Toxoplasma gondii: The effect of fluconazole combined with sulfadiazine and pyrimethamine against acute toxoplasmosis in murine model

Toxoplasma gondii is an important opportunistic pathogen for immunocompromised patients and responsible for toxoplasmic encephalitis, which is often lethal. Treatment for this infection is limited to a restricted therapeutic arsenal. In this work we tested the combination of fluconazole with the current treatment for acute toxoplasmosis on the murine model in vivo. Different experimental groups were treated with combinations of sulfadiazine plus pyrimethamine with fluconazole and pyrimethamine with fluconazole. Fluconazole is an important antifungal triazole used against others CNS related opportunistic pathogens such as Cryptococcus neoformans and Candida spp. The combinations of fluconazole plus sulfadiazine and pyrimethamine or fluconazole plus pyrimethamine were remarkably effective against T. gondii in vivo. The 10-day treatment with 10 mg/kg/day of fluconazole combined with 40/1 mg/kg/day sulfadiazine and pyrimethamine resulted in 93% survival of CF1 mice acutely infected with the highly virulent T. gondii RH strain, versus 36% of mice treated with just sulfadiazine and pyrimethamine. Combinations of fluconazole with lower doses of sulfadiazine and pyrimethamine or with just pyrimethamine were also efficient in reducing the mortality of mice compared with the treatment without fluconazole. The results obtained are promising for the treatment of human toxoplasmosis and point to the need to extend these studies to other murine models.

Highlights► The beneficial combination of fluconazole plus sulfadiazine and pyrimethamine was determined. ► Fluconazole enhanced the effect of sulfadiazine and pyrimethamine against acute toxoplasmosis. ► Fluconazole enhanced the effect of pyrimethamine alone against acute toxoplasmosis.