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Title: DETERMINATION OF THE ACTIVITY OF PYRIMETHAMINE, TRIMETHOPRIM AND SULFONAMIDES AND COMBINATIONS OF PYRIMETHAMINE AND SULFONAMIDES AGAINST SARCOCYSTIS NEURONA IN CELL CULTURES

Author
item LINDSAY, DAVID - VA TECH, BLACKSBURG, VA
item Dubey, Jitender

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: Sarcocystis neurona is a single-celled parasite. It is the main cause of a neurologic disease of horses called equine protozoal myeloencephalitis (EPM). The parasite affects the brain and spinal cord of the horses and often causes paralysis of hind limbs. There is no satisfactory treatment for EPM. Sulfonamides and pyrimethamine are the 2 drugs most commonly used to treat horses. Scientists at the Beltsville Agricultural Research Center and Virginia Tech, Blacksburg have developed an in vitro cell culture system to screen drugs against S. neurona. They found that a pyrimethamine and sulfadiazine combination was effective in suppressing the growth of S. neurona in cell culture.

Technical Abstract: Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. The activities of pyrimethamine, trimdthoprim, sulfachloropyridazine, sulfadiazine, sulfadimethoxine, sulfamethoxazole, sulfamethazine, and sulfathiazole were examined against developing S. neurona merozoites in bovine turbinate cell cultures. A microtiter plate host cell lesion based assay was used to determine the effects of agents on developing merozoites. A cell culture flask assay was used to determine if selective concentrations of the agents killed or only inhibited development of S. neurona. Pyrimethamine was coccidiocidal at 1.0 ug/ml and trimethoprim was coccidiocidal at 5.0 ug/ml. None of the sulfonamides had activity when used alone at 50.0 or 100.0 ug/ml. Combinations of sulfonamides (5.0 or 10.0 ug/ml) with 0.1 ug/ml pyrimethamine demonstrated improved activity.