Immunosuppression and toxoplasmic encephalitis: clinical and experimental aspects

Area of Science:

• Neuroscience
• Immunology
• Infectious Diseases

Background:

• Toxoplasmosis encephalitis is a serious complication in immunocompromised patients, particularly those undergoing antineoplastic therapy for conditions like Hodgkin's disease and multiple myeloma.
• Autopsies revealed toxoplasmosis as the cause of encephalitis in patients with prolonged antineoplastic treatment, with brain lesions varying significantly in size.

Purpose of the Study:

• To investigate the pathogenesis of toxoplasmosis-induced brain lesions in patients undergoing antineoplastic therapy.
• To establish and utilize an animal model to understand the mechanisms of toxoplasmosis relapse under immunosuppression.

Main Methods:

• An animal model was developed using hamsters to study toxoplasmosis relapse.
• Relapse was induced by administering immunosuppressive agents like cortisone, cyclophosphamide, and whole-body irradiation.
• The efficacy of nitrogen mustard and urethane in inducing relapse was also tested.

Main Results:

• Cortisone, cyclophosphamide, and irradiation successfully induced relapsing toxoplasmosis with brain lesions similar to those seen in humans.
• Toxic doses of nitrogen mustard and urethane did not precipitate relapse.
• Relapsing toxoplasmosis predominantly affected the brain, suggesting a specific susceptibility possibly linked to immune mechanisms.

Conclusions:

• Suppression of cellular immunity by antineoplastic agents is the primary driver of toxoplasmosis relapse in cancer patients.
• Early detection of cerebral toxoplasmosis is crucial, aided by serial serologic testing, though antibody responses can be variable.
• Histopathological diagnosis can be challenging due to poor inflammatory cell response in affected patients.