Toxoplasma gondii: disease patterns in mice treated with the folate antagonist methotrexate.

Methotrexate (MTX), a folic acid antagonist, was administered to Toxoplasma-infected mice in an attempt to inhibit acquired resistance to the parasite. Several time- and dose-dependent drug regimes were examined, with the following results.MTX administered during the first week of infection converted subclinical, nonlethal infections into severe disease with pronounced morbidity, either with or without high mortality. Depending on the drug regime employed, three different patterns of disease emerged. Constant findings in the MTX-treated mice were persistence of Toxoplasma trophozoites in peritoneal exudate and viscera; earlier appearance and increased numbers of cysts in the brain; development of many cysts in large, grapelike clusters; and a severe, disseminated meningoencephalitis.When administration of MTX was delayed until the twelfth day postexposure, its infection-modifying ability was lost, indicating that immunogenesis by this time has provided a high level of acquired resistance to Toxoplasma.MTX had no discernible effects when started 30 days postexposure. Reactivation of the latent infection did not occur.