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From: TSS ()
Subject: Re: Commission requests further investigations on three unusual cases of TSE in sheep
Date: March 9, 2006 at 10:25 am PST

In Reply to: Commission requests further investigations on three unusual cases of TSE in sheep posted by TSS on March 9, 2006 at 10:12 am:

-------- Original Message --------

Subject: DEFRA INVESTIGATES AN UNUSUAL SCRAPIE CASE (similar to exp. BSE in sheep)
Date: Wed, 7 Apr 2004 08:56:36 -0500
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy

######## Bovine Spongiform Encephalopathy #########

Date: April 07, 2004 Time: 13:45


The Veterinary Laboratories Agency (VLA) have informed Defra, the
Devolved Administrations and the Food Standards Agency of a type of
scrapie not previously seen in the UK.

The VLA and other European laboratories with expertise in scrapie-like
diseases have now applied several rapid diagnostic methods to tissue
samples from a sheep with suspected scrapie. Some of the methods have
indicated that the case does not appear to resemble previously
recognised cases of scrapie and, although there were differences, it had
some characteristics similar to experimental BSE in sheep and also to an
experimental strain of sheep scrapie. More importantly, though,
microscopic analysis of brain material showed that the case neither
resembled previously recognised types of scrapie or experimental BSE in

A meeting of the scientific experts who performed these analyses, held
on the 30th March, concluded that this case could not be considered to
be BSE in sheep, although it does not behave like known types of scrapie
either. Further investigation will be needed before more can be said
about how this unusual result should be described.

Defra's Chief Scientific Adviser, Professor Howard Dalton, said "The UK,
and especially the VLA, have played an important part in improving the
diagnostic methods available for identifying TSEs in sheep. As we
continue to assess more samples with these improved methods it is likely
that we will continue to find samples, such as this, which fall outside
our current knowledge of the disease. Defra, as it does with all
research, will continue to consult scientific experts to ensure that we
are investigating these cases using the best available techniques and

The National Scrapie Plan remains unaffected by this new result and SEAC
will be consulted in the near future.

Notes to editors

1. Scrapie is a fatal neurological sheep disease belonging to a group of
diseases called transmissible spongiform encephalopathies (TSEs),
including BSE in cattle and CJD in humans. It has been present in the
national flock for over 250 years. It is not considered to be
transmissible to humans.

2. There is a theoretical risk that BSE could be present in sheep,
masked by scrapie, but it has not been found naturally occurring in sheep.

3. There is as yet no definitive diagnostic method that can rapidly
distinguish between different TSEs for example scrapie from BSE.
Consequently, from time to time the scrapie surveillance programmes in
EU member states throw up unusual results that merit further
investigations (Defra press release 371/03 refers

4. The VLA have applied several different methods to the sample to
compare it to a wide range of previously detected scrapie cases,
experimental BSE in sheep and an experimental strain of scrapie, termed
CH1461. Two main methods have been used in this analysis:-

a. Western blot (WB)
This involves taking a sample of the brain and treating it with an
enzyme proteinase k to destroy the normal prion protein (PrPC). The
diseased form of the protein (PrPSc) is able to withstand this treatment
and is then separated from other cellular material on a gel. A blot is
taken of the gel and the PrPSc is visualised using specific antibodies.

b. Immunohistochemistry (IHC)
This involves taking thin slices of the brain, and by using special
(antibody) markers to detect the PrPSc it is possible to see disease
specific patterns of PrPSc distribution in the brain under a microscope.
The Western blot method found that the sample did not appear to resemble
previously recognised cases of scrapie and, although there were some
differences, some characteristics were similar to experimental BSE in
sheep and also the experimental strain of sheep scrapie, CH1461. IHC
found that it neither resembled previously recognised types of scrapie
or experimental BSE in sheep

5. The tissue sample has now been analysed using a total of 5 different
diagnostic methods claiming to be able to differentiate between scrapie
and experimental BSE in sheep. Two were performed at the VLA and three
were performed in other European laboratories.

6. The VLA is the European Reference Laboratory for TSEs and is
responsible for co-ordinating such investigations into unusual cases.
Their findings will be considered by the European Food Safety
Authority's committee of TSE experts and in the UK by the Spongiform
Encephalopathy Advisory Committee (SEAC).

7. The genotype of the suspect sheep was ARQ/ARQ which is known to be
susceptible to some strains of scrapie and, in experiments, to BSE.
Background information on scrapie, scrapie genotyping, and the National
Scrapie Plan is published on the Defra internet at

8. For information and advice on BSE in sheep from the FSA please
consult their web site at

Public enquiries 08459 335577;
Press notices are available on our website
Defra's aim is sustainable development


Nobel House
17 Smith Square
London SW1P 3JR


########### ############

TSE in Sheep Contingency Planning Assessment of Risk due to BSE
Infectivity from Disposal of Sheep A report for DEFRA November 2001

Management Summary It has been recognised for a considerable time that
sheep in the United Kingdom may have been infected with BSE. To date no
evidence has been found to demonstrate that the national flock is
actually infected with the disease. DEFRA have prepared a draft
contingency plan in the event that BSE were to be identified in UK
sheep. The worst case scenario under this plan is the disposal of the
entire UK flock, some 40 million sheep and lambs. This study has
estimated the potential exposure of the UK population to BSE infectivity
present in sheep in the event that this plan had to be put into effect.

but who would have guessed that such an important experiment/study would
have gotton so screwed up, by not being able to tell a sheep brain from
a cow brain;

© DEFRA 2002 Item 3- Scrapie Brain pool experiments- Update on current
position and audits of samples 3.1 Members were updated on experiments
conducted at the Institute of Animal Health (IAH) to examine a pool of
scrapie brains collected in the early 1990s for evidence of BSE. SEAC
had previously recommended that the material should be examined by DNA
analysis to assess whether the pooled brain material may have been
contaminated with bovine tissue. The Laboratory of the Government
Chemist (LGC) had been asked to perform the work. Their results were
completely unexpected as the analysis detected only bovine material in
the sample. SEAC had intended to meet on the 19 October to Agreed
version consider the experiment in detail. However, in view of the
result, the meeting was cancelled.

Executive Summary An audit of the sample handling procedures at IAH-E
was carried out on 24 October 2001 at the request of the Department of
the Environment, Food and Rural Affairs (DEFRA), by a team of two UKAS
auditors. The scope of the audit was limited to the traceability of cow
and sheep brain samples used in several experiments relating to
transmissible spongiform encephalopathy (TSE) agents. In particular, the
team focused on the audit trail of samples that had been sent to LGC,
Teddington, the audit trail of brains collected in 1990/92 by Veterinary
Investigation Centres and the audit trail for archived material held by
IAH-E. In addition the audit team evaluated the IAH-E procedures against
the specific requirements for sampling handling of international
standard, ISO 17025 and identified opportunities for improvement. The
audit established that there was no formal documented quality system
covering this work at IAH-E and that record keeping was inadequate to
give confidence in the chain of custody of samples used in the various
rendering, genotyping and strain typing experiments audited. It was not
possible to establish clear traceability between the samples that had
been used in the individual experiments carried out by IAH-E or IAH-C
with those analysed at LGC or with those that had been collected in
1990/92. The sample handling procedures covered by this audit at IAH-E
did not meet the requirements of ISO 17025.

explaining the brain mixup blunder;

An Investigation of the Substitution of Scrapie Brain Pool Samples A
report for DEFRA November 2001

Risk Solutions Page 19 Why did the experimenters not notice that they
were working with cow brains not sheep brains? The simple answer is
because for the most part they were working with brain pool macerate
(minced brain material) not brains. It is not credible that staff
collecting brains at VICs would have uniformly supplied cow brains or
cow brain parts in mistake for sheep. We have interviewed staff at VICs
and we understand from the VLA that records do not support the
possibility that significant numbers of cow brains were sent to PDM in
place of sheep brains. It is also very unlikely that the people
preparing the scrapie brain pool would not have noticed if they were for
the most part handling cow brains or cow brain parts in place of sheep
brains. We cannot rule out the possibility that some cow brain material
entered the brain pool at this stage but it is not feasible that the
majority of the material was bovine. The substitution, if substitution
occurred, must have involved brain pool macerate or rendered
products. Why cant the results of the experiments tell us what
material was used? The experiments had a number of features that make
the results of the mouse bioassay difficult to interpret unambiguously
and lead to the possibility that substitution of the samples would be
difficult to detect by examining the results of the experiments: 1. The
original experiments were not designed to determine whether BSE was
present in sheep. Reasonable efforts were taken to ensure that the brain
pool remained free from D5055 02 Issue 1 Risk Solutions Page 20
contamination during preparation but the level of control applied during
the earlier experiments (272R and 372R) was not to the standard applied
later. 2. Mouse bioassay as a method of diagnosing TSEs is not based on
a full understanding of biochemical and physical processes. It is an
empirical technique that has been widely applied, for example to show
v-CJD is similar to BSE and different from scrapie. It is a complex
process and the results need to be interpreted by experts. It can take
several years to generate a firm result. The principal data collected in
the experiments are lesion profiles (patterns of lesions in the mice
brains) and incubation period (time from injection of mice to onset of
clinical symptoms. The type of TSE is identified by comparing the
results with those of known provenance. There is no good agreed test
of sameness of lesion profile, so in marginal cases we are reduced to
using subjective observations of the form somewhat similar and
interpretation is difficult. The incubation times in principle give a
more objective signal, but the effect of concentration has to be
controlled. The mouse bioassay data that we understand has been
collected and analysed at each stage of the experiments is summarised in
Table 4.1. Several features of these experiments are not commonly
encountered in mouse bioassay of TSEs and this makes determining the
origin of the original material from the experimental results extremely
difficult. They include: a. Mouse bioassay is generally carried out on
individual brains; experience of working with brain pools is very
limited. b. The BBP exhibited a low titre of infectivity, which can
confound interpretation of results. c. The BBP comprised bovine brains
with the hindbrains removed. By contrast most of the BSE strain typing
has been carried out on the hindbrains, which may give a different
pattern of results. d. The 272R titrations used a different strain of
mice than the 372R titrations, so direct comparison of the resulting
lesion profiles cannot be made. e. The 246 experiments used brain pool
which was in an unsatisfactorily autolysed state. f. The strain typing
data collected (incubation time and lesion profiles) are very sparse.
Judging the sameness or difference of samples is a less challenging task
for strain typing than identifying a strain and it may be possible to
compare data from the 246 experiments with both the 272R and 372R
experiments to determine whether the samples are similar or clearly
different. However, the data are sparse and the result is unlikely to be
clear cut. Much of this work is currently unpublished.


The Institute is concerned, therefore, that the authors of this UKAS
report may have based their findings on an unrepresentative and limited
examination of procedures in place at IAH-E.

Transmission of prion diseases by blood transfusion

Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David

Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2




b) Fibrillar material closely similar to SAF, found in BSE/Scrapie, was
observed in 19 (4.3%) cases, all of which were hounds > 7 years of age.
14/19 of these suspected SAF results correlated with cases in the
unresolveable histopathological catergory...

HOUND SURVEY (about 72 pages)

Also, at paragraph 17, it is noted that BSE had transmitted to the NPU
negative line sheep (please not that as at January 1996, only one of six
challenged sheep was clinically affected after oral challenge, four
others have since died, and one remains alive. Following intracerebral
challenge, three out of six were clinically affected, two confirmed only
on pathology, while one was negative.)

4. Meeting 16, on 26/1/94 - the update on research (16/5) confirmed that
BSE had been transmitted to sheep, and that there was clinical evidence
of transmission to mice from the spleen of the affected sheep.






hell, they knew they were screwing up the sheep brains with cow brains
in 1992;

"The sensitivity of the project may be partially compromised by pooling
of brains, but it is considered that the success of transmission to mice
with BSE will prove advantageous."


Personal $ Confidential -- Addressee only TO ALL MEMBERS OF SEAC


a) Summary of transmission studies. b) Update

The only circumstance in which infection with the natural isolate
produces an higher incidence of disease compared to BSE, is in
intracerebrally (and possibly orally) challenged ''positive'' line
sheep. Notwithstanding the possibility of indigenous natural scrapie in
some of these sheep, there are still sufficient numbers of transmission
cases with PrP genotypes which preclude the natural disease developing
i.e. those typed as VA136/RR154/QR171.

As an extension to this study, it has been possible to recover BSE by
passage in mice from brain and spleen taken from ''negative'' line sheep
infected with BSAE by ic and oral challenge (Foster and others 1996).
The close similarity of incubation periods and pathology from the
passage of these tissues in mice to those seen in direct BSE
transmission studies from cattle to mice suggests that passaging BSE in
sheep does not alter its bilogical properties (Bruce and others 1994).
IN FACT, because it has been possible to isolate BSE infectivity from
ovine spleens, when this proved impossible from the spleens of naturally
infected BSE cows (Fraser and Foster 1993), experimentally-induced BSE
in sheep appears to behave more like the natural disease of
scrapie.Whether this putative similarity to natural scrapie extends to
the possibility of maternal transmission of experimentally-induced BSE
in sheep, has till to be elucidated...

we have found a link between BSE and CH1641, a C-group of scrapie.
Disease susceptibility of sheep to these isolates is associated with
different PrP genotypes compared to SSBP/1 scrapie...

Transmission of BSE in sheep, goats and mice.


BSE has been transmitted in two lines of genetically selected sheep
(differeing in their susceptibilities to the SSBP/1 source of scrapie),
and to goats by intracerebral injection AND BY ORAL DOSING.


Also, intermediate passage of BSE in sheep or goats did not alter these
primary transmission properties. Hamsters were susceptible to BSE only
after intervening passage through mice...


Perceptions of unconventional slow virus in the USA

3. Prof. A Robertson gave a brief account of BSE. The US approach was to
accord it a very low profile indeed. Dr. A Thiermann showed the picture
in the ''Independent'' with cattle being incinerated and thought this
was a fantical incident to be avoided in the USA AT ALL COSTS. BSE was
not reported in the USA...........(some good data on CWD)

> avoided in the USA AT ALL COSTS

and indeed they have and it continues today...TSS



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