A morphological study of chronic cerebral toxoplasmosis in mice: comparison of four different strains of Toxoplasma gondii.

The pathological changes, host-parasite relationship and structure of the tissue cysts in the brains of mice chronically infected with four different strains of Toxoplasma gondii were examined by light and electron microscopy. In mice infected with the mouse-adapted ME49 strain for 4, 8, 12, 16 and 25 weeks, the pathological changes consisted of moderate to severe meningitis and cuffing of blood vessels by inflammatory cells. At 4 weeks post-infection (p.i.), lymphocytes were the major cell type, but at later time points, plasma cells predominated. Large numbers of cysts were observed at between 4 and 12 weeks p.i., with a decrease being seen at 16 weeks p.i. Microglial nodules, many containing tachyzoites or bradyzoites, were present at all time points. In contrast, the three strains isolated from patients with the acquired immune deficiency syndrome (AIDS) resulted in no meningitis in two cases (DEY, DAG) and in mild meningitis in one case (WIL), although all three showed some cuffing of blood vessels. In addition, only very low numbers of cysts and nodules were observed. Ultrastructurally, the cysts of all four strains were seen to be located within host cells. The cysts of the ME49 strain differed from those of the other strains in that a proportion contained immature and dividing bradyzoites at all time points, whereas those of the other strains contained only mature bradyzoites. From the observation of nodules with parasites and cysts with immature zoites, it would appear that the ME49 strain may result in an unstable chronic infection with a continuous turnover of cysts, a feature that should be taken into consideration when this strain is used as an experimental model of chronic toxoplasmosis.