Immunosuppression and toxoplasmic encephalitis: clinical and experimental aspects

Abstract

Encephalitis developing after prolonged antineoplastic therapy in two patients with Hodgkin's disease and in one with multiple myeloma was found at autopsy to be caused by toxoplasmosis. To better understand the pathogenesis of the brain lesions, ranging from microscopic foci to some having a diameter of 6 cm. and characterized by proliferation of the organisms at the margins of expanding necrosis, an animal model was studied. Similar lesions were produced in hamsters by inducing relapse of chronic latent toxoplasmosis through administration of cortisone, cyclophosphamide, or whole body irradiation, but toxic doses of nitrogen mustard and urethane did not precipitate relapse. Notably, relapsing toxoplasmosis generally involves the brain exclusively, suggesting a special susceptibility related to immune mechanisms. The roles of cells and of antibodies in immune surveillance against this chronic infection in otherwise normal hosts are considered. In man the suppression of cellular immunities by certain antineoplastic agents would seem to be decisive in causing relapse of toxoplasmosis, rather than the replacement of immunologically active cells by neoplasm. Because the infection can be controlled with sulfadiazine and pyrimethamine, a high index of suspicion is essential to detect incipient cerebral toxoplasmosis. serial serologic testing is helpful by demonstrating titer elevations; however, poor antibody production or transferred antibody may be misleading clinically when single tests are evaluated. Similarly, a poor inflammatory cell response can make it difficult for the histopathologist to detect small lesions in these patients.