title: Diclazuril preventive therapy of gamma interferon knockout mice fed Sarcocystis neurona sporocysts.
abstract: 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.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Beltsville Agricultural Research Center, MD 20705-2305, USA. jdubey@ANRI.barc.usda.gov
authors.forename: J P
authors.initials: JP
authors.lastname: Dubey
authors.forename: D
authors.initials: D
authors.lastname: Fritz
authors.forename: D S
authors.initials: DS
authors.lastname: Lindsay
authors.forename: S K
authors.initials: SK
authors.lastname: Shen
authors.forename: O C
authors.initials: OC
authors.lastname: Kwok
authors.forename: K C
authors.initials: KC
authors.lastname: Thompson
mesh_terms: D000818:Animals; D003049:Coccidiostats / Q000627:therapeutic use*; D006734:Horse Diseases / Q000188:drug therapy / Q000517:prevention & control; D006736:Horses; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009570:Nitriles / Q000627:therapeutic use*; D009893:Opossums; D012522:Sarcocystis; D012523:Sarcocystosis / Q000188:drug therapy / Q000517:prevention & control / Q000662:veterinary*; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D003049:Coccidiostats; D009570:Nitriles; D014227:Triazines; D007371:Interferon-gamma; C057884:diclazuril