diclazuril and Sarcocystosis

The aim of this study was to determine if bi-weekly administration of diclazuril at half the label dose would reduce seroprevalence and magnitude of titers to S. neurona in healthy horses naturally exposed to the apicomplexan protozoal parasite. 12 healthy adult horses were moved from a low-risk exposure to a farm with high exposure rate to S. neurona in their horse population. The horses were randomly assigned to either a treatment or a control group. Treatment consisted in the administration of half the label dose (0.5 mg/kg) of diclazuril (Protazil) pelleted top dress twice weekly (every 3-4 days) for 12 months. Prior to initiation of treatment and monthly thereafter, blood was collected for the detection of antibodies to S. neurona using a quantitative immunoassay. Further, trough plasma diclazuril levels were determined every 60 days. All 20 horses remained healthy during the entire study period. Seroprevalence to S. neurona decreased initially in the treatment group to 50% at 30 days post-treatment commencement. This was followed by a slow increase in seroprevalence in the treatment group before reaching 100% in both groups by 90 days post-treatment commencement. The seroprevalence remained 100% in both groups from 90 to 360 study days. While titer distribution between the two groups was similar at study commencement, treated horses had significantly lower titers throughout the treatment period (P < 0.05). All treated study horses had detectable plasma trough diclazuril levels at the 6 time points and the levels were above the concentration known to inhibit S. neurona in vitro (1.0 ng/mL). The administration of diclazuril pelleted top dress at half the label dose twice weekly was able to maintain low titers to S. neurona in healthy adult horses naturally exposed to the protozoal parasite. Further, trough diclazuril levels were in excess of the minimal concentration known to inhibit S. neurona.

Topics: Animals; Antibodies; Horse Diseases; Horses; Kinetics; Nitriles; Sarcocystis; Sarcocystosis; Seroepidemiologic Studies; Triazines

Thirty-three foals from a farm with a high exposure rate to Sarcocystis neurona were assigned to either an untreated or a diclazuril-treated group. Treated foals received daily 0.5 mg/kg of diclazuril pellets from 1 to 12 months of age. Monthly blood was tested for IgG against S. neurona using the indirect fluorescent antibody test. Following ingestion of colostral antibodies to S. neurona, there was a steady and continuous decline in seroprevalence to S. neurona until foals from both groups reached weaning age. Thereafter, the untreated foal group showed a significant increase in monthly seroprevalence compared to the diclazuril-treated foal group. The difference in temporal seroprevalence could be explained by the successful reduction of S. neurona infection in foals receiving a daily low-dose diclazuril.

Topics: Animals; Antibodies, Protozoan; Coccidiostats; Horse Diseases; Horses; Nitriles; Sarcocystis; Sarcocystosis; Seroconversion; Time Factors; Triazines

Topics: Animals; Brain; Cerebellum; Chlorocebus aethiops; Coccidiostats; Encephalomyelitis; Enzyme-Linked Immunosorbent Assay; Feces; Female; Immunoglobulins; Immunohistochemistry; Interferon-gamma; Male; Mice; Mice, Knockout; Nitriles; Opossums; Recurrence; Sarcocystis; Sarcocystosis; Triazines; Vero Cells

Gamma interferon knockout (KO) mice (n=74) were fed a lethal dose of approximately 1000 sporocysts of the SN15-OP isolate of Sarcocystis neurona. Groups of mice were given pelleted rodent feed containing 50ppm of diclazuril at different times before and after feeding sporocysts. All mice were examined at necropsy and their tissues were examined immunohistochemically for S. neurona infection. Twenty mice were fed sporocysts and given diclazuril starting 5 days before feeding sporocysts and continuing 30-39 days post-infection (p.i.). One mouse died of causes unrelated to S. neurona with no demonstrable parasites; the remaining 19 mice remained clinically normal and S. neurona organisms were not found in their tissues. Sarcocystis neurona organisms were not demonstrable by bioassay of the brains of these 19 mice in uninfected KO mice. Sarcocystis neurona organisms were not found in tissues of five mice treated with diclazuril, starting 7 days after feeding sporocysts and continuing up to 39 days p.i. Therapy was less efficient when diclazuril was given 10 days p.i. Sarcocystis neurona organisms were found in two of 19 mice treated with diclazuril starting 10 days after feeding sporocysts, in two of five mice starting therapy 12 days p.i., and in 10 of 10 mice when treatment was delayed until 15 days p.i. All 15 mice fed S. neurona, but not given diclazuril, developed neural sarcocystosis and were euthanized 22-30 days after feeding sporocysts. Six mice not fed S. neurona, but given diclazuril for 44 days, remained clinically normal. Results indicate that diclazuril can kill the early stages of S. neurona.

Topics: Animals; Coccidiostats; Horse Diseases; Horses; Interferon-gamma; Mice; Mice, Knockout; Nitriles; Opossums; Sarcocystis; Sarcocystosis; Triazines