How Animal Prions Cause Disease in Humans

Abstract

The transmissible spongiform encephalopathies (TSEs) would seem unlikely candidates for animal disease agents that cross species barriers to cause disease in humans. TSEs are a group of rare but fatal neurodegenerative disorders in which neuronal vacuolation and cell loss within the brain lead to the characteristic spongiform changes, namely holes in the brain, which give the diseases their name. Even within a species, they are notoriously difficult to transmit via oral or other peripheral routes. Usually only transmission via direct inoculation of TSE infectivity into the brain, hardly a natural route of exposure, is very efficient at inducing disease. Additionally, even though the prototypic animal TSE, scrapie in sheep, has been recognized since the 1730s, there has never been any evidence to suggest that sheep scrapie could infect humans and induce a human TSE disease such as Creutzfeldt-Ja-kob disease or Gerstmann-Straussler-Schienker syndrome (Table 1). What, then, has changed to add TSEs to the list of animal diseases which pose a significant threat to human health?