The zoonotic potential of animal prion diseases

Bovine spongiform encephalopathy (BSE) is the only animal prion disease that has been demonstrated to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans. The link between BSE and vCJD was established by careful surveillance, epidemiologic investigations, and experimental studies using in vivo and in vitro models of cross-species transmission. Similar approaches have been used to assess the zoonotic potential of other animal prion diseases, including atypical forms identified through active surveillance. There is no epidemiologic evidence that classical or atypical scrapie, atypical forms of BSE, or chronic wasting disease (CWD) is associated with human prion disease, but the limitations of the epidemiologic data should be taken into account when interpreting these results. Transmission experiments in nonhuman primates and human PrP transgenic mice suggest that classic scrapie, L-type atypical BSE (L-BSE), and CWD may have zoonotic potential, which for L-BSE appears to be equal to or greater than that of classic BSE. The results of in vitro conversion assays to analyze the human transmission barrier correlate well with the in vivo data. However, it is still difficult to predict the likelihood that an animal prion disease will transmit to humans under conditions of field exposure from the results of in vivo or in vitro experiments. This emphasizes the importance of continuing systematic surveillance for both human and animal prion diseases in identifying zoonotic transmission of diseases other than classic BSE.