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From: TSS ()
Subject: SEAC 87th meeting on Thursday 21st April 2005
Date: April 14, 2005 at 11:02 am PST

-------- Original Message --------
Subject: SEAC 87th meeting on Thursday 21st April 2005
Date: Thu, 14 Apr 2005 13:07:15 -0500
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@KALIV.UNI-KARLSRUHE.DE


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


Agenda


87th meeting on Thursday 21st April 2005

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

Item No

Time

Item

Presenter

Paper No.

1

10:15

Chairs introduction

SEAC Chair


2

10:25

Approval of draft minutes from SEAC 86 and matters arising

SEAC Chair

87/1 (255 KB)

> 14. The cause of sCJD is unknown. It occurs worldwide with an
> incidence of about 1 case in 1 million people per annum. The
> disease presents as a number of distinct isotypes differentiated by
> clinical features and neuropathology. Most cases of sCJD occur in
> the elderly usually with a short duration of illness but there are
> large ranges in the age of onset and duration of the disease.
> Individuals homozygous at codon 129 of the PrP gene (ie. the M/M
> genotype), are over-represented in sCJD cases compared with the
> general population.


> 15. In contrast, vCJD usually occurs in younger people (20-30 years of
> age) although there is an overlap in the range of age of onset with
> sCJD. All clinical cases of vCJD have been of the M/M genotype
> although infection was found in a single asymptomatic individual of
> non-M/M genotype probably infected as a result of a blood
> transfusion. The possible phenotype of BSE infection in non-M/M
> human genotypes is unclear.

>> Individuals homozygous at codon 129 of the PrP gene (ie. the M/M
>> genotype), are over-represented in sCJD cases compared with the
>> general population.
>


SO what the hell does this mean, has nvCJD already been documented
but yet gone ignored in what few case of CJD that have been surveyed and
confirmed in the USA ??? ...TSS

======================

continued;

20. Asked whether a shift in the age distribution of sCJD cases had
been observed in recent years, Professor Ironside confirmed that
no shift had been observed. One member suggested that a
comparison of the DNA sequence of the PrP gene from diseased
areas in sCJD cases and the PrP genotype of the affected
individual may help to determine whether the origin of the disease
was related to a somatic gene mutation or the result of protein
misfolding. Professor Ironside explained that although a limited
number of such analyses had been conducted, there was no
evidence to suggest that there were differences between the
disease associated PrP sequence and the genotype of the affected
individuals. There was insufficient evidence to rule out either a
genetic mutation, protein misfolding or

__even an acquired infection
as the possible cause of sCJD.__

snip...

23. Dr Ghani explained the significant discrepancy between the
prevalence of vCJD based on clinical cases and the tonsil and
appendix study could be resolved by inclusion of a carrier state
(i.e. subclinical infection) into models of the epidemic. Models
adjusted by inclusion of a carrier state predicted a prevalence of
infection of around 3000-5400 (depending on IHC test sensitivity)
with around 10% (95% CI 5-30%) of infected people developing
clinical disease. Additional modelling had included the possibility
of a wider genetic susceptibility such that all PrP codon 129
genotypes could be infected. In the absence of clinical data about
infection of non-M/M genotypes it had been assumed that non-M/M
genotypes would be less susceptible to infection with up to four
times longer incubation periods. If it was pessimistically assumed
that M/M and non-M/M genotypes were equally susceptible the
numbers of additional clinical cases could be up to five-fold higher
than predicted.

snip...


8
27. Professor Hooper summarised a recent report by Lasmezas et al.
(2005)2 that estimated the current BSE exposure risk to the human
population based on an oral BSE transmission study of two nonhuman
primates. The primate species had been chosen because
of the similarities of gastrointestinal system physiology and BSE
neuropathology to that found in humans. The animals were M/M at
codon 129 of the PrP gene. Following oral administration of 5g of
BSE infected brain homogenate, one animal developed clinical
disease sixty months later with a vCJD-like neuropathology.
Abnormal PrP was found in the tonsil, spleen and intestine. A
tonsil biopsy conducted on the other animal at 72 months was
negative for the presence of abnormal PrP and the animal was free
of clinical signs at 76 months. A comparison of the incubation
period with that found in another study of oral transmission of BSE
between primates, suggested a species barrier ranging from a
factor of seven to twenty for oral transmission of BSE between
cattle and primates. An extrapolation based on an infective dose
of neural tissue from a cow with preclinical BSE (below the limit of
detection of BSE tests) for oral transmission of BSE to humans
indicated about 1.5 kg of neural tissue (150 g if a species barrier
was considered not to exist) would constitute an infective dose for
humans. Such a large dose to humans was considered highly
unlikely in view of the specified risk material controls. Thus, the
control measures in place were considered effective. Professor
Hooper noted that a very small number of animals were used in the
study. Adult animals had been used so there was no indication of
2 Lasmezas et al. (2005) Risk of oral infection with bovine spongiform
encephalopathy agent
in primates. Lancet.
possible age-related susceptibility. Additionally, a single dose had
been administered thus, a minimum dose for transmission of BSE
and the effect of multiple doses could not be determined. An EU
funded dose-response study in primates was underway and would
be completed in a few years time.
28. One member noted that the findings of an intracerebral
transmission study of BSE in primates suggested that the
incubation period was significantly shorter in the single young
animal inoculated compared with the incubation time in the other
adult animals inoculated. It was unclear whether young animals
had been included in the EU primate study.

snip...

" whilst limited by, for example, the very low number and the
age of animals used, the study by Lasmezas et al. (2005)
suggests the risk of primary infection has been substantially
reduced by control measures introduced to protect the food
chain. Thus, secondary infections via medical procedures
such as blood transfusion may be the major influence on the
profile of the epidemic in the future.

snip...

61. It was noted that the incidence of BARB cases was similar to that
of sCJD. A member asked whether there might have been a low
background level of BSE prior to the epidemic. Professor Hill
considered that pre-1970, cases of BSE should have been
reported by vets if it was of a similar prevalence to BARB cases.
However, members noted that a possible confounding factor in
such historical analyses might be the number of animals that
present with BSE-like clinical signs that are subsequently not
confirmed as BSE cases on post mortem. Historically, the postmortem
level for animals was very low and thus, it would not be
possible to determine the level of historical BSE cases. Professor
John Wilesmith (Defra) added that modelling work suggested that,
under the conditions prior to the feed bans, even a single case of
BSE might rapidly give rise to an epidemic.

snip...

19
ITEM 5  BSE AND GOATS (SEAC 86/4)
66. The Chair explained that in 2002, a single healthy goat had tested
positive for a TSE as part of a French surveillance programme.
Following further tests, including bioassays, a diagnosis of BSE
was confirmed by the Community TSE Reference Laboratory in
January 2005. Recently a possible case of BSE had also been
reported in Scottish goat killed in 1990.
67. Mr Alan Harvey (FSA) informed the committee that of 140 000
goats tested in the EU since 2002, 111 animals had tested positive
for TSEs. Following the finding of BSE in a French goat, the EU
had recommended testing of goats over 18 months of age intended
for the human food supply. In the UK, all goats over 18 months of
age intended for human consumption would be tested on
slaughter. The European Food Safety Authority (EFSA) would
undertake a risk assessment on consumption of goat meat later in
the year that may inform risk management options such as
extending specified risk material (SRM) controls. In view of recent
EFSA advice issued in November 2004 that milk and milk products
from goats are unlikely to present a risk provided milk is sourced
from clinically healthy animals, FSA is not advising against the
consumption of goat meat and diary products. In the light of the
recent finding of possible BSE in a UK goat, FSA wished to ask
SEAC if there was further advice it should impart to consumers and
what further information could be collected that might inform the
20
possible food safety risks. SEAC advice would be provided to
EFSA.
68. Dr Hope described the case of possible BSE in the Scottish goat.
A three year old male goat born in 1987 had shown clinical signs of
TSE in 1990. Histological analysis at the time confirmed the
diagnosis as a TSE, at that time assumed to be scrapie. Following
the recent confirmation of BSE in the French goat, historical
samples of TSE in goats, including the Scottish goat, were
analysed as part of the evaluation of an IHC method to distinguish
BSE and scrapie in goats.
69. Dr Hope explained the basis of the IHC test and provided an
overview of the test results. IHC data of a sample from the
Scottish goat were indistinguishable from that of experimental BSE
in goats leading to a diagnosis of possible BSE. Although the
samples were obviously from a small ruminant, and records kept
by the goat owner, the vet and the original histologist were
comprehensive, tests were underway to confirm that the sample
originated from goat. Brain tissue from the goat had been retained
for future research that could include bioassays.
70. Dr Hope informed the committee that a search of VLA archives for
samples from TSE goat cases had identified 10 cases of TSE
infection between 1984 and 1990. Nine out of the ten cases were
indistinguishable from scrapie by IHC. However, in one case, a
goat killed in 1984, the IHC results did not rule out BSE and would
be further investigated. Additionally, a request made to UK
veterinary schools for archived tissues of TSE cases in goats
revealed that samples from a further 24 cases going back to 1976
were available for investigation.
71. Members agreed that on the basis of the data presented, the TSE
case in the Scottish goat was very likely to be BSE. Members
recommended further investigation of this case and other suspect
cases of BSE in goats, including strain-typing bioassays possibly in
parallel with some non-BSE like TSE goat cases.
72. Members asked if abnormal PrP had been found in the lymphoid
tissue of the goat as this would provide additional information
about the infectivity of goat tissues. Dr Hope indicated that all the
available viscera had been tested by IHC and none had given a
positive on IHC testing, although this negative result was not
conclusive because of ante-mortem damage to the tissues4.
4 Notes added post-meeting by VLA
21
73. Members were informed that feed records kept by the goat owner
indicated that the Scottish goat had been fed calf weaning mixture,
which had subsequently been highly implicated in the transmission
of BSE. The committee considered that this was the likely route of
infection and that now MBM is no longer in use the risk of BSE
entering the current herd was low. Encouragingly, TSE infections
had not been reported in the progeny or subsequent generations of
the BSE infected goat.
74. The Chair asked if a theoretical maximum prevalence of BSE in
goats could be determined based on the limits of current TSE
surveillance. Professor Wilesmith responded that because the UK
goat population was very small there are insufficient data from
surveillance to estimate an age-related TSE prevalence in UK
goats.
75. Members noted that in 2004, the UK was supposed to have tested
500 goat fallen stock for TSEs. However, only 49 had been tested.
Defra reported it had plans to increase surveillance in the UK and a
legal requirement for goat fallen stock to be tested was planned.
The committee welcomed the increased surveillance planned. A
member informed the committee that in recent years the goat dairy
industry had changed to include increasingly larger and younger
herds. In view of this change there may not be accurate
information about the UK goat population.
76. A member asked if there was evidence of TSEs in the Swiss goat
population. Dr Wilesmith informed the committee that two sheep
had been found with scrapie in Switzerland, however there is no
active surveillance of goat fallen stock in Switzerland.
77. In relation to the EFSA statement on goat dairy products, members
indicated that the nature of sheep and goat milk was different,
especially with regard to the white cell content which was higher in
goats. As there were no experimental data available on the risk of
1. The IHC test allows provisional characterisation of BSE-like
infections in small ruminants
and can be applied to CNS and lymphoreticular tissues. However, the only
tissues available
from animals with experimental BSE tissues for use as test controls were
generated by
intracerebral challenge. It should be noted that sheep (and presumably
goats) infected
intracerebrally with TSE agents do not show a wide visceral distribution
of infection specific
PrP.
2. The UK goat with a BSE-like infection had a limited range of samples
of viscera available
for IHC. Unfortunately, both the spleen and the lymph nodes showed
ante-mortem damage
and in neither of the available samples of lymphoid tissue could
secondary follicles of
germinal centres be clearly recognized. Although IHC was carried out on
these tissues, due
to the poor quality of the samples, the possible presence, distribution
and nature of potential
peripheral disease specific PrP could not be determined.
BSE in goats milk some caution was expressed in trying to
extrapolate from studies on sheep or cows milk. The committee
concluded that there is currently no evidence for a risk from goats
milk, primarily because there is no evidence for BSE in the current
goat flock, although a risk cannot be excluded as surveillance in
goats has been limited.
78. Members considered the risks from goat meat and meat products.
Members asked if SRM controls included halal slaughter. The
committee was informed that these controls are rigorously
enforced by the Meat Hygiene Service, regardless of the method of
slaughter.
79. The committee concluded that there was no evidence of BSE in
current goat herds, but that this could not be excluded until further
surveillance results are assessed. The risk from consumption of
goat meat and meat products was therefore likely to be very low,
particularly in the light of SRM controls. The committee concluded
that on the basis of current evidence it was reasonable for the FSA
to continue to not advise against the consumption of goat meat or
dairy products. However, SEAC recommended a watching brief
should be kept and further information should be considered as it
accrues.

3

10:35

Current issues

SEAC Chair

4

10:45

Early phase of vCJD infection in recipients of blood transfusions

Dr Marc Turner (NBS)

87/3 (54 KB)

1
Background
2. As a pre-symptomatic diagnostic test for vCJD is currently not
available, blood, bone, tissue or organ donors with a sub- or preclinical
vCJD infection cannot be identified prior to donation.
3. Two cases of vCJD infection in recipients of blood from blood
donors that subsequently developed vCJD suggest that the
disease may be transmitted between individuals by blood
transfusion prior to development of clinical disease in the donor1,2.
Experimental evidence of BSE transmission via blood transfusion
from infected asymptomatic donor sheep to BSE-free recipient
sheep supports the possible transfer of infection by this route3,4.
4. There have been no definite or suspected cases of vCJD
transmission between humans via bone, tissue or organ
1 Llewelyn et al. (2004) Possible transmission of variant
Creutzfeldt-Jakob disease by blood
transfusion. Lancet 363, 417-421.
2 SEAC statement on the second presumed case of blood transfusion-
associated infection
with vCJD (2004).
3 Houston et al. (2000) Transmission of BSE by blood transfusion in
sheep. Lancet 356, 999-
1000.
4 Hunter et al. (2002) Transmission of prion disease by blood
transfusion. J. Gen. Virol. 83,
2897-2905.
transplantation. However, epidemiological evidence of iatrogenic
transmission of sCJD5 suggests that there is a potential risk of
vCJD transmission via some surgical procedures. ...snip...end


Greetings,

something to ponder :

WE always hear without proof
that sCJD is not a threat to the blood supply, even though old
studies show different, but my point is, IF as the state here;

> However, epidemiological evidence of iatrogenic
> transmission of sCJD5 suggests that there is a potential risk of
> vCJD transmission via some surgical procedures.


then why is there NOT the same risk for sCJD via blood,
especially considering of the multiple strains of sCJD there may be? and
im thinking accumaltion and whatever threshold factor there may be,
and what that might be, to
clinical disease...are ya confused yet...TSS
=====

Discussion
19. In the absence of robust and direct data it could be assumed that
the vCJD agent is widely distributed within the body in the first 24-
48 hours following a blood transfusion but may not necessarily
have sufficient time to replicate to a significant extent in that time.
Thus, the infectivity level in a particular tissue/organ shortly after
transfusion of infected blood may be dependent predominantly on
some or all of the following factors:
12 Kimberlin and Walker (1990) Intraperitoneal infection with scrapie is
established within
minutes of injection and is non-specifically enhanced by a variety of
different drugs. Arch
Virol. 112, 103-114.
13 e.g. Daude (2004) Prion diseases and the spleen. Viral Immunol. 17,
334-349.
14 Heikenwalder et al. (2005) Chronic Lymphocytic Inflammation Specifies
the Organ Tropism
of Prions. Science. 307, 1107-1110.

7
" type of tissue/organ
" possible clearance of infectivity
" possible infiltration and retention of the vCJD agent in
the tissue/organ
" blood content of the tissue/organ
" infectious dose in the transfused blood
20. Compared with the original infectious dose in the transfused
blood, the infectious dose in a particular tissue/organ removed for
transplantation could be significantly diluted after distribution of
the infectious dose in the body. The infectious dose could be
further diluted if the tissue/organ is washed to remove a
proportion of the infectious blood/plasma prior to transplantation.
Thus, because of the possible dilution of the infectious dose, the
risk of transmission of vCJD to a recipient of a tissue/organ
shortly after a blood transfusion may be lower compared with the
transmission risk to the tissue/organ donor that received the
blood transfusion.
21. By comparison, in a historic recipient of infected blood, the factors
that determine the possibility of a particular tissue/organ being
infective (on transplantation) may be somewhat different. The
infectivity level in a particular tissue/organ may be dependent on
some or all of the following factors:
" type of tissue/organ
" ability of that tissue/organ to replicate/accumulate
infection
" stage of incubation (i.e. the time for replication and
disease progression)
" infectivity in the blood and the blood content of the
tissue/organ
Summary
22. Due to the paucity of relevant data, it is not possible to quantify
the possible levels of infectivity in the tissues/organs of perioperative/
peri-mortem and historic recipients of transfusions of
infected blood. However, different sets of factors may influence
the level of infectivity in tissues/organs in these two groups of
blood recipients.
Advice sought from the committee
23. The committee is asked to comment and consider whether a
scientific distinction can be drawn between historic and recent
(within the 24-48 hour period prior to donation) blood recipients in
terms of the relative likelihood of passing on infection through
bone, tissue or organ transplantation.
24. Is the committee aware of further information relevant to the
discussion on the dissemination of vCJD infectivity in the first few
days following blood transfusion?
25. It is envisaged that a short statement will be produced on the
basis of the committees consideration of this issue. ...

snip...end


87/3 annex1 (12 KB)

DNV Consulting. Risk assessment of exposure to vCJD infectivity
in blood and blood products (2003)
Including appendix II. Infectivity in blood.
Available at:
http://www.dnv.com/consulting/news_consulting/riskofinfectionfromvariantCJDinblood.asp
87/3 annex2 (12 KB
87/3 annex3 (12 KB)
87/3 annex4 (13 KB)
87/3 annex5 (12 KB)

5

11:25

Report from the Chair of the SEAC ad hoc Epidemiology subgroup on UK
BARB cases

Professor Noel Gill (Subgroup Chair)

11:55

AOB
Papers for information
∑ Updated code of practice

∑ Web casting

SEAC Chair

87/5 *

87/6 (96 KB)


12:00

END


*This paper will be tabled on the day.

On the afternoon of Thursday 21st April, SEAC will consider vertebral
column as specified risk material and the use of category 3 animal
by-products in fertiliser. These discussions will be held in a closed
session at the request of the relevant Government Departments.

http://www.seac.gov.uk/agenda/agen210405.htm

TSS

######### https://listserv.kaliv.uni-karlsruhe.de/warc/bse-l.html ##########





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