COMBINATION OF PS-15, EPIROPRIM, OR PYRIMETHAMINE WITH DAPSONE IN PROPHYLAXIS OF TOXOPLASMA-GONDII AND PNEUMOCYSTIS-CARINII DUAL INFECTION IN A RAT MODEL

In a rat model of dual infection, we studied such dihydrofolate reduct ase (DHFR) inhibitors as PS-lj (25 mg/kg of body weight), epiroprim (1 00 mg/kg), and pyrimethamine (3 mg/kg) alone or in combination with va rious doses of dapsone (50, 25, or 5 mg/kg) for the prevention of pneu mocystosis and toxoplasmosis. Rats latently infected with Pneumocystis carinii were immunosuppressed by corticosteroids for 7 weeks, and the drugs were administered from the initiation of the corticosteroid tre atment, At week 5, the rats were inoculated intraperitoneally with the RH strain of Toxoplasma gondii, Infections were monitored by the coun ting of P, carinii cysts in lung homogenates and the titration of T. g ondii in organs by quantitative culture and an indirect immunofluoresc ence assay, Fourteen of the 15 untreated rats died after T. gondii cha llenge, with P, carinii infection in the lungs and T. gondii infection in the lungs, liver, spleen, and brain, Of the three tested DHFR inhi bitors, only PS-15 exhibited anti-P, carinii activity; none prevented toxoplasmosis in 100% of the rats, After the DHFR inhibitors were comb ined with dapsone (50 or 25 mg/kg), both pneumocystosis and toxoplasmo sis were completely prevented, On the basis of these results, PS-15 an d epiroprim combined with dapsone are candidates for use for the preve ntion of both pneumocystosis and toxoplasmosis.