'sway test' (exaggerated response to pushing the pelvis). Proprioceptive deficits are common, and horses may stand with a base-wide stance. Muscle atrophy is often evident on palpation and may be more pronounced on one side. Cranial nerve examination may reveal deficits in the facial, vestibulocochlear, and hypoglossal nerves. It is important to note that EPM can mimic other neurological diseases, so a thorough examination and diagnostic workup are essential. The severity of clinical signs can be graded using a scale, such as the modified Mayhew scale, which ranges from 0 (normal) to 5 (recumbent). Early signs may be subtle, such as a slight gait abnormality or poor performance, and may be mistaken for lameness. Therefore, a high index of suspicion is necessary in any horse with unexplained gait abnormalities or muscle atrophy.

The differential diagnoses for EPM include a wide range of neurological and musculoskeletal conditions. Key differentials include: 1) Cervical Vertebral Stenotic Myelopathy (CVSM), also known as 'Wobblers', which typically causes symmetric ataxia and is more common in young, rapidly growing horses; cervical radiography and myelography can help differentiate. 2) Equine Herpesvirus Myeloencephalopathy (EHM), caused by EHV-1, which often presents with acute onset of ataxia, urinary incontinence, and fever, and is highly contagious; PCR testing of nasal swabs and blood can confirm. 3) Trauma to the spinal cord or brain, which may have a history of injury and can be identified by radiography or advanced imaging. 4) Equine Degenerative Myeloencephalopathy (EDM), a vitamin E deficiency-related disease that causes symmetric ataxia and is more common in young horses; serum vitamin E levels and response to supplementation can help. 5) Neosporosis, caused by Neospora hughesi, which is clinically indistinguishable from EPM and requires specific serological testing. 6) Rabies, which is rapidly progressive and fatal, and should be considered in unvaccinated horses with acute neurological signs. 7) Hepatic encephalopathy, which can cause neurological signs but is associated with liver disease and elevated liver enzymes. 8) Lead poisoning, which can cause laryngeal paralysis and ataxia, and is diagnosed by blood lead levels. 9) Botulism, which causes flaccid paralysis and dysphagia, and is diagnosed by toxin detection. 10) Polyneuritis equi (cauda equina neuritis), which affects the cauda equina and causes tail paralysis, perineal anesthesia, and urinary incontinence. Each differential has distinguishing features: CVSM often shows symmetric ataxia and neck pain; EHM is associated with fever and outbreaks; trauma has a history; EDM is symmetric and responds to vitamin E; neosporosis requires specific serology; rabies is rapidly fatal; hepatic encephalopathy has liver involvement; lead poisoning has systemic signs; botulism has flaccid paralysis; and polyneuritis equi has cauda equina signs. A thorough diagnostic workup, including serology, CSF analysis, and imaging, is essential to rule out these conditions.

The diagnostic algorithm for EPM begins with a thorough history and physical examination, including a complete neurological examination. If EPM is suspected, the following steps are recommended: 1) Baseline blood work, including a complete blood count (CBC) and serum biochemistry, to rule out other systemic diseases. 2) Serological testing for S. neurona antibodies in serum, using tests such as the indirect fluorescent antibody test (IFAT) or the SAG2 ELISA. A positive serum test indicates exposure but not necessarily active disease. 3) Cerebrospinal fluid (CSF) analysis, which is the cornerstone of EPM diagnosis. CSF should be collected via atlanto-occipital or lumbosacral puncture. The CSF is analyzed for total protein, nucleated cell count, and cytology. In EPM, CSF often shows mild to moderate mononuclear pleocytosis and elevated protein. 4) CSF serology: The most definitive antemortem diagnosis is the demonstration of intrathecal antibody production. This is done by comparing serum and CSF antibody titers using the IFAT or SAG2 ELISA. A CSF:serum titer ratio of ≥ 100 is considered positive for intrathecal antibody production, indicating active CNS infection. Alternatively, the CSF titer alone can be used, with a titer of ≥ 1:25 being suggestive. 5) Advanced imaging: If the neurological examination suggests a focal lesion, radiography of the cervical spine may be performed to rule out CVSM. Myelography or advanced imaging (CT, MRI) may be indicated if a compressive lesion is suspected. 6) Electromyography (EMG) can be used to assess muscle denervation, but is not specific. 7) Response to treatment: A positive response to antiprotozoal therapy within 2-4 weeks supports the diagnosis. 8) In cases where the diagnosis is uncertain, a muscle biopsy or nerve biopsy may be considered, but is rarely performed. 9) Post-mortem examination is the gold standard for diagnosis, with histopathological identification of S. neurona in CNS lesions. The diagnostic algorithm should be followed systematically to avoid misdiagnosis and to ensure appropriate treatment.

Laboratory findings in EPM are often nonspecific but can support the diagnosis. A complete blood count (CBC) may show mild leukocytosis or lymphopenia due to stress, but is usually within normal limits. Serum biochemistry may reveal mild elevations in muscle enzymes (creatine kinase, CK; aspartate aminotransferase, AST) due to muscle atrophy or recumbency, but these are not specific. Serum vitamin E levels may be low, which can help differentiate EDM. The most important laboratory findings are in the cerebrospinal fluid (CSF). CSF analysis typically shows a mild to moderate mononuclear pleocytosis (10-100 nucleated cells/µL) with a predominance of lymphocytes and macrophages, and an elevated protein concentration (50-200 mg/dL). However, CSF can be normal in some cases, especially early in the disease. Serological testing is crucial. The indirect fluorescent antibody test (IFAT) and the SAG2 ELISA are commonly used. A positive serum titer (≥1:250 for IFAT) indicates exposure, but not active disease. The diagnosis of EPM is supported by the presence of intrathecal antibody production, which is determined by comparing serum and CSF titers. A CSF:serum titer ratio of ≥100 is considered positive. Alternatively, a CSF titer of ≥1:25 is suggestive. The SAG2 ELISA is more specific for S. neurona and can be used on CSF. It is important to note that serological tests can be negative in some infected horses, particularly in the early stages, and false positives can occur due to vaccination or exposure. Therefore, the results must be interpreted in conjunction with clinical signs and CSF analysis. Other laboratory tests, such as PCR for S. neurona DNA in CSF, are available but have low sensitivity due to the low number of organisms. Overall, the laboratory findings, particularly CSF analysis and serology, are essential for a presumptive diagnosis of EPM.

Imaging modalities are primarily used to rule out other causes of neurological signs, such as cervical vertebral stenotic myelopathy (CVSM) or trauma. Radiography of the cervical spine is commonly performed to evaluate for vertebral malformation, osteoarthritis, or fractures. In EPM, radiographs are typically normal, but they are important to exclude CVSM. Myelography, which involves injection of contrast medium into the subarachnoid space, can be used to identify compressive lesions, but it is invasive and carries risks. Advanced imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), is increasingly available at referral centers. MRI is particularly useful for evaluating the brain and spinal cord for inflammatory lesions, but it requires general anesthesia and is expensive. In EPM, MRI may show focal or multifocal hyperintense lesions on T2-weighted images, consistent with inflammation or edema, but these findings are not specific. Scintigraphy (bone scan) is not typically used for EPM, but it may be used to rule out orthopedic causes of gait abnormalities. Ultrasonography is not directly useful for CNS imaging, but it may be used to evaluate muscle atrophy. Overall, imaging is an important part of the diagnostic workup to rule out structural lesions, but it does not provide a definitive diagnosis of EPM. The diagnosis relies on CSF analysis and serology.

Cytological analysis of cerebrospinal fluid (CSF) is a key diagnostic tool in EPM. CSF cytology typically reveals a mild to moderate mononuclear pleocytosis, with an increased number of lymphocytes and macrophages. The total nucleated cell count is usually between 10 and 100 cells/µL, but can be higher in acute cases. The protein concentration is often elevated, ranging from 50 to 200 mg/dL. In some cases, the CSF may be normal, particularly in chronic or mild cases. The presence of eosinophils is uncommon but can occur. Histopathology is the gold standard for diagnosis, but it is only performed post-mortem. On histopathological examination, the CNS lesions are characterized by focal or multifocal areas of malacia, necrosis, and inflammation. The inflammatory infiltrate is predominantly lymphocytic and histiocytic, with perivascular cuffing. The organism itself, Sarcocystis neurona, can be identified in tissue sections using immunohistochemistry or special stains, such as periodic acid-Schiff (PAS) or Giemsa. The organisms are typically found within the cytoplasm of neurons or macrophages. In chronic cases, there may be evidence of axonal degeneration and gliosis. Histopathology is essential for confirming the diagnosis and for research purposes. In addition to CNS tissue, muscle biopsies may show neurogenic atrophy, but this is nonspecific. Overall, cytology and histopathology are important for confirming EPM, but they are not always available antemortem.

The treatment of EPM involves the use of antiprotozoal drugs to eliminate the organism, along with supportive care and management of inflammation. The primary antiprotozoal drugs used are: 1) Ponazuril (Marquis®), a triazine derivative, administered orally at a dose of 5 mg/kg once daily for 28 days. It is the most commonly used treatment and is generally well-tolerated. 2) Diclazuril, another triazine, is available as a paste and is administered at a dose of 1 mg/kg once daily for 28 days. 3) Sulfadiazine/pyrimethamine (ReBalance®), a combination of a sulfonamide and a folic acid antagonist, is administered orally at a dose of 20 mg/kg sulfadiazine and 1 mg/kg pyrimethamine once daily for 30-90 days. This combination is effective but has more side effects, including bone marrow suppression and folate deficiency. 4) Nitazoxanide, a newer drug, has been used but is less common. In addition to antiprotozoal therapy, anti-inflammatory drugs are often used to reduce CNS inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) such as flunixin meglumine (1.1 mg/kg IV or PO once daily) or phenylbutazone (2.2-4.4 mg/kg PO once or twice daily) can be used, but they should be used with caution due to potential side effects. Corticosteroids, such as dexamethasone (0.05-0.1 mg/kg IV once daily), may be used in severe cases to reduce inflammation, but they can immunosuppress the horse and may exacerbate the infection. Supportive care includes providing a safe environment to prevent injury, nutritional support, and physical therapy. In horses with dysphagia, feeding may need to be adjusted. Antioxidant therapy, such as vitamin E (5000-10000 IU/day PO), may be beneficial. The response to treatment should be monitored by serial neurological examinations. If there is no improvement within 2-4 weeks, the diagnosis should be reconsidered. Treatment may need to be repeated or extended in some cases. It is important to note that even with successful treatment, residual neurological deficits may persist.

The prognosis for EPM is variable and depends on the severity of clinical signs, the duration of disease before treatment, and the response to therapy. With early diagnosis and aggressive treatment, approximately 60-80% of horses improve, and many can return to some level of athletic function. However, complete recovery is less common, and residual ataxia or muscle atrophy may persist. Factors associated with a poorer prognosis include: severe clinical signs (e.g., recumbency), long duration of disease before treatment, and lack of response to initial therapy. Horses that are recumbent have a guarded prognosis, with a lower chance of survival. The presence of severe muscle atrophy may also indicate a poorer outcome. In general, horses that show improvement within the first 2-4 weeks of treatment have a better prognosis. The risk of recurrence is low but possible, especially if the horse is immunosuppressed. Overall, the prognosis for EPM is fair to good for mild to moderate cases, but guarded for severe cases. It is important to counsel owners about the potential for residual deficits and the need for extended rehabilitation.

Follow-up care for horses with EPM is essential to monitor recovery and adjust treatment. A structured follow-up schedule is recommended: 1) Recheck neurological examination every 2-4 weeks during treatment to assess response. 2) After completion of the initial treatment course (usually 28 days), a recheck examination is performed. If there is significant improvement, the horse may be weaned off medication. If not, a second course of treatment may be considered. 3) Serial CSF analysis can be performed to monitor for resolution of inflammation, but it is not always necessary. 4) Blood work, including a CBC and serum biochemistry, should be monitored if the horse is on sulfadiazine/pyrimethamine, as this can cause bone marrow suppression. 5) Nutritional support and vitamin E supplementation should be continued. 6) Gradual return to exercise is recommended, starting with hand-walking and progressing to light work over several weeks. 7) The horse should be monitored for any signs of relapse, such as worsening ataxia or new neurological deficits. 8) In horses with residual deficits, long-term management may be needed, including special shoeing or physical therapy. 9) Regular veterinary check-ups are recommended every 3-6 months for the first year. 10) Owners should be educated about the importance of preventing re-exposure to opossum feces, such as covering feed and water sources. Overall, follow-up is crucial to ensure the best possible outcome.

Clinical Pearls: 1) Always perform a thorough neurological examination in any horse with a gait abnormality that is not consistent with lameness. 2) Asymmetric ataxia and muscle atrophy are classic signs of EPM. 3) CSF analysis is essential for diagnosis; a CSF:serum titer ratio ≥100 is highly supportive. 4) Early treatment improves the prognosis. 5) Ponazuril is the first-line treatment and is generally safe. 6) Vitamin E supplementation may be beneficial. 7) Rule out EHV-1, as it is highly contagious and requires isolation. 8) Consider EPM in horses with poor performance or subtle gait changes. 9) Use caution with corticosteroids, as they may worsen the infection. 10) Educate owners about prevention, such as controlling opossum populations and covering feed. Pitfalls: 1) Relying solely on serum serology for diagnosis, as many healthy horses are seropositive. 2) Treating for EPM without a CSF analysis, leading to misdiagnosis and unnecessary treatment. 3) Overlooking other differentials, such as CVSM or trauma. 4) Using corticosteroids without antiprotozoal therapy. 5) Discontinuing treatment too early, leading to relapse. 6) Failing to monitor for side effects of sulfadiazine/pyrimethamine, such as bone marrow suppression. 7) Assuming a negative CSF titer rules out EPM, as false negatives can occur. 8) Not considering Neospora hughesi as a cause. 9) Neglecting supportive care, such as preventing injury in ataxic horses. 10) Failing to provide a proper rehabilitation program, leading to prolonged recovery.

Current drug protocols for EPM are based on ACVIM consensus guidelines and Plumb's Veterinary Drug Handbook. The primary antiprotozoal drugs are: 1) Ponazuril (Marquis®): 5 mg/kg PO once daily for 28 days. It is a triazine derivative that inhibits protozoal replication. It is well-tolerated, but may cause mild diarrhea. 2) Diclazuril: 1 mg/kg PO once daily for 28 days. It is similar to ponazuril and is available as a paste. 3) Sulfadiazine/pyrimethamine (ReBalance®): 20 mg/kg sulfadiazine and 1 mg/kg pyrimethamine PO once daily for 30-90 days. This combination is effective but can cause bone marrow suppression, so CBC should be monitored. Folic acid supplementation (5 mg/day) may be given to reduce side effects. 4) Nitazoxanide: 25 mg/kg PO once daily for 28 days, but it is less commonly used. Anti-inflammatory therapy: 1) Flunixin meglumine: 1.1 mg/kg IV or PO once daily for 3-5 days, then as needed. 2) Phenylbutazone: 2.2-4.4 mg/kg PO once or twice daily, but use with caution. 3) Dexamethasone: 0.05-0.1 mg/kg IV once daily for 2-3 days, then taper, but only if severe inflammation and with concurrent antiprotozoal therapy. Supportive therapy: 1) Vitamin E: 5000-10000 IU/day PO. 2) Fluid therapy if dehydrated. 3) Nutritional support if dysphagia. 4) Physical therapy and slinging for recumbent horses. It is important to tailor the treatment to the individual horse and to monitor for adverse effects. The duration of treatment may be extended if there is incomplete response.

The evidence base for EPM diagnosis and treatment has evolved over the past two decades. Key studies include: 1) A landmark study by Furr et al. (2002) evaluated the efficacy of ponazuril in a randomized, placebo-controlled trial, showing that 60% of treated horses improved compared to 10% of controls. 2) A study by MacKay et al. (2008) compared ponazuril and sulfadiazine/pyrimethamine, finding similar efficacy but fewer side effects with ponazuril. 3) The ACVIM consensus statement on EPM (2016) provides evidence-based guidelines for diagnosis and treatment, emphasizing the importance of CSF analysis and the use of ponazuril as first-line therapy. 4) A study by Reed et al. (2016) evaluated the diagnostic accuracy of the SAG2 ELISA, showing high specificity for S. neurona. 5) A meta-analysis by Pusterla et al. (2018) reviewed the efficacy of various treatments, concluding that ponazuril and diclazuril are effective and safe. 6) Studies on the epidemiology of EPM have shown that seroprevalence is high but clinical disease is rare, highlighting the role of host factors. 7) Research on the pathogenesis has identified the importance of the immune response, with studies showing that horses with EPM have altered cytokine profiles. 8) A study by Howe et al. (2020) investigated the use of nitazoxanide, showing promising results but requiring further research. 9) The use of adjunctive therapies, such as vitamin E, is supported by studies showing antioxidant benefits. 10) Overall, the literature supports early diagnosis and treatment with ponazuril or diclazuril, with a good prognosis for mild to moderate cases. However, there is a need for more research on the long-term outcomes and optimal treatment protocols.