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From: TSS ()
Subject: Re: BSE transmitted between sheep
Date: August 17, 2005 at 7:05 am PST

In Reply to: BSE transmitted between sheep posted by TSS on August 16, 2005 at 6:22 pm:

BSE and sheep contingency options stakeholder workshop - 16 June 2005
Monday, 23 May 2005

In December 2004 the Board of the Food Standards Agency began a review of the approach the Agency would take in the event of finding BSE in the present day UK sheep flock.

In deciding the way forward the FSA would like to invite stakeholders to contribute to the review of the options available.
A copy of the Board discussion paper on the topic, setting out the various options under consideration, is attached for information.

The Board’s aim is to ensure that the BSE controls are based on latest scientific knowledge and that any response to the discovery of BSE in sheep is proportionate.

Stakeholders will be able to contribute to the consideration of options through two mechanisms:

At a workshop

Through written submissions
Objectives of the workshop

The objectives of the workshop are:

To review the 4 options under consideration

To assess the advantages, disadvantages and proportionality of the options from the perspective of different stakeholders

To allow stakeholders to understand each others perspectives

To assess whether there may be a consensus across stakeholders to narrow the range of options under consideration
Participants will be drawn from across all stakeholder groups.

The workshop will be hosted by Alan Harvey, head of the FSA’s division responsible for BSE policy. It will include presentations on risk assessment, potential economic impact and the practicality of the various options under consideration to help inform stakeholders and aid subsequent discussion.

The workshop is being arranged for 16 June (probably 10am to 4 pm) and will be held in the Agency’s offices in Kingsway in Central London.

It is not intended to discuss BSE and goats at this workshop. Following the finding of BSE in a French goat in January, the EC has stepped up testing across Europe to show if the French case is an isolated one. EFSA has been asked for a risk assessment to be prepared for mid summer and it would be premature to discuss the issue further until the result of this is available.

If your organisation would like to participate in the workshop, could you please complete and return the attached expression of interest form to the address indicated. Depending on the level of interest shown, numbers may have to be restricted. If this is the case, places will be allocated so as to maintain a balance of stakeholder interests represented.

If you are unable to attend or are not allocated a place, but would still like to contribute, we would welcome your written comments and these will be fed into the workshop discussions. It would be helpful to have your written contributions by 10 June.

Could you please return your completed forms by Tuesday 31 May. We will let you know as soon as possible after this date whether or not you have been allocated a place at the Workshop.

I look forward to hearing from you.

Yours faithfully

Chris Walding
TSE Division

Workshop application form
PDF version - 22KB

http://www.food.gov.uk/bse/bsesheepbranch/bsesheepwkshop

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.

http://www.defra.gov.uk/animalh/bse/bse-publications/seac/DNVReport.pdf

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.

http://www.defra.gov.uk/animalh/bse/bse-publications/seac/mins21-11-01.pdf

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.

http://www.defra.gov.uk/animalh/bse/bse-publications/audit/ukasrept.pdf

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.

http://www.defra.gov.uk/animalh/bse/bse-publications/audit/risksol.pdf

RESPONSE TO THE UKAS REPORT
FROM THE
INSTITUTE FOR ANIMAL HEALTH

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.

http://www.defra.gov.uk/animalh/bse/bse-publications/audit/response.pdf

http://www.defra.gov.uk/animalh/bse/index.html

http://www.mad-cow.org/00/jul00_dont_eat_sheep.html

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

http://www.socgenmicrobiol.org.uk/JGVDirect/18580/18580ft.pdf

TSEs TRANSMISSION STUDIES

what a coincedence , CONVENIENTLY, MORE FLUBBED UP BRAINS;

HOUND STUDY

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...

http://www.bseinquiry.gov.uk/files/sc/seac19/tab07.pdf

HOUND SURVEY (about 72 pages)

http://www.bseinquiry.gov.uk/files/mb/m11a/tab08.pdf

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.

snip...

IN CONFIDENCE

A STUDY AIMED AT DETERMINING WHETHER OR NOT THERE
HAVE BEEN SIGNIFICANT CHANGES IN THE NEUROPATHOLOGY OF
SCRAPIE IN SHEEP AND GOATS DURING THE LAST TWO DECADES IN
MATERIAL SUBMITTED TO CVL PATHOLOGY DEPARTMENT

http://www.bseinquiry.gov.uk/files/sc/seac24/tab03.pdf

EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP

http://www.bseinquiry.gov.uk/files/sc/seac25/tab05.pdf

THE RISK OF TRANSMISSION OF BSE TO SHEEP VIA FEED

http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf

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."

'NOT'...tss

http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf

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

THE EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP

http://www.bseinquiry.gov.uk/files/sc/seac33/tab02.pdf

a) Summary of transmission studies. b) Update

http://www.bseinquiry.gov.uk/files/sc/seac33/tab03.pdf

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...

http://www.bseinquiry.gov.uk/files/mb/m09/tab01.pdf

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.

snip...

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.

snip...

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...

http://www.bseinquiry.gov.uk/files/mb/m09/tab11.pdf

IN CONFIDENCE

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

http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

BSE TRANSMISSION STUDIES

http://www.bseinquiry.gov.uk/files/sc/seac18/tab02b.pdf

Furthermore, we showed that
the strain responsible for iCJD is closely related to that of one
patient with sCJD, and, more unexpectedly, that these agents were
similar to the French scrapie strain studied (but different from the
U.S. scrapie strain). This finding requires a cautious interpretation
for several reasons, not least because of the inevitably limited number
of TSE strains that can be studied by such a cumbersome method as strain
typing. Nonetheless, it also prompts reconsideration of the possibility
that, in some instances, sheep and human TSEs can share a common origin.

snip...

http://www.pnas.org/cgi/content/full/041490898v1

STATEMENT OF DR HELEN GRANT MD FRCP
ISSUED 13/05/1999

BSE INQUIRY

http://www.bseinquiry.gov.uk/files/ws/s410.pdf
http://www.bseinquiry.gov.uk/files/ws/s410x.pdf

http://www.bseinquiry.gov.uk/evidence/ws/ws8.htm

TSS



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