Infectious and Sporadic Prion Diseases.

Abstract

Prion diseases are progressive fatal encephalopathies characterized by a neurodegenerative pathology, the tissue deposition of abnormally folded prion protein and, in general, potential transmissibility. Creutzfeldt-Jakob disease (CJD) is the commonest human prion disease and occurs in three principal forms: sporadic (idiopathic), acquired (infectious), and inherited (genetic). This chapter concerns the sporadic and acquired forms. Sporadic CJD occurs worldwide and affects mainly the middle aged and elderly. There are recognized genetic risk factors-most importantly the PRNP-129 polymorphism. The acquired forms of CJD consist of iatrogenic CJD (accidental transmission of CJD via medical or surgical procedures) and variant CJD (vJCD) (which originated as a zoonosis via bovine spongiform encephalopathy (BSE)-contamination of human food). The main causes of iatrogenic CJD are cadaveric-derived human growth hormone treatment and dura mater surgical grafts. The PRNP-129 polymorphism has important effects on iatrogenic infection, including overall susceptibility and incubation period. vCJD, resulting from dietary exposure to BSE, has affected mostly the United Kingdom, followed by France. All tested cases were originally PRNP-129MM, although two MV cases have been identified recently (one possible; one definite). vCJD has been secondarily transmitted via blood transfusion and a blood product. There is continuing concern over secondary transmission since there is evidence-from lymphoreticular tissue studies-of extensive subclinical infection in the UK general population, although a further recent study has caused uncertainty over the significance of the previous studies. While definitive diagnosis of CJD is pathological, recent developments in protein amplification and detection have led to significantly better clinical diagnosis.