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From: TSS ()
Subject: TSEAC JUNE 2, 1999 Welcome to the FDA traveling road show
Date: October 15, 2007 at 3:18 pm PST

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE MEETING
Thursday, June 2, 1999

CHAIRMAN BROWN: My name is Dr. Paul Brown. Welcome to the FDA traveling
road show. We are asked yet once more by the FDA to consider a question of
theoretical risk in the absence of sufficient knowledge on which to base any
firm conclusion.
The issue before us today is that of excluding categories of American
blood donors who have either visited or resided for longer periods of time
in Great Britain. The issue is sufficiently delicate, as you see that we
have been moved outside the Beltway.
(Laughter.)


snip...


"Dr. Alan Williams is employed by the American Red Cross, Holland Labs,
and is Scientific Adviser for the Florida Blood Services and Canadian Blood
Services. In addition, he has financial interests in firms that could be
affected by the general discussions.
"Dr. Richard Race has financial interests in firms that could be affected
by the general discussions and is a public health science researcher.
"In the event that the discussions involve specific products or specific
firms for which FDA participants have a financial interest, the participants
are aware of the need to exclude themselves from such involvement. And
their exclusion will be noted for the public record. A copy of the waivers
is available by written request under the Freedom of Information Act.
"With respect to all other meeting participants, we ask in the interest of
fairness that they address any current or previous financial involvement
with any firm whose product they may wish to comment upon."
So ends the reading of the conflict of interest statement. Dr. Brown, I
turn the meeting over to you.

snip...

DR. JACOBS: Thank you, Dr. Brown, and welcome to members of the Committee.
Today we are again bringing the question of deferral from blood donation
of persons with possible foodborne exposure to bovine spongiform
encephalopathy, BSE, as a precautionary measure to reduce the risk of blood
transmission of new variant Creutzfeldt Jakob disease. And we are asking
the Committee at this time, as we did in December, to consider this in the
light of possible shortages.
Next, the current status. So far there have been no cases of either BSE
or new variant CJD reported in the U.S. We're aware and we discussed in
December the precautionary measures which have been taken in the U.K.
First, they are not using U.K.?sourced plasma; and, secondly, they are
implementing universal leukoreduction.

snip...

Next. In December, we asked the Committee to vote on two votes. I'm going
to go through what those votes were. The first one is: Should FDA
recommend new deferral criteria for blood donors to attempt to reduce a
theoretical risk for transmitting new variant Creutzfeldt Jakob disease be
excluding donors potentially exposed to the agent of bovine spongiform
encephalopathy? The Committee voted nine yes and six no.
Next overhead. Should FDA recommend excluding donors who have resided in
the United Kingdom or other BSE countries? The Committee voted 15 yes,
unanimous, to remove "or other BSE countries."

snip...

I want to just put on the record and mention the other votes which were
taken in December. Should FDA recommend withdrawal for blood components
based on these donor deferral criteria? The vote was seven yes, five no.
And should FDA recommend withdrawal for plasma derivatives based on these
donor deferral criteria? Voted eleven no, one yes.
Next one, please. In addition to these questions on deferral of donors,
in December we also asked the Committee to consider the actions that FDA
would take if there were a report of a possible case of new variant CJD.
We're going to refer those to CDC, but considering our precautionary
withdrawal policy for new variant CJD, we asked: Should FDA recommend
precautionary quarantine or withdrawal for plasma derivatives to which a
possible new variant CJD donor contributed pending confirmation of the
clinical diagnosis?
The Committee voted eight yes, one no, one abstained, but they asked us to
revisit this question of our operational definition of a possible new
variant CJD case. And in the second part of today's deliberations, after
the vote on deferral, we will go back to that question.
The Committee also voted that a tonsil biopsy negative for
protease?resistant prion would not be sufficient to make product
withdrawals unnecessary.

snip...

We now have a presentation by Dr. Philip Comer, who will give us the Det
Norsk Veritas risk assessment. Dr. Comer?
MR. COMER: Thank you very much, Chairman, and thank you for the
opportunity to come and talk about the study that we were asked to do by the
Department of Health in the United Kingdom as a result of a recommendation
from the United Kingdom's Spongiform Encephalopathy Advisory Committee.

snip...

I am just going to go very quickly over the evidence for infectivity in
blood. I think probably that will have already been looked at significantly
by this Committee, but it was very much part of the background for what we
were doing in the study that we did.
If we look at blood transfusions, we know that all attempts to transmit
infectivity of blood, blood transfusion, so across a species barrier, have
failed and that within animal models, as far as I am aware, the one case
which has been reported by Bob Rohwer is still the only case that I have
heard of in which there has been a positive transmission by the i/v route
within an animal model.
Epidemiology studies have shown that's from sporadic CJD. There is no
evidence that there has been any transmission through the blood route. And
when we look at blood from human CJD cases, primarily sporadic CJD cases and
certainly no variant CJD cases, and look at that, their infectivity through
the i/c route into animal models, there have been a few experiments which
have shown positive infectivity into rodents but negative results from a
significant number of studies into primates and other species.
And there have been some questions asked about ?? these cases, these
experiments all involve very small numbers of animals and some sort of
significant questions asked about those and, in particular, the fact that it
is a bit odd that we have got no positive infections in the primates, which
you might have expected would be more susceptible than the rodents.
Then when we look at actually within animal models themselves, there have
been quite a number of cases, experiments where positive infections have
been reported from animals infected with some form of TSE and have been
through the i/c route infected in the same species, so again with no species
barrier.

snip...page 89

CHAIRMAN BROWN: A couple of points just to bring your experimental data up
to speed. Unpublished further experiments on the mouse model have produced
good news and bad news.
The bad news is that we have a disappointingly large number of
transmissions following intravenous inoculation of either plasma or Buffy
coat. We also have a transmission using whole blood as a transfusion into
these mice. So that's not good news.
The other thing that is not too good is that we have now got in this
particular model a ratio of five to one, as opposed to ten to one, which was
also disappointing.
The only piece of good news in that in terms of experimental data is that
we found that, again, in this model, the level of infectivity during the
entire incubation period is almost negligible compared to the level of
infectivity during the clinical phase of illness. And that is very good
news indeed. So these are data that are not yet published but ??

snip...page 105

CHAIRMAN BROWN: Right, right. And, as I say, if it turns out to be the
case with the human disease, ?? and I'm guessing it probably will be ?? with
you, I think the likelihood of disease, natural disease, whether it be
scrapie in sheep, BSE in cattle, or CJD in humans, is going to be quite a
lot less virulent than the experimentally induced disease.
Even under the experimental conditions I mentioned, however, infectivity
in all components of the blood during the incubation period is so low that
it virtually poses I think no risk, at least in terms of plasma derivatives.

snip...page 106

Dr. Chan

snip...

So the issue that we dealt with in early May was "do variants of CJD pose a
risk to blood safety?" And we sort of divided it into the classic variant
and others. The others came out of, I'm sure you're all aware, of the scare
that we all had over the Utah donor was this a possible chronic wasting
disease, etc.
So we just put that issue on the table and let's see where it went. Our
process -- we circulated a notice widely to all associations, consumer
groups. We've sort of got a mailing list that's growing.

snip...page 129

And thirdly, the question was: What is the biological plausibility, from
our experimental data, that there will be other variants of CJD? I won't go
into the attempts of answering these.

snip...page 135

The rest of the recommendations I'll go through very briefly. Health Canada
had not standardized its -- not finalized its policy on classic CJD, and we
advised that they do so.
The blood services should provide clear statements about the reasons for
believing that there are no longer concerns regarding the classic sporadic
CJD; that Health Canada and the blood services provide communication
regarding all aspects of product quarantine.
And that was because there's considerable confusion over the Utah donor
case. Health Canada identify and provide information that all products
that contain trace amounts of blood products -- this was interesting.
Many of the physicians did not even know which products that were being
distributed contained blood products. We thought this was an important
issue. All products can be tracked in the event of an infected donor. And
that they take steps to discourage manufacturers from using blood products
in the production or formulation of other products.
That mechanisms are developed to ensure that -- oh, this is the
surveillance for CJD. That criteria have to be established to determine
between classic and variant forms, which I know is the topic that you are
going to be discussing this afternoon.

snip...page 138

CHAIRMAN BROWN: This afternoon's program will begin with several
presentations as a part of the open public hearing.


snip...page 145

CAPTAIN RUTHERFORD: Good afternoon.
The Department of Defense would like to thank you for allowing us to offer
public comment.
I am Captain Bruce D. Rutherford, Medical Service Corps, United States
Navy, the present Director of the Armed Services Blood Program.
On 5 February, 1999, Dr. Sue Bailey, the Assistant Secretary of Defense
for Health Affairs, forwarded a letter to Vice Admiral David Satcher, Public
Health Service, the Surgeon General of the United States.
In that letter, Dr. Bailey expressed her opposition and the opposition of
the Surgeon Generals of the Army, Navy and Air Force on deferring
individuals as blood donors based on "perception" of a "possible" risk of
transfusion transmission of the agent for "new variant" CJD.
There has not been a single case, repeat, single case of transfusion
transmitted new variant CJD or classical CJD reported in the world in more
than 55 years since transfusion of blood products became widely accepted as
a treatment regime.
In November of 1991, the Department of Defense issued an advisory
recommending that individuals participating in Operation Desert Storm be
deferred as blood donors after a number of Desert Storm troops were
identified with cutaneous and visceral Leishmania tropica.
Knowing that Leishmania donavani was transfusion transmissible, and now
knowing the extent of infection rate of the "at risk" population, the DOD
decided to defer those individuals as blood donors who participated in
country in the Persian Gulf.
It was not until December of 1993, or two years later, that the DOD
stopped asking leishmaniasis related questions of its blood donors. The
cessation was due to a concentrated effort by the military health system in
identifying an extremely small number of infected individuals and the
follow-on screening questions' ability in identifying an extremely small
number of donors with symptoms where leishmaniasis could have been a
possibility.
However, a study in the survivability and infectivity of viscerotropic
Leishmania tropica in human blood donors from ODS participants was later
shown to support our concern and was published in the American Journal of
Tropical Medicine and Hygiene in 1993.
Transfusion transmission by Leishmania species was a known, not
theoretical. We know the calculatable risk of being injured in a car
accident, yet millions of individuals a day drive their cars with hundreds
of thousands being injured per year and tends of thousands killed each year.
It is the same with airplanes, lightening and other activities.
In theory, anything is possible. I remember back a few years ago when the
Institutes of Medicine came out with this HIV report. Yes, hindsight was
better, but that has always been true.
I think in this case we have hindsight, 55 years of hindsight. We do not
need to institute a UK deferral policy which will only lead to further
crippling of our nation's blood supply and more product shortages.

snip...page 148

CHAIRMAN BROWN: Thank you, Captain Rutherford.
Are there any questions that any of the panel would wish to address to
Captain Rutherford?
The next presentation will be by Kay R. Gregory of the American
Association of Blood Banks.
MS. GREGORY: Good afternoon.

snip...page 148

In conclusion, AABB notes that there is no evidence that nvCJD is
transmitted by blood transfusion. There are no cases of nvCJD in the United
States. It is unknown whether travel to Great Britain correlates with
exposure to or infection with the agent of BSE.
And there is no evidence that any proposed criteria will decrease the
theoretical risk of acquiring nvCJD from transfusion. In contrast, there is
good evidence that even a one to two percent loss of donors due to new
deferral criteria will have a significant impact on blood availability and,
hence, on the safety of those transfusion recipients who cannot tolerate a
delay in receiving blood products.
The country should contemplate nvCJD deferral criteria only when it is
apparent that such a policy would improve blood safety more than the loss of
donors and the associated decrease in blood availability would compromise
blood safety.
Thank you.
CHAIRMAN BROWN: Thank you, Ms. Gregory.
The word theoretical has been used many, many, many times this morning and
will continue to be used, and it's being used correctly. I'd just point out
that, for ten years, between 1985 and 1995, the risk of new variant CJD from
BSE was also theoretical.
The next speaker is Dave Cavenaugh from the Government Relations Committee
of Ten Thousand.
MR. CAVENAUGH: I'm the government relations person at the Committee of
Ten Thousand. The organization is the Committee of Ten Thousand.
CHAIRMAN BROWN: Yes, that's fine. Thank you.
MR. CAVENAUGH: Okay, COTT, which is the Committee of Ten Thousand, is
gravely concerned about the industry logic favoring UK donors over
additional U.S. replacement donors even with the survey, and even with the
lack of data on paid and unpaid high volume pheresis donors.
This morning's discussion showed a glaring omission in the analysis to
date of the impact of excluding well paid, highly educated, non-incentive
provided pheresis donors in addition to the larger, understood group of paid
pheresis donors.
We've heard quite a bit in terms of the studies and in terms of some of
the questions about the likely blood borne nature of this never documented
entity of prion and its ability to be transmitted by blood.
There's a perceived link between new variant and beef that's been raised
based on proximity, but the BSE classical CJD link should not be forgotten.
It should be entertained at the minimum. Living in the United Kingdom in the
late '80s seemed to be a major factor, for example.
What was it about living there, that's proximity. Both statistic
presenters showed clear risk of new variant in the blood, not even enlarging
the scope to include classical CJD. There are no nv cases in the U.S., but
plenty of classical -- arguably, much more than the one in one million rate
alleged.
Just ask CJD Voice, the patient-family support group which spoke before
you 18 months ago. Small then, its numbers have mushroomed. Something is
getting transmitted. Can it all be through beef? But most disturbing is
the recent news confirming a second mutated form of prions also causing
death in under a year.
This doubling of the number of ways prions can be malformed with fatal
results raises our concern levels considerably. The explanation that it is
spontaneous sounds like an early catch all. With an entity so new, so
unknown and so dangerous, the committee should be providing every protection
possible, not bowing to arguments of relative risk.
Thank you.
CHAIRMAN BROWN: Thank you.

snip...page 154

CHAIRMAN BROWN: Well, this is exactly why we're here today. Dr. Satcher
and the other groups have already decided that this is not worth significant
worry with respect to classical CJD, and that new variant was an unknown.
And so that's why we're considering specifically new variant because we
don't have information specifically on it. I mean, everything we don't have
information on becomes a subject for this committee.
(Laughter.)

snip...page 213

DR. LEITMAN: We seem to be extrapolating the partitioning data of classical
CJD -- the agent of classical CJD to the agent of new variant CJD. That may
or may not be okay.
I'd like to ask Dr. Prusiner if we can at all extrapolate the lack of
transmissibility through blood components of classical CJD agent to new
variant?
DR. PRUSINER: I don't know that I'm qualified to answer this. I can only
tell you that the little bit of work that we've done now on new variant CJD
says that it is a dramatically different strain of prion. That means that
the confirmation of PRP scrapie is dramatically different than anything else
we've studied.
So let me give you an example. We've looked at 40 different cases of
sporadic CJD, and we know that there's several different confirmations there
at least. And all of these are transmissible in about 200 days to either
mice that have a human PRP gene or have a chimeric mouse human PRP gene.
If you look at new variant CJD, it takes more than 500 days and only about
60 percent of the animals get sick. Now, as I said before, if we take new
variant CJD and we passage it into a mouse that expresses a bovine PRP gene
on a null background, then all the mice are getting sick in 240 days.
The piece of data I don't have that you want is you want to know if I take
sporadic CJD or familial CJD cases and passage those into mice with a bovine
PRP gene, do they get sick? And the answer is I don't know yet.


snip...page 218

MS. HARRELL: Well, I asked him the question, was there a deferral ?? was
there deferral criteria for blood donors for classic CJD for people who have
either resided or visited the UK.
CHAIRMAN BROWN: I'm sorry. Repeat that, the question.
MS. HARRELL: Is there a deferral policy for blood donors to attempt to
reduce the risk of transmitting classic CJD for people who either resided or
visited the UK?
DR. SCHONBERGER: The answer is no.
MS. HARRELL: And if there is no risk, if we think that there is no risk
of transmitting the whatever to ?? for CJD, what makes this different, for
new variant CJD much different?
CHAIRMAN BROWN: That's the first time, Stan, you'll ever hear of prion
referred to as a whatever.
(Laughter.)
CHAIRMAN BROWN: I mean, I've heard it referred to as a lot of different
things. I'm ??
DR. PRUSINER: You've said that many times, Paul.
(Laughter.)
CHAIRMAN BROWN: It may be that ??
DR. PRUSINER: Is that in the Congressional Record?
CHAIRMAN BROWN: The issue is not about sporadic CJD. That is the issue
we can sort of generically say CJD. Presumably, if the blood from a patient
with new variant CJD were infectious, the disease that it would transmit
would be new variant CJD. So it's not ??
MS. HARRELL: Okay. So CJD is not transmitted through the blood is what
you're saying?
CHAIRMAN BROWN: We have no evidence from looking at populations that that
has ever happened. The question is: since we know it can happen when we
use experimental models of CJD, we can take CJD blood from one animal and
produce the disease in another animal.
So there is the "theoretical possibility" that this might also happen in
humans, particularly with a different strain of the disease, which new
variant is, about which we don't know a whole lot. That's the question.
DR. SCHONBERGER: Isn't the answer to her question that the incidence of
CJD, REDS, classic CJD, is not influenced by whether or not you've lived in
the UK between 1980 and 1996 ??
CHAIRMAN BROWN: Yes.
DR. SCHONBERGER: ?? but the incidence of new variant CJD is?
CHAIRMAN BROWN: Yes, 40-love.
(Laughter.)

snip...page 240

CHAIRMAN BROWN: I agree. We're starting to vote, and we'll start with
Larry. Hold on. All right. The question is: should FDA recommend new
deferral criteria for donors of transfusable components, to attempt to
reduce the theoretical risk of transmitting new variant CJD from
transfusions based on donor exposure to BSE in the UK?
DR. SCHONBERGER: Yes.
CHAIRMAN BROWN: Incidentally, just to remind the committee, it is
possible to vote punt; that is to say, you can vote yes, no, or no vote ??
abstain.
DR. HUESTON: Well, for my own benefit, I suppose, to walk through the
logic ?? and maybe for the benefit of Barbara because I think she raises a
good point about how we proceed ?? we have a situation with a small number
of known cases of variant Creutzfeldt Jakob, all but one of which are in the
UK.
However, we know there is a potential for widespread exposure to BSE that
has already occurred. Therefore, we expect more cases, but we really don't
have a good idea of the magnitude of the epidemic that we're going to
expect.
Part number 2 says, "While there is no known whole blood or blood product
transmission of classical CJD in humans, variant Creutzfeldt Jakob differs
substantially from classical CJD." So we recognize that there is the
potential for transmission of some of the transmissible spongiform
encephalopathies via blood, albeit controversial
We have an animal model, and we can identify infectivity in lymphoid
tissues with variant Creutzfeldt Jakob, which is different from classical
Creutzfeldt Jakob.
At the same time, it has been pointed out many times by a number of people
that there have been no observed risk ?? or no observed cases at this point
of transfusion or blood product related variant Creutzfeldt Jakob cases in
the UK. I think that's a little premature. One might say the absence of
evidence is not evidence of absence.
???????????????http://www.fda.gov/o At the same time, there are look-back
studies in place in the UK, and there is a natural experiment ?? a huge
natural experiment ongoing in the United Kingdom, where if, in fact, there
is a risk, I believe that the risk will first be apparent in the United
Kingdom far before we would see it anywhere else.
At the same time, in looking at the precautionary principle ??
CHAIRMAN BROWN: Is this the preamble for a vote?
DR. HUESTON: Yes, sir. You got it.
(Laughter.)
DR. HUESTON: If our goal is to be precautionary, but at the same time we
have to preclude having more negative impacts for any action that we take,
then positive ?? in other words, impacts on the blood supply. And I have
struggled through the whole time, but I'm going to vote no at this time.
CHAIRMAN BROWN: Could I urge the remaining members of the committee ??
(Laughter.)
CHAIRMAN BROWN: ?? to vote rather than ?? I appreciate it, and I let
Will, you know, chatter on because he hasn't said a whole lot, and I wanted
to hear what he had to say. And so thank you, but we'll never get through
if we continue to explain the reasons for our votes, each one and all. So,
Susan?
DR. LEITMAN: I take the opportunity to disagree with what you just said.
I think the vote at this table is so critical, it will have such a huge
impact potentially on the way America collects its blood, that if we go
beyond our designated time it's worth it.
And I was influenced, and it was helpful to hear the last speaker's
discussion. So I think if any of us have discussions or points to mention
now, they might be valuable.
The deliberations of this committee are among the most difficult of any
advisory committee I've ever been on because there are simply inadequate
data upon which to base a decision. For myself, in the absence of data
suggesting or, rather, documenting risk, I cannot vote yes based on
assumptions, perceptions, possibilities, uncertainties, theoretical risks,
and potential risks.
On the other hand, there are tangible measurable data that deferral of any
percentage of donors, whether it's half, one and a half, two percent, will
lead to replacement by donors by a small proportion of donors that are at
increased risk for measurable diseases such as hepatitis B and C. So I vote
no.
CHAIRMAN BROWN: Dr. Leitman votes no. Dr. Prusiner?
DR. PRUSINER: I would like to vote yes, and I would like to say I have 23
points that I want to go through.
(Laughter.)
DR. PRUSINER: I only want to say very quickly that I don't think that
economics and the availability of donors is a reason to vote yes or no in
this. I think that the economy has a way of solving these problems, and I
think that will happen. I think the real problem here lies that we have a
very imperfect data set, and we're dealing with a disease which is
universally fatal. This is really the problem that we face.
CHAIRMAN BROWN: Dr. Prusiner votes yes. Dr. Roos?
DR. ROOS: I think we're dealing with a situation in which we have no
evidence of any transfusion that has transmitted either classical or new
variant Creutzfeldt. And we have a situation where there are risks involved
with blood transfusions that the donors accept at this point.
That is, we were informed about ?? I guess about 14 percent of individuals
do donate blood that have I guess the recipients. About 14 percent of
individuals that donate blood have some risky behavior. And maybe I might
include living in UK part of that risky behavior.
And so I kind of accept this as, at the moment, acceptable risk for
donated blood and I am awaiting evidence to prove that there is more danger
involved. So I'm voting no here.
CHAIRMAN BROWN: Dr. Roos votes no. Dr. Belay?
DR. BELAY: I'm concerned about two issues. The first one is the studies
that showed the presence of the new variant CJD agent in lymphoreticular
tissues. And the second concern I have is the absence of evidence against
blood-borne transmission of new variant CJD. The kind of data that's
available for classic CJD is not available for new variant CJD, so I vote
yes.
CHAIRMAN BROWN: Dr. Belay votes yes. Dr. Lurie?
DR. LURIE: Really, what we're doing is balancing one risk against two
others. The two risks are the problem of the replacement donor, which is
not zero but it is probably very small, given that we're only talking about
one, two perhaps, percent replacement of donors here, depending on what
happens in B if we get that far.
The second has to do with the diminution in the blood supply itself. And,
again, there are scenarios available to us under B that allow us to minimize
that. So we really have, on the one hand, two small risks that can more or
less be quantified, and on the other hand we have another risk, which may
itself be small, but if we are wrong could be very, very large. And that's
really the benefit ?? the risk benefit calculation that we're making.
For me, there remain too many uncertainties, and so I vote yes.
CHAIRMAN BROWN: Dr. Lurie votes yes. Dr. Hoel?
DR. HOEL: Yes. I'm changing my vote from last time, and I'm going to
vote yes, mainly because of what I see in the epidemiology data of the cases
in England and the modeling work. I think this needs to be monitored
further to see how it comes in because the risks could be quite large, and
so I would vote yes.
CHAIRMAN BROWN: Dr. Hoel votes yes. Dr. Bolton?
DR. BOLTON: I believe that there is insufficient documentation of the
risk at this time. And in light of that, I can't ?? I don't think that the
information warrants changing the current policy. I vote no.
CHAIRMAN BROWN: Dr. Bolton votes no. Dr. Nelson?
DR. NELSON: Well, this is a pretty difficult vote. Last time I voted no,
and I'm going to vote no again, although I am ?? really, it's disturbing
that there is no really good data at this point.
And I am impressed with a comment that was made earlier, and that is that
there is an experiment in the UK of many people who have been exposed to UK
donors over a period of many years. And I am somewhat reassured that there
have been no cases, and I'm also reassured with the quality of the
epidemiologic surveillance and data from the UK.
I think that that has been well done, carefully done, and presumably it
will continue to be closely monitored. You know, if a single case had
occurred, we would really need to change our policy immediately. That's
number one.
But the other problem I have is if I voted yes, then I would have to make
a decision on 1B. And the only ??
(Laughter.)
DR. NELSON: ?? the only reasonable decision on 1B would be to remove ??
to exclude all donors who had lived in the UK. I see no basis for any
arbitrary decision. Once you go down that route, then you have to exclude
anybody from the UK or who visited the UK or Ireland during this period. I
don't see any alternative.
CHAIRMAN BROWN: Dr. Nelson votes no. Dr. McCullough?
DR. McCULLOUGH: I agree with Susan. This is one of the most difficult
groups I have had to deal with. I'm impressed by the epidemiologic data.
I'm also impressed by having sat through in 1983 and 1984 discussions of
there ain't been a case reported yet, and also that we are concerned about
the impact on the blood supply.
hrms/dockets/ac/99/transcpt/3518t1.rtf???????????TRANSMISSIBLE SPONGIFORM
ENCEPHALOPATHIES ADVIS And possibly also, I'm influenced by having been the
fodder for congressional hearings and 60-minute expose on things that might
have been done differently at some of those times. So I'm going to vote
yes. I have tremendous confidence in the blood systems of this country that
they will be able to ?? not easily ?? respond if changes are made.
CHAIRMAN BROWN: Dr. McCullough votes yes. Dr. Brown votes yes. Dr.
Ewenstein?
DR. EWENSTEIN: Yes. I'm impressed by the modeling data. I believe that
we have biologic data as well as at least the potential epidemiology coming
out of England to suggest that this is a new disease and on that basis
should be handled with a lot more caution, because we don't have the comfort
that we have with the long-standing classical CJD. And so I'm going to vote
yes.
CHAIRMAN BROWN: Dr. Ewenstein votes yes. Dr. Detwiler?
ORY COMMITTEE MEETING Thursday, June 3,
1999???????http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t2.rtf DR.
DETWILER: I'm going to vote yes, because with these diseases, a long
incubation and the lack of a pre-clinical screening test, that the day you
find out there is transmission you're already years too late, and you can't
easily clean up the problem. And I think they found out that even with the
human transmission because that was based on there is no theoretical ?? or
it's only a theoretical risk until 1996.
CHAIRMAN BROWN: Dr. Detwiler votes yes. Dr. Piccardo?
DR. PICCARDO: I would vote yes because all of the data from classical CJD
cannot be extrapolated into the new variant.
CHAIRMAN BROWN: Dr. Piccardo votes yes. Dr. Williams?
DR. WILLIAMS: I'm going to vote no. I think that this is truly a
balancing act, and it's a tradeoff between a known problem, I believe
related to the blood supply, and the problems that may follow from a reduced
supply and the perception of a risk of new variant CJD.
And I completely agree that an experiment is going on right now. Those
data are going to come in, and, obviously, there is going to be close
attention paid to those data, and that surely this committee and FDA will
respond should information indicate that we need to take another look at the
issue.
CHAIRMAN BROWN: Dr. Williams votes no. Dr. Hollinger?
DR. HOLLINGER: I'm voting no also, for the same reasons that have been
addressed. I think there is ?? by doing something now doesn't mean that
everything is going to be turned around and you don't have to worry about
it, if you do have a long incubation situation and one can wait to see if
there is some risk down the line, and I think we do have those things going
on ?? natural and experimental ?? in England. So I'm voting no.
CHAIRMAN BROWN: Dr. Hollinger votes no. Ms. Harrell?
?????????????P04.49??????????Case Report of V MS. HARRELL: Okay. Sitting
next to my ex-learned colleague ??
(Laughter.)
MS. HARRELL: Okay. I'm voting to be prudent, and I think that this will
buy us time to get the data in and have it analyzed from the UK. But right
now, we don't have time, and so I vote yes.
CHAIRMAN BROWN: Ms. Harrell votes yes. Dr. Cliver?
DR. CLIVER: No.
CHAIRMAN BROWN: Dr. Cliver votes no. Dr. Burke?
DR. BURKE: This is a balancing act, and I can ?? there are measurable
negatives here. In the face of a theoretical, I vote no.
CHAIRMAN BROWN: Dr. Burke votes no. Dr. Tramont?
DR. TRAMONT: I vote yes.
CHAIRMAN BROWN: Dr. Tramont votes yes. Twelve yes. Nine no. Well, at
the least, Dr. Epstein can come away from the day with the understanding
that he has not been given a mandate.
(Laughter.)
DR. FREAS: Can I just make a comment? I did verify the count. There are
21 voting people at the table. Dr. Roos is a non-voting participant. And
the total does add up to 21.
Excuse me. I apologize. Dr. Rohwer is ??
CHAIRMAN BROWN: I don't have to ask Bob what he would have voted, had he
been allowed to vote.
(Laughter.)
CHAIRMAN BROWN: But I will if you'd like to put it on the record.
This is simply a question to Bob, since he's at the table. Were his vote
to be counted, what would it have been?
DR. ROHWER: I'll use this soapbox opportunity.
CHAIRMAN BROWN: Uh-oh.
(Laughter.)
DR. ROHWER: I am very concerned that we may be facing the grave
possibility of an epidemic of new variant CJD, an epidemic that, if it
occurs, could be made much worse through the mechanism of interspecies
transmission, such as would occur through blood products. But I recognize
the real risks of insufficient supply.
However, I am impressed by Dr. Donnelly's warning that if the feed ban in
the case of BSE had been delayed just one year, the epidemic would have been
vastly worse than it was. And, therefore, I feel we should take whatever
opportunities for implementing mitigating measures that we can that do not
simultaneously jeopardize the supply unduly.
So I recognize that what we have ?? the opportunity we have here is very,
very imperfect, but I feel like it is possible to do something, and we
should do it.
CHAIRMAN BROWN: Jay, you wanted a recount, or just a reexpression?
DR. EPSTEIN: Just a reexpression.
CHAIRMAN BROWN: Okay. The vote on question 1A is 12 votes yes, nine
votes no. Therefore, the committee is obliged now to consider what deferral
criteria might be recommended. And presumably, based on the evidence, the
only deferral criteria that are offered us that make any sense are duration
of residence in the UK.

snip...258

Dr. Scott

skip

In addition, we do know, as Dr. Prusiner has pointed out several times, that
the new variant agent is biologically different from the classical CJD
agent, so we can't necessarily extrapolate all of the information that we
have on classical CJD to new variant.
For example, he talked about the differences in the protein and its
behavior, and we also know that there is enhanced expression of the new
variant agent in lymphoid tissues compared with CJD. And we don't know much
about its virulence or infectivity compared with the classical CJD.
And, of course, we haven't had time to get or enough patients or subjects
or transfused people to get the kind of epidemiologic data that we have
which tells us that transmission of classical CJD by blood or blood products
at worst is rare and may not occur.
So, currently, the diagnosis of new variant CJD is based upon
neuropathology, and these are the three most characteristic features ??
numerous widespread kuru type amyloid plaques, which obviously can occur in
a few other kinds of CJD but are quite common in new variant CJD; spongiform
change, which is predominant in certain areas of the brain; and a high
density prion protein accumulation, especially the cerebrum and the
cerebellum by immunohistochemistry, and tonsillar biopsy may ultimately play
a role in this diagnosis as well as analysis of prion glycoforms.

Current age, if alive, or age at death, less than 55. Since the typical age
of a new variant patient is about late 20s, and the typical age of a
classical CJD patient is about 65, this is one criteria that is useful. And
new variant patients tend to have persistent painful sensory symptoms early
in presentation and/or psychiatric symptoms.
I can go into this further if people want to know about it. But there
were a couple of articles published in the Lancet from the CJD surveillance
unit in September 1997, which goes into this in great detail.
In addition, the patient must have dementia and a delayed development of
neurologic symptoms, particularly movement disorders, about a four-month
delay. And, again, this is somewhat different from classical CJD in its
course. They may have a normal or abnormal EEG, but not the diagnostic EEG,
which is a pseudo periodic sharp wave that's often seen in classical CJD.
The duration of illness should be greater than six months. Again, this is
in marked distinction to most cases of classical CJD which average four to
four and a half months of duration. Whereas, the new variant case typically
is around 14 months duration, although there is a spread.
In addition, routine investigations will not suggest an alternate
diagnosis. And this is a criteria, really, for the U.S. There should be
history of possible exposure to BSE; that is, consumption of local beef
products as resident or traveler to a BSE-affected country.
And there is only two more. No history of iatrogenic exposures that are
related to development of classical CJD, and, finally, of course, such a
patient, if they had a prion protein gene mutation, it was associated with
familiar CJD. That would not fall under ?? that would not be a patient that
we would worry about new variant CJD in.

page...284

DR. ROOS: Thanks, Dr. Scott. So we're not asked to take a vote, but just
to discuss these issues. Yes?
DR. NELSON: I'm concerned a little bit about the explanation for the age
criteria, and I can see that this is very useful because the one thing you
do know, when somebody gets sick, you can estimate what their age is. And
so that's an easy ?? you know, an easy early marker for a possible case
that's not classical.
And I assume that probably the reason for the classical CJD patients being
much older is that the incubation period is so long that they probably had
an exposure much longer. But as this epidemic ?? or as the ?? if it's
exposure to the BSE agent from the epidemic, it seems like over time this
age criteria will probably change, and that the under 55 may no longer be a
useful criteria 10 years from now or 40 years from now.
And I just wonder if Larry or anybody could comment on that.
DR. SCHONBERGER: We definitely agree, and it underscores the evolving
nature of these diagnoses. All I can say is the age is an excellent and
easy criteria for us to use now. All cases, as you know, in the world of
new variant CJD have been under age 55. In fact, I think the oldest was ??
I think the median age is like 29 or so, 28 at onset and 29 at death. So
that's why that particular criteria came into existence.
However, obviously, if the epidemic should change and we should start
seeing older cases, then, obviously, we would have to change.
There is some semantic problems. We actually investigate every case under
55. So, in a sense, all cases under 55 in the United States could be
regarded as under investigation or possible. We have not used the word
"probable," in part because that's the word they use in the United Kingdom,
and they count those cases as amongst the cases of new variant CJD that we
count.
The 40 cases in the UK, I think, includes one, is it? One probable? That
was a case in a teenager whose brain tissue was unavailable for study. And
they indicate that it's too early in the epidemic. Their experience is too
small for them to be absolutely sure about that, but they're willing to ??
at this point to call it a case.
And I've been told that with these new MRI criteria, and so on, that maybe
we'll be able to call cases without necessarily having the tissue, depending
on what they find the specificity and sensitivity of those to be. So all
cases essentially under 55 right now are under investigation.
Plus, we have established amongst pathologists the concept that any case
that has the pathology of new variant CJD, regardless of age, or even
regardless of whether they've diagnosed it as CJD, should be reported. And
those two would count as new variant even though they are not under 55.
DR. ROOS: Just a quick question, Larry. What is your timeframe of
reporting, or what is the goal here? Obviously, with respect to these new
guidelines, you want to identify these cases fairly quickly and make some
disposition as far as blood products.
DR. SCHONBERGER: Precisely because we are looking at all cases under 55,
I was encouraging FDA to encourage the blood establishments ?? or the first
to identify these cases at least, and that has been the history ?? to report
to us any case of CJD under 55.
Once we get that report, it may be very easy for us and very quickly
making it ?? to very quickly make a determination that we're dealing with,
say, a dura mater case or a human growth hormone case. But then, another
part of FDA will probably become interested in that.
So we think it's worth the blood establishments reporting all of their
cases in donors. There just are not that many CJD cases that are going to
occur among donors that the blood establishment is going to be able to
identify that quickly. But if they do, we want it reported right away.
DR. ROOS: Just a quick question. So, I mean, how about if this patient
donates to some large blood pool or has donated whole blood? It doesn't go
back to the blood establishment. It goes to a neurologist, gets diagnosed,
etcetera. What's the timeframe then?
DR. SCHONBERGER: Well, frequently, our experience with the withdrawals ??
and I'll use the Utah case as an example as that came out ?? we handled that
very, very rapidly. But even handling it very, very rapidly, you'll find
that huge, huge numbers of recipients were exposed to this donor's blood
products.
So the withdrawal program is relatively inefficient, compared to what we
just did, which was to get deferral criteria. And I think that's why it was
important to try to be preemptive in a sense and have the deferral criteria
up front.
The withdrawal procedure, even when you do it very quickly as in the Utah
case, I would not encourage people to depend on that for considerable
safety. What we will do is we will modify and ameliorate the situation.
But it certainly won't eliminate even the majority of the risk.
DR. ROOS: I just think it might be good to publicize these new policies
widely to the neurological community, so that they alert you, Larry, or the
FDA quickly. The Utah case, in fact, was kind of a very aberrant case. It
could be that there are other cases that get less sophisticated care. And
if you really want to identify things in a timely manner, you obviously have
to publicize the program and new policies to the neurological community.
DR. SCHONBERGER: Well, let me clarify that the primary group doing the
surveillance on this are blood establishments. And if this group wants to
recommend that blood establishments, you know, provide blood donors with
cards or something that would, you know, speed up any type of reporting,
that's possible.
The surveillance that CDC is conducting is not designed for that type of
rapid turnaround or rapid identification in reporting. That's another
weakness of the system and relying on this withdrawal system for tremendous
protection of the population.
DR. ROOS: Peter?
DR. LURIE: My question/concern is whether or not requiring all nine of
these criteria is too restrictive a set of criterion. I guess the data
question that I have is: of the 30-odd new variant CJD cases in Britain,
how many of them have met all nine of these criteria?
DR. SCOTT: Well, could I also respond to that question?
DR. LURIE: Yes, please do.
DR. SCOTT; I don't know the answer to how many have had all nine of those
criteria, but most. However, the CJD surveillance unit has somewhat altered
their criteria with time such that the current organization is similar to
this but not the same. And most critically, they have gotten rid of the age
criteria and added an MRI criteria. But this is not yet published material,
and it's very recent. We just got that information on May 31st.
And I think the other thing to mention is that we weren't considering only
using all nine criteria. But, really, that's the purpose of the third way,
if I can say it, which is to have a very low threshold for identifying even
potential cases and then to make a rapid decision on a case-by-case basis.
But what we're anticipating is probably what you're thinking, that not all
of those criteria are going to be met, just due to a lack of information,
time hasn't passed, we don't have material to analyze. And so I think what
we're anticipating is that we would be ?? we would err on the side of
caution unless investigation showed us that it was most unlikely that this
was a new variant case.


snip...page 292

DR. HUESTON: You don't know to what you've been exposed. So it's ?? the
second thing is it draws ?? I think it gives a false sense of security and
directs, potentially, attention to the wrong products, because the average
person thinks of beef as primal cuts of beef. And that's, at this point,
the least likely of the sources of exposure, given meat products.
The third comment is that I personally am very concerned about the
proposed ?? this criteria of possible new variant CJD by FDA. And I have
two major reasons for that. The first is that I see the potential for
conflict arising between FDA and CDC, where FDA is stepping forward or
making a pronouncement of possible new variant CJD, and at the same time CDC
says, "We're still investigating; you know, it's premature."
And I think that puts the FDA in a very awkward position, and I think an
inappropriate ?? Larry is telling me that they are investigating 25 ??
DR. SCHONBERGER: There's about 25 cases under 55 a year.
DR. HUESTON: So my fear ?? here is my fear based on my experience. Item
number 2 says, "Donor has physician's clinical or pathologic diagnosis of
CJD."
DR. SCHONBERGER: They're not all donors, by the way. Very few of them
are donors. Okay?

DR. HUESTON: Okay. Fair enough. But once you get a terminology like this
established, my concern is that it's going to spread further, that people
are going to say, "Well, the FDA would have called this a possible case."
Number 2 says, "Has a physician's clinical or pathologic diagnosis," it
doesn't say anything about the physician. And no offense to my
distinguished colleagues, but there are a number of physicians that are
simply not in the position to make a clinical diagnosis or a pathologic
diagnosis of Creutzfeldt Jakob. That has not precluded some of these same
physicians from making a proclamation.
Third, I think that the public health and the risk communication
implications of this are potentially massive. And having been on the firing
?? you know, on the other end of trying to deal with these, you know, the
press grabbing hold of a case and blowing it totally out of proportion and
creating a great deal of concern, I don't see why you need another term.
I think you coordinate with the CDC, you coordinate your investigation
when it comes back from a blood collection center that you have a donor less
than 55 years of age, where you have some suspicion of Creutzfeldt Jakob
Disease. You go through the same CDC workup, and you base ?? on a
case-by-case basis, you base your decision on that coordination with CDC.


snip...page 296


see full text and all voting results


http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t1.rtf


TSEAC MEETING JUNE 3 1999

http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t2.rtf

PLEASE NOTE IN USA CJD UPDATE AS AT JUNE 2007, please note steady increase
in ''TYPE UNKNOWN''. ...TSS


1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17
inconclusive and 9 pending (1 from 2006, 8
from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1
from 2001, 1 from 2003, 4 from 2004, 3
from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26
from 2007)

http://www.cjdsurveillance.com/pdf/case-table.pdf


USA NVCJD BLOOD RECALLS ONLY ;


http://www.google.com/search?hl=en&q=CJD+BLOOD+RECALLS+TSS&btnG=Search


vCJD case study highlights blood transfusion risk


http://vcjdblood.blogspot.com/


CREUTZFELDT JAKOB DISEASE MAD COW BASE, CWD, SCRAPIE UPDATE OCT 2007


http://cjdmadcowbaseoct2007.blogspot.com/


NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007

Tuesday, October 9, 2007
NOR-98 SCRAPIE UPDATE AUGUST 31, 2007 RISES TO 5 DOCUMENTED CASES


http://nor-98.blogspot.com/

CREUTZFELDT JAKOB DISEASE MAD COW h-BASE UPDATE USA

http://cjdmadcowbaseoct2007.blogspot.com/

ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007

Date: Mon, 24 Sep 2007 21:31:55 -0500

I suggest that you all read the data out about h-BASE and sporadic CJD, GSS,
blood, and some of the other abstracts from the PRION2007. ...

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&F=&S=&P=19744

*** PLEASE READ AND UNDERSTAND THE RAMIFICATIONS OF THIS !!! THE PRICE OF
POKER INDEED GOES UP. ...TSS

USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it
today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were
''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007
11:52 PM. ...TSS

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779

From: "Terry S. Singeltary Sr."
Subject: CWD UPDATE 88 AUGUST 31, 2007


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450


Date: Wed, 29 Aug 2007 21:13:08 -0500
From: "Terry S. Singeltary Sr."
Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again)


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=26079

Monitoring the Potential Transmission of Chronic Wasting Disease to Humans
Using a Hunter Registry Database in Wyoming (405 lines)
From: Terry S. Singeltary Sr. <[log in to unmask]>
Date: Thu, 30 Aug 2007 21:23:42 -0500


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654


Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease
creates a new prion strain

Date: August 25, 2007 at 12:42 pm PST


Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease
creates a new prion strain
Date: August 25, 2007 at 12:42 pm PST

J Biol Chem. 2007 Aug 20; : 17709374

Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a
new prion strain.

[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , Tetsuyuki
Kitamoto

The genotype (methionine or valine) at polymorphic codon 129 of the human
prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform
of PrP (PrP(Sc)) are major determinants of the clinicopathological
phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that
transmission of sCJD prions from a patient with valine homozygosity (129V/V)
and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP with
methionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate in
size between type 1 and type 2. The intermediate type PrP(Sc) was seen in
all examined dura mater graft-associated CJD cases with 129M/M and
plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions
exhibited similar transmissibility and neuropathology, and the identical
type of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or
129V/V. These findings suggest that p-dCJD could be caused by cross-sequence
transmission of sCJD-VV2 prions.


snip...


In this study, the strain-dependent traits of sCJDMM1
prions were inherited through cross-sequence
transmission without any modification. The
humanized mice with 129V/V produced type 1 PrPres
after inoculation with sCJD-MM1 prions. Because
sCJD-VV1 cases are extremely rare (at most 1-2%
of the total number of sCJD cases) and characterized
by early onset (mean age at onset: 39.3 years) (5),

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

our results raise the possibility that CJD cases
classified as VV1 may include cases caused by
iatrogenic transmission of sCJD-MM1 prions or
food-borne infection by type 1 prions from animals,
e.g., chronic wasting disease prions in cervid. In fact,
two CJD-VV1 patients who hunted deer or
consumed venison have been reported (40, 41). The
results of the present study emphasize the need for
traceback studies and careful re-examination of the
biochemical properties of sCJD-VV1 prions.

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

In conclusion, cross-sequence transmission of
sCJD-VV2 prions generates a new prion strain with
altered conformational properties and disease
phenotypes as p-dCJD prions. Furthermore, the
newly generated prions have unique transmissibility
including the traceback phenomenon. In the future, if
atypical prion strains emerge through cross-sequence
transmission, especially from animals, traceback
studies will enable us to identify the origin of the
prions.

REFERENCES...snip...end

FULL TEXT ;


http://www.jbc.org/cgi/content/abstract/M704597200v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Cross-sequence+transmission+of+sporadic+Creutzfeldt-Jakob+disease+creates+a+new+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267

Re: Colorado Surveillance Program for Chronic Wasting Disease
Transmission to Humans (TWO SUSPECT CASES)


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165


Subject: MAD COW BASE H-TYPE AND L-TYPE

Date: August 23, 2007 at 11:30 am PST


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779

Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States


Email Terry S. Singeltary:


flounder@wt.net

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to

comment on the CDC's attempts to monitor the occurrence of emerging

forms of CJD. Asante, Collinge et al [1] have reported 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. However, CJD and all human TSEs are not reportable

nationally. CJD and all human TSEs must be made reportable in every

state and internationally. I hope that the CDC does not continue to

expect us to still believe that the 85%+ of all CJD cases which are

sporadic are all spontaneous, without route/source. We have many TSEs in

the USA in both animal and man. CWD in deer/elk is spreading rapidly and

CWD does transmit to mink, ferret, cattle, and squirrel monkey by

intracerebral inoculation. With the known incubation periods in other

TSEs, oral transmission studies of CWD may take much longer. Every

victim/family of CJD/TSEs should be asked about route and source of this

agent. To prolong this will only spread the agent and needlessly expose

others. In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?


http://www.neurology.org/cgi/eletters/60/2/176#535

LANCET INFECTIOUS DISEASE JOURNAL


Volume 3, Number 8 01 August 2003


Newsdesk


http://infection.thelancet.com/journal/journal.isa

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.

http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=dignosing+and+reporting+creutzfeldt+jakob+disease&searchid=1048865596978_1528&stored_search=&FIRSTINDEX=0&journalcode=jama

BRITISH MEDICAL JOURNAL

SOMETHING TO CHEW ON

BMJ

http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406

BMJ

http://www.bmj.com/cgi/eletters/320/7226/8/b#6117


P04.49


Case Report of Variant Creutzfeldt-Jakob Disease in a Macaque after Blood
Transfusion


Lescoutra-Etchegaray, N1; Ruchoux, MM1; Correia, E1; Jolit, A1; Freire, S1;
Lasmezas,
CI2; Deslys, JP1; Comoy, E1 1CEA/DSV/IMETI/SEPIA, France; 2Scripps Florida,
USA

A fourth human case of probable transmission of vCJD through transfusion has
now
been reported but a number of features affecting transfusion-related
infection remain
imprecise, including infectious dose, length of incubation period and
critical infectious
window of blood donors.


We report here the first case of experimental transmission of vCJD in
primates by
blood transfusion. Experimental infection of Cynomolgus macaque has been
demonstrated to be a sensitive model for the investigation of human prion
diseases,
inducing similar distribution of infectivity in peripheral lymphoid tissues
and equivalent
brain pathology. In our study, transfusion was performed with 40 ml of whole
blood
drawn from a vCJD-infected macaque at the terminal stage of the disease.
Clinical
symptoms of vCJD appeared in the recipient animal after five years of
incubation. The
total amount of infectivity in the transfused blood was approximately 106
fold lower
than in the brain (titration still in progress). In several animals infected
intravenously
with brain homogenate, the presence of PrPres in serial lymph nodes biopsies
and in
other organs at autopsy was examined and results will be presented.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


P04.51


Atypical Presentation of Variant Creutzfeldt-Jakob Disease in a 73 Year Old
Blood Transfusion Recipient


Wroe, S1; Pal, S1; Webb, T1; Alner, K2; Hewitt, P3; Brander, S4; Wadsworth,
JD5; Collinge, J1 1National Hospital for Neurology and Neurosurgery,
National Prion Clinic,
UK; 2National Hospital for Neurology and Neurosurgery, Department of
Neuropsychology, UK;
3Health Protection Agency, UK; 4National Hospital for Neurology and
Neurosurgery,
Department of Neuropathology, UK; 5Institute of Neurology, UCL, UK

We report atypical presentation of variant Creutzfeldt-Jakob Disease (vCJD)
identified
ante-mortem in a 73 year-old recipient of blood products. This patient was
transfused
following orthopaedic surgery in December 1997. Tracing of blood products
identified
a single unit of non-leucodepleted red cells from an individual who
developed
neuropathologically confirmed vCJD eleven months after donation. Nine years
post
transfusion, this individual was referred to the National Prion Clinic for
specialist
investigation. Six years post transfusion the recipient complained of
fluctuating fatigue
and impaired concentration. At this time neurological examination and MRI
brain
(T1/T2 weighted/DWI) were normal. Progressive symptoms emerged six months
later
with imbalance and deteriorating cognition. Examination two months after
onset of
neurological symptoms demonstrated cognitive deficits, dyspraxia or
visuospatial
dysfunction and normal motor, sensory and gait examination. Six weeks later
cognitive
impairment was identified alongside tremulousness, impaired manual dexterity
and
limb ataxia. Serological investigations were normal. MRI (T1/T2
weighted/FLAIR/DWI)
demonstrated prominent signal change throughout the dorsal thalamus,
consistent
with vCJD. PRNP genotyping revealed no mutations and homozygosity for
methionine
at codon 129. The prolonged incubation period of vCJD and possibility of
asymptomatic carrier states pose major public health concerns. This case
highlights
the significant risk encountered by recipients of contaminated blood
products and the
necessity for their specialist monitoring.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf

P04.36

Enhanced Surveillance of Persons Identified as at Increased Risk of CJD Due
to
Blood Transfusion or Healthcare Procedures

Brookes, D1; Chow, Y1; Ward, HJT2; Will, RG2; Hewitt, P3; Gill, ON1
1HPA, CJD, UK; 2National CJD Surveillance Unit, UK; 3Colindale, NHS Blood
and Tissue, UK


Introduction:

Reports of four iatrogenic transmissions of variant-CJD (vCJD) infection
in the UK (all due to transfusion of blood from donors who later developed
vCJD),
evidence from iatrogenic transmissions of sporadic CJD and experimental work
on
CJD infectivity in tissues and on healthcare instruments have given rise to
concern
about the risks of iatrogenic transmission of CJD. This risk warrants a)
certain public
health precautions, and b) follow-up of individuals with identified risks in
order to gain
evidence about their risks and ensure appropriate management of these risks.
Evidence of transmission via iatrogenic routes is important to inform public
health
measures and so prevent ongoing transmission of CJD.


Methods:


The Health Protection Agency and Health Protection Scotland holds details
of persons identified as ‘at-risk’ of vCJD due to blood transfusion and of
persons identified as ‘at-risk’ of CJD (of any type) from other healthcare
procedures. The GPs/clinicians of all persons identified as ‘at-risk’ for
public health
purposes are provided with: information; risk assessment updates; advice on
public health
precautions and advice on referral to specialist care. Procedures are being
established to obtain enhanced surveillance data on these individuals,
including:
clinical status updates, date and cause of death, surplus tissue and blood
specimens, and
postmortem investigations.


Results:


Persons ‘at-risk’ of CJD have experienced a range of exposures. Estimated
risks are uncertain and overlapping. Some individuals - recipients of vCJD
implicated blood components - are considered to be at a clearly higher risk
of
infection: active follow-up is currently conducted for these individuals. In
time, the
enhanced surveillance of persons at increased risk of CJD will provide
estimates of
transmission risks and of the impact of iatrogenic exposures on mortality.
Conclusion: Knowledge about iatrogenic transmission of CJD is being gained
by the follow-up of individuals who have been identified as ‘at-risk’ of CJD
in the
UK. This enhanced surveillance may need to be sustained for many years.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


Prions in Plasma of Patients with Sporadic Creutzfeldt-Jakob Disease
Safar, J.G1,3, Geschwindm M.D2,3, Letessier, F1,
Kuo, A1, Pomeroy, K1, Deering, C1, Serban, A1,
Groth, D1, Miller, B.L2,3, DeArmond, S.J1,4,
Prusiner, S.B1,3,5
1Institute for Neurodegenerative Diseases,
2Memory and Aging Center, Departments of
3Neurology, 4Pathology, and 5Biochemistry
and Biophysics, University of California,
San Francisco, California 94143


http://www.prion2007.com/pdf/Prion%20Friday.pdf

http://www.prion2007.com/pdf/Prion%20Thursday.pdf

http://www.prion2007.com/pdf/Prion%20Wednesday.pdf


Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518




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