AN ULTRASTRUCTURAL-STUDY OF THE EFFECT OF TREATMENT WITH ATOVAQUONE IN BRAINS OF MICE CHRONICALLY INFECTED WITH THE ME49 STRAIN OF TOXOPLASMA-GONDII

The morphological effects of drug treatment with atovaquone in the bra ins of mice chronically infected with Toxoplasma gondii was examined b y light and electron microscopy. As early as 1 and 2 weeks of treatmen t there appeared to be fewer tissue cysts compared to untreated contro ls and this reduction was more significant after 4 weeks treatment. Th ere also appeared to be a decrease in the number of inflammatory nodul es and the severity of the meningitis. Ultrastructurally, the cysts of both treated and control animals were located within host cells. Ther e was a marked increase in both the number of cysts with lysed bradyzo ites and the number of degenerate bradyzoites after 4 weeks treatment. It is probable that the drug is more active against the metabolically active immature bradyzoites than the mature organisms. Drug treatment does not appear to result in rupture of tissue cysts or release of To xoplasma antigens since there is a reduction rather than an increase i n the inflammatory response. This drug may be useful in treating chron ic toxoplasmosis since it appears to be active against the bradyzoites reducing the parasite burden (cyst number) without initiating a destr uctive inflammatory response.