Bovine spongiform encephalopathy (BSE): its context in New Zealand and new tests

Transmissible spongiform encephalopathies (TSEs) such as Creutzfeldt-Jakob disease (CJD), scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) are infectious lethal pathologies of mammalian neurons. Protein alone is responsible for infectivity resulting from conversion of normal membrane protein PrPC to the infectious pathological "conformational isomer" called PrPSc, which has a different three-dimensional (3D) shape. Variations in the 3D shape of PrPSc in turn result in the numerous strains of TSE such as in scrapie and CJD. Understanding this key property in molecular terms is essential to recognising and controlling TSEs. Though all TSEs are infectious and can be acquired, usually by food-borne means, human TSEs originally arise from heritable mutations in PrPC (10-15%), or sporadically for unknown reasons (c. 85%), and some of these may arise by de novo, mutation. Though not yet observed, it is possible TSEs in animals could arise from similar sporadic or de novo mutation events. Accordingly, the literature on sporadic occurrence and mutant alleles is reviewed in some detail, albeit most of such literature pertains to human TSEs. BSE, scrapie, and CWD are not present in New Zealand and surveillance is conducted using an internationally validated immuno-blot test on post mortem samples that depends on relative protease resistance of PrP in diseased tissues. To date there is no validated ante mortem test. Recently developed immuno-blot tests (CDI) can differentiate strains and subtypes of TSEs and potentially are capable of detection of disease in ante mortem blood samples and possibly in subclinical infection. An amplification methodology (PCMA) can detect minimum infectious doses but CDI and PCMA require authentic PrPSc. Animal PrP(Sc)s are statutorily excluded from New Zealand, even for development of laboratory tests, out of concern for a potential biohazard should the infectious amyloid somehow escape a containment laboratory. Alternatives for obtaining a safe local PrPSc positive control allowing adaption/development of improved tests such as ante mortem testing of subclinical infection are discussed.