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Prion diseases such as Creutzfeldt-Jakob disease represent a unique infection control problem because prions exhibit an unusual resistance to conventional chemical and physical decontamination methods. This paper reviews the recent literature and provides recommendations for the prevention of nosocomial transmission of prion agents.Recommendations to prevent the cross-transmission of infection from medical devices potentially contaminated with prions have been based primarily on prion inactivation studies. Newer recommendations consider inactivation data, but also use epidemiological studies of prion transmission, the infectivity of human tissues, and the efficacy of removing microbes by cleaning. Prion-specific disinfection/sterilization is required in only limited settings. Healthcare workers are not at risk of acquiring transmissible spongiform encephalopathies. Blood or blood products have not been demonstrated to be vehicles for transmission.On the basis of scientific data, only critical (e.g. surgical instruments) and semicritical devices contaminated with high-risk tissue (i.e. brain, spinal cord, eye) from high-risk patients (e.g. with known or suspected Creutzfeldt-Jakob disease) require special treatment.