TSEAC MEETINGS

TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

2011-06-29T12:47:00.000-07:00

Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee

Center Date Time Location

CBER August 1, 2011 9:00 a.m. - 4:30 p.m.

Hilton Washington DC/North, 620 Perry Pkwy., Gaithersburg, MD

Agenda

On August 1, 2011, in the morning, the committee will discuss donor deferral for time spent in Saudi Arabia to reduce the risk of variant Creutzfeldt-Jakob disease (vCJD) by blood and blood products and human cells, tissues and cellular and tissue-based products.

Meeting Materials

Materials for this meeting will be available at:

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/default.htm1

Public Participation Information

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

Written submissions may be made to the contact person on or before July 25, 2011

Oral presentations from the public will be scheduled between approximately 2:15 p.m. and 2:45 p.m. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before July 15, 2011. Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by July 18, 2011.

Contact Information

Bryan Emery or Rosanna Harvey 1401 Rockville Pike, HFM-71, Rockville, MD 20852 301-827-1277 FAX: 301-827-0294 e-mail: Bryan.Emery@fda.hhs.gov or email: Rosanna.Harvey@fda.hhs.gov

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http://www.fda.gov/AdvisoryCommittees/Calendar/ucm261240.htm

Greetings Doctor Emery et al @ TSEAC,

I wish to kindly submit the following Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products.

My main concern is the denial of the same risk factors from atypical CJDs here in the USA from the many overly abundant strains of TSE in animals and man.

IF the study below (see Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque "BSE-L in North America may have existed for decades", IF this comes to be true, as i have believed it to be for years and years, IT is not Saudi Arabia risk factor you should be addressing, it should be the risk factor there from here in the USA and all of North America.

AS the strains, sub-strains of TSE continue to emerge and spread, more and more humans and animals for human and animal consumption will be exposed.

WE know there is some sort of risk factor from the BAXTER study on GSS and blood. WE see now that the Nor-98 atypical scrapie, H-BSE, L-BSE, TME, GSS and some sporadic CJD, all seem to be connected in some way to each other. all of which have been documented in North America. it would be negligent in my opinion to omit this from risk factor assessments. by the time the dots are connected, it will be too late. If accumulation plays a roll, and we accumulate enough of different typical and atypical TSE, what is the threshold from exposure to sub-clinical to clinical (especially now that we know more than one type of TSE can infect a species) ? you cannot answer that. nor can anyone else. so you continue to roll the dice for everyone. we must include all human Transmissible Spongiform Encephalopathy in donor deferral, and we must take an urgent and serious look at Alzheimer's and blood donor risk factor there from, in my opinion.

I hope you can submit this to the TSEAC meeting. if not, please.........PLEASE take time to read the recent scientific studies. the tides turning, however slow it may be, and the science seems to be coming together to show what i have been saying for 14 years. however, it may take another 2 decades for officials and industry to connect the dots$ or admit$ by then it will be much too late.

(please note, the blogs i post my research of data on TSE too, please note i do NOT advertise. i make no money. i simply made a promise to my Mother. i also think science and the truth there from, should be free. i simply use these blogs as a tool to educate the public. ...tss)

please see the follow ;

Bio.108: Transmission of Prion Disease by Multiple, Clinically-Relevant Blood Components Following a Single Blood Transfusion

Sandra McCutcheon,2,† Anthony R. Alejo Blanco,2 E. Fiona Houston,1 Christopher de Wolf,2 Boon Chin Tan,2 Nora Hunter,2 Valerie Hornsey,3 Ian R. MacGregor,3 Christopher V. Prowse,3 Marc Turner3, 4 and Jean C. Manson2

1The University of Glasgow; Glasgow, UK; 2The Roslin Institute and R(D)SVS, University of Edinburgh; Edinburgh, UK; 3Scottish National Blood Transfusion Service; Edinburgh, UK; 4The University of Edinburgh; Edinburgh, UK;†Presenting author; Email: sandra.mccutcheon@roslin.ed.ac.uk

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. While the epidemic appears to be waning, there is much concern that vCJD infection may be amplified/prolonged in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported. Using the most appropriate animal model available, in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion to recipients, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components can act as potential vectors for prion transmission and highlight the importance of multiple control measures to minimize the risk of human to human transmission of vCJD by blood transfusion.

PPPM.18: Induction of Ab Amyloidogenesis In Vivo by Blood Transfusion

Rodrigo Morales,1,† Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Claudio Soto1

1University of Texas Health Science Center at Houston; Houston, TX USA; 2Universidad de Los Andes; Santiago, Chile; 3Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Rodrigo.MoralesLoyola@uth.tmc.edu

Alzheimer disease (AD) is the most common type of senile dementia. Disease manifestation is characterized by progressive impairment of memory and cognition which is triggered by synaptic dysfunction and neuronal loss. Compelling evidence suggests that misfolding and aggregation of Ab is a hallmark event in the disease pathogenesis. An important unanswered question related to AD involves its etiology since over 90% of the AD cases arise sporadically. Interestingly, misfolding and aggregation of proteins is the main feature of other diseases -termed Protein Misfolding Disorders (PMDs)] which include Transmissible Spongiform Encephalopathies (TSEs), among others. Convincing experimental evidences have shown that the only component of the infectious agent in TSEs is the misfolded form of the prion protein. Strikingly, the molecular mechanisms responsible for prion replication are very similar to the process of amyloid formation in all PMDs, suggesting that all these diseases have the inherent capability of being transmissible. Recent reports have shown that intra-cerebral and intra-peritoneal administration of brain homogenates containing Ab aggregates can accelerate the generation of senile plaques in mice models of AD. However, it remains to be demonstrated if this phenomenon can occur by more relevant routes of administration. The aim of this study was to assess whether AD pathogenesis can be induced intravenously, mimicking the know transmission of prion diseases through blood transfusion. For this purpose we used young tg2576 mice which were injected with blood obtained from 12 months old tg2576 mice (AD-blood) that contains a substantial quantity of cerebral Ab deposits. Mice were sacrificed at 250 days old, a time in which these animals scarcely develop Ab deposits. Interestingly, we observed that infusion of AD-blood induces substantial Ab accumulation in animals that without treatment or injected with wild type blood would barely have any detectable Ab lesion. Plaque deposition was mainly present in cortex and hippocampus, being more abundant in the former. In addition, we observed a decrease in memory in mice challenged with AD-blood. Other features such as brain inflammation and synaptic integrity were also measured. Importantly, similar results were obtained in a second and independent experiment performed in a double transgenic mouse model that develops AD plaques as early as 4 months old. Our results indicate that an AD-like pathogenesis can be induced by intravenous administration of AD-blood, presumably through induction of protein misfolding in a similar way as prion diseases. These findings may open a new avenue to understand the origin of sporadic AD and may provide new strategies for disease intervention and prevention.

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html

IN reference to the above study, please see ;

Bio.001: Protease-Sensitive Synthetic Prions and Evidence that Tg9949 Mice Do Not Spontaneously Generate Prions

David Colby1,† and Stanley Prusiner2

1University of Delaware; Newark, DE USA; 2University of California, San Francisco; San Francisco, CA USA†Presenting author; Email: colby@udel.edu

The resistance of many forms of PrPSc to protease digestion provides a convenient assay used to identify the presence of prions in tissue samples. However, protease-sensitive prions (sPrPSc) have also been isolated, and many prion strains have been found to be composed of mixtures of sPrPSc and protease resistant prions (rPrPSc). We have generated novel synthetic prions, composed of wild-type PrP, which are serially transmissible in two lines of transgenic mice, result in neuropathology indicative of prion disease, and cause a conformational change in PrP that is not accompanied by resistance to proteinase K. Inoculation of recombinant PrP of residues 89-230, refolded into an amyloid conformation, into Tg9949 mice resulted in the generation of these protease-sensitive prions. In control experiments, Tg9949 mice, which overexpress an N-terminally truncated form of PrP, were found to be prone to late onset neurological dysfunction distinct from prion disease. Control Tg9949 mice lacked both prion neuropathology and any detectable change in the conformation of PrP. Repeated serial passage of age-matched brain material from control Tg9949 mice did not generate prions. Our results demonstrate that sPrPSc of wild-type sequence can be pathogenic and transmissible and suggest that the contribution of sPrPSc may be overlooked in many studies that rely on the measurement of rPrPSc alone.

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

Top Curr Chem (2011)

DOI: 10.1007/128_2011_161

# Springer-Verlag Berlin Heidelberg 2011

Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar

Abstract

Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.

M.A. Tranulis (*)

Norwegian School of Veterinary Science, Oslo, Norway

e-mail: Michael.Tranulis@nvh.no

S.L. Benestad

Norwegian Veterinary Institute, Oslo, Norway

T. Baron

Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France

H. Kretzschmar

Ludwig-Maximilians University of Munich, Munich, Germany

Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type

http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest

snip...

SEE FULL TEXT AND MUCH MORE HERE;

Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.html

Monday, June 27, 2011

Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html

Tuesday, June 14, 2011

Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html

Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html

Friday, June 03, 2011

Estimation of variant Creutzfeldt-Jakob disease infectivity titers in human blood

http://vcjdtransfusion.blogspot.com/2011/06/estimation-of-variant-creutzfeldt-jakob.html

Saturday, May 14, 2011

USA Blood products, collected from a donor who was at risk for vCJD, were distributed Nationally and Internationally MAY 11, 2011

http://vcjdtransfusion.blogspot.com/2011/05/usa-blood-products-collected-from-donor.html

Sunday, May 1, 2011

W.H.O. T.S.E. PRION Blood products and related biologicals May 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/who-tse-prion-blood-products-and.html

Saturday, April 30, 2011

Blood product, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease (vCJD), was distributed APRIL 27, 2011

http://vcjdtransfusion.blogspot.com/2011/04/blood-product-collected-from-donor-who.html

Sunday, March 6, 2011

U.K. and U.S.A. vCJD, CJD, TSE screen (a) the blood supply and (b) blood donors Commons Hansard Written Answers and FDA March 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/uk-and-usa-vcjd-cjd-tse-screen-the.html

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Tuesday, April 26, 2011

sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)

http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html

Tuesday, March 29, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html

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-StrÃ¤ussler-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.

Saturday, September 5, 2009

TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS

snip...

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

snip...

see full text ;

http://tseac.blogspot.com/2009/09/tseac-meeting-february-12-2004-baxter.html

Friday, June 03, 2011

Estimation of variant Creutzfeldt-Jakob disease infectivity titers in human blood

http://vcjdtransfusion.blogspot.com/2011/06/estimation-of-variant-creutzfeldt-jakob.html

Wednesday, March 2, 2011

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript Posted: 3/2/2011 Posted: 3/2/2011

October 28, 2010

http://tseac.blogspot.com/2011/03/transmissible-spongiform.html

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html

Sunday, May 10, 2009

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

TO : william.freas@fda.hhs.gov

May 8, 2009

Greetings again Dr. Freas, TSEAC et al,

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

IN reply to ;

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

Friday, June 12, 2009

vCJD-related abnormal prion protein in a person with haemophilia - an update

http://vcjdtransfusion.blogspot.com/2009/06/vcjd-related-abnormal-prion-protein-in.html

Asante/Collinge et al, that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest _sporadic_ CJD;

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm

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

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

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

Sent: Tuesday, February 18, 2003 12:45 PM

To: Freas, William

Cc: Langford, Sheila

Subject: Re: re-vCJD/blood and meeting of Feb. 20, 2003

Greetings FDA,

Asante/Collinge et al, that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest _sporadic_ CJD;

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm

Tuesday, February 8, 2011

U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001

http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html

Suppressed peer review of Harvard study October 31, 2002.

October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024

http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf

Sunday, February 14, 2010

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html

PLEASE SEE FULL TEXT 98 PAGES HERE ;

[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf

Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy

Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp).

Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.

This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf

From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION]

snip...

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

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

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

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

snip... 48 pages...page 1 starts on page 13, then come back to page 1 to finish.....tss

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

TSEAC JUNE 2, 1999

Welcome to the FDA traveling road show

From: TSS

snip...

CHAIRMAN BROWN: A couple of points just to bring your experimental data up to speed. Unpublished further experiments on the mouse model have produced good news and bad news.

The bad news is that we have a disappointingly large number of transmissions following intravenous inoculation of either plasma or Buffy coat. We also have a transmission using whole blood as a transfusion into these mice. So that's not good news.

The other thing that is not too good is that we have now got in this particular model a ratio of five to one, as opposed to ten to one, which was also disappointing.

The only piece of good news in that in terms of experimental data is that we found that, again, in this model, the level of infectivity during the entire incubation period is almost negligible compared to the level of infectivity during the clinical phase of illness. And that is very good news indeed. So these are data that are not yet published but ??

snip...

snip...page 154

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

snip...

snip...page 218

MS. HARRELL: Well, I asked him the question, was there a deferral ?? was there deferral criteria for blood donors for classic CJD for people who have either resided or visited the UK.

CHAIRMAN BROWN: I'm sorry. Repeat that, the question.

MS. HARRELL: Is there a deferral policy for blood donors to attempt to reduce the risk of transmitting classic CJD for people who either resided or visited the UK?

DR. SCHONBERGER: The answer is no.

MS. HARRELL: And if there is no risk, if we think that there is no risk of transmitting the whatever to ?? for CJD, what makes this different, for new variant CJD much different?

CHAIRMAN BROWN: That's the first time, Stan, you'll ever hear of prion referred to as a whatever. (Laughter.)

CHAIRMAN BROWN: I mean, I've heard it referred to as a lot of different things. I'm ??

DR. PRUSINER: You've said that many times, Paul. (Laughter.)

CHAIRMAN BROWN: It may be that ??

DR. PRUSINER: Is that in the Congressional Record?

CHAIRMAN BROWN: The issue is not about sporadic CJD. That is the issue we can sort of generically say CJD. Presumably, if the blood from a patient with new variant CJD were infectious, the disease that it would transmit would be new variant CJD. So it's not ??

MS. HARRELL: Okay. So CJD is not transmitted through the blood is what you're saying?

CHAIRMAN BROWN: We have no evidence from looking at populations that that has ever happened. The question is: since we know it can happen when we use experimental models of CJD, we can take CJD blood from one animal and produce the disease in another animal.

So there is the "theoretical possibility" that this might also happen in humans, particularly with a different strain of the disease, which new variant is, about which we don't know a whole lot. That's the question.

DR. SCHONBERGER: Isn't the answer to her question that the incidence of CJD, REDS, classic CJD, is not influenced by whether or not you've lived in the UK between 1980 and 1996 ??

CHAIRMAN BROWN: Yes.

DR. SCHONBERGER: ?? but the incidence of new variant CJD is?

CHAIRMAN BROWN: Yes, 40-love. (Laughter.)

snip...

see more here ;

http://tseac.blogspot.com/2011/06/tseac-june-2-1999-welcome-to-fda.html

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007.

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

my comments to PLosone here ;

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed. ***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html

14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

update October 2009

T. Singeltary

Bacliff, TX, USA

Background:

An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

Methods:

12 years independent research of available data

Results:

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

Conclusion:

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf

Thursday, February 24, 2011

The risk of variant Creutzfeldt-Jakob disease among UK patients with bleeding disorders, known to have received potentially contaminated plasma products

http://vcjdtransfusion.blogspot.com/2011/02/risk-of-variant-creutzfeldt-jakob.html

Saturday, January 22, 2011

Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html

CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

Dr McGovern From: Dr A Wight

Date: 5 January 1993

Copies: Dr Metters

Dr Skinner

Dr Pickles

Dr Morris

Mr Murray

TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES

1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.

2. Briefly, the meeting agreed that:

i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegenerative disorders;

ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and

iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.

93/01.05/4.1tss

http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf

BSE101/1 0136

IN CONFIDENCE

5 NOV 1992

CMO From: Dr J S Metters DCMO 4 November 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognized the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.

2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed'. As the report emphasizes the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.

What are the implications for public health?

3. . The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.

92/11.4/1-1

BSE101/1 0137

4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.

JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832

121/YdeStss

92/11.4/1.2

http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf

http://betaamyloidcjd.blogspot.com/

Oral presentations

Oral.01: Changing Spectrum of Prions

Stanley Prusiner

University of California San Francisco, Institute for Neurodegenerative Diseases; San Francisco, CA USA

Prions are self-propagating forms of proteins found in eukaryotes. Prions are created from benign, cellular precursor proteins by a posttranslational modification that is self-perpetuating. Often the prion form of the protein is aggregated and assembles into amyloid polymers. Prions can be inherited both genetically and epigenetically. In neurodegenerative diseases, the formation of prions is heritable through mutations in the gene encoding the cellular form of the prion protein. In fungi, the prion state is epigenetically transferred from mother to daughter cells.

Historically, prions were confined to a small group of infectious CNS illnesses including Creutzfeldt-Jakob disease (CJD) and kuru of humans, scrapie of sheep, bovine spongiform encephalopathy, and chronic wasting disease of deer and elk. CJD can present as an infectious, inherited or sporadic illness. In all three manifestations of the disease, the cellular prion protein (PrPC) refolds into the disease-causing isoform (PrPSc). A truncated form of PrPSc readily polymerizes into amyloid fibrils and forms PrP amyloid plaques. Prion strains composed of different conformers of PrPScSc have been identified. Subsequently, prions were recognized in fungi and studied extensively using yeast. Recently, self-propagation of altered proteins that cause several neurodegenerative diseases, including Alzheimer disease and the tauopathies, has been demonstrated using cultured cell and transgenic mouse models. Increasing evidence argues that the Ab peptide acts as a prion in that it stimulates the de-novo formation of more Ab peptide. Similarly, the aggregates of Tau provoke the assembly of more aggregated Tau. In addition, fetal grafts of substantia nigra in patients with advanced Parkinson’s disease exhibit Lewy bodies, arguing that a-synuclein may act as a prion. Misfolded a-synuclein is thought to transit from the patient’s neurons to those in the graft, where it stimulates the de-novo formation of aberrantly folded a-synuclein into Lewy bodies.

The spread of misprocessed proteins in the human CNS is also consistent with the Ab peptide, hyperphosphorylated Tau and misfolded a-synuclein being prions. In Alzheimer disease, Ab plaques and neurofibrillary tangles (NFTs) begin in the entorhinal cortex and spread throughout the brain. In a delayed form of traumatic brain injury, NFTs appear to spread outward from points of impact. Misfolded a-synuclein has been found along the vagus nerve where it appears to migrate retrograde into the CNS.

Increasing evidence that posttranslationally altered proteins are responsible for the major neurodegenerative diseases widens the spectrum of prion disorders. Moreover, prions with glutamine/asparagine-rich regions like those in yeast and aplysia have given unique insights into the normal function of alternatively processed, self-propagating proteins.

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions

David W. Colby1,* and Stanley B. Prusiner1,2

http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html

http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html

Friday, September 3, 2010

Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE

http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html

Thursday, December 23, 2010

Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom

http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html

Saturday, March 22, 2008

10 Million Baby Boomers to have Alzheimer's in the coming decades

snip...

Alzheimer’s disease is the seventh leading cause of all deaths in the United States and the fifth leading cause of death in Americans older than the age of 65 years. More than 5 million Americans are estimated to have Alzheimer’s disease. Every 71 seconds someone in America develops Alzheimer’s disease; by 2050 it is expected to occur every 33 seconds. During the coming decades, baby boomers are projected to add 10 million people to these numbers. By 2050, the incidence of Alzheimer’s disease is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million persons. Significant cost implications related to Alzheimer’s disease and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (eg, caregiver lost wages and out-of-pocket expenses, decreased business productivity) costs. Not included in these figures are the estimated 10 million caregivers who annually provide $89 billion in unpaid services to individuals with Alzheimer’s disease.

snip...

http://www.alzheimersanddementia.org/webfiles/images/journals/jalz/JALZ_739.pdf

see full text and more ;

http://betaamyloidcjd.blogspot.com/2008/03/10-million-baby-boomers-to-have.html

http://betaamyloidcjd.blogspot.com/

TSS

UPDATE JULY 27, 2011

August 1, 2011 Transmissible Spongiform Encephalopathies Advisory Committee Meeting Draft Agenda (PDF - 18KB)

Posted: 7/27/2011

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM265683.pdf

August 1, 2011 Transmissible Spongiform Encephalopathies Advisory Committee Meeting: Issue Summary (PDF - 154KB)
Posted: 7/27/2011

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM265682.pdf

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

From: Emery, Bryan (CBER)

To: 'Terry S. Singeltary Sr.'

Cc: Emery, Bryan (CBER)

Sent: Friday, July 22, 2011 9:47 AM

Subject: RE: TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

Hi Mr. Singeltary,

Your statement will be provided to the members and will be placed in the meetings display folder for the public to see. Come or attend via webcast.

thanks for your public participation

LCDR Bryan Emery

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

From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net]

Sent: Wednesday, June 29, 2011 3:54 PM

To: Emery, Bryan (CBER)

Cc: Harvey, Rosanna; BSE-L@LISTS.AEGEE.ORG; CJD-L@LISTS.AEGEE.ORG; cjdvoice@yahoogroups.com; BLOODCJD@YAHOOGROUPS.COM; Advocatejr@aol.com; COTTWEST@SILCOM.COM; Dave Cavenaugh

Subject: TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee

Center Date Time Location

CBER August 1, 2011 9:00 a.m. - 4:30 p.m.

Hilton Washington DC/North, 620 Perry Pkwy., Gaithersburg, MD

Agenda

snip...end...TSS

Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html

Bio.108: Transmission of Prion Disease by Multiple, Clinically-Relevant Blood Components Following a Single Blood Transfusion

Sandra McCutcheon,2,† Anthony R. Alejo Blanco,2 E. Fiona Houston,1 Christopher de Wolf,2 Boon Chin Tan,2 Nora Hunter,2 Valerie Hornsey,3 Ian R. MacGregor,3 Christopher V. Prowse,3 Marc Turner3, 4 and Jean C. Manson2

1The University of Glasgow; Glasgow, UK; 2The Roslin Institute and R(D)SVS, University of Edinburgh; Edinburgh, UK; 3Scottish National Blood Transfusion Service; Edinburgh, UK; 4The University of Edinburgh; Edinburgh, UK;†Presenting author; Email: sandra.mccutcheon@roslin.ed.ac.uk

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. While the epidemic appears to be waning, there is much concern that vCJD infection may be amplified/prolonged in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported. Using the most appropriate animal model available, in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion to recipients, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components can act as potential vectors for prion transmission and highlight the importance of multiple control measures to minimize the risk of human to human transmission of vCJD by blood transfusion.

PPPM.18: Induction of Ab Amyloidogenesis In Vivo by Blood Transfusion

Rodrigo Morales,1,† Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Claudio Soto1

1University of Texas Health Science Center at Houston; Houston, TX USA; 2Universidad de Los Andes; Santiago, Chile; 3Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Rodrigo.MoralesLoyola@uth.tmc.edu

Alzheimer disease (AD) is the most common type of senile dementia. Disease manifestation is characterized by progressive impairment of memory and cognition which is triggered by synaptic dysfunction and neuronal loss. Compelling evidence suggests that misfolding and aggregation of Ab is a hallmark event in the disease pathogenesis. An important unanswered question related to AD involves its etiology since over 90% of the AD cases arise sporadically. Interestingly, misfolding and aggregation of proteins is the main feature of other diseases -termed Protein Misfolding Disorders (PMDs)] which include Transmissible Spongiform Encephalopathies (TSEs), among others. Convincing experimental evidences have shown that the only component of the infectious agent in TSEs is the misfolded form of the prion protein. Strikingly, the molecular mechanisms responsible for prion replication are very similar to the process of amyloid formation in all PMDs, suggesting that all these diseases have the inherent capability of being transmissible. Recent reports have shown that intra-cerebral and intra-peritoneal administration of brain homogenates containing Ab aggregates can accelerate the generation of senile plaques in mice models of AD. However, it remains to be demonstrated if this phenomenon can occur by more relevant routes of administration. The aim of this study was to assess whether AD pathogenesis can be induced intravenously, mimicking the know transmission of prion diseases through blood transfusion. For this purpose we used young tg2576 mice which were injected with blood obtained from 12 months old tg2576 mice (AD-blood) that contains a substantial quantity of cerebral Ab deposits. Mice were sacrificed at 250 days old, a time in which these animals scarcely develop Ab deposits. Interestingly, we observed that infusion of AD-blood induces substantial Ab accumulation in animals that without treatment or injected with wild type blood would barely have any detectable Ab lesion. Plaque deposition was mainly present in cortex and hippocampus, being more abundant in the former. In addition, we observed a decrease in memory in mice challenged with AD-blood. Other features such as brain inflammation and synaptic integrity were also measured. Importantly, similar results were obtained in a second and independent experiment performed in a double transgenic mouse model that develops AD plaques as early as 4 months old. Our results indicate that an AD-like pathogenesis can be induced by intravenous administration of AD-blood, presumably through induction of protein misfolding in a similar way as prion diseases. These findings may open a new avenue to understand the origin of sporadic AD and may provide new strategies for disease intervention and prevention.

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Tuesday, July 26, 2011

Irhad Rizvo Durakovic has lost his fight to nvCJD R.I.P.

http://creutzfeldt-jakob-disease.blogspot.com/2011/07/irhad-rizvo-durakovic-has-lost-his.html

http://transmissiblespongiformencephalopathy.blogspot.com/

http://vcjdtransfusion.blogspot.com/

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

Wednesday, July 27, 2011

HIQA says vCJD blood filter not justified

[Posted: Wed 27/07/2011 http://www.irishhealth.com/]

http://vcjdtransfusion.blogspot.com/2011/07/hiqa-says-vcjd-blood-filter-not.html

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

From: "Terry S. Singeltary Sr."

To:

Sent: Wednesday, June 29, 2011 2:54 PM

Subject: [CJD-L] TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee

Center Date Time Location

CBER August 1, 2011 9:00 a.m. - 4:30 p.m.

Hilton Washington DC/North, 620 Perry Pkwy., Gaithersburg, MD

Agenda

On August 1, 2011, in the morning, the committee will discuss donor deferral for time spent in Saudi Arabia to reduce the risk of variant Creutzfeldt-Jakob disease (vCJD) by blood and blood products and human cells, tissues and cellular and tissue-based products.

SNIP...

Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html

TSS

TSEAC JUNE 2, 1999 Welcome to the FDA traveling road show

2011-06-29T12:25:00.000-07:00

From: TSS

Subject: TSEAC JUNE 2, 1999 Welcome to the FDA traveling road show

Date: October 15, 2007 at 3:18 pm PST

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

CHAIRMAN BROWN: My name is Dr. Paul Brown. Welcome to the FDA traveling road show. We are asked yet once more by the FDA to consider a question of theoretical risk in the absence of sufficient knowledge on which to base any firm conclusion.

The issue before us today is that of excluding categories of American blood donors who have either visited or resided for longer periods of time in Great Britain. The issue is sufficiently delicate, as you see that we have been moved outside the Beltway. (Laughter.)

snip...

"Dr. Alan Williams is employed by the American Red Cross, Holland Labs, and is Scientific Adviser for the Florida Blood Services and Canadian Blood Services. In addition, he has financial interests in firms that could be affected by the general discussions.

"Dr. Richard Race has financial interests in firms that could be affected by the general discussions and is a public health science researcher. "In the event that the discussions involve specific products or specific firms for which FDA participants have a financial interest, the participants are aware of the need to exclude themselves from such involvement. And their exclusion will be noted for the public record. A copy of the waivers is available by written request under the Freedom of Information Act. "With respect to all other meeting participants, we ask in the interest of fairness that they address any current or previous financial involvement with any firm whose product they may wish to comment upon."

So ends the reading of the conflict of interest statement. Dr. Brown, I turn the meeting over to you.

snip...

DR. JACOBS: Thank you, Dr. Brown, and welcome to members of the Committee. Today we are again bringing the question of deferral from blood donation of persons with possible foodborne exposure to bovine spongiform encephalopathy, BSE, as a precautionary measure to reduce the risk of blood transmission of new variant Creutzfeldt Jakob disease. And we are asking the Committee at this time, as we did in December, to consider this in the light of possible shortages.

Next, the current status. So far there have been no cases of either BSE or new variant CJD reported in the U.S. We're aware and we discussed in December the precautionary measures which have been taken in the U.K. First, they are not using U.K.?sourced plasma; and, secondly, they are implementing universal leukoreduction.

snip...

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

Next overhead. Should FDA recommend excluding donors who have resided in the United Kingdom or other BSE countries? The Committee voted 15 yes, unanimous, to remove "or other BSE countries."

snip...

I want to just put on the record and mention the other votes which were taken in December. Should FDA recommend withdrawal for blood components based on these donor deferral criteria? The vote was seven yes, five no. And should FDA recommend withdrawal for plasma derivatives based on these donor deferral criteria? Voted eleven no, one yes.

Next one, please. In addition to these questions on deferral of donors, in December we also asked the Committee to consider the actions that FDA would take if there were a report of a possible case of new variant CJD. We're going to refer those to CDC, but considering our precautionary withdrawal policy for new variant CJD, we asked: Should FDA recommend precautionary quarantine or withdrawal for plasma derivatives to which a possible new variant CJD donor contributed pending confirmation of the clinical diagnosis?

The Committee voted eight yes, one no, one abstained, but they asked us to revisit this question of our operational definition of a possible new variant CJD case. And in the second part of today's deliberations, after the vote on deferral, we will go back to that question.

The Committee also voted that a tonsil biopsy negative for protease?resistant prion would not be sufficient to make product withdrawals unnecessary.

snip...

We now have a presentation by Dr. Philip Comer, who will give us the Det Norsk Veritas risk assessment. Dr. Comer?

MR. COMER: Thank you very much, Chairman, and thank you for the opportunity to come and talk about the study that we were asked to do by the Department of Health in the United Kingdom as a result of a recommendation from the United Kingdom's Spongiform Encephalopathy Advisory Committee.

snip...

I am just going to go very quickly over the evidence for infectivity in blood. I think probably that will have already been looked at significantly by this Committee, but it was very much part of the background for what we were doing in the study that we did.

If we look at blood transfusions, we know that all attempts to transmit infectivity of blood, blood transfusion, so across a species barrier, have failed and that within animal models, as far as I am aware, the one case which has been reported by Bob Rohwer is still the only case that I have heard of in which there has been a positive transmission by the i/v route within an animal model.

Epidemiology studies have shown that's from sporadic CJD. There is no evidence that there has been any transmission through the blood route. And when we look at blood from human CJD cases, primarily sporadic CJD cases and certainly no variant CJD cases, and look at that, their infectivity through the i/c route into animal models, there have been a few experiments which have shown positive infectivity into rodents but negative results from a significant number of studies into primates and other species. And there have been some questions asked about ?? these cases, these experiments all involve very small numbers of animals and some sort of significant questions asked about those and, in particular, the fact that it is a bit odd that we have got no positive infections in the primates, which you might have expected would be more susceptible than the rodents. Then when we look at actually within animal models themselves, there have been quite a number of cases, experiments where positive infections have been reported from animals infected with some form of TSE and have been through the i/c route infected in the same species, so again with no species barrier.

snip...page 89

CHAIRMAN BROWN: A couple of points just to bring your experimental data up to speed. Unpublished further experiments on the mouse model have produced good news and bad news.

The bad news is that we have a disappointingly large number of transmissions following intravenous inoculation of either plasma or Buffy coat. We also have a transmission using whole blood as a transfusion into these mice. So that's not good news.

The other thing that is not too good is that we have now got in this particular model a ratio of five to one, as opposed to ten to one, which was also disappointing.

The only piece of good news in that in terms of experimental data is that we found that, again, in this model, the level of infectivity during the entire incubation period is almost negligible compared to the level of infectivity during the clinical phase of illness. And that is very good news indeed. So these are data that are not yet published but ??

snip...page 105

CHAIRMAN BROWN: Right, right. And, as I say, if it turns out to be the case with the human disease, ?? and I'm guessing it probably will be ?? with you, I think the likelihood of disease, natural disease, whether it be scrapie in sheep, BSE in cattle, or CJD in humans, is going to be quite a lot less virulent than the experimentally induced disease.

Even under the experimental conditions I mentioned, however, infectivity in all components of the blood during the incubation period is so low that it virtually poses I think no risk, at least in terms of plasma derivatives.

snip...page 106

Dr. Chan

snip...

So the issue that we dealt with in early May was "do variants of CJD pose a risk to blood safety?" And we sort of divided it into the classic variant and others. The others came out of, I'm sure you're all aware, of the scare that we all had over the Utah donor was this a possible chronic wasting disease, etc.

So we just put that issue on the table and let's see where it went. Our process -- we circulated a notice widely to all associations, consumer groups. We've sort of got a mailing list that's growing.

snip...page 129

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

snip...page 135

The rest of the recommendations I'll go through very briefly. Health Canada had not standardized its -- not finalized its policy on classic CJD, and we advised that they do so.

The blood services should provide clear statements about the reasons for believing that there are no longer concerns regarding the classic sporadic CJD; that Health Canada and the blood services provide communication regarding all aspects of product quarantine.

And that was because there's considerable confusion over the Utah donor case. Health Canada identify and provide information that all products that contain trace amounts of blood products -- this was interesting. Many of the physicians did not even know which products that were being distributed contained blood products. We thought this was an important issue. All products can be tracked in the event of an infected donor. And that they take steps to discourage manufacturers from using blood products in the production or formulation of other products.

That mechanisms are developed to ensure that -- oh, this is the surveillance for CJD. That criteria have to be established to determine between classic and variant forms, which I know is the topic that you are going to be discussing this afternoon.

snip...page 138

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

snip...page 145

CAPTAIN RUTHERFORD: Good afternoon.

The Department of Defense would like to thank you for allowing us to offer public comment.

I am Captain Bruce D. Rutherford, Medical Service Corps, United States Navy, the present Director of the Armed Services Blood Program. On 5 February, 1999, Dr. Sue Bailey, the Assistant Secretary of Defense for Health Affairs, forwarded a letter to Vice Admiral David Satcher, Public Health Service, the Surgeon General of the United States.

In that letter, Dr. Bailey expressed her opposition and the opposition of the Surgeon Generals of the Army, Navy and Air Force on deferring individuals as blood donors based on "perception" of a "possible" risk of transfusion transmission of the agent for "new variant" CJD. There has not been a single case, repeat, single case of transfusion transmitted new variant CJD or classical CJD reported in the world in more than 55 years since transfusion of blood products became widely accepted as a treatment regime.

In November of 1991, the Department of Defense issued an advisory recommending that individuals participating in Operation Desert Storm be deferred as blood donors after a number of Desert Storm troops were identified with cutaneous and visceral Leishmania tropica. Knowing that Leishmania donavani was transfusion transmissible, and now knowing the extent of infection rate of the "at risk" population, the DOD decided to defer those individuals as blood donors who participated in country in the Persian Gulf.

It was not until December of 1993, or two years later, that the DOD stopped asking leishmaniasis related questions of its blood donors. The cessation was due to a concentrated effort by the military health system in identifying an extremely small number of infected individuals and the follow-on screening questions' ability in identifying an extremely small number of donors with symptoms where leishmaniasis could have been a possibility.

However, a study in the survivability and infectivity of viscerotropic Leishmania tropica in human blood donors from ODS participants was later shown to support our concern and was published in the American Journal of Tropical Medicine and Hygiene in 1993.

Transfusion transmission by Leishmania species was a known, not theoretical. We know the calculatable risk of being injured in a car accident, yet millions of individuals a day drive their cars with hundreds of thousands being injured per year and tends of thousands killed each year. It is the same with airplanes, lightening and other activities.

In theory, anything is possible. I remember back a few years ago when the Institutes of Medicine came out with this HIV report. Yes, hindsight was better, but that has always been true.

I think in this case we have hindsight, 55 years of hindsight. We do not need to institute a UK deferral policy which will only lead to further crippling of our nation's blood supply and more product shortages.

snip...page 148

CHAIRMAN BROWN: Thank you, Captain Rutherford. Are there any questions that any of the panel would wish to address to Captain Rutherford?

The next presentation will be by Kay R. Gregory of the American Association of Blood Banks.

MS. GREGORY: Good afternoon.

snip...page 148

In conclusion, AABB notes that there is no evidence that nvCJD is transmitted by blood transfusion. There are no cases of nvCJD in the United States. It is unknown whether travel to Great Britain correlates with exposure to or infection with the agent of BSE.

And there is no evidence that any proposed criteria will decrease the theoretical risk of acquiring nvCJD from transfusion. In contrast, there is good evidence that even a one to two percent loss of donors due to new deferral criteria will have a significant impact on blood availability and, hence, on the safety of those transfusion recipients who cannot tolerate a delay in receiving blood products.

The country should contemplate nvCJD deferral criteria only when it is apparent that such a policy would improve blood safety more than the loss of donors and the associated decrease in blood availability would compromise blood safety.

Thank you.

CHAIRMAN BROWN: Thank you, Ms. Gregory.

The word theoretical has been used many, many, many times this morning and will continue to be used, and it's being used correctly. I'd just point out that, for ten years, between 1985 and 1995, the risk of new variant CJD from BSE was also theoretical.

The next speaker is Dave Cavenaugh from the Government Relations Committee of Ten Thousand.

MR. CAVENAUGH: I'm the government relations person at the Committee of Ten Thousand. The organization is the Committee of Ten Thousand. CHAIRMAN BROWN: Yes, that's fine. Thank you.

MR. CAVENAUGH: Okay, COTT, which is the Committee of Ten Thousand, is gravely concerned about the industry logic favoring UK donors over additional U.S. replacement donors even with the survey, and even with the lack of data on paid and unpaid high volume pheresis donors. This morning's discussion showed a glaring omission in the analysis to date of the impact of excluding well paid, highly educated, non-incentive provided pheresis donors in addition to the larger, understood group of paid pheresis donors.

We've heard quite a bit in terms of the studies and in terms of some of the questions about the likely blood borne nature of this never documented entity of prion and its ability to be transmitted by blood.

There's a perceived link between new variant and beef that's been raised based on proximity, but the BSE classical CJD link should not be forgotten. It should be entertained at the minimum. Living in the United Kingdom in the late '80s seemed to be a major factor, for example.

What was it about living there, that's proximity. Both statistic presenters showed clear risk of new variant in the blood, not even enlarging the scope to include classical CJD. There are no nv cases in the U.S., but plenty of classical -- arguably, much more than the one in one million rate alleged.

Just ask CJD Voice, the patient-family support group which spoke before you 18 months ago. Small then, its numbers have mushroomed. Something is getting transmitted. Can it all be through beef? But most disturbing is the recent news confirming a second mutated form of prions also causing death in under a year.

This doubling of the number of ways prions can be malformed with fatal results raises our concern levels considerably. The explanation that it is spontaneous sounds like an early catch all. With an entity so new, so unknown and so dangerous, the committee should be providing every protection possible, not bowing to arguments of relative risk.

Thank you.

CHAIRMAN BROWN: Thank you.

snip...page 154

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

snip...page 213

DR. LEITMAN: We seem to be extrapolating the partitioning data of classical CJD -- the agent of classical CJD to the agent of new variant CJD. That may or may not be okay.

I'd like to ask Dr. Prusiner if we can at all extrapolate the lack of transmissibility through blood components of classical CJD agent to new variant?

DR. PRUSINER: I don't know that I'm qualified to answer this. I can only tell you that the little bit of work that we've done now on new variant CJD says that it is a dramatically different strain of prion. That means that the confirmation of PRP scrapie is dramatically different than anything else we've studied.

So let me give you an example. We've looked at 40 different cases of sporadic CJD, and we know that there's several different confirmations there at least. And all of these are transmissible in about 200 days to either mice that have a human PRP gene or have a chimeric mouse human PRP gene. If you look at new variant CJD, it takes more than 500 days and only about 60 percent of the animals get sick. Now, as I said before, if we take new variant CJD and we passage it into a mouse that expresses a bovine PRP gene on a null background, then all the mice are getting sick in 240 days. The piece of data I don't have that you want is you want to know if I take sporadic CJD or familial CJD cases and passage those into mice with a bovine PRP gene, do they get sick? And the answer is I don't know yet.

snip...page 218

MS. HARRELL: Well, I asked him the question, was there a deferral ?? was there deferral criteria for blood donors for classic CJD for people who have either resided or visited the UK.

CHAIRMAN BROWN: I'm sorry. Repeat that, the question.

MS. HARRELL: Is there a deferral policy for blood donors to attempt to reduce the risk of transmitting classic CJD for people who either resided or visited the UK?

DR. SCHONBERGER: The answer is no.

MS. HARRELL: And if there is no risk, if we think that there is no risk of transmitting the whatever to ?? for CJD, what makes this different, for new variant CJD much different?

CHAIRMAN BROWN: That's the first time, Stan, you'll ever hear of prion referred to as a whatever. (Laughter.)

CHAIRMAN BROWN: I mean, I've heard it referred to as a lot of different things. I'm ??

DR. PRUSINER: You've said that many times, Paul. (Laughter.)

CHAIRMAN BROWN: It may be that ??

DR. PRUSINER: Is that in the Congressional Record?

CHAIRMAN BROWN: The issue is not about sporadic CJD. That is the issue we can sort of generically say CJD. Presumably, if the blood from a patient with new variant CJD were infectious, the disease that it would transmit would be new variant CJD. So it's not ??

MS. HARRELL: Okay. So CJD is not transmitted through the blood is what you're saying?

CHAIRMAN BROWN: We have no evidence from looking at populations that that has ever happened. The question is: since we know it can happen when we use experimental models of CJD, we can take CJD blood from one animal and produce the disease in another animal.

So there is the "theoretical possibility" that this might also happen in humans, particularly with a different strain of the disease, which new variant is, about which we don't know a whole lot. That's the question. DR. SCHONBERGER: Isn't the answer to her question that the incidence of CJD, REDS, classic CJD, is not influenced by whether or not you've lived in the UK between 1980 and 1996 ??

CHAIRMAN BROWN: Yes.

DR. SCHONBERGER: ?? but the incidence of new variant CJD is?

CHAIRMAN BROWN: Yes, 40-love. (Laughter.)

snip...page 240

CHAIRMAN BROWN: I agree. We're starting to vote, and we'll start with Larry. Hold on. All right. The question is: should FDA recommend new deferral criteria for donors of transfusable components, to attempt to reduce the theoretical risk of transmitting new variant CJD from transfusions based on donor exposure to BSE in the UK?

DR. SCHONBERGER: Yes.

CHAIRMAN BROWN: Incidentally, just to remind the committee, it is possible to vote punt; that is to say, you can vote yes, no, or no vote ?? abstain.

DR. HUESTON: Well, for my own benefit, I suppose, to walk through the logic ?? and maybe for the benefit of Barbara because I think she raises a good point about how we proceed ?? we have a situation with a small number of known cases of variant Creutzfeldt Jakob, all but one of which are in the UK.

However, we know there is a potential for widespread exposure to BSE that has already occurred. Therefore, we expect more cases, but we really don't have a good idea of the magnitude of the epidemic that we're going to expect.

Part number 2 says, "While there is no known whole blood or blood product transmission of classical CJD in humans, variant Creutzfeldt Jakob differs substantially from classical CJD." So we recognize that there is the potential for transmission of some of the transmissible spongiform encephalopathies via blood, albeit controversial We have an animal model, and we can identify infectivity in lymphoid tissues with variant Creutzfeldt Jakob, which is different from classical Creutzfeldt Jakob.

At the same time, it has been pointed out many times by a number of people that there have been no observed risk ?? or no observed cases at this point of transfusion or blood product related variant Creutzfeldt Jakob cases in the UK. I think that's a little premature. One might say the absence of evidence is not evidence of absence.

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http://www.fda.gov/o

At the same time, there are look-back studies in place in the UK, and there is a natural experiment ?? a huge natural experiment ongoing in the United Kingdom, where if, in fact, there is a risk, I believe that the risk will first be apparent in the United Kingdom far before we would see it anywhere else.

At the same time, in looking at the precautionary principle ??

CHAIRMAN BROWN: Is this the preamble for a vote?

DR. HUESTON: Yes, sir. You got it. (Laughter.)

DR. HUESTON: If our goal is to be precautionary, but at the same time we have to preclude having more negative impacts for any action that we take, then positive ?? in other words, impacts on the blood supply. And I have struggled through the whole time, but I'm going to vote no at this time.

CHAIRMAN BROWN: Could I urge the remaining members of the committee ?? (Laughter.)

CHAIRMAN BROWN: ?? to vote rather than ?? I appreciate it, and I let Will, you know, chatter on because he hasn't said a whole lot, and I wanted to hear what he had to say. And so thank you, but we'll never get through if we continue to explain the reasons for our votes, each one and all. So, Susan?

DR. LEITMAN: I take the opportunity to disagree with what you just said. I think the vote at this table is so critical, it will have such a huge impact potentially on the way America collects its blood, that if we go beyond our designated time it's worth it.

And I was influenced, and it was helpful to hear the last speaker's discussion. So I think if any of us have discussions or points to mention now, they might be valuable.

The deliberations of this committee are among the most difficult of any advisory committee I've ever been on because there are simply inadequate data upon which to base a decision. For myself, in the absence of data suggesting or, rather, documenting risk, I cannot vote yes based on assumptions, perceptions, possibilities, uncertainties, theoretical risks, and potential risks.

On the other hand, there are tangible measurable data that deferral of any percentage of donors, whether it's half, one and a half, two percent, will lead to replacement by donors by a small proportion of donors that are at increased risk for measurable diseases such as hepatitis B and C. So I vote no.

CHAIRMAN BROWN: Dr. Leitman votes no.

Dr. Prusiner?

DR. PRUSINER: I would like to vote yes, and I would like to say I have 23 points that I want to go through. (Laughter.)

DR. PRUSINER: I only want to say very quickly that I don't think that economics and the availability of donors is a reason to vote yes or no in this. I think that the economy has a way of solving these problems, and I think that will happen. I think the real problem here lies that we have a very imperfect data set, and we're dealing with a disease which is universally fatal. This is really the problem that we face.

CHAIRMAN BROWN: Dr. Prusiner votes yes. Dr. Roos?

DR. ROOS: I think we're dealing with a situation in which we have no evidence of any transfusion that has transmitted either classical or new variant Creutzfeldt. And we have a situation where there are risks involved with blood transfusions that the donors accept at this point.

That is, we were informed about ?? I guess about 14 percent of individuals do donate blood that have I guess the recipients. About 14 percent of individuals that donate blood have some risky behavior. And maybe I might include living in UK part of that risky behavior.

And so I kind of accept this as, at the moment, acceptable risk for donated blood and I am awaiting evidence to prove that there is more danger involved. So I'm voting no here.

CHAIRMAN BROWN: Dr. Roos votes no. Dr. Belay?

DR. BELAY: I'm concerned about two issues. The first one is the studies that showed the presence of the new variant CJD agent in lymphoreticular tissues. And the second concern I have is the absence of evidence against blood-borne transmission of new variant CJD. The kind of data that's available for classic CJD is not available for new variant CJD, so I vote yes.

CHAIRMAN BROWN: Dr. Belay votes yes. Dr. Lurie?

DR. LURIE: Really, what we're doing is balancing one risk against two others. The two risks are the problem of the replacement donor, which is not zero but it is probably very small, given that we're only talking about one, two perhaps, percent replacement of donors here, depending on what happens in B if we get that far.

The second has to do with the diminution in the blood supply itself. And, again, there are scenarios available to us under B that allow us to minimize that. So we really have, on the one hand, two small risks that can more or less be quantified, and on the other hand we have another risk, which may itself be small, but if we are wrong could be very, very large. And that's really the benefit ?? the risk benefit calculation that we're making. For me, there remain too many uncertainties, and so I vote yes.

CHAIRMAN BROWN: Dr. Lurie votes yes. Dr. Hoel?

DR. HOEL: Yes. I'm changing my vote from last time, and I'm going to vote yes, mainly because of what I see in the epidemiology data of the cases in England and the modeling work. I think this needs to be monitored further to see how it comes in because the risks could be quite large, and so I would vote yes.

CHAIRMAN BROWN: Dr. Hoel votes yes. Dr. Bolton?

DR. BOLTON: I believe that there is insufficient documentation of the risk at this time. And in light of that, I can't ?? I don't think that the information warrants changing the current policy. I vote no.

CHAIRMAN BROWN: Dr. Bolton votes no. Dr. Nelson?

DR. NELSON: Well, this is a pretty difficult vote. Last time I voted no, and I'm going to vote no again, although I am ?? really, it's disturbing that there is no really good data at this point.

And I am impressed with a comment that was made earlier, and that is that there is an experiment in the UK of many people who have been exposed to UK donors over a period of many years. And I am somewhat reassured that there have been no cases, and I'm also reassured with the quality of the epidemiologic surveillance and data from the UK.

I think that that has been well done, carefully done, and presumably it will continue to be closely monitored. You know, if a single case had occurred, we would really need to change our policy immediately. That's number one.

But the other problem I have is if I voted yes, then I would have to make a decision on 1B. And the only ?? (Laughter.)

DR. NELSON: ?? the only reasonable decision on 1B would be to remove ?? to exclude all donors who had lived in the UK. I see no basis for any arbitrary decision. Once you go down that route, then you have to exclude anybody from the UK or who visited the UK or Ireland during this period. I don't see any alternative.

CHAIRMAN BROWN: Dr. Nelson votes no. Dr. McCullough?

DR. McCULLOUGH: I agree with Susan. This is one of the most difficult groups I have had to deal with. I'm impressed by the epidemiologic data. I'm also impressed by having sat through in 1983 and 1984 discussions of there ain't been a case reported yet, and also that we are concerned about the impact on the blood supply.

hrms/dockets/ac/99/transcpt/3518t1.rtf???????????

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVIS

And possibly also, I'm influenced by having been the fodder for congressional hearings and 60-minute expose on things that might have been done differently at some of those times. So I'm going to vote yes. I have tremendous confidence in the blood systems of this country that they will be able to ?? not easily ?? respond if changes are made.

CHAIRMAN BROWN: Dr. McCullough votes yes. Dr. Brown votes yes. Dr. Ewenstein?

DR. EWENSTEIN: Yes. I'm impressed by the modeling data. I believe that we have biologic data as well as at least the potential epidemiology coming out of England to suggest that this is a new disease and on that basis should be handled with a lot more caution, because we don't have the comfort that we have with the long-standing classical CJD. And so I'm going to vote yes.

CHAIRMAN BROWN: Dr. Ewenstein votes yes. Dr. Detwiler?

ORY COMMITTEE MEETING Thursday, June 3, 1999???????http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3518t2.rtf DR.

DETWILER: I'm going to vote yes, because with these diseases, a long incubation and the lack of a pre-clinical screening test, that the day you find out there is transmission you're already years too late, and you can't easily clean up the problem. And I think they found out that even with the human transmission because that was based on there is no theoretical ?? or it's only a theoretical risk until 1996.

CHAIRMAN BROWN: Dr. Detwiler votes yes. Dr. Piccardo?

DR. PICCARDO: I would vote yes because all of the data from classical CJD cannot be extrapolated into the new variant.

CHAIRMAN BROWN: Dr. Piccardo votes yes. Dr. Williams?

DR. WILLIAMS: I'm going to vote no. I think that this is truly a balancing act, and it's a tradeoff between a known problem, I believe related to the blood supply, and the problems that may follow from a reduced supply and the perception of a risk of new variant CJD.

And I completely agree that an experiment is going on right now. Those data are going to come in, and, obviously, there is going to be close attention paid to those data, and that surely this committee and FDA will respond should information indicate that we need to take another look at the issue.

CHAIRMAN BROWN: Dr. Williams votes no. Dr. Hollinger?

DR. HOLLINGER: I'm voting no also, for the same reasons that have been addressed. I think there is ?? by doing something now doesn't mean that everything is going to be turned around and you don't have to worry about it, if you do have a long incubation situation and one can wait to see if there is some risk down the line, and I think we do have those things going on ?? natural and experimental ?? in England. So I'm voting no. CHAIRMAN BROWN: Dr. Hollinger votes no. Ms. Harrell?

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Case Report of V MS. HARRELL: Okay. Sitting next to my ex-learned colleague ?? (Laughter.)

MS. HARRELL: Okay. I'm voting to be prudent, and I think that this will buy us time to get the data in and have it analyzed from the UK. But right now, we don't have time, and so I vote yes.

CHAIRMAN BROWN: Ms. Harrell votes yes. Dr. Cliver?

DR. CLIVER: No.

CHAIRMAN BROWN: Dr. Cliver votes no. Dr. Burke?

DR. BURKE: This is a balancing act, and I can ?? there are measurable negatives here. In the face of a theoretical, I vote no.

CHAIRMAN BROWN: Dr. Burke votes no. Dr. Tramont?

DR. TRAMONT: I vote yes.

CHAIRMAN BROWN: Dr. Tramont votes yes. Twelve yes. Nine no. Well, at the least, Dr. Epstein can come away from the day with the understanding that he has not been given a mandate. (Laughter.)

DR. FREAS: Can I just make a comment? I did verify the count. There are 21 voting people at the table. Dr. Roos is a non-voting participant. And the total does add up to 21.

Excuse me. I apologize. Dr. Rohwer is ??

CHAIRMAN BROWN: I don't have to ask Bob what he would have voted, had he been allowed to vote. (Laughter.)

CHAIRMAN BROWN: But I will if you'd like to put it on the record. This is simply a question to Bob, since he's at the table. Were his vote to be counted, what would it have been?

DR. ROHWER: I'll use this soapbox opportunity.

CHAIRMAN BROWN: Uh-oh. (Laughter.)

DR. ROHWER: I am very concerned that we may be facing the grave possibility of an epidemic of new variant CJD, an epidemic that, if it occurs, could be made much worse through the mechanism of interspecies transmission, such as would occur through blood products. But I recognize the real risks of insufficient supply.

However, I am impressed by Dr. Donnelly's warning that if the feed ban in the case of BSE had been delayed just one year, the epidemic would have been vastly worse than it was. And, therefore, I feel we should take whatever opportunities for implementing mitigating measures that we can that do not simultaneously jeopardize the supply unduly.

So I recognize that what we have ?? the opportunity we have here is very, very imperfect, but I feel like it is possible to do something, and we should do it.

CHAIRMAN BROWN: Jay, you wanted a recount, or just a reexpression? DR. EPSTEIN: Just a reexpression.

CHAIRMAN BROWN: Okay. The vote on question 1A is 12 votes yes, nine votes no. Therefore, the committee is obliged now to consider what deferral criteria might be recommended. And presumably, based on the evidence, the only deferral criteria that are offered us that make any sense are duration of residence in the UK.

snip...258

Dr. Scott

skip

In addition, we do know, as Dr. Prusiner has pointed out several times, that the new variant agent is biologically different from the classical CJD agent, so we can't necessarily extrapolate all of the information that we have on classical CJD to new variant.

For example, he talked about the differences in the protein and its behavior, and we also know that there is enhanced expression of the new variant agent in lymphoid tissues compared with CJD. And we don't know much about its virulence or infectivity compared with the classical CJD. And, of course, we haven't had time to get or enough patients or subjects or transfused people to get the kind of epidemiologic data that we have which tells us that transmission of classical CJD by blood or blood products at worst is rare and may not occur.

So, currently, the diagnosis of new variant CJD is based upon neuropathology, and these are the three most characteristic features ?? numerous widespread kuru type amyloid plaques, which obviously can occur in a few other kinds of CJD but are quite common in new variant CJD; spongiform change, which is predominant in certain areas of the brain; and a high density prion protein accumulation, especially the cerebrum and the cerebellum by immunohistochemistry, and tonsillar biopsy may ultimately play a role in this diagnosis as well as analysis of prion glycoforms.

Current age, if alive, or age at death, less than 55. Since the typical age of a new variant patient is about late 20s, and the typical age of a classical CJD patient is about 65, this is one criteria that is useful. And new variant patients tend to have persistent painful sensory symptoms early in presentation and/or psychiatric symptoms.

I can go into this further if people want to know about it. But there were a couple of articles published in the Lancet from the CJD surveillance unit in September 1997, which goes into this in great detail.

In addition, the patient must have dementia and a delayed development of neurologic symptoms, particularly movement disorders, about a four-month delay. And, again, this is somewhat different from classical CJD in its course. They may have a normal or abnormal EEG, but not the diagnostic EEG, which is a pseudo periodic sharp wave that's often seen in classical CJD. The duration of illness should be greater than six months. Again, this is in marked distinction to most cases of classical CJD which average four to four and a half months of duration. Whereas, the new variant case typically is around 14 months duration, although there is a spread.

In addition, routine investigations will not suggest an alternate diagnosis. And this is a criteria, really, for the U.S. There should be history of possible exposure to BSE; that is, consumption of local beef products as resident or traveler to a BSE-affected country.

And there is only two more. No history of iatrogenic exposures that are related to development of classical CJD, and, finally, of course, such a patient, if they had a prion protein gene mutation, it was associated with familiar CJD. That would not fall under ?? that would not be a patient that we would worry about new variant CJD in.

page...284

DR. ROOS: Thanks, Dr. Scott. So we're not asked to take a vote, but just to discuss these issues. Yes?

DR. NELSON: I'm concerned a little bit about the explanation for the age criteria, and I can see that this is very useful because the one thing you do know, when somebody gets sick, you can estimate what their age is. And so that's an easy ?? you know, an easy early marker for a possible case that's not classical.

And I assume that probably the reason for the classical CJD patients being much older is that the incubation period is so long that they probably had an exposure much longer. But as this epidemic ?? or as the ?? if it's exposure to the BSE agent from the epidemic, it seems like over time this age criteria will probably change, and that the under 55 may no longer be a useful criteria 10 years from now or 40 years from now.

And I just wonder if Larry or anybody could comment on that.

DR. SCHONBERGER: We definitely agree, and it underscores the evolving nature of these diagnoses. All I can say is the age is an excellent and easy criteria for us to use now. All cases, as you know, in the world of new variant CJD have been under age 55. In fact, I think the oldest was ?? I think the median age is like 29 or so, 28 at onset and 29 at death. So that's why that particular criteria came into existence.

However, obviously, if the epidemic should change and we should start seeing older cases, then, obviously, we would have to change.

There is some semantic problems. We actually investigate every case under 55. So, in a sense, all cases under 55 in the United States could be regarded as under investigation or possible. We have not used the word "probable," in part because that's the word they use in the United Kingdom, and they count those cases as amongst the cases of new variant CJD that we count.

The 40 cases in the UK, I think, includes one, is it? One probable? That was a case in a teenager whose brain tissue was unavailable for study. And they indicate that it's too early in the epidemic. Their experience is too small for them to be absolutely sure about that, but they're willing to ?? at this point to call it a case.

And I've been told that with these new MRI criteria, and so on, that maybe we'll be able to call cases without necessarily having the tissue, depending on what they find the specificity and sensitivity of those to be. So all cases essentially under 55 right now are under investigation.

Plus, we have established amongst pathologists the concept that any case that has the pathology of new variant CJD, regardless of age, or even regardless of whether they've diagnosed it as CJD, should be reported. And those two would count as new variant even though they are not under 55. DR. ROOS: Just a quick question, Larry. What is your timeframe of reporting, or what is the goal here? Obviously, with respect to these new guidelines, you want to identify these cases fairly quickly and make some disposition as far as blood products.

DR. SCHONBERGER: Precisely because we are looking at all cases under 55, I was encouraging FDA to encourage the blood establishments ?? or the first to identify these cases at least, and that has been the history ?? to report to us any case of CJD under 55.

Once we get that report, it may be very easy for us and very quickly making it ?? to very quickly make a determination that we're dealing with, say, a dura mater case or a human growth hormone case. But then, another part of FDA will probably become interested in that.

So we think it's worth the blood establishments reporting all of their cases in donors. There just are not that many CJD cases that are going to occur among donors that the blood establishment is going to be able to identify that quickly. But if they do, we want it reported right away. DR. ROOS: Just a quick question. So, I mean, how about if this patient donates to some large blood pool or has donated whole blood? It doesn't go back to the blood establishment. It goes to a neurologist, gets diagnosed, etcetera. What's the timeframe then?

DR. SCHONBERGER: Well, frequently, our experience with the withdrawals ?? and I'll use the Utah case as an example as that came out ?? we handled that very, very rapidly. But even handling it very, very rapidly, you'll find that huge, huge numbers of recipients were exposed to this donor's blood products.

So the withdrawal program is relatively inefficient, compared to what we just did, which was to get deferral criteria. And I think that's why it was important to try to be preemptive in a sense and have the deferral criteria up front.

The withdrawal procedure, even when you do it very quickly as in the Utah case, I would not encourage people to depend on that for considerable safety. What we will do is we will modify and ameliorate the situation. But it certainly won't eliminate even the majority of the risk.

DR. ROOS: I just think it might be good to publicize these new policies widely to the neurological community, so that they alert you, Larry, or the FDA quickly. The Utah case, in fact, was kind of a very aberrant case. It could be that there are other cases that get less sophisticated care. And if you really want to identify things in a timely manner, you obviously have to publicize the program and new policies to the neurological community. DR. SCHONBERGER: Well, let me clarify that the primary group doing the surveillance on this are blood establishments. And if this group wants to recommend that blood establishments, you know, provide blood donors with cards or something that would, you know, speed up any type of reporting, that's possible.

The surveillance that CDC is conducting is not designed for that type of rapid turnaround or rapid identification in reporting. That's another weakness of the system and relying on this withdrawal system for tremendous protection of the population.

DR. ROOS: Peter?

DR. LURIE: My question/concern is whether or not requiring all nine of these criteria is too restrictive a set of criterion. I guess the data question that I have is: of the 30-odd new variant CJD cases in Britain, how many of them have met all nine of these criteria?

DR. SCOTT: Well, could I also respond to that question?

DR. LURIE: Yes, please do.

DR. SCOTT; I don't know the answer to how many have had all nine of those criteria, but most. However, the CJD surveillance unit has somewhat altered their criteria with time such that the current organization is similar to this but not the same. And most critically, they have gotten rid of the age criteria and added an MRI criteria. But this is not yet published material, and it's very recent. We just got that information on May 31st. And I think the other thing to mention is that we weren't considering only using all nine criteria. But, really, that's the purpose of the third way, if I can say it, which is to have a very low threshold for identifying even potential cases and then to make a rapid decision on a case-by-case basis. But what we're anticipating is probably what you're thinking, that not all of those criteria are going to be met, just due to a lack of information, time hasn't passed, we don't have material to analyze. And so I think what we're anticipating is that we would be ?? we would err on the side of caution unless investigation showed us that it was most unlikely that this was a new variant case.

snip...page 292

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

DR. SCHONBERGER: They're not all donors, by the way. Very few of them are donors. Okay?

DR. HUESTON: Okay. Fair enough. But once you get a terminology like this established, my concern is that it's going to spread further, that people are going to say, "Well, the FDA would have called this a possible case." Number 2 says, "Has a physician's clinical or pathologic diagnosis," it doesn't say anything about the physician. And no offense to my distinguished colleagues, but there are a number of physicians that are simply not in the position to make a clinical diagnosis or a pathologic diagnosis of Creutzfeldt Jakob. That has not precluded some of these same physicians from making a proclamation.

Third, I think that the public health and the risk communication implications of this are potentially massive. And having been on the firing ?? you know, on the other end of trying to deal with these, you know, the press grabbing hold of a case and blowing it totally out of proportion and creating a great deal of concern, I don't see why you need another term. I think you coordinate with the CDC, you coordinate your investigation when it comes back from a blood collection center that you have a donor less than 55 years of age, where you have some suspicion of Creutzfeldt Jakob Disease. You go through the same CDC workup, and you base ?? on a case-by-case basis, you base your decision on that coordination with CDC.

snip...page 296

see full text and all voting results

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

TSEAC MEETING JUNE 3 1999

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

http://transmissiblespongiformencephalopathy.blogspot.com/

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript Posted: 3/2/2011

2011-03-02T19:45:00.000-08:00

Posted: 3/2/2011

October 28, 2010

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript Posted: 3/2/2011

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm244061.htm

October 29, 2010

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Transcript Posted: 3/2/2011

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm244062.htm

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html

Monday, February 7, 2011

FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

http://tseac.blogspot.com/2011/02/fdas-currently-recommended-policies-to.html

Sunday, May 10, 2009

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

TO : william.freas@fda.hhs.gov

May 8, 2009

Greetings again Dr. Freas, TSEAC et al,

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

IN reply to ;

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

Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 INTRODUCTION The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp).

Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary. This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf

From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION

snip...

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

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

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

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

snip... 48 pages...

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

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

Tuesday, February 8, 2011

U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001

http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html

Thursday, February 24, 2011

The risk of variant Creutzfeldt-Jakob disease among UK patients with bleeding disorders, known to have received potentially contaminated plasma products

http://vcjdtransfusion.blogspot.com/2011/02/risk-of-variant-creutzfeldt-jakob.html

Friday, February 11, 2011

Creutzfeldt-Jakob disease (CJD) biannual update (2010/1) Emerging infections/CJD

http://creutzfeldt-jakob-disease.blogspot.com/2011/02/creutzfeldt-jakob-disease-cjd-biannual.html

Saturday, January 29, 2011

Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to Cynomolgus Macaques, a Non-Human Primate

Jpn. J. Infect. Dis., 64 (1), 81-84, 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/atypical-l-type-bovine-spongiform.html

Wednesday, December 29, 2010

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PRION END OF YEAR REPORT DECEMBER 29, 2010

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/transmissible-spongiform-encephalopathy.html

Thursday, February 10, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31

http://madcowtesting.blogspot.com/2011/02/transmissible-spongiform-encephalopathy.html

Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011

Prions

David W. Colby1,* and Stanley B. Prusiner1,2

http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html

TSS

U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001

2011-02-08T12:14:00.000-08:00

Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001

Date: Tue, 9 Jan 2001 16:49:00 -0800

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de

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

Greetings List Members,

I was lucky enough to sit in on this BSE conference call today and even managed to ask a question. that is when the trouble started.

I submitted a version of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so.

"They tell me it is a closed meeting and they will release whatever information they deem fit. Rather infuriating."

and i would have been doing just fine, until i asked my question. i was surprised my time to ask a question so quick.

(understand, these are taken from my notes for now. the spelling of names and such could be off.)

[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.

[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]

[host Richard] could you repeat the question?

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

[not sure whom ask this] what group are you with?

[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.

[not sure who is speaking] could you please disconnect Mr. Singeltary

[TSS] you are not going to answer my question?

[not sure whom speaking] NO

from this point, i was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;

[unknown woman] what group are you with?

[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?

at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference.

IF i were another Country, I would take heed to my notes, BUT PLEASE do not depend on them. ask for transcript from;

RBARNS@ORA.FDA.GOV 301-827-6906

he would be glad to give you one ;-)

Rockville Maryland, Richard Barns Host

BSE issues in the U.S., How they were labelling ruminant feed? Revising issues.

The conference opened up with the explaining of the U.K. BSE epidemic winding down with about 30 cases a week.

although new cases in other countries were now appearing.

Look at Germany whom said NO BSE and now have BSE.

BSE increasing across Europe.

Because of Temporary Ban on certain rendered product, heightened interest in U.S.

A recent statement in Washington Post, said the New Administration (old GW) has a list of issues. BSE is one of the issues.

BSE Risk is still low, minimal in U.S. with a greater interest in MBM not to enter U.S.

HOWEVER, if BSE were to enter the U.S. it would be economically disastrous to the render, feed, cattle, industries, and for human health.

(human health-they just threw that in cause i was listening. I will now jot down some figures in which they told you, 'no need to write them down'. just hope i have them correct. hmmm, maybe i hope i don't ???)

80% inspection of rendering

*Problem-Complete coverage of rendering HAS NOT occurred.

sizeable number of 1st time FAILED INITIAL INSPECTION, have not been reinspected (70% to 80%).

Compliance critical, Compliance poor in U.K. and other European Firms.

Gloria Dunason Major Assignment 1998 goal TOTAL compliance. This _did not_ occur. Mixed level of compliance, depending on firm.

Rendering FDA license and NON FDA license

system in place for home rendering & feed 76% in compliance 79% cross contamination 21% DID NOT have system 92% record keeping less than 60% total compliance

279 inspectors 185 handling prohibited materials

Renderer at top of pyramid, significant part of compliance. 84% compliance

failed to have caution statement render 72% compliance & cross contamination caution statement on feed, 'DO NOT FEED TO CATTLE'

56 FIRMS NEVER INSPECTED

1240 FDA license feed mills 846 inspected

"close to 400 feed mills have not been inspected"

80% compliance for feed.

10% don't have system.

NON-FDA licensed mills There is NO inventory on non licensed mills. approximately 6000 to 8000 Firms ??? 4,344 ever inspected. "FDA does not have a lot of experience with"

40% do NOT have caution statement 'DO NOT FEED'.

74% Commingling compliance

"This industry needs a lot of work and only half gotten to"

"700 Firms that were falitive, and need to be re-inspected, in addition to the 8,000 Firms."

Quote to do BSE inspection in 19 states by end of January or 30 days, and other states 60 days. to change feed status??? Contract check and ask questions and pass info.

At this time, we will take questions.

[I was about the third or fourth to ask question. then all B.S.eee broke loose, and i lost my train of thought for a few minutes. picked back up here]

someone asking about nutritional supplements and sourcing, did not get name. something about inspectors not knowing of BSE risk??? the conference person assuring that Steve Follum? and the TSE advisory Committee were handling that.

Some other Dr. Vet, whom were asking questions that did not know what to do???

[Dennis Wilson] California Food Agr. Imports, are they looking at imports?

[Conference person] they are looking at imports, FDA issued imports Bulletin.

[Linda Singeltary ??? this was a another phone in question, not related i don't think] Why do we have non-licensed facilities?

(conference person) other feed mills do not handle as potent drugs???

Dennis Blank, Ken Jackson licensed 400 non FDA 4400 inspected of a total of 6000 to 8000,

(they really don't know how many non licensed Firms in U.S. they guess 6000 to 8000??? TSS)

Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not'

Warren-Maryland Dept. Agr. Prudent to re-inspect after 3 years. concerned of Firms that have changed owners.

THE END

TSS

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

FROM New York TIMES

Subject: Re: BSE 50 STATE CONFERENCE CALL thread from BSE List and FDA Posting of cut version...

Date: Thu, 11 Jan 2001 22:02:47 -0700

From: "Sandy Blakeslee"

To: "Terry S. Singeltary Sr." References: 1

Hi terry -- thanks for all your help. I know it made a difference with the FDA getting out that release.

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

From: "Terry S. Singeltary Sr."

To: Sent: Thursday, January 11, 2001 2:06 PM

Subject: BSE 50 STATE CONFERENCE CALL thread from BSE List and FDA Posting of cut version...

hi sandy,

From the New York Times NYTimes.com, January 11, 2001

Many Makers of Feed Fail to Heed Rules on Mad Cow Disease By SANDRA BLAKESLEE

Large numbers of companies involved in manufacturing animal feed are not complying with regulations meant to prevent the emergence and spread of mad cow disease in the United States, the Food and Drug Administration said yesterday.

The widespread failure of companies to follow the regulations, adopted in August 1997, does not mean that the American food supply is unsafe, Dr. Stephen Sundlof, director of the Center for Veterinary Medicine at the F.D.A., said in an interview.

But much more needs to be done to ensure that mad cow disease does not arise in this country, Dr. Sundlof said.

The regulations state that feed manufacturers and companies that render slaughtered animals into useful products generally may not feed mammals to cud-chewing animals, or ruminants, which can carry mad cow disease.

All products that contain rendered cattle or sheep must have a label that says, "Do not feed to ruminants," Dr. Sundlof said. Manufacturers must also have a system to prevent ruminant products from being commingled with other rendered material like that from chicken, fish or pork. Finally, all companies must keep records of where their products originated and where they were sold.

Under the regulations, F.D.A. district offices and state veterinary offices were required to inspect all rendering plants and feed mills to make sure companies complied. But results issued yesterday demonstrate that more than three years later, different segments of the feed industry show varying levels of compliance.

Among 180 large companies that render cattle and another ruminant, sheep, nearly a quarter were not properly labeling their products and did not have a system to prevent commingling, the F.D.A. said. And among 347 F.D.A.-licensed feed mills that handle ruminant materials - these tend to be large operators that mix drugs into their products - 20 percent were not using labels with the required caution statement, and 25 percent did not have a system to prevent commingling.

Then there are some 6,000 to 8,000 feed mills so small they do not require F.D.A. licenses. They are nonetheless subject to the regulations, and of 1,593 small feed producers that handle ruminant material and have been inspected, 40 percent were not using approved labels and 25 percent had no system in place to prevent commingling.

On the other hand, fewer than 10 percent of companies, big and small, were failing to comply with the record-keeping regulations.

The American Feed Industry Association in Arlington, Va., did not return phone calls seeking comment.

http://www.nytimes.com/2001/01/11/science/11COW.html

Subject: USDA/APHIS response to BSE-L--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001

Date: Wed, 10 Jan 2001 14:04:21 -0500

From: "Gomez, Thomas M."

Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

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

USDA/APHIS would like to provide clarification on the following point from Mr. Singeltary's 9 Jan posting regarding the 50 state conference call.

[Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not']

Dr. Detwiler was responding to an announcement made during the call to use the FDA emergency number if anyone wanted to report a cow with signs suspect for BSE. Mr. Singeltary is correct that Dr. Detwiler asked participants to use the FDA emergency number as a last resort to report cattle suspect for BSE. What Mr. Singeltary failed to do was provide the List with Dr. Detwiler's entire statement. Surveillance for BSE in the United States is a cooperative effort between states, producers, private veterinarians, veterinary hospitals and the USDA. The system has been in place for over 10 years. Each state has a system in place wherein cases are reported to either the State Veterinarian, the federal Veterinarian in Charge or through the veterinary diagnostic laboratory system. The states also have provisions with emergency numbers. Dr. Detwiler asked participants to use the systems currently in place to avoid the possibility of a BSE-suspect report falling through the cracks. Use of the FDA emergency number has not been established as a means to report diseased cattle of any nature.

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

Subject: Re: USDA/APHIS response to BSE-L--U.S. 50 STATE CONFERENCE CALL Jan.9, 2001

Date: Wed, 10 Jan 2001 13:44:49 -0800

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de References: 1

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

Hello Mr. Thomas,

> What Mr. Singeltary failed to do was provide the List with Dr. Detwiler's entire statement.

would you and the USDA/APHIS be so kind as to supply this list with a full text version of the conference call and or post on your web-site? if so when, and thank you. if not, why not?

The system has been in place for over 10 years.

that seems to be a very long time for a system to be in place, and only test 10,700 cattle from some 1.5 BILLION head (including calf crop). Especially since French are testing some 20,000 weekly and the E.U. as a whole, are testing many many more than the U.S., with less cattle, same risk of BSE/TSEs.

Why does the U.S. insist on not doing massive testing with the tests which the E.U. are using? Why is this, please explain?

Please tell me why my question was not answered?

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

It was a very simple question, a very important question, one that pertained to the topic of BSE/feed, and asked in a very diplomatic way. why was it not answered?

If all these years, we have been hearing that pharmaceutical grade bovines were raised for pharmaceuticals vaccines etc. But yet the USA cannot comply with feed regulations of the ruminant feed ban, PLUS cannot even comply with the proper labelling of the feed, cross contamination etc. Then how in the world can you Guarantee the feed fed to pharmaceutical grade bovine, were actually non ruminant feed?

Before i was ask to be 'disconnected', i did hear someone in the background say 'we can't'-- have him ask the question again.

could you please be so kind, as to answer these questions?

thank you, Terry S. Singeltary Sr. Bacliff, Texas USA

P.S. if you will also notice, i did not post that emergency phone number and do not intend on passing it on to anyone. I was joking when i said i should call and report the whole damn U.S. Herd. So please pass that on to Dr. Detwiler, so she can rest easily.

BUT, they should be reported, some are infected with TSE. The U.S. is just acting as stupid as Germany and other Countries that insist they are free of BSE.

TSS

Subject: Report on the assessment of the Georgraphical BSE-risk of the USA July 2000 (not good)

Date: Wed, 17 Jan 2001 21:23:51 -0800

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de

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

Greetings List Members and ALL EU Countries,

Because of this report, and the recent findings of the 50-state BSE Conference call, I respectfully seriously suggest that these Countries and the SSC re-evaluate the U.S.A. G.B.R. to a risk factor of #3.

I attempted to post this to list in full text, but would not accept...

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

Report on the assessment of the Geographical BSE-risk of the USA July 2000

PART II

REPORT ON THE ASSESSMENT OF THE GEOGRAPHICAL BSE RISK OF THE UNITED STATES OF AMERICA

- 29 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

EXECUTIVE SUMMARY

OVERALL ASSESSMENT

The current geographical BSE-risk (GBR) level is II, i.e. it is unlikely but cannot be excluded that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent.

Stability: Before 1990 the system was extremely unstable because feeding of MBM to cattle happened, rendering was inappropriate with regard to deactivation of the BSE-agent and SRM and fallen stock were rendered for feed. From 1990 to 1997 it improved to very unstable, thanks to efforts undertaken to trace imported animals and exclude them from the feed chain and intensive surveillance. In 1998 the system became neutrally stable after the RMBM-ban of 1997.

External challenges: A moderate external challenge occurred in the period before 1990 because of importation of live animals from BSE-affected countries, in particular from the UK and Ireland. It cannot be excluded that some BSE-infected animals have been imported by this route and did enter the US rendering and feed production system. The efforts undertaken since 1990 to trace back UK-imported cattle and to exclude them from the feed chain reduced the impact of the external challenge significantly.

Interaction of external challenges and stability: While extremely unstable, the US system was exposed to a moderate external challenge, mainly resulting from cattle imports from the UK. It can not be excluded that BSE-infectivity entered the country by this route and has been recycled to domestic cattle. The resulting domestic cases would have been processed while the system was still very unstable or unstable and would hence have initiated a number of second or third generation cases. However, the level of the possible domestic prevalence must be below the low detection level of the surveillance in place.

As long as there are no changes in stability or challenge the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent will remain at the current level.

JUSTIFICATION

1. DATA

The available information was suitable to carry out the GBR risk assessment.

- 30 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

2. STABILITY

2.1 Overall appreciation of the ability to identify BSE-cases and to eliminate animals at risk of being infected before they are processed

· Before 1989, the ability of the system to identify (and eliminate) BSE cases was limited. · Since 1990 this ability is significantly improved, thanks to a good BSE-surveillance and culling system (contingency plan). · Today the surveillance should be able to detect clinical BSE-cases within the limits set by an essential passive surveillance system, i.e. some cases might remain undetected.

2.2 Overall appreciation of the ability to avoid recycling BSE-infectivity, should it enter processing

· Before 1997 the US rendering and feed producing system would not have been able to avoid recycling of the BSE agent to any measurable extent. If the BSE-agent was introduced the feed chain, it could probably have reached cattle. · After the introduction of the RMBM-to-ruminants-ban in August 1997 the ability of the system to avoid recycling of BSE-infectivity was somewhat increased. It is still rather low due to the rendering system of ruminant material (including SRM and fallen stock) and the persisting potential for cross-contamination of cattle feed with other feeds and hence RMBM.

2.3 Overall assessment of the Stability

· Until 1990 the US BSE/cattle system was extremely unstable as RMBM was commonly fed to cattle, the rendering system was not able to reduce BSE-infectivity and SRM were rendered. This means that incoming BSE infectivity would have been most probably recycled to cattle and amplified and the disease propagated. · Between 1990 and 1995 improvements in the BSE surveillance and the efforts to trace back and remove imported cattle gradually improved the stability but the system remained very unstable. In 1998 the system became unstable because of an RMBM-ban introduced in 1997. After 1998 the ban was fully implemented and the system is regarded to be neutrally stable since 1998. The US system is therefore seen to neither be able to amplify nor to reduce circulating or incoming BSE-infectivity.

3. CHALLENGES

A moderate external challenge occurred in the period 1980-1989 because of importation of live animals from the UK. imports from other countries are regarded to have been negligible challenges. · As a consequence of this external challenge, infectivity could have entered the feed cycle and domestic animals could have been exposed to the agent. These domestic BSE-incubating animals might have again entered processing, leading to an internal challenge since 1991. · This internal challenge could have produced domestic cases of BSE, yet prevalence levels could have been below the detection limits of the surveillance system until now. (According to US calculations, the current surveillance

-31 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

system could detect clinical incidence of 1-3 cases per year per million adult cattle, i.e. in absolute numbers 43-129 cases per year). Between 1990 und 1995, with the exclusion of the imported animals from Europe from the feed chain, the effect of the external challenges decreased.

4. CONCLUSION ON THE RESULTING RISKS

4.1 Interaction of stability and challenqe

· In the late 80s, early 90s a moderate external challenges met an extremely unstable system. This would have amplified the incoming BSE-infectivity and propagated the disease. · With the exclusion of the imported animals from Europe from the feed chain between 1990 and 1995 the effect of the external challenge decreased. · Before 1998 an internal challenge, if it developed, would have met a still unstable system (inappropriate rendering, no SRM ban, RMBM ban only after 1997) and the BSE-infectivity could have been recycled and amplified. · After 1998 the neutrally stable system could still recycle the BSE-agent but due to the RMBM-ban of 1997 the BSE-infectivity circulating in the system would probably not be amplified.

4.2 Risk that BSE-infectivity enters processing

· A very low processing risk developed in the late 80s when the UK-imports were slaughtered or died. It increased until 1990 because of the higher risk to be infected with BSE of cattle imported from the UK in 1988/89, as these animals could have been processed prior to the back-tracing of the UK-imports in 1990. · From 1990 to 1995 a combination of surviving non-traced UK imports and some domestic (pre-)clinical cases could have arrived at processing resulting in an assumed constant low but non-negligible processing risk. · After 1995 any processing risk relates to assumed domestic cases arriving at processing. · The fact that no domestic cases have been shown-up in the BSE-surveillance is reassuring - it indicates that BSE is in fact not present in the country at levels above the detection limits of the country's surveillance system. This detection level has been calculated according to US-experts to be between 1 & 3 clinical cases per million adult cattle per year.

Note: The high turnover in parts of the dairy cattle population with a young age at slaughter makes it unlikely that fully developed clinical cases would occur (and could be detected) or enter processing. However, the theoretical infective load of the pre-clinical BSE-cases that under this scenario could be processed, can be assumed to remain relatively low.

4.3 Risk that BSE-infectivity is recycled and propagated

· During the period covered by this assessment (1980-1999) the US-system was not able to prevent propagation of BSE should it have entered, even if this ability was significantly improved with the MBM-ban of 1997. · However, since the likelihood that BSE-infectivity entered the system is regarded to be small but non-negligible, the risk that propagation of the disease took place is also small but not negligible.

- 32 -

Report on the assessment of the Geographical BSE-risk of the USA July 2000

5. CONCLUSION ON THE GEOGRAPHICAL BSE-RISK

5.1 The current GBR

The current geographical BSE-risk (GBR) level is II, i.e. it is unlikely but cannot be excluded that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent.

5.2 The expected development of the GBR

As long as there are no changes in stability or challenge the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent remains at the current level.

5.3 Recommendations for influencin.q the future GBR

· As long as the stability of the US system is not significantly enbanced above neutral levels it remains critically important to avoid any new external challenges. · All measures that would improve the stability of the system, in particular with regard to its ability to avoid recycling of the BSE-agent should it be present in the cattle population, would reduce, over time, the probability that cattle could be infected with the BSE-agent. Possible actions include: removal of SRMs and/or fallen stock from rendering, better rendering processes, improved compliance with the MBM-ban including control and reduction of cross-contamination. · Results from an improved intensive surveillance programme, targeting at risk sub-populations such as adult cattle in fallen stock or in emergency slaughter, could verify the current assessment.

snip...

http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801f3413&disposition=attachment&contentType=msw8

The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.

http://www.oie.int/boutique/extrait/06heim937950.pdf

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

Saturday, January 29, 2011

Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to Cynomolgus Macaques, a Non-Human Primate

Jpn. J. Infect. Dis., 64 (1), 81-84, 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/atypical-l-type-bovine-spongiform.html

Tuesday, January 25, 2011

Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions

http://chronic-wasting-disease.blogspot.com/2011/01/generation-of-new-form-of-human-prpsc.html

Friday, February 04, 2011

NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

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

From: Terry S. Singeltary Sr.

To: President.BenShelly

Cc: sroanhorse ; opvp.nelson ; alaughing; georgehardeen; pressoffice

Sent: Thursday, February 03, 2011 12:15 PM

Subject: NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

Greetings Honorable People of the Great Navajo Nation, and the Honorable President Ben Shelly,

I send this to you with great concern. ...

BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf

PLEASE SEE FULL TEXT PLUS TRANSMISSION STUDIES ;

http://scrapie-usa.blogspot.com/2011/02/nmlb-and-usda-allow-scrapie-prion.html

Saturday, December 18, 2010

OIE Global Conference on Wildlife Animal Health and Biodiversity - Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/oie-global-conference-on-wildlife.html

Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html

http://bseusa.blogspot.com/2010/04/usda-and-oie-out-of-touch-with-risk.html

Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html

tss

FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

2011-02-07T10:00:00.000-08:00

FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

Informational Issue Summary

FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products

Transmissible Spongiform Encephalopathies Advisory Committee 22nd Meeting October 28-29, 2010

Gaithersburg, Maryland

2

Background

Beginning in 1978, results of experimental studies repeatedly demonstrated that the infectious agents causing the transmissible spongiform encephalopathies (TSE agents or prions) are often found in the blood of infected animals, both during the incubation period and throughout overt illness. Since 1983, the FDA, issuing a series of guidances, has periodically recommended to the blood industry steps intended to reduce the theoretical risk of transmitting the infectious agents of the transmissible spongiform encephalopathies (TSEs) causing Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) by blood and blood products. The risk of transmitting most forms of CJD by transfusions of blood components and injection of plasma derivatives, remains theoretical (see Appendices I and II), however, limited but convincing evidence strongly implicates transfusions with a blood component and injections of a human plasma-derived coagulation factor in iatrogenic transmissions of vCJD in the United Kingdom (UK). The history of FDA’s policies and of the science that informed the FDA in this area is summarized in Appendices I and II, with current FDA guidance in tabular form in Appendices V and VI. (Appendices III and IV summarize certain legislation implemented in the European Union and USDA regulations relevant to FDA blood safety policies.)

In principle, when possible, several approaches are taken to reduce the risk of transmitting infectious diseases from a blood or plasma donor to a recipient:

___________________________________________________________________________

Five “tiers” of safety for blood and components as related to CJD and vCJD (modified from Keeping Blood Transfusions Safe: FDA's Multi-layered Protections for Donated Blood. US FDA Publication No. FS 02-1, February 2002

http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/BloodSafety/ucm095522.htm

accessed October 2010)

___________________________________________________________________________

1. Donor screening [questionnaires]: selection of blood and plasma donors based on deferrals for medical, geographical and behavioral risk factors; deferral registries to avoid collection and use of units from identified “unsuitable” donors

2. Laboratory testing of donor blood samples for markers of blood-transmissible diseases (infectious agents)

3. Donor Deferral Registries: an additional control to avoid collecting blood or releasing blood from donors deferred as unsuitable

4. Quarantine: Donor blood [and plasma] quarantined until testing results available

5. Problems and deficiencies: manufacturing problems investigated, deficiencies corrected, FDA notified of deviations

___________________________________________________________________________

1, 3 and 5 are currently applicable to TSEs; laboratory testing (2 and 4) is not yet available for TSEs. In addition to protections listed, pathogen reduction techniques are currently under study for both conventional pathogens and TSE agents but are not yet validated, approved or available.

___________________________________________________________________________

Because no validated screening tests identify TSE-agent-infected blood and there are no US-approved devices to remove TSE infectivity from blood and blood components, CJD and vCJD safety must continue to rely on precautionary deferrals of donors at increased risk for CJD and for vCJD and withdrawal of in-date components when post-donation

3

information reveals that a donor should have been deferred; and, additionally for vCJD, withdrawal of plasma derivatives if and when a donor is found to have vCJD or possible vCJD. The FDA continues to encourage the development of donor screening tests and devices to remove the infectious agents of TSEs from blood (see below). The FDA, aware of the uncertainties surrounding the magnitude of the risk, the effectiveness of available risk-reducing measures, and the potential for contributing to shortages of life-sustaining blood products, has continued to review at frequent intervals its policies regarding CJD and vCJD. In particular, FDA blood safety policies regarding CJD and vCJD have periodically been reviewed publicly with the TSEAC, especially when new information suggested that risks should be reevaluated. In the appendices we provide additional current relevant information on risks of transfusion-transmitted and plasma-derivative-transmitted vCJD.

______________________________________________________________________________________

General approaches of FDA policies to reduce risk of transmitting CJD and vCJD by blood products

______________________________________________________________________________________ ?

Reduce risk that a donor was exposed to the agent of bovine spongiform encephalopathy (BSE)

Dietary exposure “geographic” risk-adjusted deferrals: defer some donors who resided in some BSE countries (or were potentially exposed on military bases that imported beef from UK)

Other exposure: defer donors who injected UK bovine insulin

Reduce risk that donor was exposed to vCJD agent of human origin

Defer donors with a history of transfusion in UK after 1980

Defer donors with a history of transfusion in France after 1980

Other steps were discussed at TSEAC meetings, but FDA was not advised to consider: history of transfusion in other BSE country besides UK and France after 1980; history of surgery in high-risk BSE countries after 1980 (suggested by one TSEAC member)

______________________________________________________________________________________

There have been six general bases for FDA’s recommended CJD/vCJD-related deferrals since 1983:

A. General CJD risk reduction. (1) CJD in a donor, (2) history of treatment with human cadaveric pituitary growth hormone or a dura mater allograft, and (3) history of CJD in a relative unless confirmed to be other than familial CJD or the donor PRNP genotype is found to be normal

B. vCJD risk reduction. (4) history of prolonged residence in most BSE countries (defined by USDA list of BSE-related import restrictions at 9 ) currently including UK, France or other European countries west of the Former Soviet Union (or residence/employment on a US military base in Europe during periods when beef was procured from UK), (5) history of transfusion in UK, or—more recently—history of transfusion in France, in or after 1980, and (6) injection with bovine insulin of UK origin in or after 1980

The most recent FDA CJD/vCJD-related donor deferral policies and the history of those are explained in full in FDA guidance issued on May 10, 2010

(http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf),

including minor modifications of the guidance of January 12, 2002. The following is a reduced summary of the essential features of the policy:

______________________________________________________________________________________

4

Summary of Current FDA CJD/vCJD-related Recommendations for Deferral of Blood Donors and Plasma Donors (see FDA guidance document issued May 10, 2010 at

http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf)

______________________________________________________________________________________

Indefinitely defer all donors of Whole Blood and Source Plasma who

have any form of CJD or are at increased risk of CJD (received dura mater allograft, were injected with human cadaveric pituitary growth hormone, have a relative with CJD unless familial CJD has been ruled out

spent 3 mo in UK from Jan 1, 1980 to Dec 31, 1996, or

who ever had blood transfusion in UK or in France from 1980 to present, or

who ever injected UK bovine insulin prepared in or after 1980, or

spent 5 yr in France from Jan 1, 1980 to the present

spent 6 mo on US military bases from Jan 1, 1980 to end of 1990 north of Alps or end of 1996 south of Alps Indefinitely defer all donors of Whole Blood but not donors of Source Plasma who

spent 5 yr in Europe from Jan 1, 1980 to the present (including time in spent in UK 1980-1996 and France 1980-present) Exempt from deferrals are

Donors of Source Plasma who spent time of any duration in Europe except UK and France

Donors of plasma/serum to manufacture FDA-approved non-injectable products (appropriately labeled per guidance of May 10, 2010)

______________________________________________________________________________________

The FDA-recommended CJD/vCJD-related blood safety policies are intended to reduce the risk that a blood or plasma donor might be incubating CJD of any kind while not deferring so many donors as to compromise the supply of blood products. The FDA’s assessment in advance of the January 2002 guidance estimated that the recommended deferral policy would reduce donor risk of dietary exposure to BSE agent by approximately 90% while deferring some 7% of otherwise suitable blood donors. The 2010 guidance—adding a deferral of donors transfused in France from 1980 to the present, as previously recommended for donors transfused in the UK—while reducing the risk of transfusion-transmitted vCJD by only a small amount, is expected to defer very few donors who would not have been previously deferred because they resided in France for five years or more.

As always, blood and plasma establishments may implement additional more stringent requirements. If they choose to do so, FDA encourages them to assess the possibility that such actions will contribute to shortages and to undertake preemptive donor recruitment efforts to prevent shortages. Recognition by FDA of USDA BSE-related import restrictions under 9 CFR 94.18 as a basis for FDA donor deferral policies. Since the FDA’s 1999 guidance, the FDA has acknowledged the USDA’s list of countries under restriction for the importation of live cattle and beef products into the US at 9 CFR 94.18 (“USDA BSE List” summarized in Appendix V) as a basis for identifying countries with increased risk of human food-

5

associated exposure to the BSE agent; most of the countries currently on the USDA BSE list are also listed on the current FDA donor deferral list (see Appendix IV), with three exceptions: the FDA has concluded that time spent in the UK after the end of 1996 should no longer pose an unacceptable risk of food-borne exposure to donors because of stringent food and animal feed controls implemented in the UK by that time; those measures were described at a TSEAC meeting

http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/UCM213415.pdf

Time spent in Israel (one case of BSE reported in 2001) and Japan (36 cases of BSE detected from 2001 through 2009) have not been taken as a reason to defer blood donors; FDA had no information to predict the number of otherwise suitable donors who would be deferred because of time spent in Israel or Japan, and FDA had concern that those numbers might be substantial in certain areas of the US.

Prospects for future modifications of FDA blood and plasma deferral policies to reduce the Possible Risk of Transmitting Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products

Prospects for donor screening tests. As mentioned above, the FDA recognizes the potential value of practical blood tests to detect and defer infected donors of blood and plasma during the asymptomatic incubation periods of vCJD and CJD. FDA continues to encourage the development and validation of such tests and has several times arranged for developers of candidate tests present interim progress reports of their investigations at open meetings of TSEAC and received advice from TSEAC regarding possible pathways leading to FDA licensure of validated donor screening tests

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t2.pdf

Effective testing would be a particularly attractive option for interdicting donors incubating forms of CJD other than vCJD, because no cases of transfusion-transmitted CJD or plasma-derivative-transmitted CJD have been detected in a lookback study (Dorsey, Zou et al. 2009), and many donors currently deferred because of risk factors for CJD might be re-entered if validated screening tests with high negative predictive values were not reactive. At the moment, no blood test has been validated as suitable for donor screening

http://biotuesday.ca/2010/05/31/amorfix-suspends-blood-testing-for-vcjd

Prospects for prion-protein and infectivity removal devices. Three TSE infectivity reduction devices, in development, have targeted the RBC component of Whole Blood. Two of the devices both deplete white blood cells (leukoreduction [LR]) and reduce the content of TSE agents in pilot studies. One of these devices is a modified LR filter containing several layers of prion-protein-removing material (Sowemimo-Coker, Demczyk et al. 2010. The second manufacturer is developing a combined LR and prion removal device (Miura M, Nirasawa H et al. in Abstracts of the AABB Meeting, 2006 SP221. Evaluation of a new combination filter for prion and leukoreduction (LR) of red cell concentrates (RCC), accessible at

http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2006.01023_1.x/pdf

The third filter is applied to leukoreduced RBC; the active component is a proprietary ligand claimed to adsorb both brain-derived and endogenous blood infectivity (Gregori, Gurgel et al. 2006). This filter was evaluated for safety and impact on component quality in the UK (Cahill, Murphy et al 2010; Wiltshire, Thomas et al. 2010). In April 2009 an independent UK Advisory Committee on Safety of Blood, Tissues and Organs (SaBTO recommended that “ …UK blood services … prepare to enable implementation of Prion filtration as soon as

6

practicable, should a final recommendation to do so be made.”

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_099922.pdf

and later, in October 2009, recommended, with reservations, that “… filtered red cells be provided to those born since 1 January 1996, subject to satisfactory completion of …[an ongoing]… clinical trial”

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_108860.pdf

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_112477.pdf

—presumably because the risk of food-borne exposure to the BSE agent should be considerably less in younger than for older UK residents, for whom the reduced risk offered by filtration might be more difficult to justify. No “prion filter” device has been licensed for use in the US. Representatives of the sponsors developing the three devices are to describe some of their findings at the FDA TSE Advisory Committee meeting on October 29, 2010

(http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm225805.htm).

Implementation of measures to reduce dietary risk of exposure to the BSE agent in countries other that the UK. As presented to the 21st meeting of TSEAC on June 12, 2009

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

the European Commission (EC) has promulgated legislation (EC Regulation 999, 2001) obligatory throughout the European Union (EU) requiring implementation of a number of BSE-risk-reducing steps (see Appendix IV) similar to those implemented earlier in the UK (Appendix IV). The FDA has, with some exceptions, based recommendations to defer blood and plasma donors at increased risk of BSE exposure on the USDA import restriction list at 9 CFR 94.18 to determine when those steps have been adequately and uniformly implemented in various countries.

International recognition of BSE status of countries and of the declining BSE epidemics. The EC Scientific Steering Committee, in January 2000, recommended grouping countries based on their geographical BSE risk (GBR)

http://ec.europa.eu/food/fs/sc/ssc/out68_en.pdf

Four groups were recognized:

GBR I: highly unlikely to have BSE;

GBR II: unlikely but not excluded;

GBR III: likely but not confirmed or confirmed at a low level; GBR IV: confirmed at a high level. That system for evaluating BSE risk was once widely used but is no longer supported.

The World Organisation for Animal Health (OIE) subsequently developed a system to evaluate national BSE risk based on voluntary submissions of information to an ad hoc committee for BSE status based on five main criteria used to assess the BSE risk for the cattle population of a country: risk assessment for BSE occurrence; on-going program to encourage reporting of neurological diseases in adult cattle; compulsory notification and investigation of all cattle showing BSE-like symptoms; BSE active surveillance; testing of cattle brain or other tissues. The OIE currently assigns to each country one of three BSE risk categories: negligible, controlled or undetermined (for those countries that either did not apply or failed to be classified). As of May 2010, 47 countries had been assigned a BSE risk status by the OIE: 13 countries (including three on the USDA BSE

7

Import Restriction List) had been assigned negligible BSE risk status, and 34 countries, including the US and Canada, were recognized as having controlled BSE risk—the same risk status assigned to most European countries including the UK and France (http://www.oie.int/eng/Status/BSE/en_BSE_free.htm). The FDA welcomes efforts to improve estimates of relative risk for exposure to the BSE agent in beef products of various national origins and to develop an international BSE risk evaluation system acceptable to US authorities and those of other countries. ...

snip...see full text ;

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM231179.pdf

When the OIE and the USDA et al collaborated to make legal the trading of Transmissible Spongiform Encephalopathy, when they did away with the BSE GBR risk assessments, where the USA, Canada, and Mexico were categorized as BSE GBR III.

please see ;

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

http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902594180.htm

Annex to the EFSA Scientific Report (2004) 3, 1-17 on the Assessment of the Geographical BSE Risk of USA

please see full text ;

http://www.efsa.europa.eu/en/scdocs/doc/3rax1.pdf

October 28-29, 2010:

Transmissible Spongiform Encephalopathies Advisory Committee Meeting References Document Posted: 10/26/2010

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm231016.htm

October 28-29, 2010:

Transmissible Spongiform Encephalopathies Advisory Committee Meeting A 2010 Update of the 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 (PDF - 662KB) Posted: 10/26/2010

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm231016.htm

October 28-29, 2010:

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Document: APPENDIX A Supplemental technical information for the FDA Risk Assessment (PDF - 307KB) Posted: 10/26/2010 Roster of the Transmissible Spongiform Encephalopathies Advisory Committee Updated: 10/22/2010

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM231019.pdf

Roster of the Transmissible Spongiform Encephalopathies Advisory Committee Updated: 10/22/2010

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm129556.htm

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

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

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html

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

From: Emery, Bryan (CBER)

To: CBER OCOD Consumer Account ; 'flounder9@verizon.net'

Sent: Friday, September 17, 2010 10:08 AM

Subject: FW: Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

Hi Terry,

Thank you for your comments related to the Transmissible Spongiform Encephalopathy's Advisory Committee meeting on October 28-29, 2010.

Your comments will be provided to the Committee.

Thanks

Bryan Emery

Subject: Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010

Contact Person: Bryan Emery or Rosanna Harvey, Center for Biologics Evaluation and Research (HFM-71), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0314, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512392.

http://edocket.access.gpo.gov/2010/2010-22805.htm

snip...end...full text ;

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html

Monday, October 18, 2010

TSEAC Transmissible Spongiform Encephalopathies Advisory Committee Draft Agenda and Meeting Materials, Posted: 10/18/2010

http://tseac.blogspot.com/2010/10/tseac-transmissible-spongiform.html

__._,_.___

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010

http://tseac.blogspot.com/2010/09/transmissible-spongiform.html

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

From: Emery, Bryan (CBER) To: 'Terry S. Singeltary Sr.'

Cc: Emery, Bryan (CBER)

Sent: Monday, January 24, 2011 7:35 AM

Subject: RE: October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee

Hi Terry,

The minutes have not been my primary focus at this time but when they are completed they will be put online for the public. I have nothing to hide just very busy as of late. Thank you for your interest, I hope to see you again soon.

Thanks LCDR Bryan Emery

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

From: Terry S. Singeltary Sr. [mailto:flounder9@verizon.net]

Sent: Wednesday, January 19, 2011 1:03 PM

To: Emery, Bryan (CBER)

Subject: October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee

re-October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee

Greetings Dr. Emery,

I am trying to locate the minutes or draft minutes of the October 28-29, 2010: Transmissible Spongiform Encephalopathies Advisory Committee meeting ???

seems they are long overdue to be put online.

can you please tell me when and if they are going to be made public ???

many thanks,

kindest regards, terry

Tuesday, January 18, 2011

Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.html

sadly, by only trying to reduce exposure from only nvCJD, they are seriously missing the bigger picture. hell, now we have mixtures of different phenotypes in one species, what about transmission of the TSE agent via mulitple phenotypes from one donor ??? transmission studies ??? etc. .......they missed the boat a long time ago. i believe i said in 2001 ;

"I am beginning to think that the endless attempt to track down and ban, potentia.1 victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually? AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, .eyelid test, anything at whatever cost, we need a test FAST."

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

end...tss

Saturday, September 5, 2009

TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS

http://tseac.blogspot.com/2009/09/tseac-meeting-february-12-2004-baxter.html

From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION PART III]

page 1 starts on page 13, then come back to page 1 to finish.....tss

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

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

World's first blood test for vCJD developed in MRC lab

Thursday 3 February 2011

The world's first accurate blood test for variant Creutzfeldt-Jakob disease (vCJD) has been developed by Medical Research Council (MRC) scientists. The prototype, which is 100,000 times more sensitive than any previous attempt, could transform the diagnosis and screening of the brain disease.

Variant CJD, the human form of BSE (or mad cow disease) first emerged in 1995. The disease, which affects the brain, is believed to have passed from cattle to humans through infected food. It causes personality change, loss of body function, and eventually death.

The research team from the MRC Prion Unit, based at University College London, working with the National Prion Clinic at the National Hospital for Neurology and Neurosurgery (NHNN) tested 190 blood samples, including 21 from individuals known to have vCJD. The blood test was able to detect blood spiked with a dilution of vCJD to within one part per ten billion - 100,000 times more sensitive than any other method developed so far.

Prions, the infectious proteins which cause vCJD and other fatal prion diseases, can inhabit a person's body for up to 50 years before presenting symptoms. During this time there is a chance a carrier of vCJD infection could pass on the infection to others, for example through blood transfusion or even through surgical and medical instruments as prions can easily attach onto metal surfaces.

A widely available, accurate blood test would enable people to be diagnosed earlier and could also help identify carriers of the disease. This would help measure how widespread the prion infection is in the general population and identify those who are at risk of passing on the infection to others.

Lead author Dr Graham Jackson, Programme Leader at the MRC Prion Unit, said:

"This test comes at the end of many years of meticulous, painstaking research in our Unit and the NHS National Prion Clinic. Although further larger studies are needed to confirm its effectiveness, it's the best hope yet of a successful early diagnostic test for the disease. This test could potentially go on to allow blood services to screen the population for vCJD infection, assess how many people in the UK are silent carriers and prevent onward transmission of the disease."

Professor John Collinge, Director of the MRC Prion Unit, said:

"One of the reasons that vCJD is such a dreaded disease and has caused such disruption and expense to health services is the lack of knowledge of who is and who is not a carrier of this infection. The next step will be to test anonymously several thousand blood donors from a country unaffected by BSE in order to gain a better idea of how the test fares in practice. Longer term studies will also be needed to assess what proportion of individuals who test positive for prion infection will then go on to develop the disease later in life.

"The MRC Prion Unit's research with the NHS National Prion Clinic to improve early diagnosis is an essential part of the wider MRC strategy to develop better treatments for patients. For this to develop, it will be crucial for clinicians to be able to offer treatment before extensive irreversible damage to the brain has occurred. At the moment, a firm diagnosis of vCJD can usually be made only once serious symptoms of the disease have developed which indicate extensive damage to the brain."

The study 'A blood-based assay for the detection of vCJD prion infection' is published today in the journal The Lancet.

Ends

Notes to editors:

To arrange an interview with the researchers of this paper, please call the MRC Press Office on 0207 395 2345.

For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

While the number of vCJD samples available for analysis was inherently small, and to date only a small number of healthy donors has been studied, analysis of this blinded panel indicated an assay sensitivity for vCJD of over 71% (15/21, CI 48-89%) and a specificity of 100% (0/169, CI 98-100%).

The NHNN forms part of University College London Hospitals NHS Foundation Trust, one of the largest NHS trusts in the United Kingdom providing first-class acute and specialist services. The Trust is committed to research and development and forms part of UCL Partners which in March 2009 was officially designated as one of the UK's first academic health science centres by the Department of Health. UCLH works closely with UCL, translating research into treatments for patients. www.uclh.nhs.uk

http://www.mrc.ac.uk/Newspublications/News/MRC007683

Wednesday, February 2, 2011

Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay

http://transmissiblespongiformencephalopathy.blogspot.com/2011/02/detection-of-prion-infection-in-variant.html

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

update October 2009

T. Singeltary

Bacliff, TX, USA

Background:

An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

Methods:

12 years independent research of available data

Results:

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

Conclusion:

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

page 114 ;

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf

International Society for Infectious Diseases Web: http://www.isid.org/

please see full text ;

http://transmissiblespongiformencephalopathy.blogspot.com/

Seven main threats for the future linked to prions

The NeuroPrion network has identified seven main threats for the future linked to prions.

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed. Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

Saturday, January 29, 2011

Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to Cynomolgus Macaques, a Non-Human Primate

Jpn. J. Infect. Dis., 64 (1), 81-84, 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/atypical-l-type-bovine-spongiform.html

Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html

Wednesday, July 28, 2010

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report

http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html

Thursday, November 18, 2010

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS

http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html

Friday, August 27, 2010

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010

http://nor-98.blogspot.com/2010/08/new-atypical-nor-98-scrapie-case.html

Thursday, August 19, 2010

SCRAPIE CANADA UPDATE Current as of 2010-07-31 The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2010.

Current as of: 2010-07-31

http://nor-98.blogspot.com/2010/08/scrapie-canada-update-current-as-of.html

the OIE and the USDA systematically changed the science with the BSE MRR policy, and put everyone around the globe at risk by taking us back to ground zero 1984-1985 kent bse cow.

Saturday, June 19, 2010

U.S. DENIED UPGRADED BSE STATUS FROM OIE

http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html

Tuesday, January 25, 2011

Generation of a new form of human PrPSc in vitro by inter-species transmission from cervids prions

http://chronic-wasting-disease.blogspot.com/2011/01/generation-of-new-form-of-human-prpsc.html

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html

Friday, February 04, 2011

NMLB and USDA allow scrapie prion infected mutton to enter food chain on the Navajo Reservation in New Mexico

http://scrapie-usa.blogspot.com/2011/02/nmlb-and-usda-allow-scrapie-prion.html

Wednesday, January 19, 2011

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html

Tuesday, January 18, 2011

Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.html

Tuesday, December 14, 2010

Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html

Sunday, January 30, 2011

Vaccines and Transmissible Spongiform Encephalopathy the Prion Disease, what if ?

COMMERCIAL IN CONFIDENCE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/vaccines-and-transmissible-spongiform.html

strictly NOT private and confidential $$$

Saturday, January 22, 2011

Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html

Monday, September 13, 2010

atypical BSE strains and sporadic CJD strains, is there a connection and why shouldn't there be $

http://bse-atypical.blogspot.com/2010/09/atypical-bse-strains-and-sporadic-cjd.html

Sunday, August 15, 2010

ATYPICAL BSE NOW LINKED TO CAUSING SPORADIC CJD OVERSEAS Commonwealth of Australia

http://bse-atypical.blogspot.com/2010/08/atypical-bse-now-linked-to-causing.html

Thursday, July 08, 2010

GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html

DID EVERYONE THAT LOST A LOVED ONE FILL OUT THEIR CJD QUESIONNAIRE FROM THE CDC AND OR THE CJD FOUNDATION ???

Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION

http://cjdquestionnaire.blogspot.com/

TSS

TSEAC Transmissible Spongiform Encephalopathies Advisory Committee Draft Agenda and Meeting Materials, Posted: 10/18/2010

2010-10-18T18:44:00.000-07:00

Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Center Date Time Location

CBER October 28-29, 2010

October 28 from 8:30 a.m. to approximately 5 p.m. October 29 from 8:30 a.m. to approximately 12:30 p.m. Holiday Inn, 2 Montgomery Village Avenue, Gaithersburg, MD

Agenda

On October 28, 2010 the Committee will discuss: (1) FDA’s risk assessment for potential exposure to the variant Creutzfeldt - Jakob disease (vCJD) agent in U.S.-licensed plasma-derived Factor VIII and (2) labeling of blood and blood components and plasma-derived products, including plasma-derived albumin and products containing plasma-derived albumin, to address the possible risk of transmission of vCJD. On October 29, 2010, the Committee will hear informational presentations related to FDA’s geographic donor deferral policy to reduce the possible risk of transmission of CJD and vCJD by blood and blood products and human cells, tissue and cellular and tissue based products. The Committee will also hear updates on the following topics: The development of devices to remove transmissible spongiform encephalopathy agents from blood components and chronic wasting disease.

Meeting Materials

Materials for this meeting will be available on the 2010 Meeting Materials, Transmissible Spongiform Encephalopathies Advisory Committee page.

Public Participation Information

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

Written submissions may be made to the contact person on or before October 21, 2010 Oral presentations from the public will be scheduled between approximate 11 a.m. and 11:45 a.m. and between 3:30 p.m. and 4 p.m. on October 28 and between approximately 10:30 a.m. and 11 a.m. on October 29. Those desiring to make formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before October 13, 2010. Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by October 14 , 2010. Contact Information

Bryan Emery or Rosanna Harvey 1401 Rockville Pike, HFM-71, Rockville, MD 20852 301-827-0314 FAX: 301-827-0294 e-mail: bryan.emery@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov FDA Advisory Committee Information Line 1-800-741-8138 (301-443-0572 in the Washington, DC, area) code 3014512391. Please call the Information Line for up-to-date information on this meeting. FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA’s Web site after the meeting.

A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the agency’s Web site and call the appropriate advisory committee hot line/phone line to learn about possible modifications before coming to the meeting.

Persons attending FDA’s advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets. FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Bryan Emery at least 7 days in advance of the meeting. FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site for procedures on public conduct during advisory committee meetings.

Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app. 2). Official FR Notice

http://www.fda.gov/AdvisoryCommittees/Calendar/ucm225791.htm

October 28-29, 2010

Transmissible Spongiform Encephalopathies Advisory Committee Meeting Draft Agenda

DRAFT AGENDA

Transmissible Spongiform Encephalopathies Advisory Committee 22nd Meeting, October 28-29, 2010

The Holiday Inn Gaithersburg 2 Montgomery Village Avenue Gaithersburg, MD 20879

Thursday, October 28, 2010

8:30a.m. Opening Remarks, Chair, TSEAC Statement of Conflicts of Interest, Announcements 8:40 a.m. Topic I: Review of FDA’s Risk Assessment for Potential Exposure to Variant Creutzfeldt-Jakob Disease in U.S.-licensed Plasma-Derived Factor VIII

Introduction, Steven Anderson, Ph.D., OBE, FDA (30’) Presentation of FDA Risk Assessment, Hong Yang, Ph.D., OBE, FDA (40’) Summary and Questions for the Committee, Steven Anderson, Ph.D., OBE, FDA (20’)

10:30 a.m. Break 10:45 a.m. Open Public Hearing 11:30 a.m. Open Committee Discussion

Questions for the Committee

12:30 p.m. Lunch 1:45 p.m. Topic II: Labeling of Plasma-derived Products, including Plasma-derived Albumin and Products Containing Plasma-derived Albumin to Address the Possible Risk of Transmission of V ariant Creutzfeldt-Jakob Disease

Introduction and Rationale for Proposed Labeling Change for Plasma Derivatives to Reflect Possible vCJD Risk Dorothy Scott, M.D., DH, OBRR, FDA (15’) TSE Clearance in Manufacturing of Plasma Derivatives, PPTA (25’) Summary and Questions for the Committee Dorothy Scott, M.D., DH, OBRR, FDA (20’)

2:45 p.m. Break 3:00 p.m. Open Public Hearing 3:30 p.m. Open Committee Discussion

Questions for the Committee

4:30 p.m. Adjournment

Friday, October 29, 2010

8:30 a.m. Opening Remarks, Chair, TSEAC

Statement of Conflicts of Interest, Announcements

8:40 a.m. Informational Presentations: FDA’s Geographic Donor Deferral Policy to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products and Human Cells, Tissues and Cellular and Tissue-based Products

Review of Current FDA Policies David Asher, M.D., DETTD, OBRR, FDA (30’) Elizabeth Lybarger, M.F.S., M.S. LT USPHS, DHT, OCTGT, FDA (15’) Variant CJD in the UK and Worldwide, Robert Will, M.D., UK CJD Surveillance Unit, Edinburgh (30’) BSE in the USA and Worldwide, Linda Detwiler, D.V.M., University of Mississippi (15’) USDA Updates Christopher Robinson, D.V.M., National Center for Import and Export, APHIS, USDA (15’) Troy Bigelow, D.V.M, National Center for Animal Health Programs, APHIS, USDA (15’) Questions to Speakers (10’)

11:00 a.m. Open Public Hearing 11:30 a.m. Break 11:45 a.m. Committee Updates

Recent Advances in Development of Devices to Remove TSE Agents from Blood Components. Steven J. Burton, Ph.D., Prometric BioSciences, Ltd. (15’) Sam Coker, Ph.D., Pall Medical Corporation (15’) Tomo Yokomizo, M.Sc., Asahi-Kasei Medical (15’) Questions to Speakers (10’)

12:30 p.m. Adjournment

http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm229984.htm

Module 2. Estimates of vCJD Prevalence in US Donors and US Plasma Pools

This module estimates the number of US plasma donors potentially infected with the agent that is responsible for vCJD, and this information was used to derive the number and percentage of plasma pools potentially including donations containing the vCJD agent. This module used results of a travel survey of US donors to determine numbers of US plasma donors expected to be at increased risk for vCJD, including those with history of:

Dietary exposure to BSE-contaminated beef during long-term travel or residence in UK, France and other European countries (since 1980);

US military service in European countries where beef was obtained from the UK, including US military personnel and associated civilian employees and dependents posted on or residing near military facilities in Europe during certain years; and

Transfusion with blood collected in Europe ("EuroBlood").

US plasma donors potentially at increased risk for vCJD were further characterized by:

Age,

Country of travel or residence,

Year of travel or residence,

Specific duration of travel or residence.

The model also included the factors of:

Plasma type (Source Plasma or recovered plasma),

Rate and frequency of plasma donation,

Number of donations per plasma pool, and

Effectiveness of donor deferral policies.

After accounting for the factors listed above, we used both UK prevalence estimates to predict the number of vCJD donations that might have entered into US plasma pools of various sizes under two separate prevalence scenarios.

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM230048.pdf

SPONGIFORM ENCEPHALOPATHIES

ADVISORY COMMITTEE MEETING

October 28, 2010

Gaithersburg, MD

Topic II: Proposed revisions to the labeling recommendations to reflect potential risk of vCJD in plasma derivatives

Issue: FDA seeks advice on the proposed revisions to labeling recommendations for plasma derivative package inserts, to reflect potential risk of vCJD

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM230049.pdf

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

ADVISORY COMMITTEE MEETING

28- 29 October 2010

Issue Summary

Informational Topic: FDA’s Geographic Donor Deferral Policy to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products and Human Cells, Tissues and Cellular and Tissue-based Products

Issue: FDA wishes to update the Committee on the current regulatory considerations relating to Relevant Communicable Disease Agents and Diseases (RCDADs), of which TSEs are a part, for human cell, tissue, and cellular and tissue-based products (HCT/Ps), and also would like to identify current criteria that would render an HCT/P donor ineligible as a result of TSE risk. There is no decisional issue for the committee at this time.

Regulatory Background:

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM230050.pdf

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010

(COMMENT SUBMISSION)

http://tseac.blogspot.com/2010/09/transmissible-spongiform_14.html

what about the other strains of BSE i.e. atypical BSE, and other TSE in other species here in North America, and human TSE and risk factor from blood there from ?

atypical BSE are more virulent than typical UK c-BSE, so why would we be ignoring these factors here in the USA $ i.e. the Gold Card, TRADE $

Saturday, June 19, 2010

U.S. DENIED UPGRADED BSE STATUS FROM OIE

http://www.oie.int/eng/session2010/PDF%20Press%20releases/PRESS78_EN.pdf

see full text and reasons why here ;

http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html

PLEASE NOTE *

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf

Atypical BSE in Cattle

BSE has been linked to the human disease variant Creutzfeldt Jakob Disease (vCJD). The known exposure pathways for humans contracting vCJD are through the consumption of beef and beef products contaminated by the BSE agent and through blood transfusions. However, recent scientific evidence suggests that the BSE agent may play a role in the development of other forms of human prion diseases as well. These studies suggest that classical type of BSE may cause type 2 sporadic CJD and that H-type atypical BSE is connected with a familial form of CJD.

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

Responsibilities include:

Driving research at the National and OIE BSE reference lab to ensure project milestones are met successfully. Contributing to the preparation of project progress reports. Directing technical staff working on the project. Communicating and discussing results, progress and future direction with project principle investigator(s). Communicating with collaborative project partners. Qualifications:

Successful completion of a PhD degree in an area focusing on or related to prion diseases. Extensive experience with molecular and/or morphologic techniques used in studying prion diseases and/or other protein misfolding disorders. Ability to think independently and contribute new ideas. Excellent written and oral communication skills. Ability to multitask, prioritize, and meet challenges in a timely manner. Proficiency with Microsoft Office, especially Word, PowerPoint and Excel. How to apply:

Please send your application and/or inquiry to: Dr. Stefanie Czub, DVM, Ph.D. Head, National and OIE BSE Reference Laboratory Canadian Food Inspection Agency Lethbridge Laboratory P.O. Box 640, Township Road 9-1 Lethbridge, AB, T1J 3Z4 Canada

phone: +1-403-382-5500 +1-403-382-5500 ext. 5549 email: stefanie.czub@inspection.gc.ca

Contact Info:

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

update October 2009

T. Singeltary

Bacliff, TX, USA

Background:

An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

Methods:

12 years independent research of available data

Results:

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

Conclusion:

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

page 114 ;

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf

PRODUCT Red Blood Cells. Recall # B-2300-10 CODE Unit: W001607702825 RECALLING FIRM/MANUFACTURER Recalling Firm: Department of the Air Force, Wright Patterson AFB, OH, by letter dated April 8, 2008. Manufacturer: Depart of Air Force 88th Medical Group SGQC WPAFB, Wright Patterson AFB, OH. 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 Japan

___________________________________

PRODUCT Recovered Plasma. Recall # B-2302-10 CODE Units: R08951; P90041; P90041 RECALLING FIRM/MANUFACTURER Blood Center of Northcentral Wisconsin, Inc., Wausau, WI, by fax on January 2, 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 3 units DISTRIBUTION NY

___________________________________

PRODUCT 1) Red Blood Cells Leukocytes Reduced. Recall # B-2338-10; 2) Plasma Frozen. Recall # B-2339-10 CODE 1) and 2) Unit: 5039861 RECALLING FIRM/MANUFACTURER Community Blood Center, Inc., Appleton, WI, by letter dated September 21, 2007 or by electronic notification on September 21, 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 WI, Switzerland

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 22, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm227078.htm

PRODUCT

1) Cryoprecipitated AHF, Pooled. Recall # B-2155-10;

2) Recovered Plasma. Recall # B-2156-10

CODE

1) Unit: W036309907231;

2) Unit: W036309616077

RECALLING FIRM/MANUFACTURER

BloodCenter of Wisconsin, Inc., Milwaukee, WI, by fax and internet on May 5, 2010 and May 13, 2010. 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, Switzerland

___________________________________

PRODUCT

Red Blood Cells Leukocytes Reduced. Recall # B-2157-10

CODE

Unit: 6371718

RECALLING FIRM/MANUFACTURER

South Texas Blood & Tissue Center, San Antonio, TX, by telephone on January 23, 2010 and by fax on January 25, 2010. Firm initiated recall is complete.

REASON

Blood product, collected from a donor who failed to answer questions regarding risk for vCJD, was distributed.

VOLUME OF PRODUCT IN COMMERCE

1 unit

DISTRIBUTION

TX

___________________________________

PRODUCT

Source Plasma. Recall # B-2212-10

CODE

Units: 09FMOG6851; 09FMOG3410; 09FMOG2756; 09FMOG1418; 09FMOF6640; 09FMOF2642; 09FMOF1554; 09FMOD7746; 09FMOF0063; 09FMOF7599

RECALLING FIRM/MANUFACTURER

BioLife Plasma Service LP, Springfield, MO, by fax on April 1, 2010. 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

10 units

DISTRIBUTION

CA

___________________________________

PRODUCT

1) Red Blood Cells Leukocytes Reduced. Recall # B-2213-10;

2) Recovered Plasma. Recall # B-2214

CODE

1) and 2) Unit: 6325245

RECALLING FIRM/MANUFACTURER

South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on February 8, 2010. 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, TX

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 15, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm225990.htm

PRODUCT Source Plasma. Recall # B-2056-10 CODE Units: FD0500537, FD0502880, FD0503259, FD0509894, FD0515518, FD0516063, FD0517957, FD0518606, FD0522255, FD0523346, FD0523544, FD0524204, FD0524698, FD0525142, FD0525845, FD0526653, FD0526878, FD0527579, FD0527845, FD0528519, FD0528827, FD0529544, FD0529761, FD0530471, FD0530712, FD0531425, FD0531801, FD0532483, FD0532869, FD0537501, FD0537687, FD0538370, FD0543210, FD0546250, FD0546632, FD0547328, FD0547832, FD0548286, FD0548743, FD0549325, FD0549840, FD0550427, FD0551448, FD0551572, FD0552307, FD0553173, FD0553418, FD0554063, FD0554834, FD0555041, FD0559685, FD0560235, FD0560592, FD0561168, FD0561786, FD0562212, FD0562883, FD0563248, FD0564435, FD0564723, FD0565467, FD0565880, FD0566540, FD0567053, FD0567723, FD0567965, FD0568941, FD0569180, FD0570057, FD0571177, FD0571477, FD0572411, FD0572818, FD0573582, FD0573871, FD0574531, FD0576955, FD0577140, FD0579983, FD0580403, FD0581156, FD0581623, FD0582680, FD0583090, FD0584073, FD0584500, FD0585410, FD0586089, FD0586790, FD0587500, FD0588791, FD0589023, FD0590248, FD0590600, FD0591592, FD0592445, FD0593277, FD0593712, FD0594626, FD0595049, FD0596132, FD0596519, FD0597701, FD0598681, FD0599198, FD0600210, FD0600690, FD0601755, FD0602401, FD0603415, FD0603985, FD0605122, FD0608608, FD0609074, FD0609979, FD0610508, FD0611469, FD0612006, FD0612905 RECALLING FIRM/MANUFACTURER DCI Biologicals LLC, Farmington, NM, by facsimile on September 26, 2009 and electronic mail dated January 15, 2010. 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 119 units DISTRIBUTION NY, UK

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 8, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm225223.htm

PRODUCT Source Plasma. Recall # B-2134-10 CODE Units: 3910020431, 3910019695, 3910018715, 3910018227, 3910017100, 3910016675, 3910015596, 3910015120, 3910014175, 3910013575, 3910012934, 3910012281, 3910010102, 3910009899, 3910007715, 3910007430 RECALLING FIRM/MANUFACTURER Talecris Plasma Resources, Inc., N Las Vegas, NV, by fax on July 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 16 units DISTRIBUTION NC

___________________________________

PRODUCT 1) Red Blood Cells. Recall # B-2215-10; 2) Fresh Frozen Plasma. Recall # B-2216-10 CODE 1) and 2) Unit: 0951592 RECALLING FIRM/MANUFACTURER Memorial Blood Centers, Saint Paul, MN, by letter on November 5, 2008. Firm initiated recall is complete. REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION MN

___________________________________

PRODUCT Recovered Plasma. Recall # B-2217-10 CODE Unit: 0951592 RECALLING FIRM/MANUFACTURER Memorial Blood Centers, Saint Paul, MN, by letter on November 5, 2008. Firm initiated recall is complete. REASON Blood product, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), was distributed. VOLUME OF PRODUCT IN COMMERCE 1 unit DISTRIBUTION MN

___________________________________

END OF ENFORCEMENT REPORT FOR SEPTEMBER 1, 2010

http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm224723.htm

Variant CJD: where has it gone, or has it?

The recent identification of a possible clinical case of vCJD in an individual with an MV genotype3 reinforces the long held concern that there may be further waves of vCJD cases in individuals with a non-MM codon 129 genotype. Mathematical models suggest that the number of MV and VV cases will be limited and not exceed the primary MM outbreak, but predicting infectious outbreaks is an imprecise science, as may be inferred from the recent swine flu epidemic which never materialised, at least not to the extent predicted. The adage that 'Essentially, all models are wrong but some are useful' (George Edwin Pelham Box, 2007), reinforces the need for caution in predicting the future course of the vCJD outbreak. There is also the possibility that the phenotype of vCJD may be influenced by the genetic background. It is reassuring therefore that the recent possible MV case was identified on the basis of the clinical features as this may indicate that any further such cases will also be recognised as vCJD.

However, there is clearly still a continuing need to look for new phenotypes of human prion disease. Novel forms of animal prion diseases have been identified in recent years, including atypical scrapie and the rare H and L forms of atypical BSE, probably as a result of the extensive abattoir testing of animal populations. Atypical BSE has been transmitted to a range of laboratory animals, and in a primate model the incubation period was shorter than with conventional BSE and the clinical and pathological phenotype different.4

The incubation period in human prion disease can extend to decades and there are continuing concerns and uncertainties that indicate that there are good reasons to continue research and surveillance in vCJD, despite the clear decline in the primary outbreak of vCJD.

Tuesday, September 28, 2010

Variant CJD: where has it gone, or has it?

Pract Neurol 2010; 10: 250-251

http://vcjdtransfusion.blogspot.com/2010/09/variant-cjd-where-has-it-gone-or-has-it.html

Date: June 21, 2007 at 2:49 pm PST

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.

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

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

Audit Report Animal and Plant Health Inspection Service Bovine Spongiform Encephalopathy (BSE) Surveillance Program Â Phase II and Food Safety and Inspection Service

Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat Recovery Products - Phase III

Report No. 50601-10-KC January 2006

Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain

http://www.usda.gov/oig/webdocs/50601-10-KC.pdf

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

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

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

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

http://www.upi.com/ConsumerHealthDaily/view.php?StoryID=20060315-055557-1284r

LET'S take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.

This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$

ALABAMA MAD COW g-h-BSEalabama

In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156

http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF

Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY

(see mad cow feed in COMMERCE IN ALABAMA...TSS)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html

Wednesday, July 28, 2010

re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010

http://bse-atypical.blogspot.com/2010/07/re-freedom-of-information-act-project.html

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. It also suggests a similar cause or source for atypical BSE in these countries.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf

REPORT OF THE WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY 1989

snip...

4.2.9 ...Also, if it resulted from a localised chance transmission of the scrapie strain from sheep to cattle giving rise to a mutant, a different pattern of disease would have been expected: its range would have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly, now being nearly 3 times as high as during any previous period (18).

http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf

http://collections.europarchive.org/tna/20080102193106/http://www.bseinquiry.gov.uk/files/mb/m12/tab12.pdf

CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER

" Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle."

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas. She left 6 Kids and a Husband. The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-

Physician Discharge Summary, Parkland Hospital, Dallas Texas

Admit Date: 12/29/2009

Discharge Date: 1/20/2010

Attending Provider: Greenberg, Benjamin Morris;

General Neurology Team: General Neurology Team

Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence. She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers. The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically.

Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.

http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8

Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed .

The key word here is diverse. What does diverse mean?

If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

SEE FULL TEXT ;

http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101

.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE. 32 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture. 33 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre. 34 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.

32 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606-12

33 YB88/10.00/1.1

http://web.archive.org/web/20040823105233/www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf

Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

SEE where sporadic cjd in the USA went from 59 cases in 1997, to 216 cases in 2009. a steady increase since 1997. ...TSS

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

see full text ;

http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html

Friday, August 27, 2010

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010

http://nor-98.blogspot.com/2010/08/new-atypical-nor-98-scrapie-case.html

THIS is just ONE month report, of TWO recalls of prohibited banned MBM, which is illegal, mixed with 85% blood meal, which is still legal, but yet we know the TSE/BSE agent will transmit blood. we have this l-BSE in North America that is much more virulent and there is much concern with blood issue and l-BSE as there is with nvCJD in humans. some are even starting to be concerned with sporadic CJD and blood, and there are studies showing transmission there as well. ... this is one month recall page, where 10 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE, TO BE FED OUT. very little of the product that reaches commerce is ever returned via recall, very, very little. this was 2007, TEN YEARS AFTER THE AUGUST 4, 1997, PARTIAL AND VOLUNTARY MAD COW FEED BAN IN THE USA, that was nothing but ink on paper. i have listed the tonnage of mad cow feed that was in ALABAMA in one of the links too, this is where the infamous g-h-BSEalabama case was, a genetic relation matching the new sporadic CJD in the USA. seems this saga just keeps getting better and better.......$$$

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/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Tuesday, March 2, 2010

Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded Rangen Inc 2/11/10 USA

http://madcowfeed.blogspot.com/2010/03/animal-proteins-prohibited-in-ruminant.html

Monday, March 1, 2010

ANIMAL PROTEIN I.E. MAD COW FEED IN COMMERCE A REVIEW 2010

http://madcowfeed.blogspot.com/2010/03/animal-protien-ie-mad-cow-feed-in.html

Tuesday, September 14, 2010

Feed Safety and BSE/Ruminant Feed Ban Support Project (U18)

http://madcowfeed.blogspot.com/2010/09/feed-safety-and-bseruminant-feed-ban.html

Friday, October 8, 2010

Scientific reasons for a feed ban of meat-and-bone meal, applicable to all farmed animals including cattle, pigs, poultry, farmed fish and pet food

http://madcowfeed.blogspot.com/2010/10/scientific-reasons-for-feed-ban-of-meat.html

Friday, October 15, 2010

BSE infectivity in the absence of detectable PrPSc accumulation in the tongue and nasal mucosa of terminally diseased cattle

http://bseusa.blogspot.com/2010/10/bse-infectivity-in-absence-of.html

Thursday, October 07, 2010

Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice

http://bse-atypical.blogspot.com/2010/10/experimental-transmission-of-h-type.html

Friday, August 20, 2010

USDA: Animal Disease Traceability August 2010

http://naiscoolyes.blogspot.com/2010/08/usda-animal-disease-traceability-august.html

Wednesday, September 08, 2010

Emerging Infectious Diseases: CJD, BSE, SCRAPIE, CWD, PRION, TSE Evaluation to Implementation for Transfusion and Transplantation September 2010

http://vcjdtransfusion.blogspot.com/2010/09/emerging-infectious-diseases-cjd-bse.html

Sunday, October 3, 2010

Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?

http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html

Thursday, August 12, 2010

Seven main threats for the future linked to prions

http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html

http://prionpathy.blogspot.com/

layperson

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 flounder9@verizon.net

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

2010-09-14T09:16:00.000-07:00

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

From: Terry S. Singeltary Sr.

To: william.freas@fda.hhs.gov Cc: rosanna.harvey@fda.hhs.gov ; Emery, Bryan (CBER)

Sent: Tuesday, September 14, 2010 11:15 AM

Subject: Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010

Contact Person: Bryan Emery or Rosanna Harvey, Center for Biologics Evaluation and Research (HFM-71), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0314, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512392.

http://edocket.access.gpo.gov/2010/2010-22805.htm

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010

http://tseac.blogspot.com/2010/09/transmissible-spongiform.html

Greetings Dr. Freas, Ms Rosanna Harvey, and Mr. Bryan Emery,

I wish to submit my concerns again with regards to this TSEAC meeting, human and animal TSE in the USA, and the risk from blood products there from.

I am still very concerned about the lack of sound BSE testing in the USA, the breach of the mad cow feed ban from the day the partial and voluntary feed ban was put in place August 4, 1997, to 2007 where some 10 million pounds of banned blood laced meat and bone meal went out into commerce, and fed out, the fact human CJD is on the increase in the USA, of which many cases now are of the ''UNKNOWN'' phenotype, of which claiming to be not nvCJD, but yet NOT know what the strain is, and then the potential ramifications there from in terms of blood and blood products, in my opinion, you are playing with fire to continue to believe that the nvCJD only strain from c-BSE (UK strain), is the only risk, when we now know that the atypical BSE is much more virulent, and the fact that all three strains i.e. c-BSE, h-BSE, and l-BSE have all been documented in North America. WE now have this new prionpathy or prionopathy, that is said to be of a Genetic line of human TSE, but yet has not related mutation to the family. BUT yet is identical to the g-h-BSEalabama cow, and we know that tons of mad cow feed was fed out in Alabama. WE know that CWD is spreading, the risk from CWD strains and exposure to humans, and friendly fire and or the pass if forward mode there from ? Atypical scrapie strains spreading, of which both the atypical scrapie and atypical BSE pathologically are very very similar to some sporadic CJD and GSS. The fact that the Baxter study DID produce transmission of blood from GSS to primate. All this is very disturbing, and the risk there from is very real. In my opinion, I believe that the USA FDA have now floundered too long, and that in fact we have exposed many (home and abroad) to this TSE agent via blood products, and medical procedures, simply by still believing in the UKBSEnvCJD only theory. Again, I beg that this theory be put to rest once and for all, and that the FDA et al take seriously the real threat of human TSE via animal TSE in the USA, and protect our Nations blood supply there of. IF not, the potential for further transmission is real, and in the end, for what ever it's worth, the FDA and the USA government will be fully responsible for their negligence. I present the following as evidence of my concerns. ...

PRION 2010

International Prion Congress: From agent to disease September 8-11, 2010 Salzburg, Austria

Previously published online:

www.landesbioscience.com/journals/prion/article/12764

DOI: 10.4161/pri.4.3.12764 PRION 2010 is the top Global Annual TSE Conference in prion research, following a sequence of PRION meetings that were originally organized by the EU Network of Excellence NeuroPrion. In this proud tradition, PRION 2010 covers all aspects of this fascinating scientific area. PRION 2010 is a meeting of greatest interest for neuroscientists, protein structural biologists, geneticists, medical specialists including neurologists, neuropathologists, hygiene experts and blood product providers, veterinarians, epidemiologists, laboratory technicians, industry developers, risk assessors and managers. An outstanding list of Plenary Lecture, Symposia and Workshop Speakers is complemented by the plethora of original input from Poster Presentations. Special consideration is given this year to two areas of major interest: the renewed discussion about the zoonotic potential of animal prion diseases, given the emergence of atypical BSE and scrapie strains, and the breakthrough work on synthetic prions by several groups simultaneously.

http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099

PPo3-11:

Blood Transmission Experiments in Primates: Squirrel Monkeys (the Baxter Study)

Paul Brown, James Ironside, Susan Gibson, Robert G. Will, Thomas R. Kreil and Christian Abee

Plasma and buffy coat samples from 2 sCJD and 3 vCJD cases were inoculated i.c. and i.v. into a total of 21 squirrel monkeys. Pooled brain from the 3 vCJD patients titered 106 LD50/g (i.c.). Whole blood from each of 4 monkeys inoculated with 10% vCJD brain homogenate was transfused i.v. to individual recipient monkeys at approximately 3-month intervals during the incubation and clinical stages of disease in the donor animals. Plasma, RBC's, platelets, and purified leukocytes from 6 chimpanzees infected with either human sCJD or GSS were inoculated i.c. and i.v. into 12 monkeys. In the entire group of monkeys inoculated with blood or blood components, only a single neuropathologically-verified transmission occurred within a 5-year observation period, in an animal inoculated with leukocytes from a pair of GSS-infected chimpanzee.

Conclusions. In a primate model highly susceptible to TSE (the squirrel monkey), infectivity was not detected (<10>92%. Due to limited data and knowledge of vCJD, the model estimates are uncertain. This analysis identifies critical data gaps in understanding the risk of TTvC, and provides a tool to inform regulatory decision-making.

PPo4-20:

All Clinically Relevant Components, from Prion Infected Blood Donors, can Cause Disease Following a Single Transfusion

Sandra McCutcheon,1 Fiona E. Houston,2 Anthony R. Alejo-Blanco,1 Christopher de Wolf,1 Boon Chin Tan,1 Anthony Smith,3 Nora Hunter,1 Valerie S. Hornsey,4 Ian R. MacGregor,4 Christopher V. Prowse,4 Marc Turner5 and Jean C. Manson1 1The Roslin Institute; Roslin, Edinburgh UK; 2The University of Glasgow; Glasgow, UK; 3The Institute for Animal Health; Compton, Berkshire UK; 4National Science Laboratory; Scottish National Blood Transfusion Service (SNBTS); Edinburgh, UK; 5University of Edinburgh and SNBTS; Edinburgh, UK

Key words: blood, prion, BSE, transfusion

Introduction. To date, there have been over 220 cases of vCJD worldwide, likely acquired directly from bovine sources. There is concern that human to human transmission from individuals sub-clinically infected with vCJD may amplify/prolong a vCJD epidemic. The area of greatest concern in this respect is blood transfusion, of which there have been several reported cases. Here we examined which blood components are likely to pose the greatest risk of transmitting vCJD via blood transfusion using our sheep BSE model.

Results. 67% of donors have been confirmed as having BSE. We have recorded 25 positive transmissions of BSE following transfusion of non-leucodepleted blood components and 2 transmissions resulting from the transfusion of leucoreduced red cells and leucoreduced plasma.

Conclusion. We show that all components, prepared to the same criteria as used in human medicine, contain sufficient levels of infectivity to cause disease in recipients following a single blood transfusion. Leucoreduction of plasma and red cell concentrates does not remove infectivity. These data indicate the importance of devising appropriate control measures to minimise the risk of human to human transmission of vCJD by blood transfusion. Department of Health, UK (007/0162).

Methods. Sheep were orally infected with bovine BSE brain homogenate. We collected two full-sized donations of whole blood, before the onset of clinical signs. The following components were transfused into naive recipients: whole blood, red cell concentrates buffy coat, plasma and platelet units. We also transfused leucoreduced plasma, platelets and red cells. We collected a unit of whole blood from selected primary recipients for transfusion into secondary recipients.

PPo4-21:

The Risk of Variant Creutzfeldt-Jakob Disease (vCJD) Among UK Patients with Bleeding Disorders, Known to Have Received Clotting Factors Linked to Donors who Subsequently Developed vCJD

Syed M.A. Zaman,1 Nicky Connor,1 Noel Gill,1 Carolyn M. Millar,2,6 Mike Makris,3,6 Benedict Palmer4 and Frank G.H. Hill5,6 1CJD Section, Health Protection Agency Centre for Infections; London, UK; 2Department of Haematology; Imperial College; London, UK; 3University of Sheffield; Royal Hallamshire Hospital; Sheffield, UK; 4National Haemophilia Database; Manchester, UK; 5The Children's Hospital NHS Foundation Trust; Birmingham, UK; 6Members of the Transfusion Transmitted Infection Working Party of the UK; Haemophilia Centre Doctors' Organisation (UKHCDO); Sheffield, South Yorkshire UK

The risk of Creutzfeldt-Jakob Disease (vCJD) from potentially infected plasma products remains un-quantified. This risk has been assessed for 787 UK bleeding disorder patients prospectively followed-up for 10-20 years through the UK Haemophilia Centre Doctors' Organisation (UKHCDO) Surveillance Study. These patients were treated with any of 25 'implicated' clotting factor batches from 1987-1999, which included in their manufacture plasma from eight donors who subsequently developed vCJD. VCJD infectivity of these batches was estimated using plasma fraction infectivity estimates and batch manufacturing data. The quantity of implicated batches received by these patients was obtained. Total vCJD infectivity received by each patient has been estimated by cumulating infectivity from all doses received in their lifetime. Of 787 patients, 604 (77%) were followed-up for over 13 years since exposure to an implicated batch. By end 2008, none of these patients had developed vCJD. For these 604 patients, the estimated vCJD risk is <1% for 595, <50% for 164, and 100% for 51. This is additional to the background UK population risk due to dietary exposure. Of 604 patients, 94 (16%) received implicated batches linked to donors who developed vCJD within six months of their donations. 151 (25%) had received their first dose under 10 years of age. The absence of clinical vCJD cases in this cohort to date suggests that either plasma fraction infectivity estimates are overly precautionary, or the incubation period is longer for this cohort than for implicated cellular blood product recipients. Further follow up of this cohort is needed to answer these questions.

http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099

some additional interesting studies.

O.10.5

A novel human prion disease affecting subjects with the three prion protein codon 129 genotypes: could it be the sporadic form of Gerstmann-Straussler? Pierluigi Gambetti Case Western Reserve University, USA Background: We recently described a novel prion disease, named protease-sensitive prionopathy or PSPr, characterized by the presence of an abnormal prion protein (PrP) that was 60 fold less protease resistant than that of sporadic Creutzfeldt-Jakob disease (sCJD) and on immunoblot generated a distinct ladder-like profile. All affected subjects where homozygous for valine at codon 129 (VV) and had no mutation in the PrP gene. Methods: We have characterized several new cases in our surveillance and received from Europe. Results: 1) A disease overall similar to that reported in the 129VV subjects also affects subjects that are methionine/valine heterozygous (MV) and methionine homozygous (MM) at codon 129 and have no PrP gene mutation; 2) The clinical and histopathological features of the new MV and MM PSPr cases are similar but distinguishable from those of the original VV cases; 3) The electrophoretic profiles generated by the abnormal PrP isoforms associated with the MV and MM cases are similar to VV cases but show increasing levels of proteaseresistance; 3) abnormal tau is present in all three genotypic forms of PSPr with features apparently similar to those of primary tauopathies placing PSPr at the intersection of tauopathies and prion diseases. Discussion: Will focus on: 1) the features of the abnormal PrP in the newly discovered 129MV and 129MM PSPr; 2) the effect of the 129 polymorphism on PSPr compared to that on sCJD; 3) the relationship of PSPr with tauopathies; 4) whether PSPr now with the three 129 genotypic forms is the long sought sporadic form of GSS.

(Supported by NIH AG-14359, NS052319, CDC UR8/CCU515004).

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2009/prion2009_bookofabstracts.pdf

I ask Professor Kong ;

Thursday, December 04, 2008 3:37 PM

Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment

''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''

Professor Kong reply ;

.....snip

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''

Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA END...TSS

P26

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

Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA

Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C. The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far. III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)

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

P02.35

Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden

Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.

http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf

MORE from this years PRION 2010 International Prion Congress:

From agent to disease September 8-11, 2010 Salzburg, Austria

PPo2-17:

Atypical H-type BSE Infection in Bovine-PrP Transgenic Mice Let to the Emergence of Classical BSE Strain Features

Juan Carlos Espinosa,1 Olivier Andréoletti,2 Caroline Lacroux,2 Irene Prieto,1 Patricia Lorenzo,1 Magdalena Larska,1 Thierry Baron3 and Juan María Torres1 1Centro de Investigación en Sanidad Animal; INIA; Valdeolmos, Madrid Spain; 2UMR INRA-ENVT 1225; Interactions Hôte Agent Pathogène; Ecole Nationale Vétérinaire de; Toulouse, France; 3Agence Francaise de Sécurité Sanitaire des Aliments; Lyon Cedex, France

Key words: atypical BSE, PrPres, prion strain, prion transmission

Until identification of atypical cases of Bovine Spongiform Encephalopathy (BSE) in several countries it was assumed that BSE in cattle consisted of only a unique and biologically homogeneous strain type that caused BSE epidemic in Europe. Currently, beside the classical BSE strain associated to most described cases, atypical BSE cases are identified as H- or L-type based on the differences in the western blot profiles of abnormal protease-resistant prion protein (PrPres) according to the apparent molecular mass of its unglycosilated band. In the present study, we characterized five atypical BSE-H isolates by analyzing their molecular and neuropathological properties after transmission in transgenic mice expressing homologous bovine prion protein (PrP). The results showed that most of the inoculated animals conserved the atypical BSE-H strain features. However, a number of animals inoculated with two of these isolates showed prion strain features resembling those of classical BSE in this mouse model. On each case, the strain characteristics were preserved after subsequent passage in the same mice. These data suggest that atypical BSE-H prions, can acquire epidemic BSE-like properties during propagation in a homologous bovine PrP context. Beside a new view on BSE strains diversification, our observations support the hypothesis that atypical BSE-H, which could be a sporadic form of prion disease in cattle, may be at the origin of the foodborne BSE epizooty.

PPo3-9:

Potential of Cell Substrates used for Production of Biologics to Propagate Transmissible Spongiform Encephalopathy (TSE) Agents: 5-year Update

P. Piccardo,1,* L. Cervenakova,2 I. Vasilyeva,2 O. Yakovleva,2 I. Bacik,1 J. Cervenak,1 L. Gregori,1 K. Pomeroy,1 L. Kurillova,1 C. McKenzie2 and D.M. Asher1 1Laboratory of Bacterial and TSE Agents; CBER; FDA; USA; 2J. Holland Laboratory; American Red Cross; USA *Presenting Author

Key words: cell culture, animal models, biologics, prion, TSE-agent

Background. TSE agents have contaminated human-tissue-derived therapeutics and animal vaccines. Many biologics are prepared in cell cultures. Although most cultures studied resisted infection with TSE agents, a few were susceptible.

Objectives. We are investigating susceptibility of several cell lines to infection with TSE agents. Results. We studied Vero, CHO, MDCK, HEK-393 and WI-38 cells. We also studied SH-SY5Y cells overexpressing wild-type PrP and mutant PrPs. Cells exposed to TSE agents were serially propagated for 30 passages and samples tested for TSE-associated PrP (PrPTSE) and infectivity by intracerebral inoculation into transgenic mice and squirrel monkeys (BSE-exposed cells only). No exposed cell substrate has transmitted TSE to mice or monkeys to date. No PrPTSE was found in any exposed cells after 30 passages. Known susceptible murine cells exposed to mouse-adapted scrapie agent as positive controls accumulated PrPTSE. Three monkeys inoculated with BSE reference material have developed TSE to date.

Discussion. To date, no candidate cell substrate exposed to 3 TSE agents accumulated PrPTSE or propagated a TSE agent. Squirrel monkeys provide a new model to study BSE pathogenesis.

Methods. We inoculated brain suspensions containing agents of bovine spongiform encephalopathy (BSE), variant Creutzfeldt-Jakob disease (vCJD) or sporadic CJD into several cell lines important in manufacture of biologics. Serial dilutions of the BSE reference material used as inoculum were also inoculated into mice and squirrel monkeys. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Administration determination or policy.

Acknowledgements Support. NIAID-NIH AI-4893-02/FDA 224-05-1307

PPo2-27:

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

PPo3-7:

Prion Transmission from Cervids to Humans is Strain-dependent

Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

Key words: CWD, strain, human transmission

Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.

http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099

Greetings again TSEAC et al,

Confucius ponders, IS GSS and the g-h-BSEalabama mad cow case, the birth of nvCJD-like disease from cattle to humans in the USA ???

Could it be from the ever growing cases of the Nor-98 atypical scrapie in the USA, with 6 cases documented already this year ???

Could it be possible from one of the CWD strains here in the USA ???

ARE GAMBETTI'S INFAMOUS 2ND 10+ AND GROWING, simply USA MAD COW strain in humans ???

WHY not, if US sheep scrapie transmitted to US cattle did not produce a c-BSE (UK type), then why would it produce an nvCJD strain in humans ???

THE ever growing strains of TSE in humans and animals, and classification there from, does not compute. now we are seeing atypical h-BSE cases, and atypical l-BSE cases, atypical human TSE cases that look like these atypical BSE cases, so why in the name of science is all this not acceptable to conclude that these atypical human TSE are a by-product of these atypical animal TSE $$$ and how can it be that the science that concluded IRONSIDES 1st 10+ in 1995, does not correspond with Gambetti's 2nd 10+, in that Gambetti's 2nd 10+ is not a cause from anything, just a happenstance of bad luck on a funked out twisted protein that spontaneously twist to a bad protein on it's own, or, it is familial CJD, but not related to any common family mutation, like sporadic FFI or sporadic GSS $$$ this does not compute either.

JUST HOW long can Gambetti et al hold off on a final analysis of the ever growing numbers of human TSE in the USA $$$

National Prion Disease Pathology Surveillance Center Cases Examined1 (July 31, 2010)

5 Includes 16 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 21 (19 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

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

CAN the blood from these atypical CJD cases transmit TSE prions ???

WHAT if these strange atypical case of human TSE in the USA are from USA cattle, deer, elk, sheep, goat, will blood products transmit, and why wouldn't they ???

Have there been extinsive transmission studies done with blood and all it's products there from ???

WHAT about vaccines ???

Results. We studied Vero, CHO, MDCK, HEK-393 and WI-38 cells. We also studied SH-SY5Y cells overexpressing wild-type PrP and mutant PrPs. Cells exposed to TSE agents were serially propagated for 30 passages and samples tested for TSE-associated PrP (PrPTSE) and infectivity by intracerebral inoculation into transgenic mice and squirrel monkeys (BSE-exposed cells only). No exposed cell substrate has transmitted TSE to mice or monkeys to date. No PrPTSE was found in any exposed cells after 30 passages. Known susceptible murine cells exposed to mouse-adapted scrapie agent as positive controls accumulated PrPTSE. Three monkeys inoculated with BSE reference material have developed TSE to date. ???

Thursday, August 12, 2010

USA Blood products, collected from a donor who was at risk for vCJD, were distributed July-August 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/usa-blood-products-collected-from-donor.html

Sunday, August 01, 2010

Blood product, collected from a donors possibly at increased risk for vCJD only, was distributed USA JULY 2010

http://vcjdtransfusion.blogspot.com/2010/08/blood-product-collected-from-donors.html

Sunday, May 18, 2008

MAD COW DISEASE BSE CJD CHILDREN VACCINES

Sunday, May 18, 2008

MAD COW DISEASE BSE CJD CHILDREN VACCINES TIP740203/l 0424 CONFIDENTIAL

http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html

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-StrÃ¤ussler-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 â?~prionâ?T 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 â?~shockâ?T 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

Saturday, September 5, 2009

TSEAC MEETING FEBRUARY 12, 2004

THE BAXTER STUDY GSS

http://tseac.blogspot.com/2009/09/tseac-meeting-february-12-2004-baxter.html

Thursday, July 08, 2010

Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/nosocomial-transmission-of-sporadic.html

Sunday, July 11, 2010

CJD or prion disease 2 CASES McLennan County Texas population 230,213 both cases in their 40s

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/cjd-2-cases-mclennan-county-texas.html

Thursday, July 08, 2010

GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html

Tuesday, August 03, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html

Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more Prionbaloney ?

http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html

*****Thursday, July 10, 2008*****

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008 Friday, June 20, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html

Wednesday, August 18, 2010

Incidence of CJD Deaths Reported by CJD-SS in Canada as of July 31, 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/incidence-of-cjd-deaths-reported-by-cjd.html

Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010) (please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)

http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html

Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION

http://cjdquestionnaire.blogspot.com/

ALABAMA MAD COW g-h-BSEalabama In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156

http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF

let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.

This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$

Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html

THIS is just ONE month report, of TWO recalls of prohibited banned MBM, which is illegal, mixed with 85% blood meal, which is still legal, but yet we know the TSE/BSE agent will transmit blood. we have this l-BSE in North America that is much more virulent and there is much concern with blood issue and l-BSE as there is with nvCJD in humans. some are even starting to be concerned with sporadic CJD and blood, and there are studies showing transmission there as well. ...

this is one month recall page, where 10 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE, TO BE FED OUT. very little of the product that reaches commerce is ever returned via recall, very, very little. this was 2007, TEN YEARS AFTER THE AUGUST 4, 1997, PARTIAL AND VOLUNTARY MAD COW FEED BAN IN THE USA, that was nothing but ink on paper. i have listed the tonnage of mad cow feed that was in ALABAMA in one of the links too, this is where the infamous g-h-BSEalabama case was, a genetic relation matching the new sporadic CJD in the USA. seems this saga just keeps getting better and better.......$$$

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

___________________________________ P

RODUCT 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/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Tuesday, March 2, 2010

Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded Rangen Inc 2/11/10 USA

http://madcowfeed.blogspot.com/2010/03/animal-proteins-prohibited-in-ruminant.html

Monday, March 1, 2010

ANIMAL PROTEIN I.E. MAD COW FEED IN COMMERCE A REVIEW 2010

http://madcowfeed.blogspot.com/2010/03/animal-protien-ie-mad-cow-feed-in.html

Terry S. Singeltary Sr. (Submitted question):

Monday, April 5, 2010

Update on Feed Enforcement Activities to Limit the Spread of BSE April 5, 2010

http://madcowfeed.blogspot.com/2010/04/update-on-feed-enforcement-activities.html

Subject: USDA OIG SEMIANNUAL REPORT TO CONGRESS FY 2007 1st Half (bogus BSE sampling FROM HEALTHY USDA CATTLE)

Date: June 21, 2007 at 2:49 pm PST

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

http://madcowtesting.blogspot.com/

Wednesday, March 31, 2010

Atypical BSE in Cattle To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER

"Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle."

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas.She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-

Physician Discharge Summary, Parkland Hospital, Dallas Texas

Admit Date: 12/29/2009

Discharge Date: 1/20/2010

Attending Provider: Greenberg, Benjamin Morris;

General Neurology Team: General Neurology Team

Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence. She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers. The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.

http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8

"Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle."

Monday, March 29, 2010

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas

http://creutzfeldt-jakob-disease.blogspot.com/2010/03/irma-linda-andablo-cjd-victim-she-died.html

CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER

http://cjdtexas.blogspot.com/2010/03/cjd-texas-38-year-old-female-worked.html

Terry S. Singeltary Sr. has added the following comment: "According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed .

The key word here is diverse. What does diverse mean?

If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

SEE FULL TEXT ;

http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101

.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE. 32 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture. 33 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre. 34 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.

32 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606-12

33 YB88/10.00/1.1

http://web.archive.org/web/20040823105233/www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf

34 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814-20

Friday, August 27, 2010

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010

http://nor-98.blogspot.com/2010/08/new-atypical-nor-98-scrapie-case.html

PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.

*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html

http://nor-98.blogspot.com/2010/08/scrapie-canada-update-current-as-of.html

PPo2-27:

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

PPo3-7:

Prion Transmission from Cervids to Humans is Strain-dependent

Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

Key words: CWD, strain, human transmission

Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.

http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099

http://chronic-wasting-disease.blogspot.com/2010/07/comments-sought-on-revised-plan-to.html

http://chronic-wasting-disease.blogspot.com/2009/09/experimental-oral-transmission-of.html

http://chronic-wasting-disease.blogspot.com/2009/08/susceptibilities-of-nonhuman-primates.html

http://chronic-wasting-disease.blogspot.com/

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html

Sunday, September 6, 2009

MAD COW USA 1997 SECRET VIDEO

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? see video at bottom

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

Wednesday, February 3, 2010

Import Alert 62-07 Sygen Injectable (Bovine-Extracted GMI Monosialoganglioside) manufactured from bovine brain starting material

http://bseusa.blogspot.com/2010/02/import-alert-62-07-sygen-injectable.html

Rural and Regional Affairs and Transport References Committee The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010

2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric, epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey told the committee of his concerns regarding the lengthy incubation period for transmissible spongiform encephalopathies, the inadequacy of current tests and the limited nature of our current understanding of this group of diseases.49

2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50

http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf

Wednesday, August 11, 2010

Heterozygosity at Polymorphic Codon 219 in Variant Creutzfeldt-Jakob Disease

Vol. 67 No. 8, August 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/heterozygosity-at-polymorphic-codon-219.html

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

my comments to PLosone here ;

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd

Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory

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

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

From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION PART III]

page 1 starts on page 13, then come back to page 1 to finish.....tss

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

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

Newsdesk The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

Tracking spongiform encephalopathies in North America

Xavier Bosch

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” 49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD)—the relative of mad cow disease seen among deer and elk in the USA. Although his feverish…

http://linkinghub.elsevier.com/retrieve/pii/S1473309903007151

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

http://www.mdconsult.com/das/article/body/180784492-2/jorg=journal&source=&sp=13979213&sid=0/N/368742/1.html?issn=14733099

JOURNAL OF NEUROLOGY

MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Email Terry S. Singeltary:

[log in to unmask]

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

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

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

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

Terry S. Singeltary, Sr Bacliff, Tex

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

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

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

2 January 2000

British Medical Journal

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

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

15 November 1999

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

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

THE PATHOLOGICAL PROTEIN

BY Philip Yam

Yam Philip Yam News Editor Scientific American www.sciam.com

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

CHAPTER 14

Laying Odds

Are prion diseases more prevalent than we thought?

Researchers and government officials badly underestimated the threat that mad cow disease posed when it first appeared in Britain. They didn’t think bovine spongiform encephalopathy was a zoonosis—an animal disease that can sicken people. The 1996 news that BSE could infect humans with a new form of Creutzfeldt-Jakob disease stunned the world. It also got some biomedical researchers wondering whether sporadic CJD may really be a manifestation of a zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD is?

Revisiting Sporadic CJD

It’s not hard to get Terry Singeltary going. “I have my conspiracy theories,” admitted the 49-year-old Texan.1 Singeltary is probably the nation’s most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union’s Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people's health.

Singeltary has similar inclinations. ...

http://books.google.com/books?id=ePbrQNFrHtoC&pg=PA223&lpg=PA223&dq=the+pathological+protein+laying+odds+It%E2%80%99s+not+hard+to+get+Terry+Singeltary+going&source=bl&ots=um0PFAZSZD&sig=JWaGR7M7-1WeAr2qAXq8D6J_jak&hl=en&ei=MhtjS8jMJM2ztgeFoa2iBg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CAcQ6AEwAA#v=onepage&q=&f=false

http://www.springerlink.com/content/r2k2622661473336/fulltext.pdf?page=1

http://www.thepathologicalprotein.com/

DER SPIEGEL (9/2001) - 24.02.2001 (9397 Zeichen) USA: Loch in der Mauer Die BSE-Angst erreicht Amerika: Trotz strikter Auflagen gelangte in Texas verbotenes Tiermehl ins Rinderfutter - die Kontrollen der Aufsichtsbehördensind lax.Link auf diesen Artikel im Archiv: http://service.spiegel.de/digas/find?DID=18578755

"Löcher wie in einem Schweizer Käse" hat auch Terry Singeltary im Regelwerk der FDA ausgemacht. Der Texaner kam auf einem tragischen Umweg zu dem Thema: Nachdem seine Mutter 1997 binnen weniger Wochen an der Creutzfeldt-Jakob-Krankheit gestorben war, versuchte er, die Ursachen der Infektion aufzuspüren. Er klagte auf die Herausgabe von Regierungsdokumenten und arbeitete sich durch Fachliteratur; heute ist er überzeugt, dass seine Mutter durch die stetige Einnahme von angeblich kräftigenden Mitteln erkrankte, in denen - völlig legal - Anteile aus Rinderprodukten enthalten sind.

Von der Fachwelt wurde Singeltary lange als versponnener Außenseiter belächelt. Doch mittlerweile sorgen sich auch Experten, dass ausgerechnet diese verschreibungsfreien Wundercocktails zur Stärkung von Intelligenz, Immunsystem oder Libido von den Importbeschränkungen ausgenommen sind. Dabei enthalten die Pillen und Ampullen, die in Supermärkten verkauft werden, exotische Mixturen aus Rinderaugen; dazu Extrakte von Hypophyse oder Kälberföten, Prostata, Lymphknoten und gefriergetrocknetem Schweinemagen. In die USA hereingelassen werden auch Blut, Fett, Gelatine und Samen. Diese Stoffe tauchen noch immer in US-Produkten auf, inklusive Medizin und Kosmetika. Selbst in Impfstoffen waren möglicherweise gefährliche Rinderprodukte enthalten. Zwar fordert die FDA schon seit acht Jahren die US-Pharmaindustrie auf, keine Stoffe aus Ländern zu benutzen, in denen die Gefahr einer BSE-Infizierung besteht. Aber erst kürzlich verpflichteten sich fünf Unternehmen, darunter Branchenführer wie GlaxoSmithKline, Aventis und American Home Products, ihre Seren nur noch aus unverdächtigem Material herzustellen.

"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...

http://www.spiegel.de/spiegel/print/d-18578755.html

http://wissen.spiegel.de/wissen/image/show.html?did=18578755&aref=image024/E0108/SCSP200100901440145.pdf&thumb=false

http://service.spiegel.de/digas/servlet/find/DID=18578755

Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

28 Mar 01

Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html

Friday, August 27, 2010

NEW ATYPICAL NOR-98 SCRAPIE CASE DETECTED IDAHO NOW 5 CASES DOCUMENTED 2010

http://nor-98.blogspot.com/2010/08/new-atypical-nor-98-scrapie-case.html

Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html

Thank You,

I am sincerely,

Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010

2010-09-14T07:10:00.000-07:00

[September 14, 2010]

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

Sep 14, 2010 (FIND, Inc. via COMTEX) -- This notice announces a forthcoming meeting of a public advisory committee [Page Number 55804] of the Food and Drug Administration (FDA). The meeting will be open to the public.

Name of Committee: Transmissible Spongiform Encephalopathies Advisory Committee.

General Function of the Committee: To provide advice and recommendations to the agency on FDA's regulatory issues.

Date and Time: The meeting will be held on October 28, 2010, from 8:30 a.m. to approximately 5 p.m. and on October 29, 2010, from 8:30 a.m. to approximately 12:30 p.m.

Location: Holiday Inn, Gaithersburg, 2 Montgomery Village Ave., Gaithersburg, MD, 20879.

Contact Person: Bryan Emery or Rosanna Harvey, Center for Biologics Evaluation and Research (HFM-71), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0314, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512392. Please call the Information Line for up-to-date information on this meeting. A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the agency's Web site and call the appropriate advisory committee hot line/phone line to learn about possible modifications before coming to the meeting.

Agenda: On October 28, 2010, the Committee will discuss: (1) FDA's risk assessment for potential exposure to the variant Creutzfeldt-Jakob disease (vCJD) agent in U.S.-licensed plasma-derived Factor VIII and (2) labeling of blood and blood components and plasma-derived products, including plasma- derived albumin and products containing plasma-derived albumin, to address the possible risk of transmission of vCJD. On October 29, 2010, the Committee will hear informational presentations related to FDA's geographic donor deferral policy to reduce the possible risk of transmission of CJD and vCJD by blood and blood products and human cells, and tissue and cellular and tissue based products. The Committee will also hear updates on the following topics: The development of devices to remove transmissible spongiform encephalopathy agents from blood components and chronic wasting disease.

FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA's Web site after the meeting. Background material is available at

http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm.

Scroll down to the appropriate advisory committee link.

Procedure: Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to the contact person on or before October 21, 2010. Oral presentations from the public will be scheduled on October 28, 2010, between approximately 11 a.m. and 11:45 a.m. and between approximately 3:30 p.m. and 4 p.m. and on October 29, 2010, between approximately 10:30 a.m. and 11 a.m. Those desiring to make formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before October 13, 2010. Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by October 14, 2010.

Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.

FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Bryan Emery at least 7 days in advance of the meeting.

FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at

http://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm

for procedures on public conduct during advisory committee meetings.

Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app. 2).

Dated: September 7, 2010.

Leslie Kux, Acting Assistant Commissioner for Policy.

[FR Doc. 2010-22805 Filed 9-13-10; 8:45 am] BILLING CODE 4160-01-S Vol. 75, No. 177 [Docket No. FDA-2010-N-0001] Notices

http://www.tmcnet.com/usubmit/2010/09/14/5005412.htm

http://www.federalregister.gov/articles/2010/09/14/2010-22805/transmissible-spongiform-encephalopathies-advisory-committee-notice-of-meeting

http://www.fda.gov/AdvisoryCommittees/Calendar/ucm153468.htm

From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION PART III]

page 1 starts on page 13, then come back to page 1 to finish.....tss

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

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

Friday, September 3, 2010

Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE

http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html

Wednesday, September 08, 2010

Emerging Infectious Diseases: CJD, BSE, SCRAPIE, CWD, PRION, TSE Evaluation to Implementation for Transfusion and Transplantation September 2010

http://vcjdtransfusion.blogspot.com/2010/09/emerging-infectious-diseases-cjd-bse.html

Monday, September 13, 2010

atypical BSE strains and sporadic CJD strains, is there a connection and why shouldn't there be $

http://bse-atypical.blogspot.com/2010/09/atypical-bse-strains-and-sporadic-cjd.html

TSS