Murine model of drug-induced reactivation of Toxoplasma gondii

A murine model of recrudescence of chronic toxoplasmosis, mimicking this li fe-threatening condition in immunosuppressed humans, was developed in Swiss -Webster mice infected 6 weeks previously with 10 cysts of the Me49 strain of Toxoplasma gondii, by treatment with dexamethasone (DXM, 2.5 mg/kgBM/day in drinking water), alone or combined with cortisone-acetate (CA, 50 mg/kg by subcutaneous injection 3 times a week). Treatment was continued for 7 w eeks. Both DXM and DXM+CA treatment significantly increased mortality, as c ompared to infected untreated mice (P=0.0002 and P<10(-4), respectively), a nd to uninfected DXM-treated mice (P=0.043 and P=0.001, respectively). In b oth treatment groups, mean cyst numbers were 2-9-fold increased compared wi th chronically infected untreated mice. Spleen/body mass ratios and numbers of splenocytes were significantly lower (P<10(-4)) than in untreated both infected and uninfected mice, indicating decreased immune reactivity in tre ated animals. Acquired immunity too was impaired by corticoids, as shown by lower resistance to challenge infection with the mouse-virulent RH strain of T. gondii in mice with established chronic infection treated with DXM th an in those left untreated (P=0.038). Most importantly, 8 of the 56 treated animals (14.2%) developed clinical signs of toxoplasmic encephalitis, whic h was verified histologically. In these, survival was significantly shorter (P=0.009) and cyst numbers 6-fold augmented (P<10(-4)) as compared to trea ted animals, which did not develop neurological signs. This simple model of drug-induced recrudescence of chronic toxoplasmosis, in addition to its po tential use for in vivo studies of the pathogenic mechanisms of T. gondii r eactivation, may be particularly suitable for the evaluation of chemotherap eutics.