Creutzfeldt-Jakob disease: reflections on the risk from blood product therapy

Creutzfeldt-Jakob disease (CJD) was first described as a clinical entity in the 1920s, first transmitted experimentally in 1968, and first transmitted iatrogenically in 1972 (corneal transplant). Numerous experimental studies in rodents, sheep and primates have since revealed very low levels of infectivity in blood (about 1/100 000th the level in brain tissue) that can appear as early as half-way through the incubation period, with 5-10 fold higher concentrations in leucocytes than plasma. Transfused blood from individuals incubating the variant form of CJD has transmitted infection to four recipients in the United Kingdom, and several dozen other recipients remain at risk. Plasma and plasma proteins have not been implicated in any transmissions, and no instance of transmission from the blood of individuals incubating other forms of CJD has been recognized. Strategies to prevent iatrogenic transmissions include low-risk sourcing, leucodepletion, and a variety of infectivity-reducing plasma processing steps; screening tests to detect infection in preclinical donors are under development.