NR AWGE
AU Groschup,M.H.; Hoffmann,C.; Ziegler,U.; Buschmann,A.
TI On the search for an in-vivo test for human and animal TSEs
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-43
PT Konferenz-Vortrag
AB Transmissible spongiform encephalopathies have received considerable attention because of the huge BSE epidemic which affected more than 185.000 clinically and fatally diseased bovines. It has been estimated that roughly 3 million infected animals that were still in the preclinical state were slaughtered and entered the human food chain in the United Kingdom and elsewhere. Transmission of BSE prions to man has eventually caused a variant form of Creutzfeldt-Jakob disease in more than 170 humans primarily in the UK, but also in France, Italy, Japan and elsewhere. As a preventive measure in the European Union the risk of human BSE exposure is minimized by BSE rapid testing of all cattle >30 months of age and by the removal of specified risk materials from slaughter cattle which are considered to possibly contain BSE infectivity in incubating animals. Diagnostic tests for TSEs can generally be divided into ante- (or in-vivo) and post-mortem tests. The term in-vivo diagnostic tests implies the ante-mortem diagnosis of preclinical TSE infections in humans and animals. These tests are based on the detection of abnormal prion protein in bodily fluids or easily accessible tissues (e.g. lymphatic tissue biopsies). Other tests rely on the detection of surrogate markers which are indicative for a dysfunctions in the homeostasis of the body or for cellular degenerative processes. However, depending on the species, the genetic background of the individuum and/or on the prion strain involved, there may be considerable differences in the detectability of these markers in preclinical animals. For example in variant CJD in humans, abnormal prion protein can already been found in lymphatic organs during the incubation time, while in other human prion diseases such a strong lymphotropism of the infectious agent has not been reported. In sheep, the prion spread and distribution has been thoroughly studied in the past using animals carrying the ARQ or VRQ alleles of the prion protein (PrP). In such animals BSE and scrapie PrPsc are deposited in the lymphoreticular system from early after the infection. However, the TSE pathogenesis largely depends on the PrP genotype, i.e. no such pronounced depositions are observed in sheep carrying the PrPARR allele. To elucidate the still unknown pathogenesis of bovine spongiform encephalopathy (BSE), we have carried out an oral BSE challenge and sequential kill study on 56 calves. Our results demonstrate that BSE prions spread from their primary entry site, the Peyer's patches in the distal ileum, via the autonomous nervous system to the central nervous system (CNS) with essentially no further involvement of the lymphoreticular system. Moreover, BSE associated abnormal prion protein (PrPsc) was already detected in the brainstem of an animal 24 months post infection, which is 8 months earlier than reported before. For the development of a functional in-vivo test for TSEs in humans and animals it is therefore of crucial importance to take the species specific and the prion strain specific as well as the genetic effects into consideration.
AD Friedrich-Loeffler-Institut (FLI), Institute for Novel and Emerging Infectious Diseases, Insel Riems, Germany
SP englisch
PO Italien