To: fdadockets@oc.fda.gov
CC: Freas@cber.FDA.gov
Greetings FDA,
I would kindly like to make a submission to Federal Docket Docket
#03-025IF -- Docket #03-038IF and
Docket #01-033DF -- TSS SUBMISSIONS -- USDA ISSUES NEW REGULATIONS
TO ADDRESS BSE
With regards to the 30 months of age or older rule;
There have been several cases of clinical BSE in British
cattle under 30 months and it is therefore hardly possible to think
that cattle under 30 months have virtually no risk of having BSE.
In 1988 the youngest British BSE case was 24, the second youngest
27 months old. In 1989 the youngest British BSE case was 21 and there
were 4 cases only 24 months old. In 1990 there were two cases only 24
and one 26 months old. In 1991 the youngest British BSE case was 24
and there were 3 cases only 26 months old. In 1992 the youngest British
BSE case was 20!, the second youngest 26 months old. In 1993 there was
was a 29 months old case, in 1995 the UK had a 24 months old case and
in 1996 one British BSE case was 29 months old.
http://www.defra.gov.uk/animalh/bse/bse-statistics/bse/yng-old.html
personally i think every cow going to slaughter for human/animal food
consumption should be tested, now with that said, let us be a bit more
realistic.
testing should start where they can hope to find most detectable cases, not
start where the probability of finding anything is extremely low, i.e.
1, 2, 3 month
old calves etc.
The Prusiner method has, to my knowledge, not been validated 'in the
field'. It would of course be interesting if the Prusiner method really
is more sensitive than Biorad. This should first be proved under field
conditions.
The USA has only one test lab for BSE !!! First they have to validate
more labs, teach a lot of technicians how to do Biorad and/or Prionics
or Prusiner's test.
Venemann and DeHaven may tell a lot of crap. However, the statement that
"the illness does not usually show up in animals under 30 months" is
_quite true_. Especially today, when even the UK finds BSE on very old
animals.
If the USA had a BSE-prevalence anything near the UK-prevalence of the
peak years 92-93, even the USDA would have found it long before 2003!!!
But I would not be at all surprised if the USA has a BSE-prevalence of
the same order as Germany, or even worse. I think it is very very
improbable that North America would have "one case only", such as
Finland and Austria where only one case (each) has been found since 2001.
Asking the USDA today to test all cattle from 20 months and older would
be totally unrealistic, if only for reasons of low lab capacity... First
they have to test the most risky groups (downers, dead on farm and old
healthy animals) and then they might take the problem more seriously
if/when they find other BSE-cases - Only if they do find other cases
will they possibly start testing younger cattle.
Remember that USA already test clinical suspects and downers from 20-24
months. US consumers should first fight to make USA test all downers +
many older "healthy cattle".
What does _anybody_ know about 'new' BSE-types ? Only Japan has had only
one atypical case in a young cattle. Italy and France have had very few
atypical cases in very old cattle (please see
new data out from France about new 'atypical' cases, please see at end
of this submission)
What they should do, to protect consumers, is to lower the age limit for
SRM to 12 months for brain, spinal cord etc...
Today Canada and USA have chosen an age limit of 30 months (?) for SRM,
which is much too high, and will not protect against infection by young
cases, whether atypical or classical.
Remember that the most efficient means of protecting consumers is not
the BSE-test program, but the separation and destruction of SRM, and the
prohibitions of ARM from vertbral columns and pneumatic
stunning/pithing. (powerful stun guns that shoot 4-inch bolts into a
cow’s skull prior to slaughter can also drive brain tissue into the
animal’s lungs and throughout its body , thus contaminating meat that
ends up in the supermarket with potentially infective brain tissue.
Garland et al (1996). “Brain emboli in the lungs of cattle after
stunning,” Lancet 348(9027), p. 610.).
The test program, even if up to European or Japanese standards, will not
find all positive animals, because the PrP-res level in the brain stem
will be below detection level in some animals that have not incubated
long enough.
Active surveillance aims at finding out the _prevalence_ of BSE in a
country, see how widespread the problem is, eventually find out if there
are geographic variations, and increase or decrease of prevalence over
time. Indirectly, it will also protect the consumer by removing positive
animals and their feed cohort mates + offspring from the food chain.
ALSO, considering that the USA, Mexico and Canadian cattle and feed are
so integrated,
I think it only appropriate to comment on this below;
Premier Ralph Klein said on Tuesday Alberta may test all cattle
slaughtered at a
provincial facility for BSE in an effort to restore international
confidence in its
beef industry.
IF this means all cattle period, going to slaughter for human/animal food,
it would be the smartest thing Klein has done. The ruminant to ruminant
feed ban (partial and voluntary), that was put into effect on 8/4/97, was
a half @ss measure, that has not been enforced or adhered too, SO,
in my humble opinion, this statement and potential action;
> The system will focus on animals that were born before 1997
would be another half @ss measure, and in my opinion would be a
grave mistake. ALL one has to do is look at the BABs (Born After the
(feed) Ban) in the UK;
14 November 2003
* BSE has been diagnosed in a cow born in October 1996; an
announcement[pdf file] is available.
http://www.defra.gov.uk/animalh/bse/animal-health/19-10-1996.pdf
* BSE has been diagnosed in a cow born in February 1997; an
announcement[pdf file] is available.
http://www.defra.gov.uk/animalh/bse/animal-health/13-02-1997.pdf
* BSE has been diagnosed in a cow born in August 1996; an
announcement[pdf file] is available.
http://www.defra.gov.uk/animalh/bse/animal-health/17-08-1996.pdf
* BSE has been diagnosed in a cow born in October 1996; an
announcement[pdf file] is available.
http://www.defra.gov.uk/animalh/bse/animal-health/12-10-1996.pdf
* BSE has been diagnosed in a cow born in June 1997; an announcement[pdf
file] is available.
http://www.defra.gov.uk/animalh/bse/animal-health/12-06-1997.pdf
* BSE has been diagnosed in a cow born in September 1999; an
announcement[pdf file] is available.
http://www.defra.gov.uk/animalh/bse/animal-health/19-09-1999.pdf
http://www.defra.gov.uk/animalh/bse/bse-statistics/bse/bab2.pdf
more here;
06 October 2003 - BSE has been diagnosed in a cow born in January 1997;
an announcement[pdf file] is available.
02 October 2003 - BSE has been diagnosed in a cow born in November 1998;
an announcement[pdf file] is available.
30 September 2003 - BSE and Offspring Cull compensation rates have been
announced for October.
23 September 2003 - BSE has been diagnosed in a cow born in September
1997; an announcement[pdf file] is available.
19 September 2003 - A ninth BARB case has been found in Northern
Ireland. The cow was born in December 1997.
and more here;
20 August 2003 - BSE has been diagnosed in a cow born in August 1997; an
announcement[pdf file] is available.
13 August 2003 - An eighth BARB case has been found in Northern Ireland.
The cow was born in November 1996.
12 August 2003 - Food Standards Agency seeks views on amendment to TSE
regulation[external website] - FSA website.
04 August 2003
* BSE has been diagnosed in a cow born in April 1998; an
announcement[pdf file] is available.
30 July 2003
* BSE has been diagnosed in a cow born in November 1997; an
announcement[pdf file] is available.
* BSE has been diagnosed in a cow born in April 1998; an
announcement[pdf file] is available.
23 July 2003 - A seventh BARB case has been found in Northern Ireland.
The cow was born in March 1999.
22 July 2003 - BSE has been diagnosed in a cow born in May 1997; an
announcement[pdf file] is available.
18 July 2003 - BSE has been diagnosed in a cow born in June 1998; an
announcement[pdf file] is available.
09 July 2003 - BSE has been diagnosed in a cow born in September 1996;
an announcement[pdf file] is available.
Docket Management Docket: 02N-0273 - Substances Prohibited From Use in
Animal Food or Feed; Animal Proteins Prohibited in Ruminant Feed
Comment Number: EC -10
Accepted - Volume 2
http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be07.html
PART 2
http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be09.html
something of major concern that the USA officials are conveniently
overlooking and or ignoring;
Asante/Collinge et al, that BSE transmission to the 129-methionine
genotype can lead to an alternate
phenotype that is indistinguishable from type 2 PrPSc, the commonest
_sporadic_ CJD;
http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm
Subject: PRO/AH/EDR> BSE - France: distinct molecular phenotypes
Date: Wed, 7 Jan 2004 18:16:51 -0500 (EST)
From: ProMED-mail
To: promed-ahead-edr@promedmail.org
BSE - FRANCE: DISTINCT MOLECULAR PHENOTYPES
*******************************************
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Tue 6 Jan 2004
From: Terry S. Singeltary Sr. Source: EMBO Reports, 5, 1, 110Â115,
2004 (published online: 19 Dec2003) [edited]
Distinct Molecular Phenotypes in Bovine Prion Diseases
--------------------------------------------------
The following paragraph is the Abstract from a report with the above
title by Anne-Gaelle Biacabe, Jean-Louis Laplanche, Stephen Ryder, and
Thierry Baron, published in EMBO (European Molecular Biology
Organisation) Reports. 19 Dec 2003.
"Bovine spongiform encephalopathy (BSE) in cattle, the most likely cause
of variant CreutzfeldtÂJakob disease [abbreviated as CJD (new var.) or
vCJD in ProMed-mail] in humans, is thought to be caused by a unique
infectious agent, with stable features, even when transmitted to other
species. Here, we show the existence of an atypical molecular phenotype
among cattle diagnosed with BSE in France. Following western blot
analyses, 3 cases showed unusual features of the electrophoretic
profiles of the protease-resistant prion protein (PrPres) accumulating
in the brain. The PrPres patterns were similar in these 3 atypical
cases, showing a higher molecular mass of unglycosylated PrPres and
strong labelling by P4 monoclonal antibody compared to 55 typical BSE
cases. This finding suggests either some phenotypic modifications of
PrPres following infection by the BSE agent or the existence of
alternative origins of such diseases in cattle."
--
Terry S. Singeltary Sr
[The following paragraphs comprise extracts from the authors' discussion
of their findings. The original article should be consulted for the
appropriate references.
"Our results demonstrate the finding of a distinct molecular phenotype
of prion diseases in cattle among routinely diagnosed BSE cases
following active surveillance of the disease using rapid tests for the
detection of PrPres in cattle at a slaughterhouse or in rendering
plants. The 3 cases described here had not been reported as having
clinical signs suggestive of BSE during their life and were found in old
cattle.
This atypical molecular phenotype is mainly characterized by a higher
molecular mass of the unglycosylated PrPres and PrPres labelling by P4
monoclonal antibody. This is an unexpected finding since it is believed
that this cattle disease is caused by a single strain of infectious
agent, which has shown very stable and uniform features, including
following its transmission to other species.
Several hypotheses can be considered to explain this finding. This may
be a manifestation of the BSE agent with different molecular features in
cattle, as recently described following transmission in transgenic mice
expressing the human prion protein. Mechanisms involved in such
observations remain to be established, but it should be emphasized that
such PrPres changes were only found following transmission of cattle
BSE, not of human vCJD, to these human transgenic mice.
Genetic differences in the prion genes between these atypical cattle and
the general cattle population might be expected to give rise to variants
in electrophoretic profiles of PrPres, as the sequence of the human PRNP
gene is known to influence the molecular features of PrPres in some
cases of human [sporadic] CJD. Sequencing of the entire open reading
frame of the prion genes of 2 of the atypical cases that showed the
known sequence for cattle excluded this hypothesis. Importantly, with
regard to the single polymorphism described in the bovine prnp gene,
which can contain 5 or 6 repeats of the octapeptide region, no
differences were observed between the atypical and typical BSE cases,
which could otherwise be distinguished by labelling with P4 monoclonal
antibody that recognizes an epitope very close to this region of the
protein.
In human [sporadic] CJD, it has also been shown that 2 distinct PrPres
types could be inter-converted in vitro by altering their metal ion
occupancy. Treatment with metal ion chelator EDTA, in the range of
concentrations that was shown to modify the PrPres profiles in human
CJD, did not modify the electrophoretic patterns of cattle-BSE cases.
The differences between atypical cases and typical cattle BSE were
maintained, with regard to both molecular mass of unglycosylated PrPres
and P4 labelling of PrPres.
Cattle may also have been infected by another source of infectious
agent, such as scrapie from sheep and goats. Interestingly, experimental
infection of cattle with a British natural sheep scrapie source indeed
led to similar differences in the PrPres electrophoretic profiles
compared to typical cattle BSE.
Finally, it has been suggested that a spontaneous rare sporadic form of
these diseases could exist in cattle as in humans, and might have been
the origin of the BSE epidemic. As different PrPres profiles were found
between sporadic and variant CJD in humans, this hypothesis might also
explain our finding.
Further studies are now required to determine the frequency of such
novel molecular phenotypes in cattle and the biological features of the
involved infecting strain. These may be carried out by means of mouse
transmission studies in a panel of wild-type mice with different prn-p
genotypes, as well as in bovine transgenic mice. However, in a 1st
hypothesis, our results would reinforce the possibility that BSE might
have different manifestations, and in this case might be hardly
recognized when transmitted to other species as previously suggested.
Alternatively, this may argue that different forms of the disease may
affect cattle, possibly meaning that some cases of such diseases could
be detected beyond any possibility of contamination by infected
meat-and-bone meal. While contamination and recycling of a scrapie agent
in cattle has been a major hypothesis of the origin of BSE, [direct]
infection of cattle by scrapie agents may have occurred. This may have
happened through contamination of feed as possibly occurred at the
origin of the BSE epizootic, but direct infection could also be
considered since scrapie can be transmitted between sheep and goats by
contact and/or through environmental contamination."
Japanese workers have reported recently that an atypical form of the BSE
agent was associated with cases of disease in Japan. It remains to be
established whether the atypical form detected in these French cattle in
any way resembles the atypical form described by the Japanese
scientists. - Mod.CP]
[see also:
CJD (new var.) - UK: update 2004 (01) 20040106.0064
2003
----
Scrapie - Norway: new phenotype 20031117.2857
BSE - Japan (08): 9th case, lab findings 20031115.2838
BSE, atypical case - Italy: OIE 20031022.2649
BSE - Japan (06): atypical 20031009.2547
BSE - Japan (05): atypical 20031008.2526
BSE - Japan (04): atypical 20031007.2511
CJD, iatrogenic: strain differences 20030718.1765]
.....................cp/pg/mpp
*##########################################################*
For assistance from a human being send mail to:
owner-promed@promedmail.org.
############################################################
ONE FINAL COMMENT PLEASE, on the use of bovine blood (especially from
downers)
in milk replacers for calves. As the name implies, milk replacer is used
in lieu of mother's
milk. It contains a variety of ingredients, including whey (a dairy
byproduct of
cheese making), vitamins, minerals, medications, animal fats, and, in
many replacers,
cow and pig blood. I am _deeply_ concerned with this continued practice;
STUDY DESIGN AND METHODS: BSE was passaged through macaque monkeys and
then adapted to the prosimian microcebe (Microcebus murinus ). Brain
homogenate and buffy coat from an affected microcebe were separately
inoculated intracerebrally into three healthy microcebes (two animals
received brain and one received buffy coat).
RESULTS: All three inoculated microcebes became ill after incubation
periods of 16 to 18 months. Clinical, histopathologic, and
immunocytologic features were similar in each of the recipients.
CONCLUSION: Buffy coat from a symptomatic microcebe infected 17 months
earlier with BSE contained the infectious agent. This observation
represents the first documented transmission of BSE from the blood of an
experimentally infected primate, which in view of rodent buffy coat
infectivity precedents and the known host range of BSE is neither
unexpected nor cause for alarm.
http://www.blackwell-synergy.com/servlet/useragent?func=synergy&synergyAction=showAbstract&doi=10.1046/j.1537-2995.2002.00098.x
Transmission of prion diseases by blood transfusion
1
Journal of General Virology (2002), 83, 2897–2905. Printed in Great Britain
Published ahead of print (16 July 2000) in JGV Direct as DOI
10.1099/vir.0.18580-0
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
1 Institute for Animal Health, Neuropathogenesis Unit, West Mains Road,
Edinburgh EH9 3JF,
UK
2 Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK
Author for correspondence: Nora Hunter.
Fax +44 131 668 3872. e-mail nora.hunter@bbsrc.ac.uk
Received 16 May 2002; Accepted 9 July 2002
This article is now available in the November 2002 print issue of JGV
(vol. 83, 2897–2905). The complete issue of the
journal may be seen in electronic form on JGV Online
(http://vir.sgmjournals.org).
0001-8580 © 2002 SGM
Abstract
Attempts to detect infectivity in the blood of humans and animals
affected with
transmissible spongiform encephalopathies (TSEs or prion diseases) have
often been
inconclusive because of the limitations of cross-species bioassays and
the small volumes of
blood that can be injected by the intracerebral route. A model has been
developed for the
experimental study of TSE transmission by blood transfusion using sheep
experimentally
infected with bovine spongiform encephalopathy (BSE) or natural scrapie
as donors and
susceptible scrapie-free sheep as recipients. Donors and recipients of
the same species greatly
increase the sensitivity of the bioassay and in sheep large volumes of
blood can be injected by
the intravenous (i.v.) route. Transmission of BSE to a single animal
using this approach was
reported recently. This study confirms this result with a second
transmission of BSE and four
new cases of transmission of natural scrapie. Positive transmissions
occurred with blood taken
at pre-clinical and clinical stages of infection. Initial studies
indicate that following such
infection by the i.v. route, deposition of the abnormal prion protein
isoform, PrPSc, in peripheral
tissues may be much more limited than is seen following oral infection.
These results confirm
the risks of TSE infection via blood products and suggest that the
measures taken to restrict the
use of blood in the UK have been fully justified.
Introduction
Creutzfeldt–Jakob disease (CJD) is one of a group of related diseases...
snip...
14
Discussion
With this report we have confirmed and extended our initial observation
of a single case
of BSE following transfusion of blood from a BSE-infected sheep and have
provided the first
conclusive evidence of significant levels of infectivity in blood in a
naturally occurring TSE
(scrapie). The experiment may take up to 5 years to complete; however,
so far we have clear
evidence of disease transmission by the blood transfusion route in 2 of
24 sheep (8 %) with BSE
and 4 of 21 sheep (19 %) with scrapie, with two additional animals
showing clinical signs in the
BSE group. If the clinically suspect BSE-transfused sheep progress as
expected, this would bring
the transmission rate for BSE up to 17 %, comparable with the scrapie
rate. Positive
transmissions have occurred not only with samples taken from sheep at
the clinical phase of
disease but also with those from apparently healthy donors as early as
halfway through the
incubation period (Fig. 1, lane 9; no PrPSc detection in the brain of
donor J2746). Each TSE is
transmitting to its appropriate susceptible genotype (AXQ/AXQ for BSE
and VRQ/VRQ for
scrapie) and Western blot/glycoform analyses support the conclusion that
donors and
recipients are infected with the same strains of BSE and scrapie. Our
negative controls remain
healthy, although still at relatively early stages post-transfusion and
our positive controls are
developing clinical signs at around, or greater than, 600 days
post-challenge, showing
incubation periods very similar to the transfusion cases.
Whole blood transfusion (400–450 ml) cases are presenting incubation
periods of around
600 days, which is very similar to those resulting from i.v. injection
of 0.2 g BSE cattle brain
homogenate. The transfusions might be expected to be more efficient
because they are a sheepto-
sheep transmission with no species barrier, which contrasts with the
i.v. brain infections,
which is a cattle-to-sheep transmission. A full titration of the
inoculum used in the cattle BSE
brain i.v. controls is under way in mice but is incomplete at the time
of writing. Accurate
estimation of the levels of infectivity in blood will require i.v.
titration in sheep; however, the
results presented here suggest that they are significantly higher than
suspected previously.
Another important consideration is the distribution of infectivity among
different blood
components. Perhaps surprisingly, most positive transmissions so far
have followed transfusion
of whole blood rather than buffy coat, whereas previous studies have
tended to find infectivity
concentrated in the buffy coat fraction. As we now have a clinical case
of scrapie resulting from
transfusion of buffy coat, it is clear that, in our model, infectivity
is also carried by the cells in
this fraction. However, these preliminary results suggest that
infectivity is not confined to the
buffy coat fraction and that there may also be significant levels of
infectivity in the plasma
and/or red cell fractions.
15
The presence of infectivity in blood suggests that it should be possible
to detect PrPSc or
other surrogates of infectivity by alternative methods, with obvious
benefits for development of
ante-mortem diagnostic tests. Early reports of the use of capillary
electrophoresis to detect PrPSc
in the blood of scrapie-infected sheep showed some promise (Schmerr et
al., 1997); however, a
recent study could not detect PrPSc in peripheral blood leucocytes of
scrapie-infected sheep
using immunocytochemistry (Herrmann et al., 2002). PrPC is known to be
expressed only on
peripheral blood mononuclear cells in sheep, in contrast to humans where
it is also found on
platelets and, at low levels, on erythrocytes (Barclay et al., 2002;
Herrmann et al., 2001; Holada et
al., 1998). Since tissues that express PrPC do not always equate with
areas that accumulate PrPSc
and infectivity during disease, the distribution of infectivity in blood
fractions of different
species clearly merits more detailed analysis.
Immunocytochemical detection of PrPSc in peripheral tissues of two of
the BSE
transfusion cases has shown a greatly reduced involvement of lymphoid
tissues, including
tonsil, in the peripheral pathogenesis compared with NPU Cheviot sheep
orally infected with
BSE or natural scrapie (Foster et al., 2001a). A recent report has shown
that a proportion of
Romney sheep in the late pre-clinical stages of infection with BSE
following oral dosing (22
months post-infection) have PrPSc deposits in the CNS in the absence of
any detectable
involvement of peripheral lymphoid tissues (Jeffrey et al., 2001). This
study also noted the
relatively late and variable onset of PrPSc accumulation in the lymphoid
tissues of BSE-infected
sheep. A more detailed study of BSE and scrapie transfusion cases, and
positive controls, will be
undertaken to determine whether lack of involvement of the LRS is a
consistent feature in
animals infected by the i.v. route; the results will be published at a
later date. If our preliminary
observations are confirmed, there may be implications for human patients
with the misfortune
to have received blood products from vCJD cases, because a negative
tonsil biopsy as a means
of reassurance might very well be unreliable. On the other hand, it also
may mean that if a
human patient became infected with vCJD by the i.v. route, then the
peripheral tissues and
blood of this secondary case may not themselves be highly infectious.
In conclusion, our results so far indicate that, with more than 10 % of
transfusions
resulting in disease in the recipients, blood transfusion represents an
appreciable risk for
transmission of TSEs in sheep and, by extension, of vCJD in human
beings. The relatively short
and consistent incubation periods seen in positive cases suggests that
levels of infectivity in the
blood may be higher than suspected previously, even in the pre-clinical
stages of infection,
and/or that transmission by the i.v. route is highly efficient. From
these preliminary results, it
would appear that measures taken to safeguard the blood supply in the UK
are fully justified.
However, further work, in particular a thorough investigation of the
distribution of infectivity
in different blood fractions, is required before a reliable estimate of
the risks associated with
contaminated blood products can be made.
Acknowledgements
The authors are indebted to the UK Department of Health, European Union
and DEFRA for their financial
contribution to this study.
Nora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 David
Parnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2
see full text;
http://www.socgenmicrobiol.org.uk/JGVDirect/18580/18580ft.pdf
I have been concerned about transmission of TSEs to human/animals for
some time;
http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm
PDF]Freas, William TSS SUBMISSION
File Format: PDF/Adobe Acrobat -
Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary
Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
PLUS, now we have this factor to consider;
vCJD: Blood Transfusion Incident
3.58 p.m.
Lord Warner: My Lords, with permission, I wish to repeat a Statement
made by my right honourable friend the Secretary of State for Health in
another place. The Statement is as follows:
"With permission, Mr Speaker, I wish to make a Statement about a
blood transfusion incident involving variant Creutzfeldt-Jakob
Disease (vCJD). It may assist the House if I begin by setting out
the basic facts before discussing the implications.
"In March 1996, a blood donor, who was at the time free of the
signs of variant CJD, donated blood to the National Blood Service.
Shortly after that, the donated blood was transfused into a
patient who underwent surgery for a serious illness. In
17 Dec 2003 : Column 1170
continuing my description of the events to the House, I will from
now on refer to those individuals as the 'donor' and the
'recipient' of the blood.
"The donor showed no signs of variant CJD at the time the blood
was given, but developed the disease three years later—that is, in
1999—and died from it. The recipient of the blood died in the
autumn of this year.
Initial post-mortem examination of the recipient of the blood
showed changes in the brain indicative of CJD. Further
examinations and tests of this patient's brain confirmed the
diagnosis of variant CJD. The link between the donor and the
recipient was first reported to officials in my department on 9th
December 2003 at which time the diagnosis of variant CJD in the
recipient was still being confirmed.
"I was first alerted to the developments on Friday 12th December
and was briefed by the Chief Medical Officer on Monday and Tuesday
this week. Today I am bringing this information to the House at
the earliest opportunity. I have given and will give the minimal
clinical details of the recipient, because the family has
indicated that it wishes to have its privacy respected.
"In the light of the facts I have outlined, it is therefore
possible that the disease was transmitted from donor to recipient
by blood transfusion in circumstances where the blood of the donor
was infectious three years before the donor developed variant CJD
and where the recipient developed variant CJD after a six and a
half year incubation period. This is a possibility, not a proven
causal connection, because it is also possible that both
individuals separately acquired variant CJD by eating BSE-infected
meat or meat products....
snip...full text
http://www.publications.parliament.uk/pa/ld199697/ldhansrd/pdvn/lds03/text/31217-09.htm
WE must not forget the old findings from Manuelidis et al, TATEISHI et
al, Hunter et al,
1: Science. 1978 Jun 2;200(4345):1069-71.
Viremia in experimental Creutzfeldt-Jakob disease.
Manuelidis EE, Gorgacs EJ, Manuelidis L.
Inoculation of the buffy coat of blood from guinea pigs infected with
Creutzfeldt-Jakob disease resulted in passage of this disease to
recipient animals. This demonstrates that there is a viremia in
experimental Creutzfeldt-Jakob disease. These findings suggest that the
hematogenous route may be implicated in the human infection and that the
disease may possibly be transmitted by blood transfusions.
PMID: 349691 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/quer
From: Terry S. Singeltary Sr. (216-119-130-97.ipset10.wt.net)
Subject: Other Transmission Studies of CJD from Blood and Urine Into Mice...
Date: September 18, 2000 at 2:01 pm PST
In Reply to: Transmission of BSE by blood transfusion in sheep... posted
by Terry S. Singeltary Sr. on September 15, 2000 at 9:29 am:
Transmission of Creutzfeldt-Jakob Disease from Blood and Urine Into Mice
The Lancet, November 9, 1985
Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) report
transmission to animals of Creutzfeldt-Jakob disease (CJD) from the
buffy coat from two patients. We also transmitted the disease from
whole blood samples of a patient (and of mice) infected with CJD.1
Brain, Cornea, and urine from this patient were also infectious, and
the clinicopathological findings2 are summarised as follows.
A 70-year-old man was noted to have a slowing of speech and writing
and some disorientation, all of which progressed rapidly. Decorticate
rigidity, forced grasping, positive snout reflex, and myoclonus
appeared within 2 months. Electroencephalogram revealed typical
periodic synchronous discharge, and he died of pneumonia and upper
gastrointestinal haemorrhage, about 3 months after onset of the
symptoms. The Brain weighed 1290g and showed severe histological
changes diagnostic of CJD, including spongiform change, loss of
nerve cells, and diffuse proliferation of astrocytes. There were no
inflammatory cells, microglia, neurofibrillary tangles, and
amyloid plaques, although virus-like particles were detected by
electron microscopy.
Results of innoculation in Mice
Inocula NO* Incubation period (days)+
Brain 7/10 (4) 789 (+ or - 112)
Cornea 1/6 (0) 1037
Blood 2/13 (0) 1080 (+ or - 69)
Urine 5/10 (1) 880 (+ or - 55)
CSF 0/10
* Number of mice with CJD change/number examined histologically.
Number with amyloid plaques shown in parentheses.
+ means + or - SD
Samples were taken aseptically at necropsy. 10% crude homogenates
of brain and cornea in saline, whole blood (after crushing a clot),
and untreated CSF and urine were innoculated intracerebrally into
CF1 strain mice (20 ul per animal). Some mice showed emaciation,
bradykinesia, rigidity of the body and tail, and sometimes tremor
after long incubation periods. Tissues obtained after the animal
died (or was killed) were studied histologically (table). Animals
infected by various inocula showed common pathological changes,
consisting of severe spongiform changes, glial proliferation, and
a moderate loss of nerve cells. A few mice inoculated with brain
tissue or urine had the same amyloid plaques found in patients and
animals with CJD.3
In our long-term experiments, inoculating materials taken from
twenty patients with CJD or Gerstmann-Straussler-Scheinker's
disease (GSS) into rodents, positive results were obtained in
seventeen cases, including this patient. Brain tissue transmitted
the disease most frequently within the shortes incubation period,
except for one case where the lymph node was the most infectious.
Transmission through the cornea has been noted in man4 and in
guineapigs.5 Whole blood samples taken from three patients were
inoculated and a positive transmission occured only in the case
recorded here. Mouse-to-mouse transmission through blood
inoculation was successful after a mean incubation period of 365
days.1 Transmission through urine was positive in this patient
only, and negative in one other patient and in many infected animals.
Transmission through the CSF from eight patients was negative, yet
transmission via the CSF of infected rats was positive.1
As viraemia has been proved in guineapigs,6 mice,1,7 and lately
in patients with CJD, blood for transfusion or blood products for
medical use must be tested for unconventional pathogens. For this
purpose, we inoculated blood products inot rodents.8 The CJD
pathogen was not found in the products examined. However, this
approach takes too long to be of practical value. More efficient
methods must be developed to detect pathogens and to eliminate
them from blood. One proposal9 is to apply membrane filtration to
the pruification protocol of human growth hormone suspected of
being contaminated with CJD. Similar methods are needed for blood
contamination.
Department of Neuropathology,
Neurological Institute,
Faculty of Medicine,
Kyushu University,
Fukuoka812, Japan
JUN TATEISHI
1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmission
of human subacute spongiform encephalopathy to small
rodents 1: Clinical and histological observations.
Acta Neuropathol (Berl) 1980; 51: 127.
2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob
disease with demonstration of virus-like particles.
Acta pathol Jpn 1982;32: 695.
3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the
brains of mice with Creutzfeldt-Jakob disease.
Ann Neurol 1984; 15: 278.
4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D.
Possible person-to-person transmission of Creutzfeldt-Jakob disease.
N Engl J Med 1974; 290: 692.
5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L.
Experimental Creutzfeldt-Jakob disease transmitted via the eye
with infected cornea. N Engl J Med 1977; 296: 1334.
6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental
Creutzfeldt-Jakob disease. Science 1978: 200: 1069.
7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC.
Creutzfeldt-Jakob disease in mice. Persistent viremiam and
preferential replication of virus in low-density lymphocytes.
Infect Immun 1983; 41: 154.
8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform
encephalopathis absent in blood products. J Med Virol 1985; 15: 11.
9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease
pathogen in growth hormone preparations is eliminatable.
Lancet (in press).
========================================================
also, this from the Her Majesty's Government...TSS
Subject: Transmission of TSEs through blood
Date: Tue, 28 Mar 2000 14:48:35 +0100
From: Ralph Lucas
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
The Lord Lucas asked Her Majesty's Government:
Whether there is any evidence that any Transmissible Spongiform
Encephalopathy in any species can be transmitted through blood; and
whether they will place in the Library of the House copies of the
principal relevant scientific papers. (HL1545)
The Parliamentary Under-Secretary of State, Department of Health (Lord
Hunt of Kings Heath):
Some animal studies have shown that certain transmissible spongiform
encephalopathies can be experimentally transmitted from animal to animal
through blood components. However, the Spongiform Encephalopathy
Advisory Committee at its February meeting reviewed recent research
undertaken in this area and did not consider any measures were
necessary, in addition to those already in place, to reduce any
potential risk to public health from human blood and blood products.
Copies of the following relevant scientific papers are being placed in
the Library.
Brown P, 1995, "Can Creutzfeldt-Jakob Disease be transmitted by
Transfusion?" Haematology 2: 472 - 477.
Brown et al 1999, Further studies of blood infectivity in an
experimental model of transmissible spongiform encephalopathy, with an
explanation of why blood components do not transmit Creutzfeldt - Jakob
disease in humans.
Transfusion Vol. 39, November/December 1169 - 1178.
with kindest regards,
I am sincerely,
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, TEXAS USA 77518
CJD WATCH
===============
Congressional and Public Affairs
Steven Cohen (202) 720-9113
USDA ISSUES NEW REGULATIONS TO ADDRESS BSE
WASHINGTON, Jan. 8, 2004 The U.S. Department of Agricultures Food
Safety and Inspection Service today issued four new rules to implement
announcements made last week by Agriculture Secretary Ann M. Veneman to
further enhance safeguards against Bovine Spongiform Encephalopathy (BSE).
On Dec. 30, 2003, Secretary Veneman announced a number of policies that
will further strengthen protections against BSE, including the immediate
banning of non-ambulatory (downer) animals from the human food supply.
Rules to address the remaining issues are on display at the Federal
Register today and are the result of many months of development. These
policies involve: requiring additional process controls for
establishments using advanced meat recovery (AMR) systems; holding meat
from cattle that have been tested for BSE until the test results are
received and they are negative; and prohibiting the air-injection
stunning of cattle.
The rules released today include:
Product Holding. USDA is publishing a notice announcing that FSIS
inspectors are no longer marking cattle tested for BSE as inspected and
passed until confirmation is received that the cattle have, in fact,
tested negative for BSE. FSIS will be issuing a directive to inspection
program personnel outlining this policy.
Specified Risk Material. With the filing of an interim final rule, FSIS
is declaring that skull, brain, trigeminal ganglia, eyes, vertebral
column, spinal cord and dorsal root ganglia of cattle 30 months of age
or older and the small intestine of all cattle are specified risk
materials, thus prohibiting their use in the human food supply. Tonsils
from all cattle are already considered inedible and therefore do not
enter the food supply. These enhancements are consistent with the
actions taken by Canada after the discovery of BSE there in May. These
prohibitions are effective immediately upon publication in the Federal
Register.
In this rule, FSIS is requiring federally inspected establishments that
slaughter cattle remove, segregate and dispose of these specified risk
materials so that they cannot possibly enter the food chain. To
facilitate the enforcement of this rule, FSIS has developed procedures
for verifying the approximate age of cattle that are slaughtered in
official establishments. State inspected plants must have equivalent
procedures in place to prevent these specified risk materials from
entering the food supply.
Comments on this interim final rule will be accepted for 90 days after
the publication of the rule in the Federal Register. Comments should be
directed to: FSIS Docket Clerk, Docket #03-025IF, Room 102, Cotton
Annex, 300 12th and C Street, SW, Washington, DC 20250-3700.
Advanced Meat Recovery. AMR is a technology that removes muscle tissue
from the bone of beef carcasses under high pressure without
incorporating bone material. AMR product can be labeled as meat. FSIS
has previously established and enforced regulations that prohibit spinal
cord from being included in products labeled as meat.
-MORE-
-2-
This interim final rule expands that prohibition to include dorsal root
ganglia, clusters of nerve cells connected to the spinal cord along the
vertebral column, in addition to spinal cord tissue. In addition,
because the vertebral column and skull in cattle 30 months and older
will be considered inedible, they cannot be used for AMR.
Comments on this interim final rule will be accepted for 90 days after
the publication of the rule in the Federal Register. Comments should be
directed to: FSIS Docket Clerk, Docket #03-038IF, Room 102, Cotton
Annex, 300 12th and C Street, SW, Washington, DC 20250-3700.
Air-Injection Stunning. To ensure that portions of the brain are not
dislocated into the tissues of the carcass as a consequence of humanely
stunning cattle during the slaughter process, FSIS is issuing an interim
final rule to ban the practice of air-injection stunning.
Comments on this interim final rule will be accepted for 90 days after
the publication of the rule in the Federal Register. Comments should be
directed to: FSIS Docket Clerk, Docket #01-033DF, Room 102, Cotton
Annex, 300 12th and C Street, SW, Washington, DC 20250-3700.
#
NOTE: Access news releases and other information at the FSIS web site at
http://www.fsis.usda.gov.
