TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS

Greetings,

I was looking up some old data, and ran across this TSEAC meeting back on FEBRUARY 12, 2004. I thought some might like to read over, there's some interesting comments here, and then a follow up of sorts to date on the topic. ...

kind regards, terry

UNITED STATES OF AMERICA

FOOD AND DRUG ADMINISTRATION

CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

+ + + + +

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY

COMMITTEE

MEETING

THURSDAY,

FEBRUARY 12, 2004

This transcript has not been edited

Or corrected, but appears as received

From the commerical transcribing

Service. Accordingly, the Food and

Drug Administration makes no

Representation as to its accuracy.

SNIP...

DR. GAMBETTI: Yes, much more MM. I just wanted to point out that actually it looks like the differences that are still conspicuous between variant CJD and sporadic CJD seem to kind of decrease, after a report from Switzerland, in which I'm sure you know, the scrapie prion protein was found in the spleen and muscle of about 20 to 30 percent of the cases with sporadic CJD, indicating that there must be, sometime during the course of the disease or during the entire course of the disease, some scrapie prion protein in the blood also of sporadic CJD patients, or at least a portion of sporadic CJD patients.

SNIP...

So in summary for the entire presentation here, from the animal models of blood-borne infectivity, I think we can say that we've had unequivocal demonstrations of blood-borne infectivity in rodents, sheep, and possibly now in monkeys. We've had diverse strains of agent that have been looked at, and this effect has been seen with familial Creutzfeldt-Jakob disease, the Fukuoka strain, variant CJD ?- this is Larisa Cervenakova's work ?- BSE, our work, and scrapie.

We've seen it in natural TSE infections, as well as experimental infections, and this is the Institute for Animal Health work with the sheep transfusions.

Next.

SNIP...

Next.

So if we take the presumption, and the FDA has just told us that they will presume that this was a transfusion transmission, then it fills in most of the missing gaps in this story. There can be TSE infectivity in human blood. It is present preclinically, and it is transmissible by transfusion. It may even have a virulence greater than might be expected from the incubation time in rodents, based on the incubation time in this particular case.

Next.

The only thing that's inconsistent with this story, and it is a major inconsistency, is why we haven't seen transfusion transmissions from classical cases of Creutzfeldt-Jakob disease. That has been discussed by a number of people already today. I can't really add much to that. Is it that we?re missing them, our surveillance isn't right? Is there something really truly different? We just don't know.

snip...

DR. BROWN: Thank you, Chairman Priola. I feel a little bit like I'm coming home, maybe for the last time, but it's a nice feeling.

I was asked by David Asher to present the results of the study which several years ago was undertaken by us with the funding of the Baxter Pharmaceutical Company, and it has henceforth become known as the Baxter study.

Before I do that, assuming I have my full complement of 15 minutes and I'm not down to six and a half, I wanted just to make a comment or two about one or two of the interesting questions that have been raised in the course of the morning.

The difficulty of proving that sporadic CJD could be transfusion-linked I think is probably only going to be solved by exactly the reverse of the situation that is so compelling as evidence for variant CJD transmission; and that is, instead of having a young, typical variant CJD donating blood to a person who is elderly -- when I say "elderly,? that's my age -- you're going to have to have a classic sporadic elderly patient transmitting blood to an unusually young patient, and then you'll have the same kind of certainty which is not totally certain, but you'll have some confidence that that has happened. And that's not going to be easy to find.

snip...

I was asked by David -- and with the kind permission of Corinne Lasmezas ? to also give you a summary of her studies, the studies of her group, directed by her now on what the French are up to with respect to primates.

But the first thing is our own study, and as I mentioned, it's a Baxter primate study, and those are the major participants. And the goal was twofold, and here is the first one: to see whether CJD, either sporadic or familial -- actually it turns out to be the familial CJD is incorrect. It really should be the Fukuoka strain of Gerstmann-Straussler-Scheinker disease. So it's really GSS instead of familial CJD -- when passaged through chimps into squirrel monkeys using purified blood components, very pure blood components.

So this addresses the question that was raised just recently about whether or not red cell infectivity that's been found in rodents is really in the red cells or is it contaminated.

We prepared these samples with exquisite care, and they are ultra-ultra-ultra purified. There's virtually no contamination of any of the components that we looked at ? platelets, red cells, plasma, white cells -- with any other component.

These are a sort of new set of slides, and what I've tried to do is make them less complicated and more clear, but I'm afraid I haven't included the build. So you'll just have to try and follow what I explain with this little red pointer.

There were three initial patients. Two of them had sporadic CJD. One of them had Gerstmann-Straussler-Scheinker syndrome. Brain tissue from each individual patient was inoculated intracerebrally into a pair of chimpanzees. All right?

From those chimps, either plasma or ultra purified -- in fact, everything is ultra-purified. I'll just talk about purified plasma, purified white cells -- were inoculated intracerebrally and intravenously to get the maximum amount of infective load into a pair of squirrel monkeys.

The same thing was done for each of these three sets. This monkey died from non-CJD causes at 34 months post inoculation.

Let me go back for a second. I didn't point out the fact that these were not sacrificed at this point. These chimpanzees were apheresed at 27 weeks when they were still asymptomatic. In this instance, we apheresed them terminally when they were symptomatic.

And before I forget, I want to mention just a little sidelight of this. Chimpanzees in our experience -- and I think we may be the only people that have ever inoculated chimpanzees, and that's no longer a possibility, so this was 20, 30 years ago -- the shortest incubation period of any chimpanzee that we have ever seen with direct intracerebral inoculation is 13 months.

So we chose 27 weeks, which is about seven months, and incidentally typically the incubation period is more like 16 or 18 months. The shortest was 13 months. We chose the 27th week, which is about six and a half months, thinking that this would be about halfway through the incubation period, which we wanted to check for the presence or absence of infectivity.

But within four weeks after the apheresis, which was conducted under general anesthesia for three or four hours apiece, every single one of the six chimpanzees became symptomatic. That is another experiment that I would love to conclude, perhaps because this is simply not heard of, and it very much smells like we triggered clinical illness. We didn't trigger the disease, but it certainly looks like we triggered symptomatic disease at a point that was much earlier than one would have possibly expected.

Maybe it will never be done because it would probably open the floodgates of litigation. There's no end of little things that you can find out from CJD patients after the fact. For example, the neighbor's dog comes over, barks at a patient, makes him fall down, and three weeks later he gets CJD. So you have a lawsuit against the neighbor.

I mean, this is not an unheard of matter, but I do think that physical stress in the form of anesthesia and four hours of whatever goes on with anesthesia, low blood pressure, sometimes a little hypoxemia looks like it's a bad thing.

So here we have the 31st week. All of the chimps are symptomatic, and here what we did was in order to make the most use of the fewest monkeys, which is always a problem in primate research, we took these same three patients and these six chimps. Only now we pooled these components; that is to say, we pooled the plasma from all six chimps. We pooled ultra-purified white cells from all six chimps because here we wanted to see whether or not we could distinguish a difference between intracerebral route of infection and intravenous route of infection.

With respect to platelets and red blood cells, we did not follow that. We inoculated both intracerebral and intravenously, as we had done earlier because nobody has any information on whether or not platelets and red cells are infectious, and so we wanted again to get the maximum.

This is an IV versus IC goal. This one, again, is just getting the maximum load in to see whether there is, in fact, any infectivity in pure platelets, in pure red cells.

And of all of the above, the only transmission of disease related to the inoculation was in a squirrel monkey that received pure leukocytes from the presymptomatic apheresis. So that goes some way to address the question as to whether or not it's a matter of contamination. To date the red cells have not been -- the monkeys that receive red cells have not been observed for more than a year because that was a later experiment.

So we still can't say about red cells, but we're about four and a half years down the road now, and we have a single transmission from purified leukocytes, nothing from plasma and nothing from platelets.

That was the first part of the experiment. The second part was undertaken with the cooperation of Bob Will and others supplying material to us. These were a couple of human, sporadic cases of CJD and three variant cases of CJD from which we obtained buffy coat and plasma separated in a normal way. That is, these are not purified components.

The two cases of sporadic CJD, the plasma was pooled from both patients. The buffy coat was pooled from both patients, and then inoculated intracerebrally and intravenously into three squirrel monkeys each. This is a non-CJD death five years after inoculation. The other animals are still alive.

For variant CJD we decided not to pool. It was more important to eliminate the possibility that there was just a little bit of infectivity in one patient that would have been diluted to extinction, if you like, by mixing them if it were to so occur with two patients, for example, who did not have infectivity. So each one of these was done individually, but the principle was the same: plasma and buffy coat for each patient was inoculated into either two or three squirrel monkeys. This is, again, a non-CJD related death.

In addition to that, we inoculated rain as a positive control from the two sporadic disease cases of human -- from the two human sporadic cases at ten to the minus one and ten to the minus three dilutions. We have done this many, many times in the past with other sporadic patients. So we knew what to expect, and we got exactly what we did expect, namely, after an incubation period not quite two years, all four monkeys developed disease at this dilution and at the minus three dilution, not a whole lot of difference between the two.

Now, these are the crucial monkeys because each one of these monkeys every three to four months was bled and the blood transfused into a new healthy monkey, but the same monkey all the time. So this monkey, for example, would have received in the course of 21 months about six different transfusions of blood from this monkey into this monkey, similarly with this pair, this pair, and this pair. So you can call these buddies. This is sort of the term that was used. These monkeys are still alive.

In the same way, the three human variant CJD specimens, brain, were inoculated into four monkeys, and again, each one of these monkeys has been repeatedly bled at three to four month intervals and that blood transfused into a squirrel monkey, the same one each time. Ideally we would love to have taken bleeding at three months and inoculated a monkey and then let him go, watch him, and then done the same thing at six months. It would have increased the number of monkeys eightfold and just unacceptably expensive. So we did the best we could.

That, again, is a non-CJD death, as is this.

This was of interest mainly to show that the titer of infectivity in brain from variant CJD is just about the same as it from sporadic. We didn't do a minus five and a minus seven in sporadic because we have an enormous experience already with sporadic disease in squirrel monkeys, and we know that this is exactly what happens. It disappears at about ten to the minus five. So the brain titer in monkeys receiving human vCJD is identical to the brain titer in monkeys that have been inoculated with sporadic CJD.

That's the experiment. All of the monkeys in aqua are still alive. They are approaching a five-year observation period, and I think the termination of this experiment will now need to be discussed very seriously in view of a probable six-year incubation period in the U.K. case. The original plan was to terminate the experiment after five years of observation with the understanding that ideally you would keep these animals for their entire life span, which is what we used to do when had unlimited space, money, and facilities. We can't do that anymore.

It's not cheap, but I think in view of the U.K. case, it will be very important to think very seriously about allowing at least these buddies and the buddies from the sporadic CJD to go on for several more years because although you might think that the U.K. case has made experimental work redundant, in point of fact, anything that bears on the risk of this disease in humans is worthwhile knowing, and one of the things we don't know is frequency of infection. We don't know whether this case in the U.K. is going to be unique and never happen again or whether all 13 or 14 patients have received blood components are ultimately going to die. Let's hope not.

The French primate study is primarily directed now by Corinne Lasmezas. As you know, the late Dominique Dromont was the original, originally initiated this work, and they have very active primate laboratory in France, and I'm only going to show two very simple slides to summarize what they did.

The first one is simply to show you the basis of their statement that the IV route of infection looks to be pretty efficient because we all know that the intracerebral route of infection is the most efficient, and if you look at this where they inoculated the same infective load either intracerebrally or intravenously, the incubation periods were not substantially different, which suggests but doesn't prove, but doesn't prove that the route of infection is pretty efficient.

Lower doses of brain material given IV did extend the incubation period and presumably it's because of the usual dose response phenomenon that you see in any infectious disease.

With a whopping dose of brain orally, the incubation period was even lower. Again, just one more example of inefficiency of the route of infection and the necessity to use more infective material to get transmissions.

And they also have blood inoculated IV which is on test, and the final slide or at least the penultimate slide shows you what they have on test and the time of observation, that taken human vCJD and like us inoculated buffy coat, they've also inoculated whole blood which we did not do.

So to a great extent their studies are complementary to ours and makes it all worthwhile.

We have about -- oh, I don't know -- a one to two-year lead time on the French, but they're still getting into pretty good observation periods. Here's three-plus years.

They have variant CJD adapted to the macaque. That is to say this one was passaged in macaque monkeys, the cynomolgus, and they did the same thing. Again, we're talking about a study here in which like ours there are no transmissions. I mean, we have that one transmission from leukocytes, and that's it.

Here is a BSE adapted to the macaque. Whole blood, and then they chose to inoculate leukodepleted whole blood, in both instances IV. Here they are out to five years without a transmission.

And then finally oral dosing of the macaque, which had been infected with -- which was infected with BSE, but a macaque passaged BSE, whole blood buffy coat and plasma, all by the IC route, and they're out to three years.

So with the single exception of the leukocyte transmission from our chimp that was inoculated with a sporadic case of CJD or -- excuse me -- with a GSS, Gerstmann-Straussler, in neither our study nor the French study, which are not yet completed have we yet seen a transmission.

And I will just close with a little cartoon that appeared in the Washington Post that I modified slightly lest you get too wound up with these questions of the risk from blood. This should be a "corrective."

(Laughter.)

DR. BROWN: Thanks.

Questions?

CHAIRPERSON PRIOLA: Yes. Any questions for Dr. Brown? Dr. Linden.

DR. LINDEN: I just want to make sure I understand your study design correctly. When you mention the monkeys that have the IV and IC inoculations, the individual monkeys had both or --

DR. BROWN: Yes, yes, yes. That's exactly right.

DR. LINDEN: So an individual monkey had both of those as opposed to some monkeys had one and some had the other?

DR. BROWN: Correct, correct. Where IC and IV are put down together was IC plus IV into a given monkey.

DR. LINDEN: Into a given monkey. Okay.

And the IC inoculations, where were those given?

DR. BROWN: Right parietal cortex, Southern Alabama.

(Laughter.)

DR. BROWN: Oh, it can't be that clear. Yeah, here, Pierluigi.

CHAIRPERSON PRIOLA: Dr. Epstein.

DR. BROWN: Pierluigi always damns me with feint praise. He always says that's a very interesting study, but. I'm waiting for that, Pierluigi.

I think Jay Epstein --

DR. GAMBETTI: I will say that there's an interesting study and will say, but I just --

(Laughter.)

DR. GAMBETTI: -- I just point of review. You talk about a point of information. You say that -- you mention GSS, I guess, and the what, Fukuowa (phonetic) --

DR. BROWN: Yes, Fukuoka 1.

DR. GAMBETTI: Fukuowa, and is that from the 102, if I remember correctly, of the --

DR. BROWN: Yes, that is correct.

DR. GAMBETTI: Because that is the only one that also --

DR. BROWN: No, it's not 102. It's 101. It's the standard. It's a classical GSS. Oh, excuse me. You're right. One, oh, two is classical GSS. It's been so long since I've done genetics. You're right.

DR. GAMBETTI: Because that is the only one I know, I think, that I can remember that has both the seven kv fragment that is characteristic of GSS, but also the PrPsc 2730. So in a sense, it can be stretching a little bit compared to the sporadic CJD.

DR. BROWN: Yeah, I think that's right. That's why I want to be sure that I made you aware on the very first slide that that was not accurate, that it truly was GSS.

There's a GSS strain that has been adapted to mice, and it's a hot strain, and therefore, it may not be translatable to sporadic disease, correct. All we can say for sure is that it is a human TSE, and it is not variant. I think that's about it.

DR. GAMBETTI: I agree, but this is also not perhaps the best --

DR. BROWN: No, it is not the best. We understand --

DR. GAMBETTI: -- of GSS either.

DR. BROWN: Yeah. If we had to do it over again, we'd look around for a -- well, I don't know. We'd probably do it the same way because we have two sporadics already on test they haven't transmitted, and so you can take your pick of what you want to pay attention to.

Jay?

DR. EPSTEIN: Yes, Paul. Could you just comment? If I understood you correctly, when you did the pooled apheresis plasma from the six chimps when they were symptomatic at 31 weeks, you also put leukocytes into squirrel monkeys in that case separately IV and IC, but in that instance you have not seen an infection come down in squirrel monkey, and the question is whether it's puzzling that you got transmission from the 27-week asymptomatic sampling, whereas you did not see transmission from the 31-week sampling in symptomatic animals.

DR. BROWN: Yes, I think there are two or three possible explanations, and I don't know if any of them are important. The pre-symptomatic animal was almost symptomatic as it turned out so that we were pretty close to the period at which symptoms would being, and whether you can, you know, make much money on saying one was incubation period and the other was symptomatic in this particular case because both bleedings were so close together. That's one possibility.

The other possibility is we're dealing with a very irregular phenomenon and you're not surprised at all by surprises, so to speak so that a single animal, you could see it almost anywhere.

The third is that we, in fact, did just what I suggested we didn't want to do for the preclinical, namely, by pooling we got under the threshold. See?

You can again take that for what it's worth. It is a possible explanation, and again, until we know what the levels of infectivity are and whether by pooling we get under the threshold of transmission, we simply cannot make pronouncements.

CHAIRPERSON PRIOLA: Dr. DeArmond.

DR. DeARMOND: Yeah, it was very interesting data, but the --

(Laughter.)

DR. BROWN: I just love it. Go ahead.

DR. DeARMOND: Two comments. The first one was that the GSS cases, as I remember from reading your publications -- I think Gibbs was involved with them -- when you transmitted the GSS into animals, into monkeys, perhaps I think it was chimps, the transmission was more typical of CJD rather than GSS. There were no amyloid plaques. It was vacuolar degeneration so that you may be transmitting a peculiar form, as I criticized once in Bali and then you jumped all over me about.

DR. BROWN: I may do it again.

DR. DeARMOND: Calling me a bigot and some other few things like that.

(Laughter.)

DR. BROWN: Surely not. I wouldn't have said that.

DR. DeARMOND: So there could be something strange about that particular --

DR. BROWN: Yeah. I think you and Pierluigi are on the same page here. This may be an unusual strain from a number of points of view.

DR. DeARMOND: The other question though has to do with species barrier because the data you're showing is kind of very reassuring to us that it's hard to transmit from blood, but the data from the sheep and from the hamsters and some of the work, I think, that has been done by others, that it's easy in some other animals to transmit, hamster to hamster, mouse to mouse.

Could you comment on the --

DR. BROWN: That's exactly why we went to primates. That's exactly it, because a primate is closer to a human than a mouse is, and that's just common sense.

And so to try and get a little closer to the human situation and not totally depend on rodents for transferrable data, that is why you would use a primate. Otherwise you wouldn't use them. They're too expensive and they cause grief to animal care study people and protocol makers and the whole thing.

Primate studies are a real pain.

DR. DeARMOND: But right now it's inconclusive and you need more time on it.

DR. BROWN: I believe that's true. I think if we cut it off at six years you could still say it was inconclusive, and cutting it off at all will be to some degree inconclusive, and that's just the way it is.

DR. DeARMOND: So what has to be done? Who do you have to convince, or who do we all have to convince to keep that going?

DR. BROWN: Thomas?

Without trying to be flip at all, the people that would be the first people to try to convince would be the funders of the original study. If that fails, and it might for purely practical reasons of finance, then we will have to look elsewhere because I really don't want to see those animals sacrificed, not those eight buddies. Those are crucial animals, and they don't cost a whole lot to maintain. You can maintain eight -- well, they cost a lot from my point of view, but 15 to $20,000 a year would keep them going year after year.

CHAIRPERSON PRIOLA: Dr. Johnson.

DR. JOHNSON: Yeah, Paul, I'm intrigued as you are by the shortening of the incubation period. Have you in all of the other years of handling these animals when they were transfused, when they were flown out to Louisiana at night -- a lot of the stressful things have happened to some of these chimps. Have you ever noticed that before or is this a new observation?

DR. BROWN: Brand new.

MR. JOHNSON: Brand new. Okay.

CHAIRPERSON PRIOLA: Bob, did you want to say something? Dr. Rohwer.

DR. ROHWER: The Frederick fire, wasn't that correlated with a lot of --

DR. BROWN: Not that I k now of, but you may --

DR. ROHWER: Well, that occurred shortly after I came to NIH, and what I remember is that there were a whole bunch of conversions that occurred within the few months following the fire. That was fire that occurred adjacent to the NINDS facility, but in order to protect it, they moved the monkeys out onto the tarmac because they weren't sure it wouldn't burn as well.

DR. BROWN: Well, if you're right, then it's not brand new, but I mean, I'm not sure how we'll ever know because if I call Carlton and ask him, I'm not sure but what I would trust the answer that he gives me, short of records.

You know, Carlot is a very enthusiastic person, and he might say, "Oh, yeah, my God, the whole floor died within three days," but I would want to verify that.

On the other hand, it may be verifiable. There possibly are records that are still extant.

DR. ROHWER: Actually I thought I heard the story from you.

(Laughter.)

DR. BROWN: You didn't because it's brand new for me. I mean, either that or I'm on the way

(Laughter.)

CHAIRPERSON PRIOLA: Dr. Bracey.

DR. BRACEY: I was wondering if some of the variability in terms of the intravenous infection route may be related to intraspecies barriers, that is, the genetic differences, the way the cells, the white leukocytes are processed, whether or not microchimerism is established, et cetera.

DR. BROWN: I don't think that processing is at fault, but the question, the point that you raise is a very good one, and needless to say, we have material with which we can analyze genetically all of the animals, and should it turn out that we get, for example, -- I don't know -- a transmission in one variant monkey and no transmissions in another and a transmission in three sporadic monkeys, we will at that point genetically analyze every single animal that has been used in this study, but we wanted to wait until we could see what would be most useful to analyze.

but the material is there, and if need be, we'll do it.

CHAIRPERSON PRIOLA: Okay. Thank you very much, Dr. Brown.

I think we'll move on to the open public hearing section of the morning.

snip...


http://www.fda.gov/ohrms/dockets/ac/04/transcripts/4019t1.DOC



FC5.1.1 Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD, and GSS Blood Specimens: the Baxter Study

Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5; Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama, USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK; 5Baxter BioSience, Austria

Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported. Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious. Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded ‘prion’ protein (PrPTSE). Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months. Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD.

***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the ‘shock’ of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.

FC5.1.2 Interim Transmission Results in Cynomolgus Macaques Inoculated with BSE and

vCJD Blood Specimens

Lasmezas, C1; Lescoutra, N2; Comoy, E2; Holznagel, E3; Loewer, J3; Motzkus, D4; Hunsmann, G4; Ingrosso, L5; Bierke, P6; Pocchiari, M5; Ironside, J7; Will, R7; Deslys, JP2 1Scripps Florida, Infectology, USA; 2CEA, France; 3PEI, Germany; 4DPZ, Germany; 5Istituto Superiore di Sanita, Italy; 6SMI, Sweden; 7CJD Surveillance Unit, UK

BSE and vCJD transmitted to cynomolgus macaques reproduce many features of human vCJD, including clinical symptoms, neuropathological hallmarks of vCJD, PrPres electrophoretical pattern and, most importantly, the wide distribution of infectivity in peripheral organs. The latter characteristic distinguishes vCJD from sCJD in both humans and cynomolgus macaques, and prompted us to use this non-human primate model for further investigations of vCJD and its risk for human health. The occurrence of four vCJD infections in humans transfused with blood from patients who later developed vCJD has raised concern about blood transfusion safety in countries with vCJD. In this collaborative European study, we investigated the infectivity of blood components and whole blood administered by intracerebral (ic) and intravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic and iv route, respectively, from two vCJD patients and from two clinical vCJD-inoculated macaques. Transfusions were also performed from whole blood and blood leucodepleted according to hospital practice standards from two clinical BSE inoculated macaques. Blood infectivity during the preclinical phase is being examined in orally infected macaques. Whole blood was collected and transfused from one such animal two years after oral challenge, whereas buffy-coat and plasma from two animals at 2 and 4.5 years post-challenge, respectively, have been inoculated by the ic route. This is an ongoing study in which recipient animals continue to be observed at various times post-inoculation. So far, we have had one positive transmission in one animal transfused 65 months earlier with 40 ml of whole blood from a vCJD macaque (the characteristics of the disease in this animal will be shown in a separate poster by E. Comoy). This positive transmission reproduces transfusion transmission of vCJD in humans, with an incubation of 5.5 years compatible with incubation periods observed in humans.


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



TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE

JUNE 12, 2009

REFERENCES SENT TO MEMBERS

Topic I: Modified FDA Risk Assessment for Potential Exposure to the Infectious Agent of variant Creutzfeldt-Jakob Disease (vCJD) in U.S.–licensed Plasma-Derived Factor VIII

1. Clarke P et al. Projections of the future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility. J. R. Soc. Interface 2005; 2: 19-31.

2. FDA Draft Guidance for Industry: Amendment (Donor Deferral for Transfusion in France Since 1980) to "Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products". August 2006.


http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/ucm074083.htm



3. FDA Guidance for Industry. Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products. January 2002.


http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/ucm074089.htm



4. FDA Web Posting: Potential Risk of Variant Creutzfeldt-Jakob Disease (vCJD) From Plasma-Derived Products.


http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/BloodSafety/ucm095062.htm



5. FDA Draft Quantitative Risk Assessment of vCJD Risk Potentially Associated with the Use of Human Plasma-Derived Factor VIII Manufactured Under United States (US) License From Plasma Collected in the US. November 27, 2006.


http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/BloodSafety/UCM095104.pdf




Risk Assessment Appendix


http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/BloodSafety/UCM095106.pdf



6. Foster PR. Removal of TSE agents from blood products. Vox Sanguinis 2004; 87 (Suppl. 2): 7-10.

7. Hilton D et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 2004; 203: 733-739.

8. Lee DC et al. A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins. Transfusion Complications 2001; 41: 449-455.

9. UK HPA. vCJD Abnormal Prion Protein Found in a Patient with Haemophilia at Post Mortem. February 2009.


http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1195733818681



http://www.fda.gov/downloads/AdvisoryCommittees/Calendar/UCM164326.pdf



PRODUCT Recovered Plasma, Recall # B-1413-09 CODE Unit: 1689491 RECALLING FIRM/MANUFACTURER Blood Bank of Hawaii, Honolulu, Hawaii, by facsimile on March 5, 2009. Firm initiated recall is complete. REASON Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob Disease (vCJD), was distributed. VOLUME OF PRODUCT IN COMMERCE 1 unit DISTRIBUTION NY

___________________________________

PRODUCT 1) Red Blood Cells, Recall # B-1488-09; 2) Recovered Plasma, Recall # B-1489-09 CODE 1) and 2) Unit: W126908247145 RECALLING FIRM/MANUFACTURER Southeastern Community Blood Center, Tallahassee, FL, by fax on April 8, 2009 and follow-up letter on April 17, 2009. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION FL, Austria

___________________________________

PRODUCT 1) Red Blood Cells Leukocytes Reduced Irradiated, Recall # B-1541-09; 2) Recovered Plasma, Recall # B-1542-09 CODE 1) and 2) Unit: W044108019097 RECALLING FIRM/MANUFACTURER Siouxland Community Blood Bank, Sioux City, IA, by e-mail and letter dated March 3, 2009 and follow-up letter on March 10, 2009. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION Austria, IA

___________________________________

PRODUCT 1) Red Blood Cells, Recall # B-1545-09; 2) Fresh Frozen Plasma, Recall # B-1546-09 CODE 1) and 2) Unit: W089808202149 RECALLING FIRM/MANUFACTURER Inova Health Care Services, Blood Donor Services, Sterling, VA, by letter dated January 9, 2009 and follow-up telephone call on January 23, 2009. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION VA

END OF ENFORCEMENT REPORT FOR SEPTEMBER 2, 2009

###


http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm181251.htm



PRODUCT Red Blood Cells Leukocytes Reduced. Recall # B-1148-09 CODE Unit: 3291680 RECALLING FIRM/MANUFACTURER Florida's Blood Centers, Inc, Orlando, FL, by telephone on January 12, 2009 and by letter dated January 13, 2009. Firm initiated recall is complete. REASON Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob Disease (vCJD), was distributed. VOLUME OF PRODUCT IN COMMERCE 1 unit DISTRIBUTION FL

___________________________________


PRODUCT 1) Recovered Plasma. Recall # B-1151-09; 2) Red Blood Cells Leukocytes Reduced. Recall # B-1152-09 CODE 1) and 2) Unit: 6585642 RECALLING FIRM/MANUFACTURER Carter BloodCare/ WE & Lela I Stewart Blood Center, Inc, Tyler, TX, by fax on April 23, 2007 and March 11, 2009. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX and Switzerland

___________________________________


END OF ENFORCEMENT REPORT FOR JULY 1, 2009

#


http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm170185.htm



PRODUCT 1) Red Blood Cells, Leukocytes Reduced. Recall B-1180-09; 2) Recovered Plasma. Recall # B-1181-09 CODE 1) and 2) Unit: 27LT64128 RECALLING FIRM/MANUFACTURER ARC Greater Alleghenies, Johnstown, PA, by telephone or electronic notification on December 1, 2008 and by letter dated December 3, 2008. Firm initiated recall is complete. REASON Blood products, collected from a donor who may have been at risk for Creutzfeldt-Jakob disease (CJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION CA, WV

___________________________________


PRODUCT 1) Recovered Plasma. Recall # B-1214-09; 2) Red Blood Cells. Recall # B-1215-09 CODE 1) and 2) Unit: KS25920 RECALLING FIRM/MANUFACTURER Inova Health Care Services, Blood Donor Services, Sterling, VA, by letter dated November 23, 2007. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION VA, NJ

___________________________________



http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm170893.htm




PRODUCT Source Plasma. Recall # B-1206-09 CODE Units: 07YARF0702, 07YARE9866, 07YARE9175, 07YARE8806, 07YARE6013, 07YARE6743, 07YARE7284, 07YARE3054, 07YARE1421, 07YARE1044, 07YARE0168, 07YARD9701, 07YARD8977, 07YARD8152, 07YARD7695, 07YARD6945, 07YARD6722, 07YARD5923, 06YARE3812, 06YARE4248, 06YARE4943, 06YARE5522, 06YARE6898, 06YARE7196, 07YARA0218, 07YARA0575, 07YARA1157, 07YARA1574, 07YARA2145, 07YARA2571, 07YARA5682, 07YARA8317, 07YARA9272, 07YARA9637, 07YARB0583, 07YARB1028, 07YARB1861, 07YARB2231, 07YARB2855, 07YARB3489, 07YARB4656, 07YARB5193, 07YARB5849, 07YARB6358, 07YARB7036, 07YARB7618, 07YARB8311, 07YARB8853, 07YARB9492, 07YARC0024, 07YARC0639, 07YARC1138, 07YARC1799, 07YARC2236, 07YARC3313, 07YARC4218, 07YARC4928, 07YARC5294, 07YARC5924, 07YARC7298, 07YARC8991, 07YARC9252, 07YARD3794, 07YARD4519, 07YARD5590, 07YARF3027 RECALLING FIRM/MANUFACTURER BioLife Plasma Services LP, Fayetteville, AR, by fax on January 14, 2008. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 66 units DISTRIBUTION CA

PRODUCT 1) Red Blood Cells. Recall # B-1250-09; 2) Fresh Frozen Plasma. Recall # B-1251-09 CODE 1) and 2) Unit: 4054709 RECALLING FIRM/MANUFACTURER Wellmont Health System dba Marsh Regional Blood Center, Kingsport, TN, by letter dated October 4, 2007. Firm initiated recall is complete. REASON Blood products, collected from a donor who was at risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TN

___________________________________


PRODUCT Source Plasma. Recall # B-1254-09 CODE Units: 363035924, 363035761, 363034642, 363034463, 363034153, 363033965, 363033670, 363033509, 363033093, 363032543, 363032383, 363032099, 363031873, 363031593, 363031321, 363031001, 363030738, 363030235, 363030057, 363029728, 363028978, 363028657, 363028438, 363028031, 363027863, 363027492, 363027314, 363026918, 363026688, 363026356, 363026123, 363025728, 363025483, 363025047, 363024873, 363024318, 363023960, 363023655, 363023279, 363022828, 363022612, 363020673, 363020392, 363021363, 363021144, 363019633, 363019419, 363018827, 363018647, 363016935, 363016561, 363016170, 363015723, 363014906, 363014413, 363014104, 363013235, 363012843, 363012402, 363011999, 363011601, 363011195, 363008854, 363008420, 363008054, 363007611, 363007268, 363006814, 363006486, 363006074, 363005753, 363005310, 363004961, 363004496, 363004188, 363003610, 363000147, I74029391, I74028830, I74028628, I74025361, I74024797, I74024560, I74024220, I74024002, I74023653, I74023404, I74023044, I74022854, I74022445, I74022288, I74021933, I74021763, I74021452, I74021274, I74020724, I74019586, I74025147, 363015212 RECALLING FIRM/MANUFACTURER Talecris Plasma Resources Inc, Fort Worth, TX, by facsimile on March 13, 2007. Firm initiated recall is complete. REASON Blood products, collected from a donor who was at risk for Creutzfeldt-Jakob Disease (CJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 99 units DISTRIBUTION NC

___________________________________


END OF ENFORCEMENT REPORT FOR JULY 22, 2009

###


http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm173256.htm



PRODUCT 1) Red Blood Cells Leukocytes Reduced. Recall # B-1281-09; 2) Platelets Leukocytes Reduced. Recall # B-1282-09; 3) Recovered Plasma. Recall # B-1283-09 CODE 1) Units: 1974540, W044108025910; 2) Unit: W044108025910; 3) Units: W044108025910, 1974540 RECALLING FIRM/MANUFACTURER Siouxland Community Blood Bank, Sioux City, IA, by letter and email on February 3, 2009. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 5 units DISTRIBUTION Austria, IA

___________________________________


END OF ENFORCEMENT REPORT FOR JULY 29, 2009

###


http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm174738.htm



Sunday, May 10, 2009

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)


http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html




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




Sent: Monday, July 27, 2009 10:31 PM

Subject: [CJDVoice] Re: [BSE-L] U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?

FINALLY, GOT IT UPLOADED !

SEE THE VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;


http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html



Subject: Transmission of BSE by blood transfusion in sheep... Date: Thu, 14 Sep 2000 18:19:06 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

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

Greetings List Members,

More Dredful news, but predictable...

kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA


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


It is possible to transmit BSE to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection'

It is well known that variant Creutzfeldt-Jakob disease (vCJD) is caused by the same strain of agent that causes bovine spongiform encephalopathy (BSE) in cattle. F Houston and colleagues report the preliminary findings of transfusing blood from 19 UK Cheviot sheep fed with 5 g BSE-affected cattle brain into Cheviot sheep from scrapie-free flock of New Zealand-derived animals. The investigators found BSE clinical signs and pathology in one recipient of blood taken from a BSE infected animal. Immunocytochemistry on tissues taken from the transfused sheep showed widespread PrPSC deposition throughout the brain and the periphery. This finding suggests that blood donated by symptom-free vCJD-infected human beings could transmit infection to recipients of blood transfusions. In a Commentary, Paul Brown states that these observations are consistent with previous reports in experimentally infected rodents.

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

Research letters Volume 356, Number 9234 16 September 2000

Transmission of BSE by blood transfusion in sheep

Lancet 2000; 356: 999 - 1000 Download PDF (1 Mb)

F Houston, J D Foster, Angela Chong, N Hunter, C J Bostock

See Commentary

We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) in human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission--this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK.

The demonstration that the new variant of Creutzfeldt-Jakob disease (vCJD) is caused by the same agent that causes bovine spongiform encephalopathy (BSE) in cattle1 has raised concerns that blood from human beings in the symptom-free stages of vCJD could transmit infection to recipients of blood transfusions. There is no evidence that iatrogenic CJD has ever occurred as a result of the use of blood or blood products, but vCJD has a different pathogenesis and could present different risks. CJD is one of the transmissible spongiform encephalopathies (TSEs) characterised by the deposition of an abnormal form of a host protein, PrPSc; the normal isoform (PrPC) is expressed in many body tissues. Available evidence, based on detection of infectivity in blood in rodent models, and absence of infectivity in naturally occurring TSEs, adds to the uncertainty in risk assessments of the safety of human blood. PrPSc has been reported in blood taken from preclinical TSE-infected sheep,2 but it does not follow that blood is infectious. Bioassays of human blood can only be carried out in non-human species, limiting the sensitivity of the test. One way of avoiding such a species barrier is to transfer blood by transfusion in an appropriate animal TSE model. BSE-infected sheep harbour infection in peripheral tissues3 and are thus similar to humans infected with vCJD.4 BSE infectivity in cattle does not have widespread tissue distribution.

We report preliminary data from a study involving blood taken from UK Cheviot sheep challenged orally with 5 g BSE-affected cattle brain and transfused into Cheviot sheep from a scrapie-free flock of New Zealand-derived animals (MAFF/SF flock). MAFF/SF sheep do not develop spontaneous TSE and the transfused animals are housed separately from other sheep. All sheep in the study have the PrP genotype AA136QQ171 which has the shortest incubation period of experimental BSE in sheep.5 19 transfusions from BSE-challenged sheep have been done, mostly with whole blood. Sheep have complex blood groups and only simple cross-matching can be done by mixing recipient serum and donor erythrocytes and vice versa. Therefore single transfusions only were made between sedated cross-matched animals to minimise the risk of severe reactions. Negative controls were MAFF/SF sheep transfused with blood from uninfected UK Cheviot sheep. As a positive control, MAFF/SF sheep were intravenously injected with homogenised BSE-affected cattle brain.

We have seen BSE clinical signs and pathological changes in one recipient of blood from a BSE-infected animal, and we regard this finding as sufficiently important to report now rather than after the study is completed, several years hence. The blood donation resulting in transmission of BSE to the recipient was 400 mL of whole blood taken from a healthy sheep 318 days after oral challenge with BSE. BSE subsequently developed in this donor animal 629 days after challenge, indicating that blood was taken roughly half way through the incubation period. 610 days after transfusion, the transfused sheep (D505) itself developed typical TSE signs: weight loss, moderate pruritus, trembling and licking of the lips, hind-limb ataxia, and proprioceptive abnormalities. This is the first experimental transmission of BSE from sheep to sheep and so we have nothing with which to compare this incubation period directly. In cross-species transmissions, bovine BSE injected intracerebrally gives incubation periods of about 450 days in these sheep,5 and the donor animal had an oral BSE incubation period of 629 days (see above). There are no similar data available on other infection routes. Immunocytochemistry with the antibody BG4 on tissues taken from sheep D505 showed widespread PrPSc deposition throughout the brain and periphery. Western blot analysis of brain tissue with the antibody 6H4 showed that the PrPSc protein had a glycoform pattern similar to that of experimental BSE in sheep and unlike that of UK natural scrapie (figure), indicating that the TSE signs resulted from transmission of the BSE agent. All other recipients of transfusions and positive and negative controls are alive and healthy. The positive controls, which involve a species barrier, are expected to have lengthy incubation periods. With one exception, all transfused animals are at earlier stages post-transfusion than was D505. The exception is a sheep which is healthy 635 days after transfusion with BSE-blood donated at less than 30% of the BSE incubation period of the donor sheep.

PrPSc (proteinase K treated) analysed by SDS-PAGE, immunoblotted with 6H4, and visualised with a chemiluminescent substrate

All lanes are from the same gel with different exposure times. Size markers are to the left of lane 1. Lane1: natural scrapie sheep brain, 3 min exposure. Lane 2: as lane 1, 10 min exposure. Lane 3: sheep D505, blood-transfusion recipient, 10 min exposure. Lane 4: experimental BSE-affected sheep brain, 30 s exposure. Lane 5: as lane 4, 10 min exposure. Each lane loaded with amount of protein extracted from 0·1 g wet weight of brain, except lane 3 which was extracted from 0·2 g brain.

Although this result was in only one animal, it indicates that BSE can be transmitted between individuals of the same species by whole-blood transfusion. We have no data on blood fractions or on levels of infectivity in blood of preclinical vCJD cases, but whole blood is not now used in UK transfusions. The presence of BSE infectivity in sheep blood at an early stage in the incubation period suggests that it should be possible to identify which cells are infected, to test the effectiveness of leucodepletion, and to develop a diagnostic test based on a blood sample.

We thank Karen Brown, Moira Bruce, Calum McKenzie, David Parnham, Diane Ritchie, and the Scottish Blood Transfusion Service. The project is funded by the Department of Health.

1 Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 488-501 [PubMed].

2 Schmerr MJ, Jenny A, Cutlip RC. Use of capillary sodium dodecyl sulfate gel electrophoresis to detect the prion protein extracted from scrapie-infected sheep. J Chromatogr B Biomed Appl 1997; 697: 223-29 [PubMed].

3 Foster JD, Bruce M, McConnell I, Chree A, Fraser H. Detection of BSE infectivity in brain and spleen of experimentally infected sheep. Vet Rec 1996; 138: 546-48 [PubMed].

4 Hill AF, Zeidler M, Ironside J, Collinge J. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 1997; 349: 99-100.

5 Goldmann W, Hunter N, Smith G, Foster J, Hope J. PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 1994; 75: 989-95 [PubMed].

Institute for Animal Health, Compton, Newbury, UK (F Houston PhD, CJ Bostock PhD); and Institute for Animal Health, Neuropathogenesis Unit, Edinburgh, EH9 3JF, UK (N Hunter PhD, JD Foster BSc, Angela Chong BSc)

Correspondence to: Dr N Hunter


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


Commentary Volume 356, Number 9234 16 September 2000

BSE and transmission through blood

Lancet 2000; 356: 955 - 956 Download PDF (55 Kb) Wether the outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the UK will ultimately affect hundreds, or tens of thousands of people, cannot yet be predicted.1 If large numbers of apparently healthy people are now silently incubating infections with bovine spongiform encephalopathy (BSE), the implications for public health include the possiblity that blood from such individuals may be infectious. Established facts about infectivity in the blood of human beings and animals with transmissible spongiform encephalopathies (TSEs) are as follows:2-4

Blood, especially the buffy-coat component, from animals experimentally infected with scrapie or CJD and from either a clinical or preclinical incubation phase, is consistently infectious when bioassayed by intracerebral or intraperitoneal inoculation into the same species;

In naturally infected animals (sheep and goats with scrapie, mink with transmissible mink encephalopathy, and cows with BSE), all attempts to transmit disease through the inoculation of blood have failed;

Blood from four of 37 human beings with clinically evident sporadic CJD has been reported to transmit the disease after intracerebral inoculation into guineapigs, mice, or hamsters. But each success has been questioned on technical grounds and has not been reproducible; and

Epidemiological data have not revealed a single case of CJD that could be attributed to the administration of blood or blood products among patients with CJD, or among patients with haemophilia and other congenital clotting or immune deficiencies who receive repeated doses of plasma concentrates.

No comparable information about vCJD is available. However, since lymphoreticular organs, such as tonsils have been shown to contain the prion protein (which is an excellent index of infectivity), whereas it is not detectable in patients with sporadic CJD, there is some reason to worry that blood from individuals incubating vCJD might be infectious.5 Data from studies into the ability of blood from experimentally infected rodents and primates with vCJD to transmit the disease will not be available for months or years.

In this issue of The Lancet, F Houston and co-workers report convincing evidence that blood from a seemingly healthy sheep incubating BSE (infected by the oral route with brain from a diseased cow) was able to cause the disease when transfused into another sheep. This observation is entirely consistent with past experience in experimentally infected rodents. It extends current knowledge about blood infectivity in experimental models to a host/TSE strain pair that is closer to the human vCJD situation than the earlier rodent studies. It is also the first successful transfusion of BSE from blood taken during the all-important incubation period of infection. This result is part of a larger study (n=19) that includes both positive and negative control animals, all still healthy and in various early stages of the incubation period.

Is it appropriate to publish an experimental result from a single animal in a study that is not far enough along even to have validated its positive controls? Especially a result that does not in any fundamental way change our current thinking about BSE and vCJD and which would not seem to have any practical consequences for public health? The UK National Blood Transfusion Service has already implemented leucodepletion of donated blood, and imports all plasma and plasma derivatives from BSE-free countries. No further measures would seem possible--short of a draconian decision to shut down the whole UK blood-donor system. What, therefore, is the rationale for this publishing urgency? The answer, evidently, is a perceived need to "defuse", by an immediate and accurate scientific report, public reaction to possibly inaccurate media accounts. The full study, when it appears, will be an important addition to our knowledge of TSEs, but science should not be driven to what in certain medical quarters might be termed a premature emission through fear of media misrepresentation.

Paul Brown

Laboratory of Central Nervous System Studies, National Institutes of Health, Bethesda, MD 20892, USA

1 Ghani AC, Ferguson NM, Donnelly CA, Anderson RM. Predicted vCJD mortality in Great Britain. Nature 2000; 406: 583-84 [PubMed].

2 Brown P. Can Creutzfeldt-Jakob disease be transmitted by transfusion? Curr Opin Hematol 1995; 2: 472-77 [PubMed].

3 Brown P, Cervenáková L, McShane LM, Barber P, Rubenstein R, Drohan WN. 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 1999; 39: 1169-78 [PubMed].

4 Rohwer RG. Titer, distribution, and transmissibility of blood-borne TSE infectivity. Presented at Cambridge Healthtech Institute 6th Annual Meeting "Blood Product Safety: TSE, Perception versus Reality", MacLean, VA, USA, Feb 13-15, 2000.

5 Hill AF, Butterworth RJ, Joiner S, et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999; 353: 183-89.


http://www.thelancet.com/



=================== TSS


http://www.whale.to/v/singeltary3.html



Subject: RESEARCH & FUNDING FOR HUMAN/ANIMAL TSE'S... [part 1]
Date: Thu, 06 Jul 2000 12:36:36 -0700 From: "Terry S. Singeltary Sr." <flounder@wt.net>
To: Dan.Glickman@usda.gov, President@whitehouse.gov, Vice.President@whitehouse.gov, First.Lady@whitehouse.gov, Mrs.Gore@whitehouse.gov

Dear Mr. Glickman,

could you please tell me, why certain people in your department (cutlipp, caughey, o'rourke, just to name a few) would be willing to hinder the research of certain people?

this is well known publicly (around the globe), that this is what these people are doing, so why do _you_ allow this?

why would your people NOT want a BSE test in the U.S.?

why slow this research down?

(i know the answer to that, but would like to hear it from you, but really don't expect a reply. hell, i cannot even get a reply from my state reps. on this issue, but i promise you, i am going to light a fire, that will be seen around the globe).

why is it, all this money can go for all sorts of other things, but very very little for research of human/animal TSE's?

it's not going away, it's only going to spread...

kind regards, Terry S. Singeltary SR.

THIS IS A WORLD PROBLEM...TSS


DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES

http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2000_register&docid=fr20jy00-32



DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [2]


http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2000_register&docid=fr20jy00-31



LOUPING-ILL VACCINE SCRAPIE BLUNDER


http://www.whale.to/v/singeltary.html



Manuelidis EE, Kim JH, Mericangas JR, Manuelidis L. Transmission to animals of Creutzfeldt-Jakob disease from human blood. Lancet 1985;2:896-7.

Tateishi J. Transmission of Creutzfeldt-Jakob disease from human blood and urine into mice. Lancet 1985;2:1074. "

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).


http://www.ncbi.nlm.nih.gov/pubmed/2864612



http://www.whale.to/v/singeltary4.html



*************************************************************************


http://www.cdc.gov/ncidod/eid/vol3no2/ricketts.htm



Synopses

Is Creutzfeldt-Jakob Disease Transmitted in Blood? Maura N. Ricketts,* Neil R. Cashman,† Elizabeth E. Stratton,* Susie ElSaadany* *Laboratory Centre for Disease Control, Health Canada, Ottawa, Ontario, Canada; and †Montreal Neurological Institute, Montreal, Canada

"Four Australians have been reported with CJD following transfusion (49). The patients had cerebellar signs; however, no other evidence of iatrogenic cause was described (50). The source of blood transfusions was undocumented. Genetic testing results were not provided; it is uncertain if cases were of the familial type, and no other information on alternative iatrogenic sources was provided.

In Canada, an albumin recipient died of neuropathologically confirmed CJD after receiving albumin from a pool containing blood from a person who died of neuropathologically confirmed CJD (D.G. Patry, pers. comm.). Eight months separated the receipt of albumin and development of symptoms, a much shorter period by a factor of three than seen in any other putative iatrogenic case, which makes iatrogenic transmission unlikely. A complete investigation is under way. "

", , , CJD may be uniformly underdiagnosed in older age groups; because of nv-CJD there will likely be increased attention to differential diagnoses among elderly persons dying of rapidly progressing dementing illnesses. We do not suggest that all sporadic cases are due to external exposure such as blood, but rather we draw attention to an important epidemiologic characteristic of CJD that is not consistent with an entirely stochastic or age-related event.

AUSTRALIA - ANOTHER sCJD VICTIM

Sent: Saturday, October 21, 2006 3:00 PM

Subject: australia another CJD victim - blood donor -

http://www.news.com.au/sundayheraldsun/story/0,21985,20622280-661,00.html



A MELBOURNE grandmother who died this week from suspected Creutzfeldt-Jakob disease was a blood donor for 25 years.

Valerie Powell, 68, died on Tuesday. Her husband Ron, 70, said his wife was a regular blood donor until a year ago.

But he said doctors had told him the type of CJD his wife had could not be transmitted by blood or blood products.

The Australian Red Cross said there had never been a reported case of classical CJD being passed from a blood donor anywhere in the world.

CJD expert Prof Colin Masters, head of the Department of Pathology at Melbourne University, said Victorians who may have received blood from Mrs Powell should not be alarmed because there was no evidence classical CJD was passed through the blood.

But he said in the past year there had been three cases, all in Britain, of variant CJD -- more widely known as mad cow's disease -- passed from blood donors.

Mr Powell said his wife went to her GP in July because she was feeling unwell.

"He diagnosed depression and put her on medication," he said. "It didn't help. Valerie's symptoms became worse."

Mrs Powell's family was told a test of her spinal fluid showed she "probably" had sporadic CJD, which makes up 90 per cent of all classical CJD cases.

It was not known how she developed the rare, but fatal, brain disease. Only a biopsy will confirm suspicions that Mrs Powell died from CJD.

Prof Masters said there was no way of screening blood donors. About 20 Australians a year die from classical CJD.

THERE are support groups for families of victims of CJD. Contact Suzanne Solvyns 1800 052 466, Carol Wilson 1800 181 683 or Mandy Newton 1800 884 897.


******************************************************************************


Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html



TSS

TSEAC 21st Meeting Friday, June 12, 2009 (BSE TESTING USA ???) TRANSCRIPT

DEPARTMENT OF HEALTH AND HUMAN SERVICES UNITED STATES FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

This transcript has not been edited or corrected, but appears as received from the commercial transcribing service. Accordingly the Food and Drug Administration makes no representation as to its accuracy.

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE

21st Meeting Friday, June 12, 2009 8:00 a.m. Holiday Inn

DR. ROHWER: We first detected infectivity at that point, but that was part of several measurements over the incubation period and you could extrapolate that curve and it extrapolated to zero back around 30 percent of the incubation time.

DR. HOGAN: Dr. Manuelidis?

DR. MANUELIDIS: Yes, I think there are a couple of things that concern me. One is that using one model of animals may not always be the most effective one. In 1978 we wrote an article in Science showing that infectivity was present basically from about half way in the disease and went through the end and at the end it became highly infectious, much more infectious in the guinea pig for instance than in Bob’s models. I would also like to point out that, for instance, vCJD is BSE and basically in a cow blood is not infectious and in primates it is. So, one must be very careful about this. The third thing which is a concern of mine is that in the report here it says we are talking about vCJD and my

PAPER MILL REPORTING 301 495-5831 163

concern is that we are limiting things to vCJD. It says because BSE has been detected in so few US cattleB-now, anybody who works with the USDA knows that the USDA has been impossible about letting anybody work with BSE and we actually had no surveillance. So, we have no idea about how many US cattle are really infected as compared to places like Japan that look at every single cow. The fourth thing is that there are recent reports that have been going back for several years and have now become more important of variants of BSE which are not vCJD, some of which people believe have more of a linkage to sporadic CJD. We also do not look for these things.

So, I think that in looking at what we say about what should be done, although this has no practical application right now to what the FDA is going to do about saying we can’t use this blood or that blood, I think it is a much broader problem. I also agree with people in the audience who came and said that CJD is not a reportable disease in many places, and I think this is very frustrating in terms of knowing what is really going on in our population. So, I would like to add that.

PAPER MILL REPORTING 301 495-5831 164

DR. HOGAN: I think those are most important points that a lot of us agree with, and I know that the staff is looking at some of those in the future. What we are specifically charged with today is a little bit less encompassing issue but, nonetheless, exactly what you say should be considered.

SNIP...

MR. TEMPLIN: I just want to make two comments. I am sort of troubled that we don’t know how much is actually infectious. A comment too about what Dr. Manuelidis said about cattle. If a farmer has cattle that he thinks may e

PAPER MILL REPORTING 301 495-5831 166

infectious he is going to throw it out in the back 40 and cover it up or throw it on the compost pile and never report it to the government because he is going to lose everything he or she owns.

DR. HOGAN: I think we are going to have some speakers this afternoon that are going to address the current USDA situation. So, we will have questions for them at that point. Miss Hamilton?

MS. HAMILTON: I have a comment about what Dr. Manuelidis said to a question. It troubles me because a few years ago there was a lot of hype about the downed cattle that were getting through and being used in food for animals and what-not, and now we don’t hear anything else about it, and she was saying that there is no surveillance in that area at all. My big question is why.

DR. HOGAN: Well, we will ask the USDA this afternoon, but I am not sure that zero is correct. I think it has been lowered significantly from its initial stages but it is not zero. Dr. Kreindel?

DR. KREINDEL: We are going to have a presentation on the USDA surveillance, but we do have surveillance and our surveillance is according to international standards.

PAPER MILL REPORTING 301 495-5831 167

You know, it is not surveillance that really protects the US population. You know, we do have surveillance and there was a lot of surveillance going on. We called that surveillance enhanced surveillance. We are going to have information about that. We still have surveillance going on, you know, at the level requested by international standards but we do cover a lot of mitigations about sequential interlocking that really prevent, you know, if any BSE is present to be recycled.

DR. HOGAN: Thank you. Perhaps we will defer the discussion of surveillance till this afternoon. Do any of the statistics experts on the panel have anything to say relative to the mathematical accuracy of this model, since all those equations make me dizzy?

SNIP...then the BSe picks up on page 205 with the mathmatical formula's and the junk science of the OIE, but then on page 216 please see the questions on BSE testing in the USA by Dr. Manuelidis ;

DR. MANUELIDIS: I am just curious if you can explain to me the difference between the testing that is going on now in Europe with all the other variants or other strains of BSE, the test that is used, and whether the USDA still refuses to sort of use tests that other countries use, and what might our tests have that may be different and are they still restricted, or what is the rationale for that?

DR. HUGHES: Well, the USDA uses tests that have been validated.

DR. MANUELIDIS: I believe that the tests have been validated for the European and the Japanese stuff, they all use a standard test. So, I am curious about why the USDAB-there was the import I think you were referring to where the Japanese stopped importing food because, as I understood it and this is, of course, from places like The New York Times that may be totally wrong but as I understood it, the USDAB-this must have been about three or four years ago, said that they refused to use the test even though the plant was willing to use it. They said they had their own tests and they said they would only use their own tests.

PAPER MILL REPORTING 301 495-5831 217

Maybe you can clarify that for me and tell me what the difference is between the tests, and whether you think that you can pick up the variants of BSE, not just the UK version of BSE. If there is really a difference in the sensitivity of the tests, if any independent side-by-side comparison has been done.

DR. KREINDEL: I am not sure I can answer your question but I think you are referring to the fact that they wanted to test all animals, rather than following the USDA requirements for testing.

DR. HUGHES: The question was why don’t we test all animals.

DR. MANUELIDIS: There is a test that is used in Europe and in Japan. It is used all over I think. It is a bioride[?] test and what the plant was willing to do, I understood from The New York Times, was to test their animals according to that protocol. The USDA said no, even though everybody else uses it, we want to use our own test. Then they never really did those tests. So, what I am really getting at is are our tests in the USDA as sensitive and as comprehensive even if we don’t test every animal--

PAPER MILL REPORTING 301 495-5831 218

DR. HUGHES: Yes.

DR. MANUELIDIS: -Bfor all the variants of BSE and on what basis? Have you ever picked up any cases of BSE-H or BSE-L? Would you have an independent control that shows you that you can pick up these things with the tests as currently employed? Have there been any blind controls where an animal has a little bit of this or that just to see if you can pick it up out of a group?

DR. HUGHES: I think what you might be referring to is the Creekstone case.

DR. MANUELIDIS: Yes.

DR. HUGHES: Okay. Of course, I can’t comment on current litigation but, basically, the USDA is unwilling to, you know, have a test be validated as a food safety test. Again, this gets back to what I spoke about earlier, that the BSE test really isn’t a food safety test. It is possible to test an animal for BSE and have it be negative and still have the animal be positive for BSE. So, using that to put on a package label is just very confusing and kind of disingenuous to the public because it gives them a false sense of security about it. Our main focus for protecting human health is on other

PAPER MILL REPORTING 301 495-5831 219

mitigation measures, such as the feed ban the FDA has in place; removal of specified risk materials. So, the tissues that we know are likely to contain agent never make it into the food chain in the first place. So, that is the basis of the refusal to allow that private company to do their own testing.

DR. MANUELIDIS: I don’t want to be difficult because BSE is not my specialty, minus the vCJD version of it, but as I understand, some of the BSE cases, like the typical UK BSE case, have been found in muscle where muscle has been found to be infectious. So, the food ban wouldn’t really deal with those. That is why I was asking what is the test. If you did a side-by-side comparison with blind controls would you be able to pick up what Europeans and Japanese pick up? That is really what I am asking.

DR. HUGHES: And I am afraid I can’t answer that, and I am not sureB-you know, the experts on that would be the folks at NVSL that are responsible for validating the test and choosing which test we use. But evidently they are not convinced that the other tests are better than what we use currently. But, again, I am sorry, I am not the expert

PAPER MILL REPORTING 301 495-5831 220

in that particular category.

snip...

SEE FULL TEXT 346 PAGES ;



http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM171810.pdf



Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)



http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html



Monday, June 01, 2009 Biochemical typing of pathological prion protein in aging cattle with BSE

SOMETHING TO PONDER ???

O.K. confusious asks, IF all these new atypical BSEs i.e. new strains of mad cow disease is just an 'OLD COW PRION DISEASE', why then can not the 'old human prion disease' such as the sporadic CJD, be from an 'old cow prion disease', same as the nvCJD 'young people mad cow disease' (which also happens in 74 year old), but why cannot the 'old cow prion diseases', i.e. l-BSE, h-BSE, and ibncBSE, cause the 'old people prion disease', which looks like sporadic CJD. seems that is what some of the pathology is showing ???

OH, that probably makes too much sense, and that the only answer could be that it's all just a happenstance of bad luck and or a spontaneous event, that just happens out of the clear blue sky $$$

IF this is the case, then where are all the SPONTANEOUS BSE CASES OF MAD COW DISEASE IN THE U.S.A., AND WHERE HAVE THEY BEEN BURIED IN THE USA OVER THE LAST 25 YEARS ???



http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.html



Thursday, April 9, 2009

Docket No. FDA2002N0031 (formerly Docket No. 2002N0273) RIN 0910AF46 Substances Prohibited From Use in Animal Food or Feed; Final Rule: Proposed



http://madcowfeed.blogspot.com/2009/04/docket-no-fda2002n0031-formerly-docket.html



http://prionunitusaupdate2008.blogspot.com/2009/04/r-calf-and-usa-mad-cow-problem-dont.html#comments



Sunday, April 12, 2009 r-calf and the USA mad cow problem, don't look, don't find, and then blame Canada



http://prionunitusaupdate2008.blogspot.com/2009/04/r-calf-and-usa-mad-cow-problem-dont.html



http://prionunitusaupdate2008.blogspot.com/2009/04/cjd-foundation-sides-with-r-calfers-no.html#comments



Tuesday, July 14, 2009

U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST

WHERE did we go wrong $$$



http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html



10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007



http://www.fda.gov/bbs/topics/enforce/2007/ENF00996.html



NEW URL



http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm




Thursday, March 19, 2009

MILLIONS AND MILLIONS OF POUNDS OF MAD COW FEED IN COMMERCE USA WITH ONGOING 12 YEARS OF DENIAL NOW, WHY IN THE WORLD DO WE TO TALK ABOUT THIS ANYMORE $$$



http://madcowfeed.blogspot.com/2009/03/millions-and-millions-of-pounds-of-mad.html



Sunday, May 10, 2009

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)



http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html



Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)



http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html



Tuesday, July 14, 2009

U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST

WHERE did we go wrong $$$



http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html



Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg Infect Dis. 2009 Aug; [Epub ahead of print]



http://nor-98.blogspot.com/2009/07/transgenic-mice-expressing-porcine.html



Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009



http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html



i am no doctor, i have no phd's, and I am president and ceo of nothing. ...TSS

wasted days and waste nights...freddy fender

stupid is, as stupid does...forest gump

still sadly disgusted...

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

TSEAC 21st Meeting Final Issue Summary June 12, 2009

2009 Meeting Materials, Transmissible Spongiform Encephalopathies Advisory Committee

Updated: 6/4/2009


http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm129559.htm


Transmissible Spongiform Encephalopathies Advisory Committee 21st Meeting Final Issue Summary June 12, 2009

Holiday Inn 2 Montgomery Village Avenue Gaithersburg, MD 20879

Topic I:

Modified FDA Risk Assessment for Potential Exposure to the Infectious Agent of Variant Creutzfeldt-Jakob Disease (vCJD) in US-licensed Plasma-Derived Factor VIII (pdFVIII)

ISSUE:

Plasma-derived Factor VIII (pdFVIII) products are used by blood clotting disorder patients with von Willebrand disease and some patients with hemophilia A. The announcement in February 2009 by health authorities in the United Kingdom that a vCJD infection had been recognized in a person with hemophilia treated with a UK manufactured "vCJD-implicated" pdFVIII 11 years earlier has prompted FDA to review the potential vCJD risk for US users of US-licensed pdFVIII products and current risk management strategies for such products.

Results from an updated FDA risk assessment model continue to indicate that the estimated risk of the potential for US-licensed pdFVIII products to transmit the agent of vCJD, the human form of "Mad Cow Disease," is highly uncertain but is most likely to be extremely small.

FDA seeks the advice of the Committee on whether additional risk reducing measures are needed (e.g. modifications to current donor deferral policies) to maintain the safety of plasma-derived biologic products and whether FDA should change its communications concerning the risks of vCJD associated with plasma derivatives. ...

snip...

see full text ;


http://www.fda.gov/downloads/AdvisoryCommittees/Calendar/UCM164322.pdf


http://www.fda.gov/downloads/AdvisoryCommittees/Calendar/UCM164326.pdf


http://www.fda.gov/downloads/AdvisoryCommittees/Calendar/UCM164322.pdf



this might be interesting to see what is said here too ;


SNIP...

TSEAC AGENDA, Friday, June 12, 2009 (page 2)

12:30 p.m. Lunch

1:30 p.m. Topic II: Informational Presentations

A. BSE Surveillance and USDA-Regulated Food Controls in the U.S., Janet A. Hughes, DVM, PhD, APHIS, USDA (20')

B. BSE Surveillance and Food/Feed Controls in Europe, Koen van Dyck, DVM, European Commission (20')

C. BSE Surveillance, Animal Feeds and Food Controls in Canada, Dr. Noel Murray, Canadian Food Safety Inspection Agency (20')

D. FDA Enhanced Animal "Feed Ban": Current Status, Burt Pritchett, DVM, CVM, FDA (20')

E. FDA-Regulated Food Controls in the U.S., Amber McCoig, DVM, CFSAN, FDA (20')

F. FDA Proposed BSE "Medical Products" Rule: Current Status, Theresa Finn, Ph. D., OVRR, FDA (20')


SNIP...


http://www.fda.gov/downloads/AdvisoryCommittees/Calendar/UCM164321.pdf


http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm129559.htm


Sunday, May 10, 2009

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)


http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html


Owner and Corporation Plead Guilty to Defrauding Bovine Spongiform Encephalopathy (BSE) Surveillance Program

An Arizona meat processing company and its owner pled guilty in February 2007 to charges of theft of Government funds, mail fraud, and wire fraud. The owner and his company defrauded the BSE Surveillance Program when they falsified BSE Surveillance Data Collection Forms and then submitted payment requests to USDA for the services. In addition to the targeted sample population (those cattle that were more than 30 months old or had other risk factors for BSE), the owner submitted to USDA, or caused to be submitted, BSE obex (brain stem) samples from healthy USDA-inspected cattle. As a result, the owner fraudulently received approximately $390,000. Sentencing is scheduled for May 2007.

snip...

Topics that will be covered in ongoing or planned reviews under Goal 1 include:

soundness of BSE maintenance sampling (APHIS),

implementation of Performance-Based Inspection System enhancements for specified risk material (SRM) violations and improved inspection controls over SRMs (FSIS and APHIS),

snip...

The findings and recommendations from these efforts will be covered in future semiannual reports as the relevant audits and investigations are completed.

4 USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half


http://www.usda.gov/oig/webdocs/sarc070619.pdf


-MORE Office of the United States Attorney District of Arizona FOR IMMEDIATE RELEASE For Information Contact Public Affairs February 16, 2007 WYN HORNBUCKLE Telephone: (602) 514-7625 Cell: (602) 525-2681

CORPORATION AND ITS PRESIDENT PLEAD GUILTY TO DEFRAUDING GOVERNMENT'S MAD COW DISEASE SURVEILLANCE PROGRAM

PHOENIX -- Farm Fresh Meats, Inc. and Roland Emerson Farabee, 55, of Maricopa, Arizona, pleaded guilty to stealing $390,000 in government funds, mail fraud and wire fraud, in federal district court in Phoenix. U.S. Attorney Daniel Knauss stated, "The integrity of the system that tests for mad cow disease relies upon the honest cooperation of enterprises like Farm Fresh Meats. Without that honest cooperation, consumers both in the U.S. and internationally are at risk. We want to thank the USDA's Office of Inspector General for their continuing efforts to safeguard the public health and enforce the law." Farm Fresh Meats and Farabee were charged by Information with theft of government funds, mail fraud and wire fraud. According to the Information, on June 7, 2004, Farabee, on behalf of Farm Fresh Meats, signed a contract with the U.S. Department of Agriculture (the "USDA Agreement") to collect obex samples from cattle at high risk of mad cow disease (the "Targeted Cattle Population"). The Targeted Cattle Population consisted of the following cattle: cattle over thirty months of age; nonambulatory cattle; cattle exhibiting signs of central nervous system disorders; cattle exhibiting signs of mad cow disease; and dead cattle. Pursuant to the USDA Agreement, the USDA agreed to pay Farm Fresh Meats $150 per obex sample for collecting obex samples from cattle within the Targeted Cattle Population, and submitting the obex samples to a USDA laboratory for mad cow disease testing. Farm Fresh Meats further agreed to maintain in cold storage the sampled cattle carcasses and heads until the test results were received by Farm Fresh Meats.

Evidence uncovered during the government's investigation established that Farm Fresh Meats and Farabee submitted samples from cattle outside the Targeted Cattle Population. Specifically, Farm Fresh Meats and Farabee submitted, or caused to be submitted, obex samples from healthy, USDA inspected cattle, in order to steal government moneys.

Evidence collected also demonstrated that Farm Fresh Meats and Farabee failed to maintain cattle carcasses and heads pending test results and falsified corporate books and records to conceal their malfeasance. Such actions, to the extent an obex sample tested positive (fortunately, none did), could have jeopardized the USDA's ability to identify the diseased animal and pinpoint its place of origin. On Wednesday, February 14, 2007, Farm Fresh Meats and Farabee pleaded guilty to stealing government funds and using the mails and wires to effect the scheme. According to their guilty pleas:

(a) Farm Fresh Meats collected, and Farabee directed others to collect, obex samples from cattle outside the Targeted Cattle Population, which were not subject to payment by the USDA;

(b) Farm Fresh Meats 2 and Farabee caused to be submitted payment requests to the USDA knowing that the requests were based on obex samples that were not subject to payment under the USDA Agreement;

(c) Farm Fresh Meats completed and submitted, and Farabee directed others to complete and submit, BSE Surveillance Data Collection Forms to the USDA's testing laboratory that were false and misleading;

(d) Farm Fresh Meats completed and submitted, and Farabee directed others to complete and submit, BSE Surveillance Submission Forms filed with the USDA that were false and misleading;

(e) Farm Fresh Meats falsified, and Farabee directed others to falsify, internal Farm Fresh Meats documents to conceal the fact that Farm Fresh Meats was seeking and obtaining payment from the USDA for obex samples obtained from cattle outside the Targeted Cattle Population; and

(f) Farm Fresh Meats failed to comply with, and Farabee directed others to fail to comply with, the USDA Agreement by discarding cattle carcasses and heads prior to receiving BSE test results. A conviction for theft of government funds carries a maximum penalty of 10 years imprisonment. Mail fraud and wire fraud convictions carry a maximum penalty of 20 years imprisonment. Convictions for the above referenced violations also carry a maximum fine of $250,000 for individuals and $500,000 for organizations. In determining an actual sentence, Judge Earl H. Carroll will consult the U.S. Sentencing Guidelines, which provide appropriate sentencing ranges. The judge, however, is not bound by those guidelines in determining a sentence.

Sentencing is set before Judge Earl H. Carroll on May 14, 2007. The investigation in this case was conducted by Assistant Special Agent in Charge Alejandro Quintero, United States Department of Agriculture, Office of Inspector General. The prosecution is being handled by Robert Long, Assistant U.S. Attorney, District of Arizona, Phoenix. CASE NUMBER: CR-07-00160-PHX-EHC RELEASE NUMBER: 2007-051(Farabee) # # #


http://www.usdoj.gov/usao/az/press_releases/2007/2007-051(Farabee).pdf


10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot-Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A-BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007


http://www.fda.gov/bbs/topics/enforce/2007/ENF00996.html


(please note, the FDA URLS no longer are any good anymore, again. ...tss)

Page Not Found

Our apologies. The link or location you used does not exist or was moved.

Statement on Texas Cow With Central Nervous System SymptomsUnder the current regulation, the material from this Texas cow is not allowed in feed for cattle or other ruminant animals. FDA's action specifying that the ... www.fda.gov/bbs/topics/news/2004/new01061.html - 7k - Cached - Similar pages -


http://www.fda.gov/bbs/topics/news/2004/new01061.html


FDA ANNOUNCES TEST RESULTS FROM TEXAS FEED LOTJan 30, 2001 ... Today the Food and Drug Administration announced the results of tests taken on feed used at a Texas feedlot that was suspected of containing ... www.fda.gov/bbs/topics/news/2001/new00752.html - 6k - Cached - Similar pages -


http://www.fda.gov/bbs/topics/news/2001/new00752.html


[PDF] ddc026.pdfFile Format: PDF/Adobe Acrobat - View as HTML appropriate sections of the Texas Commercial Feed Control Act. While the discussion draft provides particular issues on which the FDA seeks comment, ... www.fda.gov/cvm/Documents/ddc026.pdf - Similar pages -


http://www.fda.gov/cvm/Documents/ddc026.pdf


you can still see those violations here ;


Thursday, March 19, 2009

MILLIONS AND MILLIONS OF POUNDS OF MAD COW FEED IN COMMERCE USA WITH ONGOING 12 YEARS OF DENIAL NOW, WHY IN THE WORLD DO WE TO TALK ABOUT THIS ANYMORE $$$


http://madcowfeed.blogspot.com/2009/03/millions-and-millions-of-pounds-of-mad.html


Monday, June 01, 2009

Biochemical typing of pathological prion protein in aging cattle with BSE


http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.html


Rare BSE mutation raises concerns over risks to public health

SIR - Atypical forms (known as H- and L-type) of bovine spongiform encephalopathy (BSE) have recently appeared in several European countries as well as in Japan, Canada and the United States. This raises the unwelcome possibility that variant Creutzfeldt-Jakob disease (vCJD) could increase in the human population. Of the atypical BSE cases tested so far, a mutation in the prion protein gene (PRNP) has been detected in just one, a cow in Alabama with BSE; her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008). This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks. Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000352/!x-usc:mailto:maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA

NATUREVol 45726 February 2009


http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html


Sunday, May 10, 2009

Identification and characterization of bovine spongiform encephalopathy cases diagnosed and NOT diagnosed in the United States


http://bse-atypical.blogspot.com/2009/05/identification-and-characterization-of.html


Wednesday, February 11, 2009

Atypical BSE North America Update February 2009

Both of the BSE cases ascertained in the US native-born cattle were atypical cases (H-type), which contributed to the initial ambiguity of the diagnosis. 174, 185 In Canada, there have been 2 atypical BSE cases in addition to the 14 cases of the classic UK strain of BSE2: one was the H-type, and the other was of the L-type.198 snip...end source : Enhanced Abstract Journal of the American Veterinary Medical Association January 1, 2009, Vol. 234, No. 1, Pages 59-72 Bovine spongiform encephalopathy Jane L. Harman, DVM, PhD; Christopher J. Silva, PhD


http://avmajournals.avma.org/doi/ref/10.2460/javma.234.1.59


Atypical BSE North America Update February 2009


http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html


Thursday, April 30, 2009

FDA Issues Final Guidance for Renderers on Substances Prohibited From Use in Animal Food or Feed CVM Update Back April 30, 2009


http://madcowfeed.blogspot.com/2009/04/fda-issues-final-guidance-for-renderers.html


Friday, May 29, 2009

Characterization of a U.S. Sheep Scrapie Isolate with Short Incubation Time


http://scrapie-usa.blogspot.com/2009/05/characterization-of-us-sheep-scrapie.html


P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5 The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.


http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf


RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

___________________________________

PRODUCT

a) Elk Meat, Elk Tenderloin, Frozen in plastic vacuum packaging. Each package is approximately 2 lbs., and each case is approximately 16 lbs.; Item number 755125, Recall # F-129-9;

b) Elk Meat, Elk Trim, Frozen; Item number 755155, Recall # F-130-9;

c) Elk Meat, French Rack, Chilled. Item number 755132, Recall # F-131-9;

d) Elk Meat, Nude Denver Leg. Item number 755122, Recall # F-132-9;

e) Elk Meat, New York Strip Steak, Chilled. Item number 755128, Recall # F-133-9;

f) Elk Meat, Flank Steak Frozen. Item number 755131, Recall # F-134-9;

CODE

Elk Meats with production dates of December 29, 30, and 31

RECALLING FIRM/MANUFACTURER

Recalling Firm: Sierra Meats, Reno, NV, by telephone on January 29, 2009 and press release on February 9, 2009.

Manufacturer: Noah's Ark Holding, LLC, Dawson, MN. Firm initiated recall is ongoing.

REASON

Elk products contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD).

VOLUME OF PRODUCT IN COMMERCE

Unknown

DISTRIBUTION

NV, CA, TX, CO, NY, UT, FL, OK

___________________________________


http://www.fda.gov/bbs/topics/ENFORCE/2009/ENF01099.html


http://chronic-wasting-disease.blogspot.com/2009/05/seven-deer-test-positive-for-chronic.html


Sunday, May 17, 2009

WHO WILL WATCH THE CHILDREN ?

USDA CERTIFIED NON-AMBULATORY DEAD STOCK DOWNER COW SCHOOL LUNCH PROGRAM

UPDATE MAD COW DISEASE NORTH AMERICA, AND THE DEADSTOCK DOWNERS THAT WERE FED TO YOUR CHILDREN

see full text ;


http://downercattle.blogspot.com/2009/05/who-will-watch-children.html



CJD ON THE RISE IN THE USA ;


Monday, April 20, 2009 National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)

April 20, 2009

National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)

National Prion Disease Pathology Surveillance Center Cases Examined1

(December 31, 2008)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 42 32 28 4 0 0

1997 115 68 59 9 0 0

1998 93 53 45 7 1 0

1999 115 69 61 8 0 0

2000 151 103 89 14 0 0

2001 210 118 108 9 0 0

2002 258 147 123 22 2 0

2003 273 176 135 41 0 0

2004 335 184 162 21 0 13

2005 346 193 154 38 1 0

2006 380 192 159 32 0 14

2007 370 212 185 26 0 0

2008 383 228 182 23 0 0

TOTAL 30715 17756 1490 254 4 2

1 Listed based on the year of death or, if not available, on year of referral; 2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted; 3 Disease acquired in the United Kingdom; 4 Disease acquired in Saudi Arabia; 5 Includes 20 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 25 cases with type determination pending in which the diagnosis of vCJD has been excluded.

Rev 2/13/09 National

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

http://www.cjdsurveillance.com/resources-casereport.html

http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45

*5 Includes 20 cases in which the diagnosis is pending, and 17 inconclusive cases; *6 Includes 25 cases with type determination pending in which the diagnosis of vCJD has been excluded.

Greetings,

it would be interesting to know what year these atypical cases occurred, as opposed to lumping them in with the totals only.

are they accumulating ?

did they occur in one year, two years, same state, same city ?

location would be very interesting ?

age group ?

sex ?

how was it determined that nvCJD was ruled out ?

from 1997, the year i started dealing with this nightmare, there were 28 cases (per this report), up until 2007 where the total was 185 cases (per this report), and to date 2008 is at 182. a staggering increase in my opinion, for something that just happens spontaneously as some would have us believe. i don't believe it, not in 85%+ of all sporadic CJD cases. actually, i do not believe yet that anyone has proven that any of the sporadic CJD cases have been proven to be a spontaneous misfolding of a protein. there are many potential routes and sources for the sporadic CJD's. ...TSS

please see full text here ;


http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html



Rare BSE mutation raises concerns over risks to public health

SIR - Atypical forms (known as H- and L-type) of bovine spongiform encephalopathy (BSE) have recently appeared in several European countries as well as in Japan, Canada and the United States. This raises the unwelcome possibility that variant Creutzfeldt-Jakob disease (vCJD) could increase in the human population. Of the atypical BSE cases tested so far, a mutation in the prion protein gene (PRNP) has been detected in just one, a cow in Alabama with BSE; her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008). This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks. Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA

NATUREVol 45726 February 2009


http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html


Sunday, May 10, 2009

Identification and characterization of bovine spongiform encephalopathy cases diagnosed and NOT diagnosed in the United States


http://bse-atypical.blogspot.com/2009/05/identification-and-characterization-of.html



Wednesday, February 11, 2009

Atypical BSE North America Update February 2009

Both of the BSE cases ascertained in the US native-born cattle were atypical cases (H-type), which contributed to the initial ambiguity of the diagnosis. 174, 185 In Canada, there have been 2 atypical BSE cases in addition to the 14 cases of the classic UK strain of BSE2: one was the H-type, and the other was of the L-type.198 snip...end source : Enhanced Abstract Journal of the American Veterinary Medical Association January 1, 2009, Vol. 234, No. 1, Pages 59-72 Bovine spongiform encephalopathy Jane L. Harman, DVM, PhD; Christopher J. Silva, PhD


http://avmajournals.avma.org/doi/ref/10.2460/javma.234.1.59



Atypical BSE North America Update February 2009


http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html



Monday, June 01, 2009

Biochemical typing of pathological prion protein in aging cattle with BSE


http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.html





Monday, April 20, 2009

National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)


http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html




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

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)

TO : william.freas@fda.hhs.gov <william.freas@fda.hhs.gov>



May 8, 2009


Greetings again Dr. Freas, TSEAC et al,


I would kindly, once again, wish to comment at this meeting about the urgent actions that need to be taken asap, to the Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009. Due to my disability from my neck injury, I will not be attending this meeting either, however I hope for my submission to be read and submitted. ...


IN reply to ;


Meeting of the Transmissible Spongiform Encephalopathies Committee Center Date Time Location CBER June 12, 2009 June 12, 2009 from 8:00 a.m. to 5:45 p.m. Holiday Inn Gaithersburg, Grand Ballroom, 2 Montgomery Village Ave. Gaithersburg, Maryland 20879

Agenda On June 12, 2009, the Committee will review and discuss a recent report from the UK Health Protection Agency attributing a case of variant Creutzfeldt-Jakob (vCJD) disease infection to treatment 11 years earlier with a "vCJD-implicated" plasma-derived coagulation factor VIII (pdFVIII) and whether this information or any other recent scientific information about the vCJD epidemic substantially alters FDA's risk assessment for US-licensed preparations of pdFVIII products. In the afternoon the committee will hear informational presentations on animal models of vCJD, diagnostic test development for transmissible spongiform encephalopathies (TSEs) and bovine spongiform encephalopathy (BSE) surveillance and risk management. ...snip...end

* Written submissions may be made to the contact person on or before June 4, 2009.



http://www.fda.gov/cber/advisory/tse/tse0609.htm




My written submission as follows ;


BY lumping all CJD's as sporadic, as one strain, of young and old here in the USA, with all the different TSEs in the bovine in North America i.e. c-BSE, h-BSE, and l-BSE, CWD in deer and elk spreading, Scrapie AND the atypical Nor-98 spreading, and then claiming all of them to be of a 'spontaneous' nature, we are still in cover-up mode for mad cow disease and any human TSE thereof in North America, and any consumer of blood products from humans here in the USA that are exposed to these animal TSE via a multitude of routes and sources, needlessly exposes these consumers to these Transmissible Spongiform Encephalopathies.


YOU first have to have a CJD surveillance system that is in place, in all states, of all age groups, with a written cjd questionnaire going out to all victims and their families asking REAL questions pertaining to route and source of agent. with proper transmission studies done on all phenotypes of human TSE. until then, this study means nothing.


NOW, I know what your thinking (FDA), your thinking that present regulations in place will be sufficient.


I kindly disagree for the following reasons ;


1. atypical Transmissible Spongiform Encephalopathy in North America. we simply do NOT know how wide spread these atypical TSE are, considering the totally flawed policy of the 'Enhanced BSE surveillance Program' several years back. it was proven to be so by the GOA, OIG, and Dr. Paul Brown of the CDC confirmed it by his own words, and the industry has proven it by the total disregard of current and past regulations (no matter how weak they were). for this reason alone, the FDA cannot assure that the products in question are safe and free of the TSE Prion agent, to be passed to expose others in the years to come vie 'friendly fire' i.e. the medical, surgical, and or dental arena. ...


2. some sub-types of atypical BSE seem to be more virulent than the typical c-BSE. all of which have been documented in North America i.e. c-BSE, h-BSE, and the l-BSE. Scapie (typical and atypical Nor-98), and CWD (with an apparent second strain, the Wisconsin Variant CWD). With all these animal TSEs in North America, and the potential transmission to humans via deer, elk, sheep, goat, cattle, via a multitude of proven routes and sources (proven in the lab and in the field), to ignore the limited science to date, and continue to peddle USA blood and blood products as a safe product, in my opinion, and I have said it before, it's like playing Russian Roulette with the consumers that must use these blood and blood products. ...


3. the FDA et al have been hiding behind false fictitious firewalls, the previous partial and voluntary ruminant to ruminant feed ban, and the Enhanced BSE surveillance program, where some 800,000 cattle were tested. BOTH of which were proven to be totally flawed. To a point of criminal intent in my opinion. ...


4. several studies I would kindly like to bring to your attention below, on why I stringently urge this committee, once again, to ban all humans from past history of any TSE (family members included) from giving blood. it would also seem prudent to update and enhance the questionnaire for donors of blood, blood products, and tissue donors, and strictly enforce these regulations. just look at past history, and all the bad blood out there from suspect human nvCJD alone, let alone donors that consume potentially tainted products, including dietary nutritional supplements that contain SRMs or 'antler velvet' from either deer or elk (see May 2009 CDC warning on this). look at the weekly recalls, from blood that has been distributed all around the globe, from a faulty regulated product, via a faulty screening program. see for yourself, don't take my word for it, but then think of the 'friendly fire' issues there of, in the years, decades to come, while continuing to kid yourself about the sporadic/spontaneous CJD's. all the while, it seems that some of these human and animal TSE's, when mutated, become more virulent. you continue to roll the dice, or being ''asleep at the wheel'', as you have been in the past (my opinion), you will continue to needlessly expose and possibly kill many more humans due to this lax regulatory system, and in time, find yourself in a much worse situation that the U.K. and E.U. are now in. ...



P23

EXPRESSION OF PRION PROTEIN ON BLOOD CELLS OF HEALTHY AND TSE INFECTED CYNOMOLGUS MACAQUES

Janouskova O1, Vranac T2, Glierova H1, Comoy EE3, Curin Serbec V2, Deslys JP3, Holada K1 1Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Praque, Czech Republic; 2Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia; 3Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France

Transmissibility of TSE in experimental animals by intravenous inoculation is well documented. Ability of blood to transmit TSE was recently confirmed by four secondary vCJD infections in recipients of blood transfusion. This demonstrated the risk associated with blood transfusion and raised concerns about undetected subclinical vCJD in the donor population.

Very little is known about the nature and behavior of prions in blood. In animal models TSE infectivity seems to be distributed between plasma and blood cells in the ratio near to 1:1. The cell associated infectivity appears to concentrate in leukocytes, while its association with red cells and platelets seems to be quite limited. Detection of pathological prion protein (PrPtse) in blood is complicated by the presence of substantial amount of poorly characterized cellular prion protein (PrPc) and by unavailability of PrPtse specific antibodies.

In the present study, we have used anti-PrP monoclonal antibodies and three color flow cytometry to investigate expression or exposition of epitopes of prion protein on intact and permeabilized dendritic cells (DC) and monocytes (MC) in healthy and BSE/vCJD infected cynomolgus macaques (Macaca fascicularis). First group of animals was infected i.v. with macaque BSE brain homogenate (5 animals, 2 were 39 month post infection, 3 were 33 month post infection). Second group was infected i.v. with macaque vCJD brain homogenate (6 animals, 3 were 27 month post infection and 3 were 21 month post infection). All animals were positive for the presence of PrPtse in lymph nodes by IHC. Two antibody panels were used (DC, MC). DC were defined as lineage markers negative (CD3, CD8, CD14, CD20) and HLA-DR positive cells. MC were defined as CD14 and HLA-DR positive cells.

Four different prion monoclonal antibodies (AG4, 3F4, AH6, V5B2) were used. The antibody AG4 binds to the N-terminal part of PrP. The antibody 3F4 binds to the central part of PrP. The AH6 epitope is located on the C-terminal part of PrP. MAb V5B2 was developed against a C-terminal PrP peptide and was shown to specifically recognize human PrPtse by diverse methods (Serbec et al. J. Biol. Chem 2004, 279, 3694-98).

Permeabilization protocol for intracellular detection of prion protein was optimized to allow detection of intracellular PrPc/PrPtse by all antibodies used. Fixation and permeabilization led to decrease of PrP detection with 3F4 and AG4 in the contrast to its increase with AH6 and V5B2. While the differences in binding of MAbs to cells of healthy and infected animals did not reach statistical significance, we observed significant difference in exposition of epitopes between MC and DC in vCJD infected monkeys in contrast with healthy monkeys. The diference was detected by AH6, 3F4, AG4 on intact cells and by 3F4 and AG4 in permeabilized cells.

Information on the presence of PrPc/PrPtse after permeabilization of MC and DC, together with demonstration of significant difference in the exposition of PrP epitopes between MC and DC in vCJD group in contrast to healthy controls might be relevant to the pathology of prion diseases and may help to facilitate TSE diagnosis.



http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf



explain then about GSS and blood and the potential risk thereof ???


FC5.1.1 Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD, and GSS Blood Specimens: the Baxter Study

Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5; Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama, USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK; 5Baxter BioSience, Austria

Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported. Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious. Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded 'prion' protein (PrPTSE). Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months. Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD.

***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the 'shock' of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.


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


FC5.1.2 Interim Transmission Results in Cynomolgus Macaques Inoculated with BSE and vCJD Blood Specimens

Lasmezas, C1; Lescoutra, N2; Comoy, E2; Holznagel, E3; Loewer, J3; Motzkus, D4; Hunsmann, G4; Ingrosso, L5; Bierke, P6; Pocchiari, M5; Ironside, J7; Will, R7; Deslys, JP2 1Scripps Florida, Infectology, USA; 2CEA, France; 3PEI, Germany; 4DPZ, Germany; 5Istituto Superiore di Sanita, Italy; 6SMI, Sweden; 7CJD Surveillance Unit, UK

BSE and vCJD transmitted to cynomolgus macaques reproduce many features of human vCJD, including clinical symptoms, neuropathological hallmarks of vCJD, PrPres electrophoretical pattern and, most importantly, the wide distribution of infectivity in peripheral organs. The latter characteristic distinguishes vCJD from sCJD in both humans and cynomolgus macaques, and prompted us to use this non-human primate model for further investigations of vCJD and its risk for human health. The occurrence of four vCJD infections in humans transfused with blood from patients who later developed vCJD has raised concern about blood transfusion safety in countries with vCJD. In this collaborative European study, we investigated the infectivity of blood components and whole blood administered by intracerebral (ic) and intravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic and iv route, respectively, from two vCJD patients and from two clinical vCJD-inoculated macaques. Transfusions were also performed from whole blood and blood leucodepleted according to hospital practice standards from two clinical BSE inoculated macaques. Blood infectivity during the preclinical phase is being examined in orally infected macaques. Whole blood was collected and transfused from one such animal two years after oral challenge, whereas buffy-coat and plasma from two animals at 2 and 4.5 years post-challenge, respectively, have been inoculated by the ic route. This is an ongoing study in which recipient animals continue to be observed at various times post-inoculation. So far, we have had one positive transmission in one animal transfused 65 months earlier with 40 ml of whole blood from a vCJD macaque (the characteristics of the disease in this animal will be shown in a separate poster by E. Comoy). This positive transmission reproduces transfusion transmission of vCJD in humans, with an incubation of 5.5 years compatible with incubation periods observed in humans.


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


see full text 143 pages ;



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



FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results into a Typical BSE Phenotype and a Muscle Wasting Disease

Zanusso, G1; Lombardi, G2; Casalone, C3; D'Angelo, A4; Gelmetti, D2; Torcoli, G2; Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3; Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L2 1University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA, Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy

The clinical phenotype of bovine spongiform encephalopathy has been extensively reported in early accounts of the disorder. Following the introduction of statutory active surveillance, almost all BSE cases have been diagnosed on a pathological/molecular basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance system has uncovered atypical BSE cases, which are characterized by distinct conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose clinicopathological phenotypes remain unknown. We recently reported two Italian atypical cases with a PrPSc type similar to BSE-L, pathologically characterized by PrP amyloid plaques. Experimental transmission to TgBov mice has recently disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A major limitation of transmission studies to mice is the lack of reliable information on clinical phenotype of BASE in its natural host. In the present study, we experimentally infected Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates by i.c. route. BASE infected cattle showed survival times significantly shorter than BSE, a finding more readily evident in Fresian/Holstein, and in keeping with previous observations in TgBov mice. Clinically, BSE-infected cattle developed a disease phenotype highly comparable with that described in field BSE cases and in experimentally challenged cattle. On the contrary, BASE-inoculated cattle developed an amyotrophic disorder accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study further confirms that BASE is caused by a distinct prion isolate and discloses a novel disease phenotype in cattle, closely resembling the phenotype previous reported in scrapie-inoculated cattle *** and in some subtypes of inherited and sporadic Creutzfeldt-Jakob disease.


Oral Abstracts 14


P04.27

Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route

Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany

Background:

In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.

Aims:

The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.

Methods:

Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).

Results:

In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.

Conclusions:

Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian v CJD as fast as intracerebrally inoculated animals.

The work referenced was performed in partial fulfilment of the study "BSE in primates" supported by the EU (QLK1-2002-01096).



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




Molecular Mechanisms of Prion Pathogenesis

Adriano Aguzzi, Christina Sigurdson, and Mathias Heikenwaelder Institute of Neuropathology, University Hospital of Z¨ urich, CH-8091 Z¨ urich, Switzerland; email: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:adriano.aguzzi@usz.ch, mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:mathias.heikenwaelder@usz.ch, christina.sigurdson@usz.ch


Abstract


Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt- Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated â-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.

snip...

The United States has witnessed an enigmatic rise of chronic wasting disease (CWD) cases affecting elk and deer (7), as well as the occurrence of the first cases of BSE (8). Furthermore, there has been a recrudescence of scrapie outbreaks among European sheep flocks (e.g., Sweden, Austria, Sardinia). The resurgence of new cases might be linked to an increased sensitivity and frequency of the currently executed testing procedures. These data also underline our deficit in knowledge about prion epidemiology and possible transmission routes of prion diseases in humans and animals. As an example in the field of human medicine, four cases of vCJD have been reported to be caused by blood transfusion (9- 11). This indicates that BSE prions can be recycled among humans, which has caused considerable alarm that the supply of bloodderived pharmaceuticals may be threatened (12). In particular, the report of a subclinical blood-derived vCJD infection in an individual carrying a heterozygote methionine/ valine polymorphism at codon 129 of the human PRNP gene (10) suggests that transmission of BSE prions to humans enhances their virulence and broadens the spectrum of susceptible recipients. In this respect, it has been demonstrated that polymorphisms at codon 129 of the human PRNP gene control susceptibility and incubation time in human patients (e.g., 129MM versus 129MV or 129VV drastically increases the susceptibility of humans to BSE prions). It was reported only recently that most individuals who suffered from kuru and were polymorphic at codon 129 showed incubation times longer than 50 years (13). Moreover, recent reports indicate that there is still a lot to be learned about the mechanisms of prion transmission (e.g., human to human or within scrapie-affected animal flocks) and prion tropism underlining the complex alternating distribution patterns of PrPSc (e.g., PrPSc deposition in lymphoid tissue, the CNS) and prion infectivity under varying conditions (e.g., chronic inflammation) and hosts (e.g., sheep, elk and deer, human): Chronic inflammation can alter the tropism of prion infectivity or PrPSc to organs hitherto believed prion free (e.g., liver, pancreas, kidney of mice, mammary gland of sheep, muscle of humans) (14-16). Moreover, PrPSc was reported in spleen and muscle tissue of sporadic Creutzfeldt-Jakob disease (sCJD) patients (17), and prion infectivity was demonstrated in muscle, blood, and saliva of deer suffering from CWD (18, 189). Also, prion infectivity was shown to be excreted via urine of prion-infected nephritic mice, a process defined as prionuria (19). These results emphasize the need for further assessment of possible public health risks from TSE-affected extraneural organs. It is very well possible that preexisting pathophysiological conditions of the infected host additionally contributed to unexpected distribution patterns of prion infectivity. For example, the presence of prion infectivity in the blood of sheep or deer may influence the deposition of prion infectivity in various organs previously deemed prion free. Therefore, it should be carefully reconsidered whether only organs of the CNS and the lymphoreticular system should be included in the current risk classifications of biologicals in the future. It will be important to test altered prion tropism profiles in nonlymphoid organs and body fluids (e.g., blood, urine, milk, saliva) of ruminants (e.g., sheep, goat, cattle, elk, and deer) and human patients suffering from sCJD and vCJD. In addition to the eminent questions of the mechanisms of prion transmissions within herds of ruminants, a number of looming questions about the safety of foods and drugs with regard to prion contamination remain unanswered. Moreover, many aspects of the basic biology of prions are essentially unclear. For instance, there is very little understanding of the mechanisms of prion replication at the molecular level. Also, the mechanisms underlying the phenomena of prion strains, prion neurotoxicity, and horizontal prion transmission remain sketchy at best. Diagnostic tools etect prions with consistent, high sensitivity are still pending; in particular, no test is currently available that can detect prion infectivity in human blood. However, prion science has attracted a vibrant research community that has made scientific and technological inroads in recent years.

snip...

full text ;



http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.pathmechdis.3.121806.154326?cookieSet=1&journalCode=pathmechdis




REVIEW

Variant Creutzfeldt-Jakob disease transmission by plasma products: assessing and communicating risk in an era of scientific uncertainty

A. Farrugia 1 , J. W. Ironside 2 & P. Giangrande 3 1 Australian Therapeutic Goods Administration, Woden, ACT, Australia 2 National Creutzfeldt-Jakob, Disease Surveillance Unit, Division of Pathology, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK 3 Oxford Haemophilia Centre and Thrombosis Unit, Churchill Hospital, Oxford, UK Correspondence: A. Farrugia, Australian Therapeutic Goods Administration, PO Box 100, Woden, ACT, 2606, AustraliaE-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:albert.farrugia@health.gov.au Copyright © 2005 Blackwell Publishing Ltd

KEYWORDS plasma products . risk . vCJD

ABSTRACT

A substantial body of animal data indicates that transmissible spongiform encephalopathies (TSEs) are transmitted through blood. These data have been augmented in the past year by reports that two recipients of red cells from donors with variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom have acquired this infection. Most of the blood donations collected in countries affected by bovine spongiform encephalopathy (BSE) and vCJD also contribute plasma to fractionation pools. Thus, a number of batches of fractionated products have included plasma from donors who developed vCJD. On the basis of public health strategies influenced, in part, by risk assessments, the UK and the French authorities have instituted measures for recalling products and informing patients of the estimated risks. It is therefore relevant to review the principles used by authorities in generating risk assessments for the transmission of TSEs by blood and blood products. While the general principles are fairly straightforward, the final assessments are very dependent on the magnitude of several key parameters, which are, largely, still unknown. A critical determinant of final product risk is the extent to which the plasma fractionation process will contribute to eliminating the infectious prion agent. Therefore, regulatory and industry measures to characterize fractionation processes for their capacity to eliminate prions are to be strongly encouraged. In the interim, an understanding of the principles used to generate risk assessments should contribute to an enhanced ability to address this threat to patient safety. Authorities should recognize that adequate communication is an integral part of good risk-management practices.

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

Received: 6 February 2005, revised 14 August 2005, accepted 15 August 2005



http://cat.inist.fr/?aModele=afficheN&cpsidt=17217574



http://www3.interscience.wiley.com/journal/118648975/abstract?CRETRY=1&SRETRY=0



http://www.ncbi.nlm.nih.gov/pubmed/16262750




Review Open Access

Published: 23 June 2008

The variant Creutzfeldt-Jakob Disease: Risk, uncertainty or safety in the use of blood and blood derivatives?

Antonio Liras

Address: Department of Physiology, Biology School, Universidad Complutense of Madrid, Spain Email: Antonio Liras - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:aliras@hotmail.com

Abstract

It has been long since French physician Jean-Baptiste Denys carried out the first successful blood transfusion to a human being. Using bird feathers as canules, sheep blood was transfused to a young man. The patient died soon after Denys' treatment and Denys was accused of murder. In the XXI century, known as the biotechnology century, we face new challenges in Medicine. New emerging and reemerging diseases, such as Creutzfeldt-Jakob disease (CJD) or "mad cow disease" and its human variant (vCJD), challenge the biosafety aspects of a widely extended and extremely useful technique, that is, the perfusion of blood, of its derived components and of other pharmacological products obtained from plasma. To face these new challenges we need innovative prevention strategies.

snip...

Final conclusion The history of medicine has undoubtedly shown that a zero risk does not exist in any medical practice. Therefore, the greatest possible number of public health precautions should be taken even if statistics suggest that there are minimum risks, as it happened in 1979 for AIDS and may occur today for vCJD. A posteriori, those predictions have been shown to be clearly wrong, and HIV has infected approximately 65 million people, of whom more than 25 millions have died from AIDS [45].



http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2443133&blobtype=pdf




Archive Number 20070108.0081 Published Date 08-JAN-2007 Subject PRO/AH/EDR> CJD (new var.) update 2007




http://www.mhlw.go.jp/shingi/2007/07/dl/s0725-5f_0063.pdf



February 2009


Mapping out the consequences of screening blood donations for PrPSc


© Crown copyright 2009 First published February 2009


Published to DH website, in electronic PDF format only. http://www.dh.gov.uk/publications


snip...


Preface


For several years, and with support from both the Department of Health and the UK Blood Services, manufacturers have made efforts to develop a method of screening donated blood for the abnormal prion protein known as PrPSc. These efforts have been primarily driven by concern about the potential secondary (person-to-person) spread of variant Creutzfeldt-Jakob Disease (vCJD), which is associated with the presence of PrPSc.


To date, the number of definite or probable clinical cases of vCJD stands at 167 in the UK, including three living patients. The incidence of new cases is now very low, with only one being confirmed during the last 12 months. However, secondary infection risks are driven not by numbers of clinical cases, but by the number of people who may be carrying the infective agent without showing any clinical symptoms. Although great uncertainties remain, some evidence suggests that these may be much more numerous. Furthermore, there have been four detected instances of the infective agent being transmitted from blood donor to transfusion recipient. Three of these recipients went on to develop, and die from, vCJD.


Although various measures to reduce the risk of vCJD being spread via donated blood are already in place, screening blood to reduce risks further would obviously have attractions. Efforts to develop a technically-viable way of screening blood for PrPSc are now well-advanced. However, introducing a screening test also would also have potential disadvantages. It needs to be borne in mind that:


* For any mass screening test, reliability is a key concern. This refers both to the sensitivity of the test (its ability to detect a given marker, in this case PrPSc) and its specificity (its ability to “clear” samples that do not carry the marker). As illustrated below, unless test specificity is very good, mass screening can lead to a very large number of “false positive” results, greatly outnumbering the “true positives” detected. This problem is compounded by great uncertainty as to what the true prevalence of PrPSc amongst donors might be.


* Even if abnormal prion protein is genuinely present in a donor’s blood, the significance of this is far from clear. While a test for PrPSc may be seen (and marketed) as a vCJD screening test, this is an over-simplification. The relationships between presence of PrPSc, vCJD infection and transmission risks are not well understood. This is in contrast to screening for markers of viral infections such as HIV or Hepatitis C, where the mechanisms of infection and disease progression are quite well-understood. Although PrPSc is associated with vCJD in some way, it may well not be the infective agent. There is no certainty as to whether a donation carrying PrPSc would cause the recipient to develop vCJD, or whether the donor in question would ever do so.
The interpretation of results will therefore be problematic, particularly if there is no “gold standard” test to confirm or refute the results of initial screening. Nevertheless, there is a clear case for removing donations carrying PrPSc from the blood supply where possible. Of the prion diseases so far known, at least one, vCJD, is transmissible via blood. Even if the presence of PrPSc in blood indicates something other than vCJD infection, it might be a marker for some other prion-related disorder yet to be characterised.


Particularly given these questions of interpretation, the introduction of a blood screening test would raise significant issues:


* For individual donors. For example, what should donors whose blood has to be rejected be told - bearing in mind the potential effects, both psychologically and in practical ways such as their ability to obtain insurance? How might potential misunderstanding – especially of their chances of developing vCJD - be minimised?


* For sufficiency of the blood supply. For example, how much blood might have to be discarded due to (possibly false) test results? Might the need to undergo a test, with such uncertain yet potentially alarming results, act as a deterrent to donation? A shortage in the blood supply could seriously affect the NHS’s ability to treat other patients.


* For the NHS and its patients more widely. For example, should donors whose blood has to be rejected be subject to other precautions? Specifically, if they subsequently undergo certain forms of surgery, should the instruments used be discarded rather than re-used? How many patients might be affected, and might this compromise the availability of treatment?



This paper explores these issues in broad terms, in anticipation that decisions will need to be made in the near future. It has been developed in parallel with more technical work on test development, and on ways to assess test performance. Successive versions have been shared with bodies advising on the practicalities and consequences of a screening test, notably the Prion Assay Working Group set up by the UK Blood Services, the CJD Incidents Panel and the TSE Working Group of the Advisory Committee on Dangerous Pathogens. The material has also informed discussions of the committee on the Safety of Blood, Tissues and Organs (SaBTO). Contributions from members of all these groups are gratefully acknowledged. Rather than offering policy conclusions: the aim has been to help establish a common understanding of the key issues. This remains work in progress, and specific comments will change as more information and evidence – notably on the performance of potential tests – becomes available. It is placed in the public domain to record our current understanding of this complex set of issues.


5


Mapping out the consequences of screening blood donations for PrPSc


1. Introduction: overview of key issues


Background


snip...SEE FULL TEXT 34 PAGES ;


http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_094804?IdcService=GET_FILE&dID=185357&Rendition=Web



IMPORT picture blood products and plasma



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





Saturday, May 02, 2009 5:11 PM Subject: Re: [BLOODCJD] MORE Blood products collected from a donor considered to be at increased risk for vCJD, were distributed USA APRIL 1, 2009

END OF ENFORCEMENT REPORT FOR APRIL 29, 2009

PRODUCT a) Fresh Frozen Plasma, Recall # B-0777-09; b) Red Blood Cells, Recall # B-0778-09 CODE a) and b) Unit: 7019457 RECALLING FIRM/MANUFACTURER HemaCare, Corp., Van Nuys, CA, by telephone and letter dated February 19, 2009. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION CA

___________________________________

PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-0798-09; b) Recovered Plasma, Recall # B-0799-09 CODE a) and b) Unit: R45567 RECALLING FIRM/MANUFACTURER Michigan Community Blood Centers, Saginaw, MI, by fax and e-mail on October 22, 2008. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION MI and Switzerland

___________________________________

PRODUCT Fresh Frozen Plasma, Recall # B-0814-09 CODE Unit: Q38595 RECALLING FIRM/MANUFACTURER Michigan Community Blood Centers, Saginaw, MI, by fax on October 31, 2008. Firm initiated recall is complete. REASON Blood product, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), was distributed. VOLUME OF PRODUCT IN COMMERCE 1 unit DISTRIBUTION MI

___________________________________

END OF ENFORCEMENT REPORT FOR APRIL 29, 2009

###




http://www.fda.gov/bbs/topics/ENFORCE/2009/ENF01105.html





Animal Transmissible Spongiform Encephalopathy North America



Subject: Aspects of the Cerebellar Neuropathology in Nor98

Date: September 26, 2007 at 4:06 pm PST

P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway

Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. *** The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.




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




Saturday, May 2, 2009

APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH

Nor98-like Scrapie in the United States of America

was presented by Drs. Christina M. Loiacono, S. Mark Hall, and Bruce V. Thomsen, National Veterinary Services Laboratory, USDA-APHIS-VS.

This paper describes the first six sheep diagnosed with Nor98-like disease in the United States and serves to acknowledge the increased efforts of diagnosticians and the USDA program to control and eradicate scrapie disease. Classical scrapie, a fatal neurodegenerative disease affecting the central nervous system of sheep and goats, is among a number of diseases classified as transmissible spongiform encephalopathies (TSEs). Recently, a distinct strain of scrapie was diagnosed in sheep in Norway1 and has been identified in numerous countries of the European Union (EU). The disease has been identified, among other names, as Nor98 or Nor98-like scrapie. Distinctions between classical scrapie and Nor98-like scrapie are made based on signalment, clinical signs, histopathology and immunodiagnostic results. In the past, the classical scrapie disease was confirmed by examination of the brain tissue for a triad of histopathological signs - vacuolation, loss of neurons and gliosis - and, more recently, by immunohistochemical (IHC) or biochemical detection of abnormal prion protein (PrPSc) in the brain, or lymphoid tissues. In the case of Nor98-like scrapie there is generally little or no vacuolation in the brain and, to date, no lymphoid accumulation of PrPSc has been detected. Classical scrapie typically has the most intense PrPSc immunostaining at the obex (motor nucleus of the vagus), while this area is spared in Nor98-like scrapie. Alternatively, Nor98-like scrapie consistently has PrPSc immunostaining in the spinal nucleus of the trigeminal nerve and variable, but often an intense immunostaining for PrPSc in the cerebellum. Thus the diagnosis of Nor98 and Nor98-like disease can be based on immunohistochemistry identifying abnormal prion protein in regions of the brain not typically associated with classical scrapie. Additionally there is a distinct diagnostic western blot pattern for Nor98 and Nor-98 like disease consisting of three or more protein bands with the unglycosylated band being less than 15 kd, compared to classical scrapie in which the unglycosylated band is greater than 15 kd. Nor98 and Nor-98 like disease is associated with older sheep, usually greater than four years of age, while sheep in the range of three to five years of age are more commonly affected by classical scrapie. Clinical signs are uncommon with Nor98 and Nor98-like disease but when present most often include ataxia without pruritis. Genotypes known to provide sheep with resistance to classical scrapie are not spared from Nor98 and Nor98-like disease.

The six U.S. cases had no clinical signs reported. Three cases were detected during slaughter surveillance, two were detected as a result of classical scrapie being found in the flock, one found during testing associated with diagnostic necropsy. Five of the 6 cases had genotypes that are susceptible to classical scrapie and one was AARR. Only one Nor98-like scrapie case was found per flock.

1. Benestad SL, Sarradin P, Thu B, Schönheit J, Tranulis MA, Bratberg B., Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet. Rec.




http://www.usaha.org/committees/reports/2008/report-scr-2008.pdf




http://nor-98.blogspot.com/2009/05/aphis-and-who-plan-to-exempt-atypical.html




Saturday, December 01, 2007

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model




http://transmissible-mink-encephalopathy.blogspot.com/2007/12/phenotypic-similarity-of-transmissible.html




Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. Since previous incidences of TME were associated with common or shared feeding practices, we obtained a careful history of feed ingredients used over the past 12-18 months. The rancher was a "dead stock" feeder using mostly (>95%) downer or dead dairy cattle and a few horses. Sheep had never been fed.




http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf




http://transmissible-mink-encephalopathy.blogspot.com/




10.3201/eid1505.081458 Suggested citation for this article: Angers RC, Seward TS, Napier D, Green M, Hoover E, Spraker T, et al. Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis. 2009 May; [Epub ahead of print]

Chronic Wasting Disease Prions in Elk Antler Velvet

Rachel C. Angers,1 Tanya S. Seward, Dana Napier, Michael Green, Edward Hoover, Terry Spraker, Katherine O'Rourke, Aru Balachandran, and Glenn C. Telling Author affiliations: University of Kentucky Medical Center, Lexington, Kentucky, USA (R.C. Angers, T.S. Seward, D. Napier, M. Green, G.C. Telling); Colorado State University, Fort Collins, Colorado, USA (E. Hoover, T. Spraker); US Department of Agriculture, Pullman, Washington, USA (K. O'Rourke); and Canadian Food Inspection Agency, Ottawa, Ontario, Canada (A. Balachandran) 1Current affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.

Chronic wasting disease (CWD) is a contagious, fatal prion disease of deer and elk that continues to emerge in new locations. To explore the means by which prions are transmitted with high efficiency among cervids, we examined prion infectivity in the apical skin layer covering the growing antler (antler velvet) by using CWD-susceptible transgenic mice and protein misfolding cyclic amplification. Our finding of prions in antler velvet of CWD-affected elk suggests that this tissue may play a role in disease transmission among cervids.

*** Humans who consume antler velvet as a nutritional supplement are at risk for exposure to prions.

The fact that CWD prion incubation times in transgenic mice expressing elk prion protein are consistently more rapid raises the possibility that residue 226, the sole primary structural difference between deer and elk prion protein, may be a major determinant of CWD pathogenesis.

snip...

Discussion

Acknowledgments We thank Dongyue Zhuang for excellent technical assistance. This work was supported by grants 2RO1NS040334-04 from the National Institute




http://www.cdc.gov/eid/content/15/5/pdfs/08-1458.pdf




snip...




1998 MY SUBMISSION TO THE BSE INQUIRY ENGLAND

Sender: "Patricia Cantos" To: "Terry S Singeltary Sr. (E-mail)" Subject: Your submission to the Inquiry Date: Fri, 3 Jul 1998 10:10:05 +0100

3 July 1998 Mr Terry S Singeltary Sr. E-Mail: Flounder at wt.net Ref: E2979

Dear Mr Singeltary,

Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments. Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died.

As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments.

Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD. I would refer you to the transcripts of evidence we have already heard which are found on our internet site at http://www.bse.org.uk. Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it? In the meantime, thank you for you comments. Please do not hesitate to contact me on 0171 261 8332 should you have any queries.

Yours sincerely Patricia Cantos Families Team Leader Attachments TSS

snip... see FULL TEXT ;


10.3201/eid1505.081458 Suggested citation for this article: Angers RC, Seward TS, Napier D, Green M, Hoover E, Spraker T, et al. Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis. 2009 May; [Epub ahead of print]

Chronic Wasting Disease Prions in Elk Antler Velvet




http://chronic-wasting-disease.blogspot.com/2009/03/chronic-wasting-disease-prions-in-elk.html




CWD Infection Studies in Two Species of Non-Human Primates

Bruce Chesebro Laboratory of Persistent Virus Diseases, Rocky Mountain Laboratories, Hamilton, Montana USA 59840.

CWD is a TSE/prion disease present in wild and domestic cervid populations of North America. CWD from cervids might possibly spread to humans who hunt and eat these species and to domestic animals such as cattle, sheep or horses sharing the same habitat. Therefore, it is important to understand the potential for spread of CWD to other species. Laboratory experiments have shown that CWD does not cause disease in transgenic mice expressing human PrP, suggesting that humans and other primates might be resistant to this infection. However, earlier data from the laboratory of Richard Marsh found that squirrel monkeys could be infected by intracerebral CWD inoculation. We recently followed up this work extending it to studies of two primate species, squirrel monkeys and Cynomolgus macaques. We also compared intracerebral and oral routes of infection. To search for possible CWD variant strains we analyzed 8 different CWD pools obtained from wild or domestic elk, mule deer and white-tailed deer. The results of these experiments will be presented.




http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf




J Virol. 2005 November; 79(21): 13794-13796. doi: 10.1128/JVI.79.21.13794-13796.2005. PMCID: PMC1262585

Copyright © 2005, American Society for Microbiology

Interspecies Transmission of Chronic Wasting Disease Prions to Squirrel Monkeys (Saimiri sciureus)

Richard F. Marsh,1? Anthony E. Kincaid,2 Richard A. Bessen,3 and Jason C. Bartz4* Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison 53706,1 Department of Physical Therapy,2 Department of Medical Microbiology and Immunology, Creighton University, Omaha, Nebraska 68178,4 Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana 597183 *Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178. Phone: (402) 280-1811. Fax: (402) 280-1875. E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:jbartz@creighton.edu. ?Deceased. Received May 3, 2005; Accepted August 10, 2005. This article has been cited by other articles in PMC. Top AbstractChronic wasting disease (CWD) is an emerging prion disease of deer and elk. The risk of CWD transmission to humans following exposure to CWD-infected tissues is unknown. To assess the susceptibility of nonhuman primates to CWD, two squirrel monkeys were inoculated with brain tissue from a CWD-infected mule deer. The CWD-inoculated squirrel monkeys developed a progressive neurodegenerative disease and were euthanized at 31 and 34 months postinfection. Brain tissue from the CWD-infected squirrel monkeys contained the abnormal isoform of the prion protein, PrP-res, and displayed spongiform degeneration. This is the first reported transmission of CWD to primates.




http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1262585




P1

THE ENVIRONMENT AS A RESERVOIR OF PRION INFECTIVITY

Aiken, Judd1,2, Chris Johnson4, Debbie McKenzie1,3 and Joel Pedersen5 1 Centre for Prions and Protein Folding Diseases, 2 Department of Agriculture, Food and Nutritional Sciences, 3 Department of Biological Sciences, University of Alberta, Edmonton, Alberta Canada, 4 National Wildlife Health Center, Madison, WI and 5 Department of Soil Sciences, University of Wisconsin, Madison

An environmental reservoir of prion infectivity has long been known to be a source of infection of sheep scrapie and likely plays an even more important role in the transmission of chronic wasting disease (CWD) in elk, deer and moose. Prion infectivity is extremely resistant to degradation, resulting in an environmental persistence of infectious agent. CWD is a contagious disease of free-ranging cervids. Infected deer and elk release infectious agent into the environment from body fluids and from diseased animal carcasses. The rapid expansion of CWD in North America represents a significant and continued environmental risk not only to cervids but to other species as well. Our work has demonstrated that prion protein, including PrPCWD, binds avidly to soil and soil components. Significantly, prion/soil binding enhances disease transmission suggesting that the soils, once contaminated with infectious prions, plays a critical role in maintaining and perpetuating prion infections.

III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)




http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf




P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5 The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.




http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf





They are not recalling all this CWD postive meat from commerce, for the well being of the dead elk. ...




RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

___________________________________

PRODUCT

a) Elk Meat, Elk Tenderloin, Frozen in plastic vacuum packaging. Each package is approximately 2 lbs., and each case is approximately 16 lbs.; Item number 755125, Recall # F-129-9;

b) Elk Meat, Elk Trim, Frozen; Item number 755155, Recall # F-130-9;

c) Elk Meat, French Rack, Chilled. Item number 755132, Recall # F-131-9;

d) Elk Meat, Nude Denver Leg. Item number 755122, Recall # F-132-9;

e) Elk Meat, New York Strip Steak, Chilled. Item number 755128, Recall # F-133-9;

f) Elk Meat, Flank Steak Frozen. Item number 755131, Recall # F-134-9;

CODE

Elk Meats with production dates of December 29, 30, and 31

RECALLING FIRM/MANUFACTURER

Recalling Firm: Sierra Meats, Reno, NV, by telephone on January 29, 2009 and press release on February 9, 2009.

Manufacturer: Noah's Ark Holding, LLC, Dawson, MN. Firm initiated recall is ongoing.

REASON

Elk products contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD).

VOLUME OF PRODUCT IN COMMERCE

Unknown

DISTRIBUTION

NV, CA, TX, CO, NY, UT, FL, OK

___________________________________




http://www.fda.gov/bbs/topics/ENFORCE/2009/ENF01099.html





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

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

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.




http://www.jbc.org/




snip...

Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs.

snip...




http://www.emboj.org/current.shtml




snip


http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm




From: TSS (216-119-163-189.ipset45.wt.net) Subject: CWD aka MAD DEER/ELK TO HUMANS ??? Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias" To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias" Sent: Monday, September 30, 2002 9:22 AM Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.

That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

-----Original Message----- From: Sent: Sunday, September 29, 2002 10:15 AM To: [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask] Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

snip...

full text ;

Monday, February 09, 2009

Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin Because It May Contain Meat Derived From An Elk Confirmed To Have CWD

snip...




http://chronic-wasting-disease.blogspot.com/2009/02/exotic-meats-usa-announces-urgent.html




Wednesday, March 18, 2009 Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II




http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html




Wednesday, February 11, 2009

Atypical BSE North America Update February 2009

Both of the BSE cases ascertained in the US native-born cattle were atypical cases (H-type), which contributed to the initial ambiguity of the diagnosis. 174, 185 In Canada, there have been 2 atypical BSE cases in addition to the 14 cases of the classic UK strain of BSE2: one was the H-type, and the other was of the L-type.198

snip...end

source :

Enhanced Abstract Journal of the American Veterinary Medical Association January 1, 2009, Vol. 234, No. 1, Pages 59-72

Bovine spongiform encephalopathy

Jane L. Harman, DVM, PhD; Christopher J. Silva, PhD




http://avmajournals.avma.org/doi/ref/10.2460/javma.234.1.59




Atypical BSE North America Update February 2009




http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html




Monday, May 4, 2009

Back to the Past With New TSE Testing Agricultural Research/May-June 2009




http://madcowtesting.blogspot.com/2009/05/back-to-past-with-new-tse-testing.html





In this context, a word is in order about the US testing program. After the discovery of the first (imported) cow in 2003, the magnitude of testing was much increased, reaching a level of >400,000 tests in 2005 (Figure 4). Neither of the 2 more recently indigenously infected older animals with nonspecific clinical features would have been detected without such testing, and neither would have been identified as atypical without confirmatory Western blots. Despite these facts, surveillance has now been decimated to 40,000 annual tests (USDA news release no. 0255.06, July 20, 2006) and invites the accusation that the United States will never know the true status of its involvement with BSE.

In short, a great deal of further work will need to be done before the phenotypic features and prevalence of atypical BSE are understood. More than a single strain may have been present from the beginning of the epidemic, but this possibility has been overlooked by virtue of the absence of widespread Western blot confirmatory testing of positive screening test results; or these new phenotypes may be found, at least in part, to result from infections at an older age by a typical BSE agent, rather than neonatal infections with new "strains" of BSE. Neither alternative has yet been investigated.




http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm




CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006

The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade.

The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old.

These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen.

"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that."

Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive.

USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general.

"Everything they did on the Texas cow makes everything USDA did before 2005 suspect," Brown said. ...snip...end




http://www.upi.com/




CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... Dr. Paul Brown is Senior Research Scientist in the Laboratory of Central Nervous System ... Address for correspondence: Paul Brown, Building 36, Room 4A-05, ...




http://www.cdc.gov/ncidod/eid/vol7no1/brown.htm




PAUL BROWN COMMENT TO ME ON THIS ISSUE

Tuesday, September 12, 2006 11:10 AM

"Actually, Terry, I have been critical of the USDA handling of the mad cow issue for some years, and with Linda Detwiler and others sent lengthy detailed critiques and recommendations to both the USDA and the Canadian Food Agency."




http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0703&L=sanet-mg&T=0&P=8125




Thursday, March 12, 2009

Lack of evidence of transfusion transmission of Creutzfeldt-Jakob disease in a US surveillance study ?

ORIGINAL ARTICLE




http://vcjdtransfusion.blogspot.com/2009/03/lack-of-evidence-of-transfusion.html




J Virol. 2005 November; 79(22): 14339-14345. doi: 10.1128/JVI.79.22.14339-14345.2005. PMCID: PMC1280201

Copyright © 2005, American Society for Microbiology

PrPTSE Distribution in a Primate Model of Variant, Sporadic, and Iatrogenic Creutzfeldt-Jakob Disease

Christian Herzog, Julie Rivière, Nathalie Lescoutra-Etchegaray, Aurore Charbonnier, Virginie Leblanc, Nicole Salès, Jean-Philippe Deslys, and Corinne Ida Lasmézas* Commissariat à l'Energie Atomique, Département de Recherche Médicale, BP6, 92265 Fontenay-aux-Roses, France *Corresponding author. Present address: The Scripps Research Institute, Department of Infectology, 33458 Jupiter, FL. Phone: (561) 799-8895. Fax: (561) 799-8960. E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:lasmezas@scripps.edu. Received May 13, 2005; Accepted August 25, 2005.


Abstract

Human prion diseases, such as Creutzfeldt-Jakob disease (CJD), are neurodegenerative and fatal. Sporadic CJD (sCJD) can be transmitted between humans through medical procedures involving highly infected organs, such as the central nervous system. However, in variant CJD (vCJD), which is due to human contamination with the bovine spongiform encephalopathy (BSE) agent, lymphoreticular tissue also harbors the transmissible spongiform encephalopathy-associated prion protein (PrPTSE), which poses a particularly acute risk for iatrogenic transmission. Two blood transfusion-related cases are already documented. In addition, the recent observation of PrPTSE in spleen and muscle in sCJD raised the possibility that peripheral PrPTSE is not limited to vCJD cases. We aimed to clarify the peripheral pathogenesis of human TSEs by using a nonhuman primate model which mimics human diseases. A highly sensitive enzyme-linked immunosorbent assay was adapted to the detection of extraneural PrPTSE. We show that affected organs can be divided into two groups. The first is peripheral organs accumulating large amounts of PrPTSE, which represent a high risk of iatrogenic transmission. This category comprises only lymphoreticular organs in the vCJD/BSE model. The second is organs with small amounts of PrPTSE associated with nervous structures. These are the muscles, adrenal glands, and enteric nervous system in the sporadic, iatrogenic, and variant CJD models. In contrast to the first set of organs, this low level of tissue contamination is not strain restricted and seems to be linked to secondary centrifugal spread of the agent through nerves. It might represent a risk for iatrogenic transmission, formerly underestimated despite previous reports of low rates of transmission from peripheral organs of humans to nonhuman primates (5, 10). This study provides an additional experimental basis for the classification of human organs into different risk categories and a rational re-evaluation of current risk management measures.




http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1280201




A New Prionopathy OR more of the same old BSe and sporadic CJD




http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html




Communicated by: Terry S. Singeltary Sr.

[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]




http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html




http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963




There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.




http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm




http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf




***Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.***



Progress Report from the National Prion Disease Pathology Surveillance Center

An Update from Stephen M. Sergay, MB, BCh & Pierluigi Gambetti, MD

April 3, 2008




http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45




USA PRION UNIT BLOG




http://prionunitusaupdate2008.blogspot.com/




Sunday, April 20, 2008

Progress Report from the National Prion Disease Pathology Surveillance Center April 3, 2008

Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.

see full text ;




http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.html




April 20, 2009

National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)

National Prion Disease Pathology Surveillance Center Cases Examined1

(December 31, 2008)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 42 32 28 4 0 0

1997 115 68 59 9 0 0

1998 93 53 45 7 1 0

1999 115 69 61 8 0 0

2000 151 103 89 14 0 0

2001 210 118 108 9 0 0

2002 258 147 123 22 2 0

2003 273 176 135 41 0 0

2004 335 184 162 21 0 13

2005 346 193 154 38 1 0

2006 380 192 159 32 0 14

2007 370 212 185 26 0 0

2008 383 228 182 23 0 0

TOTAL 30715 17756 1490 254 4 2

1 Listed based on the year of death or, if not available, on year of referral; 2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted; 3 Disease acquired in the United Kingdom; 4 Disease acquired in Saudi Arabia; 5 Includes 20 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 25 cases with type determination pending in which the diagnosis of vCJD has been excluded.

Rev 2/13/09 National




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




http://www.cjdsurveillance.com/resources-casereport.html




http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45





>>> *5 Includes 20 cases in which the diagnosis is pending, and 17 inconclusive cases; *6 Includes 25 cases with type determination pending in which the diagnosis of vCJD has been excluded. <<< href="http://prionunitusaupdate2008.blogspot.com/2009/04/r-calf-and-usa-mad-cow-problem-dont.html">http://prionunitusaupdate2008.blogspot.com/2009/04/r-calf-and-usa-mad-cow-problem-dont.html




Monday, April 20, 2009

National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)




http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html




sporadic Fatal Familial Insomnia



http://sporadicffi.blogspot.com/




THE PATHOLOGICAL PROTEIN

Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9

June 2003

BY Philip Yam

CHAPTER 14 LAYING ODDS

Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.




http://www.thepathologicalprotein.com/




The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003

doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

Tracking spongiform encephalopathies in North America

Original Text

Xavier Bosch

"My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem."




http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00715-1/fulltext




http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/%20fulltext




http://www.ncbi.nlm.nih.gov/pubmed/12906010




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





JOURNAL OF NEUROLOGY

MARCH 26, 2003

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

disease in the United States

Email Terry S. Singeltary:

mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto: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




Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT




http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT




http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT




2 January 2000

British Medical Journal U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well




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




15 November 1999

British Medical Journal vCJD in the USA * BSE in U.S.




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




Creutzfeldt Jakob Disease




http://creutzfeldt-jakob-disease.blogspot.com/




CJD TEXAS (cjd clusters)




http://cjdtexas.blogspot.com/




USA WRITTEN CJD QUESTIONNAIRE ???




http://cjdquestionnaire.blogspot.com/





The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.




http://www.cjdfoundation.org/fact.html





Attending Dr.: Date / Time Admitted : 12/14/97 1228

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.




http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html




Friday, June 13, 2008

Federal Oversight of Food Safety: FDA Has Provided Few Details GAO-08-909T June 12, 2008




http://fdafailedus.blogspot.com/2008/06/federal-oversight-of-food-safety-fda.html




Thu Dec 6, 2007 11:38

FDA IN CRISIS MODE, AMERICAN LIVES AT RISK




http://www.cidrap.umn.edu/cidrap/content/fs/food-disease/news/dec0407fda.html




FDA SCIENCE AND MISSION AT RISK




http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4329b_02_01_FDA%20Report%20on%20Science%20and%20Technology.pdf




http://fdafailedus.blogspot.com/




http://sciencebushwhacked.blogspot.com/





Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of the United States of America (USA) Question number: EFSA-Q-2003-083 Adopted date: 1 July 2004 Summary (0.1Mb)

Document (0.2Mb)

Summary

The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.

The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.

A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90's when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.

EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.




http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620779461.htm




http://www.efsa.europa.eu/EFSA/Scientific_Document/sr03_biohaz02_usa_report_annex_en1.pdf?ssbinary=true




http://www.efsa.europa.eu/EFSA/Scientific_Document/sr03_biohaz02_usa_report_v2_en1.pdf?ssbinary=true




http://www.efsa.europa.eu/EFSA/Scientific_Document/sr03_biohaz02_usa_report_summary_en1.pdf?ssbinary=true




Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE-Risk (GBR) of CANADA Question N° EFSA-Q-2003-083 Adopted July 2004 Summary The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC), to provide an up-to-date scientific report on the GBR in Canada, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in Canada. This scientific report addresses the GBR of Canada as assessed in 2004 based on data covering the period 1980-2003. The BSE agent was probably imported into the country middle of the eighties and could have reached domestic cattle in the early nineties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early 90s. It is possible that imported meat and bone meal (MBM) into Canada reached domestic cattle and led to an internal challenge in the early 90s. A certain risk that BSE-infected cattle entered processing in Canada, and were at least partly rendered for feed, occurred in the early 1990s when cattle imported from UK in the mid 80s could have been slaughtered. This risk continued to exist, and grew significantly in the mid 90's when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries. EFSA concludes that the current GBR level of Canada is III, i.e. it is confirmed at a lower level that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as the system remains unstable, it is expected that the GBR continues to grow, even if no additional external challenges occur.




http://www.mvo.nl/wetgeving-dierlijk-vet/onderzoek/download/EFSA%20on%20BSE%20risk%20Canada%20jul%202004.pdf




Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE-Risk (GBR) of MEXICO Question N° EFSA-Q-2003-083 Adopted July 2004 Summary The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in Mexico, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in Mexico. This scientific report addresses the GBR of Mexico as assessed in 2004 based on data covering the period 1980-2003. The BSE agent was probably imported into Mexico and could have reached domestic cattle. These cattle imported could have been rendered and therefore led to an internal challenge in the mid to late 1990's. It is possible that imported meat and bone meal (MBM) into Mexico reached domestic cattle and leads to an internal challenge around 1993. It is likely that BSE infectivity entered processing at the time of imported 'at - risk' MBM (1993) and at the time of slaughter of imported live 'at - risk' cattle (mid to late 1990s). The high level of external challenge is maintained throughout the reference period, and the system has not been made stable. Thus it is likely that BSE infectivity was recycled and propagated from approximately 1993. The risk has since grown consistently due to a maintained internal and external challenge and lack of a stable system. EFSA concludes that the current geographical BSE risk (GBR) level is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSEagent. The GBR is likely to increase due to continued internal and external challenge, coupled with a very unstable system.




http://www.mvo.nl/wetgeving-dierlijk-vet/onderzoek/download/EFSA%20on%20BSE%20risk%20Mexico%20jul%202004.pdf





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



Sunday, April 12, 2009

TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS




http://bse-atypical.blogspot.com/2009/04/transmission-of-atypical-bovine.html





HUMAN AND ANIMAL TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY, the silent pandemic

April 28, 2009 11:13 AM

the mad cow feed ban i.e. ruminant to ruminant feed ban was a long time over due. since august 4, 1997, since the inception of the PARTIAL and VOLUNTARY ban, the ban has been flouted, and thought of as nothing more than a joke. the feed ban of august 4, 1997 was nothing more than ink on paper. in 2007 alone, in one weekly enforcement letter, 10 MILLION PLUS POUNDS OF BANNED, BLOOD LACED MEAT AND BONE MEAL went out in commerce, to be fed out from state to state. there were many more since the infamous fda mad cow feed ban that never was. the industry need not look any further than the mirror to find the one to blame. they have had 12 years to get their house in order, but they chose to ignore the ban, the science, and to conduct business as usual i.e. feeding SRMs to human and livestock producing animals. no good, prions kill. this is not rocket science. all one has to do is look at the transmission studies. it's what i call the 'silent pandemic'. most all of us have been exposed, some are dying, but it is the friendly fire, and the very long incubation period that is fooling everyone. sporadic CJDs are on the rise, and the UKBSEnvCJD hamburger eating adolescents only theory was nothing more than a pipe dream. it's wrong, and for those that continue to follow this bogus theory will only enhance and spread all TSEs globally in doing so. North America has documented not only the typical cBSE, but also the h-BSE, and the l-BSE atypicals have been documented. CWD rampant in deer and elk, Scrapie, and the Nor-98 atypical scrapie in sheep and goats, with the latest scrapie case documented in a goat in March 2009 in the USA. North America is awash in animal TSEs, and again, sporadic CJD is rising, with atypical cases of CJD in young in the USA, what's that ??? rest asure, the cdc/USDA et al will assure, it's nothing. i don't believe them. ...TSS



National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)





http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html




http://www.bizlex.com/Articles-c-2009-04-28-86561.113117_FDA_ruling_hits_area_animal_agriculture.html





Tuesday, April 28, 2009

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY UPDATE (the silent pandemic) AND Agricultural Bioterrorism




http://madcowusda.blogspot.com/2009/04/transmissible-spongiform-encephalopathy.html





Thursday, April 30, 2009

FDA Issues Final Guidance for Renderers on Substances Prohibited From Use in Animal Food or Feed CVM Update Back April 30, 2009




http://madcowfeed.blogspot.com/2009/04/fda-issues-final-guidance-for-renderers.html





Thursday, December 04, 2008 2:37 PM



"we have found that H-BSE can infect humans."

personal communication with Professor Kong. ...TSS



see full text ;




http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html





Thursday, April 02, 2009 3:45 PM

Subject: [BLOODCJD] MORE Blood products collected from a donor considered to be at increased risk for vCJD, were distributed USA APRIL 1, 2009

PRODUCT a) Red Blood Cells, Recall # B-0659-09; b) Fresh Frozen Plasma, Recall # B-0660-09; c) Platelets, Recall # B-0661-09 CODE a) and b) Units: KX07877; KX05639; c) KX05639 RECALLING FIRM/MANUFACTURER Mid-South Regional Blood Center , Memphis , TN , by letter beginning July 10, 2008. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 5 units DISTRIBUTION TN

___________________________________

PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-0684-09; b) Recovered Plasma, Recall # B-0685-09 CODE a) and b) Units: 6165539, 6184317 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center , San Antonio , TX , by fax and e-mail on November 25, 2008 and as follow-up by fax on February 5, 2009. Firm initiated recall is complete. REASON Blood products, collected from a donor with risk factors for vCJD, were distributed. VOLUME OF PRODUCT IN COMMERCE 4 units DISTRIBUTION TX, Austria

___________________________________

END OF ENFORCEMENT REPORT FOR APRIL 1, 2009




http://www.fda.gov/bbs/topics/ENFORCE/2009/ENF01101.html





sadly, that was no April fools joke.


COMPARING THE RELATIVE RISK OF vCJD TRANSMISSION VIA PLASMA

The Department of Health asked SEAC for advice on a methodology for assessing the risks of using single unit plasma as opposed to pooled plasma, either sourced from the UK or non-UK source countries.

SEAC noted that there are many large uncertainties around the potential risk of transmission of vCJD via the use of plasma products. However, as the relative risks (as opposed to absolute risks) posed by plasma products were being estimated, uncertainties around the timing, level and distribution of infectivity in blood of an infected person would not appreciably affect the estimations. The best way to manage other major uncertainties, such as those around the prevalence of vCJD in the UK and other countries, would be to develop a range of scenarios incorporating reasonable high and low value estimates for such parameters.

vCJD INFECTION IN A HAEMOPHILIAC AT POST MORTEM

SEAC considered data from investigations of a Haemophilia patient who had been shown on post mortem to have the abnormal prion protein associated with vCJD in his spleen (as reported recently by the Health Protection Agency2). In view of the fact that preliminary unpublished data were considered, this issue was discussed in a reserved business session in accordance with the SEAC Code of Practice.

SEAC agreed that, although the patient had not shown clinical signs of vCJD prior to death, this finding provides evidence of vCJD infection. It would appear more likely at this stage that the infection occurred from the administration of clotting factors prepared from the plasma of a donor who had later developed vCJD than from dietary exposure to BSE.




http://www.seac.gov.uk/summaries/seac102_summary.pdf





update ;



2009 31 March 2009 - A summary of the 102nd SEAC meeting (35 KB) held on 4th March 2009

snip...

SEAC noted that IBNC appeared to be a rare disease that occurred in older cattle, predominantly as single cases, although it is possible that surveillance may not detect all cases. Biochemical studies suggested that the prion protein may play a role in the disease. However, it is unclear whether the normal form of the protein or an abnormal form is involved. Studies are required to determine whether IBNC is transmissible or not. SEAC concluded, noting that specified risk material controls are in place to prevent cattle brain from entering the food supply, that current data on IBNC do not suggest it presents a risk to human health.




http://www.seac.gov.uk/summaries/seac102_summary.pdf





stupid is, as stupid does. (forest gump). ...TSS



>>> All of the 15 cattle tested showed that the brains had abnormally accumulated prion protein. <<< href="http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html">http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html






''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$






1995

page 9 of 14 ;

30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.

31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...

snip... see full text




http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf





Sunday, February 15, 2009

Scientists warn of first ever case of human mad cow disease from blood plasma




http://vcjdtransfusion.blogspot.com/2009/02/scientists-warn-of-first-ever-case-of.html




http://vcjdtransfusion.blogspot.com/2009/02/scientists-warn-of-first-ever-case-of.html





Thursday, March 19, 2009

MILLIONS AND MILLIONS OF POUNDS OF MAD COW FEED IN COMMERCE USA



http://madcowfeed.blogspot.com/2009/03/millions-and-millions-of-pounds-of-mad.html





Saturday, January 24, 2009

Bovine Spongiform Encephalopathy h-BSE ATYPICAL USA 2008 Annual Report Research Project: Study of Atypical Bse

Location: Virus and Prion Diseases of Livestock

2008 Annual Report




http://bse-atypical.blogspot.com/2009/01/bovine-spongiform-encephalopathy-h-bse.html





Thursday, December 04, 2008 2:37 PM

"we have found that H-BSE can infect humans."

personal communication with Professor Kong. ...TSS



see full text ;




http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html






Thursday, April 9, 2009

Docket No. FDA2002N0031 (formerly Docket No. 2002N0273) RIN 0910AF46 Substances Prohibited From Use in Animal Food or Feed; Final Rule: Proposed




http://madcowfeed.blogspot.com/2009/04/docket-no-fda2002n0031-formerly-docket.html





Sunday, April 12, 2009



r-calf and the USA mad cow problem, don't look, don't find, and then blame Canada




http://prionunitusaupdate2008.blogspot.com/2009/04/r-calf-and-usa-mad-cow-problem-dont.html





Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)




http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html





Sunday, August 10, 2008 A New Prionopathy OR more of the same old BSe and sporadic CJD




http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html





Sunday, March 16, 2008

MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE




http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html





HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008

snip...

Tissue infectivity and strain typing of the many variants Manuscript of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

snip...




http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html





Elsevier Editorial System(tm) for The Lancet Infectious Diseases Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary

Abstract:

TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007. snip...

see full text 31 pages ;




http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf





TSS TO FREAS TSEAC 2006 CJD BLOOD ISSUES





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

From: Terry S. Singeltary Sr.

To: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:FREAS@CBER.FDA.GOV

Cc: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:rosanna.harvey@fda.hhs.gov

Sent: Wednesday, November 29, 2006 1:24 PM Subject: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION]

November 29, 2006

Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,

a kind and warm Holiday Greetings to you all.

i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derived antihemophilic factor (FVIII) products manufactured from U.S. plasma donors and related communication material ;




http://a257.g.akamaitech.net/7/257/2422/01jan20061800/edocket.access.gpo.gov/2006/E6-20251.htm




i see the media picked up on this as a 'low risk', from what the gov. agency perceived to be to them;




http://www.newsday.com/news/health/ats-ap_health14nov27,0,7955259.story?coll=ny-leadhealthnews-headlines





however, i seem to disagree. from my primitive ciphering, i see it another way. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, what about the mixed genotypes/mixed susceptibility? what about the silent carriers that donated tainted blood? what about the sporadic CJDs of UNKNOWN strain or phenotype? this risk assessment is just more BSe to me. Just another in a long line of industry fed crap. i pray that my assessment is the one that is wrong. but it is THEY who roll the dice with your life. It is THEY who refuse to regulate an industry that has run amok. just from a recall aspect of potentially tainted blood, and these are just recent recalls ;



snip...



Greetings again Dr. Freas et al at FDA,



WITH new atypical TSE in the bovine, in the sheep, goat, and humans, and the fact that the new BASE TSE in cattle being very very similar to sporadic CJD, rather than the nvCJD, the fact that now science showing the TSE agent of the atypical cattle in Japan showing infectivity other than CNS tissue, the fact that the latest Texas mad cow and the recent Alabama mad cow both being of the atypical strain, it would seem prudent to include all human TSE in the blood ban, in my opinion. with sporadic CJD, you have many strains and or phenotypes, some of which are 'UNKNOWN', so we do not know how this will transmit, what tissues are infectious and or if blood transmits. that's the bottom line, however it has been reported that the BASE is more virulent to humans. With this, and the fact that sporadic CJD has tripled in the past few years or so, i see it as being prudent to take serious and immediate action ;

PERSPECTIVE

On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and Creutzfeldt-Jakob Disease

Paul Brown,* Lisa M. McShane,? Gianluigi Zanusso,? and Linda Detwiler§

snip...

ONE FINAL COMMENT PLEASE, (i know this is long Dr. Freas but please bear with me)

THE USA is in a most unique situation, one of unknown circumstances with human and animal TSE. THE USA has the most documented TSE in different species to date, with substrains growing in those species (BSE/BASE in cattle and CWD in deer and elk, there is evidence here with different strains), and we know that sheep scrapie has over 20 strains of the typical scrapie with atypical scrapie documented and also BSE is very likely to have passed to sheep. all of which have been rendered and fed back to animals for human and animal consumption, a frightening scenario. WE do not know the outcome, and to play with human life around the globe with the very likely TSE tainted blood from the USA, in my opinion is like playing Russian roulette, of long duration, with potential long and enduring consequences, of which once done, cannot be undone.

These are the facts as i have come to know through daily and extensive research of TSE over 9 years, since 12/14/97. I do not pretend to have all the answers, but i do know to continue to believe in the ukbsenvcjd only theory of transmission to humans of only this one strain from only this one TSE from only this one part of the globe, will only lead to further failures, and needless exposure to humans from all strains of TSE, and possibly many more needless deaths from TSE via a multitude of proven routes and sources via many studies with primates and rodents and other species. ...

snip...

snip... see full text 48 pages, 1st page starts on page 13. ...TSS




http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8






TSS TO FREAS TSEAC 2001 CJD BLOOD ISSUES





Freas, William

From:Terry S. Singeltary Sr. [flounder@wt.net]

Sent: Monday, January 08, 200l 3:03 PM

To: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000039/!x-usc:mailto:freas@CBS5055530.CBER.FDA.GOV

Subject:CJD, BSE (aka madcow) Human/Animal TSE's--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)

Greetings again Dr. Freas and Committee Members,

I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version).

I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:


remember AIDS/HIV, 'no problem to heterosexuals in the U.S.? no need to go into that, you know of this blunder:


DO NOT make these same stupid mistakes again with human/animal TSE's aka MADCOW DISEASE. I lost my Mom to hvCJD, and my neighbor lost his Mother to sC3D as well (both cases confirmed). I have seen many deaths, from many diseases. I have never seen anything as CJD, I still see my Mom laying helpless, jerking tremendously, and screaming "God, what's wrong with me, why can't I stop this". I still see this, and will never forget. Approximately 10 weeks from 1st of symptoms to death. This is what drives me. I have learned more in 3 years about not only human/animal TSE's but the cattle/rendering/feeding industry/government than i ever wished to.


I think you are all aware of CJD vs vCJD, but i don't think you all know the facts of human/animal TSE's as a whole, they are all very very similar, and are all tied to the same thing, GREED and MAN.


I am beginning to think that the endless attempt to track down and ban, potential victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually? AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, .eyelid test, anything at whatever cost, we need a test FAST.


DO NOT let the incubation time period of these TSEs fool you.


To think of Scrapie as the prime agent to compare CJD, but yet overlook the Louping-ill vaccine event in 1930's of which 1000's of sheep where infected by scrapie from a vaccine made of scrapie infected sheep brains, would be foolish. I acquired this full text version of the event which was recorded in the Annual Congress of 1946 National Vet. Med. Ass. of Great Britain and Ireland. from the BVA and the URL is posted in my (long version).


U.S.A. should make all human/animal TSE's notifiable at all ages, with requirements for a thorough surveillance and post-mortem examinations free of charge, if you are serious about eradicating this horrible disease in man and animal.


There is histopathology reports describing o florid plaques" in CJD victims in the USA and some of these victims are getting younger. I have copies of such autopsies, there has to be more. PLUS, sub-clinical human TSE's will most definitely be a problem.


THEN think of vaccineCJD in children and the bovine tissues used in the manufacturing process, think of the FACT that this agent surviving 6OO*C.


PNAS -- Brown et al. 97 (7): 3418 scrapie agent live at 600*C


Then think of the CONFIDENTIAL documents of what was known of human/animal TSE and vaccines in the mid to late 8Os, it was all about depletion of stock, to hell with the kids, BUT yet they knew. To think of the recall and worry of TSE's from the polio vaccine, (one taken orally i think?), but yet neglect to act on the other potential TSE vaccines (inoculations, the most effective mode to transmit TSEs) of which thousands of doses were kept and used, to deplete stockpile, again would be foolish.


--Oral polio; up to 1988, foetal calf serum was used from UK and New Zealand (pooled); since 1988 foetal calf serum only from New Zealand. Large stocks are held.


--Rubella; bulk was made before 1979 from foetal calf serum from UK and New Zealand. None has been made as there are some 15 years stock.


--Diphtheria; UK bovine beef muscle and ox heart is used but since the end of 1988 this has been sourced from Eire. There are 1,250 litres of stock.


--Tetanus; this involves bovine material from the UK mainly Scottish. There are 21,000 litres of stock.


--Pertussis; uses bovine material from the UK. There are 63,000 litres of stock.


--They consider that to switch to a non-UK source will take a minimum of 6-18 months and to switch to a non-bovine source will take a minimum of five years.


3. XXXXXXXXXXX have measles, mumps, MMR, rubella vaccines. These are sourced from the USA and the company believes that US material only is used.


89/2.14/2.1


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


BSE3/1 0251


4. XXXXXXXXXXX have a measles vaccine using bovine serum from the UK. there are 440,000 units of stock. They have also got MMR using bovine serum from the UK.


5. XXXXXXXXXXX have influenza, rubella, measles,' MMR vaccines likely to be used in children. Of those they think that only MMR contains bovine material which is probably a French origin.


6. XXXXXXXXXXX have diphtheria/tetanus and potasses on clinical trial. hese use veal material, some of which has come from the UK and has been ade by XXXXXXXXXXX (see above).


I have documents of imports from known BSE Countries, of ferments, whole blood, antiallergenic preparations, human blood plasma, normal human blood sera, human immune blood sera, fetal bovine serum, and other blood fractions not elsewhere specified or included, imported glands, catgut, vaccines for both human/animal, as late as 1998.


Let us not forget about PITUITARY EXTRACT. This was used to help COWS super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.


ANNEX 6

MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TO BIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIAL

How much of this was used in the U.S.?

Please do not keep making the same mistakes;

'Absence of evidence is not evidence of absence'.

What are the U.S. rules for importing and manufacturing vaccines, medicines and medical devices?

Does the U.S.A. allow sourcing of raw material of ruminants from the U.S.A.?

U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds.?

The U.S. rendering system would easily amplify T.S.E.'s:

Have we increased the stability of the system (improved heat treatments) since the EU SSC report on the U.S.A. was published in july 2000?

What is done to avoid cross-contaminations in the U.S.A.?

How can the U.S. control absence of cross-contaminations of animal TSE's when pig and horse MBM and even deer and elk are allowed in ruminant feed, as well as bovine blood? I sadly think of the rendering and feeding policy before the Aug. 4, 1997 'partial' feed ban, where anything went, from the city police horse, to the circus elephant, i will not mention all the scrapie infected sheep. I am surprised that we have not included man 'aka soyent green'. It is a disgusting industry and nothing more than greed fuels it.

When will the U.S.. start real surveillance of the U.S. bovine population (not passive, this will not work)?

When will U.S. start removing SRMs?

Have they stopped the use of pneumatic stunners in the U.S.? If so, will we stop it in all U.S. abattoirs or only in those abattoirs exporting to Europe? If not, WHY NOT?

same questions for removal of SRM in the U.S.A., or just for export? If not, WHY NOT?

How do we now sterilize surgical/dental instruments in the U.S.A.?

Where have we been sourcing surgical catgut? (i have copies of imports to U.S., and it would floor you)

When will re-usable surgical instruments be banned?

'Unregulated "foods" such as 'nutritional supplements' containing various extracts from ruminants, whether imported or derived from US cattle/sheep/cervids ("antler velvet" extracts!) should be forbidden or at least very seriously regulated. (neighbors Mom, whom also died from CJD, had been taking bovine based supplement, which contained brain, eye, and many other bovine/ovine tissues for years, 'IPLEX').

What is the use of banning blood or tissue donors from Germany, France, etc... when the U.S.A. continues exposing cattle, sheep and people to SRM, refuses to have a serious feed ban, refuses to do systematic BSE-surveillance?

The FDA should feel responsible for the safety of what people eat, prohibit the most dangerous foods, not only prohibit a few more donors - the FDA should be responsible for the safe sourcing of medical devices, not only rely on banning donors "from Europe", The 'real' risks are here in the U.S. as well, and have been for some time.

We must not forget the studies that have proven infectivity in blood from TSE's.

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.l Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.

snip...

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 infracerebrally into CFl 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

snip...

Department of Neuropathology, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka812, Japan

JUN TATEISHI

(full text-long version)

and

CWD and transmission to man will be no different than other TSE's.

"Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has

4

caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs,"

G.J. Raymondl, A. BossersZ, L.D. Raymondl, K.I. O'Rourke3, L.E. McHolland4, P.K. Bryant 1114, M.W. MillerS, E.S. Williams6, M. Smits2 and B. Caugheyl,7

or more recently transmission of BSE to sheep via whole blood Research letters Volume 356, Number 9234 16 September 2000

Transmission of BSE by blood transfusion in sheep

Lancet 2000; 356: 999 - 1000

F Houston, J D Foster, Angela Chong, N Hunter, C J Bostock

See Commentary

"We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) in human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission-- this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK."

. "The demonstration that the new variant of Creutzfeldt-Jakob disease (vCJD) is caused by the same agent that causes bovine spongiform encephalopathy (BSE) in cattle1 has raised concerns that blood from human beings in the symptom-free stages of vCJD could transmit infection to recipients of blood transfusions (full text long version)"

and...

"The large number of cases (1040), temporal clustering of the outbreaks (15 in the first 6 months of 1997), the high in-flock incidence, and the exceptional involvement of goats (390 cases), suggested an accidental infection. The source of the epidemic might have been TSE-contaminated meat and bonemeal, but eight flocks had never been fed any commercial feedstuff. Infection might have risen from the use of a formol-inactivated vaccine against contagious agalactia prepared by a single laboratory with brain and mammary gland homogenates of sheep infected with Mycoplasma agalactiae. Although clinical signs of TSE in the donor sheep have not been found, it is possible that one or more of them were harbouring the

infectious agent. Between 1995 and 1996, this vaccine was given subcutaneously to 15 of the affected flocks (to one flock in 1994) ; in these animals the disease appeared between 23 and 35 months after vaccination. No information is available for herd 13 because it was made up of stolen animals. Sheep from the remaining three flocks (l-3, figure) did not receive the vaccine, thus suggesting a naturally occurring disease." (again, full text long version).

IN SHORT, please do under estimate this data and or human/animal TSE's including CWD in the U.S.A.

A few last words, please.

The cattle industry would love to have us turn our focus to CWD and forget about our own home grown TSE in Bovines. This would be easy to do. Marsh's work was from downer cattle feed, NOT downer deer/elk feed. This has been proven.

DO NOT MAKE THAT MISTAKE.

There should be NO LESS THAN l,OOO,OOO tests for BSE/TSE in 2001 for U.S.A. French are testing 20,000 a week. The tests are available. Why wait until we stumble across a case from passive surveillance, by then it is to late. IF we want the truth, this is a must???

United States Total ,Bovine Brain Submissions by State,

May 10,1990 thru October 31, 2000

Total 11,700

FROM 1.5 BILLION HEAD OF CATTLE since 1990 ???

with same feeding and rendering practices as that of U.K. for years and years, same scrapie infected sheep used in feed, for years and years, 950 scrapie infect FLOCKS in the U.S. and over 20 different strains of scrapie known to date. (hmmm, i am thinking why there is not a variant scrapie, that is totally different than all the rest)? just being sarcastic. (NOT...TSS...2009)

with only PARTIAL FEED BAN implemented on Aug. 4, 1997??? (you really need to reconsider that blood meal etc. 'TOTAL BAN')




http://www.aphis.usda.gov/oa/bse/bsesurv,ey.html#charts





AND PLEASE FOR GODS SAKE, STOP saying vCJD victims are the only ones tied to this environmental death sentence. "PROVE IT". It's just not true. The 'CHOSEN ONES' are not the only ones dying because of this man-made death sentence. When making regulations for human health from human/animal TSEs, you had better include ALL human TSE's, not just vCJD. Do NOT underestimate sporadic CJD with the 'prehistoric' testing available to date. This could be a deadly mistake. Remember, sCJD kills much faster from 1st onset of symptoms to death, and hvCJD is the fastest. Could it just be a higher titre of infectivity, or route or source, or all three?

Last, but not least. The illegal/legal harvesting of body parts and tissues will come back to haunt you. Maybe not morally, but due to NO background checks and human TSEs, again it i will continue to spread.

Stupidity, Ignorance and Greed is what fuels this disease. You must stop all of this, and ACT AT ONCE...




http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf





2009



Thursday, April 02, 2009

MORE Blood products collected from a donor considered to be at increased risk for vCJD, were distributed USA APRIL 1, 2009




http://vcjdtransfusion.blogspot.com/2009/04/more-blood-products-collected-from.html





There is a new sheriff in town, and I hope he plans on 'sound science', to take the reins, instead of the previous 8 years of 'junk science'.



The UKBSEnvCJD only theory is wrong, and to continue with this policy, will only enhance the spread of human and animal TSE Globally. ...




Thank You,

With Kindest Regards,

I am sincerely,

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

Transmissible Spongiform Encephalopathies Advisory Committee September 18-19, 2006 Meeting

Transmissible Spongiform Encephalopathies Advisory Committee September 18-19, 2006 Meeting

Date and Time: The meeting will be held on September 18, 2006, 8 a.m. to 4:30 p.m. and September 19, 2006, 8 a.m. to 1 p.m.

Location: Holiday Inn Gaithersburg, MD, 2 Montgomery Village Avenue, Gaithersburg, MD 20879

Contact Person: William Freas, or Rosanna L. Harvey, 301-827-0314, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512392. Please call the Information Line for up-to-date information on this meeting.

Agenda: On September 18, 2006 the Committee will hear updates on the following topics: United States and worldwide bovine spongiform encephalopathies (BSE); variant Creutzfeldt-Jakob disease (vCJD) epidemiology and transfusion-transmission; blood and plasma donor deferral for transfusion in France since 1980, guidance; FDA’s current assessment and plans regarding the potential exposure to vCJD from an investigational product, FXI, that was manufactured from UK donor plasma; and a summary of World Heath Organization Consultation on distribution of infectivity in tissues of animals and humans with transmissible spongiform encephalopathies. The Committee will then discuss experimental clearance of transmissible spongiform encephalopathy infectivity in plasma-derived Factor VIII products. In the afternoon, the Committee will discuss FDA’s risk assessment for potential exposure to vCJD from human plasma-derived antihemophilic factor (FVIII) products and potential responses. On September 19, 2006 the Committee will discuss possible criteria for approval of donor screening tests for vCJD.

Oral presentations from the public will be scheduled between approximately 10:45 a.m. and 11:15 p.m. and 2:30 p.m. and 3:00 p.m. on September 18, 2006 and between approximately 10:15 a.m. and 11:45 a.m. on September 19, 2006. Those desiring to make formal oral presentations should notify the contact person on or before September 11, 2006.

http://www.fda.gov/cber/advisory/tse/tse0906.htm



Transmissible Spongiform Encephalopathies Advisory Committee December 15, 2006 Meeting

Date and Time: The meeting will be held on December 15, 2006, 8 a.m. to 3:30 p.m.

Location:Crown Plaza Silver Spring, 8777 Georgia Ave., Silver Spring, MD 20910, 301-589-0800.

Contact Person: William Freas, or Rosanna L. Harvey, 301-827-0314, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512392. Please call the Information Line for up-to-date information on this meeting.

Agenda: On December 15, 2006, the Committee will discuss FDA's risk assessment for potential exposure to vCJD in human plasma-derived antihemophilic factor (FVIII) products manufactured from US plasma donors and related communication materials. In the afternoon, the Committee will discuss levels of transmissible spongiform encephalopathy clearance in the manufacture of plasma-derived Factor VIII products.

Oral Presentations: Oral presentations from the public will be scheduled between approximately 10:25 and 10:55 a.m. and 1:35 and 2:05 p.m. on December 15, 2006. Those desiring to make formal oral presentations should notify the contact person on or before December 7, 2006.

Unofficial Summary

for the

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

ADVISORY COMMITTEE Meeting on

December 15, 2006



http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4271t-unofficial.htm

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4271t1.pdf

http://www.fda.gov/ohrms/dockets/ac/cber06.html#TransmissibleSpongiform

http://www.fda.gov/cber/advisory/tse/tse1206.htm



TSE advisory committee for the meeting December 15, 2006

(MICROSOFT WORD FILE)


please note, the beginning starts on page 13.

page 1 - 13 are parts II and Parts III that were added later. ...tss


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

From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Wednesday, November 29, 2006 1:24 PM

Subject: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION]

November 29, 2006

Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,

a kind and warm Holiday Greetings to you all. i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derived antihemophilic factor (FVIII) products manufactured from U.S. plasma donors and related communication material ;


http://a257.g.akamaitech.net/7/257/2422/01jan20061800/edocket.access.gpo.gov/2006/E6-20251.htm

i see the media picked up on this as a 'low risk', from what the gov. agency perceived to be to them;

http://www.newsday.com/news/health/ats-ap_health14nov27,0,7955259.story?coll=ny-leadhealthnews-headlines

however, i seem to disagree. from my primitive ciphering, i see it another way. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, what about the mixed genotypes/mixed susceptibility? what about the silent carriers that donated tainted blood? what about the sporadic CJDs of UNKNOWN strain or phenotype? this risk assessment is just more BSe to me. Just another in a long line of industry fed crap. i pray that my assessment is the one that is wrong. but it is THEY who roll the dice with your life. It is THEY who refuse to regulate an industry that has run amok. just from a recall aspect of potentially tainted blood, and these are just recent recalls ;


snip.. please see full text 48 pages @ ;

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8



DER SPIEGEL (9/2001) - 24.02.2001 (9397 Zeichen)USA: Loch in der MauerDieBSE-Angst erreicht Amerika: Trotz strikter Auflagen gelangte inTexasverbotenes Tiermehl ins Rinderfutter - die Kontrollen derAufsichtsbehördensind lax. Link auf diesen Artikel im Archiv:

http://service.spiegel.de/digas/find?DID=18578755


"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...

http://service.spiegel.de/digas/servlet/find/DID=18578755


Thu Dec 6, 2007 11:38

FDA IN CRISIS MODE, AMERICAN LIVES AT RISK

http://www.cidrap.umn.edu/cidrap/content/fs/food-disease/news/dec0407fda.html


FDA SCIENCE AND MISSION AT RISK

http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4329b_02_01_FDA%20Report%20on%20Science%20and%20Technology.pdf


2 January 2000

British Medical Journal

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

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


15 November 1999

British Medical JournalvCJD in the USA * BSE in U.S.

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


BSE (Mad Cow) Update: Do Reports of sCJD Clusters Matter?

snip...

see full text ;

http://cjdtexas.blogspot.com/


16 January 2008 - The final minutes of the 98th SEAC meeting have been published.

PUBLIC QUESTION AND ANSWER SESSION 2© SEAC 2007

SEAC considered a question about possible links between CJD cases and animal TSEs in the United States of America (USA).

http://www.seac.gov.uk/summaries/seac99_summary.pdf


SEAC 99th meeting on Friday 14th December 2007

http://seac992007.blogspot.com/



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

TSEAC MEETINGS

----- Original Message ----- From: Terry S. Singeltary Sr.To: FREAS@CBER.FDA.GOVCc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.govSent: Wednesday, November 29, 2006 1:24 PMSubject: TSE advisory committee for the meeting December 15, 2006 [TSSSUBMISSION]November 29, 2006Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,a kind and warm Holiday Greetings to you all.i kindly wish to submit the following to the TSE advisory committee for themeeting December 15, 2006,about the assessment for potential exposure to vCJD in human plasma-derivedantihemophilic factor (FVIII) productsmanufactured from U.S. plasma donors and related communication material ;http://a257.g.akamaitech.net/7/257/2422/01jan20061800/edocket.access.gpo.gov/2006/E6-20251.htmi see the media picked up on this as a 'low risk', from what the gov. agencyperceived to be to them;http://www.newsday.com/news/health/ats-ap_health14nov27,0,7955259.story?coll=ny-leadhealthnews-headlineshowever, i seem to disagree. from my primitive ciphering, i see it anotherway. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2%which is 1 in 50 or twenty per thousand or 20,000 per million. also, whatabout the mixed genotypes/mixed susceptibility? what about the silentcarriers that donated tainted blood? what about the sporadic CJDs of UNKNOWNstrain or phenotype? this risk assessment is just more BSe to me. justanother in a long line of industry fed crap. i pray that my assessment isthe one that is wrong. but it is THEY who roll the dice with your life. itis THEY who refuse to regulate an industry that has run amok. just from arecall aspect of potentially tainted blood, and these are just recentrecalls ;PRODUCTSource Plasma, Recall # B-0054-7CODEUnits: 03MMNC5465, 03MMNC6361, 03MMNC6801, 03MMNC7510, 03MMNC7891,03MMNC8252, 03MMNC8801, 03MMNC9144, 03MMND1122, 03MMND1478, 03MMND1969,03MMND2350, 03MMND2825, 03MMND3211, 03MMND3708, 03MMND4072, 03MMND4588,03MMND4831, 03MMND5320, 03MMND5719, 03MMND6268, 03MMND6683, 03MMND7228,03MMND7656, 03MMND8211, 03MMND8652, 03MMND9195, 03MMND9618, 03MMNE0628,03MMNE0884, 03MMNE1597, 03MMNE1979, 03MMNE2644, 03MMNE3064, 03MMNE3707,03MMNE4122, 03MMNE4750, 03MMNE5080, 03MMNE5876, 03MMNE6218, 03MMNE7189,03MMNE7587, 03MMNE8027, 03MMNE8645, 03MMNE9029, 03MMNE9641, 03MMNE9979,03MMNF0491, 03MMNF0685, 03MMNF0937, 03MMNF1260, 04MMNA0351, 04MMNA0707,04MMNA1241, 04MMNA1650, 04MMNA2291, 04MMNA2646, 04MMNA3340, 04MMNA3719,04MMNA4312, 04MMNA4683, 04MMNA5298, 04MMNA5750, 04MMNA6407, 04MMNA6816,04MMNA7482, 04MMNA7915, 04MMNA8632, 04MMNA9076, 04MMNA9723, 04MMNB0063,04MMNB0696, 04MMNB1100, 04MMNB1845, 04MMNB2285, 04MMNB3035, 04MMNB3485,04MMNB4213, 04MMNB4672, 04MMNB5841, 04MMNB6652, 04MMNB7162, 04MMNB7930,04MMNB8453, 04MMNB9239, 04MMNB9747, 04MMNC0456, 04MMNC0931, 04MMNC1578RECALLING FIRM/MANUFACTURERBioLife Plasma Services, L.P., Mankato, MN, by facsimile on June 4, 2004.Firm initiated recall is complete.REASONBlood products, collected from a donor who was at increased risk for newvariant Creutzfeldt-Jakob Disease (nvCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE89 unitsDISTRIBUTIONCA and AustriaEND OF ENFORCEMENT REPORT FOR October 25, 2006###http://www.fda.gov/bbs/topics/enforce/2006/ENF00975.htmlUSA FDA MAD COW BLOOD HUMANS RECALL (these are dime a dozen)RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS II______________________________PRODUCTSource Plasma, Recall # B-1708-6CODEUnits: MI180733, MI180927, MI181625, MI181780, MI182337, MI182519, MI183140,MI183311, MI183955, MI185006, MI185278, MI185822, MI186081, MI186855,MI187183, MI187903, MI188273, MI188695, MI189257, MI189553, MI190136,MI190473, MI191073, MI191395, MI191972, MI192303, MI193473, MI194343,04MINA0377, 04MINA0801, 05MINA7147, 05MINA7451, 05MINA8094, 05MINA8504,05MINA9548, 05MINA9883, 05MINB0489, 05MINB0875, 05MINB1469, 05MINB1874,05MINB3116, 05MINB7192, 05MINB7529, 05MINB8246, 05MINB8612, 05MINB9236,05MINB9366, 05MINB9475, 05MINB9641, 05MINC0031, 05MINC0237, 05MINC0336,05MINC0894, 05MINC0964, 05MINC1138, 05MINC1619, 05MINC1750, 05MINC1907,05MINC1977, 05MINC2375, 05MINC2774, 05MINC3113, 05MINC3484, 05MINC4277,05MINC4623, 05MINC5623, 05MINC5914, 05MINC7545, 05MINC7870, 05MINC8355,05MINC8689, 05MINC9437, 05MINC9775, 05MIND0067, 05MIND0393, 05MIND0892,05MIND0951, 05MIND1836, 05MIND2183 and 05MIND2962RECALLING FIRM/MANUFACTURERBioLife Plasma Services L.P., Muncie, IN, by facsimile on November 22, 2005.Firm initiated recall is complete.REASONBlood products, collected from unsuitable donors based on risk factors forCreutzfeldt-Jakob Disease (CJD), were distributed.VOLUME OF PRODUCT IN COMMERCE80 unitsDISTRIBUTIONCA, NC, and MD______________________________PRODUCTa) Red Blood Cells, Leukocytes Reduced, Recall # B-1714-6;b) Fresh Frozen Plasma, Recall # B-1715-6;c) Platelets, Recall # B-1716-6CODEa), b), and c) Unit: 2443732RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by letters datedNovember 11, 2003 and December 18, 2003. Firm initiated recall is complete.REASONBlood products, collected from a donor who was at increased risk for newvariant Creutzfeldt-Jakob Disease (nvCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE3 unitsDISTRIBUTIONTX and WIEND OF ENFORCEMENT REPORT FOR SEPTEMBER 13, 2006###http://www.fda.gov/bbs/topics/enforce/2006/ENF00969.htmlPRODUCTFresh Frozen Plasma, Recall # B-1751-6CODEUnit: 4936623RECALLING FIRM/MANUFACTURERGulf Coast Regional Blood Center, Houston, TX, by facsimile dated September16, 2005. Firm initiated recall is complete.REASONBlood product, which was collected from an unsuitable donor based on riskfactors for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.VOLUME OF PRODUCT IN COMMERCE1 unitDISTRIBUTIONTXEND OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006###http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.htmlMon Aug 7, 2006 10:2471.248.132.189PRODUCTa) Red Blood Cells, Recall # B-1587-6;b) Cryoprecipitated AHF, Recall # B-1588-6;c) Recovered Plasma, Recal # B-1589-6CODEa), b) and c) Unit: 2016719RECALLING FIRM/MANUFACTURERWalter Shepeard Community Blood Center, Inc., Augusta, GA, by facsimile onMarch 13, 2003. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE3 unitsDISTRIBUTIONGA and Germany______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1590-6;b) Fresh Frozen Plasma, Recall # B-1591-6CODEa) and b) Unit: 2443595RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June30, 2004. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONTX______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1592-6;b) Fresh Frozen Plasma, Recall # B-1593-6CODEa) and b) Unit: 2545596RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by facsimile onDecember 14, 2004 and January 3, 2005. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONTX______________________________http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.htmlPRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1550-6;b) Fresh Frozen Plasma, Recall # B-1551-6CODEa) and b) Unit 2395371RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by fax on August 20,2003. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONTX______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1552-6;b) Platelets, Recall # B-1553-6;c) Fresh Frozen Plasma, Recall # B-1554-6CODEa), b) and c) Unit 2438702RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by fax on May 29,2003. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE3 unitsDISTRIBUTIONTX______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1555-6;b) Fresh Frozen Plasma, Recall # B-1556-6CODEa) and b) Unit 2454970RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by fax on July 23 andDecember 11. 2003. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONTX______________________________PRODUCTa) Red Blood Cells, Recall # B-1494-6b) Cryoprecipitated AHF, Recall # B-1495-6CODEa) and b) Unit 5013100RECALLING FIRM/MANUFACTURERWalter L. Shepeard Community Blood Center, Inc., Augusta, GA, by fax on May17, 2005. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONGA______________________________PRODUCTSource Plasma, Recall # B-1450-6CODEUnit numbers ST0824313 and ST0824764RECALLING FIRM/MANUFACTURERStillwater Plasma Center LLC, Stillwater, OK, by fax on November 21, 2003.Firm initiated recall is complete.REASONBlood products, which were collected from a donor whose suitabilitypertaining to risk factors for Creutzfeldt-Jakob Disease (vCJD) was notadequately determined, were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONUK______________________________PRODUCTPlasma Frozen, Recall # B-1422-6;Recovered Plasma, Recall # B-1423-6CODEa) Unit 03E42218;b) Unit 03E38153RECALLING FIRM/MANUFACTURERAmerican Red Cross Blood Services, Atlanta, GA, by telephone, e-mail orletter on February 20 or 21, 2004. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONGA and Switzerland______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1374-6;b) Recovered Plasma, Recall # B-1375-6CODEa) and b) unit 2453906RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by fax on October 31and November 5, 2003. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONTX and Austria______________________________PRODUCTSource Plasma. Recall # B-1295-6CODEUnits: NG0046551, NG0045950RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002, Firm initiated recall is complete.REASONBlood products, collected from a donor who did not answer the questions onthe new variant Creutzfeldt-Jacob disease (nvCJD) questionnaireappropriately, were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONKY______________________________PRODUCTSource Plasma. Recall # B-1296-6CODEUnit: NG 0044520RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 12, 2002. Firm initiated recall is complete.REASONBlood product, collected from a donor who did not answer the questions onthe new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire, wasdistributed.VOLUME OF PRODUCT IN COMMERCE1 unitDISTRIBUTIONKY______________________________PRODUCTSource Plasma. Recall # B-1297-6CODEUnits: NG0042874, NG0043139, NG0043312, NG0043618, NG0043797, NG0044020,NG0044209, NG0044507, NG0044718, NG0044977, NG0045161, NG0045412, NG0045555RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.REASONBlood products, collected from a donor considered to be at increased riskfor variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE13 unitsDISTRIBUTIONKY______________________________PRODUCTSource Plasma, Recall # B-1298-6CODEUnits: NG 0046823, NG 0046671, NG 0045205, NG 0044635, NG 0043095, NG0042525, NG 0042341RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.REASONBlood products, collected from a donor who answered questions on the variantCreutzfeldt-Jacob disease (vCJD) questionnaire inappropriately, weredistributed.VOLUME OF PRODUCT IN COMMERCE7 unitsDISTRIBUTIONKY______________________________PRODUCTRecovered Plasma, Recall # B-1299-6CODEUnit: 4357117RECALLING FIRM/MANUFACTURERDepartment of the Navy, Naval Medical Center, San Diego, CA, by fax andletter on September 25, 2003. Firm initiated recall is complete.REASONBlood product, collected from a donor considered to be at risk of exposureto Creutzfeldt-Jacob Disease (CJD), was distributed.VOLUME OF PRODUCT IN COMMERCE1 unitDISTRIBUTIONGermanyEND OF ENFORCEMENT REPORT FOR July 12, 2006###http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.htmlCJD WATCH MESSAGE BOARDTSSFDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULYFri Jul 7, 2006 09:3770.110.83.160FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULYPRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1379-6;b) Platelets, Recall # B-1380-6;c) Fresh Frozen Plasma, Recall # 1381-6;d) Recovered Plasma, Recall # B-1382-6CODEa) Unit numbers: 2343106, 2377779, and 2403533;b) and c) Unit numbers: 2377779;d) Unit numbers: 2343106 and 2403533RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June12, 2003. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE7 unitsDISTRIBUTIONTX and Austria______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1467-6;b) Recovered Plasma, Recall # B-1468-6CODEa) and b) Unit numbers: 2329380RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by facsimile on May 8,2003. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONTX and Switzerland______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1479-6;b) Cryoprecipitated AHF, Recall # B-1480-6;c) Recovered Plasma, Recall # B-1481-6CODEa), b), and c) Unit numbers: 2383280RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by facsimile on July23 and 29, 2004. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE3 unitsDISTRIBUTIONTX and Switzerland______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1482-6;b) Fresh Frozen Plasma, Recall # B-1483-6CODEa) and b) Unit number: 2501452RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by facsimile onOctober 5, 2004. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE2 unitsDISTRIBUTIONTX and NY______________________________PRODUCTa) Red Blood Cells Leukocytes Reduced, Recall # B-1484-6;b) Plasma Cryoprecipitated Reduced, Recall # B-1485-6;c) Recovered Plasma, Recall # B-1486-6CODEa) and c) Unit number: 2554077;b) Unit number: 2415708RECALLING FIRM/MANUFACTURERSouth Texas Blood and Tissue Center, San Antonio, TX, by facsimile on August13, 2004. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.VOLUME OF PRODUCT IN COMMERCE3 unitsDISTRIBUTIONTX and Austria_____________________________________END OF ENFORCEMENT REPORT FOR July 5, 2006###http://www.fda.gov/bbs/topics/enforce/2006/ENF00959.htmlGreetings again Dr. Freas et al at FDA,WITH new atypical TSE in the bovine, in the sheep, goat, and humans,and the fact that the new BASE TSE in cattle being very very similar tosporadicCJD, rather than the nvCJD, the fact that now science showing the TSE agentof the atypical cattle in Japan showing infectivity other than CNS tissue,the fact that the latest Texas mad cow and the recent Alabama mad cow bothbeing of the atypical strain, it would seem prudent to include all human TSEin the blood ban, in my opinion. with sporadic CJD, you have many strainsandor phenotypes, some of which are 'UNKNOWN', so we do not know how thiswill transmit, what tissues are infectious and or if blood transmits. that'sthe bottomline, however it has been reported that the BASE is more virulent to humans.Withthis, and the fact that sporadic CJD has tripled in the past few years orso, i see itas being prudent to take serious and immediate action ;PERSPECTIVEOn the Question of Sporadicor Atypical Bovine SpongiformEncephalopathy andCreutzfeldt-Jakob DiseasePaul Brown,* Lisa M. McShane,? Gianluigi Zanusso,? and Linda Detwiler§Strategies to investigate the possible existence of sporadicbovine spongiform encephalopathy (BSE) requiresystematic testing programs to identify cases in countriesconsidered to have little or no risk for orally acquired disease,or to detect a stable occurrence of atypical cases incountries in which orally acquired disease is disappearing.To achieve 95% statistical confidence that the prevalenceof sporadic BSE is no greater than 1 per million (i.e., theannual incidence of sporadic Creutzfeldt-Jakob disease[CJD] in humans) would require negative tests in 3 millionrandomly selected older cattle. A link between BSE andsporadic CJD has been suggested on the basis of laboratorystudies but is unsupported by epidemiologic observation.Such a link might yet be established by the discoveryof a specific molecular marker or of particular combinationsof trends over time of typical and atypical BSE and varioussubtypes of sporadic CJD, as their numbers are influencedby a continuation of current public health measures thatexclude high-risk bovine tissues from the animal andhuman food chains. ......PLEASE READ FULL TEXT ;http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm?s_cid=eid06_0965_eCDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006The U.S. Department of Agriculture was quick to assure the public earlierthis week that the third case of mad cow disease did not pose a risk tothem, but what federal officials have not acknowledged is that this latestcase indicates the deadly disease has been circulating in U.S. herds for atleast a decade.The second case, which was detected last year in a Texas cow and which USDAofficials were reluctant to verify, was approximately 12 years old.These two cases (the latest was detected in an Alabama cow) present apicture of the disease having been here for 10 years or so, since it isthought that cows usually contract the disease from contaminated feed theyconsume as calves. The concern is that humans can contract a fatal,incurable, brain-wasting illness from consuming beef products contaminatedwith the mad cow pathogen."The fact the Texas cow showed up fairly clearly implied the existence ofother undetected cases," Dr. Paul Brown, former medical director of theNational Institutes of Health's Laboratory for Central Nervous SystemStudies and an expert on mad cow-like diseases, told United PressInternational. "The question was, 'How many?' and we still can't answerthat."Brown, who is preparing a scientific paper based on the latest two mad cowcases to estimate the maximum number of infected cows that occurred in theUnited States, said he has "absolutely no confidence in USDA tests beforeone year ago" because of the agency's reluctance to retest the Texas cowthat initially tested positive.USDA officials finally retested the cow and confirmed it was infected sevenmonths later, but only at the insistence of the agency's inspector general."Everything they did on the Texas cow makes everything USDA did before 2005suspect," Brown said. ...snip...endhttp://www.upi.com/*** Inherent Challenges in Identifying and Testing High-Risk Cattle StillRemainhttp://www.usda.gov/oig/webdocs/50601-10-KC.pdf3:00 Afternoon Refreshment Break, Poster and Exhibit Viewing in the ExhibitHall3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized MouseModelsQingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western ReserveUniversityBovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE straindiscovered recently in Italy, and similar or different atypical BSE caseswere also reported in other countries. The infectivity and phenotypes ofthese atypical BSE strains in humans are unknown. In collaboration withPierluigi Gambetti, as well as Maria Caramelli and her co-workers, we haveinoculated transgenic mice expressing human prion protein with brainhomogenates from BASE or BSE infected cattle. Our data shows that about halfof the BASE-inoculated mice became infected with an average incubation timeof about 19 months; in contrast, none of the BSE-inoculated mice appear tobe infected after more than 2 years. ***These results indicate that BASE istransmissible to humans and suggest that BASE is more virulent thanclassical BSE in humans***.6:30 Close of Day Onehttp://www.healthtech.com/2007/tse/day1.aspSEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotypeof 'UNKNOWN' strain growing. ...http://www.cjdsurveillance.com/resources-casereport.htmlThere is a growing number of human CJD cases, and they were presented lastweek in San Francisco by Luigi Gambatti(?) from his CJD surveillancecollection.He estimates that it may be up to 14 or 15 persons which display selectivelySPRPSC and practically no detected RPRPSC proteins.http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htmhttp://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdfPrion infections, blood and transfusionsAdriano Aguzzi* and Markus GlatzelPrion infections lead to invariably fatal diseases of the CNS, includingCreutzfeldt-Jakob disease (CJD) in humans, bovine spongiformencephalopathy (BSE), and scrapie in sheep. There have been hundredsof instances in which prions have been transmitted iatrogenically amonghumans, usually through neurosurgical procedures or administration ofpituitary tissue extracts. Prions have not generally been regarded asbloodborneinfectious agents, and case-control studies have failed to identifyCJD in transfusion recipients. Previous understanding was, however,questioned by reports of prion infections in three recipients of blooddonated by individuals who subsequently developed variant CJD. Onreflection, hematogenic prion transmission does not come as a surprise, asinvolvement of extracerebral compartments such as lymphoid organs andskeletal muscle is common in most prion infections, and prions have beenrecovered from the blood of rodents and sheep. Novel diagnostic strategies,which might include the use of surrogate markers of prion infection, alongwith prion removal strategies, might help to control the risk of iatrogenicprion spread through blood transfusions. ...snip...Last, despite all epidemiological evidence tothe contrary, patients who are methionine/valineheterozygous at codon 129 of the PRNP gene aresusceptible to infection with vCJD prions, whichraises several important questions. Is the virulenceof BSE prions enhanced when passagedfrom human to human, as opposed to theoriginal bovine to human situation? Passagingexperiments of scrapie infectivity between miceand hamsters indicate that this scenario is highlyplausible.6 Even more importantly, can vCJDinfection of heterozygous individuals establisha permanent subclinical carrier state? Althoughthis situation might constitute a best-casescenario for the infected individuals, it could bedisastrous from an epidemiological viewpoint,as it might lead to an unrecognized and possiblyself-sustaining epidemic. ...snip... full text ;JUNE 2006 VOL 2 NO 6 AGUZZI AND GLATZEL NATURE CLINICAL PRACTICE NEUROLOGY329www.nature.com/clinicalpractice/neuroFDA Fines American Red Cross $4.2 Million (BLOOD CJD)Fri Sep 8, 2006 20:0171.248.154.242FDA StatementFOR IMMEDIATE RELEASEStatementSeptember 8, 2006Media Inquiries:301-827-6242Consumer Inquiries:888-INFO-FDAFDA Fines American Red Cross $4.2 Million for Failure to Meet EstablishedBlood Safety Lawshttp://www.fda.gov/cber/talkpapers.htm#arcsnip...One way the Red Cross erred was by failing to ask donors about travelhistory that could increase the chances of having malaria or the humanversion of mad cow disease, FDA officials said.snip...http://today.reuters.co.uk/news/articlenews.aspx?type=healthNews&storyID=2006-09-08T224834Z_01_N08403053_RTRIDST_0_HEALTH-REDCROSS-DC.XMLhttp://today.reuters.co.uk/news/articlenews.aspx?type=healthNews&storyID=2006-09-08T224834Z_01_N08403053_RTRIDST_0_HEALTH-REDCROSS-DC.XML&pageNumber=1&imageid=&cap=&sz=13&WTModLoc=NewsArt-C1-ArticlePage1Greetings again Dr. Freas et al at FDA,THIS was like closing the barn door after the mad cows got loose. not onlythe red cross,but the FDA has failed the public in protecting them from the TSE aka madcow agent.TSE agent i.e. bse, base, cwd, scrapie, tme, and any sub strains thereof.we do not know if these strains will or have transmitted to humans assubclinical TSE or clinicaldisease, and we do not know if they have or will transmit second, third,forth passage viafriendly fire i.e. multiple potential routes via medical, surgical,pharmaceutical etc.IF you remember correctly Dr. Freas et al, i called this long ago, almost 6years ago ;PDF]Freas, William TSS SUBMISSIONFile Format: PDF/Adobe Acrobat -Page 1. J Freas, William From: Sent: To: Subject: Terry S. SingeltarySr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...Freas, WilliamFrom: Terry S. Singeltary Sr. [flounder@wt.net]Sent: Monday, January 08,200l 3:03 PMTo: freas@CBS5055530.CBER.FDA.GOVSubject: CJDIBSE (aka madcow) Human/Animal TSE?s--U.S.--Submission ToScientific Advisors andConsultants Staff January 2001 Meeting (short version)Greetings again Dr. Freas and Committee Members,I wish to submit the following information to theScientific Advisors and Consultants Staff2001 Advisory Committee (short version).I understand the reason of having to shorten my submission,but only hope that you add it to a copy of the long version,for members to take and read at their pleasure,(if cost is problem, bill me, address below).So when they realize some time in the near futureof the 'real' risks i speak of from human/animal TSEs andblood/surgical products. I cannot explain the 'real' riskof this in 5 or 10 minutes at some meeting,but will attempt here:remember AIDS/HIV, 'no problem to heterosexuals in the U.S.?no need to go into that, you know of this blunder:DO NOT make these same stupid mistakes again withhuman/animal TSE's aka MADCOW DISEASE. I lost my Mom to hvCJD,and my neighbor lost his Mother to sCJD as well (both casesconfirmed). I have seen many deaths, from many diseases.I have never seen anything as CJD, I still see my Mom laying helpless,jerking tremendously, and screaming "God, what's wrongwith me, why can't I stop this". I still see this, and willnever forget. Approximately 10 weeks from 1st of symptoms to death.This is what drives me. I have learned more in 3 years about not onlyhuman/animal TSE's but the cattle/rendering/feeding industry/governmentthan i ever wished to.I think you are all aware of CJD vs vCJD, but i don't thinkyou all know the facts of human/animal TSE's as a whole,they are all very very similar, and are all tied to thesame thing, GREED and MAN.I am beginning to think that the endless attempt to trackdown and ban, potential victims from known BSE Countriesfrom giving blood will be futile. You would have to baneveryone on the Globe eventually? AS well, I think weMUST ACT SWIFTLY to find blood test for TSE's,whether it be blood test, urine test, eyelid test,anything at whatever cost, we need a test FAST.DO NOT let the incubation time period of these TSEs fool you.To think of Scrapie as the prime agent to compare CJD,but yet overlook the Louping-ill vaccine event in 1930'sof which 1000's of sheep where infected by scrapiefrom a vaccine made of scrapie infected sheep brains,would be foolish. I acquired this full text version of theevent which was recorded in the Annual Congress of 1946National Vet. Med. Ass. of Great Britain and Ireland.>From the BVA and the URL is posted in my (long version).U.S.A. should make all human/animal TSE's notifiable at all ages,with requirements for a thorough surveillance and post-mortemexaminations free of charge, if you are serious about eradicatingthis horrible disease in man and animal.There is histopathology reports describing "florid plaques"in CJD victims in the USA and some of these victims are gettingyounger. I have copies of such autopsies, there has tobe more. PLUS, sub-clinical human TSE's will most definitelybe a problem.THEN think of vaccineCJD in children and the bovine tissuesused in the manufacturing process, think of the FACT thatthis agent surviving 6OO*C.PNAS -- Brown et al. 97 (7): 3418 scrapie agent live at 600*CThen think of the CONFIDENTIAL documents of what was known ofhuman/animal TSE and vaccines in the mid to late 8Os, it was all aboutdepletion of stock, to hell with the kids, BUT yet they knew.To think of the recall and worry of TSE's from the polio vaccine,(one taken orally i think?), but yet neglect to act on theother potential TSE vaccines (inoculations, the most effective mode totransmit TSEs) of which thousands of doses were kept and used,to deplete stockpile, again would be foolish.--Oral polio; up to 1988, foetal calf serum was used from UK andNew Zealand (pooled); since 1988 foetal calf serum only from NewZealand. Large stocks are held.--Rubella; bulk was made before 1979 from foetal calf serum from UKand New Zealand. None has been made as there are some 15 years stock.--Diphtheria; UK bovine beef muscle and ox heart is used but since theend of 1988 this has been sourced from Eire. There are 1,250 litres ofstock.. .--Tetanus; this involves bovine material from the UK mainly Scottish.There are 21,000 litres of stock.--Pertussis; uses bovine material from the UK. There are 63,000 litresof stock.--They consider that to switch to a non-UK source will take a minimum of6-18 months and to switch to a non-bovine source will take a minimum offive years.3. XXXXXXXXXXX have measles, mumps, MMR, rubella vaccines. Theseare sourced from the USA and the company believes that US material onlyis used.89/2.14/2.1============BSE3/1 02514. XXXXXXXXXXX have a measles vaccine using bovine serum from the UK.there are 440,000 units of stock. They have also got MMR using bovineserum from the UK.5. XXXXXXXXXXX have influenza, rubella, measles,' MMR vaccineslikely to be used in children. Of those they think that only MMRcontains bovine material which is probably a French origin.6. XXXXXXXXXXX have diphtheria/tetanus and potasses on clinical trial.hese use veal material, some of which has come from the UK and has beenade by XXXXXXXXXXX (see above).I have documents of imports from known BSE Countries,of ferments, whole blood, antiallergenic preparations,2human blood plasma, normal human blood sera, human immuneblood sera, fetal bovine serum, and other blood fractionsnot elsewhere specified or included, imported glands,catgut, vaccines for both human/animal, as late as 1998.Let us not forget about PITUITARY EXTRACT. This was used to help COWSsuper ovulate. This tissue was considered to be of greatest risk ofcontaining BSE and consequently transmitting the disease.ANNEX 6MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TOBIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIALHow much of this was used in the U.S.?Please do not keep making the same mistakes.'Absence of evidence is not evidence of absence'.What are the U.S. rules for importing and manufacturing vaccines,medicines and medical devices?Does the U.S.A. allow sourcing of raw material of ruminants fromthe U.S.A.?U.S. cattle, what kind of guarantee can you give for serum ortissue donor herds.?The U.S. rendering system would easily amplify T.S.E.'s:Have we increased the stability of the system (improved heat treatments)since the EU SSC report on the U.S.A. was publishedin july 2000?What is done to avoid cross-contaminations in the U.S.A.?How can the U.S. control absence of cross-contaminations of animalTSE's when pig and horse MBM and even deer and elk are allowed inruminant feed, as well as bovine blood? I sadly think of the renderingand feeding policy before the Aug. 4, 1997 'partial'feed ban, where anything went, from the city police horse, to the circuselephant, i will not mention all the scrapie infected sheep.I am surprised that we have not included man 'aka soyent green'.It is a disgusting industry and nothing more than greed fuels it.When will the U.S.. start real surveillance of the U.S. bovinepopulation (not passive, this will not work)?When will U.S. start removing SRMs?Have they stopped the use of pneumatic stunners in the U.S.?If so, will we stop it in all U.S. abattoirs or only in thoseabattoirs exporting to Europe?If not, WHY NOT?same questions for removal of SRM in the U.S.A.,or just for export?If not, WHY NOT?How do we now sterilize surgical/dental instruments in the U.S.A.?Where have we been sourcing surgical catgut?(i have copies of imports to U.S., and it would floor you)When will re-usable surgical instruments be banned?'Unregulated "foods" such as 'nutritional supplements' containing variousextracts from ruminants, whether imported or derived fromUS cattle/sheep/cervids ("antler velvet" extracts!) should beforbidden or at least very seriously regulated.(neighbors Mom, whom also died from CJD, had been takingbovine based supplement, which contained brain, eye, and manyother bovine/ovine tissues for years, 'IPLEX').What is the use of banning blood or tissue donors from Germany, France,etc... when the U.S.A. continues exposing cattle, sheep and people toSRM, refuses to have a serious feed ban, refusesto do systematic BSE-surveillance?The FDA should feel responsible for the safety of what people eat.prohibit the most dangerous foods, not only prohibit a few more donors,the FDA should be responsible for the safe sourcing of medical devices,not only rely on banning donors "from Europe",The 'real' risks are here in the U.S. as well, and have been for sometime.We must not forget the studies that have proveninfectivity in blood from TSE's.The Lancet, November 9, 1985" Sir, --Professor Manuelidis and his colleagues (Ott 19, p896) reporttransmission to animals of Creutzfeldt-Jakob disease (CJD) from thebuffy coat from two patients. We also transmitted the disease from ,whole blood samples of a patient (and of mice) infected with CJD.lBrain, Cornea, and urine from this patient were also infectious,and the clinicopathological findings2 are summarised as follows.snip...full text ;http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdfGreetings again Dr. Freas et al at FDA,NOW, here we are in 2006, worried and still fumbling around with what shouldhave beendone long, long ago ;Subject: 91ST MEETING OF THE SEAC MEETING LONDON 24TH FEB 2006Date: March 10, 2006 at 7:36 am PST1© SEAC 2006NINETY FIRST MEETING OF THE SPONGIFORMENCEPHALOPATHY ADVISORY COMMITTEEThe Spongiform Encephalopathy Advisory Committee held its 91stmeeting in London on 24th February 2006.snip...MEDICAL IMPLANTS CONTAINING BOVINE MATERIALSEAC considered the risk to human health from medical implantsthat include bovine material sourced from the USA. This materialwas used for a wide range of medical devices, some of which arelife saving and for which there are no alternative products.SEAC considered that the source of the animal was crucial tomanage the risk. The committee suggested that otherprecautionary steps be taken where practicable, such as usingmaterial from young animals, sourcing material from countries withgood surveillance procedures and a low prevalence of disease. ......snip...http://www.seac.gov.uk/minutes/final90.pdfA BIT OF HISTORY ON THIS TOPICTWA LITTLE minutehttp://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdfCOMMERCIAL IN CONFIDENCEhttp://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdfNOT FOR PUBLICATIONhttp://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdfhttp://www.bseinquiry.gov.uk/yb/1988/11/04003001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1989/01/30001001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdfNON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLEsnip...I was quite prepared to believe in unofficial pituitary hormones, also inthe 1970's, whether as described by Dr. Little, or in other circumstances,for animal use.snip...The fact that there were jars of pituitaries (or extract) around on shelvesis attested by the still potent 1943 pituitaries, described in StockellHartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill.Having taken the trouble to collect them, they were not lightly thrownout...http://www.bseinquiry.gov.uk/files/ws/s467bx.pdfmore on the 1968 medicine act, they forgot to followhttp://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf8. The Secretary of State has a number of licences. We understand thatthe inactivated polio vaccine is no longer being used. There is a stockof smallpox vaccine. We have not been able to determine the sourcematerial. (Made in sheep very unlikely to contain bovine ingredients).http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1989/02/14011001.pdfalthough 176 products do _not_ conform to the CSM/VPCguidelines.http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdfDraft cover letter to product licence holders (considered by Human and VetMedicines including deer)http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf(It was noted with concern that hormone extracts could be manufactured by aveterinary surgeon for administration to animals under his care without anyMedicines Act Control.)http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdfhttp://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdfTWA LITTLE STATEMENT 331http://www.bseinquiry.gov.uk/files/ws/s331.pdfWE know about USA serum and tissue donor herds from the now infamousJan. 9, 2001 FDA emergency 50 state BSE conference call, that in fact, USAserumand tissue donor herds were eating banned ruminant feed as well ;Date: Sun, 7 Jan 2001 09:45:19 -0800Reply-To: Sustainable Agriculture Network Discussion Group<[log in to unmask]>Sender: Sustainable Agriculture Network Discussion Group<[log in to unmask]>From: Beth von Gunten <[log in to unmask]>Subject: [BSE] FDA/IMPORTANT NOTICE: 50 STATE CONFERENCE CALLIMPORTANT NOTICE: 50 STATE CONFERENCE CALL - BSETUESDAY, JANUARY 9, 20011:00-2:00 PM EST CALL: 1-888-273-9887A special "50 STATE CONFERENCE CALL" to discuss BSE (BovineSpongiform Encephalopathy) issues for Food and Drug Administration(FDA) regulated animal feed products in the United States andimported animal feeds. The conference call willdiscuss the FDA proposed response to the current BSE issue and theassistance needed from state feed and agriculture programs. THISISSUE MAY IMPACT ALL STATES AND ALL ANIMAL FEED AND PRODUCTIONINDUSTRIES.The 50 State call is scheduled for Tuesday, January 9, 2001 from1:00-2:00 pm EST. Any state agency responsible for animal feed issueswishing to participate should call 1-888-273-9887 and ask to beconnected to the "50 State BSE Call". The conference host operatorwill explain how to participate, including asking questions duringthe call. If possible, please coordinate within your state to utilizeonly one phone line per state agency.We request that you forward this message to your agency managementand feed coordinators or other agencies or departments who may beresponsible for any animal feed issues related to FDA regulatedproducts.The agenda will be as follows:1. Center For Veterinary Medicine (FDA) - Discussion of the problemrelated to BSE events in Europe and the impact on US feed ingredientsfor animals and feed operations. Discussion of the proposedactions/inspections/compliance of licensed and unlicensed feed mills,commercial feed manufacturers, animal feed imports, renderer's,protein blenders, on-farm mixers, and ruminant feeders.2. Office of Regional Operations (FDA) - Discussion ofcontracting/working with states to inspect the universe of feedmills/industry for "Animal Proteins Prohibited from Use in AnimalFeed". Discussion of working with FDA field offices.3. Questions and answers.Richard H. Barnes, DirectorDivision of Federal-State Relations (HFC-150)5600 Fishers Lane Room 1207Rockville, Md. 20857ph: (301) 827-6906 FAX: (301) 443-2143Email: [log in to unmask]http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0101&L=sanet-mg&P=13410Subject: BSE--U.S. 50 STATE CONFERENCE CALLJan. 9, 2001 Date: Tue, 9 Jan 2001 16:49:00 -0800From: "Terry S. Singeltary Sr."Reply-To: Bovine Spongiform EncephalopathyTo: BSE-L@uni-karlsruhe.de######### Bovine Spongiform Encephalopathy #########Greetings List Members,I was lucky enough to sit in on this BSE conference call today and evenmanaged to ask a question. that is when the trouble started. I submitted aversion of my notes to Sandra Blakeslee of the New York Times, whom seemedvery upset, and rightly so. "They tell me it is a closed meeting and theywill release whatever information they deem fit. Rather infuriating." and iwould have been doing just fine, until i asked my question. ...snip...endhttp://lists.iatp.org/listarchive/archive.cfm?id=121143



TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE MEETINGThursday, June 2, 1999CHAIRMAN BROWN: My name is Dr. Paul Brown. Welcome to the FDA travelingroad show. We are asked yet once more by the FDA to consider a question oftheoretical risk in the absence of sufficient knowledge on which to base anyfirm conclusion. The issue before us today is that of excluding categories of Americanblood donors who have either visited or resided for longer periods of timein Great Britain. The issue is sufficiently delicate, as you see that wehave 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 BloodServices. In addition, he has financial interests in firms that could beaffected by the general discussions. "Dr. Richard Race has financial interests in firms that could be affectedby the general discussions and is a public health science researcher. "In the event that the discussions involve specific products or specificfirms for which FDA participants have a financial interest, the participantsare aware of the need to exclude themselves from such involvement. Andtheir exclusion will be noted for the public record. A copy of the waiversis available by written request under the Freedom of Information Act. "With respect to all other meeting participants, we ask in the interest offairness that they address any current or previous financial involvementwith any firm whose product they may wish to comment upon." So ends the reading of the conflict of interest statement. Dr. Brown, Iturn 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 donationof persons with possible foodborne exposure to bovine spongiformencephalopathy, BSE, as a precautionary measure to reduce the risk of bloodtransmission of new variant Creutzfeldt Jakob disease. And we are askingthe Committee at this time, as we did in December, to consider this in thelight of possible shortages. Next, the current status. So far there have been no cases of either BSEor new variant CJD reported in the U.S. We're aware and we discussed inDecember the precautionary measures which have been taken in the U.K.First, they are not using U.K.?sourced plasma; and, secondly, they areimplementing universal leukoreduction.snip...Next. In December, we asked the Committee to vote on two votes. I'm goingto go through what those votes were. The first one is: Should FDArecommend new deferral criteria for blood donors to attempt to reduce atheoretical risk for transmitting new variant Creutzfeldt Jakob disease beexcluding donors potentially exposed to the agent of bovine spongiformencephalopathy? The Committee voted nine yes and six no. Next overhead. Should FDA recommend excluding donors who have resided inthe 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 weretaken in December. Should FDA recommend withdrawal for blood componentsbased on these donor deferral criteria? The vote was seven yes, five no. And should FDA recommend withdrawal for plasma derivatives based on thesedonor 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 FDAwould 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 precautionarywithdrawal policy for new variant CJD, we asked: Should FDA recommendprecautionary quarantine or withdrawal for plasma derivatives to which apossible new variant CJD donor contributed pending confirmation of theclinical diagnosis? The Committee voted eight yes, one no, one abstained, but they asked us torevisit this question of our operational definition of a possible newvariant CJD case. And in the second part of today's deliberations, afterthe vote on deferral, we will go back to that question. The Committee also voted that a tonsil biopsy negative forprotease?resistant prion would not be sufficient to make productwithdrawals unnecessary.snip...We now have a presentation by Dr. Philip Comer, who will give us the DetNorsk Veritas risk assessment. Dr. Comer? MR. COMER: Thank you very much, Chairman, and thank you for theopportunity to come and talk about the study that we were asked to do by theDepartment of Health in the United Kingdom as a result of a recommendationfrom the United Kingdom's Spongiform Encephalopathy Advisory Committee.snip...I am just going to go very quickly over the evidence for infectivity inblood. I think probably that will have already been looked at significantlyby this Committee, but it was very much part of the background for what wewere doing in the study that we did. If we look at blood transfusions, we know that all attempts to transmitinfectivity of blood, blood transfusion, so across a species barrier, havefailed and that within animal models, as far as I am aware, the one casewhich has been reported by Bob Rohwer is still the only case that I haveheard of in which there has been a positive transmission by the i/v routewithin an animal model. Epidemiology studies have shown that's from sporadic CJD. There is noevidence that there has been any transmission through the blood route. Andwhen we look at blood from human CJD cases, primarily sporadic CJD cases andcertainly no variant CJD cases, and look at that, their infectivity throughthe i/c route into animal models, there have been a few experiments whichhave shown positive infectivity into rodents but negative results from asignificant number of studies into primates and other species. And there have been some questions asked about ?? these cases, theseexperiments all involve very small numbers of animals and some sort ofsignificant questions asked about those and, in particular, the fact that itis a bit odd that we have got no positive infections in the primates, whichyou might have expected would be more susceptible than the rodents. Then when we look at actually within animal models themselves, there havebeen quite a number of cases, experiments where positive infections havebeen reported from animals infected with some form of TSE and have beenthrough the i/c route infected in the same species, so again with no speciesbarrier.snip...page 89CHAIRMAN BROWN: A couple of points just to bring your experimental data upto speed. Unpublished further experiments on the mouse model have producedgood news and bad news. The bad news is that we have a disappointingly large number oftransmissions following intravenous inoculation of either plasma or Buffycoat. We also have a transmission using whole blood as a transfusion intothese mice. So that's not good news. The other thing that is not too good is that we have now got in thisparticular model a ratio of five to one, as opposed to ten to one, which wasalso disappointing. The only piece of good news in that in terms of experimental data is thatwe found that, again, in this model, the level of infectivity during theentire incubation period is almost negligible compared to the level ofinfectivity during the clinical phase of illness. And that is very goodnews indeed. So these are data that are not yet published but ??snip...page 105CHAIRMAN BROWN: Right, right. And, as I say, if it turns out to be thecase with the human disease, ?? and I'm guessing it probably will be ?? withyou, I think the likelihood of disease, natural disease, whether it bescrapie in sheep, BSE in cattle, or CJD in humans, is going to be quite alot less virulent than the experimentally induced disease. Even under the experimental conditions I mentioned, however, infectivityin all components of the blood during the incubation period is so low thatit virtually poses I think no risk, at least in terms of plasma derivatives.snip...page 106Dr. Chansnip...So the issue that we dealt with in early May was "do variants of CJD pose arisk to blood safety?" And we sort of divided it into the classic variantand others. The others came out of, I'm sure you're all aware, of the scarethat we all had over the Utah donor was this a possible chronic wastingdisease, etc. So we just put that issue on the table and let's see where it went. Ourprocess -- we circulated a notice widely to all associations, consumergroups. We've sort of got a mailing list that's growing.snip...page 129And thirdly, the question was: What is the biological plausibility, fromour experimental data, that there will be other variants of CJD? I won't gointo the attempts of answering these.snip...page 135The rest of the recommendations I'll go through very briefly. Health Canadahad not standardized its -- not finalized its policy on classic CJD, and weadvised that they do so. The blood services should provide clear statements about the reasons forbelieving that there are no longer concerns regarding the classic sporadicCJD; that Health Canada and the blood services provide communicationregarding all aspects of product quarantine. And that was because there's considerable confusion over the Utah donorcase. Health Canada identify and provide information that all productsthat contain trace amounts of blood products -- this was interesting. Many of the physicians did not even know which products that were beingdistributed contained blood products. We thought this was an importantissue. All products can be tracked in the event of an infected donor. Andthat they take steps to discourage manufacturers from using blood productsin the production or formulation of other products. That mechanisms are developed to ensure that -- oh, this is thesurveillance for CJD. That criteria have to be established to determinebetween classic and variant forms, which I know is the topic that you aregoing to be discussing this afternoon.snip...page 138CHAIRMAN BROWN: This afternoon's program will begin with severalpresentations as a part of the open public hearing.snip...page 145CAPTAIN RUTHERFORD: Good afternoon. The Department of Defense would like to thank you for allowing us to offerpublic comment. I am Captain Bruce D. Rutherford, Medical Service Corps, United StatesNavy, the present Director of the Armed Services Blood Program. On 5 February, 1999, Dr. Sue Bailey, the Assistant Secretary of Defensefor Health Affairs, forwarded a letter to Vice Admiral David Satcher, PublicHealth Service, the Surgeon General of the United States. In that letter, Dr. Bailey expressed her opposition and the opposition ofthe Surgeon Generals of the Army, Navy and Air Force on deferringindividuals as blood donors based on "perception" of a "possible" risk oftransfusion transmission of the agent for "new variant" CJD. There has not been a single case, repeat, single case of transfusiontransmitted new variant CJD or classical CJD reported in the world in morethan 55 years since transfusion of blood products became widely accepted asa treatment regime. In November of 1991, the Department of Defense issued an advisoryrecommending that individuals participating in Operation Desert Storm bedeferred as blood donors after a number of Desert Storm troops wereidentified with cutaneous and visceral Leishmania tropica. Knowing that Leishmania donavani was transfusion transmissible, and nowknowing the extent of infection rate of the "at risk" population, the DODdecided to defer those individuals as blood donors who participated incountry in the Persian Gulf. It was not until December of 1993, or two years later, that the DODstopped asking leishmaniasis related questions of its blood donors. Thecessation was due to a concentrated effort by the military health system inidentifying an extremely small number of infected individuals and thefollow-on screening questions' ability in identifying an extremely smallnumber of donors with symptoms where leishmaniasis could have been apossibility. However, a study in the survivability and infectivity of viscerotropicLeishmania tropica in human blood donors from ODS participants was latershown to support our concern and was published in the American Journal ofTropical Medicine and Hygiene in 1993. Transfusion transmission by Leishmania species was a known, nottheoretical. We know the calculatable risk of being injured in a caraccident, yet millions of individuals a day drive their cars with hundredsof 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 theInstitutes of Medicine came out with this HIV report. Yes, hindsight wasbetter, but that has always been true. I think in this case we have hindsight, 55 years of hindsight. We do notneed to institute a UK deferral policy which will only lead to furthercrippling of our nation's blood supply and more product shortages.snip...page 148CHAIRMAN BROWN: Thank you, Captain Rutherford. Are there any questions that any of the panel would wish to address toCaptain Rutherford? The next presentation will be by Kay R. Gregory of the AmericanAssociation of Blood Banks. MS. GREGORY: Good afternoon.snip...page 148In conclusion, AABB notes that there is no evidence that nvCJD istransmitted by blood transfusion. There are no cases of nvCJD in the UnitedStates. It is unknown whether travel to Great Britain correlates withexposure to or infection with the agent of BSE. And there is no evidence that any proposed criteria will decrease thetheoretical risk of acquiring nvCJD from transfusion. In contrast, there isgood evidence that even a one to two percent loss of donors due to newdeferral criteria will have a significant impact on blood availability and,hence, on the safety of those transfusion recipients who cannot tolerate adelay in receiving blood products. The country should contemplate nvCJD deferral criteria only when it isapparent that such a policy would improve blood safety more than the loss ofdonors and the associated decrease in blood availability would compromiseblood safety. Thank you. CHAIRMAN BROWN: Thank you, Ms. Gregory. The word theoretical has been used many, many, many times this morning andwill continue to be used, and it's being used correctly. I'd just point outthat, for ten years, between 1985 and 1995, the risk of new variant CJD fromBSE was also theoretical. The next speaker is Dave Cavenaugh from the Government Relations Committeeof Ten Thousand. MR. CAVENAUGH: I'm the government relations person at the Committee ofTen 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, isgravely concerned about the industry logic favoring UK donors overadditional U.S. replacement donors even with the survey, and even with thelack of data on paid and unpaid high volume pheresis donors. This morning's discussion showed a glaring omission in the analysis todate of the impact of excluding well paid, highly educated, non-incentiveprovided pheresis donors in addition to the larger, understood group of paidpheresis donors. We've heard quite a bit in terms of the studies and in terms of some ofthe questions about the likely blood borne nature of this never documentedentity of prion and its ability to be transmitted by blood. There's a perceived link between new variant and beef that's been raisedbased 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 thelate '80s seemed to be a major factor, for example. What was it about living there, that's proximity. Both statisticpresenters showed clear risk of new variant in the blood, not even enlargingthe scope to include classical CJD. There are no nv cases in the U.S., butplenty of classical -- arguably, much more than the one in one million ratealleged. Just ask CJD Voice, the patient-family support group which spoke beforeyou 18 months ago. Small then, its numbers have mushroomed. Something isgetting transmitted. Can it all be through beef? But most disturbing isthe recent news confirming a second mutated form of prions also causingdeath in under a year. This doubling of the number of ways prions can be malformed with fatalresults raises our concern levels considerably. The explanation that it isspontaneous sounds like an early catch all. With an entity so new, sounknown and so dangerous, the committee should be providing every protectionpossible, not bowing to arguments of relative risk. Thank you. CHAIRMAN BROWN: Thank you.snip...page 154CHAIRMAN BROWN: Well, this is exactly why we're here today. Dr. Satcherand the other groups have already decided that this is not worth significantworry with respect to classical CJD, and that new variant was an unknown. And so that's why we're considering specifically new variant because wedon't have information specifically on it. I mean, everything we don't haveinformation on becomes a subject for this committee. (Laughter.)snip...page 213DR. LEITMAN: We seem to be extrapolating the partitioning data of classicalCJD -- the agent of classical CJD to the agent of new variant CJD. That mayor may not be okay. I'd like to ask Dr. Prusiner if we can at all extrapolate the lack oftransmissibility through blood components of classical CJD agent to newvariant? DR. PRUSINER: I don't know that I'm qualified to answer this. I can onlytell you that the little bit of work that we've done now on new variant CJDsays that it is a dramatically different strain of prion. That means thatthe confirmation of PRP scrapie is dramatically different than anything elsewe've studied. So let me give you an example. We've looked at 40 different cases ofsporadic CJD, and we know that there's several different confirmations thereat least. And all of these are transmissible in about 200 days to eithermice 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 about60 percent of the animals get sick. Now, as I said before, if we take newvariant CJD and we passage it into a mouse that expresses a bovine PRP geneon 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 takesporadic CJD or familial CJD cases and passage those into mice with a bovinePRP gene, do they get sick? And the answer is I don't know yet.snip...page 218MS. HARRELL: Well, I asked him the question, was there a deferral ?? wasthere deferral criteria for blood donors for classic CJD for people who haveeither 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 toreduce the risk of transmitting classic CJD for people who either resided orvisited the UK? DR. SCHONBERGER: The answer is no. MS. HARRELL: And if there is no risk, if we think that there is no riskof transmitting the whatever to ?? for CJD, what makes this different, fornew variant CJD much different? CHAIRMAN BROWN: That's the first time, Stan, you'll ever hear of prionreferred to as a whatever. (Laughter.) CHAIRMAN BROWN: I mean, I've heard it referred to as a lot of differentthings. 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 issuewe can sort of generically say CJD. Presumably, if the blood from a patientwith new variant CJD were infectious, the disease that it would transmitwould be new variant CJD. So it's not ?? MS. HARRELL: Okay. So CJD is not transmitted through the blood is whatyou're saying? CHAIRMAN BROWN: We have no evidence from looking at populations that thathas ever happened. The question is: since we know it can happen when weuse experimental models of CJD, we can take CJD blood from one animal andproduce the disease in another animal. So there is the "theoretical possibility" that this might also happen inhumans, particularly with a different strain of the disease, which newvariant 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 ofCJD, REDS, classic CJD, is not influenced by whether or not you've lived inthe 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 240CHAIRMAN BROWN: I agree. We're starting to vote, and we'll start withLarry. Hold on. All right. The question is: should FDA recommend newdeferral criteria for donors of transfusable components, to attempt toreduce the theoretical risk of transmitting new variant CJD fromtransfusions based on donor exposure to BSE in the UK? DR. SCHONBERGER: Yes. CHAIRMAN BROWN: Incidentally, just to remind the committee, it ispossible 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 thelogic ?? and maybe for the benefit of Barbara because I think she raises agood point about how we proceed ?? we have a situation with a small numberof known cases of variant Creutzfeldt Jakob, all but one of which are in theUK. However, we know there is a potential for widespread exposure to BSE thathas already occurred. Therefore, we expect more cases, but we really don'thave a good idea of the magnitude of the epidemic that we're going toexpect. Part number 2 says, "While there is no known whole blood or blood producttransmission of classical CJD in humans, variant Creutzfeldt Jakob differssubstantially from classical CJD." So we recognize that there is thepotential for transmission of some of the transmissible spongiformencephalopathies via blood, albeit controversial We have an animal model, and we can identify infectivity in lymphoidtissues with variant Creutzfeldt Jakob, which is different from classicalCreutzfeldt Jakob. At the same time, it has been pointed out many times by a number of peoplethat there have been no observed risk ?? or no observed cases at this pointof transfusion or blood product related variant Creutzfeldt Jakob cases inthe UK. I think that's a little premature. One might say the absence ofevidence is not evidence of absence.???????????????http://www.fda.gov/o At the same time, there are look-backstudies in place in the UK, and there is a natural experiment ?? a hugenatural experiment ongoing in the United Kingdom, where if, in fact, thereis a risk, I believe that the risk will first be apparent in the UnitedKingdom 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 wehave to preclude having more negative impacts for any action that we take,then positive ?? in other words, impacts on the blood supply. And I havestruggled 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 letWill, you know, chatter on because he hasn't said a whole lot, and I wantedto hear what he had to say. And so thank you, but we'll never get throughif 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 hugeimpact potentially on the way America collects its blood, that if we gobeyond our designated time it's worth it. And I was influenced, and it was helpful to hear the last speaker'sdiscussion. So I think if any of us have discussions or points to mentionnow, they might be valuable. The deliberations of this committee are among the most difficult of anyadvisory committee I've ever been on because there are simply inadequatedata upon which to base a decision. For myself, in the absence of datasuggesting or, rather, documenting risk, I cannot vote yes based onassumptions, perceptions, possibilities, uncertainties, theoretical risks,and potential risks. On the other hand, there are tangible measurable data that deferral of anypercentage of donors, whether it's half, one and a half, two percent, willlead to replacement by donors by a small proportion of donors that are atincreased risk for measurable diseases such as hepatitis B and C. So I voteno. CHAIRMAN BROWN: Dr. Leitman votes no. Dr. Prusiner? DR. PRUSINER: I would like to vote yes, and I would like to say I have 23points that I want to go through. (Laughter.) DR. PRUSINER: I only want to say very quickly that I don't think thateconomics and the availability of donors is a reason to vote yes or no inthis. I think that the economy has a way of solving these problems, and Ithink that will happen. I think the real problem here lies that we have avery imperfect data set, and we're dealing with a disease which isuniversally 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 noevidence of any transfusion that has transmitted either classical or newvariant Creutzfeldt. And we have a situation where there are risks involvedwith blood transfusions that the donors accept at this point. That is, we were informed about ?? I guess about 14 percent of individualsdo donate blood that have I guess the recipients. About 14 percent ofindividuals that donate blood have some risky behavior. And maybe I mightinclude living in UK part of that risky behavior. And so I kind of accept this as, at the moment, acceptable risk fordonated blood and I am awaiting evidence to prove that there is more dangerinvolved. 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 studiesthat showed the presence of the new variant CJD agent in lymphoreticulartissues. And the second concern I have is the absence of evidence againstblood-borne transmission of new variant CJD. The kind of data that'savailable for classic CJD is not available for new variant CJD, so I voteyes. CHAIRMAN BROWN: Dr. Belay votes yes. Dr. Lurie? DR. LURIE: Really, what we're doing is balancing one risk against twoothers. The two risks are the problem of the replacement donor, which isnot zero but it is probably very small, given that we're only talking aboutone, two perhaps, percent replacement of donors here, depending on whathappens 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 minimizethat. So we really have, on the one hand, two small risks that can more orless be quantified, and on the other hand we have another risk, which mayitself be small, but if we are wrong could be very, very large. And that'sreally 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 tovote yes, mainly because of what I see in the epidemiology data of the casesin England and the modeling work. I think this needs to be monitoredfurther to see how it comes in because the risks could be quite large, andso I would vote yes. CHAIRMAN BROWN: Dr. Hoel votes yes. Dr. Bolton? DR. BOLTON: I believe that there is insufficient documentation of therisk at this time. And in light of that, I can't ?? I don't think that theinformation 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 disturbingthat there is no really good data at this point. And I am impressed with a comment that was made earlier, and that is thatthere is an experiment in the UK of many people who have been exposed to UKdonors over a period of many years. And I am somewhat reassured that therehave been no cases, and I'm also reassured with the quality of theepidemiologic surveillance and data from the UK. I think that that has been well done, carefully done, and presumably itwill continue to be closely monitored. You know, if a single case hadoccurred, we would really need to change our policy immediately. That'snumber one. But the other problem I have is if I voted yes, then I would have to makea 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 anyarbitrary decision. Once you go down that route, then you have to excludeanybody from the UK or who visited the UK or Ireland during this period. Idon't see any alternative. CHAIRMAN BROWN: Dr. Nelson votes no. Dr. McCullough? DR. McCULLOUGH: I agree with Susan. This is one of the most difficultgroups 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 ofthere ain't been a case reported yet, and also that we are concerned aboutthe impact on the blood supply.hrms/dockets/ac/99/transcpt/3518t1.rtf???????????TRANSMISSIBLE SPONGIFORMENCEPHALOPATHIES ADVIS And possibly also, I'm influenced by having been thefodder for congressional hearings and 60-minute expose on things that mighthave been done differently at some of those times. So I'm going to voteyes. I have tremendous confidence in the blood systems of this country thatthey 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 thatwe have biologic data as well as at least the potential epidemiology comingout of England to suggest that this is a new disease and on that basisshould be handled with a lot more caution, because we don't have the comfortthat we have with the long-standing classical CJD. And so I'm going to voteyes. 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 longincubation and the lack of a pre-clinical screening test, that the day youfind out there is transmission you're already years too late, and you can'teasily clean up the problem. And I think they found out that even with thehuman transmission because that was based on there is no theoretical ?? orit'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 CJDcannot 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 abalancing act, and it's a tradeoff between a known problem, I believerelated to the blood supply, and the problems that may follow from a reducedsupply and the perception of a risk of new variant CJD. And I completely agree that an experiment is going on right now. Thosedata are going to come in, and, obviously, there is going to be closeattention paid to those data, and that surely this committee and FDA willrespond should information indicate that we need to take another look at theissue. CHAIRMAN BROWN: Dr. Williams votes no. Dr. Hollinger? DR. HOLLINGER: I'm voting no also, for the same reasons that have beenaddressed. I think there is ?? by doing something now doesn't mean thateverything is going to be turned around and you don't have to worry aboutit, if you do have a long incubation situation and one can wait to see ifthere is some risk down the line, and I think we do have those things goingon ?? 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. Sittingnext to my ex-learned colleague ?? (Laughter.) MS. HARRELL: Okay. I'm voting to be prudent, and I think that this willbuy us time to get the data in and have it analyzed from the UK. But rightnow, 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 measurablenegatives 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, atthe least, Dr. Epstein can come away from the day with the understandingthat he has not been given a mandate. (Laughter.) DR. FREAS: Can I just make a comment? I did verify the count. There are21 voting people at the table. Dr. Roos is a non-voting participant. Andthe 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 hebeen 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 voteto 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 gravepossibility of an epidemic of new variant CJD, an epidemic that, if itoccurs, could be made much worse through the mechanism of interspeciestransmission, such as would occur through blood products. But I recognizethe real risks of insufficient supply. However, I am impressed by Dr. Donnelly's warning that if the feed ban inthe case of BSE had been delayed just one year, the epidemic would have beenvastly worse than it was. And, therefore, I feel we should take whateveropportunities for implementing mitigating measures that we can that do notsimultaneously 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 weshould 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, ninevotes no. Therefore, the committee is obliged now to consider what deferralcriteria might be recommended. And presumably, based on the evidence, theonly deferral criteria that are offered us that make any sense are durationof residence in the UK.snip...258Dr. ScottskipIn addition, we do know, as Dr. Prusiner has pointed out several times, thatthe new variant agent is biologically different from the classical CJDagent, so we can't necessarily extrapolate all of the information that wehave on classical CJD to new variant. For example, he talked about the differences in the protein and itsbehavior, and we also know that there is enhanced expression of the newvariant agent in lymphoid tissues compared with CJD. And we don't know muchabout its virulence or infectivity compared with the classical CJD. And, of course, we haven't had time to get or enough patients or subjectsor transfused people to get the kind of epidemiologic data that we havewhich tells us that transmission of classical CJD by blood or blood productsat worst is rare and may not occur. So, currently, the diagnosis of new variant CJD is based uponneuropathology, and these are the three most characteristic features ??numerous widespread kuru type amyloid plaques, which obviously can occur ina few other kinds of CJD but are quite common in new variant CJD; spongiformchange, which is predominant in certain areas of the brain; and a highdensity prion protein accumulation, especially the cerebrum and thecerebellum by immunohistochemistry, and tonsillar biopsy may ultimately playa 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 ageof a new variant patient is about late 20s, and the typical age of aclassical CJD patient is about 65, this is one criteria that is useful. Andnew variant patients tend to have persistent painful sensory symptoms earlyin presentation and/or psychiatric symptoms. I can go into this further if people want to know about it. But therewere a couple of articles published in the Lancet from the CJD surveillanceunit in September 1997, which goes into this in great detail. In addition, the patient must have dementia and a delayed development ofneurologic symptoms, particularly movement disorders, about a four-monthdelay. And, again, this is somewhat different from classical CJD in itscourse. 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 isin marked distinction to most cases of classical CJD which average four tofour and a half months of duration. Whereas, the new variant case typicallyis around 14 months duration, although there is a spread. In addition, routine investigations will not suggest an alternatediagnosis. And this is a criteria, really, for the U.S. There should behistory of possible exposure to BSE; that is, consumption of local beefproducts as resident or traveler to a BSE-affected country. And there is only two more. No history of iatrogenic exposures that arerelated to development of classical CJD, and, finally, of course, such apatient, if they had a prion protein gene mutation, it was associated withfamiliar CJD. That would not fall under ?? that would not be a patient thatwe would worry about new variant CJD in.page...284DR. ROOS: Thanks, Dr. Scott. So we're not asked to take a vote, but justto discuss these issues. Yes? DR. NELSON: I'm concerned a little bit about the explanation for the agecriteria, and I can see that this is very useful because the one thing youdo know, when somebody gets sick, you can estimate what their age is. Andso that's an easy ?? you know, an easy early marker for a possible casethat's not classical. And I assume that probably the reason for the classical CJD patients beingmuch older is that the incubation period is so long that they probably hadan exposure much longer. But as this epidemic ?? or as the ?? if it'sexposure to the BSE agent from the epidemic, it seems like over time thisage criteria will probably change, and that the under 55 may no longer be auseful 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 evolvingnature of these diagnoses. All I can say is the age is an excellent andeasy criteria for us to use now. All cases, as you know, in the world ofnew 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. Sothat's why that particular criteria came into existence. However, obviously, if the epidemic should change and we should startseeing older cases, then, obviously, we would have to change. There is some semantic problems. We actually investigate every case under55. So, in a sense, all cases under 55 in the United States could beregarded 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 wecount. The 40 cases in the UK, I think, includes one, is it? One probable? Thatwas a case in a teenager whose brain tissue was unavailable for study. Andthey indicate that it's too early in the epidemic. Their experience is toosmall 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 maybewe'll be able to call cases without necessarily having the tissue, dependingon what they find the specificity and sensitivity of those to be. So allcases essentially under 55 right now are under investigation. Plus, we have established amongst pathologists the concept that any casethat has the pathology of new variant CJD, regardless of age, or evenregardless of whether they've diagnosed it as CJD, should be reported. Andthose two would count as new variant even though they are not under 55. DR. ROOS: Just a quick question, Larry. What is your timeframe ofreporting, or what is the goal here? Obviously, with respect to these newguidelines, you want to identify these cases fairly quickly and make somedisposition 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 firstto identify these cases at least, and that has been the history ?? to reportto us any case of CJD under 55. Once we get that report, it may be very easy for us and very quicklymaking 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, anotherpart of FDA will probably become interested in that. So we think it's worth the blood establishments reporting all of theircases in donors. There just are not that many CJD cases that are going tooccur among donors that the blood establishment is going to be able toidentify 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 patientdonates to some large blood pool or has donated whole blood? It doesn't goback 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 thatvery, very rapidly. But even handling it very, very rapidly, you'll findthat huge, huge numbers of recipients were exposed to this donor's bloodproducts. So the withdrawal program is relatively inefficient, compared to what wejust did, which was to get deferral criteria. And I think that's why it wasimportant to try to be preemptive in a sense and have the deferral criteriaup front. The withdrawal procedure, even when you do it very quickly as in the Utahcase, I would not encourage people to depend on that for considerablesafety. 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 policieswidely to the neurological community, so that they alert you, Larry, or theFDA quickly. The Utah case, in fact, was kind of a very aberrant case. Itcould be that there are other cases that get less sophisticated care. Andif you really want to identify things in a timely manner, you obviously haveto publicize the program and new policies to the neurological community. DR. SCHONBERGER: Well, let me clarify that the primary group doing thesurveillance on this are blood establishments. And if this group wants torecommend that blood establishments, you know, provide blood donors withcards 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 ofrapid turnaround or rapid identification in reporting. That's anotherweakness of the system and relying on this withdrawal system for tremendousprotection of the population. DR. ROOS: Peter? DR. LURIE: My question/concern is whether or not requiring all nine ofthese criteria is too restrictive a set of criterion. I guess the dataquestion 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 thosecriteria, but most. However, the CJD surveillance unit has somewhat alteredtheir criteria with time such that the current organization is similar tothis but not the same. And most critically, they have gotten rid of the agecriteria 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 onlyusing 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 evenpotential 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 allof 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 whatwe're anticipating is that we would be ?? we would err on the side ofcaution unless investigation showed us that it was most unlikely that thiswas a new variant case.snip...page 292DR. HUESTON: You don't know to what you've been exposed. So it's ?? thesecond thing is it draws ?? I think it gives a false sense of security anddirects, potentially, attention to the wrong products, because the averageperson 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 theproposed ?? this criteria of possible new variant CJD by FDA. And I havetwo major reasons for that. The first is that I see the potential forconflict arising between FDA and CDC, where FDA is stepping forward ormaking a pronouncement of possible new variant CJD, and at the same time CDCsays, "We're still investigating; you know, it's premature." And I think that puts the FDA in a very awkward position, and I think aninappropriate ?? 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. Itemnumber 2 says, "Donor has physician's clinical or pathologic diagnosis ofCJD." DR. SCHONBERGER: They're not all donors, by the way. Very few of themare donors. Okay?DR. HUESTON: Okay. Fair enough. But once you get a terminology like thisestablished, my concern is that it's going to spread further, that peopleare going to say, "Well, the FDA would have called this a possible case." Number 2 says, "Has a physician's clinical or pathologic diagnosis," itdoesn't say anything about the physician. And no offense to mydistinguished colleagues, but there are a number of physicians that aresimply not in the position to make a clinical diagnosis or a pathologicdiagnosis of Creutzfeldt Jakob. That has not precluded some of these samephysicians from making a proclamation. Third, I think that the public health and the risk communicationimplications 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, thepress grabbing hold of a case and blowing it totally out of proportion andcreating a great deal of concern, I don't see why you need another term. I think you coordinate with the CDC, you coordinate your investigationwhen it comes back from a blood collection center that you have a donor lessthan 55 years of age, where you have some suspicion of Creutzfeldt JakobDisease. You go through the same CDC workup, and you base ?? on acase-by-case basis, you base your decision on that coordination with CDC.snip...page 296see full text and all voting resultshttp://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t1.rtfTSEAC MEETING JUNE 3 1999http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t2.rtfPLEASE NOTE IN USA CJD UPDATE AS AT JUNE 2007, please note steady increasein ''TYPE UNKNOWN''. ...TSS1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17inconclusive and 9 pending (1 from 2006, 8from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1from 2001, 1 from 2003, 4 from 2004, 3from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26from 2007)http://www.cjdsurveillance.com/pdf/case-table.pdfUSA NVCJD BLOOD RECALLS ONLY ;http://www.google.com/search?hl=en&q=CJD+BLOOD+RECALLS+TSS&btnG=SearchvCJD case study highlights blood transfusion riskhttp://vcjdblood.blogspot.com/CREUTZFELDT JAKOB DISEASE MAD COW BASE, CWD, SCRAPIE UPDATE OCT 2007http://cjdmadcowbaseoct2007.blogspot.com/NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007Tuesday, October 9, 2007NOR-98 SCRAPIE UPDATE AUGUST 31, 2007 RISES TO 5 DOCUMENTED CASEShttp://nor-98.blogspot.com/CREUTZFELDT JAKOB DISEASE MAD COW h-BASE UPDATE USAhttp://cjdmadcowbaseoct2007.blogspot.com/ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007Date: Mon, 24 Sep 2007 21:31:55 -0500I 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 OFPOKER INDEED GOES UP. ...TSSUSA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSShttp://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779From: "Terry S. Singeltary Sr."Subject: CWD UPDATE 88 AUGUST 31, 2007http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450Date: Wed, 29 Aug 2007 21:13:08 -0500From: "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=26079Monitoring the Potential Transmission of Chronic Wasting Disease to HumansUsing 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 -0500http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strainDate: August 25, 2007 at 12:42 pm PSTSubject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strainDate: August 25, 2007 at 12:42 pm PSTJ Biol Chem. 2007 Aug 20; : 17709374Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates anew prion strain.[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , TetsuyukiKitamotoThe genotype (methionine or valine) at polymorphic codon 129 of the humanprion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoformof PrP (PrP(Sc)) are major determinants of the clinicopathologicalphenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found thattransmission of sCJD prions from a patient with valine homozygosity (129V/V)and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP withmethionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate insize between type 1 and type 2. The intermediate type PrP(Sc) was seen inall examined dura mater graft-associated CJD cases with 129M/M andplaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prionsexhibited similar transmissibility and neuropathology, and the identicaltype of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or129V/V. These findings suggest that p-dCJD could be caused by cross-sequencetransmission of sCJD-VV2 prions.snip...In this study, the strain-dependent traits of sCJDMM1prions were inherited through cross-sequencetransmission without any modification. Thehumanized mice with 129V/V produced type 1 PrPresafter inoculation with sCJD-MM1 prions. BecausesCJD-VV1 cases are extremely rare (at most 1-2%of the total number of sCJD cases) and characterizedby early onset (mean age at onset: 39.3 years) (5),####################################our results raise the possibility that CJD casesclassified as VV1 may include cases caused byiatrogenic transmission of sCJD-MM1 prions orfood-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 orconsumed venison have been reported (40, 41). Theresults of the present study emphasize the need fortraceback studies and careful re-examination of thebiochemical properties of sCJD-VV1 prions.###################################In conclusion, cross-sequence transmission ofsCJD-VV2 prions generates a new prion strain withaltered conformational properties and diseasephenotypes as p-dCJD prions. Furthermore, thenewly generated prions have unique transmissibilityincluding the traceback phenomenon. In the future, ifatypical prion strains emerge through cross-sequencetransmission, especially from animals, tracebackstudies will enable us to identify the origin of theprions.REFERENCES...snip...endFULL 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=HWCIThttp://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267Re: Colorado Surveillance Program for Chronic Wasting DiseaseTransmission to Humans (TWO SUSPECT CASES)http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165Subject: MAD COW BASE H-TYPE AND L-TYPEDate: August 23, 2007 at 11:30 am PSThttp://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakobdisease in the United StatesEmail Terry S. Singeltary:flounder@wt.netI lost my mother to hvCJD (Heidenhain Variant CJD). I would like tocomment on the CDC's attempts to monitor the occurrence of emergingforms of CJD. Asante, Collinge et al [1] have reported that BSEtransmission to the 129-methionine genotype can lead to an alternatephenotype that is indistinguishable from type 2 PrPSc, the commonestsporadic CJD. However, CJD and all human TSEs are not reportablenationally. CJD and all human TSEs must be made reportable in everystate and internationally. I hope that the CDC does not continue toexpect us to still believe that the 85%+ of all CJD cases which aresporadic are all spontaneous, without route/source. We have many TSEs inthe USA in both animal and man. CWD in deer/elk is spreading rapidly andCWD does transmit to mink, ferret, cattle, and squirrel monkey byintracerebral inoculation. With the known incubation periods in otherTSEs, oral transmission studies of CWD may take much longer. Everyvictim/family of CJD/TSEs should be asked about route and source of thisagent. To prolong this will only spread the agent and needlessly exposeothers. In light of the findings of Asante and Collinge et al, thereshould be drastic measures to safeguard the medical and surgical arenafrom sporadic CJDs and all human TSEs. I only ponder how many sporadicCJDs in the USA are type 2 PrPSc?http://www.neurology.org/cgi/eletters/60/2/176#535LANCET INFECTIOUS DISEASE JOURNALVolume 3, Number 8 01 August 2003Newsdeskhttp://infection.thelancet.com/journal/journal.isaDiagnosis and Reporting of Creutzfeldt-Jakob DiseaseSingeltary, 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=jamaBRITISH MEDICAL JOURNALSOMETHING TO CHEW ONBMJhttp://www.bmj.com/cgi/eletters/319/7220/1312/b#5406BMJhttp://www.bmj.com/cgi/eletters/320/7226/8/b#6117P04.49Case Report of Variant Creutzfeldt-Jakob Disease in a Macaque after BloodTransfusionLescoutra-Etchegaray, N1; Ruchoux, MM1; Correia, E1; Jolit, A1; Freire, S1;Lasmezas,CI2; Deslys, JP1; Comoy, E1 1CEA/DSV/IMETI/SEPIA, France; 2Scripps Florida,USAA fourth human case of probable transmission of vCJD through transfusion hasnowbeen reported but a number of features affecting transfusion-relatedinfection remainimprecise, including infectious dose, length of incubation period andcritical infectiouswindow of blood donors.We report here the first case of experimental transmission of vCJD inprimates byblood transfusion. Experimental infection of Cynomolgus macaque has beendemonstrated to be a sensitive model for the investigation of human priondiseases,inducing similar distribution of infectivity in peripheral lymphoid tissuesand equivalentbrain pathology. In our study, transfusion was performed with 40 ml of wholeblooddrawn from a vCJD-infected macaque at the terminal stage of the disease.Clinicalsymptoms of vCJD appeared in the recipient animal after five years ofincubation. Thetotal amount of infectivity in the transfused blood was approximately 106fold lowerthan in the brain (titration still in progress). In several animals infectedintravenouslywith brain homogenate, the presence of PrPres in serial lymph nodes biopsiesand inother organs at autopsy was examined and results will be presented.http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdfP04.51Atypical Presentation of Variant Creutzfeldt-Jakob Disease in a 73 Year OldBlood Transfusion RecipientWroe, 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 ofNeuropsychology, UK;3Health Protection Agency, UK; 4National Hospital for Neurology andNeurosurgery,Department of Neuropathology, UK; 5Institute of Neurology, UCL, UKWe report atypical presentation of variant Creutzfeldt-Jakob Disease (vCJD)identifiedante-mortem in a 73 year-old recipient of blood products. This patient wastransfusedfollowing orthopaedic surgery in December 1997. Tracing of blood productsidentifieda single unit of non-leucodepleted red cells from an individual whodevelopedneuropathologically confirmed vCJD eleven months after donation. Nine yearsposttransfusion, this individual was referred to the National Prion Clinic forspecialistinvestigation. Six years post transfusion the recipient complained offluctuating fatigueand impaired concentration. At this time neurological examination and MRIbrain(T1/T2 weighted/DWI) were normal. Progressive symptoms emerged six monthslaterwith imbalance and deteriorating cognition. Examination two months afteronset ofneurological symptoms demonstrated cognitive deficits, dyspraxia orvisuospatialdysfunction and normal motor, sensory and gait examination. Six weeks latercognitiveimpairment was identified alongside tremulousness, impaired manual dexterityandlimb ataxia. Serological investigations were normal. MRI (T1/T2weighted/FLAIR/DWI)demonstrated prominent signal change throughout the dorsal thalamus,consistentwith vCJD. PRNP genotyping revealed no mutations and homozygosity formethionineat codon 129. The prolonged incubation period of vCJD and possibility ofasymptomatic carrier states pose major public health concerns. This casehighlightsthe significant risk encountered by recipients of contaminated bloodproducts and thenecessity for their specialist monitoring.http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdfP04.36Enhanced Surveillance of Persons Identified as at Increased Risk of CJD DuetoBlood Transfusion or Healthcare ProceduresBrookes, D1; Chow, Y1; Ward, HJT2; Will, RG2; Hewitt, P3; Gill, ON11HPA, CJD, UK; 2National CJD Surveillance Unit, UK; 3Colindale, NHS Bloodand Tissue, UKIntroduction:Reports of four iatrogenic transmissions of variant-CJD (vCJD) infectionin the UK (all due to transfusion of blood from donors who later developedvCJD),evidence from iatrogenic transmissions of sporadic CJD and experimental workonCJD infectivity in tissues and on healthcare instruments have given rise toconcernabout the risks of iatrogenic transmission of CJD. This risk warrants a)certain publichealth precautions, and b) follow-up of individuals with identified risks inorder to gainevidence about their risks and ensure appropriate management of these risks.Evidence of transmission via iatrogenic routes is important to inform publichealthmeasures and so prevent ongoing transmission of CJD.Methods:The Health Protection Agency and Health Protection Scotland holds detailsof persons identified as ‘at-risk’ of vCJD due to blood transfusion and ofpersons identified as ‘at-risk’ of CJD (of any type) from other healthcareprocedures. The GPs/clinicians of all persons identified as ‘at-risk’ forpublic healthpurposes are provided with: information; risk assessment updates; advice onpublic healthprecautions and advice on referral to specialist care. Procedures are beingestablished to obtain enhanced surveillance data on these individuals,including:clinical status updates, date and cause of death, surplus tissue and bloodspecimens, andpostmortem investigations.Results:Persons ‘at-risk’ of CJD have experienced a range of exposures. Estimatedrisks are uncertain and overlapping. Some individuals - recipients of vCJDimplicated blood components - are considered to be at a clearly higher riskofinfection: active follow-up is currently conducted for these individuals. Intime, theenhanced surveillance of persons at increased risk of CJD will provideestimates oftransmission risks and of the impact of iatrogenic exposures on mortality.Conclusion: Knowledge about iatrogenic transmission of CJD is being gainedby the follow-up of individuals who have been identified as ‘at-risk’ of CJDin theUK. This enhanced surveillance may need to be sustained for many years.http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdfPrions in Plasma of Patients with Sporadic Creutzfeldt-Jakob DiseaseSafar, 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.B1,3,51Institute for Neurodegenerative Diseases,2Memory and Aging Center, Departments of3Neurology, 4Pathology, and 5Biochemistryand Biophysics, University of California,San Francisco, California 94143http://www.prion2007.com/pdf/Prion%20Friday.pdfhttp://www.prion2007.com/pdf/Prion%20Thursday.pdfhttp://www.prion2007.com/pdf/Prion%20Wednesday.pdf



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