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Donor-derived infections (DDI) are an infrequent event in solid organ transplant (SOT) due to advances in screening recommendations, prophylaxis, and surveillance of common infections. However, unexpected pathogen transmission can still occur when a donor is not known to be infected prior to organ procurement, which can lead to significant morbidity and mortality in the organ recipient. Solid organ donors with central nervous system (CNS) pathogens are an uncommon but deadly source of unexpected DDI. Clinically recognizing these CNS infections in a potential deceased donor is enormously challenging as many are clinically silent or overshadowed by other confounding events. Because of this, expert panels caution against transplanting organs from decedents who die with possible or proven encephalitis of unknown etiology. In this review, we discuss the epidemiology, donor characteristics, and outcomes of cases of DDI in SOT recipients with unusual CNS pathogens, and provide a discussion on methods of identifying and reporting possible DDI with these pathogens.

The Great Masquerade: Donor-derived Infections with Uncommon Central Nervous System Pathogens