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Title: DICLAZURIL THERAPY OF GAMMA INTERFERON KNOCKOUT MICE FED SARCOCYSTIS NEURONA SPOROCYSTS

Author
item Dubey, Jitender
item FRITZ, D - FT DETRICK MD
item LINDSAY, D - BLACKSBURG VA
item Shen, Samuel
item Kwok, Oliver
item THOMPSON, K - SCHERING-PLOUGH

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2000
Publication Date: N/A
Citation: N/A

Interpretive Summary: Sarcocystis neurona is a single celled parasite of animals. It causes a fatal neurologic disease (EPM) of horses in the U.S. At present there is no effective tratment for this disease in horses. Scientists at the Beltsville Agricultural Research Center and Schering-Plough Inc. have found that diclazuril therapy is very effective against Sarcocystis neurona ainfection in mice. These results will be of interest to horse owners, veterinarians and parasitologists.

Technical Abstract: Gamma interferon knockout (KO) mice (n = 74) were fed a lethal dose of approximately 1000 sporocysts of SN15-OP isolate of Sarcocystis neurona. Groups of mice were given pelleted rodent feed containing 50 parts per million 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 to 39 days post-infection (p.i.), 1 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; S. neurona organisms were not demonstrable by bioassay of brains of these mice into uninfected KO mice. Sarcocystis neurona organisms were not found in tissues of 5 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 2 or 19 mice treated with diclazuril starting 10 days after feeding sporocysts, in 2 of 5 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 to 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.