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



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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.


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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

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