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From: TSS ()
Subject: BSE immunohistochemical patterns in the brainstem: a comparison between UK and Italian cases
Date: April 25, 2006 at 10:56 am PST


Acta Neuropathologica
Publisher: Springer Berlin / Heidelberg
ISSN: 0001-6322 (Paper) 1432-0533 (Online)
DOI: 10.1007/s00401-005-0012-1
Issue: Online First

Original Paper
BSE immunohistochemical patterns in the brainstem: a comparison between UK and Italian cases
C. Casalone1, M. Caramelli1, M. I. Crescio1, Y. I. Spencer2 and M. M. Simmons2

(1) CEA, Istituto Zooprofilattico del Piemonte, Via Bologna 148, 10154 Turin, Italy
(2) Department of Pathology, VLA Weybridge, Woodham Lane, KT15 3NB Addlestone, Surrey, UK

Received: 18 April 2005 Revised: 18 October 2005 Accepted: 18 October 2005 Published online: 14 April 2006

Abstract The continuous monitoring of bovine spongiform encephalopathy (BSE) cases is an integral component of European research and surveillance programmes, to ensure that any changes in the presentation of transmissible spongiform encephalopathies (TSE) in cattle can be detected and defined. Monitoring is generally limited to the brainstem at the level of the obex, for reasons of practicality, safety and cost. Demonstration of disease-specific prion protein (PrPd) by immunohistochemistry is currently the most widely used confirmatory tool for both active and passive surveillance. This study assessed PrPd immunostaining in the brainstems (obex) of cattle with BSE in the UK and Italy. Immunoreactivity ‘profiles’ were created for each case based on the nature of the immunostaining, its relative intensity and precise neuroanatomical location. This study compares the obex immunostaining patterns of Italian cases (only active surveillance) and two UK groups (both active and passive surveillance). The neuroanatomical distribution and relative intensity of PrPd was highly reproducible in all cases. The overall staining intensity varied widely but was generally stronger in the active than in the passive surveillance populations. The conclusion to be drawn from this comparative study is that the pattern of immunopathology in these routine screening samples for BSE diagnosis and surveillance is the same in the UK and Italy, whether or not the animal was displaying typical, or indeed any, clinical signs at the time of sampling. This indicates that the current confirmatory diagnostic strategy remains appropriate for active surveillance applications.
Keywords BSE - PrP - Immunohistochemistry - Surveillance - Brainstem


--------------------------------------------------------------------------------


M. M. Simmons
Email: m.m.simmons@vla.defra.gsi.gov.uk
Fax: +44-1932-357805

http://www.springerlink.com/(nr3t22ep0fbzjxewejg2q3ra)/app/home/contribution.asp?referrer=parent&backto=issue,3,21;journal,1,511;linkingpublicationresults,1:100394,1

RESPONSE TO SEAC RECOMMENDATIONS ON THE DIFFERENTIAL

DIAGNOSIS OF BSE IN CATTLE

SUMMARY

SEAC members have noted their interest in the differential diagnosis, variations in

phenotype and strain stability of BSE in cattle in view of phenotypic differences recorded in

TSE infections in humans and in sheep.

From the clinical suspect cases in cattle that are reported each year there is a proportion

that are subsequently not confirmed as positive BSE cases. The aetiology of these nonconfirmed

suspect cases includes a very long list of potential conditions and 40-60% of

cases show no significant neuropathological lesions. Given these two observations and the

limitations of veterinary clinical neurology Defra does not see a proportionate value in

attempting to arrive at a definitive diagnosis for all non-BSE suspect cases.

Notwithstanding this view, Defra would require the more detailed investigation of cases

which may give rise to a suspicion of clinical or pathological BSE variant, when sufficient

appropriate material is available. Efforts will also be maintained to optimise the clinical

screening of suspect cases to reduce the number of unconfirmed cases.

Work carried out by Defra (and previously by MAFF) on surveillance and testing of suspect

cases during the course of the BSE epidemic in cattle has not found evidence for strain

variation or change in the neuropathological or molecular characteristics of the disease.

There is scope for applying more recently developed methods retrospectively to samples

collected during the epidemic.

The disease phenotype of BSE is defined on the basis of clinical signs and post-mortem

neuropathology. The known phenotypic expression of all TSE diseases both clinically and

pathologically involves the central nervous system. Defra therefore consider that it is

appropriate to use clinical and case history together with post-mortem screening of

changes in the brain as indicators for phenotypic variation of BSE in cattle. Phenotype

discrimination can also be monitored by variations in PrPres molecular profile using

advances in immunoblotting methods that have been developed in recent years. The focus

of resources to these areas of activity is considered to be proportionate and appropriate for

the monitoring of possible changes in BSE in cattle.

It is recognised that with the falling numbers of clinical BSE cases the opportunities for

prospective study will be limited. The remaining infected animals are principally detected

through surveillance testing of cattle at slaughter. There is very little sample material

available from these cases and it is often of variable condition. Furthermore any clinical

investigation is retrospective and possibly influenced by virtue of a known diagnosis.

This paper outlines the approaches that have been taken by Defra (MAFF) during the

course of the BSE epidemic in cattle. ...

SNIP...FULL TEXT;

http://www.seac.gov.uk/papers/88-3annex1.pdf

Review of BSE strain typing

Issue

1. At their meeting held in February 2004 SEAC requested an update

on BSE strain typing results.

Background

2. Recently through surveillance of cattle and sheep in a number of

countries and application of advanced biochemical tests and

bioassays, a number of atypical cases of scrapie have emerged

together with a report of a possible new type of BSE with some

biochemical characteristics in common with sporadic CJD. In the

light of these findings a review of strain typing methods is provided to

SEAC for information.

TSE strains

3. Distinct TSE strains have been identified in mice by serially

passaging scrapie, BSE or CJD from sheep, goat, cattle and human

sources. Different scrapie strains have been characterised but so far

only one BSE strain has been apparent. Recent work by Italian

researchers (Casalone et al., (2004), presented to SEAC in February

2004) has indicated a form of bovine amyloid spongiform

encephalopathy, however studies are at an early stage. It is still not

clear what the basis of strain variation is at the molecular level,

although recent papers by King and Diaz-Avalos (2004) and Tanaka

et al. (2004) using a yeast model add weight to the hypothesis that

the infectious agent for TSEs is protein-based and that prion strains

may arise as a result of the same protein being able to adopt a range

of different shapes or ’conformations’.

What is strain typing?

snip...

Studies in transgenic mice expressing human PrP methionine at codon

129 by Asante et al. (2002) indicated that BSE transmission to these

mice, in addition to producing a vCJD-like phenotype, could also give

rise to a distinct molecular phenotype indistinguishable from that of

sporadic CJD with PrPsc type 2. Further studies in transgenic mice may

further our understanding of prion strains and their propagation. A

number of projects have been funded to examine strain typing, a list of

those funded by Defra is attached at Annex 6 for information.

References

snip...

full text ;

http://www.seac.gov.uk/papers/seac82_4.pdf

TSS




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