TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS

Greetings,

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

kind regards, terry

UNITED STATES OF AMERICA

FOOD AND DRUG ADMINISTRATION

CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

+ + + + +

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY

COMMITTEE

MEETING

THURSDAY,

FEBRUARY 12, 2004

This transcript has not been edited

Or corrected, but appears as received

From the commerical transcribing

Service. Accordingly, the Food and

Drug Administration makes no

Representation as to its accuracy.

SNIP...

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

SNIP...

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

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

Next.

SNIP...

Next.

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

Next.

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

snip...

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

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

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

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

snip...

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

(Laughter.)

DR. BROWN: Thanks.

Questions?

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

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

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

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

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

DR. LINDEN: Into a given monkey. Okay.

And the IC inoculations, where were those given?

DR. BROWN: Right parietal cortex, Southern Alabama.

(Laughter.)

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

CHAIRPERSON PRIOLA: Dr. Epstein.

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

I think Jay Epstein --

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

(Laughter.)

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

DR. BROWN: Yes, Fukuoka 1.

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

DR. BROWN: Yes, that is correct.

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

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

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

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

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

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

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

DR. GAMBETTI: -- of GSS either.

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

Jay?

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

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

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

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

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

CHAIRPERSON PRIOLA: Dr. DeArmond.

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

(Laughter.)

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

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

DR. BROWN: I may do it again.

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

(Laughter.)

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

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

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

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

Could you comment on the --

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

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

Primate studies are a real pain.

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

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

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

DR. BROWN: Thomas?

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

CHAIRPERSON PRIOLA: Dr. Johnson.

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

DR. BROWN: Brand new.

MR. JOHNSON: Brand new. Okay.

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

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

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

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

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

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

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

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

(Laughter.)

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

(Laughter.)

CHAIRPERSON PRIOLA: Dr. Bracey.

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

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

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

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

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

snip...


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



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

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

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

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

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

vCJD Blood Specimens

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

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


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



TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE

JUNE 12, 2009

REFERENCES SENT TO MEMBERS

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

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

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


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



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


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



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


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



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


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




Risk Assessment Appendix


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



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

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

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

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


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



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



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

___________________________________

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

___________________________________

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

___________________________________

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

END OF ENFORCEMENT REPORT FOR SEPTEMBER 2, 2009

###


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



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

___________________________________


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

___________________________________


END OF ENFORCEMENT REPORT FOR JULY 1, 2009

#


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



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

___________________________________


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

___________________________________



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




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

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

___________________________________


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

___________________________________


END OF ENFORCEMENT REPORT FOR JULY 22, 2009

###


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



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

___________________________________


END OF ENFORCEMENT REPORT FOR JULY 29, 2009

###


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



Sunday, May 10, 2009

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


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




PDF]Freas, William TSS SUBMISSION

File Format: PDF/Adobe Acrobat -

Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary

Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...


http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf




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

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

FINALLY, GOT IT UPLOADED !

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


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



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

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

Greetings List Members,

More Dredful news, but predictable...

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


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


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

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

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

Research letters Volume 356, Number 9234 16 September 2000

Transmission of BSE by blood transfusion in sheep

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

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

See Commentary

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Correspondence to: Dr N Hunter


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


Commentary Volume 356, Number 9234 16 September 2000

BSE and transmission through blood

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

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

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

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

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

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

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

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

Paul Brown

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

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

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

3 Brown P, Cervenáková L, McShane LM, Barber P, Rubenstein R, Drohan WN. Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt-Jakob disease in humans. Transfusion 1999; 39: 1169-78 [PubMed].

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

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


http://www.thelancet.com/



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


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



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

Dear Mr. Glickman,

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

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

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

why slow this research down?

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

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

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

kind regards, Terry S. Singeltary SR.

THIS IS A WORLD PROBLEM...TSS


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

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



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


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



LOUPING-ILL VACCINE SCRAPIE BLUNDER


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



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

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

The Lancet, November 9, 1985

Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from whole blood samples of a patient (and of mice) infected with CJD.1 Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.

A 70-year-old man was noted to have a slowing of speech and writing and some disorientation, all of which progressed rapidly. Decorticate rigidity, forced grasping, positive snout reflex, and myoclonus appeared within 2 months. Electroencephalogram revealed typical periodic synchronous discharge, and he died of pneumonia and upper gastrointestinal haemorrhage, about 3 months after onset of the symptoms. The Brain weighed 1290g and showed severe histological changes diagnostic of CJD, including spongiform change, loss of nerve cells, and diffuse proliferation of astrocytes. There were no inflammatory cells, microglia, neurofibrillary tangles, and amyloid plaques, although virus-like particles were detected by electron microscopy.

Results of innoculation in Mice

Inocula NO* Incubation period (days)+ Brain 7/10 (4) 789 (+ or - 112) Cornea 1/6 (0) 1037 Blood 2/13 (0) 1080 (+ or - 69) Urine 5/10 (1) 880 (+ or - 55) CSF 0/10

* Number of mice with CJD change/number examined histologically. Number with amyloid plaques shown in parentheses.

+ means + or - SD

Samples were taken aseptically at necropsy. 10% crude homogenates of brain and cornea in saline, whole blood (after crushing a clot), and untreated CSF and urine were innoculated intracerebrally into CF1 strain mice (20 ul per animal). Some mice showed emaciation, bradykinesia, rigidity of the body and tail, and sometimes tremor after long incubation periods. Tissues obtained after the animal died (or was killed) were studied histologically (table). Animals infected by various inocula showed common pathological changes, consisting of severe spongiform changes, glial proliferation, and a moderate loss of nerve cells. A few mice inoculated with brain tissue or urine had the same amyloid plaques found in patients and animals with CJD.3

In our long-term experiments, inoculating materials taken from twenty patients with CJD or Gerstmann-Straussler-Scheinker's disease (GSS) into rodents, positive results were obtained in seventeen cases, including this patient. Brain tissue transmitted the disease most frequently within the shortes incubation period, except for one case where the lymph node was the most infectious. Transmission through the cornea has been noted in man4 and in guineapigs.5 Whole blood samples taken from three patients were inoculated and a positive transmission occured only in the case recorded here. Mouse-to-mouse transmission through blood inoculation was successful after a mean incubation period of 365 days.1 Transmission through urine was positive in this patient only, and negative in one other patient and in many infected animals. Transmission through the CSF from eight patients was negative, yet transmission via the CSF of infected rats was positive.1

As viraemia has been proved in guineapigs,6 mice,1,7 and lately in patients with CJD, blood for transfusion or blood products for medical use must be tested for unconventional pathogens. For this purpose, we inoculated blood products inot rodents.8 The CJD pathogen was not found in the products examined. However, this approach takes too long to be of practical value. More efficient methods must be developed to detect pathogens and to eliminate them from blood. One proposal9 is to apply membrane filtration to the pruification protocol of human growth hormone suspected of being contaminated with CJD. Similar methods are needed for blood contamination.

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

JUN TATEISHI

1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmission of human subacute spongiform encephalopathy to small rodents 1: Clinical and histological observations. Acta Neuropathol (Berl) 1980; 51: 127.

2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob disease with demonstration of virus-like particles. Acta pathol Jpn 1982;32: 695.

3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the brains of mice with Creutzfeldt-Jakob disease. Ann Neurol 1984; 15: 278.

4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974; 290: 692.

5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L. Experimental Creutzfeldt-Jakob disease transmitted via the eye with infected cornea. N Engl J Med 1977; 296: 1334.

6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental Creutzfeldt-Jakob disease. Science 1978: 200: 1069.

7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC. Creutzfeldt-Jakob disease in mice. Persistent viremiam and preferential replication of virus in low-density lymphocytes. Infect Immun 1983; 41: 154.

8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform encephalopathis absent in blood products. J Med Virol 1985; 15: 11.

9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease pathogen in growth hormone preparations is eliminatable. Lancet (in press).


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



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



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


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



Synopses

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

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

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

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

AUSTRALIA - ANOTHER sCJD VICTIM

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

Subject: australia another CJD victim - blood donor -

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



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

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

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

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

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

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

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

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

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

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

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

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


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


Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

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



TSS

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

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

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

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE

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

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

DR. HOGAN: Dr. Manuelidis?

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

PAPER MILL REPORTING 301 495-5831 163

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

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

PAPER MILL REPORTING 301 495-5831 164

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

SNIP...

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

PAPER MILL REPORTING 301 495-5831 166

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

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

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

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

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

PAPER MILL REPORTING 301 495-5831 167

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

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

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

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

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

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

PAPER MILL REPORTING 301 495-5831 217

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

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

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

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

PAPER MILL REPORTING 301 495-5831 218

DR. HUGHES: Yes.

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

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

DR. MANUELIDIS: Yes.

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

PAPER MILL REPORTING 301 495-5831 219

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

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

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

PAPER MILL REPORTING 301 495-5831 220

in that particular category.

snip...

SEE FULL TEXT 346 PAGES ;



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



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



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



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

SOMETHING TO PONDER ???

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

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

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



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



Thursday, April 9, 2009

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



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



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



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



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



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



Tuesday, July 14, 2009

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

WHERE did we go wrong $$$



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



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

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

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

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

CODE

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

RECALLING FIRM/MANUFACTURER

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

Firm initiated recall is ongoing.

REASON

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

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

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

CODE

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

RECALLING FIRM/MANUFACTURER

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

REASON

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

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007



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



NEW URL



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




Thursday, March 19, 2009

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



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



Sunday, May 10, 2009

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



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



Wednesday, July 1, 2009

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



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



Tuesday, July 14, 2009

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

WHERE did we go wrong $$$



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



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



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



Saturday, June 13, 2009

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



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



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

wasted days and waste nights...freddy fender

stupid is, as stupid does...forest gump

still sadly disgusted...

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

TSEAC 21st Meeting Final Issue Summary June 12, 2009

2009 Meeting Materials, Transmissible Spongiform Encephalopathies Advisory Committee

Updated: 6/4/2009


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


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

Holiday Inn 2 Montgomery Village Avenue Gaithersburg, MD 20879

Topic I:

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

ISSUE:

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

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

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

snip...

see full text ;


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


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


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



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


SNIP...

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

12:30 p.m. Lunch

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

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

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

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

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

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

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


SNIP...


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


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


Sunday, May 10, 2009

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


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


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

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

snip...

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

soundness of BSE maintenance sampling (APHIS),

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

snip...

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

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


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


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

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

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

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

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

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

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

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

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

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

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

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


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


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

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

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

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

CODE

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

RECALLING FIRM/MANUFACTURER

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

Firm initiated recall is ongoing.

REASON

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

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

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

CODE

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

RECALLING FIRM/MANUFACTURER

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

REASON

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

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007


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


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

Page Not Found

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

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


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


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


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


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


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


you can still see those violations here ;


Thursday, March 19, 2009

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


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


Monday, June 01, 2009

Biochemical typing of pathological prion protein in aging cattle with BSE


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


Rare BSE mutation raises concerns over risks to public health

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

NATUREVol 45726 February 2009


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


Sunday, May 10, 2009

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


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


Wednesday, February 11, 2009

Atypical BSE North America Update February 2009

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


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


Atypical BSE North America Update February 2009


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


Thursday, April 30, 2009

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


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


Friday, May 29, 2009

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


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


P35

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

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


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


RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

___________________________________

PRODUCT

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

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

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

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

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

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

CODE

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

RECALLING FIRM/MANUFACTURER

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

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

REASON

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

VOLUME OF PRODUCT IN COMMERCE

Unknown

DISTRIBUTION

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

___________________________________


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


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


Sunday, May 17, 2009

WHO WILL WATCH THE CHILDREN ?

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

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

see full text ;


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



CJD ON THE RISE IN THE USA ;


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

April 20, 2009

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

National Prion Disease Pathology Surveillance Center Cases Examined1

(December 31, 2008)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 42 32 28 4 0 0

1997 115 68 59 9 0 0

1998 93 53 45 7 1 0

1999 115 69 61 8 0 0

2000 151 103 89 14 0 0

2001 210 118 108 9 0 0

2002 258 147 123 22 2 0

2003 273 176 135 41 0 0

2004 335 184 162 21 0 13

2005 346 193 154 38 1 0

2006 380 192 159 32 0 14

2007 370 212 185 26 0 0

2008 383 228 182 23 0 0

TOTAL 30715 17756 1490 254 4 2

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

Rev 2/13/09 National

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

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

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

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

Greetings,

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

are they accumulating ?

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

location would be very interesting ?

age group ?

sex ?

how was it determined that nvCJD was ruled out ?

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

please see full text here ;


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



Rare BSE mutation raises concerns over risks to public health

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

NATUREVol 45726 February 2009


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


Sunday, May 10, 2009

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


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



Wednesday, February 11, 2009

Atypical BSE North America Update February 2009

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


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



Atypical BSE North America Update February 2009


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



Monday, June 01, 2009

Biochemical typing of pathological prion protein in aging cattle with BSE


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





Monday, April 20, 2009

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


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




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