Progress and limits of TSE diagnostic tools

Abstract

-Following the two "mad cow" crises of 1996 and 2000, there was an urgent need for rapid and sensitive diagnostic methods to identify animals infected with the bovine spongiform encephalopathy (BSE) agent. This stimulated research in the field of prion diagnosis and led to the establishment of numerous so-called "rapid tests" which have been in use in Europe since 2001 for monitoring at-risk populations (rendering plants) and animals slaughtered for human consumption (slaughterhouse). These rapid tests have played a critical role in the management of the mad cow crisis by allowing the removal of prion infected carcasses from the human food chain, and by allowing a precise epidemiological monitoring of the BSE epizootic. They are all based on the detection of the abnormal form of the prion protein (PrP Sc or PrP res ) in brain tissues and consequently are only suitable for post-mortem diagnosis. Since it is now very clear that variant Creutzfeldt-Jakob disease (vCJD) can be transmitted by blood transfusion, the development of a blood test for the diagnosis of vCJD is a top priority. Although significant progress has been made in this direction, including the development of the protein misfolding cyclic amplification (PMCA) technology, at the time this paper was written, this objective had not yet been achieved. This is the most important challenge for the years to come in this field of prion research.

Modelling BSE trend over time in Europe, a risk assessment perspective

“…BSE cases identified between 2001 and 2007 in all three BSE surveillance streams (clinical surveillance, risk animals and healthy slaughter animals) were used. All positives were confirmed at the Member States' National Reference Laboratories using validated tests (OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals Chapter 2.4.6) [19,20]. Data from the three surveillance streams were merged to facilitate comparison between countries based on the assumption that the surveillance streams varied little among countries (with the exception of the UK with mainly clinical surveillance) and that rapid tests for BSE are detecting infected animals close to onset of clinical disease.…”

Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models

“…The presence of PrP res is considered to be pathognomonic of prion diseases and correlates with the presence of infectivity. All attempts to develop a diagnosis assay based on the direct detection of PrP res in blood have failed (20). The minute amount of TSE agent in blood is the most likely explanation for this failure; however, an alternative explanation is that the TSE agent in blood is associated with PK-sensitive PrP species (16).…”

Quantum dots and prion proteins

“…five kDa) of the PrP c , due to the partial degradation of the N-terminal part of the protein. 28 Immunohistochemical analysis detected intense cellular-specific PrP C staining in neurons, thymocytes and lymphocytes. PrP C was also detected in the enteric wall, pancreatic islets of Langerhans, myocardium, pulmonary alveolar sacs, renal glomeruli, and dermal epithelial cells.…”

“…31 The animal infection is too laborious and time-consuming to be used for routine high-throughput screening. 28 . It has to be noted that none of these tests is able to identify infected animal at the pre-symptomatic stage and therefore the risk of the infectious agents entering the food chain is not completely eliminated.…”