Immunological, histopathological, and ultrastructural evidence of steroid-induced reactivation of chronic murine toxoplasmosis.

We developed a model of steroid-induced reactivation of chronic murine toxoplasmosis to mirror similar effects of steroids or other immunosuppressants in infected humans. Immunological, histopathological, and ultrastructural parameters were reported. Prior to steroid administration, mice were infected with 10 cysts of the Me49 strain of Toxoplasma gondii. Mice were treated with dexamethasone (DXM, 2.5 mg/kg/day in drinking water), alone or combined with Solu-Cortef (SOLU, 50 mg/kg by subcutaneous injection 3 times a week) for 7 weeks or left untreated as control. Histopathological changes and ultrastructural effects of steroids on the course of chronic toxoplasmosis were recorded. By electron microscopy, the brains of infected combined treated mice showed an increase in number of tachyzoites and bradyzoites, degeneration, and necrosis of neural cells and hydropic degeneration besides the observed rupture of toxoplasma cysts releasing free tachyzoites in brain tissue. DXM+SOLU-combined treatment also significantly increased mortality, mean brain cyst count as compared to infected untreated mice (P = .01 and). Moreover, 3/12 (25%) treated animals developed clinical signs of toxoplasmic encephalitis. This simple model of drug-induced reactivation of chronic toxoplasmosis permits investigation of host-parasite interaction and may be used for the evaluation of chemotherapeutics in immunocompromised infected patients.