Pathogenesis and transfusion risk of transmissible spongiform encephalopathies

The genesis (and pathogenesis) of sporadic and familial forms of human transmissible spongiform encephalopathy (TSE) is unknown, but the disease process may originate spontaneously in the brain as a statistically random event involving misfolding and amyloid formation of the "prion" protein. The pathogenesis of environmentally acquired TSE depends on the route of infection and is likely to involve both neural and haematogenous paths of neuro-invasion. Blood infectivity is well documented in experimental rodent models of TSE and in natural scrapie infections, but has not yet been proved to occur in humans. The knowledge that many plasma pools have included donations from individuals who later died of sporadic Creutzfeldt-Jakob disease (sCJD), together with the failure to identify any affected recipients, implies that the risk is either negligible or absent. In sharp contrast, two out of 26 recipients of labile blood products from individuals who later died from the variant form of CJD (vCJD) have became infected, and the still-living at-risk recipients are under continuing surveillance.