Is stage conversion the initiating event for reactivation of Toxoplasma gondii in brain tissue of AIDS patients?

Reactivation of chronic toxoplasmosis resulting in Toxoplasma encephalitis (TE) is a common event in acquired immune deficiency syndrome (AIDS) patien ts. Conversion from Toxoplasma gondii bradyzoites to tachyzoites is a prere quisite for reactivation. Until recently, the study of stage conversion in human tissue was not possible due to the lack of antibodies that recognize stage-specific epitopes after long-term formaldehyde fixation. Using the co mbination of a polyclonal anti-T. gondii antibody, the cyst-stage-specific monoclonal antibody CC2, and a tachyzoite-specific polyclonal antibody (ant i-SAG1, recombinant), we tried to demonstrate parasite differentiation in t he brain tissue of 10 AIDS patients with clinically suspected TE. Double la beling of the stage-specific antibodies enabled us to demonstrate interconv ersion between tachyzoites and bradyzoites for the first rime in human tiss ue. The study confirmed that the transformation process is nonsynchronous a nd that the manifestation of TE depends on the degree and site of tissue de struction caused by invading tachyzoites. The original source of tachyzoite s could never be located, but a few samples suggested that tachyzoites may invade by dissemination across the blood-brain barrier. Cyst rupture as the first event in the process of reactivation was not seen. We conclude that the initial site(s) of reactivation will be destroyed by tissue-destructive tachyzoites long before clinical symptoms occur.