Effect of a single dose of ponazuril on neural infection and clinical disease in Sarcocystis neurona-challenged interferon-gamma knockout mice

• Published in: Veterinary parasitology 2003-05, Vol.114 (2), p.123-130
• Main Authors: Franklin, Robert P., MacKay, Robert J., Gillis, Karen D., Tanhauser, Susan M., Ginn, Pamela E., Kennedy, Thomas J.
• Format: Article
• Language: English
• Subjects: Animals; Body Weight; Cerebellum - parasitology; Disease Models, Animal; Encephalomyelitis - drug therapy; Encephalomyelitis - prevention & control; Encephalomyelitis - veterinary; Equine protozoal myeloencephalitis; Female; Horse Diseases - drug therapy; Horse Diseases - prevention & control; Horses; Interferon-gamma - genetics; Interferon-gamma knockout mouse; Mice; Mice, Inbred BALB C; Mice, Knockout; Opossums; Ponazuril; Prevention; Sarcocystis - drug effects; Sarcocystis - isolation & purification; Sarcocystis neurona; Sarcocystosis - drug therapy; Sarcocystosis - prevention & control; Sarcocystosis - veterinary; Sporocysts; Triazines - administration & dosage
• ISSN: 0304-4017; 1873-2550
• DOI: 10.1016/S0304-4017(03)00127-4

Interferon γ-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 200 mg/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 200 mg/kg ponazuril between days 4 and 14 pi. Weight gain over the course of the experiment occurred only in mice that were given 200 mg/kg ponazuril on day 7 or 10 pi. With the exception of groups given 200 mg/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 20 mg/kg on day 7 pi or 200 mg/kg on day 1, 7, 10, or 14 pi. This effect was not significant. Mice given 200 mg/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.