ponazuril and Sarcocystosis

To evaluate the effect of intermittent oral administration of ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts.. 20 healthy horses that were seronegative for S neurona-specific IgG.. 5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day - 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia.. Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 of 5 horses that were treated weekly; all other challenged horses immunoconverted within 84 days. Weekly administration of ponazuril significantly reduced the antibody response against the S neurona 17-kd antigen in CSF. Neurologic signs consistent with EPM did not develop in any group; likewise, histologic examination of CNS tissue did not reveal protozoa or consistent degenerative or inflammatory changes.. Administration of ponazuril every 7 days, but not every 14 days, significantly decreased intrathecal anti-S neurona antibody responses in horses inoculated with S neurona sporocysts. Protocols involving intermittent administration of ponazuril may have application in prevention of EPM.

Topics: Administration, Oral; Animals; Antibodies, Protozoan; Blotting, Western; Brain; Coccidiostats; Encephalomyelitis; Female; Histocytochemistry; Horse Diseases; Horses; Male; Sarcocystis; Sarcocystosis; Triazines

Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses most commonly caused by the protozoan parasite Sarcocystis neurona. Until recently the only treatment option was the combination of a sulfonamide with pyrimethamine. The present study was performed to assess the efficacy of ponazuril, an anticoccidial triazine-based compound, as a treatment for naturally occurring EPM. One hundred one horses with EPM were randomly allocated to treatment with ponazuril 15% oral paste at either 5 or 10 mg/kg body weight for 28 consecutive days. Horses were evaluated clinically and by analysis of blood and cerebrospinal fluid (CSF) before and 28 and 118 days after the start of treatment. Clinical success was defined as either an improvement in neurologic score by at least one grade (on a 0 to 5 scale) or conversion to negative status on Western blot for S. neurona antibodies by 90 days following cessation of treatment. Overall, 62% of the horses, including 28 of 47 treated with ponazuril at 5 mg/kg and 35 of 54 treated with 10 mg/kg, met the criteria for successful treatment. The Western blot for CSF became negative in 10% (10/101) of the horses. Quantification of the anti-17kDa antibody response in Western blot (relative quantity CSF) did not reveal a significant change in response to treatment. However, immunoglobulin index did decrease significantly during treatment (P = .01). The findings of this study support the efficacy of ponazuril for the treatment of EPM.

Topics: Administration, Oral; Animals; Antiprotozoal Agents; Encephalomyelitis; Horse Diseases; Horses; Sarcocystosis; Triazines

Topics: Animals; Antibodies, Protozoan; Encephalomyelitis; Female; Horse Diseases; Horses; Kinetics; Male; Sarcocystis; Sarcocystosis; Treatment Outcome; Triazines

A captive harbor seal (Phoca vitulina) presented with partial anorexia, ataxia, and head bobbing, which progressed to complete anorexia, lethargy, and persistent whole-body intention tremors within several days. Response to treatment with ponazuril, serology, and cerebrospinal fluid analysis supported a diagnosis of Sarcocystis neurona. Analysis of serum levels for ponazuril indicated that therapeutic levels could be achieved at a dosage of 5 mg/kg p.o. s.i.d., whereas clinical response was improved at a dosage of 10 mg/kg. Several months after initiation of antiprotozoal therapy, the neurologic signs resolved, although rare intermittent tremors were seen with significant exertion.

Topics: Animals; Antibodies, Protozoan; Central Nervous System; Coccidiostats; Phoca; Sarcocystis; Sarcocystosis; Treatment Outcome; Triazines

The ability of ponazuril to prevent or limit clinical signs of equine protozoal myeloencephalitis (EPM) after infection with Sarcocystis neurona was evaluated. Eighteen horses were assigned to 1 of 3 groups: no treatment, 2.5 mg/kg ponazuril, or 5.0 mg/kg ponazuril. Horses were administered ponazuril, once per day, beginning 7 days before infection (study day 0) and continuing for 28 days postinfection. On day 0, horses were stressed by transport and challenged with 1 million S. neurona sporocysts per horse. Sequential neurologic examinations were performed, and serum and cerebrospinal fluid were collected and assayed for antibodies to S. neurona. All horses in the control group developed neurologic signs, whereas only 71 and 40% of horses in the 2.5 and 5.0 mg/kg ponazuril groups, respectively, developed neurologic abnormalities. This was significant at P = 0.034 by using Fisher exact test. In addition, seroconversion was decreased in the 5.0 mg/kg group compared with the control horses (100 vs. 40%; P = 0.028). Horses with neurologic signs were killed, and a post-mortem examination was performed. Mild-to-moderate, multifocal signs of neuroinflammation were observed. These results confirm that treatment with ponazuril at 5.0 mg/kg minimizes, but does not eliminate, infection and clinical signs of EPM in horses.

Topics: Animals; Antibodies, Protozoan; Antiprotozoal Agents; Blotting, Western; Cell Count; Central Nervous System; Cerebrospinal Fluid; Encephalomyelitis; Erythrocyte Count; Female; Horse Diseases; Horses; Male; Neurologic Examination; Random Allocation; Sarcocystis; Sarcocystosis; Severity of Illness Index; Triazines

Interferon gamma-knockout mice were challenged with 5000 Sarcocystis neurona sporocysts acquired from a naturally infected opossum. Ponazuril was administered once, by gavage, at day 1, 3, 7, 10, or 14 post-infection (pi). Ponazuril was given at either 20 or 200mg/kg. Mice that survived to day 30 pi were euthanized. Severity of CNS infection was quantified as schizont density in the cerebellum. Unchallenged mice in treatment and non-treatment groups remained free of disease and gained weight throughout the experiment. All challenged mice, regardless of treatment, developed histologic evidence of CNS infection even though clinical signs were prevented in some groups. The greatest treatment benefits were seen in mice given 200mg/kg ponazuril between days 4 and 14 pi. Weight gain over the course of the experiment occurred only in mice that were given 200mg/kg ponazuril on day 7 or 10 pi. With the exception of groups given 200mg/kg ponazuril on day 7 or 14 pi, mice in groups that got sporocysts developed abnormal neurologic signs. No deaths before day 30 pi occurred in mice given ponazuril at 20mg/kg on day 7 pi or 200mg/kg on day 1, 7, 10, or 14 pi. This effect was not significant. Mice given 200mg/kg on day 7 pi had significantly fewer cerebellar schizonts than did those of the control group that was not given ponazuril. These results indicate that single-dose administration of ponazuril for prevention of CNS infection is partially protective when given between days 4 and 14 pi.

Topics: Animals; Body Weight; Cerebellum; Disease Models, Animal; Encephalomyelitis; Female; Horse Diseases; Horses; Interferon-gamma; Mice; Mice, Inbred BALB C; Mice, Knockout; Opossums; Sarcocystis; Sarcocystosis; Triazines

The present study examined the efficacy of ponazuril in inhibiting merozoite production of Sarcocystis neurona in cell cultures. Ponazuril inhibited merozoite production by more that 90% in cultures of S. neurona treated with 1.0 microg/ml ponazuril and greater than 95% inhibition of merozoite production was observed when infected cultures were treated with 5.0 microg/ml ponazuril. Ponazuril may have promise as a therapeutic agent in the treatment of S. neurona induced equine protozoal myeloencephalitis (EPM) in horses.

Topics: Animals; Antiprotozoal Agents; Cell Line; Encephalomyelitis; Horse Diseases; Horses; Sarcocystis; Sarcocystosis; Triazines