THE PUBLIC HEALTH IMPACT OF PRION DISEASES1

INTRODUCTION Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of animal and human brain diseases that are uniformly fatal and often characterized by a long incubation period and a multifocal neuropathologic picture of neuronal loss, spongiform changes, and astrogliosis (3). Investigators believe the etiologic agents of TSEs are abnormal conformers of a host-encoded cellular protein known as the prion protein. Prion diseases do not characteristically elicit an immune response by the host, and the mechanism of brain damage is poorly understood. However, progressive neuronal accumulation of the disease-associated prions may damage neurons directly, and diminished availability of the normal prion protein may interfere with the presumed neuroprotective effect of the normal prion protein, contributing to the underlying neurodegenerative process. 1The U.S. Government has the right to retain a nonexclusive, royalty-free license in and to any copyright covering this paper. /05/$20.00 191 Annu. Rev. Public. Health. 2005.26:191-212. Downloaded from 10 Feb 2005 13:10 AR AR238-PU AR238-PU LaTeX2e(2002/01/18) P1: IBD 10.1146/ealth.26.021304.144536 by IRMO/Information Center on 03/14/05. For personal use only. 192 BELAY . SCHONBERGER Prion diseases attracted much attention and public concern after an outbreak of bovine spongiform encephalopathy (BSE) occurred among cattle in many European countries and scientific evidence indicated the foodborne transmission of BSE to humans (67, 74). Variant Creutzfeldt-Jakob disease (vCJD), the new form of human disease resulting from BSE transmission, is distinguished from the classic form of CJD by the much younger median age of affected patients, its clinical and neuropathologic features, and the biochemical properties of the protease-resistant prion protein (5, 7, 25, 72). The classic form of CJD was first reported in the 1920s, decades before the first BSE cases were identified in the mid-1980s (3). About 10%–15% of CJD cases occur as a familial disease associated with pathogenic mutations of the prion protein gene, and about 85% of classic CJD cases occur as a sporadic disease with no recognizable pattern of transmission. The stable, almost predictable, occurrence of the disease in many areas of the world, primarily in the elderly, led to the speculation that sporadic CJD may occur from de novo spontaneous generation of the self-replicating prions, presumably facilitated by somatic random mutations. Beginning in the 1970s, iatrogenic person-to-person transmission of the CJD agent was reported in a small percentage of CJD patients (12). This iatrogenic spread involved the use of contaminated corneal and dura mater grafts, neurosurgical equipment, and cadaver-derived human growth hormone. At present, the number of iatrogenic CJD cases is on the decline as a result of public health preventive measures implemented as the various modes of transmission were identified. In addition to BSE and iatrogenically transmitted CJD, another prion disease of potential public health concern in the United States is chronic wasting disease (CWD) of deer and elk. CWD in free-ranging cervids has been endemic in a tricorner area of Colorado, Nebraska, and Wyoming, and new foci of infection have been detected in others parts of the United States and the Canadian province of Saskatchewan (6). ETIOLOGIC AGENT OF PRION DISEASES Most of the earliest studies done to identify the a